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Solid state photochemistry and X-ray crystallography of carbonyl-containing compounds Cheung, Eugene 2000

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SOLID STATE PHOTOCHEMISTRY A N D X - R A Y C R Y S T A L L O G R A P H Y OF CARBONYL-CONTAINING COMPOUNDS by EUGENE CHEUNG B.Sc , University of British Columbia, 1995 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE F A C U L T Y OF G R A D U A T E STUDIES (DEPARTMENT OF CHEMISTRY) We accept this thesis as conforming to the required standard THE UNIVERSITY OF BRITISH C O L U M B I A September 2000 ©Eugene Cheung, 2000 In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Department of f.' H ^ M ^ T r^Y The University of British Columbia Vancouver, Canada Date DE-6 (2/88) ABSTRACT This thesis reports the role of the crystalline environment in influencing the solid state photochemistry of carbonyl-containing compounds. Two types of photochemical reactions were studied: electrocyclization and hydrogen atom abstraction. The structure-reactivity relationships in systems undergoing these reactions were revealed with the use of single crystal X-ray crystallography using the X-ray Structure-Solid State Reactivity Correlation Method. chiral conformations. The prospect of using this conformational chirality for studies of absolute asymmetric synthesis was explored. The effects of halogen substitution on the crystal packing are also discussed. A series of halo-substituted enamides (I) was synthesized and the photochemical behaviour of each enamide was studied. These substrates undergo a concerted photochemical ring closure in solution. Although formally achiral, the enamides can adopt The crystal structures of a homologous series of spiro-benzoyladamantanes (III - VI) were determined. These compounds undergo photochemical y-hydrogen atom abstraction in the solid state. The fates of their 1,4-III - VI biradicals can be rationalized using biradical geometries derived from the crystal data. 11 XI 0© Y = F, CN, COOCH3, COO N H 3 R * The crystal structures of a series of cw-9-decalyl Y aryl ketones (XI) were determined. These compounds undergo hydrogen atom abstraction reactions in the solid state. The role of the crystalline environment in directing the formation of regio- and diastereoselective photoproducts was determined. Asymmetric synthesis in the carboxylic acid derivatives of XI was studied using the Ionic Chiral Auxilary Concept, and the photochemical results obtained from this approach were rationalized from the crystal structures. The crystal structures of a series of a-mesitylacetophenones (XVI) were determined, and correlated with their photochemical reactivities. These compounds undergo 5-hydrogen atom abstraction in the solid state, and the photochemistry is discussed in terms of the molecular abstraction geometries derived from the crystal data. Asymmetric induction in the optically active salts of the carboxylic acid derivative of this system was also studied, and the photochemical results were rationalized from the crystal structures. 0 © X = F, Cl, Br, CN, COO N H 3 R * iii TABLE OF CONTENTS Abstract i i Table of Contents iv List of Figures x List of Tables xix List of Symbols and Abbreviations xxv Acknowledgments xxvii Dedication xxix INTRODUCTION Chapter 1 Introduction 1 1.1. General considerations 1 1.2. The crystal structure and its effects in solid state chemistry. 3 1.3. Electronic aspects of photoexcitation 11 1.4. Photoelectrocyclizations 13 1.5. The photochemistry of ketones 17 1.6. Geometric requirements for intramolecular hydrogen atom abstraction in ketones 19 1.7. Crystal concepts and crystal packing 21 1.8. Asymmetric induction in the solid state: Crystal to molecular chirality transfer 22 1.9. The ionic chiral auxiliary in asymmetric synthesis 27 1.10. Research objectives 31 1.11. References 34 iv RESULTS AND DISCUSSION Chapter 2 Conformational Chirality and the 'Wta-Steering Effect" in the Crystal Packing and Photochemistry of Enamides 42 2.1. General considerations 42 2.2. The "meta-Steering effect" 45 2.3. The photochemistry of A^benzyl-A^3,4-dihydro-l-naphthyl )benzamide 48 2.4. Photochemical and crystallographic studies of enamide derivatives 50 2.5. Synthesis of halo-substituted enamides 50 2.6. Photochemistry of the halo-substituted enamides 51 2.7. X-ray crystallographic analysis of the enamides 52 2.8. The "meta-Steering effect" on Crystal packing 65 2.9. Conclusions 73 2.10. References 74 Chapter 3 The Partitioning of 1,4-Biradicals in the Norrish Type II Reaction in Spiro-benzoyladamantanes 77 3.1. General considerations 77 3.2. Solid state reactivity 79 3.3. X-ray crystallographic analysis of molecular structure 87 3.4. X-ray crystallographic analysis of the stereochemistry of the photoproducts and their crystal packing 96 3.5. Conclusions 104 3.6. References 105 Chapter 4 Regio-, Diastereo-, and Enantioselective Reactions in the Photochemistry of Aryl derivatives of the c/s-9-Decalyl Ketones 107 4.1. General considerations 107 4.2. Solution and solid state photochemistry of the aryl ketones 108 v 4.3. X-ray crystallographic analysis of the solid state photochemistry of two benzoyl derivatives of the c/s-9-decalyl system I l l 4.4. The competition between (3- and y-hydrogen atom abstraction in the solution and solid state photochemistry of the keto ester derivative of the c/s-9-decalyl system 116 4.5. Solid state photochemical asymmetric induction and X-ray crystallographic analysis of optically pure salts of the czs-9-decalyl system 122 4.6. Conclusions 129 4.7. References 131 Chapter 5 Structure-Reactivty Correlations and Asymmetric Synthesis of Five-membered Rings from the Photochemistry of Sterically Congested a-Arylacetophenones 133 5.1. General considerations 133 5.2. Solid state photochemistry of substituted a-mesitylacetophenones 135 5.3. Crystal structure-reactivity relationships 137 5.4. Molecular mechanics calculations 147 5.5. X-ray crystallographic analysis of the crystal packing of the a-mesitylacetophenones 150 5.6. Solid state photochemical studies of 4-[2-(2,4,6-trimethyl-phenyl)-acetyl]benzoic acid and its optically pure salts 158 5.6.1. The solid state photochemistry of 4-[2-(2,4,6-trimethyl-phenyl)-acetyl]benzoic acid 158 5.6.2. Asymmetric induction in the solid state photochemistry of three optically pure salts of 4-[2-(2,4,6-trimethyl-phenyl)-acetyl]benzoic acid 161 5.7. Conclusions 170 5.8. References 172 vi E X P E R I M E N T A L Chapter 6 Experimental (Organic) 174 6.1. General Considerations 174 6.2. Syntheses of Photochemical Substrates 177 6.3. Photochemical Reactions 186 6.3.1. Photochemical Procedures and Spectral Characterization of Photoproducts 187 6.4. References 197 Chapter 7 Experimental (Crystallographic) 198 7.1. General considerations 198 7.1.1 Selection of a crystal for the X-ray diffraction experiment 198 7.1.2 Data collection on the Rigaku AFC6S 199 7.1.3. Data reduction on the AFC6S 201 7.1.4. Data collection on the Rigaku AFC7-ADSC Quantum C C D 202 7.1.5. Data reduction on the Rigaku AFC7-ADSC Quantum C C D 203 7.1.6. The phase problem 204 7.1.7. Structure solution 205 7.1.8. Structure refinement 210 7.1.9. Treatment of disorder 213 7.1.10. Structure completion 214 7.2. Crystallographic data and details of the structure determinations 214 7.2.1. N-benzyl-AK3,4-dihydro-l-naphthyl)benzamide (la) 214 7.2.2. A^-benzyl-4-fluoro-A''-(3,4-dihydro-l-naphthyl)benzamide (Ib) 218 7.2.3. A^-benzyl-4-chloro-A^-(3,4-dihydro-l-naphthyl)benzamide (Ic) 221 7.2.4. A^-benzyl-4-bromo-N-(3,4-dihydro-l-naphthyl)benzamide (Id) 227 7.2.5. 7V-benzyl-3-fluoro-N-(3,4-dihydro-l-naphthyl)benzamide (le) 230 7.2.6. /V-benzyl-3-chloro-A''-(3,4-dihydro-l-naphthyl)benzamide (If) 234 vii 7.2.7. A^-benzyl-3-bromo-A^-(3,4-dihydro-l-naphthyl)benzam (Ig) 237 7.2.8. Trans-5-benzyl-8-chloro-4b,10b,ll,12-tetrahydro-benzo[c]phenanthridin-6[5h]-one (Uf) 240 7.2.9. Trans-5-benzyl-8-bromo-4bJ0bJ1424etrahydro-benzo[c]phenanthridin-6[5h]-one (Ug) 244 7.2.10. Spiro[2h-indene-2,2'-tricyclo(3.3.1.13,7)decan]-l(3/f)-one (III) 247 7.2.11. 3,4-dihydro-spiro(naphthalene-2(lh),2'-tricyclo(3.3.1.13,7)-decan]-I- one (IV). 252 7.2.12. 8,9-dihydro-spiro[67/-benzocycloheptene-6,2'-tricyclo-[3.3.1.13,7]decan]-5(7#)-one (V) 255 7.2.13 3,4-dihydro-spiro(naphthalene-2(l/T),2'-tricyclo(3.3.1.13,7)-decan]-l-one (VI) 258 7.2.14. l,2,33a,4,5,6JJlcJld-decahydro-2,5-methano-5aH-benzo-[c]cyclopropa[ef]-phenanthren-5a-ol (VIII) 261 7.2.15. (7aS,7bS,9R,l 15,1 la^,llbS,13/?)-6,7,7b,8,9,10,l 1,1 la-octahydro-9,7a,l 1-[l,2,3]propanetriyl-7aH-benzo[a]benzo[3,4]cyclobuta[l,2-c]cyclohepten-II- b(5H)-ol (IX) 273 7.2.16. (7aS,7b5,9i?,115,lla^,llbS,13/?)-6,7,7b,8,9,10,ll,lla-octahydro-9,7a,ll-[l,2,3]propanetriyl-7aH-benzo[a]benzo[3,4]cyclobuta[l,2-c]cyclohepten-ll-b(5#)-ol (X) 276 7.2.17. (a'5-Octahydro-naphthalen-4a-yl)phenylmethanone (XIa) 279 7.2.18. (4-fluoro-phenyl)-(cw-octahydro-naphthalen-4a-yl)methanone (Xlb) 283 7.2.19. 4-[(cw-Octahydro-4a-(27T)-naphthalenyl)carbonyl]benzoic acid methyl ester (XIc) 286 7.2.20. 4-[(4a/?,85',8a/?,95)-Octahydro-9-hydroxy-2H-4a,8-methanonaphthalen-9-yl]benzoic acid methyl ester (XIIc) 290 7.2.21. l,2,3,4-Tetrahydro-9-oxo-4a,9a-butano-9H-fluorene-6-carboxylic acid methyl ester (XIVc) 293 7.2.22. 4-[(cw-Octahydro-4a-(2^)-naphthalenyl)carbonyl]benzoic acid (IR,2S)-(+)-norephedrine salt (SI) 296 viii 7.2.23. 4-[(cis-octahydro-4a-(2//)-naphthalenyl)carbonyl]benzoic acid (Sj-(-)-a-methylbenzylamine salt (S2) 302 7.2.24. l-(4-fluoro-phenyl)-2-(2,4,6-trimethyl-phenyl)ethanone (XVIa) 305 7.2.25. 4-[2-(2,4,6-trimethyl-phenyl)-acetyl]benzonitrile (XVIb) 308 7.2.26. l-(3-fluoro-phenyl)-2-[(2,4,6-trimethyl-phenyl)ethanone (XVIc) 311 7.2.27. l-(3-chloro-phenyl)-2-[(2,4,6-trimethyl-phenyl)ethanone (XVId) 315 7.2.28. l-(3-bromo-phenyl)-2-[(2,4,6-trimethyl-phenyl)ethanone (XVIe) 317 7.2.29. 3-[2-(2,4,6-trimethyl-phenyl)-acetyl]benzonitrile (XVIf) 320 7.2.30. 4-[2-(2,4,6-trimethyl-phenyl)-acetyl]benzoic acid (XVIg) 324 7.2.31. 4-[2-(2,4,6-trimethyl-phenyl)-acetyl]benzoic acid (15,2/?)-(+)-norephedrine salt (S3) 329 7.2.32. 4-[2-(2,4,6-trimethyl-phenyl)-acetyl]benzoic acid (/?)-(+)-a,4-dimethyl-benzylamine salt (S4) 333 7.2.33. 4-[2-(2,4,6-trimethyl-phenyl)-acetyl]benzoic acid (7?)-(+)-/V,a-dimethyl-benzylamine salt (S5) 337 .3. References 342 ix LIST OF FIGURES Figure Caption Page Figure 1.1. The photochemistry of santonin (1) 2 Figure 1.2. Compounds displaying medium-dependent photoreactivity 5 Figure 1.3. The photochemistry of rrarcs-cinnamic acid (14) in solution and the solid state 6 Figure 1.4. Pictorial representation of the "reaction cavity" (solid line), the reactant (shaded), the allowed transition state (shaded) and the disallowed transition state (hatched) 9 Figure 1.5. Steric compression control in the solid state photochemistry of (18) 10 Figure 1.6. Jablonski diagram for general molecular photophysical processes 13 Figure 1.7. Electrocyclic reaction of a triene 14 Figure 1.8. The photochemical electrocyclic reaction of stilbene (21) 14 Figure 1.9. The photochemical electrocyclic reaction of l,2-di(3-furyl)ethene (23) 15 Figure 1.10. The photochemistry of l,2-bis(2,5-dimethyl-3-thienyl)-perfluorocyclopentene 16 Figure 1.11. The Norrish Type I reaction 17 Figure 1.12. The Norrish Type II photochemical reaction 18 Figure 1.13. The abstraction parameters defining the spatial relationship for the abstraction of a hydrogen atom by the excited carbonyl oxygen atom 20 Figure 1.14. Solid state asymmetric synthesis of 30 24 Figure 1.15. Absolute asymmetric solid state [2 + 2] photodimerization of 31 and 32 25 Figure 1.16. Absolute asymmetric solid state [2 + 2] photodimerization of 36 25 Figure 1.17. Unimolecular absolute asymmetric synthesis in chiral crystals 26 Figure 1.18. Asymmetric induction using crystalline complexes 28 x Figure 1.19. Differences in diastereomeric transition state energies in a chiral crystal as a consequence of the ionic chiral auxiliary concept 29 Figure 1.20. Asymmetric induction of a carboxylic acid and a chiral amine via the di-7r-methane rearrangement 30 Figure 1.21. Asymmetric induction of an amine and a chiral carboxylic acid via the di-7r-methane rearrangement 30 Figure 1.22. Asymmetric induction of a carboxylic acid and a chiral amine via the Norrish Type II reaction 31 Figure 1.23. Systems studied in this thesis 32 Figure 2.1. A^benzyl-N-(3,4-dihydro-l-naphthyl )benzamide 42 Figure 2.2. Enantiomeric chiral conformations of 6,6'-dinitro-2,2'-diphenic acid 43 Figure 2.3. 1,1'- Binaphthyl (54) 43 Figure 2.4. The structures of benzophenone (55) ands its substituted derivatives 56 and 57 44 Figure 2.5. The photochemical reaction of a substituted a-oxoamide (59) 46 Figure 2.6. Photochemical rearrangement of substituted 4-benzyloxy-2-pyridone derivatives 47 Figure 2.7. The photoelectrocyclization of A^benzyl-./V-(3,4-dihydro-l-naphthyl)-benzamide (la) 48 Figure 2.8. Mechanism of the electrocyclization of la 49 Figure 2.9. Synthesis of enamides I(a-g) 51 Figure 2.10. Photochemistry of the halo-substituted enamides I(b-g) 51 Figure 2.11. ORTEP diagram of la 53 Figure 2.12. ORTEP diagram of Ib 54 Figure 2.13. ORTEP diagram of Ic 54 Figure 2.14. ORTEP diagram of Id 55 Figure 2.15. ORTEP diagram of le 55 Figure 2.16. ORTEP diagram of If 56 Figure 2.17. ORTEP diagram of Ig 58 xi Figure 2.18. Top-eye view of an ideally conjugated enamide system. The atoms involved in the electrocyclic ring closure (C9-C10-N1-C18-C19-C24) are labelled 58 Figure 2.19. The twist of the benzoyl phenyl ring from planarity with the amide reduces conjugation between these two moieties, and the almost orthogonal spatial arrangement between the [3H,4H]-dihydronaphth-l-yl and the amide prevents the two from being well-conjugated 59 Figure 2.20. The reaction cavity of lb 61 Figure 2.21. ORTEP diagram of photoproduct Uf showing the trans-C9-C10 junction 62 Figure 2.22. ORTEP diagram of photoproduct Ug showing the trans-C9-C10 junction 62 Figure 2.23. Superimposition of the photoproduct Hf (dark) onto the reactant If (light) 64 Figure 2.24. The packing diagram of la. A 2\-screw axis is shown parallel to the a-axis 66 Figure 2.25. The packing diagram of le. This derivative's crystal structure is isostructural to la 66 Figure 2.26. The packing diagram of If. Rotation and translation around a 2i-screw axis generate the symmetry-related molecules 67 Figure 2.27. The packing diagram of Ig. This derivative's crystal structure is isostructural to la 67 Figure 2.28. The packing diagram of lb. Rotation and translation around a 2]-screw axis generate the symmetry-related molecules 68 Figure 2.29. The packing diagram of Ic. Two molecules are present in the asymmetric unit, and a molecule of methanol resides on a centre of symmetry 69 Figure 2.30. The packing diagram of Id. A molecule of methanol resides on a centre of symmetry 69 Figure 2.31. The packing diagram of Hf. The crystal structure is C-centred 71 xii Figure 2.32. The packing diagram of I l g . The crystal structure is isostructural to Hf. 71 Figure 3.1. The spiro-benzoyladamantane system 77 Figure 3.2. Partitioning of the 1,4-biradicals formed from y-hydrogen abstraction of ketones I I I - V I 78 Figure 3.3. The photochemistry of an unconstrained adamantyl system 63. The title compounds III - V I are structurally similar to 63 78 Figure 3.4. Solid state photochemistry of III 80 Figure 3.5. Photochemistry of I V in a water suspension 80 Figure 3.6. Solid state photochemistry of V 81 Figure 3.7. Solid state photochemistry of V I 81 Figure 3.8. The 1,4-biradical geometry of the spiro-adamantyl system, in which two half-filled p-orbitals are located on carbons 1 and 4, and the a-P sigma orbital is located between carbons 2 and 3 83 Figure 3.9. ORTEP diagram of the five-membered ring spiro-benzoyladamantane III. illustrating the symmetric shape of the molecule, with the carbonyl O l - C l bond pointing along the C2-C5 vector, and bisecting the adamantyl skeleton 88 Figure 3.10. ORTEP diagram of the six-membered ring spiro-benzoyladamantane I V . The carbonyl O l - C l bond swings away from the C2-C5 vector, and now eclipses the sigma orbital lying between the a and P carbons 89 Figure 3.11. ORTEP diagram of the seven-membered ring spiro-benzoyladamantane V . The carbonyl O l - C l bond has now swung beyond the C2-C3 bond 89 Figure 3.12. ORTEP diagram of the eight-membered ring spiro-benzoyladamantane V I . The carbonyl O l - C l bond now swings back towards the C2-C3 bond 90 Figure 3.13. Intra-annular angles of the phenyl group 94 Figure 3.14. Atoms on the carbonyl plane, (a) The torsional angle (x4) of the atoms: 01, C l , C a _i , and Cp-i. (b) The angle u l consists of the atoms: xiii C a , C i , and Ca-i- (c) A least squares plane is defined for the atoms: Oi , C i , C a , a n d C a - i 96 Figure 3.15. ORTEP diagram of the cyclobutanol photoproduct IX. The stereochemistry of the hydroxyl group is exo to the adamantyl skeleton. .97 Figure 3.16. ORTEP diagram of the cyclobutanol photoproduct X. The stereochemistry of the hydroxyl group is exo to the adamantyl skeleton. .98 Figure 3.17. ORTEP diagram of the unusual photoproduct VIII. This compound is envisioned to arise from a cyclobutyl to a cyclopropylcarbinyl cation rearrangement 98 Figure 3.18. Adamantyl compounds which do not form hydrogen bonds with adjacent molecules, (a) 2-cumyladamantan-2-ol. (b) 2-(2,4,6-trimethylphenyl)adamantan-2-ol 100 Figure 3.19. Packing diagram of IX. This packing motif is almost identical to that of X 101 Figure 3.20. Packing diagram of X. The crystal structure of this compound can be considered as virtually isostructural to that of IX. 102 Figure 3.21. Packing diagram of VIII illustrating the tetrameric hydrogen bonding motif in the crystal structure. The hydrogen bonds are shown with dashed lines 103 Figure 4.1. Aryl derivatives (XI) of the ds-decalyl system 107 Figure 4.2. Various conformations that the c/s-decalyl molecule can possess by rotation of the aryl group and ring-flipping of the decalin system 109 Figure 4.3. Photochemistry of the aryl ketones (XI) of the cz's-decalyl system 110 Figure 4.4. ORTEP diagram of XIa. 113 Figure 4.5 ORTEP diagram of Xlb 115 Figure 4.6. ORTEP diagram of XIc 118 Figure 4.7. ORTEP diagram of photoproduct XIIc 118 Figure 4.8. ORTEP diagram of XIVc 119 Figure 4.9. The reaction pathways of the 1,3-biradical formed from p-hydrogen atom abstraction 119 xiv Figure 4.10. The 1,4-biradical geometry of the c/s-decalyl system, (a) Thebiradical resulting from H A / H A ' abstraction. Two half-filled p-orbitals are located on C2 and C l 1, and the a-P sigma orbital is located between C l and CIO. (b) The biradical resulting from H B / H B - abstraction. Two half-filled p-orbitals are located on C4 and C l 1, and the a-P sigma orbital is located between C5 and CIO 121 Figure 4.11. Solid state photochemistry of the optically pure salts SI and S2 123 Figure 4.12 ORTEP diagram of an Xld anion in the asymmetric unit of SI 125 Figure 4.13 The packing diagram of SI. The asymmetric unit illustrates the non-crystallographic symmetry of the two nearly mirror-symmetric Xld molecules. An infinite two-dimensional hydrogen bonding motif (parallel to the a and b axes) is present. This network utilizes every hydrogen atom that is capable of hydrogen bonding 125 Figure 4.14 The superimposition of the two acid molecules of SI. The X-ray coordinates of one of the carboxylates (dark) has been inverted and overlaid onto the coordinates of the non-inverted molecule (light) 126 Figure 4.15 The packing diagram of S2. An infinite one-dimensional hydrogen bonding motif (parallel to the a-axis) utilizes every hydrogen atom that is capable of hydrogen bonding 128 Figure 4.16 ORTEP diagram of Xld in S2 129 Figure 5.1. The a-Mesitylacetophenone system (XVI) 133 Figure 5.2. Photochemical 8-hydrogen atom abstraction. The photoexcited carbonyl oxygen of a molecule of XVI abstracts a 8-hydrogen atom to form a 1,5-biradical which cyclizes to a five-membered ring (indanol XVII) 134 Figure 5.3. The solid state photochemistry of the a-mesityacetophenone system (XVI) 136 Figure 5.4. Some possible positions (a, b, c, d) for methyl hydrogen atoms adjacent to an aromatic ring 139 xv Figure 5.5. (a) The geometric parameters for 8-hydrogen atom abstraction, (b) The new abstraction parameter L expresses the separation distance between the carbonyl oxygen atom and the closest 8-carbon atom 140 Figure 5.6. A plot of the separation distance between the carbonyl oxygen atom and the closest 8-methyl carbon for derivatives XVI(a-f) and the separation distance between the closest 8-hydrogen atom on this carbon and the carbonyl oxygen (d). Together, these two graphs illustrate the excellent correlation between L and d 140 Figure 5.7. The dihedral angle between the carbonyl plane and the mesityl ring is designated K i 144 Figure 5.8. A plot of the separation distance L against the dihedral angle K I . Ascending values of the dihedral angle K i of the a -mesitylacetophenones 144 Figure 5.9. ORTEP diagram of the para-fluoro derivative XVIa. The carbonyl group is in a nearly bisecting position with respect to the mesityl ring...145 Figure 5.10. ORTEP diagram of the para-cyano derivative XVIb. The carbonyl oxygen favours the abstraction of H a on C17 146 Figure 5.11. ORTEP diagram of the meta-chloro derivative XVId. The carbonyl group is in a nearly bisecting position with respect to the mesityl ring... 146 Figure 5.12. ORTEP diagram of the meta-bromo derivative XVIe. The carbonyl group is in a nearly bisecting position with respect to the mesityl ring... 146 Figure 5.13. ORTEP diagram of the mefa-cyano derivative XVIf. The carbonyl group is 14° from a bisecting position with respect to the mesityl ring. The substituent is anti to the carbonyl oxygen 01 147 Figure 5.14. The dihedral angle between the carbonyl plane and the mesityl ring is designated K2 148 Figure 5.15. Lowest energy conformation of XVIa from molecular mechanics calculations. The carbonyl group bisects the mesityl ring (KI = 90°). The para-fluoro phenyl ring is fully conjugated with the carbonyl plane ( K 2 = 0°) 148 xvi Figure 5.16. The packing diagram of XVIa . There are significant %• • • % interactions between the benzoyl rings 151 Figure 5.17. The packing diagram of XVIb . The packing motif is almost identical to that of X V I a above, with n- • • n interactions between the benzoyl rings 152 Figure 5.18. The packing diagram of X V I d , showing the ir • • n interactions between the benzoyl rings 153 Figure 5.19. The packing diagram of XVIe, showing the %• • • n interactions between the benzoyl rings 154 Figure 5.20. The packing diagram of XVIf , showing the n- • • n interactions between the benzoyl rings 154 Figure 5.21. ORTEP diagram of the major conformation of XVIc . The fluoro substituent is syn to the carbonyl group 156 Figure 5.22. ORTEP diagram of the minor conformation of XVIc . The fluoro substituent is and to the carbonyl group 156 Figure 5.23. The packing diagram of XVIc showing only the conformation of the major disordered component 157 Figure 5.24. An illustration of the cavity around a reactant molecule of XVIc 157 Figure 5.25. The solid state photochemistry of the carboxylic acid derivative of X V I 159 Figure 5.26. An illustration of the unit cell of XVIg , showing the long c-axis and the four different conformations of the carboxylic acids in the asymmetric unit. Two of the four molecules appear to be nearly related by a centre of symmetry 160 Figure 5.27. The solid state photochemical results of X V I g with ionic chiral auxiliaries 163 Figure 5.28. A diagram illustrating the Re and Si faces of X V I g 165 Figure 5.29. A molecule of X V I g in S3. The closest abstractable 8-hydrogen atom i s H b o n C 1 7 167 xvii Figure 5.30. The packing diagram of S3. The TI- • • n interactions that are found in the crystal structures of the molecular ketones are not present in this crystal packing 167 Figure 5.31. ORTEP diagram of XVIg in S4 168 Figure 5.32. ORTEP diagram of one of the two independent anions of XVIg in S7. The conformation shown above favours the abstraction of F£a 169 Figure 5.33. The packing diagram of S5 shows the hydrogen bonding of the XVIg anions with the ionic auxiliaries 170 Figure 7.1. A four-circle diffractometer illustrating the four angular settings co, 20, x, and (j) measured for each reflection 190 xviii LIST OF TABLES Table 2.1. Crystallographic data of the enamides I(a-g) 53 Table 2.2. Distances, angles, and least squares planes derived from crystallographic data 58 Table 2.3. Torsional angles i i and x% 60 Table 2.4. Differences in displacement (A) of If and Hf after least squares minimization 63 Table 3.1. Hydrogen atom abstraction parameters for the spiro-benzoyladamantanes 82 Table 3.2. Geometric data for biradicals III - VI 83 Table 3.3. Crystal data of the starting ketones III - VI 88 Table 3.4. Diagonal elements of the translational tensor T (A 2 ) for III - VI 92 Table 3.5. Diagonal elements of the librational tensor L (°) 2 and R for III - VI 92 Table 3.6. Angular deviations of the phenyl rings in compounds III - VI 94 Table 3.7. Angles and least squares plane residuals describing the orientation of the carbonyl group in ketones III - VI 95 Table 3.8. Crystal data of photoproducts VIII - X 100 Table 4.1. Photolysis of the aryl ketones XI in solution and the solid state I l l Table 4.2. Hydrogen atom abstraction parameters of XIa 112 Table 4.3. Crystallographic data of the molecular ketones Xl(a-c) and photoproducts XIIc and XIVc 114 Table 4.4. Hydrogen abstraction parameters of Xlb 115 Table 4.5. Hydrogen abstraction parameters of XIc 120 Table 4.6. Orbital overlap and torsional angle T5 in compounds Xl(a-c) 121 Table 4.7. Crystallographic data of the chiral salts SI and S2 123 Table 4.8. Photochemical yields from the irradiation of SI and S2 124 Table 4.9. Hydrogen atom abstraction parameters of salt SI 127 xix Table 4.10. Hydrogen abstraction parameters of S2 128 Table 5.1. Temperature-dependent conversions in the solid state photolysis of XVI(a-f) 136 Table 5.2. X-ray crystal data of ketones XVI(a-f) 137 Table 5.3. Crystallographically derived C=0 8-H abstraction geometries for ketones XVI(a-f) 141 Table 5.4. Values for the dihedral angle between the carbonyl plane and the mesityl ring 144 Table 5.5. The hydrogen atom abstraction geometries of the two closest hydrogen atoms (H a and Hb) on the o/t/io-methyl carbons of the lowest energy conformations of XVI(a,b,d,f) 149 Table 5.6. The dihedral angle between the carbonyl plane and the attached substituted benzoyl group (K2) from X-ray crystallographic data 152 Table 5.7. Crystallographic data of XVIg 159 Table 5.8. Conformational angles of the four molecules found in the crystal structure of XVIg 161 Table 5.9. The abstraction geometries of the closest 8-hydrogen atoms for XVIg. .161 Table 5.10. Solid state photolysis results for the chiral salts of keto acid XVIg 163 Table 5.11. Crystallographic data of the optically pure salts of XVIg 165 Table 5.12. The abstraction geometries of the closest 8-hydrogen atoms in the optically pure salts S3-S5 166 Table 5.13. Conformational angles of the four molecules of XVIg found in the crystal structures of S3-S5 166 Table 7.1. Crystallographic data of la and Ib 216 Table 7.2. Final atomic coordinates (fractional) and B(eq) (A 2 ) of la 217 Table 7.3. Bond lengths (A) of la with estimated standard deviations 217 Table 7.4. Bond angles (°) of la with estimated standard deviations 218 Table 7.5. Final atomic coordinates (fractional) and B(eq) (A 2) of Ib 219 Table 7.6. Bond lengths (A) of Ib with estimated standard deviations 220 Table 7.7. Bond angles (°) of Ib with estimated standard deviations 220 Table 7.8. Crystallographic data of Ic and Id 222 xx Table 7.9. Final atomic coordinates (fractional) and B(eq) (A 2 ) of Ic 223 Table 7.10. Bond lengths (A) of Ic with estimated standard deviations 225 Table 7.11 Bond angles (°) of Ic with estimated standard deviations 225 Table 7.12. Final atomic coordinates (fractional) and B(eq) (A 2) of Id 228 Table 7.13. Bond lengths (A) of Id with estimated standard deviations 229 Table 7.14. Bond angles (°) of Id with estimated standard deviations 229 Table 7.15. Crystallographic data of le, If, and Ig 231 Table 7.16. Final atomic coordinates (fractional) and B(eq) (A 2) of le 231 Table 7.17. Bond lengths (A) of le with estimated standard deviations 232 Table 7.18. Bond angles (°) of le with estimated standard deviations 233 Table 7.19. Final atomic coordinates (fractional) and B(eq) (A 2) of If 235 Table 7.20. Bond lengths (A) of If with estimated standard deviations 236 Table 7.21. Bond angles (°) of If with estimated standard deviations 236 Table 7.22. Final atomic coordinates (fractional) and B(eq) (A 2) of Ig 238 Table 7.23. Bond lengths (A) of Ig with estimated standard deviations 239 Table 7.24 bond angles (°) of Ig with estimated standard deviations 239 Table 7.25. Crystallographic data of IK and Ilg 241 Table 7.26. Final atomic coordinates (fractional) and B(eq) (A 2) of Hf 242 Table 7.27. Bond lengths (A) of Hf with estimated standard deviations 243 Table 7.28. Bond angles (°) of Hf with estimated standard deviations 249 Table 7.29. Final atomic coordinates (fractional) and B(eq) (A 2) of Ilg 245 Table 7.30. Bond lengths (A) of Ilg with estimated standard deviations 246 Table 7.31. Bond angles (°) of Ilg with estimated standard deviations 247 Table 7.32. Crystallographic data of III and IV 249 Table 7.33. Final atomic coordinates (fractional) and B(eq) (A 2) of III 250 Table 7.34. Bond lengths (A) of III with estimated standard deviations 251 Table 7.35. Bond angles (°) of III with estimated standard deviations 251 Table 7.36. Final atomic coordinates (fractional) and B(eq) (A 2) of IV 253 Table 7.37. Bond lengths (A) of IV with estimated standard deviations 254 Table 7.38. Bond angles (°) of IV with estimated standard deviations 254 Table 7.39. Crystallographic data of V and VI 256 xxi Table 7.40. Final atomic coordinates (fractional) and B(eq) (A 2) of V 257 Table 7.41. Bond lengths (A) of V with estimated standard deviations 257 Table 7.42. Bond angles (°) of VI with estimated standard deviations 258 Table 7.43. Final atomic coordinates (fractional) and B(eq) (A 2) of VI 260 Table 7.44. Bond lengths (A) of VI with estimated standard deviations 260 Table 7.45. Bond angles (°) of VI with estimated standard deviations 261 Table 7.46. Crystallographic data of VIII, IX, and X 263 Table 7.47. Final atomic coordinates (fractional) and U(eq) (A 2) of VIII 264 Table 7.48. Bond lengths (A) of VIII with estimated standard deviations 267 Table 7.49. Bond angles (°) of VIII with estimated standard deviations 270 Table 7.50. Final atomic coordinates (fractional) and B(eq) (A 2) of IX 275 Table 7.51. Bond lengths (A) of IX with estimated standard deviations 275 Table 7.52. Bond angles (°) of IX with estimated standard deviations 276 Table 7.53. Final atomic coordinates (fractional) and U(eq) (A 2) of X 278 Table 7.54. Bond lengths (A) of X with estimated standard deviations 278 Table 7.55. Bond angles (°) of X with estimated standard deviations 279 Table 7.56. Crystallographic data of XIa, Xlb, and XIc 281 Table 7.57. Final atomic coordinates (fractional) and B(eq) (A 2) of XIa 282 Table 7.58. Bond lengths (A) of XIa with estimated standard deviations 282 Table 7.59. Bond angles (°) of XIa with estimated standard deviations 282 Table 7.60. Final atomic coordinates (fractional) and B(eq) (A 2) of Xlb 284 Table 7.61. Bond lengths (A) of Xlb with estimated standard deviations 285 Table 7.62. Bond angles (°) of Xlb with estimated standard deviations 285 Table 7.63. Crystallographic data of XIc, XIIc, and XIVc 287 Table 7.64. . Final atomic coordinates (fractional) and B(eq) (A 2) of XIc 288 Table 7.65. Bond lengths (A) of XIc with estimated standard deviations 289 Table 7.66. Bond angles (°) of XIc with estimated standard deviations 289 Table 7.67. Final atomic coordinates (fractional) and B(eq) (A 2) of XIIc 291 Table 7.68. Bond lengths (A) of XIIc with estimated standard deviations 292 Table 7.69. Bond angles (°) of XIIc with estimated standard deviations 292 Table 7.70. Final atomic coordinates (fractional) and B(eq) (A 2) of XIVc 294 xxii Table 7.71. Bond lengths (A) of XIVc with estimated standard deviations 295 Table 7.72. Bond angles (°) of XIVc with estimated standard deviations 295 Table 7.73. Crystallographic data of SI and S2 297 Table 7.74. Final atomic coordinates (fractional) and B(eq) (A2) of SI 298 Table 7.75. Bond lengths (A) of SI with estimated standard deviations 300 Table 7.76. Bond angles (°) of SI with estimated standard deviations 301 Table 7.77. Final atomic coordinates (fractional) and B(eq) (A 2 ) of S2 303 Table 7.78. Bond lengths (A) of S2 with estimated standard deviations 304 Table 7.79. Bond angles (°) of S2 with estimated standard deviations 304 Table 7.80. Crystallographic data of XVIa and XVIb 306 Table 7.81. Final atomic coordinates (fractional) and B(eq) (A 2) of XVIa 307 Table 7.82. Bond lengths (A) of XVIa with estimated standard deviations 307 Table 7.83. Bond angles (°) of XVIa with estimated standard deviations 308 Table 7.84. Final atomic coordinates (fractional) and B(eq) (A 2 ) of XVIb 309 Table 7.85. Bond lengths (A) of XVIb with estimated standard deviations 310 Table 7.86. Bond angles (°) of XVIb with estimated standard deviations 310 Table 7.87. Crystallographic data of XVIc, XVId, and XVIe 312 Table 7.88. Final atomic coordinates (fractional) and U(eq) (A 2 ) of XVIc 313 Table 7.89. Bond lengths (A) of XVIc with estimated standard deviations 314 Table 7.90. Bond angles (°) of XVIc with estimated standard deviations 314 Table 7.91. Final atomic coordinates (fractional) and B(eq) (A 2 ) of XVId 316 Table 7.92. Bond lengths (A) of XVId with estimated standard deviations 317 Table 7.93. Bond angles (°) of XVId with estimated standard deviations 317 Table 7.94. Final atomic coordinates (fractional) and B(eq) (A 2) of XVIe 319 Table 7.95. Bond lengths (A) of XVIe with estimated standard deviations 319 Table 7.96. Bond angles (°) of XVIe with estimated standard deviations 320 Table 7.97 crystallographic data for XVIf and XVIg 321 Table 7.98. Final atomic coordinates (fractional) and B(eq) (A 2 ) of XVIf 322 Table 7.99. Bond lengths (A) of XVIf with estimated standard deviations 323 Table 7.100. Bond angles (°) of XVIf with estimated standard deviations 323 Table 7.101. Final atomic coordinates (fractional) and B(eq) (A 2 ) of XVIg 325 xxiii Table 7.102. Bond lengths (A) of XVIg with estimated standard deviations 327 Table 7.103. Bond angles (°) of XVIg with estimated standard deviations 328 Table 7.104. Crystallographic data for S3, S4, and S5 330 Table 7.105. Final atomic coordinates (fractional) and B(eq) (A 2 ) of S3 331 Table 7.106. Bond lengths (A) of S3 with estimated standard deviations 332 Table 7.107. Bond angles (°) of S3 with estimated standard deviations 333 Table 7.108. Final atomic coordinates (fractional) and B(eq) (A 2 ) of S4 335 Table 7.109. Bond lengths (A) of S4 with estimated standard deviations 335 Table 7.110. Bond angles (°) of S4 with estimated standard deviations 336 Table 7.111. Final atomic coordinates (fractional) and B(eq) (A 2 ) of S5 338 Table 7.112. Bond lengths (A) of S5 with estimated standard deviations 340 Table 7.113. Bond angles (°) of S5 with estimated standard deviations 341 xxiv LIST OF SYMBOLS AND ABBREVIATIONS A angstrom Anal. elemental analysis calcd calculated D hydrogen atom abstraction parameter d hydrogen atom abstraction parameter d doublet d. e. diastereomeric excess e. e. enantiomeric excess EI electron impact mass spectrometry GC gas chromatography GOF goodness-of-fit FfPLC high performance liquid chromatography HRMS high resolution mass spectra Hz hertz hn light energy IR Infrared light J coupling constant in Hz L R M S low resolution mass spectra m multiplet mmol millimole MM+ Molecular Mechanics calculation M P melting point MS mass spectra N M R nuclear magnetic resonance ppm parts per million R fl-factor Rw weighted /^-factor s singlet xxv q quartet t triplet T L C thin-layer chromatography uv ultraviolet light V volume z number of molecules in the unit cell 5 chemical shift A angular hydrogen atom abstraction parameter s linear extinction coefficient ( U V ) e angular hydrogen atom abstraction parameter X wavelength secondary extinction coefficient (X-ray) CO angular hydrogen atom abstraction parameter xx vi ACKNOWLEDGMENT I have been honoured to be a graduate student jointly supervised by two of the most outstanding scientists and pioneers in their fields. Professor James Trotter has shown me the wonderful world of X-ray crystallography and Professor John R. Scheffer has cultivated my interest in organic synthesis and photochemistry. In the last five years, they have guided me with patience, encouragement, and wealth of experience. No words can express my gratitude towards their tutelage and regard. I have been fortunate to have known and worked with Dr. Steven J. Rettig, whom I will always miss. He was among the most dedicated and productive of crystallographers, and a great friend. I could not have finished my work here without my friend and colleague in the X-ray Lab, Dr. Brian Patrick. He has a heart of gold. I am always cheered by his optimism, and he truly deserves the name "Seed Crystal of Fun". It has been a privilege to have collaborated with many talented individuals in Professor Scheffer's research group. Among them are Mr. Matthew N . Netherton, who synthesized and studied photochemically the compounds in Chapter 3 of this thesis. His passion for synthesis is both outstanding and infectious. I thank Mr. Ting Kang for his work on the compounds discussed in Chapter 4. He has become a good friend over the last four years. Dr. Katja Rademacher synthesized and photolyzed the compounds presented in Chapter 5. She is a great companion in our outdoor adventures, and she lets me eat all her gummy bears. Professor Clair Cheer was very xxvii helpful in suggesting new ideas for projects, and kept us all laughing with his humour. I thank Dr. Heiko Ihmels for being an excellent friend when he was at UBC, and I am grateful to all of the members (past and present) of Professor Scheffer's research group for their camaraderie, especially when they all joined my hockey team. There are many others who I have to thank. Among them are Dr. Andrew R. Lewis, whose enthusiasm is always uplifting, and Professor Colin Fyfe and his research group for their friendship and generosity. The staff of the Electronic and Mechanical Shops have been a key part of the X-ray Lab, and I could not have maintained and repaired the various equipment without their expertise and invaluable help. Finally, I would like to thank Professor Frederick H.-K. Cheung, who has been an inspirational guide from the very start. xxviii DEDICATION To my family, whom I will always remember, and To my dear friend and colleague, Dr. Steven J. Rettig (1948 - 1998), whom I will never forget. xxix Chapter 1 Introduction Chapter 1 Introduction 1.1. General Considerations For the better part of the last two hundred years, studies of chemical reactions have been focussed on the liquid and gaseous phases. Molecules in these two states were perceived to have the spatial freedom that allowed them to form new or break old bonds, whereas molecules in solid media were considered to have very small translational and vibrational motions, thus limiting the number and scope of reactivities that they were allowed. The idea that atoms and molecules move in crystals, sometimes with large amplitudes, was an outlandish thought, and many chemists, even up to the middle of the 20th century, subscribed to the belief that "a crystal is a chemical cemetery."1 Although there was a fundamental lack of understanding with regard to the arrangement of molecules in solids, transformations in the crystalline state were not unknown, even if they could not yet be explained. From time to time, resourceful and observant chemists investigated some of these behaviours, and quite often they noticed that it was light, in particular sunlight, which caused the changes to occur. These early photochemical discoveries were the result of time-consuming and weather-dependent experiments, often noticed entirely by serendipity.2 As early as 1834, Hermann Trommsdorff reported that crystals of santonin (1, Figure 1.1) yellowed and ruptured upon exposure to sunlight in what would become not only the first known 1 Chapter 1 Introduction photochemical reaction of an organic molecule, but also the first known photochemical reaction of an organic crystalline material.3 Many chemists would eventually work on this discovery, among them Stanislao Cannizzaro, who would be one of the first to isolate the photoproducts in 1886, although it would be 1958 before the structures of the photoproducts were finally confirmed.4 The lack of knowledge of molecular structure within crystals impeded the progress of solid state studies, even as organic photochemistry in solution was quickly developing into a field of its own by the turn of the 19th century,5 with intensive investigations into phenomena such as the cis-trans isomerization of cinnamic acids in solution.6 Figure 1.1. The photochemistry of santonin (1). 2 Chapter 1 Introduction The advent of X-ray crystallography in the early part of the 20th century forever changed the field of solid state chemistry.7 Single crystal X-ray diffraction techniques finally revealed the details of molecular packing that had eluded scientists for so long, making it possible to correlate reactivity with structure. In the X-ray diffraction experiment, a single crystal is irradiated with X-rays, and the diffraction pattern from the crystal is recorded by a detector (photographic film, scintillation counters, or recently, CCD cameras). The spatial relationship between the spots of the diffraction pattern is related to the arrangement of the points in a crystal lattice, and the intensities of these spots contain information about the location of the atoms in the unit cell. The diffraction pattern is used with the aid of mathematical transforms to reconstruct the contents of a crystal. In the past forty years, the understanding of photochemical reactions in the solid state has benefited enormously from the knowledge of the arrangement of molecules in crystal structures, and the X-ray Crystal Structure-Reactivity Correlation Method has become instrumental to the study of solid Q state organic photochemistry. 1.2. The Crystal Structure and its Effects in Solid State Chemistry Of the many types of constrained media, it is in the crystalline medium that molecular structure can be best envisioned.9 A crystal may be defined as an ordered atomic arrangement of atoms that is periodic in three dimensions and bound by straight edges and plane faces. The ordering of a crystal is its most important property, 3 Chapter 1 Introduction as this repetition allows each reacting molecule to exist in the same rigid environment, and hence, experience the same external and internal conditions. In other constrained media, where molecular flexibility and rotation is allowed, there is a lesser degree of organization among the molecules, resulting in molecules experiencing random fluctuations in an environment more akin to a fluid. Why study and perform reactions in the solid state? The solid state offers many advantages, including: reduced complexity of the experimental apparatus, economic savings by using a solvent-less reaction procedure, and environmentally-friendly reduction of solvent waste. But perhaps the most exciting application lies in solid state organic photochemistry's ability to synthesize compounds of all forms that cannot be produced by conventional solution chemistry. The consequence of constrained media is often seen when one product is observed in solution irradiation, and an entirely different product is formed in the crystal structure-controlled reaction in the solid state (Figure 1.2). Complex or very strained molecules which may be essentially unavailable except through tedious organic syntheses can be elegantly synthesized by photochemistry. 4 Chapter 1 Introduction dimers Figure 1.2. Compounds displaying medium-dependent photoreactivity 10,11,12 The study of reactions within crystals led to Kohlschutter's topochemical posutlate in 1918, the first theory that attempted to explain the results observed in solid state chemical reactions.13 Kohlschutter proposed that solid state reactions differ from solution reactions because they are governed by a solid environment or surface. A set of topochemical rules finally emerged during the 1960's when Schmidt and co-workers focussed on the solid state [2 + 2] photocycloaddition of rrans-cinnamic acid and its derivatives (14, Figure 1.3).14 5 Chapter 1 Introduction Ph. 14 COOH hv solution Ph. .COOH 15 Ph. HOOC. \ COOH Ph hv a form Ph HOOCv 16 COOH Ph Ph. Ph. \ COOH COOH Ph. HOOC COOH Ph hv (3 form hv y form Ph Ph, 17 COOH COOH No Reaction Figure 1.3. The photochemistry of rrans-cinnamic acid (14) in solution and the solid state. The cinnamic acid dimerization studies by Schmidt and co-workers have become one of the most widely cited works in the chemical literature. Today, almost every review article and compilation of solid state organic photochemistry refers to their findings and their topochemical exposition. The reactions of cinnamic acid were studied many years earlier, but it was not until 1943 that Bernstein and Quimby interpreted the formation of oc-truxillic and (3-truxinic acids from crystals of rrans-cinnamic acid as a reaction controlled by the crystal structure.15 Schmidt and co-workers expanded on this work, proposing that the 6 Chapter 1 Introduction photocycloaddition in the crystal is governed by molecular packing in the crystal structure, which determines the orientation and separation distances between two reactive double bonds. Solid state reactions occur in a constrained environment, and according to Schmidt's topochemical postulate, "reaction in the solid state occurs with a minimum of atomic or molecular movement". This postulate implies that there is an upper limit for distances between reactive centres beyond which no reaction will occur, and also forbids certain types of reactions which are associated with large-scale atomic movements (e.g. cis-trans isomerizations). In other words, only those reactions that satisfy the minimum motion criterion will occur in the solid state. These topochemical rules are followed closely by cinnamic acid and its derivatives. Both substituted and unsubstituted cinnamic acids have three packing motifs in the solid state, designated as the a, P, and y polymorphs. In the a-form the intermolecular -centre-to-centre distance between the overlapping double bonds of adjacent molecules is between 3.6 - 4.1 A , and the adjacent molecular pairs are related by a centre of symmetry. In the P-form, the adjacent molecules are parallel and slightly translated so that neighbouring double bonds have centre-to-centre separation distances of 3.9 to 4.1 A. In the y-form, the adjacent molecules are related by translation but the double bonds are offset in such a way that they do not overlap, and the closest centre-to-centre distances are between 4.7 - 5.2 A. Dissolution of any of these forms of cinnamic acids, and their subsequent photolyses result in a mixture of trans-cis products. In the solid state, however, no isomerization takes place, and photolysis of the a polymorph gives only the [2 + 2] photocycloaddition product 1 6 , 7 Chapter 1 Introduction and photolysis of the (3 polymorph only 17. The y polymorph is photostable. The inertness of this form was reasoned to be caused by crystal structure restraints which do not permit the potentially reactive centres to move sufficiently close together for the dimerization to occur. From these experiments, the upper limit of displacement o between two reaction centres was determined to be 4.2 A . In addition to the distance requirement, the [2 + 2] photocycloaddition is also dependent on the parallel alignment of the reacting double bonds. The orbitals on the reacting centres need to have good geometric overlap for the dimerization; no solid state dimerization is observed in cases where the centres of adjacent double bonds are within the proposed limit of 4.2 A but the double bond orientation is poor.1 6 Cohen and co-workers introduced the concept of the reaction cavity as a corollary to the topochemical rules.17 According to this idea, the reacting molecule exists in a cavity that is formed by its nearest neighbours, and as this central molecule reacts, its geometry changes within the cavity. Reactions which involve minor changes in reactant geometry will proceed without restriction from the cavity walls, but reactions with transition state geometries that are incompatible with the cavity will be strongly disfavoured (Figure 1.4). This concept has now been applied to other organized media.1 8 8 Chapter 1 Introduction Figure 1.4. Pictorial representation of the "reaction cavity" (solid line), the reactant (shaded), the allowed transition state (shaded) and the disallowed transition state (hatched). Other investigators of the reaction cavity concept include Gavezzotti, who suggested that the free space in the crystals determines reactivity in the solid state.19 Ohashi and co-workers studied the reaction rates of cobaloxime complexes, and observed from their results that those crystal structures which possessed the largest reaction cavities housing the complexes were also the ones which reacted the fastest. Related to the reaction cavity concept is that of steric compression control.21 In this approach, solid state reactivity between molecules may be forbidden even if they are well-aligned. For example, molecules of compound (18, Figure 1.5) crystallize in an orientation favourable for [2 + 2] photocycloaddition but do not form 9 Chapter 1 Introduction product due to the steric compression of the two methyl groups in the reacting molecules with those of the surrounding molecules. Neighbouring molecule Steric compresssion ~ upon dimerization i\S\S\S\/\S\S\S\j Neighbouring molecule Figure 1.5. Steric compression control in the solid state photochemistry of 18. Most experiments in the crystalline state treat the crystal as a perfectly homogenous medium, which is not entirely true, as dislocations and other imperfections are present in all crystals. The number of molecules located at these defect sites is generally very small compared to the vast number of molecules that reside in their regular positions in the crystal structure. When crystals are irradiated three events can occur in the excited state: (1) deactivation of the excited state; (2) reaction; and (3) transfer of excitation to another site. When reactivity is very low at the regular sites, the process of energy transfer to a neighbouring site has a higher probability of occurring, and because the normal symmetry of sites is disrupted at dislocations, molecules at defect sites are likely to act as trapping centres for excitation 10 Chapter 1 Introduction because they cannot transmit the energy. Defect sites can thus function as areas of 22 reaction. These sites are often the governing factor in solid state reactions in which the crystal structures do not predict reaction to occur, or in which the reaction that is observed is unusual with respect to the known chemistry of its system.23 Therefore, if the transfer of the excitation of molecules to defect sites happens rapidly, then the crystal structure is no longer the all-important factor in determining reactivity.24 As the reactions at the defect sites progress, the number of defect sites will multiply, and an appreciable amount of product can be obtained. 1.3. Electronic Aspects of Photoexcitation When a molecule in the ground state absorbs a photon, an electronic excited state is produced. The electronically excited molecule is described in terms of its molecular orbitals, of which five are important in photochemical excitation: the sigma bonding orbital (a), the sigma anti-bonding (a*), the pi bonding (n), the pi anti-bonding (Tt*), and the non-bonding orbital (n). The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) are involved in the photochemical excitation.25 When a molecule is excited, an electron from the HOMO is transferred to the L U M O , and the old L U M O becomes the new HOMO. In organic photochemistry, the transitions that can occur are: 11 Chapter 1 Introduction 1. 2. 3. 7t n n These transitions are listed in order of decreasing energy, with the n —> n* transition being the lowest in energy.26 A molecule that resides in the singlet ground state S Q , is excited photochemically to the singlet excited state, S\. The electron promoted to a higher molecular orbital retains its original spin. This electron can spin invert to give the triplet excited state, T\. This spin inversion is termed intersystem crossing (ISC). Once a molecule is in the excited state, it can decay to the ground state or react to form product via a singlet or triplet excited state. Two types of decay are possible: radiative (luminescent) and non-radiative (radiationless). Radiative decay involves the emission of light and can occur through either fluorescence, in which the molecule returns to the ground state from the singlet excited state via emission of a photon, or phosphorescence, in which a molecule emits a photon and returns to the ground state from the triplet excited state. Non-radiative decay to the ground state can occur via internal conversion from the singlet excited state, or via intersystem crossing from the triplet excited state. Figure 1.6 below illustrates the photophysical processes after molecular excitation by light. 12 Chapter 1 Introduction ^2 Legend abs = absorption isc = intersystem crossing fluor = fluoresence phos = phosphoresence rp ic = internal conversion 1 ] S = singlet level \ T = triplet level \ Triplet reaction Figure 1.6. Jablonski diagram for general molecular photophysical processes. 1.4. Photoelectrocyclizations One reaction that an excited molecule can undergo is photochemical electrocyclization. A well-known example of such a reaction is the ring closure of a triene (19, Figure 1.7) to a cyclodiene (20).27 This process is a concerted photochemical reaction, as indicated from the stereospecificity between reactant and product. 13 Chapter 1 Introduction . C H , " C H , hv ^ C H . 3 19 20 Figure 1.7. Electrocyclic reaction of a triene. c/s-Stilbene (21, Figure 1.8) can be converted photochemically to dihydro-phenanthrene (22).28 The reaction is a conrotatory conversion of a 1,3,5-hexatriene to a cyclohexadiene. hv hv' 21 22 Figure 1.8. The photochemical electrocyclic reaction of stilbene (21). It has been found that heterocycles can be formed from compounds (23, Figure 1.9) containing hetero-atoms, allowing for a wide range of synthetic schemes. hv hv' H O H O 24 Figure 1.9. The photochemical electrocyclic reaction of c/s-l,2-di(3-furyl)ethene (23).29 14 Chapter 1 Introduction When investigating solid state photochemical reactions, it is often assumed that the transition states of the excited state reactants are limited to conformations that closely resemble the ground state reactants. As a result, the X-ray crystal structures give a wealth of information about the shape of the molecule in the excited state, and can act as a predictive tool. Compounds with the general structure 25 (Figure 1.10) have been studied in detail recently.30 When they are in the proper orientation, these compounds have been found to undergo a reversible cyclization to 26, which is intensely coloured. Compound 25 exists in solution in two conformations: the open-ring anti-parallel form and the open-ring parallel form. In the open-ring anti-parallel form, the p-orbitals that are involved in cyclization are well-aligned for reaction, and 26 can be obtained after irradiation. In the open-ring parallel form of 25, the p-orbitals that are needed for cyclization are poorly aligned (i.e. not well-conjugated), and hence, reaction does not occur. Crystallization of 25 results in the presence of only the open-ring anti-parallel conformation, and photolysis of the crystals gives rise to a reaction progressing very rapidly from starting material to photoproduct. 15 Chapter 1 Introduction 26 (a) R = CH(CH 3 ) , (b) R = C H 3 Figure 1.10. The photochemistry of l,2-bis(2,5-dimethyl-3-thienyl)perfluoro-cyclopentene. The application of electrocyclic reactions to organic synthesis is well-known, but in solution, the products are typically racemic. The constraints of the solid state on the photochemistry of compounds which undergo electrocyclic reactions may be a factor in promoting different reactivities from those in solution, and so there is reason to believe that electrocyclic reactions in the crystalline state need to be further explored. 16 Chapter 1 Introduction 1.5. The Photochemistry of Ketones Ketones have probably undergone more photochemical investigation than any other type of organic compound. This is likely due to their ability to absorb light of ultraviolet to visible wavelengths. Among the more common photochemical reactions that can occur after excitation of the carbonyl moiety by light are: photoreduction, Norrish type I reaction, and intramolecular hydrogen atom abstraction. Photoreduction is largely an intermolecular phenomenon, involving hydrogen transfer to neighbouring molecules. The Norrish type I reaction (also known as oc-cleavage) involves the fission of the bond between the carbonyl carbon and the oc-carbon, resulting in an acyl radical and an alkyl radical (Figure 1.11). The two radicals that are formed will undergo various reactions to achieve stability, or join together again to regenerate the starting material. Figure 1.11. The Norrish type I reaction.31 The third type of reaction, intramolecular hydrogen atom abstraction, can occur on |3, y, and 8 carbons, although examples of y-hydrogen atom abstraction far exceed the number of observations of (3- and 5-hydrogen atom abstraction. The name given to o O 17 Chapter 1 Introduction the specific case of y-hydrogen atom abstraction is the Norrish type II reaction (Figure 1.12). Figure 1.12. The Norrish type II photochemical reaction. R and R' can be alkyl or aromatic moieties. The Norrish type IJ reaction is probably the most well-known photochemical reaction involving ketones. The mechanistic details are illustrated in Figure 1.12. Upon irradiation by U V light, the y-hydrogen atom is abstracted by the (n, TC*) excited carbonyl oxygen via a cyclic transition state to produce a 1,4-biradical intermediate, which can either cyclize to a cyclobutanol (Yang cyclization), cleave (Norrish type II 18 Chapter 1 Introduction cleavage) to an olefin and enol which tautomerizes to the ketone, or undergo reverse hydrogen transfer to regenerate the starting compound. A linear transition state is the ideal geometry in hydrogen transfer between two atoms, but this arrangement is geometrically impossible in the 5-, 6-, and 7-membered transition states of P-, y-, and 8-hydrogen atom abstraction. There is evidence that the 6-membered transition state of y-hydrogen atom abstraction is the most favourable of the three,32'33 and this is witnessed experimentally from the multitude of Norrish type II reactions and the paucity of P- and 8-hydrogen abstraction examples. Abstractions of P- and 8-hydrogen atoms are known to occur only when there are no y-hydrogen atoms available for abstraction.34 1.6. Geometric Requirements for Intramolecular Hydrogen Atom Abstraction in Ketones The Norrish type II reaction involving aryl ketones occurs via a triplet excited state and the geometry of the abstracted hydrogen atom with respect to the triplet n,7t* excited state oxygen is the most important factor in determining whether an abstraction reaction can take place. Early theoretical work proposed that interatomic separations of 1.8 A between the y-hydrogen and oxygen atoms (d, Figure 1.13) was o the upper limit of hydrogen atom abstraction, and this value was increased to 2.1 A 19 Chapter 1 Introduction when conformationally rigid steroidal systems were examined.36 Later studies of ene-37 dione compounds by Scheffer and co-workers led to the re-evaluation of these limits. Scheffer and co-workers discovered that intramolecular hydrogen atom A 38 _ , , which is approximately the sum of the van der Waals radii of oxygen and hydrogen (2.72 A ) . 3 9 Subsequent studies on substituted acetophenones revealed hydrogen atom abstraction to occur even for distances that exceed this sum. 4 0 Figure 1.13. The abstraction parameters defining the spatial relationship for the abstraction of a hydrogen atom by the excited carbonyl oxygen atom, d = distance between oxygen and hydrogen, O - H ; 0 = 0---H-C angle; A = C = 0 - H angle, and co = dihedral angle formed between the O - H vector and its projection on the nodal plane of the C=0 group. For hydrogen atom abstraction to take place, there must be substantial overlap between the non-bonding n-orbital of the oxygen atom and the hydrogen atom that is to be abstracted. This n-orbital is in the nodal plane of the n bond, and the optimal placement of the abstractable hydrogen atom should also be in this plane 4 1 resulting in an ideal co value of 0°. The slowest rate of reaction would occur when the hydrogen atom is orthogonal to the plane (i.e. co = 90°). However, there are many documented 20 Chapter 1 Introduction cases in which co is much larger than 0°, and hydrogen abstraction has been found to occur in solid complexes of acetophenone and deoxycholic acid even when co is 33 42 90°. ' Consequently, a small value of co is not strictly required for reaction. Wagner has suggested that the rate of reaction may be cos2co dependent.43 As mentioned previously, the favoured transition state arrangement for hydrogen atom abstraction is a linear C-H - - -0 orientation (0 = 180° ) . 4 4 Because this is not possible, values of 0 significantly less than 180° have been found. 3 3 ' 3 8 ' 4 3 The optimal value of the C = 0 - H angle A also varies.45 The ideal values of the geometrical parameters that describe hydrogen atom abstraction are summarized in Table 1.1.32 Table 1.1. Ideal values of the geometric parameters for hydrogen atom abstraction by an excited carbonyl oxygen. d (A) c o n A ( ° ) e n 2.7 0 90 - 120 180 1.7. Crystal Concepts and Crystal Packing Optically pure compounds are required to crystallize in space groups with no inversion centres or mirror planes 4 6 There are 65 of these so-called chiral space groups. Achiral molecules are not restricted in this manner, though they usually crystallize in centrosymmetric space groups.47 However, in the process of spontaneous 21 Chapter 1 Introduction resolution, achiral molecules can crystallize in a chiral space group, but there is equal probability of crystals of either "handedness" being present, as demonstrated by Pincock and co-workers.48 Various environmental effects, intentional seeding, and stirring can cause the formation of enantiomorphously-pure crystals 4 9 Chiral crystals are media for solid state photochemical asymmetric synthesis. 1.8. Asymmetric Induction in the Solid State: Crystal to Molecular Chirality Transfer As knowledge of chirality in molecules increased in the last few decades, the physical phenomena responsible for asymmetry have become better understood, and the demand for optically active compounds has expanded tremendously.50 Not only are chiral molecules desirable, but the ability to synthesize these compounds in high optical purity is enticing.51 Single enantiomers are produced in numerous ways. The earliest method of resolution was by mechanically separating enantiomorphous crystals grown from solution. This time-consuming method was labour-intensive and only applicable to 52 enantiomers which spontaneously resolved into enantiomorphous crystals. Modern 53 chromatographic techniques have enabled much more efficient separations, but are still beleaguered by the problem of discarding the unwanted enantiomer. The search for an improved method that saves time, material, and money, has led to enzymatic 22 Chapter 1 Introduction processes that often mimic nature's method of biosynthesizing chiral compounds. Asymmetric synthesis is another approach to solving this dilemma. Asymmetric synthesis is the process in which an achiral or racemic unit is converted into a chiral unit in unequal amounts.54 The synthesis is measured in terms of enantiomeric excess (e.e.). When diastereomers are produced, the term diastereomeric excess (d.e.) is used. Equations 1 and 2 define the e.e., in which R and S are the two enantiomers, and d.e., in which A and B are the two diastereomers. Specific rotations are indicated by the symbols [oc]mj x and [oc]pU r e for a (+/-)-mixture and an optically pure sample, respectively. e.e.% = [ S ] x 100% = %R-%S= x 100% E q ' 1 [R] + [S] [a] pure d.e.% = [ A ] [ g ] x 100% = % A - %B E q ' 2 [A] + [B] Asymmetric synthesis can be achieved by the use of chiral solvents, reactants, and auxiliaries, which result in energetically unequal diastereomeric transition states in which one enantiomer (or diastereomer) is generated preferentially. In solution state photochemical reactions, use of these methods typically gives low e.e. or d.e. because molecules are too loosely coordinated to assert a definite asymmetric influence over one another. 23 Chapter 1 Introduction Enantiomorphously pure crystals can provide optically active environments for solid state reactions. The first demonstration of successful asymmetric synthesis in the crystalline medium was by Schmidt and co-workers in 1969.55 They found that treatment of single crystals (space group P2\2\2\) of achiral 4,4'-dimethyl-chalcone (29, Figure 1.14) with gaseous bromine, produced the chiral dibromide in 6% e.e. This process in which an achiral starting material is converted to a chiral photoproduct without the use of any chiral auxiliaries, was termed absolute asymmetric synthesis. The first photochemical absolute asymmetric synthesis was reported by the same research group in 1973, in which they revealed that [2 + 2] photodimerization of compounds 31 and 32 (Figure 1.15) in crystals with the space group P2\2\2\ affords up to 70% e.e. of heterodimers 35(a-b).56 Absolute asymmetric [2 + 2] photodimerizations of single component crystals (36, Figure 1.16) have been known since 1982.57 24 Chapter 1 Introduction Chapter 1 Introduction Photochemical absolute syntheses using unimolecular reactions have also been successful. Absolute asymmetric synthesis has been observed in intramolecular [2 + 2] photocycloadditions (38),58 the di-rc-methane rearrangement (40), 5 9 ' 6 0 ' 6 1 and Norrish/Yang photocyclization (42) (Figure 1.17).59 Figure 1.17. Unimolecular absolute asymmetric synthesis in chiral crystals. 26 Chapter 1 Introduction 1.9. The Ionic Chiral Auxiliary in Asymmetric Synthesis Although the concept of absolute asymmetric synthesis is an exciting one, it has the disadvantage of requiring the spontaneous resolution of achiral molecules into chiral space groups; crystallization in chiral space groups is both difficult to predict and also rare. An alternate approach is to force an achiral compound into a chiral space group by the addition of an externally resolved chiral auxiliary. This is achieved practically by co-crystallizing an achiral photoreactive compound with a photostable but optically pure counterpart. Because the optically pure molecule is present, crystallization in a chiral space group is essentially secured. Co-crystallization of neutral molecules is best achieved with the formation of complexes. Crystalline complexes of a dibenzobarrelene derivative (44, Figure 1.18) with optically active diphosphine oxides 46 were found to yield 45a and 45b in low to moderate e.e. upon irradiation.62 27 Chapter 1 Introduction ph" 46 Ar = p-Tolyl, m-Tolyl, CO,H .C0 2 H Et0 2 C EtQ 2C hv, P 2,2,2, %> R = i-Pr, Et 44 45a 45b Figure 1.18. Asymmetric induction using crystalline complexes. The Ionic Chiral Auxiliary Concept takes the two component method a step further by employing acid-base chemistry.63 Prochiral acids and amines can be forced to crystallize in chiral space groups by the formation of salts with resolved amines or acids, respectively. This approach has numerous advantages because the organic salts formed: (1) have strong intermolecular forces, (2) can be brought to higher levels of conversion with topotactic control, (3) have higher melting points than molecular crystals, (4) and permit the easy removal of the ionic chiral auxiliary. The concept relies on the differences in energy between the diastereomeric transition states leading to product formed in the crystal structure. One of the transition states will be higher in energy than the other, and the reaction will favour the 28 Chapter 1 Introduction formation of the photoproduct derived from the lower energy transition state (Figure 1.19). 0 coo © (-)-Chiral product A © © (+)-Chiral product coo 0 © J Photolysis in the crystalline state 0 © COO w Chiral Crystal Acid-base reaction ,COOH Achiral acid Photoreactive substrate + 1 "H J Optically active amine Auxiliary Figure 1.19. Differences in diastereomeric transition state energies in a chiral crystal as a consequence of the Ionic Chiral Auxiliary Concept. Several examples in which high enantioselectivities were obtained using ionic chiral auxiliaries are illustrated below in Figures 1.20 - 1.22. Solution reactions of these compounds resulted in racemic photoproducts, as expected. The solid state di-rc-methane rearrangement of salts 47 and 49 gave high optical yields, demonstrating that the method works regardless of whether the photolabile compound is an acid or an 29 Chapter 1 Introduction amine.64 Salt 51 undergoes the Norrish type II reaction in the solid state, yielding a product with high optical purity.65 In addition, the reaction of 51 to 52 was found to be a single crystal-to-single crystal reaction,66 a rare find in solid state organic photochemistry.67 co2x Figure 1.20. Asymmetric induction of a carboxylic acid and a chiral amine via the di-rc-methane rearrangement. E = ester Figure 1.21. Asymmetric induction of an amine and a chiral carboxylic acid via the di-rc-methane rearrangement. 30 Chapter 1 Introduction > 96% e. e. Figure 1.22. Asymmetric induction of a carboxylic acid and a chiral amine via the Norrish type II reaction. 1.10. Research Objectives This thesis reports the use of single crystal X-ray crystallography in order to determine structure-reactivity relationships in solid state photochemical reactions. The role of the crystalline environment in influencing asymmetric synthesis was examined in two different photochemical reactions: electrocyclization of enamide I, and hydrogen atom abstraction by a carbonyl group in the systems III - VI, XI, and XVI (Figure 1.23). 31 Chapter 1 Introduction x UJ o n= 1,2,3,4 X = H, F, Cl, Br HI - VI X X XI XVI 0 © 0 © Y = F, CN, C 0 2 C H 3 , COO NH 3 R* X = F, Cl, Br, CN, COO NH 3 R* Figure 1.23. Systems studied in this thesis. The study of the solution and solid state photo-reactivity of enamide system I served three purposes. The first goal was to investigate this system as a candidate for absolute asymmetric synthesis. The second was to evaluate the effects of conformational chirality on crystal packing. The third was to study the effects of meta- and para-halogen substituents on the space group. The results of these studies comprise Chapter 2 of this thesis. The studies presented in Chapters 3 to 5 concentrate on the reactions involved in hydrogen atom abstraction by carbonyl-containing compounds. Compounds III -VI were designed to probe the effect of the crystal structure on product selectivity; the goal was to obtain a detailed understanding of the partitioning of the 1,4-biradical 32 Chapter 1 Introduction intermediates formed from the Norrish type U reaction. Compound XI was studied as an extension to the Norrish type U reaction. 8-Hydrogen atom abstraction was examined in the solid state photochemistry for compound XVI. Finally, the primary goal of asymmetric induction in the photochemistry of optically active salts of chiral amines with the carboxylic acid derivatives of XI and XVI, was achieved with the use of the Ionic Chiral Auxiliary Concept. 33 Chapter 1 Introduction 1.11. 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Tetrahedron Lett. 1992, 33, 5481. 6 6 Leibovitch, M . ; Olovsson, G.; Scheffer, J. R.; Trotter, J. J. Am. Chem. Soc. 1998, 120, 12755. 6 7 Examples found in the literature include: (a) Kobatake, S.; Yamada, T.; Uchida, K.; Kato, N . ; Irie, M . J. Am. Chem. Soc. 1999, 121, 2380. (b) Suzuki, T.; Fukushima, T.; Yamashita, Y . ; Miyashi, T. J. Am. Chem. Soc. 1994,116, 2793. (c) Enkelmann, V. ; Wegner, G.; Novak, K.; Wagener, K. B. J. Am. Chem. Soc. 1993,115, 10390. (d) Novak, K. ; Enkelmann, V. ; Wegner, G.; Wagener, K. B. Angew. Chem. Int. Ed. Engl. 1993, 32, 1614. (e) Vaida, M . ; Popovitz-Biro, R.; Leiserowitz, L . ; Lahav, M . In Photochemistry in Organized and Constrained Media; Ramamurthy, V. , Ed; Verlag 40 Chapter 1 Introduction Chemie: New York, 1991; Chapter 6. (f) Ohashi, Y . Acc. Chem. Res. 1988, 21, 268. (g) Wang, W.-N.; Jones, W. Tetrahedron 1987, 43, 1273. (h) Tieke, B. J. J. Polym. Sci., Polym. Chem. Ed. 1984, 22, 2895. (i) Miller, E.; Bril l , T. B.; Rheingold, A. L. ; Fultz, W. C. J. Am. Chem .Soc. 1983, 105, 7580. (j) Hasegawa, M . Chem Rev. 1983, 83, 507. (k) Thomas, J. M . Nature 1981, 289, 633. (1) Thomas, J. M . ; Morsi, E. E.; Desvergne, J. P. Adv. Phys. Org. Chem. 1977, 15, 63. (m) Cheng, K. ; Foxman, B. J. Am. Chem. Soc. 1977, 99, 8102 (n) Wegner, G. Pure Appl. Chem. 1977, 49, 443. (o) Osaki, K. ; Schmidt, G. M . Isr. J. Chem. 1972,10, 189. 41 Chapter 2 Results/Discussion Chapter 2 Conformational Chirality and the "meta- Steering" Effect in the Crystal Packing and Photochemistry of Enamides 2.1. General Considerations X = halogen Figure 2.1. /V-Benzyl-/V-(3,4-Dihydro-l-naphthyl)benzamide. The enamide system (I, Figure 2.1) belongs to a class of compounds which is formally achiral, yet can adopt a conformation that is non-superimposable on its mirror image. Rotation around the single bonds between moieties gives rise to these chiral conformations. If interconversion is slow between the enantiomers of these chiral conformations, it is possible that these enantiomers can be resolved.1 This type of enantiomerism, in which a formally achiral molecule can become non-superimposable on its mirror-image through rotational isomerism, was first discovered in meta-substituted biphenyl derivatives (53), which were found to adopt non-planar conformations (Figure 2.2) 2,3 42 Chapter 2 Results/Discussion C0 2H H0 2C f/—{H°2C^, > c ° 2 H ) ^ Q^ >=> — <=^Q \ 0 2N ^ N 0 2 / ) ' N 0 2 0 2N 53 Figure 2.2. Enantiomeric chiral conformations of 6,6'-dinitro-2,2'-diphenic acid. The spontaneous resolution of binaphthyl (54, Figure 2.3) into enantiomorphous crystals (space group P4i2i2) has been studied extensively in a series of elegant experiments performed by Pincock and co-workers.4 Using carefully controlled conditions, this compound can be crystallized so that only one of the two enantiomers is primarily obtained, thus generating spontaneously optical activity from an achiral substrate. Derivatives of this compound have been widely studied, and have been used as sensitizing agents in solution photolyses. Reports of the acceptor molecules affording small amounts of enantio-enriched photoproducts stemming from the binaphthyl derivatives' conformational chirality have been documented.5 Figure 2.3. U'-Binaphthyl (54).6 43 Chapter 2 Results/Discussion Benzophenone (55, Figure 2.4) is another well-known example of an achiral compound which crystallizes in a chiral space group (P2i2^2i). 7 Its derivative, 4-o methylbenzophenone (56, Figure 2.4), also crystallizes in a chiral space group (P3j). The derivative 4,4'-dimethylbenzophenone (57, Figure 2.4) was found to crystallize in chiral space group P2\l\l\, and undergo a photochemical reaction.9 The reaction proceeds via an intermolecular hydrogen atom abstraction to yield the adduct 58. Figure 2.4. The structures of benzophenone (55) and its substituted derivatives 56 and 57. The derivative 4,4'-dimethylbenzophenone (57) is photolabile and undergoes an intermolecular hydrogen atom abstraction. These examples demonstrate that when enantiomers of formally achiral molecules crystallize out of solution and aggregate into a solid, there arises the 44 Chapter 2 Results/Discussion possibility that the compounds will crystallize as if they are truly chiral, and spontaneously resolve into crystals of either hand.10 As our goal of absolute asymmetric synthesis relies on the asymmetry of the crystal environment, studying whether the conformationally chirality of the enamide system (I) will promote crystal packing in a chiral space group is particularly intriguing. 2.2. The "meta-Steering Effect" Achiral compounds possessing meta-substituted aromatic moieties are also known to crystallize spontaneously in chiral space groups.11 This phenomenon may be partially explained by the existence of a "mefa"-crystal packing effect that causes aromatic compounds containing meta-substituents to favour crystallization in polar space groups.1 2'1 3 By definition, chiral space groups cannot possess roto-inversion symmetry elements, and thus, are necessarily polar. The meta-chloro substituted a-oxoamide 59b shown in Figure 2.5 was found to crystallize in P2\2\2\, and yield optically pure lactam 60b upon irradiation.14 On the other hand, the ortho- and para-chloro substituted compounds 59(a,c) crystallized in achiral space groups, P2\ln and Pbca, respectively. The conformation of 59b was different from those of 59a and 59c, and the rate of cyclization of 59 to 60 occurred in the order of meta » para > ortho. Crystallographic analysis of 59b revealed that a -8° to -11° rotation of its phenyl ring is necessary for photocyclization to 60b, whereas the ortho- and para-substituted compounds 59(a,c), require more sterically demanding 45 Chapter 2 Results/Discussion 38° rotations. These large rotations are restricted by intermolecular repulsions from the walls of the crystal cavity. •Me 'Pr (a) X = o-Cl (b) X = m-Cl (c) X = p-C\ Figure 2.5. The photochemical reaction of a substituted a-oxoamide (59). The meta-substituted derivatives of 2-pyridone 61 (Figure 2.6) were found to crystallize in P2\l\2\, whereas the ortho- and para-substituted compounds crystallized in achiral space groups.15 When compounds 61(a-d) were used in asymmetric synthesis studies, enantiomeric excesses as high as 90% were achieved, indicating synthetic viability. 46 Chapter 2 Results/Discussion I or H 61 hv, Pyrex crystal o -NH 62 (a) X = m-Cl (b) X = m-Me (c) X = m-OMe (d) X = w-Br (e) X = H (f) X = o-Cl (g) X = p-Cl (h) X = p-f-Bu Figure 2.6. Photochemical rearrangement of substituted 4-benzyloxy-2-pyridone derivatives (61). Based on the examples seen thus far, the idea that conformationally chiral molecules incorporating meta-substituents can be designed to crystallize in chiral space groups does not seem far-fetched. It is with this thought in mind that the formally achiral enamide system I (Figure 2.1), with its numerous localities available for meta-substitution, was chosen for study. Synthesis of meta-substituted halogen derivatives of I, followed by comparisons of their photochemistry and crystal structures with the corresponding unsubstituted and para-substituted derivatives, could point the way to making absolute asymmetric synthesis and chiral crystal packing more predictable. 47 Chapter 2 Results/Discussion 2.3. The Photochemistry of Af-Benzyl-AK3,4-Dihydro-l-naphthyl)-Benzamide A survey of the literature for the photochemistry of the enamide system I was undertaken to assess its potential in solid state asymmetric synthesis. The photochemistry of the unsubstituted enamide, la (Figure 2.7), was briefly studied by Ninomiya and co-workers.16 They reported that la reacted in solution via an electrocyclic ring closure followed by a 1,5-sigmatropic hydrogen shift (Figure 2.8) to yield a trans-fused ring system possessing two new chiral centres (Ha). The photocyclization is reversible, and a stable photoproduct is formed after the thermal aromatization of the initial cyclized intermediate. In Ninomiya's work, there was no evidence of the intermediate cyclization product, and the re-aromatization step was concluded to be very fast and the driving force of the reaction. enantiomer Figure 2.7. The photoelectrocyclization of JV-benzyl-./V-(3,4-dihydro-1 -naphthyl)benzamide (la). 48 Chapter 2 Results/Discussion la Ila Figure 2.8. Mechanism of the electrocyclization of la . The key requirement for this reaction is the presence of a well-conjugated system of p-orbitals in the dipolar resonance form needed for a concerted photocyclization process. Photocyclizations of bulky aromatic compounds in solution may be slow because only a small population of the molecules at any one time is in the 17 conformation having the proper geometry for a concerted reaction. This has implications in the solid state, where steric difficulties in achieving the reactive conformation may prevent the starting materials from reacting photochemically. 49 Chapter 2 Results/Discussion 2.4. Photochemical and Crystallographic Studies of Enamide Derivatives No interest in compound la was shown again until the 1990's, when solid state 18 studies were performed on la, and it was found to be photostable. Nevertheless, this system remained appealing, as the photochemistry of its halo-derivatives had yet to be studied, and their conformations and packing in the crystalline state were unknown. Thus, we began photochemical and crystallographic investigations of these compounds, and the results of my work are discussed from this point to the end of the chapter. 2.5. Synthesis of Halo-substituted Enamides Derivatives of A^-benzyl-A^-(3,4-dihydro-l-naphthyl)benzamide (la) were synthesized by the process shown in Figure 2.9. An imine was formed from cc-tetralone, which was then reacted with the acid chloride to yield the final enamide. Three para-substituted derivatives were synthesized, the para-fluoro, para-chloro, and para-bromo (I(b-d)), along with three me/a-substituted derivatives (I(e-g)). The products were isolated and spectrally characterized, and purified compounds were used for photochemical studies. X-ray quality crystals were eventually obtained for all the starting enamides. 50 Chapter 2 Results/Discussion + n 2 H 7 N I (a) X = H (b) X = para-F (c) X = para-Cl (d) X = para-Br (e) X = meta-F (f) X = meta-C\ (g) X = meta-Br Figure 2.9. Synthesis of enamides I(a-g). 2.6. Photochemistry of the Halo-substituted Enamides Irradiation of compounds I(b-g) in methanol solution yielded the fused ring system II (Figure 2.10) that Ninomiya found from photolysis of la. hv, Pyrex solution S^ 1 enantiomer (b) x = F, Y = H (c) X = Cl, Y = H (d) X = Br, Y = H (e) Y = F, X = H (f) Y = C1,X = H (g) Y = Br,X = H Figure 2.10. Photochemistry of the halo-substituted enamides I(b-g). 51 Chapter 2 Results/Discussion In general, conversions greater than 90% are obtainable after 20 hours of irradiation, with 100% conversions achievable after 25 hours. X-ray crystal structures of photoproducts H(f-g) were determined from crystals obtained from solution after numerous recrystallization attempts. When enamides I(a-g) were irradiated in the solid state, they exhibited the same photostability as that of la , unfortunately indicating that neither the nature of the halogen nor the location of the substituent affects the reactivity. 2.7. X-ray Crystallographic Analysis of the Enamides The nature of the photostability of these enamides was addressed from the data obtained via crystallographic studies. X-ray diffraction experiments were carried out on single crystals of each of the materials I(a-g), revealing that the compounds crystallize with two different motifs occurring simultaneously: (1) a chiral conformation regardless of space group or substitution, and (2) a two-fold screw axis regardless of the crystal system (Table 2.1). The chiral conformation of the enamides can be seen from the ORTEP diagrams illustrated below in Figures 2.11 - 2.17. 52 Chapter 2 Results/Discussion Table 2.1. Crystallographic data of the enamides I(a-g).' Compound a b c P V(A 3) Space Group la 9.6818(7) 20.024(3) 9.386(1) 90 1819.7(3) P 2 i 2 i 2 i lb 9.8754(6) 9.7644(5) 19.628(2) 99.197(3) 1868.4(2) P2\lc Ic 20.850(5) 9.597(2) 21.181(4) 108.21(2) 4026(2) P2\la Id 11.980(2) 9.495(2) 17.927(2) 92.244(9) 2037.7(6) P2\ln le 9.747(2) 20.087(4) 9.472(5) 90 1854(1) P 2 i 2 i 2 i If 12.574(2) 9.822(2) 15.523(3) 90.41(1) 1917.1(5) P2\ln Ig 12.627(2) 9.843(2) 15.334(7) 90.88(1) 1905.5(8) P2\ln Figure 2.11. ORTEP diagram of la. 1 The a and y angles are 90° in these compounds. Complete crystallographic data are presented in Chapter 7. 53 Chapter 2 Results/Discussion Chapter 2 Results/Discussion Chapter 2 Results/Discussion Chapter 2 Results/Discussion By observing the conformations of the substituted and unsubstituted molecules, we can see that the halogen atoms, regardless of their size or placement, do not alter the general conformation of la. Cyclization to photoproduct II in these compounds requires two geometric features: (1) a favourable separation distance between the two centres that form the new bond; (2) good conjugation among the p-orbitals that will allow a concerted reaction involving a three electron pair pericyclic process to occur. Cyclization entails the formation of a bond between either C9 and C20 or C9 and C24. The distances separating these atoms are listed in Table 2.2. Typically, separation distances up to the sum of the van der Waals radii of the two reactive atoms allow cyclization to take place in well-conjugated systems (the sum of the van der Waals radii for two carbon atoms is 3.4 A). The distances from C9 to C24 fall within this range for the majority of the compounds, with distances from C9 to C24 consistently shorter than those from C9 to C20. The second geometric requirement is of greater importance. Pericyclic reactions by their very nature involve the movement of electrons delocalized among conjugated p-orbitals. Without this conjugation, concerted processes cannot occur. Conjugation increases as systems become planar, but this planarity is clearly impossible for I because of enormous steric repulsions between the rings as the system is flattened. The further the system deviates from planarity, the lower the conjugation. Figures 2.18 and 2.19 depict the atomic arrangement of I in the well-conjugated and poorly-conjugated cases, respectively. 57 Chapter 2 Results/Discussion Table 2.2. Distances, angles, and least-squares planes derived from crystallographic data. Compound Distances from X-ray Crystallographic Data (A) Dihedral Angle At (°)f C9 to C20 C9 to C24 la 4.085 3.366 71.6 Ib 3.898 3.404 70.4 Ic 4.137 3.376 79.1 4.070* 3.383* 77.2* Id 4.070 3.393 78.5 le 4.109 3.341 75.7 If 3.988 3.506 77.5 Ig 3.983 3.518 76.5 Hf n/a 1.492 28.6 n/a 1.491 28.0 fThis is the dihedral angle formed between the least-squares planes of the following atoms: (C19-C20-C21-C22-C23-C24) and (C1-C6-C7-C8-C9-C10). *lc crystallizes with two molecules in the asymmetric unit; these are the corresponding values for the second molecule. Figure 2.18. Top view of an ideally conjugated enamide system. The atoms involved in the electrocylic ring closure (C9-C10-N1-C18-C19-C24) are labelled. 58 Chapter 2 Results/Discussion Figure 2.19. The twist of the benzoyl phenyl group from planarity with the amide reduces conjugation between these two moieties, and the almost orthogonal spatial arrangement between the [3H,4H]-dihydronaphth-l-yl ring and the amide prevents the two from being well-conjugated. The ORTEP diagrams of the seven enamide reactants and Figure 2.19 show quite clearly that the molecules are not planar, resulting in poor p-orbital conjugation among the atoms involved in the electrocyclic reaction. The dihedral angle Ai (Table 2.2) ranges from 70° for lb to 79° for Ic. The torsional angle of C9-C10-N1-C18 (designated Ti) reflects the degree of conjugation between the amide and the [3F£,4H]-dihydronaphth-l-yl moiety, and the torsional angle of N1-C18-C19-C24 (designated T2) reflects the degree of conjugation between the carbonyl group and the halo-substituted aromatic ring. The values for these torsional angles are 0° for a planar system, but as the data in Table 2.3 and the ORTEP diagrams in Figures 2.11 - 2.17 illustrate, these angles deviate significantly from 0°. This is a good indication that electrocyclic reactions cannot occur with such large angular deviations from planarity between the double bonds involved in the reaction. Without a conjugated system of three electron pairs present, the double bonds of the atoms that are involved in the 59 Chapter 2 Results/Discussion cyclic process would simply possess the reactive properties of isolated alkenes, thus precluding the possibility of a concerted reaction." Table 2.3. Torsional angles Xi and Xi. Compound T2 la -122.9(2) 44.6(3) lb -116.2(3) 51.2(4) Ic -123.3(5) 41.8(7) 125.3(5)* -43.2(7) * Id -124.8(3) 43.3(5) le -119.8(4) 43.2(6) If -118.4(2) 50.8(3) Ig -117.6(5) 52.4(7) Ilf 179.8(3) -21.7(4) Ug 179.7(3) -21.1(4) *for Ic, the corresponding torsional angles of the second molecule are xC25-C34-N2-C42 and xN2-C42-C43-C48. The role of the surrounding crystalline environment of each molecule was also considered in order to determine whether rotation of the rings to a conjugated and reactive conformation in the solid state is possible. The ellipsoids in the ORTEP diagrams do not display any irregular shapes that would suggest motion is occurring in the crystal structure. A drawing of the reaction cavity can be constructed by performing volume calculations of the free space of the cavity after the molecule of interest is removed. Reaction cavities were calculated assuming that the neighbouring atoms have spheres of radii greater than their van der Waals radii by 1.2 A . 1 9 " It is conceivable that a [2 + 2] photocycloaddition between the localized electrons of C9-C10 and C19-C24 could occur instead of an electrocyclic reaction, but the lack of product formation indicates that this reaction does not occur at this radiation wavelength. 60 Chapter 2 Results/Discussion Figure 2.20 depicts the space that surrounds a molecule of Ib. The rotational motion of the [3H,4H]-dihydronaphth-l-yl ring is clearly restricted by the walls of the reaction cavity. The cavity diagrams for enamides I(a,c-g) are virtually identical to that of Ib. The X-ray crystal structures of photoproducts Il(f-g) (Figures 2.21 - 2.22) display a molecular shape that is quite different than the reactant in the crystal cavity. Figure 2.20. The reaction cavity of Ib. 61 Chapter 2 Results/Discussion C 1 6 ( f V C 1 5 ^ Figure 2.21. ORTEP diagram of photoproduct Hf showing the trans-C9-ClO junction. Figure 2.22. ORTEP diagram of photoproduct Hg showing the frans-C9-C10 junction. 62 Chapter 2 Results/Discussion The difference in atomic positions between the starting enamide and its photoproduct can be quantified by superimposing the coordinates of the photoproduct onto those of the starting material, and then refining the initial atomic fit by iterative least-squares to minimize the sum of the squares of the deviations of equivalent atoms.20 A root-mean-square misfit value (r.m.s.) is obtained, with a lower value indicating a better fit. Table 2.4 lists the atoms of reactant If and photoproduct Hf that exceed 1 A difference in displacement after the r.m.s. calculation. Figure 2.23 shows the overlay of these two structures. Table 2.4. Differences in displacement (> 1 A) of atoms in If and Hf after superimposition and least-squares.'" Atom Displacement Difference (A) Atom Displacement Difference (A) C l 1.28 C9 2.18 C2 3.59 C13 1.65 C3 4.90 C14 1.92 C4 3.97 C15 1.30 C5 1.81 C16 1.45 C7 2.31 C17 1.34 C8 2.53 C23 1.03 See Figure 2.16 and Figure 2.21 for the numbering schemes of If and Hf. 63 Chapter 2 Results/Discussion Figure 2.23. Superimposition of the photoproduct H f (dark) onto the reactant If (light). The maximum atomic displacement between the starting material and the photoproduct is 4.9 A for atom C3. This is a very large displacement, and the torus of atoms that is generated from rotation of C3 around the N1-C10 bond would spatially exceed the confines of the reaction cavity. The difference in the torsional angles Ti and t2 (Table 2.3) of If and its photoproduct Hf are 62° and 29°, respectively. Thus, the enamides crystallize in conformations which are chiral, but unreactive. 64 Chapter 2 Results/Discussion 2.8. The "meta-Steering" Effect on Crystal Packing Although all seven crystal structures have the same conformation, they do not all share the same packing arrangement. Studies of the crystal packing of I(a-g) can offer insight into the effects of halo-substitution. Crystals of l a and le are isostructural, indicating that the fluorine atom in le introduces minimal substituent effects into the parent crystal structure, and demonstrating that the crystal packing of le relies primarily on its structural similarity to the conformation present in the crystal of la . This favoured chiral conformation of I has a profound effect on the way that the molecules pack together in the crystal. Despite the introduction of halogen substituents, one motif common to all seven enamides is the 2i-screw axis. The space groups of the enamides are either P2\2\2\ or P2\lc (and its other two settings, P2\la and P2\ln). Compounds l a and le are enantiomerically resolved by their crystallization in P2\2\2\, whereas the other enamides crystallize as racemates. Packing diagrams of I show the relationship of the molecules across the screw axes (Figures 2.24 - 2.30). It is apparent from these diagrams that this structural packing motif is conserved for all the seven compounds. 65 Chapter 2 Results/Discussion Figure 2.24. The packing diagram of la . A 2i-screw axis is parallel to the a-axis. Figure 2.25. The packing diagram of le. This meta-fluoro derivative's crystal structure is isostructural to la . Rotation and translation around a 2i-screw axis generate the symmetry-related molecules. 66 Chapter 2 Results/Discussion Figure 2.26. The packing diagram of If. Rotation and translation around a 2i-screw axis generate the symmetry-related molecules. Figure 2.27. The packing diagram of Ig. This meta-bromo derivative's crystal structure is isostructural to If. 67 Chapter 2 Results/Discussion Figure 2.28 The packing diagram of lb. Rotation and translation around a 2i-screw axis generate the symmetry-related molecules. 68 Chapter 2 Results/Discussion Figure 2.29. The packing diagram of Ic. Two molecules of Ic are present in the asymmetric unit, and a molecule of methanol resides on a centre of symmetry. Figure 2.30. The packing diagram of Id. Rotation and translation around a 2i-screw axis generate the symmetry-related molecules. A molecule of methanol resides on a centre of symmetry. 69 Chapter 2 Results/Discussion A crystal structure containing solvent is usually an indication that the molecules do not crystallize well on their own, and solvent inclusion is necessary to stabilize the crystal packing.21 This observation explains some of the experimental difficulty in recrystallizing enamides Ic and Id. The crystal structure of Id contains destabilizing voids, even after the disordered methanol is modelled, with 48 A 3 cavities existing in the crystal structure. A close-packing calculation reveals that the 22 packing coefficient is 67.5%, which is a little lower than that found for most organic compounds. Yet despite the solvent in the crystal structures, I(c,d) still possess x\ and %2 values almost identical with the other enamides. The 2^-screw axis is present even when solvent is incorporated in these crystal structures. Cyclization of I to II reduces flexibility of the molecule because a new bond is formed between C9 and C24. The crystal structures of compound II no longer possess the 21-screw axis that is present in all the reactant crystals. A higher symmetry in the crystal packing of Il(f-g) occurs, with these derivatives adopting the C-centred space group C2/c instead of P2\/c adopted by its reactant precursors I(f-g). The meta-substitution in Hf and Ug do not bring about spontaneous resolution of these compounds into chiral space groups. The packing diagrams of photoproducts Il(f-g) are shown below in Figures 2.31 - 2.32. 70 Chapter 2 Results/Discussion 71 Chapter 2 Results/Discussion 23 The halogen group is notable for its substituent cooperative effect, in which atoms of the same family may replace one another and retain the isostructural crystal packing. Hence, if one halo-substituted compound crystallizes in a chiral space group, there is a high probability that its analogues will also crystallize in this space group. However, the crystal data for I(a-g) show isostructural trends in only the meta-substituted chloro- and bromo-compounds I(f,g), and these derivatives do not crystallize in chiral space groups. Introduction of a meta-substituent has actually resulted in the enamide molecule crystallizing in an achiral space group. These results reveal the unpredictable nature of crystal packing, and illustrate the limitations of relying on halogen atoms and the "meta-steering effect" as synthons for crystal engineering and asymmetric synthesis.IV Intermolecular halogen-•-halogen interactions are often important in crystal packing.2 4 These interactions do not appear to be significant in the crystal packing of I(a-g). In the unsubstituted enamide la, there are no such interactions, and crystallization occurs without the aid of these contacts. Compound le, which is isostructural to la, does not display significant F---F interactions. This is not unexpected because F---F contacts have never been fully substantiated as being structure-determining.25 Substitution at the meta-position by the larger halogens, chlorine and bromine, changes the space group of the crystal structure. Examination of the packing diagrams and halogen-•-halogen distances indicate that there are no 1 V A synthon is a structural unit within a molecule which can be formed or assembled by known or conceivable units (Corey, E. J. Pure Appl. Chem. 1967, 14, 19). A "supramolecular synthon" is a structural unit assembled using intermolecular interactions (see reference 24a). 72 Chapter 2 Results/Discussion significant C1---C1 and B r - B r contacts in the crystal structures of compounds I(f,g). Thus, substituent size and not intermolecular halogen contacts is the likely reason why the meta-fluoro derivative can exist in the same crystal structure as la, whereas the meta-chloro- and meta-bromo-substituted derivatives do not crystallize in the same space group as la. The crystal structure of la does not appear to tolerate any substituent larger than a hydrogen atom at the para-position. The structural modification of la to I(b-d), which involves changes from hydrogen to fluorine, chlorine, and bromine on the periphery of the molecule, is enough to alter entirely the overall packing of the molecules while retaining the 2 \-symmetry element. 2.9. Conclusions Although unanswered questions remain regarding the generality of the "meta-steering" effect in promoting crystal packing, we can conclude that the meta-halogen substituents present in I(a-g) do not alter the molecular conformation of I. The preferred conformation of I favours the presence of a screw axis in the crystal structures. However, this conformation does not undergo photochemical electrocyclization in the crystalline state despite the proximity of the carbon atoms which can potentially form a new bond. In solution, where the conformation is free to change, the correct geometry needed for electrocyclic ring closure is achievable, and photoproduct II is observed upon irradiation. 73 Chapter 2 Results/Discussion 2.10. References for Chapter 2 1 In the majority of cases, chiral conformations pack together in enantiomeric pairs in crystals; however, when interconversion between enantiomers of these formally achiral molecules is slow, such conformationally chiral molecules can spontaneously resolve into chiral crystals. For a discussion, see: Jacques, J.; Collet, Andre; Wilen, S. H . Enantiomers, Racemates, and Resolutions; John Wiley and Sons: New York, 1981; Chapter 1, and references cited therein. 2 Christie, G. H. ; Kenner, J. H. J. Chem. Soc. 1922,121, 614. Eliel, E. L . ; Wilen, S. H. Stereochemistry of Organic Compounds; Wiley and Sons: New York, 1993, Chapter 14, and references therein. 4 (a) Pincock, R. E.; Lu, M . D . -M. J. Org. Chem. 1978, 43, 601. (b) Pincock, R. E.; Wilson, K. R. J. Am. Chem. Soc. 1975, 97, 1414. (c) Pincock, R. E.; Perkins, R. R.; Ma, A . S.; Wilson, K. R. Science 1971,174, 1018. 5 Inoue, Y . Chem. Rev. 1992,92,741. 6 Duesler, E. N . ; Etter, M . C ; Paul, I. C ; Curtin, D. Y . J. Am. Chem. Soc. 1980,102, 7709. 7 Lobanova, G. M . Kristallografiya 1968,13, 984. 8 Kutzke, H . J. Mol. Struct. 1996, 374, 129. 9Ito, Y . ; Matsuura, T.; Tabata, K.; Meng, J.-B. Tetrahedron 1987, 43, 1307. 74 Chapter 2 Results/Discussion 1 0 For examples, see: (a) L'Esperance, R. P.; van Engen, D.; Dayal, R.; Pascale, Jr., R. A. J. Org Chem. 1991, 688, 56. (b) Kuroda, R.; Mason, S. F. Tetrahedron 1981, 37, 1995. (c) Lobanova, G. M . Kristallografiya 1968,13, 984. 1 1 (a) Bryant, G. L. , Jr.; Nye, S. A. Acta Crystallogr. 1992, C48, 389. (b) Williams, D. J.; Colquhoun, H . M . ; O'Mahoney, C. A. Chem. Commun. 1994,1643. 1 2 (a) Rez, I. S. Kristallografiya 1960, 5, 63. (b) Skrapski, A . C ; J. Chem. Soc, Perkin Trans. 1973, 2, 1197. 1 3 Curt in ,D. Y . ; Paul, I. C. Chem. Rev. 1981, 81, 525. 1 4 Hashizume, D.; Kogo, H. ; Sekine, A. ; Ohashi, Y . ; Miyamoto, Ff.; Toda, F. / . Chem. Soc, Perkin Trans. 2. 1996, 61. 1 5 Cheer, C. J.; Wu, L. ; Olovsson, G.; Scheffer, J. R.; Trotter, J.; Wang, S.; Liao, F. Tetrahedron. Lett. 1997, 3135. 1 6 (a) Ninomiya, I.; Naito, T.; Kiguchi, T.; Mori, T. / . Chem. Soc, Perkin Trans. 1 1973, 1696. (b) Ninomiya, I.; Naito, T.; Mori, T. / . Chem. Soc, Perkin Trans. 1 1973,505. (c) Ninomiya, I.; Naito, T.; Mori, T. Tetrahedron. Lett. 1969,3643. 1 7 Wu, J. Y . ; Ho, J. H . ; Shih, S. M . ; Hsieh, T. L . ; Ho, T. I. Org. Lett. 1999, 7, 1039. 18Personal communication from Professor Clair Cheer, Department of Chemistry, San Jose State University. 1 9 Ohashi, Y . ; Yanagi, K.; Kurihara, T.; Sasada, Y . ; Ohgo, Y . J. Am. Chem. Soc. 1981,103, 5805. 2 0 Gould, R. O.; Moulden, N . ; Taylor, P. IDEAL; University of Edinburgh, 1988. 2 1 Gavezotti, A . Crystallography Reviews 1998, 7, 5. 75 Chapter 2 Results/Discussion 2 2 Kitaigorodskii, A . I. Molecular Crystals and Molecules. Academic Press: New York , 1973. 2 3 (a) Kalman, A. ; Fabian L . Acta Crystallogr. 1999, B55, 1099. (b) Ianelli, S.; Nardelli, M . ; Giordano, C ; Coppi, L. ; Restelli, A . Acta Crystallogr. 1992, C48, 1722. (c) Kalman, A. ; Parkanyi, L . ; Argay, G. Acta Crystallogr. 1993, B49, 1039. 2 4 (a) Desiraju, G. Angew. Chem. Int. Ed. 1995, 34, 2311. (b) Bar, I.; Bernstein, J. Tetrahedron 1987, 43, 1299. (c) Ramasubbu, N . ; Parthasarathy, R.; Murray-Rust, P. J. Am. Chem. Soc. 1986, 108, 4308. (d) Durrand, A. ; Gerdil, R. Acta Crystallogr. 1984, B40, 59. (e) Durrand, A. ; Gerdil, R. Acta Crystallogr. 1982, B38, 570. (f) Murray-Rust, P.; Motherwell, W. D. S. J. Am. Chem. Soc. 1979,101, 4374. (a) Desiraju, G. R. In Crystal Engineering: The Design of Organic Solids; Elsevier: Amsterdam, 1989. (b) Desiraju, G. R. Acc. Chem. Res. 1986,19, 222. (c) Murray-Rust, P.; Stallings, W. C ; Monti, C. T.; Preston, R. K. ; Glusker, J. P. J. Am. Chem. Soc. 1983,105, 3206. 76 Chapter 3 Results/Discussion Chapter 3 The Partitioning of 1,4-biradicals in the Norrish Type II Reaction in Spiro-Benzoyladamantanes 3.1. General Considerations (III)n= 1, (IV)n = 2, (V)n = 3, (VI) n = 4 The 1,4-hydroxybiradical intermediates derived from the solid state photochemistry of a homologous series of spiro-benzoyladamantanes III -V I (Figure 3.1) undergo the full range of Norrish type II reactions - from cleavage to cyclobutanol formation (Figure 3.2) - making this system an excellent choice for solid state studies of structure-reactivity Figure 3.1. The spiro-benzoyladamantane system. relationships by X-ray crystallography. Although the multitude of Norrish type II photochemical studies performed in the last few decades has revealed that the Norrish 1,4-hydroxy biradical either cyclizes to form the cyclobutanol, cleaves its oc-P bond to form the enol, or reverts to reactant via reverse hydrogen atom abstraction, fundamental questions regarding the degree of orbital overlap that determines which of these reactions occurs have been left unanswered. An understanding of the basis for the selection between these pathways is desirable as it allows prediction of which photoproducts are generated from the Norrish type II reaction. 77 Chapter 3 Results/Discussion cyclization (III) n = 1, (IV) n = 2, (V) n = 3, (VI) n = 4 1,4-biradical intermediate t cleavage Figure 3.2. Partitioning of the 1,4-biradicals formed from y-hydrogen abstraction of ketones III - VI . Previous studies of compounds closely related to the spiro-benzoyladamantanes III - V I (63, Figure 3.3) reveal that the solid state irradiations of such derivatives result only in cyclobutanols.1 Substitution at the para-position of the benzoyl group does not alter the reactivity of the biradical. Because no other photoproducts are formed, system 63 does not provide the structure-reactivity relationships needed for insight into the partitioning of the 1,4-biradicals. X = F, CN, COOH Figure 3.3. The photochemistry of an unconstrained adamantyl system 63. The title compounds III - V I are structurally similar to 63. 78 Chapter 3 Results/Discussion The advantage of the spiro-benzoyladamantanes III - VI lies in the fact that their key structural geometry, the orientation of the benzoyl moiety with respect to the adamantyl ring, can be controlled via ring size. The increase in the number of methylene units spiro to the adamantyl skeleton results in variations in the orientation of the carbonyl group that are specific to each ketone. Consequently, the biradicals generated from y-hydrogen abstraction have geometries dependent on the number of methylene units. By studying the reactions that occur as a result of these changes in structure, the effect of biradical geometry can be suitably correlated with photochemical product studies and knowledge derived from the X-ray crystal structures; thus, these studies enable insight into the factors that are responsible for the clear-cut specificity between cleavage, cyclization, and reverse hydrogen atom transfer among these intermediates. 3.2. Solid State Reactivity Compound III (n = 1) readily photolyzes to an oil in the solid state, which when isolated and characterized, is found to be the cleavage product VII (Figure 3.4). Compound IV (n = 2) does not react in single crystal form, but reacts in a suspension of water with a small amount of surfactant to form an interesting compound that is not the cyclobutanol expected from Yang cyclization (VIII, Figure 3.5). The seven- and 79 Chapter 3 Results/Discussion eight-membered ring ketones, V (n = 3) and V I (n = 4), both yield the expected Yang cyclobutanol photoproducts IX and X , respectively (Figure 3.6 - Figure 3.7). Chapter 3 Results/Discussion Figure 3.6. Solid state photochemistry of V. VI X Figure 3.7. Solid state photochemistry of VI . The X-ray crystal structures of these four starting ketones were determined, and the hydrogen abstraction parameters for the biradical intermediates were calculated (Table 3.1). The values in Table 3.1 show that the hydrogen atom abstraction process is favourable in all four compounds. The 5-membered ring spiro-benzoyladamantane III is distinct in having two y-hydrogen atoms nearly equidistant to the carbonyl oxygen, and so the parameters for both hydrogen atoms are included. The ideal parameters are also listed for comparison. 81 Chapter 3 Results/Discussion Table 3.1. Hydrogen atom abstraction parameters for the spiro-benzoyladamantanes.' Compound d(A) ton A( ° ) e n D(A) ideal <2.72 0 90 - 120 180 <3.4 III 2.36 41 90 124 3.03 2.32 24 98 121 3.08 IV 2.41 35 96 118 3.07 V 2.48 55 85 119 3.02 VI 2.34 41 94 121 3.05 By knowing that biradical formation is possible in all four ketones, we can focus the study on how the biradicals differ. The picture that chemists have so far consists of cleavage occurring from conformations in which there is overlap of the breaking sigma bond with the half-occupied p-orbitals at the two radical centres (Figure 3.8). Cyclization, on the other hand, is envisioned to be all the other cases in which there is poor orbital overlap for cleavage.3 Intuitively, it appears reasonable that Yang photocyclization will be favoured when the radical-containing carbon atoms C l and C4 are close to one another (i.e. probably < 3.4 A, which is the sum of the van der Waals radii for two carbon atoms). 1 The abstraction parameters define the spatial relationship for the abstraction of a hydrogen atom by the excited carbonyl oxygen atom, d = distance between oxygen and hydrogen, 0 - H ; c o = dihedral angle formed between the O - H vector and its projection on the nodal plane of the C=0 group; A = C=0- • H angle, and 0 = 0 - H - C angle; D = distance between oxygen and carbon. See Chapter 1 for a more detailed discussion. 82 Chapter 3 Results/Discussion Figure 3.8. The 1,4-biradical geometry of the spiro-adamantyl system, in which two half-filled p-orbitals are located on carbons 1 and 4, and the a-P sigma orbital is located between carbons 2 and 3. The geometry critical to the 1,4 biradical partitioning can be expressed in terms of angles that relate the sigma bond overlap to the p-orbitals at the radical centres. The following conditions are applied to Figure 3.8 above: the biradical hybridization is assumed to be sp2; cpi is defined as the dihedral angle between the C2-C3 sigma bond and the p-orbital lobe on C l with which it most nearly overlaps; 94 is defined as the angle involving the C2-C3 sigma bond and the most favourably oriented p-orbital lobe on C4. The values of tpi and (P4, from X-ray crystal analysis of ketones III to VI are listed in Table 3.2. The angles (p\ and (P4 have also been converted into cos cpi and cos cp4, as these functions are proportional to the overlap between the 2p z atomic orbital and an adjacent a type orbital.4 83 Chapter 3 Results/Discussion Table 3.2. Geometric data for biradicals III -VI. Biradical (pt (°) coscpi q>4 (°) cos(p4 Reaction IV V VI II -21 40 -87 70 -89 0.93 0.77 0.05 0.34 0.02 29 -30 31 30 -31 0.87 0.87 0.86 0.87 0.86 Cleavage Cyclization Cyclization Cyclization Biradical cleavage is most favoured when there is maximum overlap between the orbitals of the cleaving central sigma bond and the two p-orbitals (i.e., cpl = (P4 = 0° and coscpi = coscp4 =1). Of the four ketones investigated, III possesses the only biradical which has good overlapping geometry for both coscpi and COSCP4, being 93% and 87%, and 77% and 87%, respectively, depending on which of the two hydrogen atoms is abstracted. It is apparent from these values that both sides of the sigma orbital are in positions of good overlap. The biradicals derived from IV and VI possess good overlap on one side and poor on the other; thus, they prefer cyclization to cleavage. We can see quite plainly that excellent overlap on one side and poor overlap on the other does not result in cleavage. Thus, it is concluded from this data that perfect orbital overlap is not required for cleavage, but it should certainly involve both p-orbitals. In fact, the rigidity of the adamantyl skeleton, which fixes 9 4 at approximately 30°, reduces the number of variables important in cleavage and cyclization to only cpi because the values of (P4 will always be quite good. The X-ray crystal structures of the ketones (Figures 3.9 - 3.12) display the change in orientation of the carbonyl group as the number of methylene groups 84 Chapter 3 Results/Discussion increases from III to VI. The five-membered ring ketone III has its carbonyl group nearly bisecting the adamantyl ring, whereas the six-membered ring ketone IV possesses a carbonyl group C=0 bond that eclipses the sigma orbital lying between the a and (3 carbons (i.e. the C2-C3 bond, Figure 3.8). The next larger analogue V has a C=0 bond that swings even further away from the bisecting position, and as the ring is expanded even more in ketone VI, the carbonyl C=0 swings back towards the C 2 -C3 bond. By looking at Table 3.1 we can also see that the 1,4-biradicals generated in this study are capable of cyclization, having D values under 3.4 A. Maximum overlap occurs when the C l p-orbital is pointing directly at C4 (i.e. the C l p-orbital is parallel to the C2 - C4 vector and the angle between them is 0°). The crystal structure data reveal that ketone III deviates from the ideal angle by up to 69°, and that the corresponding deviation from the ideal geometry in ketones IV, V and VI is 59°, 39° and 35°, respectively. These values show that biradical III, which has the most favourable geometry for cleavage, has the least favourable geometry for cyclization. Cyclization may also be difficult for III because of the formation of a very strained cyclobutanol photoproduct. Compound IV deserves further examination because it is the only ketone which does not react in the anhydrous crystalline state to form photoproduct. The distance and angular parameters in Table 3.1 suggest that with hydrogen atom abstraction being favourable, the likely reason that no reactivity is observed is that the ensuing 1,4-hydroxy biradical does not cyclize or cleave. The X-ray crystal structure 85 Chapter 3 Results/Discussion of IV suggests that this biradical has a structural geometry that is poor for both processes. With neither reaction being favourable, reverse hydrogen atom abstraction is probably the fastest pathway, and recovery of starting material is the final outcome. Irradiation of IV in solution also results in only the recovery of starting ketone. However, in a suspension of water and a trace amount of surfactant, IV does react, yielding the highly strained photoproduct which is the result of a cationic rearrangement of the adamantane ring. Although uncertain at this time, the reaction is probably a surface reaction with water, with the product sloughing off into solution as irradiation progresses, and exposing new reaction surface. It is probably not a defect site reaction because no product is observed in the solid state. Ketones V and VI react to form cyclobutanols IX and X, respectively. The reactivity of the biradical of V can be rationalized because V does not have particularly favourable orbital overlap for cleavage, and displays a geometry better suited for cyclization. The biradical formed from VI is interesting because its geometry resembles that of the biradical derived from IV, as can be seen from Table 3.2 which shows that the angles in IV and VI are approximately the same, but the photochemical outcome of the two biradicals is quite different. Cyclization is observed in the photochemistry of VI and not in that of IV probably because the larger eight-membered ring reduces the ring strain in cyclobutanol X. The trans-6,4 cyclobutanol that would be formed from cyclization of the biradical of IV is highly strained. The overlap of the p-orbital of C l with that of the orbital of C4 is also greater in VI than in 86 Chapter 3 Results/Discussion IV (35° from the ideal geometry in V I as opposed to 59° in IV), and this should also be a contributing factor to cyclization. 3.3. X-ray Crystallographic Analysis of Molecular Structure Our vision of the orbital geometry of compounds III - V I and the subsequent rationalization of the solid state reactivity of these ketones from orbital overlap arguments, are derived from the molecular geometry analysis of the X-ray crystallographic data. The X-ray crystal structures enable a clear depiction of each ketone, and the ORTEP diagrams shown in Figures 3.9 - 3.12 illustrate the orientation of the carbonyl group with increasing ring size. The only motif common to the reactants is the adamantane skeleton, which remains rigid. The crystal data of each ketone are listed in Table 3.3 below. 87 Chapter 3 Results/Discussion Table 3.3. Crystal data of the starting ketones III - VI." Compound III IV V VI Crystal system monoclinic monoclinic triclinic orthorhombic Space group P2j/c C2/c PI Pna2\ a, A 6.7952(6) 17.788(2) 10.898(4) 19.318(4) b,k 6.7557(8) 12.827(2) 11.213(2) 8.282(2) c, A 28.909(3) 12.960(1) 7.218(6) 10.045(1) <x(°) 90 90 99.52(3) 90 P O 92.94(1) 104.178(7) 109.01(4) 90 Y(°) 90 90 62.27(2) 90 V 1325.3(2) 2867.0(5) 738.1(7) 1607.1(4) z 4 8 2 4 Figure 3.9. ORTEP diagram of the five-membered ring spiro-benzoyladamantane III, illustrating the symmetric shape of the molecule, with the carbonyl O l - C l bond pointing along the C2-C5 vector, and bisecting the adamantyl skeleton. 11 Complete crystallographic data are presented in Chapter 7. 88 Chapter 3 Results/Discussion Figure 3.10. ORTEP diagram of the six-membered ring spiro-benzoyladamantane IV. The carbonyl O l - C l bond swings away from the C2-C5 vector, and now eclipses the sigma orbital lying between the a and p carbons (i.e. the C2-C3 bond). Figure 3.11. ORTEP diagram of the seven-membered ring spiro-benzoyladamantane V. The carbonyl O l - C l bond has now swung beyond the C2-C3 bond. 89 Chapter 3 Results/Discussion Figure 3.12. ORTEP diagram of the eight-membered ring spiro-benzoyladamantane VI. The carbonyl O l - C l bond now swings back towards the C2-C3 bond. The homologues IV - VI were synthesized with the idea that the spiro ring junction would force these compounds to adopt non-symmetric conformations. This notion that the orientation of the carbonyl group can be controlled by ring size is of considerable value to the design of compounds which undergo y-hydrogen atom abstraction because the partitioning of 1,4-biradicals can be altered with the appropriate use of torsional and angular strain. Increasing ring size is of less value if the structure gains too much flexibility, because any loss of molecular rigidity reduces the certainty of obtaining only one conformation in the crystalline state, although even for very flexible molecules, only one conformation is usually present.5 90 Chapter 3 Results/Discussion In order to answer the question of the molecular rigidity of the spiro-adamantyl ketone system, thermal motion analyses6 in terms of rigid-body modes of translation, libration, and screw oscillations7 were performed on III - VI, and the experimental bond lengths were corrected accordingly. The overall translational motion of a molecule that arises from the cumulative bond bending and stretching of its constituent atoms can be described by the tensor T. The rotational motion of a molecule is the result of the angular deviation of its atoms from their equilibrium position by movement around a pivot. This libration is expressed using the tensor L. The most general motion for a rigid body is rotation about an axis coupled with a translation parallel to this axis. This so-called screw oscillation is the matrix S. In thermal motion analysis, fitting of the components of T, L, and S to the observed atomic displacement parameters (ADP) of each atom is performed by the method of by least-squares. The agreement between the observed and calculated ADP's is expressed as a residual, R: R ^ K b s - U c a l c \ Eq. 3.1. where U0oS and UCalc a r e t n e observed and calculated anisotropic displacement parameters. The lower the value of R, the better the rigid-body approximation. The R-values obtained for III - VI are 0.090, 0.079, 0.090, and 0.089, respectively.8 Although these residuals hover around 8 - 9%, they are indicative of molecules which approximate rigid bodies.9'1 0 91 Chapter 3 Results/Discussion The components of the principal axes of the T and L tensors are listed in Tables 3.4 - 3.5. The data from Table 3.4 indicate that the translational motion for all four ketones is roughly isotropic, with maximum and minimum r.m.s displacements of 0.224 A and 0.187 A, respectively for III; 0.203 A and 0.162 A, respectively for I V ; 0.177 A and 0.159 A, respectively for V ; and 0.207 A and 0.171 A, respectively for V I . The librational motion is more anisotropic, with maximum and minimum r.m.s librations of 5.85° and 1.70°, respectively for III; 4.78° and 2.37°, respectively for I V ; 4.09° and 2.02°, respectively for V ; and 4.55° and 2.28°, respectively for V I (Table 3.5). T a b l e 3.4. Components of T (A 2) for III - V I . — — - V I T(l) 0.0502 0.04132 0.0315 0.04269 T(2) 0.04302 0.03231 0.02639 0.03893 T(3) 0.03507 0.02614 0.02514 0.02914 T a b l e 3.5. Components of L (°) 2 for III - V I . Ill IV V VI L(l) 34.25 22.87 16.69 20.74 L(2) 8.93 5.86 6.07 7.43 L(3) 2,89 5^ 64 AA 5.22 The rigidity of compound III imposed by a strained five-membered ring spiro to the adamantyl group locks the carbonyl group in a bisecting position with respect to the adamantyl skeleton (i.e. along the C2 - C5 vector). The resulting C s symmetry 92 Chapter 3 Results/Discussion (Figure 3.9) can be quantified by obtaining a value of its symmetry measure S(G) using the expression: where a given shape of np points P, (i = 1 , n p ) is fitted to np points P ,• of a symmetry element G (e.g. C s symmetry), and the expression S(G) becomes a function of the minimal displacement that the points P, must undergo in order to achieve this G-symmetry.11 The smaller the value of S(G), the closer the structure is to possessing the G-symmetry, and a value of S(G) = 0 indicates that the structure has the perfect G-symmetry.12 The results of this calculation gave a low S(CS) value of 1.422 for III. The consequence of the C s symmetry in III is manifested in its y-hydrogen atoms which are nearly equidistant to O l . In the other ketones, which are less symmetric, there is a definite preference for the abstraction of only one of the two y-hydrogen atoms. The effects of ring strain on the ketones are disclosed by the rather large variation of intra-annular benzene-spiro angles p and 8 (Figure 3.13). Significant deviations are observed from the trigonal planar angle of 120° found in typical sp2 hybridized benzene ring carbons. The experimental values are shown below in Table Eq. 3.2. A 3.6. 93 Chapter 3 Results/Discussion Figure 3.13. Intra-annular angles of the phenyl group. Table 3.6. Angular deviations of the phenyl rings in compounds III - VI. Compound p(°) f £(°)f III 129.3(2) 118.6(2) 128.5(2) 122.6(2) IV 121.3(1) 120.6(1) 119.2(1) 120.3(1) V 120.2(2) 121.7(2) 118.2(2) 121.9(2) VI 119.5(2) 122.5(3) 121.3(2) 118.5(3) +There are two sets of p and e angles, one set for each phenyl-alkyl junction. Although the angles in III deviate up to 9°, they do seem consistent with the observation that strain induced in the benzene ring system by fusion to cycloalkanes (especially small rings) is reflected by angular deformations.13 The ring strain also has an impact on the direction of the carbonyl group with respect to the (3-carbon, and the conjugation of the carbonyl group with respect to the phenyl ring. The torsional angle 13 which consists of the atoms 01-C1-C2-C3 (Figures 3.9 - 3.12) describes the orientation of the carbonyl oxygen to the (3-carbon atom (Table 3.7). An eclipsed torsional angle (i.e. T3 = 0°) would mean that the oxygen is pointing directly at the (3-carbon atom, as in compounds IV and VI. The 94 Chapter 3 Results/Discussion torsional angle (14) of the atoms 0 1 - C l - C c c _ i - C P _ i describes the conjugation of the carbonyl group to the phenyl ring (Figure 3.14). A value of 0° depicts planarity. Table 3.7 illustrates that as n increases, the conjugation of the carbonyl group with the phenyl ring decreases. Table 3.7. Angles and least squares plane residuals describing the orientation of the carbonyl group in ketones III-VI. Compounds x 3 (°) x 4 (°) %2for carbonyl group III 68.7(3) -4.6(3) 109.2(1) 0.0 IV -0.4(2) 30.8(2) 115.3(1) 169.5 V -21.4(2) 62.4(2) 119.7(2) 23.8 VI -4.9(4) 107.3(3) 118.3(2) 194.9 The trigonal planar geometry of the carbonyl group, which is the angle between the atoms C a - C l - C a . ^ , is represented by the angle v \ (Table 3.7). The values of \)\ are less than 120° in the two smaller ring compounds III and IV, but approach a trigonal arrangement with increasing n. Table 3.7 also shows large least squares plane %2 values (based on the four atoms that make up the least-squares carbonyl plane: O l , C l , C a , and Ca_i) for IV and VI. From these dihedral angles and the %2 residuals, we can see that the spiro-adamantyl ketone III attains a planar carbonyl group at the expense of a trigonal dihedral angle, whereas compounds IV and VI assume near 120° angles by deforming the carbonyl plane. Compound V appears to have the proper number of carbon atoms in the spiro-ring to achieve both planarity and a trigonal planar geometry. 95 Chapter 3 Results/Discussion Figure 3.14. Atoms on the carbonyl plane, (a) The torsional angle T4 consists of the atoms: O l , C l , Ca_{, and c p . j . (b) The angle x>i consists of the atoms: Ca , C l , and Ca_ i . (c) A least squares plane is defined for the atoms: 01, C l , Ca , and Ca.1. 3.4. X-ray Crystallographic Analysis of the Stereochemistry of the Photoproducts and their Crystal Packing The X-ray structures of photoproducts IX (Figure 3.15) and X (Figure 3.16) obtained from irradiation of V (Figure 3.6) and VI (Figure 3.7), illustrate the exo-hydroxyl stereochemistry present at C l . This stereochemistry can be explained by invoking the topochemical rules for least-motion cyclization of 1,4-biradicals in the solid state. The crystal structures of their ketone precursors V (Figure 3.11) and VI (Figure 3.12) show a "pre-exo" arrangement of the carbonyl group; thus, the minimum amount of motion needed for the Yang cyclization will result in the production of cyclobutanols possessing an exo-hydroxy stereochemistry. These two cyclobutanols do not differ very much structurally from their reactant ketones; compound VIII, however, shows a large difference in structure with respect to its precursor IV. This 96 Chapter 3 Results/Discussion discrepancy is caused by the cationic rearrangement of its initially formed cyclobutanol. Figure 3.15. ORTEP diagram of the cyclobutanol photoproduct IX. The stereochemistry of the hydroxyl group is exo to the adamantyl skeleton. 97 Chapter 3 Results/Discussion Figure 3.16. ORTEP diagram of the cyclobutanol photoproduct X. The stereochemistry of the hydroxyl group is exo to the adamantyl skeleton. 98 Chapter 3 Results/Discussion It is often found that similar geometric shapes pack in the same fashion, and this is most clearly seen in examples of analogous molecules, as demonstrated in the previous chapter. But there is no steadfast crystal packing rule for a series of compounds which progressively increase in molecular size. The spiro-benzoyladamantanes III - VI, which differ in the number of methylene units present, are very similar in molecular structure - as can be seen from their ORTEP diagrams -yet display entirely different orderings in the crystalline state (Table 3.3)."' Photoproducts IX and X, however, pack in a comparable manner (Figures 3.19 -3.20), and can be regarded as almost isostructural despite being homologues.1V Compounds IX and X are atypical in that they do not exhibit classic hydrogen bonding that is expected for alcohols. A study of the packing diagrams shows that the absence of hydrogen bonding stems from the large separation distances between the hydroxyl oxygen atoms in these bulky adamantane derivatives. Hydrogen bond formation is not favoured if a close-packing arrangement needs to be sacrificed in order to bring the hydroxyl groups closer together.14 Thus, for sterically hindered compounds, the contributions to crystal stability from hydrogen bonding may not be desirable. In fact, a search of the Cambridge Structural Database15 shows several I I I Theoretical crystal structure predictions for a given molecule always estimate that between ten and one hundred crystal structures are within lOkJ/mol in lattice energy.18 With this large number of possible packing patterns for any given molecule, it is not surprising that the homologous compounds (III - VI) exhibit different crystal structures. I V The atoms of IX and X can be mapped almost exactly onto one another. The fractional coordinates for each compound are listed in Chapter 7. 99 Chapter 3 Results/Discussion adamantyl compounds containing alcohol functionalities which do not hydrogen bond, two of which are illustrated in Figure 3.18. Table 3.8. Crystal data of photoproducts VIII-X. V Compound VIII IX X Crystal system triclinic monoclinic monoclinic Space group PI P2]/c P2\/c a, A 19.871(3) 8.763(3) 8.8308(1) b, A 24.676(4) 14.060(5) 14.646(3) c, A 12.999(2) 11.890(2) 12.0651(1) a(°) 99.87(1) 90 90 P O 101.20(1) 90.51(2) 90.954(1) Y O 109.14(1) 90 90 V 5714.4(1) 1464.9(7) 1560.3(4) z 8 4 4 Figure 3.18. Adamantyl compounds which do not form hydrogen bonds with adjacent molecules, (a) 2-cumyladamantan-2-ol.16 (b) 2-(2,4,6-17 trimethylphenyl)adamantan-2-ol. v Complete crystallographic data are presented in Chapter 7. 100 Chapter 3 Results/Discussion Figure 3.19. Packing diagram of IX. This packing motif is almost identical to that of X. The difficulties for hydrogen bonding is evident from the large separation distances between the oxygen atoms. 101 Chapter 3 Results/Discussion Figure 3.20. Packing diagram of X . The crystal structure of this compound can be considered virtually isostructural to that of IX. Compound VIII (Figure 3.17) is distinct in being the only one of three photoproducts that exhibits classic hydrogen bonding. Each molecule of VIII actually hydrogen bonds with two other molecules, forming a tetrameric hydrogen bonded structure (Figure 3.21). One such tetrameric structure makes up the asymmetric unit in the crystal structure, giving 8 molecules in the unit cell. Previous studies of crystal structures containing alcohols find that Z ' > 1 is uncommon but not rare. 1 4 ' 1 8 ' 1 9 Gavezotti states: "In alcohols, the hydrogen bond is rather a source of mischief than of ordered patterns, as alcohols form an unusually high percentage of crystals with more 102 Chapter 3 Results/Discussion than one molecule in the asymmetric unit and with largely unpredictable cyclic oligomers."18 It is quite possible that this hydrogen bonding pattern is carried over from solution and into the crystal structure during the crystallization process. b Figure 3.21. Packing diagram of VIII illustrating the tetrameric hydrogen bonding motif in the crystal structure. The hydrogen bonds are shown with dashed lines. 103 Chapter 3 Results/Discussion 3.5. Conclusions This series of compounds illustrates that the overlap between the p-orbitals and sigma bond in the 1,4-biradicals can be altered by imposing a rigid angular strain on the molecule. The overlap, in turn, affects the photochemistry of each reactant, and the reactivity of such strained compounds reveals insight into the degree of orbital overlap necessary for cleavage in the Norrish type II biradicals. The potential of using ring strain for the control of biradical partitioning is particularly intriguing because of possible synthetic applications. By altering the orientation of the carbonyl group, the partitioning of the 1,4-biradicals can be controlled, resulting in different photoproducts. 104 Chapter 3 Results/Discussion 3.6. References for Chapter 3 1 Leibovitch, L . ; Olovsson, G.; Scheffer, J. R.; Trotter, J. J. Am. Chem. Soc. 1998, 120, 12755. 2 The compounds discussed in this chapter were synthesized by Netherton, M . R., University of British Columbia. 3 Wagner, P. J. In CRC Handbook of Organic Photochemistry and Photobiology; Horspool, W. M . , Song, P.-S., Eds.; CRC Press: Boca Raton, FL, 1995. (b) Scaiano, J. C ; Lissi, E. A. , Encina, M . V . Rev. Chem. Intermed. 1978, 2, 139. 4Burdett, J.K. Molecular Shapes; Wiley-Interscience: New York, 1980, p. 6. 5 For an example of y-hydrogen atom abstraction in a disordered macrocyclic system, see: Cheung, E.; Netherton, M . R.; Scheffer, J. R.; Trotter, J. J. Am. Chem. Soc. 1999, 727,2919. 6 (a) Schomaker, V. ; Trueblood, K. N . Acta Crystallogr. 1968, B24, 63. (b) Dunitz, J. D.; White, D. N . J. Acta Crystallogr. 1973, A29, 93. 7 (a) Cruickshank, D. W. J. Acta Crystallogr. 1956, 9, 754. (b) Cruickshank, D. W. J. Acta Crystallogr. 1956, 9, 757. (c) Cruickshank, D. W. J. Acta Crystallogr. 1961, 14, 896. 8 These calculations were performed using the most recent version of Thermal Motion Analysis. Maverick, E. F.; Trueblood, K. N . THMA11 - TLS Thermal Motion 105 Chapter 3 Results/Discussion Analysis Program. Department of Chemistry, University of California: Los Angeles, 1991. 9 Dunitz, J. D. X-ray Analysis and the Structure of Organic Molecules; Cornell University Press: New York, 1979, pp. 244-260. 1 0 A good least-squares fit of the anisotropic displacement parameters only implies that the molecule is rigid. For a detailed discussion of common abuses in the interpretation of ADP's from diffraction data of crystals, see: (a) Dunitz, J. D.; Schomaker, V . ; Trueblood, K. N . J. Phys. Chem. 1988, 92, 856. (b) Dunitz, J. D.; Maverick, E. F.; Trueblood, K. N . Angew. Chem., Int. Ed. Engl. 1988, 27, 880. 1 1 Zabrodsky, H. ; Peleg, S.; Avnir, D. / . Am. Chem. Soc. 1993,115, 8278. 1 2 Pilati, T.; Forni, A . J. Appl. Crystallogr. 1998, 31, 503. 1 3 Allen, F. Acta Crystallogr. 1981, B37, 900. 1 4 Brock, C. P.; Duncan, L . L . Chem. Mater. 1994, 6, 1307. 15 Cambridge Structural Database, Cambridge Crystallographic Data Centre: Cambridge, U.K. , 2000. 1 6 Choi, H ; Pinkerton, A . A. ; Fry, J. L . Chem. Commun. 1987, 225. 1 7 Baran, J.; Kanters, J. A. ; Lutz, E. T. G.; van der Maas, J. H . ; Schouten, A. ; Wierzejewska-Hnat, M . J. Mol. Struct. 1990, 222, 305. Gavezotti, A . Crystallography Reviews 1998, 7, 5. 1 9 Gavezotti, A ; Fillippini, G. J. Phys. Chem. 1994, 98, 4831. 106 Chapter 4 Results/Discussion Chapter 4 Regio-, Diastereo-, and Enantioselective Reactions in the Photochemistry of cis-9-Decalyl Aryl Ketones cw-9-Decalyl aryl ketones ( X I , Figure 4.1) are ideal for exploring the role of the crystalline environment in directing the formation of regio- and diastereomeric cyclobutanol products in the Norrish type II photochemical reaction. This system offers four abstractable y-hydrogen atoms ( H A , H A , H B , and H B ) which reside in positions proximal to the carbonyl group. In solution it is expected that any one of these hydrogen atoms may be abstracted because of the equilibria among various low energy conformations which can bring each hydrogen atom into the vicinity of the photoexcited carbonyl oxygen atom. The 1,4-biradicals formed from such a Norrish type II reaction are free to undergo bond rotations which will reduce the diastereoselectivity of the subsequent Yang cyclization. However, when these compounds are irradiated in the solid state, the rigid medium is expected to encourage both the regioselectivity of the hydrogen atom abstraction reaction ( H A / H A ' vs 4 . 1 . General Considerations X I e © X = H , F, C 0 2 C H 3 , C O O N H 3 R * Figure 4 . 1 . Aryl derivatives ( X I ) of the cw-9-decalyl system. 107 Chapter 4 Results/Discussion H R/H B ')> and the diastereoselectivity of the Yang cyclization reaction (either exo-aryl or endo-aryl at the hydroxyl-bearing carbon). Moreover, by tethering a carboxylic acid moiety to the system (X = COO"), and subsequently introducing a resolved chiral amine into the system to prepare optically active salts using the ionic chiral auxiliary approach, the solid state photochemical reactions can be investigated for their enantioselectivity ( H A vs H A ' and H B vs H B ' ) . 4.2. Solution and Solid State Photochemistry of the Aryl Ketones In solution, the benzoyl group is free to rotate, and the decalin ring system, which is not conformationally-locked, can interconvert between low energy conformations (Figure 4.2). The carbonyl oxygen will be able to abstract any of the y-hydrogen atoms H A and Hg, and their enantiotopic equivalents HA> and H B ' . 108 Chapter 4 Results/Discussion x (a) (b) (c) Figure 4.2. Various conformations that the cw-decalyl molecule can possess by rotation of the benzoyl group and ring-flipping of the decalin system. These two transitions directly affect the stereoselectivity of the hydrogen abstraction reaction, (a) The conformation favours abstraction of H A . (b) Rotation of the benzoyl group results in a conformation favouring abstraction of H B . (c) A ring flip and rotation of the benzoyl group results in a conformation that favours abstraction of H A ' . Molecular mechanics calculations of the benzoyl ketones XI(a - c) show that the lowest energy conformation favours the abstraction of H A , and the second lowest energy conformation favours Hg. 1 In solution, where both conformations can exist, a mixture of cyclobutanols consisting of enantio- and regioisomers would be obtained from the irradiation of XI. The reactivity observed in solution is precisely what the M M + calculations indicate. Solution photolysis of ketones Xl(a-c) results in abstraction of the four y-hydrogen atoms to form their corresponding biradicals, which then Yang cyclize to yield a racemic mixture of cyclobutanols composed primarily of XII and XIII (Figure 4.3 and Table 4.1). Rather suprisingly, the cyclopentanone XIVc is also formed from the solution irradiation of XIc. This photoproduct does not appear to be derived from a Norrish type II mechanism. 109 Chapter 4 Results/Discussion XIV X V (a) X = H (b) X = F (c) X = C O O C H 3 Figure 4.3. Photochemistry of the benzoyl ketones of the cw-decalyl system (XI). In the solid state, however, only one of the two conformations is present in the crystal structure, and only one photoproduct is typically observed (either XII or XIII) after irradiation (Table 4.1). Photolysis of crystals of compound XIa yields photoproduct XIIIa exclusively at low conversion, whereas photolysis of compound X l b gives mainly X H b . At higher conversion, the breakdown of the crystal structure is evident in the product selectivity ratios which show that mixtures of alcohols are obtained. As in the case of the solution photolysis, solid state irradiation of ester XIc affords another compound which cannot be formed from a Norrish type II mechanism (cyclopropanol XVc) . 110 Chapter 4 Results/Discussion Table 4.1. Photolysis of the aryl ketones XI in solution and the solid state. Compound Temp Medium Conversion XII XIII XIV X V (°C) (%) (%) (%) (%) (%) XIa r.t. acetonitrile 100 60.0 40.0 0 0 -20 crystal 8.1 0 100 0 0 Xlb r.t. acetonitrile* 100 55.0 40.0 0 0 -20 crystal1 8.6 100 0 0 0 XIc r.t. acetonitrile 100 46.7 47.1 6.2 0 -20 crystal 100 81.1 0 0 18.9 f At higher conversions, the crystalline environment is lost and a mixture of cyclobutanols is obtained. *For this photolysis, the combined percentage of reported photoproducts is less than unity because of unidentified compounds. 4.3. X-ray Crystallographic Analysis of the Solid State Photochemistry of Two Benzoyl Derivatives of the cw-9-Decalyl system The regioselective hydrogen atom abstraction and diastereoselective Yang cyclization of the 1,4-biradicals derived from XIa and Xlb in the solid state can be rationalized from their X-ray crystal structures. The conformation of the carbonyl group in ketone XIa as determined by X-ray crystallography (Figure 4.4) is clearly set up for abstraction of only one y-hydrogen atom, namely, the axial hydrogen atom on C2 (i.e. H A ) , which is at a separation distance of 2.65 A from O l (Table 4.2). The biradical formed from abstraction of this hydrogen atom cyclizes to a cyclobutanol possessing endo-ary\ stereochemistry at the hydroxyl-bearing carbon. This stereochemistry can be explained by invoking the topochemical postulate. The crystal structure of XIa reveals that the pathway with the least amount of motion for 1,4-biradical closure will maintain the phenyl ring over C5 and result in a cyclobutanol 111 Chapter 4 Results/Discussion with an endo-ary\ stereocentre. Formation of the alternate diastereomer in which the hydroxyl group is situated over C5 requires a 180° rotation of the entire benzoyl moiety (i.e. a 180° rotation along the C10-C11 bond) that would be forbidden in the solid state. Table 4.2. Hydrogen atom abstraction parameters of XIa. 1 Carbon # H x d(A) c o ( ° ) A ( ° ) e n D(A) C(2 ) H A 2.65 56 84 113 3.08 C(4 ) H B 3.52 44 44 107 3.09 C (6 ) H B ' 5.65 10 26 36 3.90 C (8 ) H A ' 5.22 31 49 47 3.85 C ( 5 ) H C 3.83 8 10 69 2.55 1 The abstraction parameters define the spatial relationship for the abstraction of a hydrogen atom by the excited carbonyl oxygen atom, d = distance between oxygen and hydrogen, O • H ; co = dihedral angle formed between the O - H vector and its projection on the nodal plane of the C=0 group; A = C=0- • H angle, and 0 = 0 - H - C angle; D = distance between oxygen and carbon. See Chapter 1 for a more detailed discussion. 112 Chapter 4 Results/Discussion Figure 4.4. ORTEP diagram of XIa. Figure 4.4 and the y-hydrogen atom abstraction parameters in Table 4.2 show that the hydrogen atoms enantiotopic to H A and H B (i.e. HA> and H B ' , respectively) cannot be abstracted. Thus, the reason that racemic photoproducts are observed in the solid state irradiations is because the XIa crystallizes in an achiral space group (Table 4.3). 113 Chapter 4 Results/Discussion Table 4.3. Crystallographic data of the molecular ketones Xl(a-c) and photoproducts XIIc and XIVc.11 Compound XIa Xlb XIc XIIc XIVc Crystal system monoclinic monoclinic monoclinic triclinic monoclinic Space group P2i/c Fl\la Pill a PI P2, a, A 7.3068(6) 13.952(2) 13.881(5) 8.8083(3) 11.209(1) b, A 19.757(2) 6.4153(9) 6.362(2) 17.365(7) 10.149(1) c, A 9.958(1) 16.271(1) 18.197(8) 6.182(2) 7.5641(8) a(°) 90 90 90 90.99(3) 90 P(°) 108.452(7) 109.170(9) 97.77(4) 109.53(3) 70.368(9) Y(°) 90 90 90 79.04(3) 90 v,A 3 1363.7(3) 1375.6(3) 1591(1) 801.9(5) 810.5(2) z 4 4 4 2 2 Whereas the aryl group in XIa is situated over C5, the aryl group in the fluoro-substituted derivative (Xlb) is rotated approximately 180° in the other direction, and thus situating the carbonyl group over C5. Consequently, the oxygen atom in this ketone favours the abstraction of H B . At low conversions in the solid state, Xlb (Figure 4.5) yields only one product, cyclobutanol Xllb, which is the cyclization product of the biradical formed from F£B abstraction (Table 4.4). The endo-aryl stereochemistry of the hydroxyl-bearing carbon can be explained using the same argument as invoked above for XIa. Abstraction of H g by the carbonyl oxygen is followed by least motion 1,4-biradical coupling, which yields compounds of the general structure XII. " Complete crystallographic data are presented in Chapter 7. 114 Chapter 4 Results/Discussion Table 4.4. Hydrogen abstraction parameters of X l b . C a r b o n # Hx d(X) ^7) M ° i B O D (A) C(2) HA 3.49 46 46 106 3.09 C(4) HB 2.66 55 85 112 3.07 C(6) H B' 4.63 7 78 59 3.90 C(8) HA. 5.21 30 52 45 3.86 C(5) HC 2.37 1 85 100 2.52 Figure 4.5 ORTEP diagram of X l b . It would appear from the data in Table 4.4 that the p-hydrogen atom He on C5 in X l b has quite good abstraction geometry. However, the five-membered transition state occurring in p-hydrogen atom abstraction is not as favourable as that of the six-115 Chapter 4 Results/Discussion membered transition state involved in y-hydrogen atom abstraction, and this is the reason for the large number of compounds which undergo Norrish type II photochemistry.3 4.4. The Competition between P- and y-Hydrogen Atom Abstraction in the Solution and Solid State Photochemistry of the Keto-Ester Derivative of the m-9-DecaIyI System As mentioned previously, keto-ester XIc (Figure 4.6) affords unique products in both solution and solid state photolyses in addition to the Yang cyclobutanol XIIc (Figure 4.7). In solution, this novel photoproduct is cyclopentanone XIVc (Figure 4.8), which is envisioned to be the product of a P-hydrogen abstraction process in which HQ is abstracted, followed by a 180° rotation of the aryl group of the resulting biradical, which then undergoes a radical recombination at the orr/io-position of the aryl ring (Figure 4.9). Cyclopentanone XIVc is obtained after subsequent tautomerization and oxidation. In the solid state, the major photoproduct is still the y-hydrogen atom abstraction product XIIc. The P-hydrogen abstraction product XIVc is not observed, and instead, the novel cyclopropanol XVc is isolated in significant amounts. Photoproduct XVc is thought to occur through the same P-hydrogen atom abstraction biradical intermediate that results in the formation of XIVc in solution (see Table 4.5 for the abstraction geometries of XIc). However, in the crystalline state, the 180° 116 Chapter 4 Results/Discussion swing of the aryl group which is needed for cyclopentanone formation is disallowed by the neighbouring molecules that make up the reaction cavity. Thus, the only permitted reaction is the direct cyclization of the 1,3-biradical, which affords the strained cyclopentanol XVc. The reason why XVc is not observed in solution is not clear at this time, because the short separation distance between the biradical centres seems to indicate that this direct cyclization would be the fastest reaction. However, the cyclopropanol is highly strained and the transition state leading to it may be unfavourable compared to that of the cyclopentanone. The orientation of the carbonyl group in XIc resembles that in the fluoro-derivative, favouring the abstraction of H g . Hence, it is not surprising that both derivatives yield cyclobutanol XII and not XIII (which can arise only from H ^ abstraction). 117 Chapter 4 Results/Discussion Chapter 4 Results/Discussion Figure 4.8. ORTEP diagram of XIVc. Figure 4.9. The reaction pathways of the 1,3-biradical formed from P-hydrogen atom abstraction. 119 Chapter 4 Results/Discussion Photochemical P-hydrogen abstraction is very rare,4 and abstraction of a (3-hydrogen atom in the presence of suitable y-hydrogen atoms in the solid state is unprecedented. The rate of hydrogen atom abstraction is often related to the stability of the ensuing radicals,5 which are quite stable for XIc. One radical centre resides on the tertiary carbon C5, and the other radical centre residing on C l l can be delocalized throughout the aryl ring and into the ester group. Compounds XIa and X l b do not have this additional ester group, and the occurrence of the P-hydrogen abstraction reaction solely upon irradiation of XIc and not upon these other ketones would then be attributed to the stabilizing electronic effects that the ester group brings to the biradical moiety. Table 4.5. Hydrogen abstraction parameters of XIc. Carbon # H x d(A) A(°) 9(°) D(A) C(2) H A 3.47 45 45 107 3.07 C(4) H B 2.55 56 85 116 3.05 C(6) H B ' 4.63 7 78 56 3.85 C(8) H A . 5.14 31 54 47 3.87 C(5) H C 2.38 2 85 99 2.51 Although, the overlap between the y-carbon and the a~P bond (92, Table 4.6) will always be good because of the rigidity of the decalin system (Figure 4.10), these compounds do not cleave. Despite being free to rotate, the carbonyl groups in all three ketones adopt conformations in which there is poor orbital overlap between the p-orbital on the carbonyl carbon and cc-P sigma bond ((pi, Table 4.6). As seen in the 120 Chapter 4 Results/Discussion previous chapter, good orbital overlap on both sides of the sigma bond are required for cleavage. x Figure 4.10. The 1,4-biradical geometry of the cw-decalyl system, (a) The biradical resulting from H A / H A ' abstraction. Two half-filled p-orbitals are located on C2 and C l l , and the a-P sigma orbital is located between C l and CIO. (b) The biradical resulting from H B / H B ' abstraction. Two half-filled p-orbitals are located on C4 and C l l , and the a-P sigma orbital is located between C5 and CIO. Table 4.6. Orbital overlap and torsional angle 15 in compounds Xl(a-c). Compound (PI (°) coscpi <P2 (°) coscp2 *5 (°) XIa 66.1 0.41 -35.9 0.81 -145 Xlb 70.4 0.34 36.1 0.81 -19.6 XIc -67.8 0.38 35.0 0.82 21.5 The torsional angle O l - C l 1-C10-C5 (designated 15, Figure 4.10 and Table 4.6) describes the orientation of the carbonyl group with respect to the decalyl ring. The value of T5 in XIa is very different from X l b and XIc because the carbonyl is 121 Chapter 4 Results/Discussion facing in the opposite direction. The magnitudes of T5 in Xlb and XIc are quite similar, and this is reflected in the reactivity of the biradicals of Xlb and XIc, both of which abstract Hg to yield the cyclobutanol XII. 4.5. Solid State Photochemical Asymmetric Induction and X-ray Crystallographic Analysis of Optically Pure Salts of the cw-9-Decalyl System As mentioned in Chapter 1 and expanded upon in Chapter 2, achiral molecules usually crystallize in centric space groups. The molecules may themselves be in chiral conformations, but the nature of a centric space group requires that equal amounts of molecules with opposing conformational chiralities be present in the crystal, thus leading to an overall environment that is racemic. For solid state asymmetric induction studies, adoption of the ionic chiral auxiliary concept allows for the circumvention of this crystallization problem, because crystals of optically pure salts prepared from achiral carboxylic acids and enantio-pure amines must pack in chiral space groups. Using this method of chiral induction, two optically pure organic salts which gave X-ray quality crystals were prepared using the carboxylate derivative Xld (Figure 4.11) and the enantiomerically pure amines (li?,25')-(-)-norephedrine (65) and (S)-(-)-a-methylbenzylamine (66).6 The salts of these amines with Xld are designated SI and S2, accordingly. A summary of their crystal data is listed in Table 4.7. 122 Chapter 4 Results/Discussion Xld X l l d Figure 4.11. Solid state photochemistry of the optically pure salts Sl and S 2 . Table 4.7. Crystallographic data of the chiral salts Sl and S 2 . Compound Sl S 2 Crystal system monoclinic orthorhombic Space group P2X P2i2i2i a, A 13.959(2) 6.5004(5) b, A 6.396(2) 14.947(1) c,k 26.705(5) 23.025(2) a ( ° ) 90 90 P ( ° ) 97.58(2) 90 Y(°) 90 90 v,A 3 2363.5(9) 2237.2(3) z 4 4 Complete crystallographic data are presented in Chapter 7. 123 Chapter 4 Results/Discussion The photolyses performed on SI in the solid state gave X l l d in low e.e. (20-30% range, Table 4.8).1V This behaviour was explained once the X-ray structures were determined. Chiral salt SI crystallizes in the chiral space group P2\ with two formula units in the asymmetric unit (Figures 4.12 - 4.13). There exists a near-mirror relationship between the two acid molecules X l d , and the conformations of the acids are such that they are predisposed toward formation of products of opposite configuration (see abstraction values in Table 4.9). The competing reactions of the acids occur in a chiral environment where their transition states are diastereomeric. The unequal energy of the transition states will lead to different rates of reactions, and thus, the photoproducts will be non-racemic. Table 4.8. Photochemical yields from the irradiation of SI and S2. Salt Time (h) % Conversion X l l d % % e.e. SI 0.5 10 94 (-) 30 2 24 93 23 4 55 95 30 S 2 F 1 17 74 (+)>98 3 35 69 >98 4 55 67 >98 TFor these photolyses, the combined percentage of reported photoproducts is less than 100% because of unidentified compounds. I V The optically pure salt of X l d and (15,2/?)-(+)-norephedrine was found to yield the same photoproduct as its optical antipode SI, but with opposing optical rotations. The crystal structure was determined to be exactly the same as SI but with the opposite absolute configuration. 124 Chapter 4 Results/Discussion Figure 4.12 ORTEP diagram of an anion X l d in the asymmetric unit of SI. Figure 4.13 The packing diagram of SI, illustrating the non-crystallographic symmetry of the two nearly mirror-symmetric X l d anions (blue and purple) in the asymmetric unit. The y-carbons are shown in yellow. An infinite two-dimensional hydrogen bonding motif is present. This network utilizes every hydrogen atom that is capable of hydrogen bonding. 125 Chapter 4 Results/Discussion The two anions were superimposed upon one another (Figure 4.14), and their "near-enantiomeric" nature quantified by calculating a root-mean-square misfit of the atoms after minimization of their differences using a least-squares routine. A low r.m.s value of 0.078 A was obtained, indicating a good fit. We define this type of near-mirror relationship in the asymmetric unit with the term "conformational enantiomerism". Figure 4.14 The superimposition of the two acid molecules of SI. The crystallographic coordinates of one of the carboxylates (dark) has been inverted and overlaid onto the coordinates of the non-inverted molecule (light). 126 Chapter 4 Results/Discussion Table 4.9. Hydrogen atom abstraction parameters of salt S l . Carbon # H X D ( A ) co(°) A O o o D ( A ) Molecule 1 C2 H A 3.58 41 42 107 3.10 C4 H B 2.70 56 80 114 3.08 C6 H B - 4.68 7 77 54 3.89 C8 H A ' 5.07 33 56 48 3.84 C5 H C 2.40 4.8 84 101 2.52 Molecule 2 C20 H A 3.54 44 44 107 3.10 C22 H B 2.64 55 83 114 3.08 C24 HB' 4.65 6 78 57 3.88 C26 H A ' 5.11 33 54 48 3.86 C23 H C 2.38 2 85 101 2.51 Asymmetric induction studies of salt S2 were more successful. Photolysis of the optically pure salt of X l d and (5)-(-)-a-methylbenzylamine resulted in excellent e.e.'s even at high conversion (Table 4.8). This salt crystallizes in the chiral space group P2\l\l\ with only one formula unit in the asymmetric unit (Figure 4.15) and with the anion moiety possessing a carbonyl group which is inclined to abstract only one hydrogen atom, namely H B ' (Table 4.10 and Figure 4.16). Hence, using the X-ray structure, we can explain the high photochemical enantioselectivity and good regioselectivity found for this compound. 127 Chapter 4 Results/Discussion Figure 4.15 The packing diagram of S 2 . An infinite one-dimensional hydrogen bonding motif (parallel to the a-axis) utilizes every hydrogen atom that is capable of hydrogen bonding. Table 4.10. Hydrogen abstraction parameters of S 2 . Carbon # H x d(A) can A(°) e n D(A) C(2) H A ' 3.43 45 45 109 3.04 C(4) H B . 2.62 55 84 115 3.07 C(6) H B 4.65 7 78 58 3.88 cm H A 5.06 14 41 54 3.86 C(5) H C 2.40 0 84 100 2.51 128 Chapter 4 Results/Discussion Figure 4.16 ORTEP diagram of X l d in S2. 4.6. Conclusions The stereoselective photochemical reactions of the c/s-decalyl derivatives that have been discussed in this chapter are excellent illustrations of the advantages of solid state organic photochemistry. These compounds yielded a mixture of products in solution, but their reactions were much more stereoselective in the crystalline state. Moreover, the X-ray Structure - Solid State Reactivity Correlation Method enabled the rationalization of the formation of the products from their starting materials, including the novel P-hydrogen atom abstraction products. The photochemistry of salt S l 129 Chapter 4 Results/Discussion indicates that the regioselectivity of a photochemical reaction is not necessarily affected by the presence of two independent anions in the asymmetric unit. However, the enantiomeric excesses associated with the photoproducts are lower. The key point that has been illustrated in using the Ionic Chiral Auxiliary Method is that with the appropriate chiral amine, only one anion will be present in the asymmetric unit, and both excellent regio- and enantio-selectivities can be achieved. 130 Chapter 4 Results/Discussion 4.7. References for Chapter 4 1 Kang, T.; Scheffer, J. R. Unpublished results. The compounds discussed in this chapter were synthesized by Kang, T., University of British Columbia. 3 (a) Scheffer, J. R. In Organic Solid State Photochemistry; Desiraju, G. R., Ed.: Elsevier Science Publishers: New York, 1987; Chapter 1. (b) Wagner, P. J.; Kelso, P. A. ; Kemppainen, A . E.; Zepp, R. G. J. Am. Chem. Soc. 1972, 94, 7500. (c) Dorigo, A. E.; Houk, K. N . J. Org. Chem. 1988, 53, 1650. (d) Dorigo, McCarrick, M . A. ; Loncharich, R. J.; A. E.; Houk, K. N . ; J. Am. Chem. Soc. 1990,112, 7508. (e) O'Neil, H . E.; Miller, R. G.; Gunderson, E. J. Am. Chem. Soc. 1974, 96, 3351. (g) Coxon, J. M . ; Halton, B. In Organic Photochemistry; Cambridge University Press: London, 1987. 4 For examples see: (a) Wagner, P. J.; Weigel, W. J. Am. Chem. Soc. 1996,118, 12858. (b) Henning, H.-G. In The CRC Handbook of Organic Photochemistry and Photobiology; Horspool, W. M . ; Song, P.-S., Eds.; CRC Press; Boca Raton, 1995; Chapter 40. (c) Scheffer, J. R.; Dzakpasu, A . A . / . Am. Chem. Soc. 1978,100, 2163. (d) Couture, A. ; Hoshino, M . ; de Mayo, P. J. Chem. Soc, Chem. Commun. 1976, 131. (e) Padwa, A. ; Gruber, R. / . Am. Chem. Soc. 1970, 92, 107. 5 Wagner, P. J. Acc. Chem. Res. 1971, 4, 168. 131 Chapter 4 Results/Discussion 6 The optically pure salts of these chiral amines prepared with organic acids of other systems have been found to give good e.e.'s. See (a) Leibovitch, M . ; Olovsson, G.; Scheffer, J. R.; Trotter, J. J. Am. Chem. Soc. 1998,120, 12755. (b) Leibovitch, M Ph.D. Thesis, University of British Columbia, 1997. 7 Gould, R. O.; Moulden, N . ; Taylor, P. IDEAL; University of Edinburgh, 1988. 132 Chapter 5 Results/Discussion Chapter 5 Structure-Reactivity Correlations and Asymmetric Synthesis of Five-Membered Rings from the Photochemistry of Sterically Congested oc-Arylacetophenones 5.1. General Considerations c.0 Since the 1980's, there has been growing interest among synthetic chemists in the preparation of five-membered rings by non-ionic routes,1 often involving mechanisms which utilize radical cyclizations or photocyclizations. For example, photochemical 8-hydrogen atom abstraction in ketones generates 1,5-biradicals which can, under certain circumstances, recombine to yield cyclopentane derivatives. The mechanism is similar to that of the Norrish type JJ reaction discussed in the previous chapters. A system that has been found to react in this manner is XVI (Figure 5.1). Irradiation of XVI at the proper wavelength initiates a 8-hydrogen atom abstraction by the photoexcited carbonyl oxygen. The biradical which is formed does not have the option of cleaving, and instead, cyclizes to cyclopentanol XVII (Figure 5.2). X V I Figure 5.1. The a-mesitylacetophenone system (XVI). 133 Chapter 5 Results/Discussion XVII Figure 5.2. Photochemical 8-hydrogen atom abstraction. The photoexcited carbonyl oxygen of a molecule of X V I abstracts a 8-hydrogen atom to form a 1,5-biradical which cyclizes to a five-membered ring (indanol XVII) . Wagner and co-workers have studied the 1,5-biradicals and five-membered rings generated by intramolecular 8-hydrogen atom abstraction in photoexcited ketones.3 They conclude that 8-hydrogen atom abstraction competes poorly against y-hydrogen atom abstraction in molecules possessing both types of hydrogen atoms and that the efficiency of the cyclization of 1,5-biradicals compared to that of 1,4-biradicals is low. 4 Systems studied generally have a y : 8 abstraction preference of approximately 20 : l . 5 In the absence of y-hydrogen atoms, higher yields of the cyclization product from the coupling reaction of the 1,5-biradicals are obtained. Although many studies of photochemical abstraction are carried out in solution, there is an inherent advantage in performing 8-hydrogen atom abstraction reactions in the crystalline state, namely the efficiency of 1,5-biradical coupling is increased owing to the reduced mobility of the radicals in the crystal structure. The cc-mesitylacetophenone system (XVI) was chosen for our 8-hydrogen atom abstraction studies in view of the fact that y-hydrogen atoms are not present, and similar derivatives have been found to react cleanly to afford 2-indanols.6 Thus, there is an excellent opportunity to evaluate the synthetic potential of intramolecular 134 Chapter 5 Results/Discussion hydrogen atom transfer in the synthesis of five-membered rings. One goal of this study is to obtain 8-hydrogen atom abstraction parameters and compare and contrast them to the data from Y-hydrogen atom abstraction.7 Secondly, we can continue our investigations into the effects of para versus meta substitution on the crystal packing of achiral molecules. Finally, a recurring theme in this thesis is the use of ionic chiral auxiliaries for the purpose of asymmetric induction in optically active salts, and these studies are performed by using salts of the acid analogue of XVI. 5.2. Solid State Photochemistry of Substituted oc-Mesitylacetophenones Two para- and four meta-substituted oc-mesitylacetophenone derivatives (XVI(a-f), Figure 5.3) were synthesized and their solid state photochemical reactivities were studied.8 It was anticipated that 8-hydrogen atom abstraction would be observed in these experiments, and that some or all of the meta-substituted compounds would display a "meta-steering effect" in the crystal packing. A l l the starting ketones XVI(a-f) photolyzed cleanly to products that were determined to be the 2-indanols XVII (Table 5.1) by NMR. 135 Chapter 5 Results/Discussion (a) para-F (c) meta-F (e) meta-Bt (b) para-CN (d) meta-Ci (f) meta-CN Figure 5.3. The solid state photochemistry of the a-mesityacetophenone system (XVI). Table 5.1. Temperature-dependent conversions in the solid state photolysis of the molecular ketones XVI(a-f). T (°C) t Time(h) XVIIa (%) XVIIb (%) XVIIc(%) XVIId (%) XVIIe(%) XVIIf(%) r.t. 1 0 56 49 82 r.t. 2 0 96 m.t.* m.t.* 6 100 r.t. 8 3 m.t.* m.t.* m.t.* 14 m.t.* -18 2 0 6 21 2 70 -18 6 0 43 r.t. = ambient room temperature in the photolysis box (30-40°). *m.t. = sample showed signs of melting upon photolysis during or after this interval. The photochemistry of XVI(b,c,f) offers encouraging results by demonstrating rapid and clean solid state reactions to photoproduct X V I I with yields as high as 82% achievable after only one hour of irradiation. Photolyses performed at low temperature minimized melting of the samples but the reactivities of the ketones were somewhat reduced. 136 Chapter 5 Results/Discussion 5.3. Crystal Structure-Reactivity Relationships Perhaps the most striking photochemical result from Table 5.1 is the dissimilarity in percent conversion of the seven reactants to photoproduct after certain intervals. These compounds differ only in the substituent at the periphery of each molecule, and their different reactivities in the solid state must be attributed to the crystalline environment. X-ray crystallographic analyses of XVI(a-f) reveal that many of these structures share a common crystal system and space group (Table 5.2). However, there must be significant differences in the abstraction parameters or molecular packing of the compounds in order to reflect such disparities in reactivity. Table 5.2. X-ray crystal data of ketones XVI(a-f).' XVIa XVIb XVIc XVId XVIe XVIf Crystal system monoclinic monoclinic orthorhombic monoclinic monoclinic monoclinic Space group Pill a P2j/a Pbca P2yla Pl-Ja Pill a a, A 10.151(3) 10.586(1) 9.985(3) 7.984(5) 7.996(2) 7.962(1) b,k 8.687(4) 8.377(2) 33.586(7) 15.621(3) 15.755(3) 15.840(3) c A 16.802(4) 17.539(2) 8.457(4) 11.770(1) 11.843(1) 12.119(3) a ( ° ) 90 90 90 90 90 90 P O 104.99(2) 107.325(8) 90 100.68(2) 101.06(1) 107.40(1) Y(°) 90 90 90 90 90 90 y,A 3 1431.1(7) 1484.9(4) 2836(1) 1443(1) 1464.1(5) 1458.5(5) z 4 4 8 4 4 4 The derivation of abstraction values of the six ketones XVI(a-f) from X-ray data is more complex than for the other compounds discussed thus far because the abstractable 5-hydrogen atoms reside on rotating methyl carbons. In the X-ray 1 Complete crystallographic data is presented in Chapter 7. 137 Chapter 5 Results/Discussion diffraction experiment, the scattering power of the hydrogen atom is weak and its location in the presence of heavy atoms has a larger degree of error than for atoms with higher scattering efficiency. It is sufficient for hydrogen atom positions to be placed in idealized positions based on chemical hybridization rules in cases where the hydrogen atoms are not mobile. In the present situation, however, accurate placement of mobile 8-hydrogen atoms requires a more rigorous method employing both idealizing calculations and electron difference maps." It is essential that we accurately locate the hydrogen atom positions on the methyl carbons by first determining their torsional vectors from the Fourier difference maps followed by an idealization calculation.1" As a further check on the accuracy of their positions, calculations were performed which searched for the torsional angle that maximized electron density around the methyl carbon and this angle was compared to those from the Fourier map (Figure 5.4).9 11 Placement of hydrogen atoms at calculated positions generally results in hydrogen atoms which are normally staggered with respect to their neighbouring atoms but this is not necessarily the case for methyl groups attached to an aromatic ring. 1 , 1 The difference map provides the torsional angle which describes where most of the hydrogen atom electron density may be found, and the idealizing calculation furnishes the hydrogen atoms with chemically reasonable bond lengths and angles. 138 Chapter 5 Results/Discussion ( c ) (d) Figure 5.4. Some possible positions (a, b, c, d) for methyl hydrogen atoms adjacent to an aromatic ring. Once the hydrogen atoms are placed in their final atomic positions, their abstraction parameters can be calculated (Figure 5.5a). Because of possible methyl group rotation in the solid state, we introduce a new hydrogen atom abstraction parameter L (Figure 5.5b), which is the separation distance between the carbonyl oxygen and the nearest 8-carbon atom. L is independent of methyl group rotation, and intuitively, the closer the photoexcited carbonyl oxygen atom is to one of the methyl carbons (i.e. a small L value), the closer the hydrogen atoms of that methyl carbon are to the oxygen atom (i.e. small d values). This is observed experimentally in the crystal structures of the a-mesitylacetophenone derivatives (Figure 5.6). Thus, should the hydrogen atoms be disordered on the 8-carbon, the uncertainty of the positional parameters of the hydrogen atoms can be overcome by invoking L as an approximate description of the separation between the photoexcited oxygen atom and the abstractable hydrogen atoms. The abstraction geometries of XVI(a-f) are listed below in Table 5.3. 139 Chapter 5 Results/Discussion Figure 5.5. (a) The geometric parameters for 8-hydrogen atom abstraction.1" (b) The new abstraction parameter L expresses the separation distance between the carbonyl oxygen atom and the closest 8-carbon atom. Figure 5.6. A plot of the separation distance between the carbonyl oxygen atom and the closest S-methyl carbon ( O - 8 - C distance, L ) for derivatives XVI(a-f) and the separation distance between the closest 8-hydrogen atom on this carbon and the carbonyl oxygen ( O - 8 - H distance, d). Together, these two graphs illustrate the excellent correlation between L and d. 1 V The abstraction parameters define the spatial relationship for the abstraction of a hydrogen atom by the excited carbonyl oxygen atom, d = distance between oxygen and hydrogen, O • H ; co = dihedral angle formed between the O - H vector and its projection on the nodal plane of the C=0 group; A = C=0- • H angle, and 0 = O • Ff-C angle; D = distance between oxygen and carbon. See Chapter 1 for a more detailed discussion. 140 Chapter 5 Results/Discussion Table 5.3. Crystallographically derived C=0- • -5-Ff abstraction geometries for ketones XVI(a-f). f Compound d(A) co(°) A(°) e n D(A) L (A) para-substituted XVIa 2.93 59 78 122 3.45 3.56 XVIb 2.71 63 86 121 3.32 3.33 /neta-substituted XVIc 2.80 57 83 125 3.43 3.44 XVId 3.08 61 68 123 3.41 3.71 XVIe 3.12 62 70 121 3.41 3.72 XVIf 2.73 64 83 124 3.30 . 3.38 Average 2.90 61 78 123 3.38 3.52 Y-H-Exp 1 0 2.54-2.90 34-64 76-92 113-117 2.95-3.10 -Y-H-Ideal 2.72 0 90-120 180 <3.4 3.70 fOnly the parameters for the closest methyl group and 5-hydrogen atom to the carbonyl oxygen are tabulated. Two major observations can be made from the data in Table 5.3. First, the typical 5-hydrogen atom abstraction parameters are within range of those found for y-hydrogen atom abstraction; the most notable difference is the larger separation distance between the two radical centres of the 1,5-biradical (D). Secondly, there appears to be an approximate correlation between the d values and the percent conversion of the compounds (see Table 5.1), with smaller separation distances representing faster reaction rates in the para- and meta-substituted derivatives. Intuitively, this second observation appears reasonable because the separation distances between the abstracted 5-hydrogen atom and the photoexcited carbonyl group can be assumed to determine the rate of hydrogen atom abstraction, k H , which is proportional to the overall quantum efficiency of the reaction, <E> (Equation 5.1): 141 Chapter 5 Results/Discussion # = <t>isc k HxP Eq. 5.1 where O is the quantum yield, <J>isc is the quantum yield of intersystem crossing from the singlet excited state to the triplet excited state, % is the lifetime of the biradical, and P is the probability of biradical cyclization.1 1 If the values of (j^ sc, and P are similar for the two para-substituted ketones, which is not unreasonable due to their structural 1 9 similarities, then Table 5.3 becomes an approximate guide to the overall quantum yield of the reaction for these two para-substituted derivatives. Despite the difficulties involved in making quantitative measurements in solids, this estimate of reactivity with geometry appears to be well-founded, because the para-fluoro substituted ketone o (XVIa) with its 2.93 A d-value, reacts much more slowly than the para-cyano substituted ketone (XVIb), which has a more favourable d-value of 2.71 A . v A comparison of the four meta-substituted ketones reveals that the ketones which react slowly (XVId and XVIe in Table 5.3) have less favourable geometries, whereas the ketones which react faster (XVIb and XVIf) have more favourable geometries. In any event, it is difficult to attribute the reaction rates solely to the differences in the C=0--8-H separation distance and geometry, although this simple approach to the photochemistry of X V I agrees quite well with the experimental results. Returning to the discussion of the reactivity of the two para-substituted a-v A larger reaction cavity may permit the geometric changes that are necessary during photoexcitation and biradical cyclization. However, a study of the reaction cavity sizes of XVII(a-b) reveals that these two compounds have very similar reaction space surrounding each molecule (117 A 3 vs 114 A for XVIIa and XVIIb , respectively), thus suggesting that the reaction cavity does not play a large role in determining the reaction rates in this system. 142 Chapter 5 Results/Discussion mesitylacetophenones, we find that the crystal structures of X V I a and X V I b are isostructural (Table 5.2) but that dissimilarities arise in the molecular conformations of these two compounds (Figures 5.7 - 5.8). The dihedral angle between the carbonyl plane and the mesityl ring is quite different in X V I a and X V I b . This dihedral angle between the mesityl and the carbonyl planes can be described with the parameter K\ (Figure 5.7 and Table 5.4), which is the angle between their least-squares plane. The greater the deviation from a bisecting position (a bisecting position would have a value of K{ = 90°), the closer the carbonyl oxygen approaches one of the two 8-carbons. The relationship between K\ and the distance from the oxygen atom to the methyl carbons (L) can be visualized by plotting the 0---8-C separation distances of each derivative against the dihedral angle between the carbonyl plane and the mesityl ring (Figure 5.8). It can be seen from Figure 5.8 that as decreases, the oxygen atom approaches closer to one of the 8-carbons. At the other extreme, when the two planes are bisecting (i.e. K\ = 90°) the oxygen atom is approximately equidistant from the two methyl carbons, favouring neither. Thus, one would expect that a bisecting position is the least reactive conformation, and this is exactly what is observed photochemically. Tables 5.1 and 5.4 show that the fastest reacting ketones have the smallest values of K i . 143 Chapter 5 Results/Discussion *1 Figure 5.7. The dihedral angle between the carbonyl plane and the mesityl ring is designated K.\. Table 5.4. Values for the dihedral angle between the carbonyl plane and the mesityl ring. Compound K l ( ° ) XVIa 85.0 XVIb 76.0 XVIc 81.0 XVId 88.9 XVIe 89.1 XVIf 76.3 ^4.4 j Figure 5.8. A plot of the separation distance L against the dihedral angle K\. Ascending values of the dihedral angle Ki of the cc-mesitylacetophenones are plotted along the x-axis in the following order: XVIb , XVIf , XVIc , X V I a , X V I d , and XVIe. The separation distance between 01 and the closer 8-C atom is designated L ' ; the separation distance between O l and the farther 5-C atom is designated L " . A dihedral angle of 90° ( K I ) brings the carbonyl into a bisecting position with respect to the mesityl ring, resulting in approximately equal separation distances between O l and the two methyl carbons (i.e. L ' ~ L " ) . 144 Chapter 5 Results/Discussion The meta-substituted derivatives also follow this reactivity trend - the meta-cyano compound (XVIf), which has short d and D values compared to the other meta-substituted ketones, reacts fastest, whereas the slower-reacting meta-substituted derivatives (XVId - XVIe) possess YL\ values approaching a bisecting angle of 90°. The d-values of these ketones exceed 3 A , and can be considered as approaching the upper abstraction distance limit. The meta-fluoro ketone XVIc possesses parameters intermediate to the other mefa-substituted ketones, and not surprisingly, its reactivity also lies between their extremes. The crystal structures of the a-mesitylacetophenones XVI(a,b,d-f) are illustrated below in Figures 5.9 - 5.13. Figure 5.9. ORTEP diagram of the para-ihiovo derivative X V I a . The carbonyl group is in a nearly bisecting position with respect to the mesityl ring. 145 Chapter 5 Results/Discussion Chapter 5 Results/Discussion Figure 5.13. ORTEP diagram of the meta-cyano derivative XVIf. The carbonyl group is 14° from a bisecting position with respect to the mesityl ring. The substituent is anti to the carbonyl oxygen O l , in contrast with the two meta-substituted halo derivatives XVI(e-f) (previous two figures) which see their substituents syn to 01. 5.4. Molecular Mechanics Calculations A conformational search for the lowest energy conformations of these a-mesitylacetophenone derivatives shows the same energy-mimimized conformation (MM+) regardless of the substituent.13 In this conformation, the carbonyl group bisects the mesityl ring (i.e. K\ = 90°) so that the methyl groups on the ortho-position of the mesityl ring are equidistant to O l . This conformation also has a dihedral angle of 0° between the substituted phenyl ring and the carbonyl group (designated K2, Figure 5.14). A diagram of XVIa is illustrated below in Figure 5.15. Hydrogen atom parameters from molecular mechanics simulations for XVII(a,b,d,f) are listed in Table 5.5. 147 Chapter 5 Results/Discussion <2 Figure 5.14. The dihedral angle between the carbonyl plane and the phenyl ring is designated K2-Figure 5.15. Lowest energy conformation of X V I a from molecular mechanics calculations. The carbonyl group bisects the mesityl ring (iq = 90°). The para-fluoro phenyl ring is fully conjugated with the carbonyl plane (Kr? = 0°). 148 Chapter 5 Results/Discussion Table 5.5. The hydrogen atom abstraction geometries of the two closest hydrogen atoms ( H a and H^) on the orr/zo-methyl carbons of the lowest energy conformations of XVI(a,b,d,f). Compound Energy (kj) H# d(A) w o A(°) o n D(A) L (A) K l ( ° ) K 2 ( ° ) XVIa H a 3.01 58 74 117 3.56 3.66 90 0 8.22 H b 3.01 58 74 117 3.55 3.66 XVIb H a 3.01 58 74 117 3.55 3.66 90 0 8.47 H b 3.01 58 74 117 3.55 3.66 XVId 9.26 H a H b 3.01 3.01 58 58 74 74 117 117 3.55 3.55 3.66 3.66 90 0 XVIf 9.07 H a H b 3.00 3.01 58 58 74 74 117 117 3.55 3.55 3.66 3.66 90 0 The computational structure of XVIa, which locates the carbonyl group at a dihedral angle (KI ) that nearly bisects the mesityl group, strongly resembles the conformation determined from X-ray crystallography. However, M M + calculations for the other substituted ketones in Table 5.5 yield this same bisecting conformation. Because these molecular mechanics calculations search for the lowest energy conformations of molecules in the gas phase and completely neglect neighbouring molecular effects, it appears that substitution does not alter the conformation of these molecules in the gas phase. If this is indeed the case, then the large differences in conformation and reactivity as determined from the crystal structures of the derivatives are largely derived from intermolecular interactions. Clearly, the mathematical expressions used in these molecular mechanics calculations will inadequately describe the energy of the molecules in the crystal, and hence, molecular 149 Chapter 5 Results/Discussion modelling is a poor method for predicting the structure and reactivity of these compounds in the solid state at the present time. 5.5. X-ray Crystallographic Analysis of the Crystal Packing of the a-Mesitylacetophenones In Chapter 2, meta-substituted enamides were synthesized and studied crystallographically in order to ascertain the presence or absence of the "meta-steering" effect. Only one of the three halo-derivatives (le) was found to crystallize in a chiral space group, and its behaviour was attributed to its inherent conformational chirality, and not to the "meta-steering" effect. In the present chapter, the crystal structures of para-substituted a-mesitylacetophenones are compared to those of the meta-substituted derivatives in a continuing search for the "meta-steering" effect. As Table 5.2 has already shown, five of the six halo-substituted a-mesitylacetophenones crystallize in the monoclinic achiral space group P2\/a, regardless of the substituent location. The crystal packings of the six ketones XVI(a-f) were examined further in order to distinguish the differences between the effects of para- and meta-substitution. Because these are molecular crystals, the forces that need to be investigated are primarily van der Waals forces, and a search was initiated for close contacts in the crystal structures. A study of the packing diagrams of the two para-substituted compounds (Figures 5.16 - 5.17) shows that their packing motif is virtually identical, with 150 Chapter 5 Results/Discussion significant Jl—% interactions in the crystal structures. These crystal structures are isostructural/1 In both cases, these special contacts exist only between the less bulky benzoyl rings, and not between the mesityl rings. The centroid-to-centroid distances of the interacting rings in the crystal structures of X V I a and X V I b are 3.7 A and 3.8 A, respectively. The mesityl rings do not show any close n—n interactions with the benzoyl rings. The identity of the para-substituent on the benzoyl ring does not alter the conjugation of the carboxyphenyl ring with its attached carbonyl group. Both derivatives are well-conjugated, the angle K2 between the carbonyl group and the para-substituted phenyl ring being 3.0° and 3.3°, respectively. F i g u r e 5.16. The packing diagram of X V I a . There are significant 7i—7t interactions between the benzoyl rings. The fractional coordinates for these compounds are listed in Chapter 7. 151 Chapter 5 Results/Discussion Figure 5.17. The packing diagram of XVIb. The packing motif is identical to that of XVIa above, with n—n interactions between the benzoyl rings. The meta-substituted ketones have their own packing patterns (Figures 5.18 and 5.19). With the exception of the meta-fluovo substituted derivative (XVIc), these meta-substituted ketones have almost identical unit cells (although XVIf has a larger (3 angle). However, there are some differences in the conjugation of the carbonyl group with the meta-substituted phenyl ring (Table 5.6). These values are in sharp contrast to the MM+ calculated dihedral angles of 0° (Table 5.5). Table 5.6. The dihedral angle between the carbonyl plane and the attached substituted benzoyl group (ie>) from X-ray crystallographic data. para-derivative K 2 ( ° ) meta-derivative K 2 (°) XVIa 3.0 XVIc 4.9 XVIb 3.3 XVId 5.8 XVIe 9.3 XVIf 18.8 152 Chapter 5 Results/Discussion The most striking deviation found in Table 5.6 is for XVIf, which has a K2 value of 19°. Despite showing this difference in molecular shape with respect to the chloro- and bromo-substituted derivatives, XVIf crystallizes in almost exactly the same way as XVId and XVIe (Figures 5.18 - 5.20). These crystals are isostructural. A search for intermolecular contacts between substituent groups in XVI(d-f) failed to locate any significant weak intermolecular interactions. The closest C1---C1 , Br- -Br , and C=N---N=C contact distances are 4.73 A, 4.76 A, and 4.37 A, respectively. Figure 5.18. The packing diagram of XVId, showing the n---n interactions between the benzoyl rings. 153 Chapter 5 Results/Discussion Figure 5.19. The packing diagram of XVIe, showing the n--n interactions between the benzoyl rings. • * AV Figure 5.20. The packing diagram of XVIf, showing the 7t---7t interactions between the benzoyl rings. 154 Chapter 5 Results/Discussion A search for aryl-•-aryl interactions reveals that the distance between the centroids of interacting benzoyl rings in the crystal structures of XVI(d-f) are approximately the same, being 3.67 A, 3.63 A, and 3.67 A, respectively. The packing coefficients for these compounds were also calculated and their values are not significantly different, 69.7%, 68.1%, and 68.2%, respectively. Thus, it appears that the differences in molecular packing between XVIf and the two halo-substituted derivatives XVI(e-d) are not extensive, but their impact on molecular conformation is quite measurable. The crystal structure of the meta-fluoro tx-mesitylacetophenone (XVIc) deviates substantially from the other three meta-substituted derivatives. Compound XVIc crystallizes in an orthorhombic space group with the fluorine atom disordered over two sites - the phenyl ring is flipped along the C3 - C6 axis so that the fluorine atom is either syn (Figure 5.21) or anti (Figure 5.22) to the carbonyl oxygen. Because this disorder does not directly involve the methyl carbons, it is not expected to affect hydrogen atom abstraction. A study of the unit cell packing indicates that there are no significant F - F or aryl-••aryl contacts in the crystal structure (Figure 5.23). An analysis of the cavity of this compound shows that there is not enough free space for phenyl rotation around the C3 - C6 axis to occur, and the fluorine disorder must be static (Figure 5.24). 155 Chapter 5 Results/Discussion Figure 5.21. ORTEP diagram of the major conformation of XVIc. The fluoro substituent is syn to the carbonyl group. Figure 5.22. ORTEP diagram of the minor conformation of XVIc. The fluoro substituent is onti to the carbonyl group. 156 Chapter 5 Results/Discussion Figure 5.23. The packing diagram of XVIc showing only the conformation of the major disordered component (fluoro group syn to the carbonyl oxygen). Figure 5.24. A n illustration of the cavity around a reactant molecule of XVIc . The packing coefficient of the crystal structure of XVIc was calculated to be 69.3%. 157 Chapter 5 Results/Discussion 5.6. Solid State Photochemical Studies of 4-[2-(2,4,6-Trimethylphenyl)-acetyl] benzoic acid and its Optically Pure Salts The photochemistry of the a-mesitylacetophenone system thus far has indicated that 5-hydrogen atom abstraction occurs readily in this system. The preparation of optically active salts from the carboxylate derivative of XVI and optically pure amines (i.e. using the Ionic Chiral Auxiliary Concept) allows for the further evaluation of enantioselective hydrogen atom abstraction. The photochemistry of 4-[2-(2,4,6-trimethylphenyl)-acetyl]benzoic acid (XVIg) and of its optically active salts (S3, S4, and S5) is presented in the following sections. 5.6.1. The Solid State Photochemistry of 4-[2-(2,4,6-Trimethylphenyl)-acetyl] benzoic acid As a prelude to the study of asymmetric synthesis of 2-indanols from the a-mesitylacetophenone system (XVI), the para-carboxylic acid of a-mesitylacetophenone (XVIg, Figure 5.25) was synthesized, and its solid state photochemistry studied. Compound XVIg reacts to yield the 2-indanol product (XVIIg) after irradiation. X-ray quality crystals of XVIg were grown, and preliminary diffraction measurements of a single crystal revealed a very long c-axis of 52.8 A . When the unit cell was fully refined at high angles, it was found to incorporate a volume of 6102 A 3 with a Z value of 16 (Table 5.7) even though the molecule is quite small. After a long run of direct methods, the crystal structure was finally solved and revealed to have four hydrogen bonded molecules of XVIg in the 158 Chapter 5 Results/Discussion asymmetric unit (Figure 5.26). The four acid molecules in the asymmetric unit form two pairs of dimers, thus explaining the unit cell elongation. XVIg XVIIg Figure 5.25. The solid state photochemistry of the carboxylic acid derivative of XVI. Table 5.7. Crystallographic data of 4-[2-(2,4,6-trimethylphenyl)-acetyl]benzoic acid (XVIg).vii xyjg. Crystal system monoclinic Space group Flllc a, A 12.590(1) b, A 9.201(1) c A 52.865(4) <x(°) 90 P(°) 94.451(8) Y ( ° ) 90 v, A 3 6102(1) z 16 11 Complete crystallographic details are presented in Chapter 7. 159 Chapter 5 Results/Discussion Figure 5.26. A n illustration of the unit cell of XVIg, showing the long c-axis and the four different conformations of the carboxylic acids in the asymmetric unit. Two of the four molecules appear to be nearly related by a centre of symmetry. A s Figure 5.26 above illustrates, the four molecules of XVIg in the asymmetric unit have different conformations. The dihedral angles that describe these conformations (iq and K 2 ) are listed below in Table 5.8. Only two of the four molecules have reasonable hydrogen atom abstraction distances (Table 5.9).vm v m In order to try to observe a single crystal-to-single crystal reaction, and hence, define which of the acid molecules are the first to react, single crystals of XVIIg were irradiated for very short intervals and their structures were monitored using X-ray crystallography. However, attempts to index the unit cells of these partially irradiated crystals were unsuccessful, indicating that the reaction was not topotactic under the applied conditions, and the samples were no longer truly crystalline. 160 Chapter 5 Results/Discussion Table 5.8. Conformational angles of the four molecules found in the crystal structure of XVIg. Molecule # *1 K 2 1 89.5 8.7 2 76.3 29.3 3 82.2 24.6 4 88.3 3.4 Table 5.9. The abstraction geometries of the closest 5-hydrogen atoms for XVIg. Molecule # d co A e D L 1 3.31 42 86 117 3.78 3.85 2 2.79 59 88 119 3.37 3.38 3 2.77 46 91 128 3.53 3.46 4 3.15 59 61 122 3.31 3.77 The data in Table 5.8 reveal some serious deviations from planarity between the carbonyl group and the attached carboxyphenyl group in molecules 2 and 3. The previously studied ketones XVI(a-f) do not exhibit such large deviations from planarity; hence, the reduced conjugation in molecules of XVIg is likely the result of hydrogen bonding effects. 5.6.2. Asymmetric Induction in the Solid State Photochemistry of Three Optically Pure Salts of a-Mesitylcarboxyacetophenone Using the Ionic Chiral Auxiliary Method, three optically pure organic salts were prepared from the title compound XVIg and the enantiomerically pure amines (15',2/?)-(+)-norephedrine (67), (7?)-(+)-a,4-dimethylbenzylamine (68), and (/?)-(+)-161 Chapter 5 Results/Discussion A^a-dimethyl-benzylamine (69) . These salts are designated S 3 , S 4 , and S 5 , respectively. Solid state irradiations were conducted on these salts at room temperature until high conversion to photoproduct was achieved. A low temperature irradiation of S 3 was also performed. The extent of conversion was estimated by gas chromatography following workup with diazomethane, and enantiomeric excesses were measured using chiral HPLC. The results of the photolyses are compiled in Table 5.10. Irradiations of two of the three salts, S 3 and S 4 , gave excellent e.e.'s even at high conversion. At low conversion, an e.e. as high as 98% could be achieved upon irradiation of salt S 3 . Photolysis of S 3 , whether at room temperature or -20°C, afforded predominately one enantiomer of XVIIg, whereas irradiation of S 4 afforded the enantiomer of opposite optical rotation. Hence, by substituting one optically pure amine with the other, both enantiomers of the 2-indanol photoproduct can be obtained quite readily. The third salt, S 5 , however, reacted relatively slowly and failed to give any appreciable e.e. 162 Chapter 5 Results/Discussion Figure 5.27. The solid state photochemical results of X V I g with ionic chiral auxiliaries. Table 5.10. Solid state photolysis results for the chiral salts of keto acid X V I g . Salt Ionic Chiral Auxiliary Temp Time (min) Conversion e.e. (%) (°C)f (%) S3 (15,2/?)-(+)-Norephedrine r.t. 130 80 80 -20 62 30 98 S4 (/?)-(+)-a,4-Dimethylbenzylaime r.t. 180 89 83 S5 (7?)-(+)-A',a-Dimethylbenzylamine r.t. 280 14 0 fr.t. = Ambient temperature in the photolysis box (30-40 °C). An explanation for the photochemical enantioselectivity of these salts was sought from X-ray crystallographic analysis of the crystal structures (Table 5.11). If we are to assume that the reactivities are governed by structural factors, then the 163 Chapter 5 Results/Discussion origins of the enantioselectivity of the 8-hydrogen abstraction reaction may be the result of the conformational geometry of the carbonyl group with respect to the methyl groups ( KJ ) . Although the theoretical calculations in section 5.4 predict that Ki = 90° regardless of substituent, crystallographic evidence from XVI(b,c,f,g) indicates otherwise. Thus, there is reason to believe that the oc-mesitylacetophenone system can selectively abstract a 8-hydrogen atom from one of the two enantiotopic orr/io-methyl groups. If the methyl group proximal to the Re face of the photoexcitable carbonyl group is labelled as a and the methyl group proximal to the Si face is labelled as b (Figure 5.28), and if the crystalline state prohibits large-scale bond rotations of the 1,5-biradical that is formed from 8-hydrogen atom abstraction, then abstraction of a hydrogen atom from a should lead to the (S)-enantiomer, and abstraction of a hydrogen atom from b should lead to the opposite (R)-enantiomer. Should the compound crystallize in a conformation in which the carbonyl oxygen is closer to one ortho-methyl group than the other (i.e. Kj * 90°), the formation of one enantiomer will be favoured over the other in a chiral space group (see Table 5.11 for the space groups), and thus, we can propose that the enantiomeric excesses that are observed in this system arise due to the deviation in the dihedral angle between the carbonyl group and mesityl plane. 164 Chapter 5 Results/Discussion Si H b O / = = o H Re Figure 5.28. A diagram illustrating the Re and Si faces of X V I g . Table 5.11. Crystallographic data for the optically pure salts of keto acid (XVIg) . l x S3 S4 S5 Crystal system monoclinic monoclinic triclinic Space group C2 PI a, A 17.732(5) 7.182(1) 10.519(3) b,k 5.612(2) 6.048(1) 13.927(5) c, A 25.720(4) 27.779(2) 9.501(3) a(°) 90 90 99.57(3) P(°) 109.18(2) 97.094(9) 114.97(2) Y(°) 90 90 101.68(3) v, A 3 2417(1) 1197.4(2) 1184.9(8) z 4 2 2 The X-ray crystal structure of S3 clearly shows a hydrogen atom on methyl group b in a favourable position for 5-hydrogen abstraction (Table 5.12). The distance o o d between the carbonyl oxygen and H5 is 2.69 A , over 1 A shorter than the corresponding distance to H a . These values are a reflection of the twisted conformation of the molecule that is emphasized by the 12° deviation of the dihedral angle K i from its bisecting angle of 90° (Table 5.13). According to this crystal structure, hydrogen atom abstraction should occur preferentially from methyl group b, Complete crystallographic data are presented in Chapter 7. 165 Chapter 5 Results/Discussion and the formation of the (7?)-enantiomer should be in excess. The formation of the alternate enantiomer would require a 180° rotation of the acyl group, which is unlikely from topochemical considerations. Thus, this rationale explains the high enantioselectivity that is found for S3. By comparing the geometric parameters for ketones XVI(a-f) with S3, we also see the favourable abstraction values which likely account for its relatively rapid reaction rate. An ORTEP diagram of XVIg in S3 is shown below in Figure 5.29, and a packing diagram in Figure 5.30 Table 5.12. The abstraction geometries of the closest 5-hydrogen atoms in the optically pure salts S3-S5. Salt H x d co A 0 D L S3 H b 2.69 54 84 127 3.45 3.38 S4 H a 2.60 50 90 128 3.46 3.29 S5* H a 3.07 58 60 126 3.32 3.74 H b 3.05 51 53 126 3.26 3.71 Average 2.85 53 71 127 3.37 3.53 *There are two molecules in the asymmetric unit. One molecule slightly favours the abstraction of F£a and the other favours Hb-Table 5.13. Conformational angles of the four molecules of XVIg found in the crystal structures of S3-S5. Compound Ki K2 53 77.8 5.5 54 74.9 3.7 S5* 88.7 25.1 88.0 23.9 *Two independent molecules in the asymmetric unit. 166 Chapter 5 Results/Discussion Figure 5.30. The packing diagram of S3. The n- • -n interactions that are found in the crystal structures of the molecular ketones are not present in this crystal packing. 167 Chapter 5 Results/Discussion Further support for the picture presented above comes from the crystal structure of salt S4 (Figure 5.31), which as mentioned previously, predominately gives rise to the enantiomer of opposite rotation to that obtained from photolysis of S3. The crystal structure of S4 shows that the conformation of the reacting molecule possesses a carbonyl group that is closer to H a than H ^ , as suggested by the geometric parameters and the K 4 value (Tables 5.12 and 5.13). The Re face is favoured in S4, hence the (S)-photoproduct is expected to form from photolysis of S4. In both S3 and S4, excellent e.e. is obtained even at high conversion, indicating synthetic viability. Crystal structure analysis of the optically pure salt S5 (Figure 5.32) also explains why it gives only racemic photoproduct upon solid state irradiation. The crystals of this salt contain equal amounts of two independent conformational isomers of XVIg in the asymmetric unit. These conformers have a near mirror-image relationship (i.e. they have opposite conformational chiralities), and each favours 168 Chapter 5 Results/Discussion slightly the abstraction of the opposite 8-hydrogen atom (Error! Reference source not found.). With one molecule abstracting H a and the other abstracting H^, low e.e. is to be expected. Similar observations have been already made in the chiral salts of the ds-decalyl system in Chapter 4, where low e.e. was observed.14 The carbonyl group nearly bisects the mesityl ring in both molecules in S5, and hence, the geometric parameters are poor for hydrogen atom abstraction. This explains the lower reactivity of S5 compared to S3 and S4. Figure 5.32. ORTEP diagram of one of the two independent anions of XVIg in salt S5. The conformation shown above favours the abstraction of F£a. 169 Chapter 5 Results/Discussion Figure 5.33 The packing diagram of salt S5 illustrates the hydrogen bonding of the X V I g anions with the ionic auxiliaries. The two independent formula units in the asymmetric unit are coloured (cyan and purple). 5.7. Conclusions The reactions discussed in this chapter demonstrate once more the extent to which reactivity and selectivity in the solid are controlled by the conformation adopted by each component in the crystal structure. We have shown that five-membered rings can be synthesized, often in high yields, indicating synthetic value. Moreover, this synthesis can be enantioselective because application of the Ionic Chiral Auxiliary Method allows for the governing of enantioselectivity in solid state photochemical 170 Chapter 5 Results/Discussion reactions. This mode of asymmetric synthesis may become the most valuable procedure for the formation of highly-strained enantio-pure molecules. The investigations into the "meta-steering" effect in the crystal packing of XVI result in inconclusive observations similar to those found in Chapter 2, and the existence of the mem-steering effect remains unsubstantiated. Compounds which contain the heavier halogens, chlorine and bromine, tend to follow the substituent cooperative effect, and crystallize isostructurally, whereas fluorine introduces entirely different effects into the crystal packing. 171 Chapter 5 Results/Discussion 5.8. References for Chapter 5 1 Wender, P. A. ; Howbart, J. J. J. Am. Chem. Soc. 1981,103, 688. 2 (a) Hart, D. J.; Tsai Y . - M . J. Am. Chem. Soc. 1982, 104, 1430. (b) Stork, G.; Blaine, N . H. J. Am. Chem. Soc. 1982,104, 2321. 3 For a general review of 8-hydrogen atom abstraction reactions, see Wagner, P. J.; Park, B.-S.; In Organic Photochemistry; Padwa, A . Ed.; Marcel Dekker: New York, 1991. 4 Wagner, P. J.; Zepp, R. G. J. Am. Chem. Soc. 1971, 93, 4958. 5 Wagner, P. J.; Kelso, P. A. ; Kemppainen, A . E., Zepp, R. G. J. Am. Chem. Soc. 1972, 94, 7500. 6 Wagner, P. J.; Meador, M . A. ; Zhou, B.; Park, B. -S. 7. Am. Chem. Soc. 1991,113, 9630. 7 Although much is known about the geometric requirements for y-hydrogen atom abstraction, this cannot be said for 8-hydrogen atom abstraction. There have been few papers in the literature reporting such data. Among them are: (a) Irngartinger, H. ; Fettel, P. W.; Siemund, V . Eur. J. Org. Chem. 1998, 2079. (b) Wagner, P.J.; Zhou, B.; Hasegawa, T.; Ward, D. L . J. Am. Soc. Chem. 1991,113, 9640. The compounds discussed in this chapter were synthesized and studied photochemically by Rademacher, R., University of British Columbia. 172 Chapter 5 Results/Discussion 9 Sheldrick, G. M . SHELX-97 - Programs for Crystal Structure Analysis; Institut fiir Anorganische Chemie der Universitat, Tamrnaristrasse 4, D-3400, Gottingen, Germany, 1998. 1 0 Ihmels, H. ; Scheffer, J. R. Tetrahedron 1999, 55, 885. 1 1 Turro, N . J. Modern Molecular Photochemistry; Benjamin/Cummins: Menlo Park, CA, 1978; Chapter 10. 1 2 The effects of para-substitution on phenyl ketones, in particular, para-fluoro derivatives of the mesitylketones, have been found to have minor effects on their electronic features: (a) Wagner, P. J.; Truman, R. J.; Scaiano, J. C. J. Am. Chem. Soc. 1985, 107, 7093. (b) Wagner, P. J.; Kemppainen, A . E.; Schott, H . N . J. Am. Chem. Soc. 1973,95,5604. 1 3 Molecular mechanics calculations and conformational searches were performed using the Hyperchem software package for PC computers. Hyperchem and ChemPlus; Hypercube, Inc.: Gainesville, Fla., 1996. 1 4 For other examples of low e.e. derived from two independent molecules in the asymmetric unit, see: (a) Koshima, H. ; Maeda, A. ; Masuda, N . ; Matsuura, T.; Hirotsu, K. ; Okada, K.; Mizutani, H. ; Ito, Y . ; Fu, T. Y . ; Scheffer, J. R.; Trotter, J. Tetrahedron Asymmetry 1994, 5, 1415. (b) Jones, R.; Scheffer, J. R.; Trotter, J.; Yang, J. Tetrahedron Lett. 1992, 33, 5481. 173 Chapter 6 Experimental/Synthesis Chapter 6 Experimental (Organic Synthesis) 6.1. General Considerations Infrared Spectra (IR) Infrared spectra were recorded on a Perkin-Elmer 1700 Fourier transform infrared spectrometer, with the absorption maxima of the spectral bands reported in reciprocal centimetres (cnr 1 ). A l l samples were prepared as K B r pellets by grinding 100-150 mg of K B r and 5 -10 mg of sample together and compressing the mixture in a Perkin-Elmer evacuated die (186-0002) with a Carver Laboratory Press (Model B, 18000 psi). Nuclear Magnetic Resonance (NMR) Spectra Proton nuclear magnetic resonance (*H NMR) spectra were recorded on Bruker AC-200 (200 MHz) or Bruker WH-400 (400 MHz) spectrometers at ambient temperature in C D C I 3 unless otherwise noted. Signal positions are reported as chemical shift (8) in parts per million (ppm), with the residual solvent peaks used as the internal standard against tetramethylsilane (TMS, 8 = 0.00 ppm). The multiplicity of the signals, number of protons, and assignments are given in parentheses following 174 Chapter 6 Experimental/Synthesis the chemical shifts. The multiplicities of the signals are abbreviated as follows: s = singlet, d = doublet, t = triplet, q = quartet, and m = multiplet. Carbon nuclear magnetic resonance ( l^C NMR) spectra were recorded on Bruker AC-200 (50.3 MHz), Bruker Avance 300 (75.5), or Bruker AM-400 (100.6 MHz) spectrometers. A l l spectra were run under broad band proton decoupling ^C-{iH}. Chemical shifts (5) are reported in ppm. Mass Spectra (MS) Low and high resolution mass spectra (LRMS and HRMS) were recorded on a Kratos MS 50 instrument operating at 70 eV using electron impact ionization (EI). Mass to charge ratios (m/e) are reported with relative intensities in parentheses. Molecular ions are designated as M + . Mass spectral analyses were performed by the departmental staff in Mass Spectral Services. Ultraviolet (UV) Spectra Ultraviolet spectra were recorded on a Perkin Eimer Lambda-4B UV/Vis spectrophotometer. Spectral grade solvents (Fischer) were used without further purification. Wavelengths (k) in nanometers (nm) are reported and the extinction coefficients (e) are given in parentheses in units of M^cm" 1 . 175 Chapter 6 Experimental/Synthesis Melting Point Measurements (MP) Melting points were determined on a Fisher-Johns hot stage apparatus and are uncorrected. Microanalyses Elemental analyses were obtained for new compounds. These were performed on a Carlo Erba C H N Model 1106 analyzer by the departmental microanalyst, Mr. P. Borda. Gas Chromatography Gas chromatography (GC) analyses were performed on a Hewlett Packard 5890 A gas chromatograph fitted with a flame ionization detector and a Hewlett Packard 3392 A integrator. The following fused silica capillary column was used: HP-5 (30 m x 0.25 mm, Hewlett Packard). Chromatography Analytical thin layer chromatography (TLC) was performed on pre-coated silica gel plates (E. Merck, type 5554). Preparative chromatography was performed using either the flash column method1 using Merck 9385 silica gel (particle size 230 -176 Chapter 6 Experimental/Synthesis 400 mesh) or radial elution chromatography using a chromatotron (Harrison Research). Solvents and Reagents HPLC grade solvents were used for spectroscopic and photochemical studies. Solvents were purchased from Sigma-AIdrich or Fischer. A l l solvents and reagents were used directly without further purification unless otherwise stated. 6.2. Syntheses of Photochemical Substrates General Procedure A : Synthesis of A7-benzyl-./V-substituted-(3,4-dihvdro-l-naphthvDbenzamides (I) A two-neck round-bottomed flask fitted with a Dean-Stark trap, a reflux condenser, and a septum, was charged with a-tetralone (1 equiv), dry benzene (50 mL), and one crystal of p-toluenesulphonic acid. The Dean-Stark trap was filled with benzene (17 mL). The contents of the flask were heated to reflux, and then a syringe was used for the dropwise addition of benzylamine (1.1 equiv). The reaction was monitored by T L C with 40% diethyl ether in petroleum ether (v/v) as eluent until completion. The contents of the flask were allowed to cool, and the solvent was rotary evaporated. The mixture was then dissolved in chloroform and dried over magnesium sulphate. The magnesium sulphate was filtered, and the chloroform was removed. To the residue 177 Chapter 6 Experimental/Synthesis was added triethylamine (1.5 equiv) and chloroform (25 mL). A solution of the substituted benzoyl chloride (1.5 equiv) in chloroform (10 mL) was added dropwise to this mixture. The reaction was allowed to proceed overnight. The solvent was subsequently removed, and the residue was extracted with diethyl ether. The' extract was washed with brine, dried over magnesium sulphate, and evaporated. Ib Synthesis of A7-benzyl-4-fluoro-A^-(3,4-dihydro-l-naphthyl)benzamide (Ib) Following general procedure A , benzylamine (2.1 mL, 19 mmol) was added dropwise to a solution of cc-tetralone (2.45 g, 17 mmol) in dry benzene. The residue was treated with triethylamine (2.66 g, 26 mmol) in chloroform, and then a solution of p-fluorobenzoyl chloride (4.12 g, 26 mmol) in chloroform was added dropwise to the resulting mixture. Purification of the crude product provided a brown solid (6.67 g). Recrystallization from methanol afforded enamide (Ib) (3.3 g, 54% yield). M P 65-66 °C. IR (KBr disc) 1636 (amide C=0) cm" 1 . 178 Chapter 6 Experimental/Synthesis !H N M R ( C D C I 3 , 200 MHz) 5 1.80 - 2.23 (2H, m, C H 2 ) , 2.55 - 2.70 (2H, m, C H 2 ) , 4.10 ( IH , d, / = 15 Hz, benzylic), 5.23 (IH, t, J = 7 Hz, N-C=CH), 5.61 (IH, d, J = 15 Hz, benzylic), 7.11 - 7.59 (13H, m, aromatic).2 1 3 C N M R ( C D C I 3 , 75 MHz) 5 22.68, 27.05, 50.45, 114.49 and 114.78 ( 2/ C- F = 22 Hz), 122.52, 122.95, 127.36, 128.12, 128.21, 128.22, 129.29, 129.70, 129.81, 131.35, 132.09 and 132.13 ( 4 7 C F = 1 Hz), 137.21 and 137.29 (3JC-F=6 H Z ) , 138.29, 161.80 and 165.11 ('JC-F = 250 Hz), 170.12 (C=0) ppm. L R M S (EI), m/e (relative intensity) 357 (M+ 9.9), 266 (100), 234 (18.1), 145 (77.3), 123 (72.3), 117 (28.5), 91 (82.0), 65 (12.0). HRMS exact mass calcd for C 2 4 H 2 0 N O F 357.1529, found 357.1530. U V (MeOH) 212 (15600), 262 (10400) nm. Anal. Calcd for C 2 4 H 2 0 N O F : C, 80.65; H, 5.64, N , 3.92. Found C, 80.64; H , 5.59; N , 3.99. V Ic Synthesis of A7-benzyl-4-chIoro-A/-(3,4-dihydro-l-naphthyl)benzamide (Ic) Following general procedure A , benzylamine (2.1 mL, 19 mmol) was added dropwise 179 Chapter 6 Experimental/Synthesis to a solution of a-tetralone (2.40 g, 16 mmol) in dry benzene. The residue was treated with triethylamine (2.75 g, 27 mmol) in chloroform, and then a solution of p-chlorobenzoyl chloride (4.38 g, 25 mmol) in chloroform was added dropwise to the resulting mixture. Purification of the crude product provided a brown solid (4.38 g). Recrystallization from methanol afforded enamide (Ic) (3.6 g, 60% yield). M P 75 - 76 °C. IR (KBr disc): 1631 (amide C=0) cm" 1 . ! H N M R (CDC1 3 , 200 MHz) 8 1.80 - 2.20 (2H, m, C H 2 ) , 2.55 - 2.71 (2H, m, C H 2 ) , 4.10 (1H , d, J = 15 Hz, benzylic), 5.22 (1H, t, J = 7 Hz, N-C=CH), 5.65 (1H , d, J = 15 Hz, benzylic), 7.11 - 7.59 (13H, m, aromatic). 1 3 C N M R (CDCI3, 75 MHz) 8 22.67, 27.01, 50.38, 122.48, 126.94, 127.38, 127.87, 128.11, 128.16, 128.21, 128.89, 129.29, 129.97, 131.25, 134.45, 135.77, 137.14, 137.18, 138.07, 170.06 (C=0) ppm. L R M S (EI), mJe (relative intensity) 373 (M+, 9.1), 282 (73.8), 234 (21.2), 145 (86.8), 117 (32.8), 91 (100). HRMS exact mass calcd for C 2 4H 2 oN0 3 5 Cl 373.1233, found 373.1230. U V (MeOH) 220 (16900), 262 (10600) nm. Anal. Calcd for C 2 4 H 2 ( ) N 0 C 1 : C, 77.10; H , 5.39, N , 3.75. Found C, 77.29; H , 5.37; N , 3.85. 180 Chapter 6 Experimental/Synthesis Id Synthesis of N-benzyM-bromo-AMS^-dihydro-l-naphthyObenzamide (Id) Following general procedure A , benzylamine (2.0 mL, 18 mmol) was added dropwise to a solution of a-tetralone (2.40 g, 16 mmol) in dry benzene. The residue was treated with triethylamine (2.66 g, 26 mmol) in chloroform, and then a solution of p-bromobenzoyl chloride (5.57 g, 25 mmol) in chloroform was added dropwise to the resulting mixture. Purification of the crude product provided a brown solid (4.05 g). Recrystallization from methanol afforded enamide (Id) (3.6 g, 54% yield). M P 87 - 88 °C. IR (KBr disc): 1625 (amide C=0) cm" 1 . ! H N M R (CDCI3, 200 MHz) 8 1.80 - 2.19 (2H, m, C H 2 ) , 2.55 - 2.71 (2H, m, C H 2 ) , 4.10 (IH , d, / = 15 Hz, benzylic), 5.25 (IH, t, J = 1 Hz, N-C=CH), 5.62 (IH , d, J = 15 Hz, benzylic), 7.01 - 7.70 (13H, m, aromatic). 1 3 C N M R (CDCI3, 75 MHz) 5 22.73, 27.06, 50.42, 122.52, 126.99, 127.44, 127.86, 128.09, 128.16, 128.26, 129.13, 129.35, 130.07, 131.28, 134.99, 135.74, 137.17, 137.23, 138.08, 170.16 (C=0) ppm. 181 Chapter 6 Experimental/Synthesis L R M S (EI), m/e (relative intensity) 417 (M+, 10.8), 326 (0.08), 234 (31.0), 145 (0.09), 117 (24.6), 91 (100). HRMS exact mass calcd for C 2 4 H 2 o N 0 7 9 B r 417.0728, found 417.0719. U V (MeOH) 228 (18400), 262 (11000) nm. Anal. Calcd for C 2 4 H 2 0 N O B r : C, 68.91; H , 4.82, N , 3.35. Found C, 68.95; H , 4.77; N , 3.44. l e Synthesis of A^-benzyl-3-fluoro-Ar-(3,4-dihydro-l-naphthyl)benzamide (le) Following general procedure A, benzylamine (2.1 mL, 19 mmol) was added dropwise to a solution of oc-tetralone (2.41 g, 16 mmol) in dry benzene. The residue was treated with triethylamine (2.66 g, 26 mmol) in chloroform, and then a solution of m-fluorobenzoyl chloride (4.12 g, 26 mmol) in chloroform was added dropwise to the resulting mixture. Purification of the crude product provided a brown solid (5.60 g). Recrystallization from methanol afforded enamide (le) (3.6 g, 63% yield). M P 136 - 137 °C. IR (KBr disc): 1631 (amide C=0) cm" 1 . 182 Chapter 6 Experimental/Synthesis i H N M R (CDCI3, 200 MHz) 8 1.81 - 2.23 (2H, m, C H 2 ) , 2.51- 2.79 (2H, m, C H 2 ) , 4.16 (1H , d, / = 15 Hz, benzylic), 5.29 (1H, t, J = 7 Hz, N-C=CH), 5.65 (1H , d, J = 15 Hz, benzylic), 7.11 - 7.62 (m, 13H, aromatic). 1 3 C N M R (CDCI3, 75 MHz) 8 22.66, 27.02, 50.41, 114.56 and 114.87 ( 2 / C -F = 23 Hz), 116.56 and 116.84 (27C-F= 21 Hz), 122.47, 122.86 and 122.90 ( 4/ C-F= 3 Hz), 126.95, 127.42, 128.08, 128.15, 129.29, 129.90, 131.26, 137.13, 137.98, 138.21 and 138.31 (3JC-F = 7 Hz), 160.36 and 163.63 ( ;7C-F= 246 Hz), 169.80 (C=0) ppm. L R M S (EI), m/e (relative intensity) 357 (M+, 13.5), 266 (100), 234 (21.0), 145 (80.9), 123 (40.6), 117 (28.1), 91 (91.9), 65 (11.7). HRMS exact mass calcd for C 2 4 H 2 Q N O F 357.1529, found 357.1525. U V (MeOH) 214 (23600), 262 (8400) nm. Anal. Calcd for C 2 4 H 2 0 N O F : C, 80.65; H , 5.64, N , 3.92. Found C, 80.67; H , 5.66; N , 4.00. If Synthesis of A^-benzyl-3-chloro-A^-(3,4-dihydro-l-naphthyl)benzamide (If) Following general procedure A , benzylamine (2.2 mL, 20 mmol) was added dropwise 183 Chapter 6 Experimental/Synthesis to a solution of a-tetralone (2.41 g, 16 mmol) in dry benzene. The residue was treated with triethylamine (2.66 g, 26 mmol) in chloroform, and then a solution of m-chlorobenzoyl chloride (5.00 g, 29 mmol) in chloroform was added dropwise to the resulting mixture. Purification of the crude product provided a brown solid (5.20 g). Recrystallization from methanol afforded enamide (If) (3.9 g, 65% yield). M P 98 - 99 °C. IR (KBr disc): 1646 (amide C=0) cm" 1 . ! H N M R (CDC1 3 , 200 MHz) 5 1.79 - 2.19 (2H, m, C H 2 ) , 2.48 - 2.76 (2H, m, C H 2 ) , 4.10 (IH , d, J = 15 Hz, benzylic), 5.23 (IH, t, J = 7 Hz, N-C=CH), 5.66 (IH , d, J = 15 Hz, benzylic), 7.02 - 7.59 (13H, m, aromatic). 1 3 C N M R (CDCI3, 75 MHz) 6 22.70, 27.01, 50.58, 122.48, 125.55, 126.99, 127.54, 128.45, 128.99, 128.35, 129.68, 129.74, 130.31, 130.56, 131.10, 132.89, 137.10, 137.19, 138.07, 169.41 (C=0) ppm. L R M S (EI), m/e (relative intensity) 373 (M+, 2.59), 282 (0.10), 234 (12.7), 145 (0.34), 117 (0.14), 91 (100). HRMS exact mass calcd for C 2 4 H 2 f j N 0 3 5 C l 373.1233, found 373.1226. U V (MeOH) 216 (23400), 262 (9000) nm. Anal. Calcd for C 2 4 H 2 0 N O C 1 : C, 77.10; H , 5.39, N , 3.74. Found C, 77.24; H, 5.28; N , 3.82. 184 Chapter 6 Experimental/Synthesis Ig Synthesis of A^-benzyl-S-bromo-A^-CS^-dihydro-l-naphthyObenzamide (Ig) Following general procedure A , benzylamine (2.2 mL, 20 mmol) was added dropwise to a solution of a-tetralone (2.41 g, 16 mmol) in dry benzene. The residue was treated with triethylamine (2.75 g, 27 mmol) in chloroform, and then a solution of m-bromobenzoyl chloride (5.00 g, 23 mmol) in chloroform was added dropwise to the resulting mixture. Purification of the crude product provided a brown solid (4.38 g). Recrystallization from methanol afforded enamide (Ig) (3.4 g, 51% yield). M P 111 - 112 °C. IR (KBr disc) 1635 (amide C=0) cm" 1 . !H N M R (CDC1 3 , 200 MHz) 8 1.80 - 2.19 (2H, m, C H 2 ) , 2.50 - 2.72 (2H, m, C H 2 ) , 4.1 (1H , d, J= 15 Hz, benzylic), 5.25 (1H, t, / = 7 Hz, N-C=CH), 5.64 (1H , d, / = 15 Hz, benzylic), 6.98 - 7.71 (13H, m, aromatic). 1 3 C N M R (CDCI3, 100 MHz) 8 22.74, 27.07, 50.62, 122.48, 125.60, 126.95, 127.48, 128.07, 128.20, 128.30, 129.08, 129.34, 129.97, 130.35, 130.96, 132.74, 137.13, 137.22, 138.13, 169.51 (C=0) ppm. 185 Chapter 6 Experimental/Synthesis L R M S (EI), m/e (relative intensity) 417 (M+, 4.50), 326 (0.12), 234 (19.6), 145 (0.53), 117 (29.6), 91 (100). HRMS exact mass calcd for C 2 4H 2 oN0 7 9 Br 417.0728, found 417.0718. U V (MeOH) 212 (34600), 262 (9800) nm. Anal. Calcd for C 2 4 H 2 0 N O B r : C, 68.91; H , 4.82, N , 3.35. Found C, 68.98; H , 4.74; N , 3.41. 6.3. Photochemical Reactions General Procedures Light Sources A 450 W Hanovia medium pressure mercury arc lamp housed in a Pyrex jacket was used for irradiation conducted at ~k > 290 nm. Solid State Irradiations Single crystal photolyses were performed by irradiating samples sealed in a polyethylene bag under a nitrogen atmosphere. For polycrystalline irradiations, solid samples were sandwiched between two Pyrex plates and placed in a polyethylene bag sealed under nitrogen gas. The photolyses were followed using gas chromatography and thin-layer chromatography. 186 Chapter 6 Experimental/Synthesis Solution Phase Irradiations Solutions for photolyses were prepared using the following procedure. A solution of the reactant was placed in a Pyrex test tube containing a stir bar, and the test tube was sealed with a septum threaded with a polyethylene tube through which nitrogen gas flowed. The joints were wrapped with Parafilm, and then with aluminium foil. The sample was degassed for twenty minutes prior to irradiation, and nitrogen was bubbled into the solution throughout the duration of irradiation. 6.3.1. Photochemical Syntheses and Spectral Characterization of Photoproducts Solution State Photolysis of A/-benzyl-4-fluoro-A7-(3,4-dihydro-l-naphthyl)benzamide (Ib). Compound Ib (65.8 mg, 0.18 mmol) was ground to fine powder and then dissolved in methanol. The solution was irradiated at > 290 nm through a Pyrex filter. The reaction was complete in 9 h. The mixture was subjected to chromatography using 10% ethyl acetate in hexanes (v/v) as eluent. The slightly yellow solid obtained was recrystallized from methanol to afford a white powder, lib (55.2 mg, 84% yield). 187 Chapter 6 Experimental/Synthesis lib ^rans-5-benzyl-9-fluoro-4b,10b41»12-tetrahydro-benzo[c]phenanthridin-6[5H]-one (lib) M P 120-121 °C. IR (KBr disc) 1631 (amide C=0) cm" 1 . ! H N M R ( C D C 1 3 , 200 MHz) 5 1.37 - 3.04 (5H, m), 4.56 (1H , d, J = 15 Hz, benzylic), 4.90 (1H, d, J = 10 Hz, N-CH) , 5.38 (1H , d, J = 15 Hz, benzylic), 7.01 - 7.43 (12H, m, aromatic) ppm.3 13c N M R (CDCI3, 100 MHz) 5 23.72, 29.82, 42.78, 46.19, 62.44, 115.84 and 116.07 ( 27 C-F= 23 Hz), 118.32 and 118.54 ( 2 / C - F = 22 Hz), 123.80 and 123.87 ( % . ? = ! Hz), 125.86, 126.90, 127.66, 128.03 and 128.16 ( 37 C-F = 8 Hz), 128.47, 129.27, 130.34, 131.40, 132.58 and 132.66 (3JC-F = 8 H z ) - 138.91, 139.18, 139.40, 160.76 and 163.19 ( ;7 C-F= 243 Hz), 166.50 ppm. L R M S (EI) m/e (relative intensity) 357 (M+, 39.1), 266 (18.1), 252 (25.4), 249 (17.0), 234 (28.4), 220 (10.6), 106 (100), 91 (63.0), 65 (10.4). HRMS exact mass calcd for C 2 4 H 2 0 N O F 357.1529, found 357.1529. 188 Chapter 6 Experimental/Synthesis Anal. Calcd for C24H20NOF: C, 80.65; H , 5.64, N , 3.92. Found C, 80.70; H , 5.75; N , 4.10. He Solution State Photolysis of N-benzyM-chloro-AMS^-dihydro-l-naphthyl)-benzamide (Ic) Compound Ic (60.5 mg, 0.16 mmol) was ground to fine powder and then dissolved in methanol. The solution was irradiated at > 290 nm through a Pyrex filter. The reaction was complete in 14 h. The mixture was subjected to chromatography using 10% ethyl acetate in hexanes (v/v) as eluent. The slightly yellow powder obtained was recrystallized from methanol to afford a white powder, He (52.1 mg, 86% yield). rrans-5-benzyl-9-chloro-4b,10b,ll,12-tetrahydro-benzo[c]phenanthridin-6[5H]-one (He) M P 133 - 134 °C. IR (KBr disc) 1634 (amide C=0) cm" 1 . 189 Chapter 6 Experimental/Synthesis ! H N M R (CDCI3, 200 MHz) 8 1.37 - 3.04 (5H, m), 4.56 (1H , d, J = 15 Hz, benzylic), 4.90 (1H, d, J = 10 Hz, N-CH) , 5.38 (1H , d, / = 15 Hz, benzylic), 7.01 - 7.43 (12H, m, aromatic) ppm. 1 3 C N M R (CDCI3, 75 MHz) 8 23.64, 29.83, 42.90, 46.24, 62.29, 125.67, 125.93, 126.69, 126.96, 127.73, 128.09, 128.19, 128.52, 129.19, 129.30, 130.37, 131.61, 132.22, 132.92, 133.33, 138.91, 139.18, 142.01, 166.43 ppm. L R M S (EI) m/e (relative intensity) 373 (M+, 28.8), 282 (11.9), 268 (17.7), 252 (3.6), 233 (11.9), 215 (28.5), 202 (12.5), 106 (100), 91 (63.1), 77 (5.7), 65 (10.6). HRMS exact mass calcd for C 2 4 H 2 o N 0 3 5 C l 373.1233, found 373.1231. Anal. Calcd for C24H20NOCI: C, 77.10; H , 5.39, N , 3.74. Found C, 77.30; H, 5.45; N , 3.77. Solution State Photolysis of A^-benzyl-4-bromo-A7-(3,4-dihydro-l-naphthyl)-benzamide (Id) Compound Id (56.7 mg, 0.14 mmol) was ground to fine powder and then dissolved in methanol. The solution was irradiated at > 290 nm through a Pyrex filter. The reaction was complete in 16 h. The mixture was subjected to chromatography using 10% ethyl acetate in hexanes (v/v) as eluent. The slightly yellow powder obtained was recrystallized from methanol to afford a white powder, lid (43.7 mg, 77% yield). 190 Chapter 6 Experimental/Synthesis lid ^"ans-5-benzyl-9-bromo-4b,10b,ll,12-tetrahydro-benzo[c]phenanthridin-6[5H]-one (lid) M P 143 - 144 °C. IR (KBr disc) 1636 (amide C=0) cm" 1 . ! H N M R (CDCI3, 200 MHz) 8 1.41 - 3.01 (5H, m), 4.56 (IH , d, J = 15 Hz, benzylic), 4.91 (IH, d, J = 10 Hz, N-CH) , 5.38 (IH , d, J = 15 Hz, benzylic), 7.01 - 7.43 (12H, m, aromatic) ppm. 1 3 C N M R (CDCI3, 75 MHz) 5 23.61, 29.82, 42.90, 46.19, 62.29, 125.67, 125.93, 126.69, 126.96, 127.73, 128.09, 128.19, 128.52, 129.19, 129.30, 130.37, 131.61, 132.22, 132.92, 133.33, 138.91, 139.18, 142.01, 166.43 ppm. L R M S (EI) m/e (relative intensity) 373 (M+, 28.82), 282 (11.85), 268 (17.68), 233 (11.92), 216 (12.83), 215 (28.50), 202 (12.48), 106 (100), 91 (63.12), 65 (10.63). HRMS exact mass calcd for C 2 4 H 2 o N 0 7 9 B r 417.0728, found 417.0717. Anal. Calcd for C 2 4 H 2 0 N O B r : C, 68.91; H , 4.82, N , 3.35. Found C, 68.97; H , 4.88; N , 3.40. 191 Chapter 6 Experimental/Synthesis Solution State Photolysis of A^-benzyl-3-fluoro-A^-(3,4-dihydro-l-naphthyl)-benzamide (le) Compound le (54.9 mg, 0.15 mmol) was ground to fine powder and then dissolved in methanol. The solution was irradiated at > 290 nm through a Pyrex filter. The reaction was complete in 24 h. The mixture was subjected to chromatography using 10% ethyl acetate in hexanes (v/v) as eluent. The white solid obtained was recrystallized from methanol to afford colourless prisms He (43.9 mg, 80% yield). He /rans-5-benzyl-8-fluoro-4b,10b,ll,12-tetrahydro-benzo[c]phenanthridin-6[5H]-one (He) M P 147 - 148 °C. IR (KBr disc) 1633 (amide C=0) cm" 1 . * H N M R (CDC1 3 , 200 MHz) 5 1.37 - 3.01 (5H, m), 4.58 (1H , d, J= 15 Hz, benzylic), 4.90 (1H, d, J = 10 Hz, N-CH) , 5.38 (1H , d, J = 15 Hz, benzylic), 7.01 - 7.43 (12H, m, aromatic) ppm. 192 Chapter 6 Experimental/Synthesis !3C N M R (CDCI3, 100 MHz) 8 23.72, 29.82, 42.78, 46.19, 62.44, 115.84 and 116.07 (27C-F= 23 Hz), 118.32 and 118.54 ( 2 / C -F= 22 Hz), 123.80 and 123.87 (47C-F= 7 Hz), 125.86, 126.90, 127.66, 128.03 and 128.16 (3JC.F= 13 Hz), 128.47, 129.27, 130.34, 131.40, 132.58 and 132.66 (3JC-F= 8 Hz), 138.91, 139.18, 139.40, 160.76 and 163.19 (77C-F= 243 Hz), 166.50 ppm. L R M S (EI) m/e (relative intensity) 357 (M+, 29.42), 266 (15.88), 252 (20.54), 234 (29.40), 220 (13.76), 106 (100), 91 (77.01), 65 (15.09. HRMS exact mass calcd for C24H20NOF 357.1529, found 357.1527. Anal. Calcd for C24H20NOF: C, 80.65; H , 5.64, N , 3.92. Found C, 80.68; H, 5.71; N , 3.98. Solution State Photolysis of A7-benzyI-3-chloro-A7-(3,4-dihydro-l-naphthyl)-benzamide (If) Compound If (47.5 mg, 0.13 mmol) was ground to fine powder and then dissolved in methanol. The solution was irradiated at > 290 nm through a Pyrex filter. The reaction was complete in 25 h. The mixture was subjected to chromatography using 10% ethyl acetate in hexanes (v/v) as eluent. The white solid obtained was recrystallized from hexane to afford colourless prisms Hf (39.4 mg, 77% yield). 193 Chapter 6 Experimental/Synthes ilf <rans-5-benzyl-8-chloro-4b,10b41»12-tetrahydro-benzo[c]phenanthridin-6[5H]-one (Ilf) M P 185 - 187 °C. IR (KBr disc) 1646 (amide C=0) cm" 1 . *H N M R (CDCI3, 200 MHz) 5 1.41 - 3.01 (5H, m), 4.57 (1H , d, J = 15 Hz, benzylic), 4.93 (1H, d, J = 10 Hz, N-C=CH), 5.32 (1H , d, J = 15 Hz, benzylic), 7.05 - 7.42 (12H, m, aromatic) ppm. 1 3 C N M R (CDCI3, 75 MHz) 6 23.61, 29.82, 42.90, 46.19, 62.29, 125.67, 125.93, 126.69, 126.96, 127.73, 128.09, 128.19, 128.52, 129.19, 129.30, 130.37, 131.61, 132.22, 132.92, 133.33, 138.91, 139.18, 142.01, 166.43 ppm. L R M S (EI) m/e (relative intensity) 373 (M+, 10.56), 282 (7.13), 268 (10.89), 233 (8.02), 216 (18.14), 215 (28.50), 202 (8.23), 106 (100), 91 (51.01), 65 (10.05) ppm. HRMS exact mass calcd for C 2 4 H 2 o N 0 3 5 C l 373.1233, found 373.1227. Anal. Calcd for C 2 4 H 2 0 N O C 1 : C, 77.10; H , 5.39, N , 3.74. Found C, 77.15; H , 5.30; N , 3.68. 194 Chapter 6 Experimental/Synthesis Solution State Photolysis of N-benzyl-S-bromo-AMS^-dihydro-l-naphthyl)-benzamide (Ig) Compound Ig (45.2 mg, 0.11 mmol) was ground to fine powder and then dissolved in methanol. The solution was irradiated at > 290 nm through a Pyrex filter. The reaction was complete in 20 h. The mixture was subjected to chromatography using 10% ethyl acetate in hexanes (v/v) as eluent. The white solid obtained was recrystallized from hexane to afford colourless prisms Hd (35.7 mg, 79% yield). ng ^rans-5-benzyl-8-bromo-4b,10b,ll,12-tetrahydro-benzo[c]phenanthridin-6[5H]-one (Ilg) M P 198 - 199 °C. IR (KBr disc) 1639 (amide C=0) cm" 1 . i H N M R (CDCI3, 200 MHz) 5 1.37 - 3.03 (5H, m), 4.56 (IH , d, J = 15 Hz, benzylic), 4.90 (IH, d, J = 10 Hz, N-C=CH), 5.38 (IH , d, J = 15 Hz, benzylic), 7.01 - 7.42 (12H, m, aromatic) ppm. 195 Chapter 6 Experimental/Synthesis 1 3 C N M R (CDCI3, 75 MHz) 5 23.61, 29.82, 42.90, 46.19, 62.29, 125.67, 125.93, 126.69, 126.96, 127.73, 128.09, 128.19, 128.52, 129.19, 129.30, 130.37, 131.61, 132.22, 132.92, 133.33, 138.91, 139.18, 142.01, 166.43 ppm. L R M S (EI) m/e (relative intensity) 417 (M+, 10.64), 326 (3.12), 272 (7.08), 232 (17.01), 183 (11.92), 155 (7.59), 91 (100), 65 (7.20). HRMS exact mass calcd for C 2 4H 2 oN0 7 9 Br 417.0728, found 417.0721. Anal. Calcd for C 2 4 H 2 0 N O B r : C, 68.91; H , 4.82, N , 3.35. Found C, 68.89; H, 4.79; N , 3.50. 196 Chapter 6 Experimental/Synthesis 6.4. References for Chapter 6 1 Still, W. C ; Kahn, M . ; Mitra, A . J. Org. Chem. 1978, 43, 2923. 2 The chemical shifts of the proton N M R of this compound Ib (and the other analogues I(c-g)) agree with those of the unsubstituted analogue (la), synthesized by Ninomiya and co-workers. Ninomiya, I.; Naito, T.; Kiguchi, T.; Mori, T. J. Chem. Soc., Perkin Trans. 1 1973, 1696. The reported chemical shifts are: 8(CDC13) 4.12 (IH, J = 14 Hz, benzylic), 5.26 (IH, t, / = 5 Hz, N-C=C-H), and 5.67 (IH, 7=14 Hz, benzylic). 3 The chemical shifts of the proton N M R of this photoproduct l i b (and the other analogues Il(c-g)) agree with those of the unsubstituted analogue (Ha), synthesized by Ninomiya and co-workers (see reference 2 above). The reported chemical shifts of l i a are: 5(CDC13) 4.48 (IH, J = 15 Hz, benzylic), 4.85 (IH, d, J = 11.5 Hz, N-CH) , and 5.30 (IH, J= 15 Hz, benzylic). 197 Chapter 7 Experimental/Crystallography Chapter 7 Experimental (X-Ray Crystallography) 7.1. General Considerations The X-ray data reported in this thesis were obtained by using intensity measurements from either a Rigaku AFC6S diffractometer equipped with a scintillation counter and a sealed tube X-ray source, or a Rigaku AFC7 diffractometer equipped with an ADSC-Quantum CCD camera and a sealed tube X-ray source. 7.1.1. Selection of a Crystal for the X-ray Diffraction Experiment The crystals used for data collection in the X-ray diffraction experiment were selected by their external appearances under an optical microscope, cut to appropriate dimensions if necessary, and cleaned of microcrystalline shards or surface impurities. A single crystal was adhered with minute amounts of silicone or epoxy onto the tip of a glass fiber embedded on an AFC6 goniometer head, which was then mounted into the diffractometer where the crystal was centred in the X-ray beam. 198 Chapter 7 Experimental/Crystallography 7.1.2. Data Collection on the Rigaku AFC6S Data were collected on a Rigaku AFC6S serial diffractometer which was configured with an incident beam collimator of 1 mm in diameter and a crystal to detector distance of 285 mm. The horizontal and vertical aperatures of the detector were fixed at 6.0 mm by manually insertable slits. Data collection procedures were controlled by the T E X R A Y 1 software supplied by Molecular Structure Corporation. The following routine was typically employed for data collection. The shutter was opened and the crystal was rotated systematically to search for up to 25 reflections. These reflections were indexed to a primitive cell and an orientation matrix was calculated. The primitive cell was reduced and transformed to a cell of the highest possible symmetry. If indexing was unsuccessful, generally due to poor crystal quality or small size, a different crystal would be chosen and the whole search and cell reduction process would be repeated. Once a unit cell was found, the data collection limits were programmed based on the Laue symmetry of the reciprocal lattice and the unit cell volume. Data were collected at 20 °C. Figure 7.1 defines the four angular settings to, 20, %, <j), measured for each reflection using the Rigaku AFC6S diffractometer. Three standard reflections were chosen based on their intensity and spatial distribution in %. Once the unit cell and orientation matrix were determined, the detector was moved to the proper position to scan for a given reflection. The scan width in co was determined by scanning the standard reflections. Scan width was expressed as A + B tanO, where A is dependent 199 Chapter 7 Experimental/Crystallography on the mosaic spread of the crystal and B tan0 is dependent on variation in the Ka\ - K a 2 splitting of the radiation used. The scan speed in co was chosen to be 8, 16 or 32° min ' l , depending on the average intensity of the reflections in the working list. Figure 7.1. A four-circle diffractometer illustrating the four angular settings co, 20, %, (j) measured for each reflection.2 Two X-ray sources were available, C u - K a and M o - K a . Data were collected in two shells of 20 if C u - K a was used, and in three shells of 20 if Mo-Ko. was used. Weak reflections with I < 40.0o~(i) were rescanned up to 10 scans and the counts were accumulated to improve the counting statistics. Reflections with I < 3.0CT(I) were tagged unobserved. Stationary background measurements were made at the beginning and end of each scan with the scan-to-background counting time in the ratio of 2:1. Three standard reflections were monitored every 200 reflections collected, for crystal orientation and decay correction. In situations where the deviation in any of the angular settings of the standard reflections was greater than preset deviation values, all the reflections in the working list were re-centred and a new orientation matrix was calculated. 200 Chapter 7 Experimental/Crystallography At the end of the data collection, more accurate cell dimensions were calculated by high angle cell refinement using the positions of strong reflections with high 29 values. Up to 25 reflections from the data collected satisfying the requirement for Fobs (- 50.0) were re-centred accurately and used. Finally, three strong reflections with % n e a r 90° were selected for \jr-scans that were used for absorption corrections. 7.1.3. Data Reduction on the AFC6S Raw intensity data from the AFC6S were processed using the teXsan software3 provided by the Molecular Structure Corporation. Intensities were corrected for background, and the standard deviations, o(I)'s, were calculated using the following expressions: I = C - 2 ( b i + b 2 ) Eq. 7.1 G 2 (I) = [ C + 4 (bi + b 2 ) + (pi) 2 ] Eq. 7.2 where C is the total scan counts, b^ and b 2 are background counts, and p is a factor used to correct for the underestimation of o"(I)'s for the strong reflections. The corrected intensities were then used to calculate observed structure factor amplitudes: \Fo\ = <J{llLp) Eq. 7.3 201 Chapter 7 Experimental/Crystallography where | F Q | is the structure factor amplitude, and Lp stands for Lorentz-polarization factors. The Lorentz factor corrects for the different amount of time each reflection spends in its diffracting position. The polarization correction is needed as a result of the partial polarization of the incident X-ray beam by either the crystal monochromator or from the sample crystal itself. 7.1.4. Data Collection on the Rigaku A F C 7 - A D S C Quantum C C D The Rigaku AFC7 was configured with an incident beam collimator of 1 mm in diameter and a detector aperture size of 94 x 94 mm on the A D S C Quantum CCD at a distance of approximately 40 mm from the crystal. The X-ray source was M o - K a . Data collection procedures were controlled by the d*TREK software4 developed by Molecular Structure Corporation (MSC). A typical X-ray diffraction experiment consisted of the following procedures. First, a set of dark images was collected for background subtraction with the X-ray shutter closed. Then the X-ray shutter was opened and a series of initial frames was collected and the quality of the diffraction pattern was assessed. If the crystal diffracted weakly or resulted in an otherwise poor diffraction pattern, a different crystal would be chosen and the evaluation process would be repeated. When a good quality crystal was found, the diffraction experiment was started, and data was collected in two scan sets at 20 °C (at % = -90° and at % = 0°) with <|> and CO oscillations of 0.5° increments, or in one scan set at -100 °C (at % = -90°) 202 Chapter 7 Experimental/Crystallography with <p and co oscillations of 0.5° increments. Images were collected twice, and any spot not present in both frames was ignored (de-zingering). 7.1.5. Data Reduction on the Rigaku A F C 7 - A D S C Quantum C C D After the data set is collected, the spots from the two scan sets are chosen according to intensity (I/a(I)), integrated, scaled, and merged using the d*TREK software. The spots on at least twenty frames of the raw images from the Rigaku/ADSC C C D are used to index a unit cell. The primitive cell which is obtained is reduced to many possible Bravais lattices, and a least-squares fit of each lattice gives residual values, with a lower residual (other than P I , whose residual is always 0.0) indicating a better fit. The cell choice is usually based on the Bravais lattice with the lowest residual. Uncertainties in the residuals and cell parameters allow for the cell to be indexed as triclinic or as a lattice with a higher residual. The crystal rotations and detector distance are refined to diminish the difference between the observed and calculated positions of the spots on each frame. Once an orientation matrix is produced, the position of each reflection on a given frame is determined and the area around that calculated position is integrated. The data from the <j) and co oscillations are merged, corrected for absorption, and averaged, with an / ? m e r g e value being calculated, which can be used to judge the accuracy of the indexing and the quality of the data: 203 Chapter 7 Experimental/Crystallography n m X E (^2)-(^)| Rm = Eq. 7.4 /I 5>(*)2) where rc is the number of unique reflections that are observed more than once, m is the number of times a given reflection is observed, (F/ 2) is the average value of the unique reflections i, and (Fjj2) is the value of the yth reflection. 7.1.6. The Phase Problem The scattering of monochromatic X-rays upon interaction with a crystal lattice results in a diffraction pattern that consists of spots of differing intensities and loci. The X-ray diffraction pattern is a record of the amplitude of the scattered X-rays for each reflection but the phases of the X-rays are not recorded. In order to obtain structural information from the diffraction pattern, both the scattered X-ray amplitudes and phases must be known. The phases must be derived mathematically, and this is known as the "phase problem". Each reflection has associated with it a structure factor amplitude | | and a phase angle a ^ . The structure factor is written as: F 0(hkl) = | F 0 ( h k l ) | e x p a h k l Eq. 7.5 204 Chapter 7 Experimental/Crystallography In this equation, a^ki is unknown and must be estimated using methods described in the following section. 7.1.7. Structure Solution Before structure solution can be attempted, a space group must first be assigned to the data. Statistical analysis of the distribution of intensities (E-statistics) can be used to determine the centricity of the space group. The space group is selected based on this centricity, the Laue class, and systematic absences in the data. Wilson analysis5 of the intensities of the reflections is performed to estimate an overall temperature factor and a scale factor for the data. Most of the structures reported in this thesis are solved by direct methods using the Semi-Invariants Representation Method (SIR) series of programs: SIR92 6 and SIR97.7 Direct methods are those methods which attempt to derive the structure factor phases directly from the observed amplitudes through mathematical relationships. The SIR routines are designed to derive the phases for each reflection and to calculate a Fourier map (E-map) that represents electron density for peak intrepretation. Invariant and semi-in variant triplets are used extensively in phasing of the reflections. The term structure invariant (s.i.) is given to those cases where information about the phases can be obtained solely from the amplitudes. Structure semi-invariants (s.s.) are single phases or linear combination of phases which are invariant with respect to a shift in origin, provided that the position of origin is restricted to those points in the cell which 205 Chapter 7 Experimental/Crystallography possess the same point symmetry. In general, the amplitudes are independent of the reference system whereas the phases are not. An outline of direct methods phasing is presented below. The first step of this procedure is to normalize the observed structure factor amplitudes to give the normalized structure factor amplitudes (|E|) for each reflection. The normalized structure factors have the advantage in that they allow the normalization of all classes of reflections to a common basis: |E 0(hkl)| 2 = K 2 |F 0(hkl)| 2 / £ Zj if E q - 7 - 6 where K is a scale factor, e is an integer and fj is the scattering factor for atom j corrected for thermal motion and dependent upon 6. Because the data must be on an absolute scale, K is 1, and e is an integer that is generally 1, but may assume other values for special sets of reflections in particular space groups (e.g. in P2\lc, e = 2 for hOl and OkO reflections and 1 for all others).8 The scattering factor f^  is corrected for isotropic thermal motion, and rapid fall off in scattering with respect to 0. fj = fjfi exp (-B sin 20 / X2 ) Eq. 7.7 where f^ Q is the number of electrons in the atom. B is the isotropic temperature factor which is: 206 Chapter 7 Experimental/Crystallography B = 87t2u2 Eq. 7.8 and u 2 is the mean-square amplitude of vibration of atom j. The magnitudes of the normalized structure factors are examined, and the method of triplets is used to help assign phases to the reflections. These "triplets" are a set of three reflections whose indices sum to zero, such that: hi+h2 + ( h l + h 2 ) = 0 Eq. 7.9 where hi = h i , k i , l i and h2 = h 2 , k 2 , 12. The phase relationship belonging and corresponding to these reflections, called the Z 2 relationship, is: ^h l + 4>h2 + 4>(hT + h~2) = 4>(hl,h2) Eq. 7.10 where (p(hl,h2) * s m e phase of the relationship, which'is constant regardless of the choice of the "origin" to which the individual phases are being referred, and is approximately zero. Each of these relationship is given a weight K ( h i > n 2 ) which is, in general, proportional to the product of the |E|'s that make up the relationship. The triplets are chosen based on the magnitudes of |E|. A special case of the above relationship, called the relationship, arises when two of the three reflections involved are the same. In such cases, the phase of a reflection can be estimated directly from the intensity data with a given probability that 207 Chapter 7 Experimental/Crystallography the assigned phase is correct. These are the semi-invariants (s.i.) which give the SIR program its name. When a large number of Z 2 relationships is assembled, a search is initiated for sets of reflections that participate in a large number of Z 2 relationships. Reflections which appear in many Z 2 relationships and reflections developed from the S i relationships are used as a "starting set" for phasing. A l l the reflections in this starting set are assigned phases, and the phases for the other reflections in the data set are derived from Karle and Hauptman's "tangent formula":9 In this way, a complete set of phases, known as a phase set is obtained. Once these have been determined, new phase sets are established by assigning new phases to the starting set, and re-iterating the process using Eq. 7.11. The phases are evaluated, and the results are appropriately weighted and a combined figure of merit (CFOM) is calculated for every phase set. With the SIR programs, a large C F O M is more likely to give the correct solution to the structure. Subsequent Fourier synthesis produces an E-map of the unit cell, with the electron density corresponding to some or all of the atoms in the molecule: 2 h l K(hl,h2) s i n (4>h2 + 4>(hl + h2)) Eq. 7.11 tan (|)hi = s h 2 K(hl,h2) c o s (<t>h2 + 4>(hl + h2)) p(x, y, z) = — X £ E expO'a) exp[-2m'(hx + ky + lz)] V h k 1 Eq. 7.12 208 Chapter 7 Experimental/Crystallography where p(x,y,z) is the electron density at (x,y,z), a is the phase taken from the best phase set, and V is the volume of the unit cell. The electron density at any point (x, y, z) in the unit cell can be described as: p(x,y,z)= —SSSlFChkl^exp^iKhx + ky + ^ -a^ , ] Eq. 7.13 V h k 1 where V is the volume of the unit cell. Often, only a partial structure can be located in the electron density map from direct methods. In these instances, a difference synthesis using the program DIRDIF, 1 0 a direct methods phase refinement and extension program, can be used to locate the remaining atoms. DERDIF uses the starting phases of the partial structure obtained from direct phasing to calculate the difference between the observed and calculated structure factors, F0 - F c : p 0(x,y,z)- p c(x,y,z) = —XEE(|Fo|-|Fc|)exp(/a)exp[-2m'[(hx + ky + lz)] Eq. 7.14 V h k 1 where AF is F Q - Fc and a is the phase of F 0 . This difference between the observed and calculated structure factors represents the difference between the actual electron density and that of the incomplete model. Large peaks in this map are the missing atoms while smaller peaks and holes may represent disorder or incorrectly assigned atoms. The procedure using difference synthesis is repeated until all or most of the non-hydrogen atoms are found and available for refinement. 209 Chapter 7 Experimental/Crystallography 7.1.8. Structure Refinement Once the phases are properly determined and a partial or completed structure is modelled, the atoms of the model can undergo least-squares refinement to obtain a better fit between the observed structure factors and those calculated for the model structure. The atoms will have three positional paramters (x, y, z) and one isotropic thermal parameter (B) which'can be refined, preferably using full-matrix least squares refinement to minimize the function: Sw(|F 0 | - k|F c |) , where w is the weight given to each reflection and k is the scale factor which brings the F c ' s and F G ' s onto the same scale. The weights are derived from the counting statistics by: w = l / o 2 ( F 0 ) Eq. 7.15 When the model is refined sufficiently well, anisotropic thermal parameters (Uy) for the atoms can be introduced to the model. The U/y's are expressed in terms of mean-square vibrational amplitudes, and the general form of the anisotropic temperature factor expression for reflection (hkl) is: exp(-2n2(a*2Unh2+b*2U22k2+c*2U33l2+2a*b*^ where a*, b*, and c* are the reciprocal lattice axes. A l l non-hydrogen atoms are normally refined with anisotropic thermal parameters unless severe disorder is present. 210 Chapter 7 Experimental/Crystallography Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms are taken from the International Tables for X-ray Crystallography.12'13 The scattering factor for anisotropic thermal motion is expressed as: f = f 0 exp (-27T2 SjSy U/y h; hj af af) Eq. 7.16 Particularly in cases of strong absorption by the crystal, a secondary extinction coefficient, Zachariasen isotropic Type I, (g) may be refined:14 | F o C o r r e c t e d | = | p o e x t i n c t i o n | ( 1 + g |p|2 L p ) Eq. 7.17 A difference Fourier map that is computed after a certain number of refinement cycles is used to locate any missing atoms in the model structure, such as hydrogen atoms or solvent atoms. Hydrogen atoms may be placed in idealized positions (typically, C - H = 0.95 or 0.98 A, B H = 1.2 Btwnded atom). Hydrogen atoms which are involved in hydrogen bonding or which are situated on atoms possessing non-ideal geometries can be refined isotropically. The refinement is carried out over a number of cycles until the refinement converges. A refinement is considered converged when the shifts in any of the parameters being refined are negligible compared to their standard deviations. A full-matrix least-squares refinement should be used in the final stages of refinement unless there is an excessive number of parameters which prohibits this method. 211 Chapter 7 Experimental/Crystallography If necessary, empirical absorption and decay corrections were applied to the individual reflections based on the transmission factors calculated from the average \|/-scan curve of the three standard reflections on the AFC6S data.15 The measure of reliability of the modelled crystal structure is quoted using the following values: (1) The fl-factor, R = [ S | F 0 | - |F C | ]/ [ 2 |F Q | ]. (2) The weighted K-factor, Rw = [ 2 w ( |F 0 | - |F C | ) 2 / 2 w | F G | 2 ] 1 / 2 (3) The goodness of fit, GOF = [ I w ( |F 0 | - |F C | ) 2 / (m-n) ] 1 / 2 where m and n are the number of observations and variables, respectively. (4) The residual electron density in the final difference map (eA ). The closer the R-values approach zero, the better the model structure describes the "real" structure. The Goodness of Fit is ideally equal to 1, although it has been shown that models based on excellent data refine to an GOF of 2-3. 1 6 The residual peaks represent the electron density not accounted for by the model structure, and for a well-solved structure, these peaks should be small. Programs used in the refinements were teXsan3 and SHELX-97. 1 7 212 Chapter 7 Experimental/Crystallography 7.1.9. Treatment of Disorder Disorder in a crystal structure can occur when two or more conformations have near-equivalent energy minima. For molecules with flexible moieties, dynamic disorder is observed in the form of large atomic movements or oscillations. Static disorder occurs when two or more conformations are adopted throughout the crystal, but oscillation between the two conformations does not occur. These types of disorder are seen because the diffraction experiment records both the time-averaged and the space-averaged contents of the unit cell. Minor disorder in a structure is normally included in the model as split atoms with distributed occupancies. The disordered atoms are refined isotropically at two or more different positions, with the occupancies adjusted such that the B(eq) values for these positions are roughly equal. When suitable occupancies are determined, the model is refined with anisotropic thermal parameters. In general, abnormally large thermal motion about an atom or large residual electron density peaks near an atom may be evidence of disorder. 213 Chapter 7 Experimental/Crystallography 7.1.10. Structure Completion After the refinement is converged, all bond lengths, angles, and their estimated standard deviations (e.s.d.) are derived from the final atomic positions and the unit cell errors. 18 In addition to drawing the completed structure as ball-and-stick type figures, the crystallographic data can be used to draw molecular structures using ORTEP, 1 9 which can display much information about the nature of the molecule. In this thesis, ORTEP diagrams are drawn with 50% probability ellipsoids.2 0 7.2. Crystallographic Data and Details of the Structure Determinations Thirty-three crystal structure determinations are reported in this thesis. The details for each diffraction experiment and crystal structure analysis are summarized in the sections below. 7.2.1. A^-benzyl-A/CS^-dihydro-l-naphthyDbenzamide (la) A crystal of approximate dimensions of 1.00 x 0.13 x 0.10 mm size was chosen for data collection. Crystallographic data of la appear in Table 7.1. An orthorhombic cell with Z = 4 (the calculated density was 1.24 gem - 3) was indicated by preliminary measurements. Of the 2168 reflections collected, 2168 were unique and 1851 214 Chapter 7 Experimental/Crystallography observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles of 24 carefully centred reflections in the range 54.96 < 20 < 8 7 . 4 6 ° . The data for la were processed,3 and corrected for Lorentz and polarization effects. The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as P 2 i 2 j 2 i based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (Shelxs-86)2 1 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. The hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. A secondary extinction correction was applied (final coefficient = 1.0 x 10"^). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.1 2 , 1 3 The refinement converged at R = 0.033, Rw = 0.035 for 236 variables (GOF = 2.37; including zeros: R = 0.046, Rw = 0.036), with the largest parameter shift in the final cycle being 0 .00a. The final difference map showed electron density between -0.12 and 0.13 eA"3. This compound is isostructural to le. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.2 - 7.4. 215 Chapter 7 Experimental/Crystallography Table 7.1. Crystallographic data of la and Ib. Ia Ib Formula c y ^ N o fw 339.44 357.43 Colour, habit colourless, prism colourless, prism Crystal size, mm 1.00x0.13x0.10 0.50 x 0.20 x 0.20 Crystal system orthorhombic monoclinic Space group P2.2.2, FIJc a, A 9.6818(7) 9.8754(6) b, A 20.024(3) 9.7644(5) c,A 9.386(1) 19.628(2) <x(°) 90 90 PO 90 99.197(3) Y(°) 90 90 v,A 3 1819.7(3) 1868.4(2) z 4 4 Dcalc, g/cm3 1.24 1.27 F(000) 720 752 Radiation Cu- K a Mo- K a ]U, mm"1 0.583 0.08 Transmission factors 0.92-1.00 0.77-1.00 Scan type co - 20 if and co Scan range, ° in to 0.94 + 0.20 tanO -19 - 23+, 0 - 190* Scan speed, 7min 16.0 35s* Data collected +h, +k, +1 ±h, ±k, ±1 20max, ° 155 55 Crystal decay, % -0.27 0.00 Data collection temperature (K) 293 173 Total reflections 2168 15581 Total unique reflections 2168 4068 ^merge 0.00 0.05 No. of reflections with I > 3a(I) 1851 2518 No. of variables 236 245 p-factor 0.00 0.00 R 0.033 0.034 Rw 0.035 0.043 Goodness of fit (GOF) 2.37 1.23 Max A/a (final cycle) 0.00 0.00 Residual density e/A"3 -0.12, 0.13 -0.27, 0.24 C C D data; this is the co scan range (°). C C D data; this is the (j) scan range (°). * C C D data; exposure time per frame. 216 Chapter 7 Experimental/Crystallography Table 7.2. Final atomic coordinates (fractional) and B(eq) (A ) of la. atom X y z B(eq) 0(1) 0.9036(1) 0.12641(6) 0.3932(1) 3.92(2) N(l ) 0.6794(1) 0.13407(6) 0.3287(1) 2.80(2) C( l ) 0.4403(1) 0.09534(7) 0.2849(2) 2.77(3) C(2) 0.4848(1) 0.03707(7) 0.2176(2) 3.32(3) C(3) 0.3928(2) -0.00431(7) 0.1464(2) 4.15(4) C(4) 0.2535(2) 0.01211(8) 0.1448(2) 4.74(4) C(5) 0.2082(2) 0.06953(8) 0.2126(2) 4.37(4) C(6) 0.2986(1) 0.11140(7) 0.2824(2) 3.24(3) C(7) 0.2517(1) 0.17546(8) 0.3520(2) 3.96(4) C(8) 0.3373(2) 0.19128(8) 0.4833(2) 4.02(4) C(9) 0.4887(2) 0.18669(7) 0.4502(2) 3.33(3) C(10) 0.5350(1) 0.14114(7) 0.3594(2) 2.77(3) C ( l l ) 0.7236(2) 0.15013(7) 0.1816(2) 3.27(3) C(12) 0.7647(1) 0.22202(7) 0.1606(2) 3.24(3) C(13) 0.9023(2) 0.24022(8) 0.1566(2) 4.15(3) C(14) 0.9396(2) 0.3066(1) 0.1364(2) 5.14(4) C(15) 0.8405(2) 0.35450(9) 0.1201(2) 5.36(4) C(16) 0.7028(2) 0.33701(9) 0.1250(2) 5.42(4) C(17) 0.6653(2) 0.27139(8) 0.1448(2) 4.29(4) C(18) 0.7806(1) 0.12202(7) 0.4260(2) 2.82(3) C(19) 0.7424(1) 0.10175(7) 0.5745(2) 2.72(3) C(20) 0.8221(1) 0.12741(7) 0.6850(2) 3.32(3) C(21) 0.7992(2) 0.10727(8) 0.8237(2) 3.76(3) C(22) 0.7003(2) 0.05994(8) 0.8528(2) 3.68(3) C(23) 0.6218(2) 0.03301(7) 0.7442(2) 3.53(3) C(24) 0.6419(1) 0.05437(7) 0.6050(2) 3.22(3) 7.3. Bond lengths (A) of l a with estimated standard deviations. atom atom distance atom atom distance O(l) C(18) 1.233(2) C ( l l ) C(12) 1.506(3) N(l ) C(10) 1.435(3) C(12) C(13) 1.382(3) N(l ) C ( l l ) 1.481(3) C(12) C(17) 1.388(3) N( l ) C(18) 1.362(3) C(13) C(14) 1.390(4) C( l ) C(2) 1.395(3) C(14) C(15) 1.365(4) C( l ) C(6) 1.410(3) C(15) C(16) 1.379(4) C( l ) C(10) 1.473(3) C(16) C(17) 1.376(4) C(2) C(3) 1.388(3) C(18) C(19) 1.498(3) C(3) C(4) 1.389(4) C(19) C(20) 1.391(3) C(4) C(5) 1.385(4) C(19) C(24) 1.389(3) C(5) C(6) 1.377(3) C(20) C(21) 1.381(3) C(6) C(7) 1.509(3) C(21) C(22) 1.375(3) C(7) C(8) 1.519(4) C(22) C(23) 1.381(3) C(8) C(9) 1.501(3) C(23) C(24) 1.388(3) C(9) C(10) 1.326(3) 217 Chapter 7 Experimental/Crystallography Table 7.4. Bond angles (°) of l a with estimated standard deviations. atom atom atom angle atom atom atom angle C(10) N( l ) C ( l l ) 116.6(2) C ( l l ) C(12) C(13) 120.7(2) C(10) N( l ) C(18) 125.7(2) C ( l l ) C(12) C(17) 120.7(2) C ( l l ) N( l ) C(18) 117.1(2) C(13) C(12) C(17) 118.6(2) C(2) C( l ) C(6) 118.9(2) C(12) C(13) C(14) 120.4(2) C(2) C( l ) C(10) 122.9(2) C(13) C(14) C(15) 120.3(2) C(6) C( l ) C(10) 118.1(2) C(14) C(15) C(16) 119.8(3) C( l ) C(2) C(3) 121.3(2) C(15) C(16) C(17) 120.1(3) C(2) C(3) C(4) 119.2(2) C(12) C(17) C(16) 120.8(2) C(3) C(4) C(5) 119.9(2) 0(1) C(18) N( l ) 121.0(2) C(4) C(5) C(6) 121.5(2) 0(1) C(18) C(19) 119.4(2) C( l ) C(6) C(5) 119.2(2) N( l ) C(18) C(19) 119,7(2) C( l ) C(6) C(7) 118.6(2) C(18) C(19) C(20) 117.2(2) C(5) C(6) C(7) 122.1(2) C(18) C(19) C(24) 123.4(2) C(6) C(7) C(8) 111.4(2) C(20) C(19) C(24) 119.1(2) C(7) C(8) C(9) 110.6(2) C(19) C(20) C(21) 120.4(2) C(8) C(9) C(10) 120.3(2) C(20) C(21) C(22) 120.0(2) N( l ) C(10) C( l ) 116.7(2) C(21) C(22) C(23) 120.4(2) N( l ) C(10) C(9) 121.8(2) C(22) C(23) C(24) 119.8(2) C( l ) C(10) C(9) 121.5(2) C(19) C(24) C(23) 120.2(2) N( l ) C ( l l ) C(12) 113.9(2) 7.2.2. A^-benzyl^-fluoro-A^O^-dihydro-l-naphthyObenzamide (Ib) A crystal of approximate dimensions of 0.50 x 0.20 x 0.20 mm size was chosen for data collection. Crystallographic data of Ib appear in Table 7.1. A monoclinic cell with Z = 4 (the calculated density was 1.27 gem"3) was indicated by preliminary measurements. Of the 15581 reflections collected, 4068 were unique and 2518 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares on the setting angles for 15581 reflections in the range 3.19 < 0 < 27.88°. The data for Ib were processed.3'4 An absorption correction (empirical, based on a three-dimensional 218 Chapter 7 Experimental/Crystallography analysis of symmetry-equivalent data using 4 t h order spherical harmonics) was applied (transmission factors: 0.77 to 1.00). The space group was assigned as Ply/c based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. The hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.034, Rw = 0.043 for 245 variables (GOF =1.23; including zeros: R = 0.056, Rw = 0.095), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.27 and 0.24 eA"3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.5 -7.7, respectively. Table 7.5. Final atomic coordinates (fractional) and B(eq) (A 2) of Ib. atom X y z B(eq) F(l) 1.00378(8) 0.1096(1) 0.95402(5) 3.63(2) 0(1) 0.4135(1) -0.14344(9) 0.87261(5) 2.81(2) N(l) 0.3574(1) 0.0809(1) 0.86304(5) 1.80(2) C(l) 0.3524(1) 0.3178(1) 0.90894(6) 1.59(2) C(2) - 0.3099(1) 0.2728(1) 0.96958(6) 1.97(3) C(3) 0.2776(2) 0.3658(1) 1.01780(7) 2.37(3) C(4) 0.2875(2) 0.5045(1) 1.00594(7) 2.50(3) C(5) 0.3296(2) 0.5507(1) 0.94573(7) 2.34(3) 219 Chapter 7 Experimental/Crystallography C(6) 0.3615(1) 0.4593(1) 0.89683(6) 1.84(3) C(7) 0.4052(2) 0.5070(1) 0.83042(7) 2.54(3) C(8) 0.5114(1) 0.4114(1) 0.80824(7) 2.31(3) C(9) 0.4663(1) 0.2653(1) 0.80982(6) 1.88(3) C(10) 0.3930(1) 0.2226(1) 0.85750(6) 1.64(2) C ( l l ) 0.2099(1) 0.0459(1) 0.84868(7) 2.17(3) C(12) 0.1573(1) 0.0118(1) 0.77406(7) 2.39(3) C(13) 0.1514(2) -0.1225(2) 0.75167(9) 3.59(4) C(14) 0.0960(2) -0.1533(2) 0.6834(1) 5.05(5) C(15) 0.0466(2) -0.0522(3) 0.6382(1) 5.25(5) C(16) 0.0540(2) 0.0806(3) 0.6597(1) 5.31(5) C(17) 0.1096(2) 0.1137(2) 0.72744(9) 3.88(4) C(18) 0.4493(1) -0.0227(1) 0.87711(6) 1.89(3) C(19) 0.5970(1) 0.0138(1) 0.89921(6) 1.90(3) C(20) 0.6957(2) -0.0520(1) 0.86752(7) 2.45(3) C(21) 0.8330(2) -0.0203(2) 0.88560(8) 2.89(3) C(22) 0.8696(1) 0.0743(1) 0.93691(7) 2.49(3) C(23) 0.7766(1) 0.1363(1) 0.97186(7) 2.28(3) C(24) 0.6389(1) 0.1066(1) 0.95210(7) 2.09(3) Table 7.6. Bond lengths (A) of Ib with estimated standard deviations. atom atom distance atom atom distance F (D C(22) 1.359(2) C(9) C(10) 1.338(2) O(l) C(18) 1.229(2) C ( l l ) C(12) 1.511(2) N( l ) C(10) 1.436(2) C(12) C(13) 1.382(2) N( l ) C ( l l ) 1.479(2) C(12) C(17) 1.382(2) N( l ) C(18) 1.358(2) C(13) C(14) 1.396(3) C( l ) C(2) 1.395(2) C(14) C(15) 1.365(3) C ( l ) C(6) 1.407(2) C(15) C(16) 1.361(3) C( l ) C(10) 1.475(2) C(16) C(17) 1.393(3) C(2) C(3) 1.386(2) C(18) C(19) 1.497(2) C(3) C(4) 1.381(2) C(19) C(20) 1.394(2) C(4) C(5) 1.389(2) C(19) C(24) 1.390(2) C(5) C(6) 1.384(2) C(20) C(21) 1.380(2) C(6) C(7) 1.511(2) C(21) C(22) 1.371(2) C(7) C(8) 1.519(2) C(22) C(23) 1.372(2) C(8) C(9) 1.496(2) C(23) C(24) 1.384(2) Table 7.7. Bond angles (°) of Ib with estimated standard deviations. atom atom atom angle atom atom atom angle C(10) N( l ) C ( l l ) 117.0(1) C ( l l ) C(12) C(17) 120.7(1) C(10) N(l) C(18) 124.7(1) C(13) C(12) C(17) 118.7(1) C ( l l ) N(l) C(18) 118.2(1) C(12) C(13) C(14) 120.0(2) C(2) C( l ) C(6) 119.3(1) C(13) C(14) C(15) 120.9(2) 220 Chapter 7 Experimental/Crystallography C(2) C( i ) C(10) 122.5(1) C(14) C(15) C(16) 119.4(2) C(6) C( l ) C(10) 118.1(1) C(15) C(16) C(17) 120.7(2) C( l ) C(2) C(3) 120.6(1) C(12) C(17) C(16) 120.4(2) C(2) C(3) C(4) 119.9(1) O(l) C(18) N( l ) 121.7(1) C(3) C(4) C(5) 120.1(1) 0(1) C(18) C(19) 120.3(1) C(4) C(5) C(6) 120.8(1) N( l ) C(18) C(19) 118.0(1) C( l ) C(6) C(5) 119.2(1) C(18) C(19) C(20) 118.7(1) C( l ) C(6) C(7) 118.9(1) C(18) C(19) C(24) 122.1(1) C(5) C(6) C(7) 121.9(1) C(20) C(19) C(24) 119.2(1) C(6) C(7) C(8) 111.3(1) C(19) C(20) C(21) 120.7(1) C(7) C(8) C(9) 111.1(1) C(20) C(21) C(22) 118.2(1) C(8) C(9) C(10) 120.5(1) F( l) C(22) C(21) 119.0(1) N( l ) C(10) C( l ) 117.3(1) F( l) C(22) C(23) 117.9(1) N( l ) C(10) C(9) 121.3(1) C(21) C(22) C(23) 123.1(1) C( l ) C(10) C(9) 121.3(1) C(22) C(23) C(24) 118.2(1) N( l ) C ( l l ) C(12) 114.3(1) C(19) C(24) C(23) 120.5(1) C ( l l ) C(12) C(13) 120.5(1) 7.2.3. A Z - b e n z y l ^ - c h l o r o - A ^ - C S ^ - d i h y d r o - l - n a p h t h y O b e n z a m i d e (Ic) A crystal of approximate dimensions of 0.30 x 0.10 x 0.10 mm size was chosen for data collection. Crystallographic data of Ic appear in Table 7.8. A monoclinic cell with Z = 8 (the calculated density was 1.26 g c n r 3 ) was indicated by preliminary measurements. O f the 8348 reflections collected, 8188 were unique and 3408 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles of 24 carefully centred reflections in the range 35.20 < 20 < 58.6°. The data for Ic were processed,3 and corrected for Lorentz and polarization effects. A n absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.88 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed minimal decay. The space group was assigned as P2 1 / a based on E -221 Chapter 7 Experimental/Crystallography statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal and B H = 1.2 Bbonded atom. The difference Fourier map indicated a disordered methanol molecule located on an inversion centre. Hydrogen atoms on the methanol were placed in calculated positions by using Shelxl-97 rotating group instructions. Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.057, Rw = 0.058 for 503 variables (GOF = 2.74; including zeros: R = 0.173, Rw = 0.065), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.25 and 0.38 eA"3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.9 -7.11, respectively. Table 7.8. Crystallographic data of Ic and Id. o parameters. The hydrogen atoms were fixed in idealized positions with C - H = 0.98 A Ic Id C 2 4H 2oNOCl-C 0 5H 20 ( 373.88 0.5 C 2 4H 2 0NOBr.CH 4O 418.33 colourless, prism 0.30x0.10x0.10 monoclinic colourless, prism 0.25 x 0.10x0.10 monoclinic P2Ja 20.850(5) 9.597(2) P2Jn 11.980(2) 9.495(2) 222 Chapter 7 Experimental/Crystallography c,A 21.181(4) 17.927(2) a(°) 90 90 PO 108.21(2) 92.244(9) Y O 90 90 v,A 3 4026(2) 2037.7(6) z 8 4 Dcalc, g/cm3 1.26 1.42 F(000) 1604 892 Radiation Cu- K a Cu- K a u., mm'1 1.77 2.88 Transmission factors 0.88-1.00 0.90-1.00 Scan type to - 26 (0-20 Scan range, ° in to 0.94 + 0.20 tan6 1.05 + 0.20 tan0 Scan speed, °/min 8.0 32.0 Data collected +h, +k, ±1 +h, +k, ±1 20max, ° 155 155 Crystal decay, % -8.81 -1.21 Data collection temperature (K) 293 293 Total reflections 8348 4693 Total unique reflections 8188 4494 ^merge 0.10 0.04 No. of reflections with I > 3a(I) 3408 2714 No. of variables 503 260 p-factor 0.012 0.011 R 0.057 0.043 Rw 0.058 0.050 Goodness of fit (GOF) 2.74 2.64 Max A/a (final cycle) 0.00 0.00 Residual density e/A3 -0.25, 0.38 -0.77,0.41 Table 7.9. Final atomic coordinates (fractional) and B(eq) (A2) of Ic. atom x y z B(eq) Occupancy Cl(l) 0.57113(7) 0.8946(2) 1.18546(7) 5.87(4) Cl(2) 0.0907(1) 0.4208(2) 0.7263(1) 9.87(7) O(l) 0.3273(2) 1.1323(3) 0.9279(2) 5.1(1) 0(2) 0.1167(2) 0.6615(3) 0.4431(2) 5.2(1) 0(3) 0.5506(7) 0.652(2) 0.5189(7) 13.5(5) N(l) 0.3067(2) 0.9088(4) 0.8956(2) 3.62(9) N(2) 0.1170(2) 0.4371(4) 0.4124(2) 3.6(1) C(l) 0.3295(2) 0.6699(5) 0.8654(2) 3.3(1) C(2) 0.3648(3) 0.7159(5) 0.8234(3) 4.5(1) C(3) 0.3857(3) 0.6246(6) 0.7837(3) 5.3(2) C(4) 0.3708(3) 0.4836(6) 0.7852(4) 6.1(2) C(5) 0.3361(3) 0.4366(6) 0.8262(3) 5.5(2) C(6) 0.3147(3) 0.5263(5) 0.8667(3) 4.1(1) C(7) 0.2751(3) 0.4775(5) 0.9099(3) 4.9(1) 223 Chapter 7 Experimental/Crystallography C(8) 0.2931(3) 0.5598(5) 0.9749(3) 4.5(1) C(9) 0.2902(2) 0.7134(5) 0.9602(3) 3-6(1) C(10) 0.3078(2) 0.7621(5) 0.9098(3) 3-4(1) C ( l l ) 0.2554(3) 0.9559(5) 0.8334(2) 4.0(1) C(12) 0.1891(3) 0.9898(5) 0.8441(2) 3.8(1) C(13) 0.1694(3) 1.1285(5) 0.8459(3) 4.5(1) C(14) 0.1088(3) 1.1597(6) 0.8567(3) 5.3(2) C(15) 0.0660(3) 1.0570(7) 0.8642(3) 5.9(2) C(16) 0.0846(3) 0.9195(6) 0.8619(3) 5.7(2) C(17) 0.1453(3) 0.8879(6) 0.8513(3) 4.9(1) C(18) 0.3409(3) 1.0078(5) 0.9392(3) 3.6(1) C(19) 0.3961(2) 0.9661(5) 1.0008(2) 3.3(1) C(20) 0.4046(3) 1.0473(5) 1.0570(3) 4.2(1) C(21) 0.4576(3) 1.0245(5) 1.1144(3) 4.3(1) C(22) 0.5036(2) 0.9227(5) 1.1133(3) 3-9(1) C(23) 0.4983(2) 0.8424(5) 1.0586(3) 3-9(1) C(24) 0.4441(2) 0.8639(5) 1.0018(2) 3.6(1) C(25) 0.0782(2) 0.1932(5) 0.3879(2) 3.3(1) C(26) 0.0133(2) 0.2365(5) 0.3525(3) 4.1(1) C(27) -0.0333(3) 0.1412(6) 0.3155(3) 5.0(1) C(28) -0.0158(3) 0.0048(6) 0.3138(3) 5.1(2) C(29) 0.0484(3) -0.0407(5) 0.3497(3) 4.6(1) C(30) 0.0957(2) 0.0530(5) 0.3865(2) 3.5(1) C(31) 0.1663(3) 0.0093(5) 0.4251(3) 4.3(1) C(32) 0.1945(2) 0.0937(5) 0.4881(3) 4.2(1) C(33) 0.1842(2) 0.2463(5) 0.4733(2) 3-7(1) C(34) 0.1291(2) 0.2917(5) 0.4270(2) 3.3(1) C(35) 0.1160(3) 0.4832(5) 0.3460(3) 4.1(1) C(36) 0.1849(3) 0.5214(5) 0.3420(2) 3.6(1) C(37) 0.2012(3) 0.6602(5) 0.3366(3) 4.5(1) C(38) 0.2634(3) 0.6958(6) 0.3322(3) 5.6(2) C(39) 0.3111(3) 0.5962(7) 0.3358(3) 5.8(2) C(40) 0.2957(3) 0.4576(7) 0.3410(3) 5.4(2) C(41) 0.2325(3) 0.4223(5) 0.3438(3) 4.6(1) C(42) 0.1160(2) 0.5366(5) 0.4574(3) 4.0(1) C(43) 0.1115(3) 0.4981(5) 0.5243(3) 3.9(1) C(44) 0.1478(3) 0.5751(5) 0.5784(3) 5.0(2) C(45) 0.1430(3) 0.5506(7) 0.6404(3) 5.7(2) C(46) 0.0988(4) 0.4496(7) 0.6476(3) 5.7(2) C(47) 0.0609(3) 0.3731(6) 0.5945(4) 5-7(2) C(48) 0.0681(3) 0.3957(6) 0.5330(3) 4.6(1) C(49) 0.5 0.5 0.5 15.7(8) 224 Chapter 7 Experimental/Crystallography Table 7.10. Bond lengths (A) of Ic with estimated standard deviations. atom atom distance atom atom distance Cl( l ) C(22) 1.745(5) C(14) C(15) 1.372(8) Cl(2) C(46) 1.750(6) C(15) C(16) 1.381(8) 0(1) C(18) 1.234(5) C(16) C(17) 1.386(8) 0(2) C(42) 1.237(5) C(18) C(19) 1.500(7) 0(3) C(49) 1.77(2) C(19) C(20) 1.387(6) N( l ) C(10) 1.439(6) C(19) C(24) 1.395(6) N( l ) C ( l l ) 1.485(6) C(20) C(21) 1.381(7) N( l ) C(18) 1.361(6) C(21) C(22) 1.374(7) N(2) C(34) 1.435(5) C(22) C(23) 1.367(7) N(2) C(35) 1.467(6) C(23) C(24) 1.386(6) N(2) C(42) 1.354(6) C(25) C(26) 1.390(6) C( l ) C(2) 1.391(7) C(25) C(30) 1.396(6) C( l ) C(6) 1.414(6) C(25) C(34) 1.469(6) C( l ) C(10) 1.463(6) C(26) C(27) 1.384(6) C(2) C(3) 1.375(7) C(27) C(28) 1.363(7) C(3) C(4) 1.391(8) C(28) C(29) 1.386(7) C(4) C(5) 1.366(8) C(29) C(30) 1.382(6) C(5) C(6) 1.385(7) C(30) C(31) 1.503(6) C(6) C(7) 1.487(8) C(31) C(32) 1.514(7) C(7) C(8) 1.529(7) C(32) C(33) 1.500(6) C(8) C(9) 1.503(6) C(33) C(34) 1.328(6) C(9) C(10) 1.318(7) C(35) C(36) 1.510(6) C ( l l ) C(12) 1.504(7) C(36) C(37) 1.388(6) C(12) C(13) 1.397(7) C(36) C(41) 1.368(7) C(12) C(17) 1.380(7) C(37) C(38) 1.372(7) C(13) C(14) 1.384(7) C(38) C(39) 1.365(8) C(39) C(40) 1.381(8) C(44) C(45) 1.368(8) C(40) C(41) 1.380(7) C(45) C(46) 1.378(8) C(42) C(43) 1.496(7) C(46) C(47) 1.368(8) C(43) C(44) 1.375(7) C(47) C(48) 1.374(8) C(43) C(48) 1.386(7) Table 7.11 Bond angles (°) of Ic with estimated standard deviations. atom atom atom angle atom atom atom angle C(10) N( l ) C ( l l ) 116.3(4) C(39) C(40) C(41) 119.3(6) C(10) N( l ) C(18) 124.8(4) C(12) C(13) C(14) 120.2(5) C ( l l ) N( l ) C(18) 118.0(4) C(13) C(14) C(15) 121.6(5) C(34) N(2) C(35) 116.7(4) C(14) C(15) C(16) 118.9(6) C(34) N(2) C(42) 125.0(4) C(15) C(16) C(17) 119.6(6) C(35) N(2) C(42) 117.6(4) C(12) C(17) C(16) 122.3(5) C(2) C( l ) C(6) 118.9(5) 0(1) C(18) N( l ) 120.3(5) C(2) C( l ) C(10) 123.4(5) 0(1) C(18) C(19) 119.6(4) C(6) C( l ) C(10) 117.6(5) N( l ) C(18) C(19) 120.1(4) 225 Chapter 7 Experimental/Crystallography C(l ) C(2) C(3) 121.3(5) C(2) C(3) C(4) 119.3(6) C(3) C(4) C(5) 120.1(6) C(4) C(5) C(6) 121.6(5) C( l ) C(6) C(5) 118.6(6) C( l ) C(6) C(7) 119.1(5) C(5) C(6) C(7) 122.3(5) C(6) C(7) C(8) 111.4(4) C(7) C(8) C(9) 109.7(5) C(8) C(9) C(10) 120.8(5) N( l ) C(10) C( l ) 116.4(5) N( l ) C(10) C(9) 121.8(5) C( l ) C(10) C(9) 121.8(4) N( l ) C ( l l ) C(12) 112.0(4) C ( l l ) C(12) C(13) 120.3(5) C ( l l ) C(12) C(17) 122.4(5) C(13) C(12) C(17) 117.4(5) C(25) C(30) C(31) 118.4(4) C(29) C(30) C(31) 122.0(5) C(30) C(31) C(32) 112.0(4) C(31) C(32) C(33) 110.3(4) C(32) C(33) C(34) 120.6(4) N(2) C(34) C(25) 117.1(4) N(2) C(34) C(33) 122.1(4) C(25) C(34) C(33) 120.7(4) N(2) C(35) C(36) 113.5(4) C(35) C(36) C(37) 120.0(5) C(35) C(36) C(41) 121.7(5) C(37) C(36) C(41) 118.4(5) C(36) C(37) C(38) 120.4(5) C(37) C(38) C(39) 120.7(5) C(38) C(39) C(40) 119.7(6) C(18) C(19) C(20) 116.9(5) C(18) C(19) C(24) 123.5(4) C(20) C(19) C(24) 118.9(4) C(19) C(20) C(21) 121.2(5) C(20) C(21) C(22) 118.0(5) Cl( l ) C(22) C(21) 118.2(4) Cl( l ) C(22) C(23) 119.0(4) C(21) C(22) C(23) 122.8(5) C(22) C(23) C(24) 118.7(5) C(19) C(24) C(23) 120.2(5) C(26) C(25) C(30) 119.5(4) C(26) C(25) C(34) 121.5(4) C(30) C(25) C(34) 119.0(4) C(25) C(26) C(27) 120.0(5) C(26) C(27) C(28) 120.2(5) C(27) C(28) C(29) 120.6(5) C(28) C(29) C(30) 120.0(5) C(25) C(30) C(29) 119.6(5) Cl(2) C(46) C(47) 119.7(6) C(45) C(46) C(47) 121.5(6) C(46) C(47) C(48) 119.2(6) C(43) C(48) C(47) 120.4(6) C(36) C(41) C(40) 121.6(5) 0(2) C(42) N(2) 120.5(5) 0(2) C(42) C(43) 118.7(5) N(2) C(42) C(43) 120.8(5) C(42) C(43) C(44) 118.4(5) C(42) C(43) C(48) 122.5(5) C(44) C(43) C(48) 118.9(5) C(43) C(44) C(45) 121.4(6) C(44) C(45) C(46) 118.6(6) Cl(2) C(46) C(45) 118.9(6) 226 Chapter 7 Experimental/Crystallography 7.2.4. A7-benzyl-4-bromo-A^-(3,4-dihydro-l-naphthyl)benzamide (Id) A crystal of approximate dimensions of 0.25 x 0.10 x 0.10 mm size was chosen for data collection. Crystallographic data of Id appear in Table 7.8. A monoclinic cell with Z = 4 (the calculated density was 1.42 gem - 3) was indicated by preliminary measurements. Of the 4693 reflections collected, 4494 were unique and 2714 observed (> 3tf(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles of 23 carefully centred reflections in the range 81.20 < 20 < 101.80°. The data for Id were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.90 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as P2j/n based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. The hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. The difference Fourier map indicated a disordered methanol molecule located on an inversion centre. Hydrogen atoms on the methanol were placed in calculated positions by using Shelxl-97 rotating group instructions. Neutral atom scattering factors for all atoms and 227 Chapter 7 Experimental/Crystallography anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the 12 13 International Tables for X-ray Crystallography. ' The refinement converged at R = 0.043, Rw = 0.050 for 260 variables (GOF = 2.64; including zeros: R = 0.088, Rw = 0.055), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.77 and 0.41 eA"3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.12 - 7.14, respectively. Table 7.12. Final atomic coordinates (fractional) and B(eq) (A 2) of I d . atom x y z B(eq) Occupancy Br( l) 0.66018(4) 0.41675(6) 0.62640(3) 6.95(1) 0(1) 0.9403(2) 0.6699(3) 0.3355(1) 4.89(6) 0(2) 0.927(1) 0.854(1) 0.4674(5) 14.0(4) N( l ) 0.9752(2) 0.4447(3) 0.3057(1) 3.45(6) C( l ) 1.0391(2) 0.1974(3) 0.3203(2) 3.04(7) C(2) 1.1407(3) 0.2386(4) 0.3541(2) 3.80(8) C(3) 1.2239(3) 0.1406(4) 0.3690(2) 4.43(9) C(4) 1.2069(3) 0.0023(4) 0.3501(2) 4.39(9) C(5) 1.1069(3) -0.0407(4) 0.3171(2) 3.99(8) C(6) 1.0221(3) 0.0565(3) 0.3014(2) 3.31(7) C(7) 0.9121(3) 0.0127(4) 0.2650(2) 4.08(8) C(8) 0.8167(3) 0.1000(4) 0.2936(2) 4.20(8) C(9) 0.8433(3) 0.2533(4) 0.2921(2) 3.63(7) C(10) 0.9470(2) 0.2981(3) 0.3052(2) 3.07(7) C ( l l ) 1.0488(3) 0.4920(4) 0.2463(2) 3.93(8) C(12) 0.9859(3) 0.5313(4) 0.1746(2) 3.63(7) C(13) 0.9710(3) 0.6700(4) 0.1544(2) 4.47(9) C(14) 0.9140(4) 0.7056(5) 0.0884(2) 5.5(1) C(15) 0.8706(4) 0.6029(5) 0.0436(2) 6.0(1) C(16) 0.8848(4) 0.4635(5) 0.0624(2) 6.1(1) C(17) 0.9433(3) 0.4276(4) 0.1274(2) 4.82(9) C(18) 0.9274(3) 0.5444(4) 0.3483(2) 3.75(8) C(19) 0.8606(3) 0.5010(4) 0.4135(2) 3.58(7) C(20) 0.7662(3) 0.5801(4) 0.4277(2) 4.44(9) 228 Chapter 7 Experimental/Crystallography C(21) 0.7049(3) 0.5536(4) 0.4901(2) 4.85(9) C(22) 0.7411(3) 0.4496(4) 0.5389(2) 4.52(9) C(23) 0.8348(3) 0.3721(4) 0.5267(2) 4.38(9) C(24) 0.8942(3) 0.3965(4) 0.4635(2) 3.87(8) C(25) 1 1 0.5 16.0(5) 1.0 Table 7.13. Bond lengths (A) of Id with estimated standard deviations. atom atom distance atom atom distance Br(l) C(22) 1.901(3) C(9) C(10) 1.326(4) 0(1) C(18) 1.226(4) C ( l l ) C(12) 1.510(5) 0(2) C(25) 1.73(1) C(12) C(13) 1.376(5) N(l ) C(10) 1.433(4) C(12) C(17) 1.384(5) N( l ) C ( l l ) 1.478(4) C(13) C(14) 1.384(5) N(l) C(18) 1.357(4) C(14) C(15) 1.354(6) C( l ) C(2) 1.394(4) C(15) C(16) 1.375(6) C( l ) C(6) 1.394(4) C(16) C(17) 1.379(6) C( l ) C(10) 1.477(4) C(18) C(19) 1.499(5) C(2) C(3) 1.383(5) C(19) C(20) 1.390(5) C(3) C(4) 1.370(5) C(19) C(24) 1.387(5) C(4) C(5) 1.378(5) C(20) C(21) 1.385(5) C(5) C(6) 1.392(4) C(21) C(22) 1.379(5) C(6) C(7) 1.506(5) C(22) C(23) 1.367(5) C(7) C(8) 1.517(5) C(23) C(24) 1.382(4) C(8) C(9) 1.490(5) Table 7.14. Bond angles (°) of Id with estimated standard deviations. atom atom atom angle atom atom atom angle C(10) N( l ) C ( l l ) 116.0(3) C ( l l ) C(12) C(17) 120.4(3) C(10) N( l ) C(18) 125.1(3) C(13) C(12) C(17) 118.6(3) C ( l l ) N( l ) C(18) 118.0(3) C(12) C(13) C(14) 120.9(4) C(2) C( l ) C(6) 119.5(3) C(13) C(14) C(15) 119.8(4) C(2) C( l ) C(10) 122.1(3) C(14) C(15) C(16) 120.5(4) C(6) C( l ) C(10) 118.4(3) C(15) C(16) C(17) 119.9(4) C( l ) C(2) C(3) 120.4(3) C(12) C(17) C(16) 120.3(4) C(2) C(3) C(4) 119.9(3) 0(1) C(18) N(l) 120.9(3) C(3) C(4) C(5) 120.6(3) 0(1) C(18) C(19) 119.2(3) C(4) C(5) C(6) 120.4(3) N(l ) C(18) C(19) 119.8(3) C(l ) C(6) C(5) 119.2(3) C(18) C(19) C(20) 117.2(3) C( l ) C(6) C(7) 119.2(3) C(18) C(19) C(24) 123.4(3) C(5) C(6) C(7) 121.6(3) C(20) C(19) C(24) 119.1(3) C(6) C(7) C(8) 111.2(3) C(19) C(20) C(21) 120.7(3) C(7) C(8) C(9) 111.3(3) C(20) C(21) C(22) 118.7(3) C(8) C(9) C(10) 120.7(3) Br(l) C(22) C(21) 119.0(3) 229 Chapter 7 Experimental/Crystallography N(l) C(10) C( l ) 117.0(3) Br( l) C(22) C(23) 119.5(3) N( l ) C(10) C(9) 122.2(3) C(21) C(22) C(23) 121.5(3) C( l ) C(10) C(9) 120.9(3) C(22) C(23) C(24) 119.6(3) N( l ) C ( l l ) C(12) 113.3(3) C(19) C(24) C(23) 120.3(3) C ( l l ) C(12) C(13) 121.1(3) 7.2.5. A^-benzyl-S-fluoro-AZ-CS^-dihydro-l-naphthyObenzamide (le) A crystal of approximate dimensions of 0.50 x 0.20 x 0.10 mm size was chosen for data collection. Crystallographic data of le appear in Table 7.15. An orthorhombic cell with Z = 4 (the calculated density was 1.28 gem"3) was indicated by preliminary measurements. Of the 2259 reflections collected, 2259 were unique and 1664 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles of 25 carefully centred reflections in the range 75.40 < 20 < 95.20°. The data for le were processed,3 and corrected for Lorentz and polarization effects. The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as P2{1{2.\ based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by 7 10 direct methods (SIR97) and expanded using Fourier techniques. The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. The hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. A secondary extinction correction was applied (final coefficient = 1.0 x 10~5). Neutral atom 230 Chapter 7 Experimental/Crystallography scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.046, Rw = 0.057 for 245 variables (GOF = 3.60; including zeros: R = 0.080, Rw = 0.062), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.16 and 0.15 eA"3. This compound is isostructural to la. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.16-7.18, respectively. Table 7.15. Crystallographic data of le, If, and Ig. . - - — Formula C ^ N O F c^ujsroci cyysroBr fw 357.43 373.88 418.33 Color, habit colourless, prism colourless, prism colourless, prism Crystal size, mm 0.50x0.20x0.10 1.00x0.50x0.50 0.40 x 0.35 x 0.20 Crystal system orthorhombic monoclinic monoclinic Space group F2,2,2, FIJn P2xln a, A 9.747(2) 12.574(2) 12.627(2) b, A 20.0874(4) 9.822(2) 9.843(2) c, A 9.472(5) 15.523(3) 15.334(7) a(° ) 90 90 90 e n 90 90.41(1) 90.88(1) Y(°) 90 90 90 V 1854(1) 1917.1(5) 1905.5(8) Z 4 4 4 Dcalc, g/cm3 1.28 1.30 1.46 F(000) 752 784 856 Radiation Cu- K a Cu- K a Mo- K a u., mm'1 0.679 1.86 2.17 Transmission factors 0.76-1.00 0.79-1.00 0.69-1.00 Scan type to - 20 to - 28 § and to Scan range, ° in co 1.00 + 0.20 tanO 1.15 + 0.20 tanO -19 - 23 +, 0 - 190* Scan speed, °/min 32.0 32.0 12s* Data collected +h, +k, +1 +h, +k, ±1 ±h, ±k, ±1 29max, ° 155 155 50 Crystal decay, % -1.66 -1.74 0.00 231 Chapter 7 Experimental/Crystallography Data collection temperature (K) 293 293 173 Total reflections 2259 4354 14834 Total unique reflections 2259 4174 3519 P 0.00 0.04 0.05 merge No. of reflections with I > 3o(I) 1664 3098 2525 No. of variables 245 245 245 p-factor 0.008 0.02 0.00 R 0.046 0.054 0.025 Rw 0.057 0.079 0.033 Goodness of fit (GOF) 3.6 3.43 0.89 Max A/o (final cycle) 0.00 0.00 0.00 Residual density e/A3 -0.16, 0.15 -0.18,0.17 -0.53, 0.34 C C D data; this is the to scan range (°). CCD data; this is the <|> scan range (°). *CCD data; exposure time per frame. ° 2 Table 7.16. Final atomic coordinates (fractional) and B(eq) (A ) of le. atom x y z B(eq) F(l) 0.8850(3) 0.1186(2) 0.9076(2) 7.66(2) O(l) 0.9012(2) 0.1241(1) 0.3852(3) 5.04(2) N(l) 0.6809(3) 0.1360(1) 0.3210(3) 3.97(2) C(l) 0.4420(3) 0.0983(2) 0.2774(4) 3.85(2) C(2) . 0.4860(4) 0.0412(2) 0.2079(4) 4.51(2) C(3) 0.3939(4) 0.0008(2) 0.1399(5) 5.45(3) C(4) 0.2554(4) 0.0167(2) 0.1397(6) 6.08(3) C(5) 0.2109(4) 0.0721(2) 0.2089(6) 5.87(3) C(6) 0.3018(4) 0.1146(2) 0.2782(4) 4.52(2) C(7) 0.2560(4) 0.1773(2) 0.3499(5) 5.24(3) C(8) 0.3420(4) 0.1929(2) 0.4776(5) 5.44(3) C(9) 0.4915(4) 0.1879(2) 0.4432(4) 4.49(3) C(10) 0.5363(3) 0.1436(2) 0.3512(4) 3.82(2) C( l l ) 0.7250(4) 0.1530(2) 0.1767(4) 4.52(3) C(12) 0.7705(4) 0.2244(2) 0.1604(4) 4.37(3) C(13) 0.9081(4) 0.2412(2) 0.1595(5) 5.29(3) C(14) 0.9495(4) 0.3059(2) 0.1438(5) 6.13(3) C(15) 0.8545(5) 0.3559(2) 0.1290(5) 6.55(4) C(16) 0.7167(5) 0.3400(2) 0.1291(6) 6.52(4) C(17) 0.6750(4) 0.2754(2) 0.1453(5) 5.26(3) C(18) 0.7791(4) 0.1210(2) 0.4172(4) 4.10(2) C(19) 0.7400(3) 0.0991(2) 0.5617(4) 3.83(2) 232 Chapter 7 Experimental/Crystallography C(20) 0.8238(4) 0.1206(2) 0.6701(4) 4.43(2) C(21) 0.8005(4) 0.0979(2) 0.8041(4) 4.56(3) C(22) 0.6988(4) 0.0543(2) 0.8353(4) 4.73(3) C(23) 0.6175(4) 0.0315(2) 0.7277(4) 4.82(3) C(24) 0.6358(4) 0.0540(2) 0.5911(4) 4.42(3) Table 7.17. Bond lengths (A) of le with estimated standard deviations. atom atom distance atom atom distance F( l ) C(21) 1.347(5) C(9) C(10) 1.317(5) O(l) C(18) 1.229(4) C ( l l ) C(12) 1.504(6) N( l ) C(10) 1.448(4) C(12) C(13) 1.382(5) N(l) C ( l l ) 1.471(5) C(12) C(17) 1.396(6) N( l ) C(18) 1.357(5) C(13) C(14) 1.364(6) C( l ) C(2) 1.385(5) C(14) C(15) 1.378(7) C( l ) C(6) 1.407(5) C(15) C(16) 1.384(7) C( l ) C(10) 1.469(5) C(16) C(17) 1.363(6) C(2) C(3) 1.372(6) C(18) C(19) 1.489(6) C(3) C(4) 1.389(6) C(19) C(20) 1.381(5) C(4) C(5) 1.357(6) C(19) C(24) 1.386(5) C(5) C(6) 1.391(6) C(20) C(21) 1.371(6) C(6) C(7) 1.500(6) C(21) C(22) 1.349(6) C(7) C(8) 1.506(7) C(22) C(23) 1.373(6) C(8) C(9) 1.501(6) C(23) C(24) 1.383(6) Table 7.18. Bond angles (°) of le with estimated standard deviations. atom atom atom angle atom atom atom angle C(10) N( l ) C ( l l ) 116.4(3) C ( l l ) C(12) C(17) . 120.8(3) C(10) N( l ) C(18) 125.3(3) C(13) C(12) C(17) 117.7(4) C ( l l ) N( l ) C(18) 117.9(3) C(12) C(13) C(14) 121.6(4) C(2) C( l ) C(6) 119.5(4) C(13) C(14) C(15) 120.4(4) C(2) C( l ) C(10) 123.2(3) C(14) C(15) C(16) 118.7(5) C(6) C( l ) C(10) 117.3(4) C(15) C(16) C(17) 120.9(5) C(l) C(2) C(3) 120.8(4) C(12) C(17) C(16) 120.7(4) C(2) C(3) C(4) 119.9(4) 0(1) C(18) N( l ) 120.5(4) C(3) C(4) C(5) 119.8(4) 0(1) C(18) C(19) 119.4(4) C(4) C(5) C(6) 121.8(4) N( l ) C(18) C(19) 120.1(3) C(l) C(6) C(5) 118.2(4) C(18) C(19) C(20) 115.9(3) C( l ) C(6) C(7) 119.2(4) C(18) C(19) C(24) 124.4(4) C(5) C(6) C(7) 122.6(4) C(20) C(19) C(24) 119.3(4) C(6) C(7) C(8) 112.0(4) C(19) C(20) C(21) 118.9(4) C(7) C(8) C(9) 110.8(4) F( l ) C(21) C(20) 117.9(4) C(8) C(9) C(10) 120.5(4) F( l) C(21) C(22) 119.3(4) N(l) C(10) C( l ) 116.5(3) C(20) C(21) C(22) 122.8(4) 233 Chapter 7 Experimental/Crystallography N(l) C(10) C(9) 121.4(3) C(21) C(22) C(23) 118.6(4) C( l ) C(10) C(9) 122.1(4) C(22) C(23) C(24) 120.6(4) N( l ) C ( l l ) C(12) 113.9(3) C(19) C(24) C(23) 119.8(4) C ( l l ) C(12) C(13) 121.5(4) 7.2.6. A^-benzyl-S-chloro-A^-CS^-dihydro-l-naphthyObenzamide (If) A crystal of approximate dimensions of 1.00 x 0.50 x 0.50 mm size was chosen for data collection. Crystallographic data of If appear in Table 7.15. A monoclinic cell with Z = 4 (the calculated density was 1.30 gem"3) was indicated by preliminary measurements. Of the 4354 reflections collected, 4174 were unique and 3098 observed (> 3o(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles of 24 carefully centred reflections in the range 107.09 < 20 < 113.63°. The data for If were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.79 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed minimal decay. The space group was assigned as P2\ln based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR92)6 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. The hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. A secondary 234 Chapter 7 Experimental/Crystallography extinction correction was applied (final coefficient = 1.2 x 10~5). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.1 2 , 1 3 The refinement converged at R = 0.054, Rw = 0.079 for 245 variables (GOF = 3.43; including zeros: R = 0.080, Rw = 0.100), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.18 and 0.17 eA"3. This compound is isostructural to Ig. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.19 - 7.21, respectively. 0 2 Table 7.19. Final atomic coordinates (fractional) and B(eq) (A ) of If. atom X y z B(eq) Cl( l ) -0.09987(7) 0.3990(1) 0.88021(6) 7.53(2) 0(1) 0.1434(1) 0.3579(2) 0.5975(1) 4.72(4) N( l ) 0.1881(1) 0.5773(2) 0.5747(1) 3.33(4) C( l ) 0.1565(1) 0.8146(2) 0.5258(1) 3.10(4) C(2) 0.1113(2) 0.7716(2) 0.4484(1) 3.74(5) C(3) 0.0812(2) 0.8646(3) 0.3862(1) 4.15(5) C(4) 0.0964(2) 1.0024(3) 0.4008(2) 4.15(5) C(5) 0.1420(2) 1.0464(2) 0.4769(1) 3.86(5) C(6) 0.1726(2) 0.9546(2) 0.5399(1) 3.29(4) C(7) 0.2239(2) 1.0003(3) 0.6229(1) 4.10(5) C(8) 0.1906(2) 0.9105(2) 0.6984(1) 3.88(5) C(9) 0.2000(2) 0.7629(2) 0.6764(1) 3.47(4) C(10) 0.1833(1) 0.7191(2) 0.5962(1) 3.12(4) C ( l l ) 0.2765(2) 0.5328(2) 0.5190(1) 3.77(5) C(12) 0.3726(2) 0.4832(2) 0.5692(1) 3.60(4) C(13) 0.3935(2) 0.3460(3) 0.5780(2) 4.78(6) C(14) 0.4833(3) 0.3011(4) 0.6214(2) 6.12(8) C(15) 0.5536(2) 0.3938(4) 0.6567(2) 5.97(7) C(16) 0.5337(2) 0.5302(4) 0.6486(2) 5.48(7) 235 Chapter 7 Experimental/Crystallography C(17) 0.4441(2) 0.5759(3) 0.6046(1) 4.34(5) C(18) 0.1250(2) 0.4793(2) 0.6088(1) 3.44(4) C(19) 0.0288(2) 0.5203(2) 0.6593(1) 3.40(4) C(20) 0.0107(2) 0.4516(2) 0.7360(1) 3.89(5) C(21) -0.0813(2) 0.4786(3) 0.7813(2) 4.49(5) C(22) -0.1565(2) 0.5686(3) 0.7515(2) 4.68(6) C(23) -0.1390(2) 0.6342(3) 0.6744(2) 4.55(6) C(24) -0.0463(2) 0.6127(2) 0.6284(2) 4.00(5) Table 7.20. Bond lengths (A) of If with estimated standard deviations. atom atom distance atom atom distance Cl( l ) C(21) 1.740(3) C(9) C(10) 1.332(3) 0(1) C(18) 1.227(3) C ( l l ) C(12) 1.513(3) N( l ) C(10) 1.433(3) C(12) C(13) 1.380(4) N( l ) C ( l l ) 1.479(3) C(12) C(17) 1.391(3) N( l ) C(18) 1.358(3) C(13) C(14) 1.383(4) C( l ) C(2) 1.391(3) C(14) C(15) 1.379(5) C( l ) C(6) 1.408(3) C(15) C(16) 1.369(5) C( l ) C(10) 1.477(3) C(16) C(17) 1.388(4) C(2) C(3) 1.380(3) C(18) C(19) 1.501(3) C(3) C(4) 1.385(4) C(19) C(20) 1.388(3) C(4) C(5) 1.379(3) C(19) C(24) 1.393(3) C(5) C(6) 1.382(3) C(20) C(21) 1.384(3) C(6) C(7) 1.506(3) C(21) C(22) 1.372(4) C(7) C(8) 1.528(3) C(22) C(23) 1.379(4) C(8) C(9) 1.495(3) C(23) C(24) 1.387(3) Table 7.21. Bond angles (°) of If with estimated standard deviations. atom atom atom angle atom atom atom angle C(10) N( l ) C ( l l ) 117.1(2) C(18) C(19) C(24) 122.8(2) C(10) N( l ) C(18) 124.9(2) C(20) C(19) C(24) 119.8(2) C ( l l ) N( l ) C(18) 117.5(2) C(19) C(20) C(21) 119.1(2) C(2) C( l ) C(6) 119.2(2) Cl( l ) C(21) C(20) 118.7(2) C(2) C( l ) C(10) 122.4(2) Cl( l ) C(21) C(22) 119.4(2) C(6) C( l ) C(10) 118.3(2) C(20) C(21) C(22) 121.8(2) C( l ) C(2) C(3) 120.7(2) C(21) C(22) C(23) 118.7(2) C(2) C(3) C(4) 119.7(2) C(7) C(8) C(9) 111.2(2) C(3) C(4) C(5) 120.2(2) C(8) C(9) C(10) 121.0(2) C(4) C(5) C(6) 120.9(2) N( l ) C(10) C( l ) 117.0(2) C( l ) C(6) C(5) 119.3(2) N( l ) C(10) C(9) 121.7(2) C( l ) C(6) C(7) 119.0(2) C( l ) C(10) C(9) 121.3(2) C(5) C(6) C(7) 121.7(2) N( l ) C ( l l ) C(12) 113.3(2) C(6) C(7) C(8) 111.5(2) C ( l l ) C(12) C(13) 121.1(2) C(14) C(15) C(16) 119.6(3) C ( l l ) C(12) C(17) 120.3(2) C(15) C(16) C(17) 120.6(3) C(13) C(12) C(17) 118.6(2) 236 Chapter 7 Experimental/Crystallography C(12) C(17) C(16) 120.2(3) C(12) C(13) C(14) 120.9(3) 0(1) C(18) N( l ) 121.4(2) C(13) C(14) C(15) 120.1(3) 0(1) C(18) C(19) 119.3(2) C(22) C(23) C(24) 121.0(2) N( l ) C(18) C(19) 119.2(2) C(19) C(24) C(23) 119.5(2) C(18) C(19) C(20) 117.1(2) 7.2.7. N-benzyl-S-bromo-AMS^-dmydro-l-naphthyObenzamide (Ig) A crystal of approximate dimensions of 0.40 x 0.35 x 0.20 mm size was chosen for data collection. Crystallographic data of Ig appear in Table 7.15. A monoclinic cell with Z = 4 (the calculated density was 1.46 gem"3) was indicated by preliminary measurements. Of the 14834 reflections collected, 3519 were unique and 2525 observed (> 3o(I)). The final unit-cell parameters were obtained by least-squares on the setting angles for 14834 reflections in the range 3.09 < 9 < 25.02°. The data for I g were processed, and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on a three-dimensional analysis of symmetry-equivalent data using 4 t h order spherical harmonics) was applied (transmission factors: 0.69 to 1.00). The space group was assigned as P2i/n based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. The hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. Neutral atom scattering factors for all atoms and anomalous dispersion corrections" for the non-237 Chapter 7 Experimental/Crystallography hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.025, Rw = 0.033 for 245 variables (GOF = 0.89; including zeros: R = 0.044, Rw = 0.069), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.53 and 0.34 eA"3. This compound is isostructural to If. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.22 - 7.24, respectively. Table 7.22. Final atomic coordinates (fractional) and B(eq) (A 2) of Ig. atom X y z B(eq) Br(l) -0.09741(2) 0.39972(3) 0.89412(1) 2.933(6) 0(1) 0.1405(1) 0.3590(1) 0.59604(9) 1.83(3) N(l) 0.1861(1) 0.5780(2) 0.5729(1) 1.12(3) C(l) 0.1547(1) 0.8159(2) 0.5240(1) 1.03(4) C(2) 0.1089(2) 0.7722(2) 0.4453(1) 1.38(4) C(3) 0.0774(2) 0.8664(2) 0.3824(1) 1.60(4) C(4) 0.0916(2) 1.0036(2) 0.3975(1) 1.65(4) C(5) 0.1374(2) 1.0479(2) 0.4753(1) 1.40(4) C(6) 0.1699(1) 0.9556(2) 0.5386(1) 1.13(4) C(7) 0.2227(2) 1.0009(2) 0.6226(1) 1.55(4) C(8) 0.1913(2) 0.9110(2) 0.6992(1) 1.49(4) C(9) 0.2003(1) 0.7632(2) 0.6764(1) 1.21(4) C(10) 0.1824(1) 0.7202(2) 0.5948(1) 1.05(4) C( l l ) 0.2736(2) 0.5332(2) 0.5166(1) 1.36(4) C(12) 0.3695(1) 0.4827(2) 0.5674(1) 1.25(4) C(13) 0.3873(2) 0.3439(2) 0.5781(1) 1.83(4) C(14) 0.4774(2) 0.2982(2) 0.6220(1) 2.52(5) C(15) 0.5498(2) 0.3903(3) 0.6553(1) 2.57(5) C(16) 0.5325(2) 0.5278(3) 0.6455(1) 2.24(5) C(17) 0.4427(2) 0.5745(2) 0.6015(1) 1.71(4) C(18) 0.1231(1) 0.4808(2) 0.6075(1) 1.26(4) 238 Chapter 7 Experimental/Crystallography C(19) 0.0284(1) 0.5227(2) 0.6590(1) 1.12(4) C(20) 0.0108(2) 0.4551(2) 0.7373(1) 1.33(4) C(21) -0.0798(2) 0.4832(2) 0.7837(1) 1.54(4) C(22) -0.1557(2) 0.5734(2) 0.7531(1) 1.75(4) C(23) -0.1389(2) 0.6384(2) 0.6741(1) 1.71(4) C(24) -0.0472(2) 0.6155(2) 0.6274(1) 1.48(4) Table 7.23. Bond lengths (A) of Ig with estimated standard deviations. atom atom distance atom atom distance Br(l) C(21) 1.898(2) C(9) C(10) 1.336(3) 0(1) C(18) 1.232(2) C ( l l ) C(12) 1.512(3) N( l ) C(10) 1.440(2) C(12) C(13) 1.395(3) N( l ) C ( l l ) 1.480(2) C(12) C(17) 1.389(3) N( l ) C(18) 1.358(3) C(13) C(14) 1.388(3) C( l ) C(2) 1.399(3) C(14) C(15) 1.380(4) C(l) C(6) 1.406(3) C(15) C(16) 1.380(3) C( l ) C(10) 1.475(3) C(16) C(17) 1.388(3) C(2) C(3) 1.390(3) C(18) C(19) 1.501(3) C(3) C(4) 1.382(3) C(19) C(20) 1.393(3) C(4) C(5) 1.389(3) C(19) C(24) 1.402(3) C(5) C(6) 1.386(3) C(20) C(21) 1.384(3) C(6) C(7) 1.509(3) C(21) C(22) 1.384(3) C(7) C(8) 1.528(3) C(22) C(23) 1.389(3) C(8) C(9) 1.501(3) C(23) C(24) 1.388(3) Table 7.24 Bond angles (°) of Ig with estimated standard deviations. atom atom atom angle atom atom atom angle C(10) N( l ) C ( l l ) 116.9(2) C ( l l ) C(12) C(17) 120.2(2) C(10) N( l ) C(18) 124.9(2) C(13) C(12) C(17) 119.2(2) C ( l l ) N( l ) C(18) 117.7(2) C(12) C(13) C(14) 120.3(2) C(2) C(l) C(6) 119.4(2) C(13) C(14) C(15) 120.0(2) C(2) C( l ) C(10) 122.0(2) C(14) C(15) C(16) 120.0(2) C(6) C(l) C(10) 118.5(2) C(15) C(16) C(17) 120.3(2) C(l) C(2) C(3) 120.2(2) C(12) C(17) C(16) 120.1(2) C(2) C(3) C(4) 120.1(2) 0(1) C(18) N( l ) 121.5(2) C(3) C(4) C(5) 120.1(2) 0(1) C(18) C(19) 119.3(2) C(4) C(5) C(6) 120.7(2) N(l ) C(18) C(19) 119.2(2) C(l) C(6) C(5) 119.4(2) C(18) C(19) C(20) 117.4(2) C(l) C(6) C(7) 118.8(2) C(18) C(19) C(24) 122.7(2) C(5) C(6) C(7) 121.8(2) C(20) C(19) C(24) 119.5(2) C(6) C(7) C(8) 111.6(2) C(19) C(20) C(21) 119.4(2) C(7) C(8) C(9) 111.2(2) Br(l) C(21) C(20) 118.8(1) C(8) C(9) C(10) 120.8(2) Br(l) C(21) C(22) 119.3(2) 239 Chapter 7 Experimental/Crystallography N(l ) C(10) C( l ) 117.2(2) C(20) C(21) C(22) 121.9(2) N( l ) C(10) C(9) 121.3(2) C(21) C(22) C(23) 118.5(2) C( l ) C(10) C(9) 121.5(2) C(22) C(23) C(24) 121.0(2) N( l ) C ( l l ) C(12) 113.4(2) C(19) C(24) C(23) 119.7(2) C ( l l ) C(12) C(13) 120.6(2) 7.2.8. frans-5-benzyl-8-chloro-4b,10b,ll,12-tetrahydro-benzo[c]phenan-thridin-6[5H]-one (Ilf) A crystal of approximate dimensions of 0.30 x 0.25 x 0.25 mm size was chosen for data collection. Crystallographic data of Ilf appear in Table 7.25. A monoclinic cell with Z = 8 (the calculated density was 1.34 gem - 3) was indicated by preliminary measurements. Of the 5836 reflections collected, 5708 were unique and 2127 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles of 24 carefully centred reflections in the range 9.65 < 20 < 19.75°. The data for Hf were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.94 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as C2/c based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR92)6 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. Hydrogen atoms were located 240 Chapter 7 Experimental/Crystallography from difference Fourier syntheses and refined isotropically. Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.048, Rw = 0.042 for 324 variables (GOF = 2.03; including zeros: R = 0.183, Rw = 0.051), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.24 and 0.32 e A 3 . This compound is isostructural to Ilg. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.26 - 7.28, respectively. Table 7.25. Crystallographic data of I l f and Ilg. iif iig Formula C ^ N O C l C ^ N O B r fw 373.88 418.33 Color, habit colourless, prism colourless, prism Crystal size, mm 0.30 x 0.25 x 0.25 0.75 x 0.35 x 0.25 Crystal system monoclinic monoclinic Space group C2/c C2/c a, A 23.479(7) 23.473(4) b, A 9.736(2) 9.682(1) c ,A 19.288(6) 20.997(4) a(° ) 90 90 P(°) 122.63(2) 128.904(5) Y(°) 90 90 V 3713(2) 0 3714(1) 8 Dcalc, g/cm3 o 1.34 O 1.50 F(000) 1568 1712 Radiation Mo- K a Mo- K a mm'1 0.22 2.23 Transmission factors 0.94-1.00 0.57-1.00 Scan type co - 20 (J) and co Scan range, ° in co 1.15 + 0.35 tanO - 1 9 - 2 3 f , 0 - 190* Scan speed, 7min 16.0 35s* Data collected +h, +k, ±1 ±h, ±k, ±1 241 Chapter 7 Experimental/Crystallography 20max, ° 60 50 Crystal decay, % -0.77 0.00 Data collection temperature (K) 293 173 Total reflections 5836 17163 Total unique reflections 5708 8206 P merge 0.06 0.04 No. of reflections with I > 3o(I) 2127 4532 No. of variables 324 245 p-factor 0.02 0.00 R 0.048 0.058 Rw 0.042 0.092 Goodness of fit (GOF) 2.03 1.77 Max Ala (final cycle) 0.00 0.01 Residual density e/A3 -0.24, 0.32 -1.10, 0.90 C C D data; this is the co scan range (°). CCD data; this is the <|> scan range (°). * C C D data; exposure time per frame. Table 7.26. Final atomic coordinates (fractional) and B(eq) (A 2 ) of Ilf. atom X y z B(eq) Cl( l ) -0.05208(4) 0.4187(1) 0.33779(5) 6.30(2) O(l) 0.1242(1) 0.0098(2) 0.4674(1) 5.03(6) N( l ) 0.1579(1) -0.0091(2) 0.6010(1) 3.46(5) C( l ) 0.1953(1) -0.0182(3) 0.7515(2) 3.83(7) C(2) 0.2652(2) -0.0276(3) 0.7874(2) 4.52(8) C(3) 0.3068(2) -0.0782(3) 0.8654(2) 4.41(8) C(4) 0.2805(2) -0.1149(3) 0.9111(2) 4.78(8) C(5) 0.2122(2) -0.0997(3) 0.8782(2) 4.50(9) C(6) 0.1687(1) -0.0536(3) 0.7986(2) 3.68(7) C(7) 0.0948(2) -0.0341(4) 0.7658(2) 4.79(9) C(8) 0.0641(2) 0.0809(4) 0.7041(2) 4.59(9) C(9) 0.0779(1) 0.0588(4) 0.6373(2) 4.07(8) C(10) 0.1514(1) 0.0491(4) 0.6679(2) 4.32(8) C ( l l ) 0.1971(2) -0.1312(3) 0.6080(2) 3.84(8) C(12) 0.2622(1) -0.1053(3) 0.6119(2) 3.38(7) C(13) 0.2949(2) -0.2156(4) 0.6039(2) 4.49(9) C(14) 0.3553(2) -0.1992(5) 0.6092(2) 5.5(1) C(15) 0.3836(2) -0.0720(5) 0.6224(2) 5.4(1) C(16) 0.3517(2) 0.0393(4) 0.6294(2) 4.90(9) C(17) 0.2907(2) 0.0223(4) 0.6236(2) 4.17(8) C(18) 0.1197(1) 0.0468(3) 0.5250(2) 3.52(7) C(19) 0.0682(1) 0.1509(3) 0.5126(2) 3.35(6) C(20) 0.0391(1) 0.2329(3) 0.4432(2) 4.01(7) C(21) -0.0129(1) 0.3205(3) 0.4268(2) 4.21(7) C(22) -0.0360(2) 0.3248(4) 0.4787(2) 4.75(9) C(23) -0.0078(2) 0.2421(4) 0.5465(2) 4.60(8) C(24) 0.0450(1) 0.1533(3) 0.5652(2) 3.57(7) 242 Chapter 7 Experimental/Crystallography H(l) -0.070(1) 0.383(3) 0.466(2) 5.2(8) H(2) -0.022(1) 0.245(3) 0.582(2) 5.1(8) H(3) 0.055(1) 0.226(3) 0.407(2) 4.1(6) H(4) 0.168(1) -0.184(3) 0.561(2) 4.7(7) H(5) 0.207(1) -0.182(3) 0.659(2) 4.2(6) H(6) 0.272(1) 0.098(2) 0.627(1) 3.0(6) H(7) 0.368(1) 0.128(3) 0.637(2) 3.8(7) H(8) 0.422(2) -0.060(3) 0.622(2) 6.2(8) H(9) 0.376(2) -0.279(3) 0.602(2) 7.0(9) H(10) 0.276(1) -0.302(3) 0.593(2) 3.8(7) H ( l l ) 0.284(1) -0.001(3) 0.756(2) 4.4(7) H(12) 0.354(1) -0.085(3) 0.886(2) 5.0(7) H(13) 0.311(1) -0.144(3) 0.968(2) 4.6(7) H(14) 0.195(1) -0.119(3) 0.909(2) 4.5(7) H(15) 0.070(1) -0.124(3) 0.742(2) 5-9(8) H(16) 0.091(1) -0.020(3) 0.812(2) 4.4(7) H(17) 0.081(1) 0.172(3) 0.729(2) 5.5(8) H(18) 0.019(2) 0.082(3) 0.681(2) 5.9(8) H(19) 0.065(1) -0.039(3) 0.621(2) 5-4(8) H(20) 0.166(2) 0.158(3) 0.678(2) 7.6(9) 7.27. Bond lengths (A) of Hf with estimated standard deviations. atom atom distance atom atom distance Cl( l ) C(21) 1.733(3) C(9) C(24) 1.491(4) 0(1) C(18) 1.224(3) C ( l l ) C(12) 1.511(4) N( l ) C(10) 1.490(3) C(12 ) C(13) 1.375(4) N( l ) C ( l l ) 1.464(3) C(12 ) C(17) 1.372(4) N( l ) C(18) 1.353(3) C(13 ) C(14) 1.376(5) C( l ) C(2) 1.399(4) C(14 ) C(15) 1.363(5) C( l ) C(6) 1.393(4) C(15 ) C(16) 1.364(5) C( l ) C(10) 1.516(4) C(16 ) C(17) 1.385(4) C(2) C(3) 1.369(4) C(18 ) C(19) 1.496(4) C(3) C(4) 1.369(4) C(19 ) C(20) 1.383(4) C(4) C(5) 1.378(4) C(19 ) C(24) 1.385(4) C(5) C(6) 1.382(4) C(20 ) C(21) 1.380(4) C(6) C(7) 1.506(4) C(21 ) C(22) 1.371(4) C(7) C(8) 1.505(5) C(22 ) C(23) 1.364(5) C(8) C(9) 1.502(4) C(23 ) C(24) 1.390(4) C(9) C(10) 1.497(4) 243 Chapter 7 Experimental/Crystallography Table 7.28. Bond angles (°) of Ilf with estimated standard deviations. atom atom atom angle atom atom atom angle C(10) N( l ) C ( l l ) 125.5(2) C ( l l ) C(12) C(17) 123.4(3) C(10) N( l ) C(18) 117.9(2) C(13) C(12) C(17) 118.2(3) C ( l l ) N( l ) C(18) 116.3(2) C(12) C(13) C(14) 121.1(4) C(2) C( l ) C(6) 118.6(3) C(13) C(14) C(15) 119.9(4) C(2) C( l ) C(10) 119.8(3) C(14) C(15) C(16) 120.2(3) C(6) C( l ) C(10) 121.0(2) C(15) C(16) C(17) 119.7(4) C( l ) C(2) C(3) 121.3(3) C(12) C(17) C(16) 120.9(3) C(2) C(3) C(4) 119.9(3) 0(1) C(18) N( l ) 122.3(3) C(3) C(4) C(5) 119.5(3) 0(1) C(18) C(19) 120.8(3) C(4) C(5) C(6) 121.7(3) N( l ) C(18) C(19) 116.8(2) C( l ) C(6) C(5) 118.9(3) C(18) C(19) C(20) 118.7(3) C( l ) C(6) C(7) 121.0(3) C(18) C(19) C(24) 119.9(3) C(5) C(6) C(7) 120.0(3) C(20) C(19) C(24) 121.1(3) C(6) C(7) C(8) 112.1(3) C(19) C(20) C(21) 119.4(3) C(7) C(8) C(9) 109.8(3) Cl( l ) C(21) C(20) 119.9(3) C(8) C(9) C(10) 114.1(3) Cl( l ) C(21) C(22) 120.0(2) C(8) C(9) C(24) 118.0(3) C(20) C(21) C(22) 120.1(3) C(10) C(9) C(24) 108.2(2) C(21) C(22) C(23) 120.2(3) N( l ) C(10) C( l ) 115.4(2) C(22) C(23) C(24) 121.3(3) N( l ) C(10) C(9) 108.5(2) C(9) C(24) C(19) 117.6(2) C( l ) C(10) C(9) 115.0(3) C(9) C(24) C(23) 124.5(3) N( l ) C ( l l ) C(12) 116.0(2) C(19) C(24) C(23) 117.9(3) C ( l l ) C(12) C(13) 118.4(3) 7.2.9. rrans-5-benzyl-8-bromo-4b,10b,ll,12-tetrahydro-benzo[c]phenanthridin-6[5Z/]-one (Ug) A crystal of approximate dimensions of 0.75 x 0.35 x 0.25 mm size was chosen for data collection. Crystallographic data of Ilg appear in Table 7.25. A monoclinic cell with Z = 8 (the calculated density was 1.50 gem"3) was indicated by preliminary measurements. Of the 17163 reflections collected, 8206 were unique and 4532 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares on the setting angles for 14814 reflections in the range 1.25 < 0 < 30.1°. The data for Ilg 244 Chapter 7 Experimental/Crystallography were processed,3 and an absorption correction (empirical, based on a three-dimensional analysis of symmetry-equivalent data using 4 t h order spherical harmonics) was applied (transmission factors: 0.57 to 1.00). The space group was assigned as C2/c based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by 7 10 direct methods (SIR97) and expanded using Fourier techniques. The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. The hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bonded atom. Neutral atom scattering factors for all atoms and anomalous dispersion corrections" for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.1 2 , 1 3 The refinement converged at R = 0.058, Rw = 0.092 for 245 variables (GOF = 1.70; including zeros: R = 0.079, Rw = 0.155), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -1.10 and 0.90 eA"3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.29 -7.31, respectively. Table 7.29. Final atomic coordinates (fractional) and B(eq) (A ) of Ilg. atom x y 5 B(eq) Br(l) -0.05749(2) 0.42300(4) 0.32693(2) 3.266(9) 0(1) 0.1230(1) 0.0071(3) 0.4670(1) 2.73(5) N(l) 0.1558(1) -0.0113(3) 0.6002(1) 1.86(4) C(l) 0.1932(1) -0.0180(3) 0.7504(2) 2.21(6) 245 Chapter 7 Experimental/Crystallography C(2) 0.2628(2) -0.0288(4) 0.7849(2) 2.65(6) C(3) 0.3048(2) -0.0804(3) 0.8633(2) 2.54(6) C(4) 0.2784(2) -0.1159(4) 0.9096(2) 2.80(6) C(5) 0.2098(2) -0.1004(3) 0.8776(2) 2.42(6) C(6) 0.1667(2) -0.0517(3) 0.7982(2) 2.07(5) C(7) 0.0935(2) -0.0294(4) 0.7670(2) 2.60(6) C(8) 0.0628(2) 0.0868(4) 0.7046(2) 2.54(6) C(9) 0.0765(2) 0.0610(3) 0.6375(2) 2.25(6) C(10) 0.1499(2) 0.0502(4) 0.6669(2) 2.47(6) C(ll) 0.1947(1) -0.1345(3) 0.6069(2) 2.06(5) C(12) 0.2598(1) -0.1077(3) 0.6099(2) 1.79(5) C(13) 0.2926(2) -0.2199(3) 0.6021(2) 2.38(6) C(14) 0.3525(2) -0.2017(4) 0.6052(2) 3.02(7) C(15) 0.3801(2) -0.0721(4) 0.6162(2) 2.92(7) C(16) 0.3472(2) 0.0402(4) 0.6230(2) 2.62(6) C(17) 0.2868(1) 0.0233(3) 0.6192(2) 2.08(5) C(18) 0.1181(1) 0.0445(3) 0.5239(2) 1.88(5) C(19) 0.0673(1) 0.1505(3) 0.5121(2) 1.75(5) C(20) 0.0381(1) 0.2320(3) 0.4421(2) 2.05(5) C(21) -0.0137(1) 0.3199(3) 0.4261(2) 2.25(5) C(22) -0.0371(2) 0.3284(3) 0.4787(2) 2.63(6) C(23) -0.0082(2) 0.2463(3) 0.5474(2) 2.50(6) C(24) 0.0443(1) 0.1560(3) 0.5656(2) 1.94(5) Table 7.30. Bond lengths (A) of I lg with estimated standard deviations. atom atom distance atom atom distance Br( l) C(21) 1.903(3) C(9) C(24) 1.492(4) O(l) C(18) 1.219(4) C ( l l ) C(12) 1.520(4) N( l ) C(10) 1.491(4) C(12) C(13) 1.387(4) N( l ) C ( l l ) 1.465(4) C(12) C(17) 1.386(4) N( l ) C(18) 1.363(4) C(13) C(14) 1.390(4) C( l ) C(2) 1.402(4) C(14) C(15) 1.380(5) C( l ) C(6) 1.399(4) C(15) C(16) 1.376(5) C( l ) C(10) 1.523(4) C(16) C(17) 1.386(5) C(2) C(3) 1.387(5) C(18) C(19) 1.496(4) C(3) C(4) 1.376(5) C(19) C(20) 1.390(4) C(4) C(5) 1.391(5) C(19) C(24) 1.399(4) C(5) C(6) 1.394(4) C(20) C(21) 1.379(4) C(6) C(7) 1.504(5) C(21) C(22) 1.390(5) C(7) C(8) 1.520(5) C(22) C(23) 1.376(5) C(8) C(9) 1.511(4) C(23) C(24) 1.394(4) 246 Chapter 7 Experimental/Crystallography C(9) C(10) 1.503(4) Table 7.31. Bond angles (°) of Ilg with estimated standard deviations. atom atom atom angle atom atom atom angle C(10) N( l ) C ( l l ) 126.1(2) C ( l l ) C(12) C(17) 117.9(3) C(10) N( l ) C(18) 118.0(2) C(13) C(12) C(17) 119.2(3) C ( l l ) N( l ) C(18) 115.7(2) C(12) C(13) C(14) 119.9(3) C(2) C( l ) C(6) 119.0(3) C(13) C(14) C(15) 120.6(3) C(2) C( l ) C(10) 119.2(3) C(14) C(15) C(16) 119.4(3) C(6) C( l ) C(10) 121.2(3) C(15) C(16) C(17) 120.5(3) C( l ) C(2) C(3) 121.1(3) C(12) C(17) C(16) 120.3(3) C(2) C(3) C(4) 119.7(3) O(l) C(18) N( l ) 122.5(3) C(3) C(4) C(5) 120.0(3) 0(1) C(18) C(19) 121.2(3) C(4) C(5) C(6) 121.0(3) N( l ) C(18) C(19) 116.3(2) C( l ) C(6) C(5) 119.2(3) C(18) C(19) C(20) 118.4(2) C( l ) C(6) C(7) 121.2(3) C(18) C(19) C(24) 120.3(3) C(5) C(6) C(7) 119.6(3) C(20) C(19) C(24) 120.9(3) C(6) C(7) C(8) 112.4(3) C(19) C(20) C(21) 119.1(3) C(7) C(8) C(9) 109.3(3) Br(l) C(21) C(20) 119.2(2) C(8) C(9) C(10) 114.3(3) Br(l) C(21) C(22) 119.5(2) C(8) C(9) C(24) 117.4(2) C(20) C(21) C(22) 121.2(3) C(10) C(9) C(24) 107.8(2) C(21) C(22) C(23) 119.1(3) N( l ) C(10) C( l ) 115.0(3) C(22) C(23) C(24) 121.4(3) N( l ) C(10) C(9) 108.5(2) C(9) C(24) C(19) ' 117.4(2) C( l ) C(10) C(9) 114.5(3) C(9) C(24) C(23) 124.3(3) N( l ) C ( l l ) C(12) 115.5(2) C(19) C(24) C(23) 118.3(3) C ( l l ) C(12) C(13) 122.9(3) 7.2.10. Spiro[2//-indene-2,2'-tricyclo(3.3.1.13'7)decan]-l(3//)-one(III) A crystal of approximate dimensions of 0.55 x 0.50 x 0.25 mm size was chosen for data collection. Crystallographic data of III appear in Table 7.32. A monoclinic cell with Z = 4 (the calculated density was 1.27 gem"3) was indicated by preliminary measurements. Of the 3218 reflections collected, 2958 were unique and 2129 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 23 carefully centred reflections in the range 108.09 247 Chapter 7 Experimental/Crystallography < 20 < 114.32°. The data for III were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.83 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed minimal decay. The space group was assigned as P2\lc based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR92).6 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. Hydrogen atoms were refined isotropically. A secondary extinction correction was applied (final coefficient = 1.31 x 10~4). Neutral atom scattering factors for all atoms and anomalous dispersion corrections" for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.053, Rw = 0.050 for 253 variables (GOF = 1.55; including zeros: R = 0.069, Rw = 0.058), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.15 and 0.16 eA"3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.33 -7.35, respectively. 248 Chapter 7 Experimental/Crystallography Table 7.32. Crystallographic data of III and IV. Ill IV Formula fw Color, habit Crystal size, mm Crystal system Space group a, A b, A c, A a(° ) P C ) Y(°) V Z Dcalc, g/cm3 F(000) Radiation u, mm'1 Transmission factors Scan type Scan range, ° in co Scan speed, °/min Data collected 20max, ° Crystal decay, % Data Collection Temperature (K) Total reflections Total unique reflections merge No. of reflections with I > 3a(I) No. of variables p-factor R Rw Goodness of fit (GOF) Max A/a (final cycle) Residual density e/A3 C.sH^O 252.36 colourless, plate 0.55 x 0.50 x 0.25 monoclinic P2Jc 6.7952(6) 6.7557(8) 28.909(3) 90 92.94(1) 90 1325.3(2) 4 1.27 544 Cu- K a 0.585 0.83-1.00 co - 20 1.52 + 0.20 tan0 32.0 +h, +k, ±1 155 -1.00 293 3218 2958 0.07 2129 253 0.02 0.053 0.050 1.55 0.00 -0.15,0.16 266.38 colourless, cube 0.50 x 0.50 x 0.50 monoclinic C2/c 17.788(2) 12.827(2) 12.960(1) 90 104.178(7) 90 2867.0(5) 8 1.23 1152 Cu- K a 0.566 0.83-1.00 co - 20 1.42 + 0.20 tanO 32.0 +h, +k, ±1 155 0.97 293 3149 3054 0.02 2424 270 0.02 0.050 0.069 3.93 0.00 -0.17,0.24 2 4 9 Chapter 7 Experimental/Crystallography Table 7.33. Final atomic coordinates (fractional) and B(eq) (A 2) of III. atom X y z B(eq) 0(1) 0.3904(2) 0.2382(3) 0.65377(5) 5.79(4) C( l ) 0.5612(3) 0.2269(3) 0.66826(7) 3.92(4) C(2) 0.7450(3) 0.2122(3) 0.63987(6) 3.54(4) C(3) 0.7775(3) 0.4105(3) 0.61404(7) 3.75(4) C(4) 0.6063(3) 0.4517(3) 0.57867(8) 4.48(5) C(5) 0.5937(3) 0.2861(4) 0.54264(7) 4.79(5) C(6) 0.5603(4) 0.0887(4) 0.56665(8) 4.87(5) C(7) 0.7300(3) 0.0486(3) 0.60218(7) 4.17(5) C(8) 0.9224(4) 0.0406(4) 0.57691(9) 4.94(5) C(9) 0.9552(3) 0.2368(4) 0.55213(7) 4.80(5) C(10) 0.7844(4) 0.2782(4) 0.51721(8) 5.36(6) C ( l l ) 0.9681(3) 0.4030(3) 0.58828(8) 4.42(5) C(12) 0.9123(3) 0.1701(4) 0.67749(7) 4.57(5) C(13) 0.8214(3) 0.1886(3) 0.72297(7) 3.87(4) C(14) 0.9086(4) 0.1693(3) 0.76783(8) 4.92(5) C(15) 0.7941(4) 0.1918(4) 0.80477(8) 5.39(6) C(16) 0.5938(4) 0.2321(3) 0.79947(8) 5.41(6) C(17) 0.5056(4) 0.2484(3) 0.75541(8) 4.73(5) C(18) 0.6216(3) 0.2253(3> 0.71805(6) 3.65(4) H( l ) 0.704(3) -0.078(3) • 0.6183(7) 5.2(5) H(2) 1.035(3) 0.011(4) 0.5979(8) 6.1(6) H(3) 0.910(3) -0.064(4) 0.5519(8) 5.8(5) H(4) 0.557(3) -0.017(4) 0.5422(8) 5.9(5) H(5) 0.425(3) 0.088(3) 0.5821(7) 4.8(5) H(6) 1.088(3) 0.235(3) 0.5356(7) 5.0(5) H(7) 0.814(4) 0.404(4) 0.5007(8) 6.7(6) H(8) 0.781(3) 0.171(4) 0.4933(8) 6.1(6) H(9) 0.491(3) 0.316(3) 0.5197(7) 5.4(5) H(10) 0.635(3) 0.581(4) 0.5631(7) 5.3(5) H ( l l ) 0.477(3) 0.460(3) 0.5952(7) 4.5(5) H(12) 0.784(3) 0.513(3) 0.6395(7) 4.5(4) H(13) 1.081(3) 0.379(3) 0.6097(7) 4.4(4) H(14) 0.983(3) 0.535(3) 0.5703(7) 5.4(5) H(15) 0.368(3) 0.274(3) 0.7493(7) 5.1(5) H(16) 0.516(3) 0.246(3) 0.8263(8) 5.5(5) H(17) 0.851(4) 0.178(4) 0.8373(9) 7-4(6) H(18) 1.055(3) 0.133(4) 0.7711(8) 6.3(6) H(19) 0.971(3) 0.037(4) 0.6731(8) 6.3(6) H(20) 1.035(3) 0.253(3) 0.6740(8) 5.8(5) 250 Chapter 7 Experimental/Crystallography Table 7.34. Bond lengths (A) of III with estimated standard deviations. atom atom distance atom atom distance 0(1) C( l ) 1.216(2) C(7) C(8) 1.531(3) C( l ) C(2) 1.532(3) C(8) C(9) 1.528(3) C( l ) C(18) 1.476(3) C(9) C(10) 1.525(3) C(2) C(3) 1.555(3) C(9) C ( l l ) 1.534(3) C(2) C(7) 1.552(3) C(12) C(13) 1.487(3) C(2) C(12) 1.559(3) C(13) C(14) 1.404(3) C(3) C(4) 1.534(3) C(13) C(18) 1.380(3) C(3) C ( l l ) 1.528(3) C(14) C(15) 1.362(4) C(4) C(5) 1.528(3) C(15) C(16) 1.388(4) C(5) C(6) 1.526(3) C(16) C(17) 1.384(3) C(5) C(10) 1.523(3) C(17) C(18) 1.378(3) C(6) C(7) 1.529(3) Table 7.35. Bond angles (°) of III with estimated standard deviations. atom atom atom angle atom atom atom angle O(l) C( l ) C(2) 127.5(2) C(6) C(7) C(8) 108.6(2) O(l) C( l ) C(18) 123.3(2) C(7) C(8) C(9) 110.0(2) C(2) C( l ) C(18) 109.2(1) C(8) C(9) C(10) 110.2(2) C( l ) C(2) C(3) 110.0(2) C(8) C(9) C ( l l ) 108.7(2) C( l ) C(2) C(7) 113.3(2) C(10) C(9) C ( l l ) 109.4(2) C( l ) C(2) C(12) 102.9(1) C(5) C(10) C(9) 108.9(2) C(3) C(2) C(7) 106.4(1) C(3) C ( l l ) C(9) 109.6(2) C(3) C(2) C(12) 112.1(2) C(2) C(12) C(13) 106.3(2) C(7) C(2) C(12) 112.3(2) C(12) C(13) C(14) 129.3(2) C(2) C(3) C(4) 110.8(2) C(12) C(13) C(18) 112.1(2) C(2) C(3) C ( l l ) 110.5(2) C(14) C(13) C(18) 118.6(2) C(4) C(3) C ( l l ) 108.3(2) C(13) C(14) C(15) 118.9(2) C(3) C(4) C(5) 109.6(2) C(14) C(15) C(16) 122.1(2) C(4) C(5) C(6) 109.5(2) C(15) C(16) C(17) 119.5(2) C(4) C(5) C(10) 109.6(2) C(16) C(17) C(18) 118.3(2) C(6) C(5) C(10) 109.8(2) C( l ) C(18) C(13) 108.9(2) C(5) C(6) C(7) 109.6(2) C( l ) C(18) C(17) 128.5(2) C(2) C(7) C(6) 111.4(2) C(13) C(18) C(17) 122.6(2) C(2) C(7) C(8) 109.5(2) 251 Chapter 7 Experimental/Crystallography 7.2.11. 3,4-dihydro-spiro(naphthalene-2(li/),2'-tricyclo(3.3.1.13'7)decan]-l-one (IV) A crystal of approximate dimensions of 0.50 x 0.50 x 0.50 mm size was chosen for data collection. Crystallographic data of IV appear in Table 7.32. A monoclinic cell with Z = 8 (the calculated density was 1.23 gem"3) was indicated by preliminary measurements. Of the 3149 reflections collected, 3054 were unique and 2424 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 23 carefully centred reflections in the range 107.79 < 20 < 114.74°. The data for IV were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.83 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as C2/c based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR88).2 2 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. Hydrogen atoms were refined isotropically. A secondary extinction correction was applied (final coefficient = 4.7 x 10~5). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.050, Rw = 0.069 for 270 252 Chapter 7 Experimental/Crystallography variables (GOF = 3.93; including zeros: R = 0.062, Rw = 0.074), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.17 and 0.24 eA"3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.36 -7.38, respectively. Table 7.36. Final atomic coordinates (fractional) and B(eq) (A 2) of IV. atom X y z B(eq) O(l) 0.85382(7) 0.80841(9) 0.32895(9) 4.76(3) C( l ) 0.86724(8) 0.7413(1) 0.3969(1) 3.14(3) C(2) 0.93336(8) 0.74601(9) 0.4975(1) 2.69(3) C(3) 0.98218(9) 0.8467(1) 0.5026(1) 3.26(3) C(4) 1.0227(1) 0.8512(1) 0.4105(1) 3.72(3) C(5) 1.07585(9) 0.7568(1) 0.4155(1) 3.84(3) C(6) 1.02734(9) 0.6569(1) 0.4083(1) 3.53(3) C(7) 0.98874(8) 0.6514(1) 0.5024(1) 2.79(3) C(8) 1.05210(8) 0.6537(1) 0.6073(1) 3.47(3) C(9) 1.09919(9) 0.7549(1) 0.6138(1) 3.94(3) C(10) 1.1381(1) 0.7575(1) 0.5206(2) 4.47(4) C ( l l ) 1.0458(1) 0.8495(1) 0.6074(1) 3.87(3) C(12) 0.88878(9) 0.7421(1) 0.5863(1) 3.37(3) C(13) 0.84585(9) 0.6394(1) 0.5890(1) 3.65(3) C(14) 0.80483(8) 0.5998(1) 0.4801(1) 3.18(3) C(15) 0.75527(9) 0.5142(1) 0.4680(1) 4.02(3) C(16) 0.7193(1) 0.4767(1) 0.3683(1) 4.31(4) C(17) 0.73019(9) 0.5252(1) 0.2778(1) 4.30(4) C(18) 0.77735(9) 0.6118(1) 0.2877(1) 3.92(3) C(19) 0.81533(8) 0.6487(1) 0.3884(1) 3.16(3) H( l ) 0.9458(9) 0.908(1) 0.498(1) 3.9(3) H(2) 0.987(1) 0.854(1) 0.342(1) 4.2(4) H(3) 1.056(1) 0.916(1) 0.419(1) 4.4(4) H(4) 1.102(1) 0.757(1) 0.359(1) 4.3(4) H(5) 1.063(1) 0.595(1) 0.413(1) 4.3(4) H(6) 0.989(1) 0.651(1) 0.339(1) 4.3(4) H(7) 0.9598(9) 0.586(1) 0.497(1) 3.3(3) H(8) 1.0877(9) 0.591(1) 0.611(1) 3.7(3) H(9) 1.026(1) 0.644(1) 0.669(1) 5.0(4) H(10) 1.139(1) 0.756(1) 0.681(1) 4.6(4) H ( l l ) 1.173(1) 0.821(1) 0.526(1) 4.9(4) H(12) 1.173(1) 0.696(2) 0.528(2) 5.9(5) H(13) 1.073(1) 0.914(1) 0.607(1) 4.6(4) 253 Chapter 7 Experimental/Crystallography H(14) 1.022(1) 0.853(1) 0.672(1) 4.9(4) H(15) 0.786(1) 0.649(1) 0.225(1) 4.4(4) H(16) 0.703(1) 0.496(2) 0.207(2) 6.3(5) H(17) 0.685(1) 0.416(2) 0.361(1) 5.4(4) H(18) 0.744(1) 0.478(2) 0.530(2) 5.7(5) H(19) 0.884(1) 0.584(1) 0.625(1) 4.2(4) H(20) 0.807(1) 0.647(1) 0.628(1) 4.8(4) H(21) 0.849(1) 0.800(2) 0.574(2) 5.3(4) H(22) 0.923(1) 0.754(1) 0.660(1) 4.2(4) Table 7.37. Bond lengths (A) of IV with estimated standard deviations. atom atom distance atom atom distance O(l) C( l ) 1.213(2) C(8) C(9) 1.536(2) C( l ) C(2) 1.528(2) C(7) C(8) 1.539(2) C( l ) C(19) 1.492(2) C(8) C(9) 1.536(2) C(2) C(3) 1.549(2) C(9) C(10) 1.533(3) C(2) C(7) 1.554(2) C(9) C ( l l ) 1.530(2) C(2) C(12) 1.551(2) C(12) C(13) 1.527(2) C(3) C(4) 1.539(3) C(13) C(14) 1.509(2) C(3) C ( l l ) 1.540(2) C(14) C(15) 1.393(2) C(4) C(5) 1.528(2) C(14) C(19) 1.397(2) C(5) C(6) 1.535(2) C(15) C(16) 1.380(2) C(5) C(10) 1.531(2) C(16) C(17) 1.383(3) C(6) C(7) 1.541(2) C(17) C(18) 1.379(2) C(7) C(8) 1.539(2) C(18) C(19) 1.397(2) Table 7.38. Bond angles (°) of IV with estimated standard deviations. atom atom atom angle atom atom atom angle 0(1) C( l ) C(2) 124.4(1) C(13) C(14) C(15) 121.3(1) 0(1) C( l ) C(19) 120.2(1) C(13) C(14) C(19) 120.6(1) C(2) C( l ) C(19) 115.3(1) C(15) C(14) C(19) 118.1(1) C( l ) C(2) C(3) 112.1(1) C(5) C(6) C(7) 110.1(1) C( l ) C(2) C(7) 110.6(1) C(2) C(7) C(6) 109.4(1) C( l ) C(2) C(12) 101.8(1) C(2) C(7) C(8) 109.9(1) C(3) C(2) C(7) 107.8(1) C(6) C(7) C(8) 109.0(1) C(3) C(2) C(12) 112.2(1) C(7) C(8) C(9) 109.7(1) C(7) C(2) C(12) 112.2(1) C(8) C(9) C(10) 108.7(1) C(2) C(3) C(4) 111.2(1) C(8) C(9) C ( l l ) 110.1(1) C(2) C(3) C ( l l ) 109.9(1) C(10) C(9) C ( l l ) 109.5(1) C(4) C(3) C ( l l ) 107.5(1) C(5) C(10) C(9) 109.4(1) C(3) C(4) C(5) 109.9(1) C(14) C(15) C(16) 121.1(2) C(4) C(5) C(6) 109.0(1) C(15) C(16) C(17) 120.5(2) C(4) C(5) C(10) 109.8(1) C(16) C(17) C(18) 119.5(1) C(6) C(5) C(10) 109.4(1) C(17) C(18) C(19) 120.3(2) C(3) C ( l l ) C(9) 110.0(1) C( l ) C(19) C(14) 120.3(1) C(2) C(12) C(13) 113.2(1) C( l ) C(19) C(18) 119.2(1) C(12) C(13) C(14) 113.5(1) C(14) C(19) C(18) 120.5(1) 254 Chapter 7 Experimental/Crystallography 7.2.12. 8,9-dihydro-spiro[6//-benzocycloheptene-6,2'-tricyclo[3.3.1.13'7]decan]-5(7i/)-one (V) A crystal of approximate dimensions of 0.50 x 0.50 x 0.50 mm size was chosen for data collection. Crystallographic data of V appear in Table 7.39. A triclinic cell with Z = 2 (the calculated density was 1.26 gem"3) was indicated by preliminary measurements. Of the 4513 reflections collected, 4305 were unique and 2345 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 22 carefully centred reflections in the range 25.34 < 20 < 37.02°. The data for V were processed,3 and corrected for Lorentz and polarization effects. Absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.99 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as PI based on E-statistics, no systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. The hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and J3H = 1.2 Bbonded atom. A secondary extinction correction was applied (final coefficient = 7.6 x 10"6). Neutral atom 255 ' Chapter 7 Experimental/Crystallography scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.1 2 , 1 3 The refinement converged at R = 0.048, Rw = 0.050 for 191 variables (GOF = 2.15; including zeros: R = 0.12, Rw = 0.055), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.11 and 0.10 e A 3 . Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.40 -7.42, respectively. T a b l e 7.39. Crystallographic data of V and V I . V VI Formula cji»o C 2 1 H 2 6 0 fw 280.41 294.44 Color, habit colourless, cube colourless, prism Crystal size, mm 0.50 x 0.50 x 0.50 0.60 x 0.50 x 0.25 Crystal system triclinic orthorhombic Space group P-l Pna2x a, A 10.898(4) 19.318(4) b, A 11.213(2) 8.282(2) c,A 7.218(6) 10.045(1) a(°) 99.52(3) 90 PC) 109.01(4) 90 YC) 62.27(2) 90 V 738.1(7) 1607.1(4) z 2 4 Dcalc, g/cm3 1.26 1.22 F(000) 304 640 Radiation Mo- K a Cu- K a U, mm"1 0.075 0.550 Transmission factors 0.99-1.00 0.72-1.00 Scan type co - 28 co - 26 Scan range, ° in co 1.21 +0.35 tan9 1.05 + 0.20 tanO Scan speed, °/min 32.0 32.0 Data collected +h, ±k, ±1 +h, +k, +1 26max, 0 60 155 Crystal decay, % -0.74 -2.76 Data Collection Temperature (K) 293 293 256 Chapter 7 Experimental/Crystallography Total reflections 4513 1903 Total unique reflections 4305 1903 Emerge 0-02 0.00 No. of reflections with I > 3o(I) 2345 1564 No. of variables 191 199 p-factor 0.01 0.006 R 0.048 0.041 Rw 0.050 0.049 Goodness of fit (GOF) 2.15 3.68 Max A/a (final cycle) 0.00 0.00 Residual density e/A 3 -0.11,0.10 -0.17,0.23 Table 7.40. Final atomic coordinates (fractional) and B(eq) (A ) of V . atom X y z B(eq) O(l) 0.2183(1) 0.0476(1) 0.6393(2) 3.36(3) C( l ) 0.1917(2) 0.1367(2) 0.7628(2) 2.33(4) C(2) 0.0518(2) 0.1924(2) 0.8228(2) 2.16(4) C(3) -0.0654(2) 0.1633(2) 0.6616(3) 2.68(4) C(4) -0.1048(2) 0.2332(2) 0.4699(3) 3.15(4) C(5) -0.1635(2) 0.3855(2) 0.5043(3) 3.06(4) C(6) -0.0491(2) 0.4161(2) 0.6648(3) 2.85(4) C(7) -0.0112(2) 0.3478(2) 0.8561(2) 2.27(4) C(8) -0.1490(2) 0.3997(2) 0.9192(3) 2.87(4) C(9) -0.2641(2) 0.3697(2) 0.7594(3) 3.07(5) C(10) -0.3002(2) 0.4390(2) 0.5704(3) 3.41(5) C ( l l ) -0.2051(2) 0.2170(2) 0.7217(3) 3.31(5) C(12) 0.0978(2) 0.1141(2) 1.0107(3) 3.06(5) C(13) 0.1998(2) 0.1417(2) 1.1947(3) 3.46(5) C(14) 0.3532(2) 0.0946(2) 1.1879(3) 3.67(5) C(15) 0.3748(2) 0.1734(2) 1.0605(3) 2.82(4) C(16) 0.4788(2) 0.2225(2) 1.1377(3) 3.72(5) C(17) 0.5071(2) 0.2874(2) 1.0220(4) 4.16(6) C(18) 0.4346(2) 0.3027(2) 0.8251(3) 3.95(6) C(19) 0.3334(2) 0.2532(2) 0.7452(3) 3.19(5) C(20) 0.3011(2) 0.1909(2) 0.8611(3) 2.43(4) 41. Bond lengths (A) of V with estimated standard deviations. atom atom distance atom atom distance O(l) C( l ) 1.217(2) C(8) C(9) 1.530(3) C( l ) C(2) 1.535(2) C(9) C(10) 1.528(3) C( l ) C(20) 1.508(2) C(9) C ( l l ) 1.535(3) C(2) C(3) 1.545(2) C(12) C(13) 1.522(3) C(2) C(7) 1.556(2) C(13) C(14) 1.518(3) C(2) C(12) 1.550(2) C(14) C(15) 1.511(3) C(3) C(4) 1.540(3) C(15) C(16) 1.401(3) C(3) C ( l l ) 1.536(3) C(15) C(20) 1.396(2) C(4) C(5) 1.528(3) C(16) C(17) 1.378(3) C(5) C(6) 1.530(3) C(17) C(18) 1.378(3) 257 Chapter 7 Experimental/Crystallography C(5) C(10) 1.531(3) C(18) C(19) 1.381(3) C(6) C(7) 1.532(2) C(19) C(20) 1.387(3) C(7) C(8) 1.532(3) Table 7.42. Bond angles (°) of V with estimated standard deviations. atom atom atom angle atom atom atom angle O(l) C( l ) C(2) 121.6(2) C(7) C(8) C(9) 110.4(1) 0(1) C( l ) C(20) 118.6(2) C(8) C(9) C(10) 109.5(1) C(2) C( l ) C(20) 119.7(2) C(8) C(9) C ( l l ) 109.1(2) C( l ) C(2) C(3) 110.9(1) C(10) C(9) C ( l l ) 109.1(2) C( l ) C(2) C(7) 111.4(1) C(5) C(10) C(9) 109.3(2) C( l ) C(2) C(12) 103.9(1) C(3) C ( l l ) C(9) 110.1(1) C(3) C(2) C(7) 107.3(1) C(2) C(12) C(13) 118.3(2) C(3) C(2) C(12) 110.2(1) C(12) C(13) C(14) 116.0(2) C(7) C(2) C(12) 113.3(1) C(13) C(14) C(15) 116.8(2) C(2) C(3) C(4) 110.7(1) C(14) C(15) C(16) 120.2(2) C(2) C(3) C ( l l ) 111.2(1) C(14) C(15) C(20) 121.7(2) C(4) C(3) C ( l l ) 107.1(2) C(16) C(15) C(20) 118.0(2) C(3) C(4) C(5) 109.9(1) C(15) C(16) C(17) 121.5(2) C(4) C(5) C(6) 109.1(1) C(16) C(17) C(18) 119.9(2) C(4) C(5) C(10) 109.9(2) C(17) C(18) C(19) 119.5(2) C(6) C(5) C(10) 109.0(2) C(18) C(19) C(20) 121.1(2) C(5) C(6) C(7) 110.6(1) C( l ) C(20) C(15) 121.9(2) C(2) C(7) C(6) 109.6(1) C( l ) C(20) C(19) 118.0(2) C(2) C(7) C(8) 110.0(1) C(15) C(20) C(19) 119.9(2) C(6) C(7) C(8) 108.6(1) 7.2.13. 5,6,7,8-Tetrahydro-spiro[benzo[8]annulene]-9(lH),9'-tricyclo(3.3.1.13,7)decan]-10-one (VI) A crystal of approximate dimensions of 0.60 x 0.50 x 0.25 mm size was chosen for data collection. Crystallographic data of VI appear in Table 7.39. An orthorhombic cell with Z = 4 (the calculated density was 1.22 gem"3) was indicated by preliminary measurements. Of the 1903 reflections collected, 1903 were unique and 1564 observed (> 3rj(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 20 carefully centred reflections in the range 96.12 258 Chapter 7 Experimental/Crystallography < 20 < 112 .03° . The data for VT were processed, and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.72 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed minimal decay. The space group was assigned as Pndl\ based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. The hydrogen atoms were fixed in idealized positions with C-Ff = 0.98 A and J 3 H = 1.2Bbonded atom. A secondary extinction correction was applied (final coefficient = 2.0 x 10"^). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.1 2 1 3 The refinement converged at R = 0.041, Rw = 0.049 for 199 variables (GOF = 3.68; including zeros: R = 0.047, Rw = 0.050), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed O O electron density between -0.17 and 0.23 eA . Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.43 -7.45, respectively. 259 Chapter 7 Experimental/Crystallography 0 2 Table 7.43. Final atomic coordinates (fractional) and B(eq) (A ) of VI . atom X y z B(eq) 0(1) 0.9152(1) 0.6800(2) 0.1269 4.89(5) C(l) 0.9145(1) 0.6428(3) 0.2424(4) 3.01(5) C(2) 0.8879(1) 0.4798(3) 0.2915(4) 2.91(5) C(3) 0.8571(1) 0.3791(3) 0.1755(4) 3.57(6) C(4) 0.7931(2) 0.4638(4) 0.1160(4) 4.57(7) C(5) 0.7379(2) 0.4858(4) 0.2228(5) 5.08(8) C(6) 0.7678(1) 0.5856(4) 0.3368(5) 4.65(7) C(7) 0.8306(1) 0.4979(4) 0.3973(4) 3.64(6) C(8) 0.8064(2) 0.3314(4) 0.4479(4) 4.54(7) C(9) 0.7777(2) 0.2330(4) 0.3317(5) 4.98(7) C(10) 0.7146(2) 0.3201(5) 0.2746(5) 5.74(9) C ( H ) 0.8333(2) 0.2134(4) 0.2270(4) 4.49(7) C(12) 0.9532(1) 0.3982(3) 0.3536(4) 3.41(5) C(13) 1.0170(1) 0.3819(3) 0.2616(4) 4.18(7) C(14) 1.0771(2) 0.5000(4) 0.2886(4) 4.40(7) C(15) 1.0655(1) 0.6758(4) 0.2484(4) 4.19(6) C(16) 1.0196(1) 0.7724(3) 0.3409(4) 3.21(5) C(17) 1.0494(1) 0.8830(3) 0.4283(4) 3.98(6) C(18) 1.0103(2) 0.9735(4) 0.5149(5) 4.59(8) C(19) 0.9397(2) 0.9561(3) 0.5158(4) 4.44(7) C(20) 0.9082(1) 0.8477(3) 0.4290(4) 3.87(6) C(21) 0.9478(1) 0.7557(3) 0.3425(4) 3.06(5) 44. Bond lengths (A) of V I with estimated standard deviations. atom atom distance atom atom distance 0(1) C( l ) 1.201(3) C(8) C(9) 1.527(5) C( l ) C(2) 1.526(3) C(9) C(10) 1.529(5) C(l) C(21) 1.517(4) C(9) C(ll) 1.512(5) C(2) C(3) 1.551(4) C(12) C(13) 1.546(4) C(2) C(7) 1.542(4) C(13) C(14) 1.542(4) C(2) C(12) 1.561(4) C(14) C(15) 1.528(5) C(3) C(4) 1.542(4) C(15) C(16) 1.513(4) C(3) C ( l l ) 1.537(4) C(16) C(17) 1.394(4) C(4) C(5) 1.523(5) C(16) C(21) 1.394(3) C(5) C(6) 1.526(5) C(17) C(18) 1.375(5) C(5) C(10) 1.536(5) C(18) C(19) 1.372(5) C(6) C(7) 1.540(4) C(19) C(20) 1.392(4) C(7) C(8) 1.543(4) C(20) C(21) 1.387(4) 260 Chapter 7 Experimental/Crystallography Table 7.45. Bond angles (°) of VI with estimated standard deviations. atom atom atom angle atom atom atom angle 0(1) C( l ) C(2) 122.9(3) C(7) C(8) C(9) 109.6(3) 0(1) C( l ) C(21) 118.5(2) C(8) C(9) C(10) 108.9(3) C(2) C( l ) C(21) 118.3(2) C(8) C(9) C ( l l ) 109.4(3) C( l ) C(2) C(3) 111.2(2) C(10) C(9) C ( l l ) 110.9(3) C ( l ) C(2) C(7) 112.2(2) C(5) C(10) C(9) 108.4(2) C( l ) C(2) C(12) 103.9(2) C(3) C ( l l ) C(9) 110.5(3) C(3) C(2) C(7) 107.1(2) C(2) C(12) C(13) 116.3(2) C(3) C(2) C(12) 112.2(2) C(12) C(13) C(14) 116.1(3) C(7) C(2) C(12) 110.3(2) C(13) C(14) C(15) 116.6(3) C(2) C(3) C(4) 110.7(2) C(14) C(15) C(16) 115.3(3) C(2) C(3) C ( l l ) 110.0(2) C(15) C(16) C(17) 119.5(2) C(4) C(3) C ( l l ) 107.3(2) C(15) C(16) C(21) 122.5(3) C(3) C(4) C(5) 110.1(3) C(17) C(16) C(21) 118.0(3) C(4) C(5) C(6) 109.1(2) C(16) C(17) C(18) 122.0(3) C(4) C(5) C(10) 109.7(3) C(17) C(18) C(19) 119.6(3) C(6) C(5) C(10) 109.9(3) C(18) C(19) C(20) 119.9(3) C(5) C(6) C(7) 109.8(3) C(19) C(20) C(21) 120.4(3) C(2) C(7) C(6) 109.9(3) C( l ) C(21) C(16) 118.5(3) C(2) C(7) C(8) 111.0(2) C( l ) C(21) C(20) 121.3(2) C(6) C(7) C(8) 108.2(2) C(16) C(21) C(20) 120.1(3) 7.2.14. l,2,3,3aA5,6,741c,lld-Decahydro-2,5-methano-5a//-benzo-[c]cyclopropa[c/]phenanthren-5a-ol (VIII) A crystal of approximate dimensions of 0.30 x 0.25 x 0.20 mm size was chosen for data collection. Crystallographic data of VIII appear in Table 7.46. An triclinic cell with Z = 16 (the calculated density was 1.24 gem - 3) was indicated by preliminary measurements. Of the 24083 reflections collected, 23350 were unique and 13412 observed (> 2o(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 24 carefully centred reflections in the range 82.40 < 20 < 86.80°. A higher crystal system could not be derived by cell reduction. The data for VIII were processed,3 and corrected for Lorentz and polarization effects. No 261 Chapter 7 Experimental/Crystallography absorption correction was applied. The intensities of three standard reflections measured every 200 reflections throughout the data collection showed minimal decay. The space group was assigned as PI based on E-statistics, no systematic absences, and subsequent successful structure solution. The structure failed to solve after a long run of direct methods using SIR97. Random phasing was necessary to finally solve the structure. The raw data was used as a test structure for an unreleased version of SIR99, which has been designed to phase small macromolecules. SIR99 was successful in solving this structure without the need for random phasing.24 The structure was expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters using teXsan. Hydrogen atoms o were fixed in idealized positions with C—H = 0.98 A and B-.- = 1.2 Bbonded atom. The structure was refined using full-matrix least-squares by running S H E L X H , a refinement program dimensioned for very large structures.17 A secondary extinction correction was applied (final coefficient = 9.3 x 10*4). Hydrogen atoms involved in hydrogen bonding were placed in calculated positions using the HFIX 147 instruction. Neutral atom scattering factors for all atoms and anomalous dispersion corrections" for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.1 2 , 1 3 The refinement converged at R = 0.050, Rw = 0.149 for 1450 variables (GOF = 1.02; including zeros: R = 0.112, Rw = 0.174), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.23 and 0.24 eA"3. No additional symmetry was found in 262 Chapter 7 Experimental/Crystallography the unit cell, and the large value of Z was attributed to the hydrogen bonding among the molecules, with each molecule of VIII hydrogen bonded to two other molecules to result in two tetramers in the unit cell. . Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.47 -7.49, respectively. A crystal of VIII from a different batch was used in a second data collection on the AFC6S diffractometer, and when the data was indexed, the same unit cell was derived from the orientation matrix. The data was not used for structure solution. A third crystal was placed onto the AFC7-Quantum CCD diffractometer for data collection, and the same unit cell was obtained. The data set was used for structure solution using SIR97' in the manner described above, and resulted in the same structure. The structure was not refined. Table 7.46. Crystallographic data of VIII, IX, and X . VIII IX X Formula C . ^ O C, 0 H 2 4 O C 2 1 H 2 6 0 fw 266.38 280.41 294.44 Color, habit colourless, prism colourless, prism colourless, prism Crystal size, mm 0.30 x 0.25 x 0.20 0.25 x 0.10x0.10 0.30 x 0.25 x 0.20 Crystal system triclinic monoclinic monoclinic Space group P-\ Pljc FIJc a, A 19.871(3) 8.763(3) 8.8308(1) b,A 24.676(4) 14.060(5) 14.646(3) cA 12.999(2) 11.890(2) 12.0651(1) a ( ° ) 99.87(1) 90 90 P(°) 101.20(1) 90.51(2) 90.954(1) Y(°) 109.14(1) 90 90 V 5714.4(1) 1464.9(7) 1560.3(4) z 16 4 4 Dcalc, g/cm3 1.24 1.27 1.25 F(000) 2304 608 640 263 Chapter 7 Experimental/Crystallography Radiation Cu- K a Cu- K a Cu- K a u., mm'1 0.568 0.579 0.567 Transmission factors n/a 0.72-1.00 0.39-1.00 Scan type co - 20 co -20 co-20 Scan range, ° in co 0.94 + 0.20 tan0 0.84 + 0.20 tanO 1.00 + 0.20 tan9 Scan speed, °/min 32.0 16.0 16.0 Data collected +h, ±k, ±1 +h, +k, ±1 +h, +k, ±1 20max, ° 155 155 155 Crystal decay, % -3.08 -4.06 -0.24 Data Collection Temperature (K) 293 293 293 Total reflections 24083 3312 3468 Total unique reflections 23350 3118 3259 ^merge 0.01 0.03 0.09 No. of reflections with I > 3a(I) 13412r 1930 2129 1 No. of variables 1450 195 202 p-factor n/a 0.009 n/a R 0.050 0.045 0.054 Rw 0.149 0.049 0.149 Goodness of fit (GOF) 1.02 2.64 1.066 Max A /a (final cycle) 0.00 0.00 0.00 Residual density e/A 3 -0.23, 0.24 -0.18,0.17 -0.21,0.23 no.of reflections > 2a(I) Table 7.47. Final atomic coordinates (fractional) and U(eq) (A2) of VIII. atom x y z U(eq) O(l) 0.7763(1) 0.8067(1) -0.0919(1) 0.0666(4) 0(2) 0.8051(1) 0.8110(1) 0.6067(1) 0.0651(4) 0(3) 0.7812(1) 0.7230(1) 0.7330(1) 0.0550(3) 0(4) 0.7109(1) 0.3704(1) 0.8894(1) 0.0588(4) 0(5) 0.7876(1) 0.2960(1) 0.8299(1) 0.0732(5) 0(6) 0.7325(1) 0.3368(1) 1.0868(1) 0.0627(4) 0(7) 0.7071(1) 0.2247(1) 0.9522(1) 0.0671(4) 0(8) 0.7308(1) -0.1386(1) 0.7440(1) 0.0763(5) C( l ) 0.7925(1) 0.8252(1) 0.0249(2) 0.0546(5) C(2) 0.7198(1) 0.8197(1) 0.0537(2) 0.0694(6) C(3) 0.6617(2) 0.7585(1) 0.0062(2) 0.0789(7) C(4) 0.6889(1) 0.7115(1) 0.0335(2) 0.0653(6) C(5) 0.6385(2) 0.6554(1) 0.0265(2) 0.0873(8) C(6) 0.6599(2) 0.6112(2) 0.0519(3) 0.100(1) C(7) 0.7337(2) 0.6227(1) 0.0882(3) 0.095(1) C(8) 0.7860(2) 0.6778(1) 0.0951(2) 0.0760(7) C(9) 0.7649(1) 0.7233(1) 0.0653(2) 0.0594(5) C(10) 0.8221(1) 0.7814(1) 0.0676(2) 0.0520(5) C ( l l ) 0.8930(1) 0.8055(1) 0.1609(2) 0.0627(6) C(12) 0.9333(2) 0.8720(1) 0.2106(2) 0.0738(7) C(13) 0.8798(2) 0.9038(1) 0.1910(2) 0.0757(7) C(14) 0.8463(2) 0.8904(1) 0.0689(2) 0.0647(6) C(15) 0.9084(2) 0.9099(1) 264 0.0145(2) 0.0741(7) Chapter 7 Experimental/Crystallography C(16) 0.9684(2) 0.8847(1) 0.0410(2) 0.0753(7) C(17) 0.9973(2) 0.8968(1) 0.1632(2) 0.0844(8) C(18) 0.9407(1) 0.8179(1) -0.0104(2) 0.0686(6) C(19) 0.8946(1) 0.7794(1) 0.0487(2) 0.0598(5) C(20) 0.8475(1) 0.8173(1) 0.5277(2) 0.0530(5) C(21) 0.7975(1) 0.7756(1) 0.4183(2) 0.0658(6) C(22) 0.7265(1) 0.7855(1) 0.3852(2) 0.0741(7) C(23) 0.7406(1) 0.8495(1) 0.3874(2) 0.0632(6) C(24) 0.6866(2) 0.8638(2) 0.3260(2) 0.0835(8) C(25) 0.6978(2) 0.9212(2) 0.3219(3) 0.0931(9) C(26) 0.7642(2) 0.9656(1) 0.3787(2) 0.0846(8) C(27) 0.8184(2) 0.9525(1) 0.4417(2) 0.0662(6) C(28) 0.8078(1) 0.8944(1) 0.4488(2) 0.0556(5) C(29) 0.8672(1) 0.8813(1) 0.5195(2) 0.0509(5) C(30) 1.0054(1) 0.8892(1) 0.5318(2) 0.0619(6) C(31) 0.9469(1) 0.9168(1) 0.5212(2) 0.0570(5) C(32) 0.9182(1) 0.9311(1) 0.6171(2) 0.0582(5) C(33) 0.9509(1) 0.9218(1) 0.7250(2) 0.0675(6) C(34) 1.0003(1) 0.8859(1) 0.7200(2) 0.0705(6) C(35) 0.9561(1) 0.8198(1) 0.6794(2) 0.0663(6) C(36) 0.9146(1) 0.7995(1) 0.5587(2) 0.0585(5) C(37) 0.9698(1) 0.8221(1) 0.4939(2) 0.0639(6) C(38) 1.0516(1) 0.9066(1) 0.6497(2) 0.0733(7) C(39) 0.7595(1) 0.6597(1) 0.7203(2) 0.0448(4) C(40) 0.8224(1) 0.6486(1) 0.7906(2) 0.0548(5) C(41) 0.8949(1) 0.6760(1) 0.7654(2) 0.0606(5) C(42) 0.8884(1) 0.6584(1) 0.6465(2) 0.0528(5) C(43) 0.9519(1) 0.6627(1) 0.6124(2) 0.0721(7) C(44) 0.9481(2) 0.6458(1) 0.5040(3) 0.0828(8) C(45) 0.8814(2) 0.6249(1) 0.4288(2) 0.0752(7) C(46) 0.8189(1) 0.6211(1) 0.4607(2) 0.0607(6) C(47) 0.8201(1) 0.6378(1) 0.5699(2) 0.0477(4) C(48) 0.7502(1) 0.6336(1) 0.6015(1) 0.0430(4) C(49) 0.6887(1) 0.6381(1) 0.5162(2) 0.0524(5) C(50) 0.6812(1) 0.5787(1) 0.5386(2) 0.0506(5) C(51) 0.6226(1) 0.5511(1) 0.5936(2) 0.0574(5) C(52) 0.5585(1) 0.5724(1) 0.5700(2) 0.0668(6) C(53) 0.5882(1) 0.6399(1) 0.6117(2) 0.0662(6) C(54) 0.6303(1) 0.6592(1) 0.7307(2) 0.0663(6) C(55) 0.6893(1) 0.6339(1) 0.7583(2) 0.0545(5) C(56) 0.6556(1) 0.5663(1) 0.7151(2) 0.0595(5) C(57) 0.6361(1) 0.6673(1) 0.5411(2) 0.0639(6) C(58) 0.6740(1) 0.4105(1) 0.8684(2) 0.0463(4) C(59) 0.7298(1) 0.4735(1) 0.9197(2) 0.0566(5) C(60) 0.7985(1) 0.4857(1) 0.8803(2) 0.0627(6) C(61) 0.7800(1) 0.4719(1) 0.7587(2) 0.0536(5) C(62) 0.8327(1) 0.5004(1) 0.7090(2) 0.0669(6) C(63) 0.8174(2) 0.4914(1) 0.5990(2) 0.0745(7) C(64) 0.7489(2) 0.4529(1) 0.5358(2) 0.0745(7) 265 Chapter 7 Experimental/Crystallography C(65) 0.6961(1) 0.4238(1) 0.5829(2) 0.0613(6) C(66) 0.7105(1) 0.4324(1) 0.6960(2) 0.0502(5) C(67) 0.6514(1) 0.4005(1) 0.7457(2) 0.0482(4) C(68) 0.5721(1) 0.3923(1) 0.6898(2) 0.0576(5) C(69) 0.5961(1) 0.3403(1) 0.6774(2) 0.0598(5) C(70) 0.5619(2) 0.2887(1) 0.7230(2) 0.0732(7) C(71) 0.5160(2) 0.3002(1) 0.7997(2) 0.0745(7) C(72) 0.4676(2) 0.3315(1) 0.7527(2) 0.0822(8) C(73) 0.5167(1) 0.3941(1) 0.7547(2) 0.0660(6) C(74) 0.5570(1) 0.4295(1) 0.8715(2) 0.0657(6) C(75) 0.6085(1) 0.4004(1) 0.9202(2) 0.0560(5) C(76) 0.5630(1) 0.3359(1) 0.9132(2) 0.0665(6) C(77) 0.8241(1) 0.3005(1) 0.7439(2) 0.0628(6) C(78) 0.7668(2) 0.2903(1) 0.6397(2) 0.0830(8) C(79) 0.7029(2) 0.2321(2) 0.6156(3) 0.113(1) C(80) 0.7286(2) 0.1810(1) 0.6153(3) 0.101(1) C(81) 0.6801(3) 0.1242(2) 0.5589(3) 0.140(2) C(82) 0.7030(5) 0.0759(3) 0.5521(5) 0.177(3) C(83) 0.7720(5) 0.0857(2) 0.6012(5) 0.167(3) C(84) 0.8217(3) 0.1414(2) 0.6601(3) 0.119(1) C(85) 0.8006(2) 0.1908(1) 0.6698(2) 0.0851(9) C(86) 0.8537(2) 0.2508(1) 0.7350(2) 0.0672(6) C(87) 0.9124(2) 0.2522(2) 0.8311(2) 0.0889(9) C(88) 0.9340(2) 0.2655(1) 0.7313(2) 0.0887(9) C(89) 0.9841(2) 0.3277(2) 0.7371(4) 0.111(1) C(90) 1.0326(2) 0.3605(2) 0.8518(4) 0.141(2) C(91) 0.9829(2) 0.3618(2) 0.9266(3) 0.114(1) C(92) 0.9289(2) 0.3904(2) 0.8869(3) 0.0977(9) C(93) 0.8837(2) 0.3626(1) 0.7683(2) 0.0768(7) C(94) 0.9365(2) 0.3614(2) 0.6959(3) 0.1041) C(95) 0.9442(2) 0.2997(2) 0.9362(3) 0.106(1) C(96) 0.7565(1) 0.3564(1) 1.2043(2) 0.0556(5) C(97) 0.6957(2) 0.3206(1) 1.2482(2) 0.0700(6) C(98) 0.6222(1) 0.3244(1) 1.2019(2) 0.0761(7) C(99) 0.6282(1) 0.3872(1) 1.2120(2) 0.0619(6) C(100) 0.5643(2) 0.4001(2) 1.2055(2) 0.0875(8) C(101) 0.5667(2) 0.4571(2) 1.2151(3) 0.097(1) C(102) 0.6329(2) 0.5025(1) 1.2330(2) 0.0794(8) C(103) 0.6963(1) 0.4908(1) 1.2391(2) 0.0607(5) C(104) 0.6960(1) 0.4329(1) 1.2275(2) 0.0501(5) C(105) 0.7661(1) 0.4214(1) 1.2316(1) 0.0473(4) C(106) 0.8261(1) 0.4663(1) 1.1998(2) 0.0537(5) C(107) 0.8781(1) 0.4518(1) 1.1394(2) 0.0704(6) C(108) 0.9262(2) 0.4225(2) 1.1966(2) 0.0834(8) C(109) 0.8841(2) 0.3574(1) 1.1839(2) 0.0829(8) C( l lO) 0.8271(2) 0.3447(1) 1.2479(2) 0.0697(6) C ( l l l ) 0.8631(2) 0.3798(1) 1.3670(2) 0.0740(7) C(112) 0.8958(1) 0.4452(1) 1.3714(2) 0.0687(6) C(113) 0.9583(2) 0.4563(2) 1.3163(2) 0.0857(8) 266 Chapter 7 Experimental/Crystallography C(114) 0.8360(1) 0.4657(1) 1.3173(2) 0.0555(5) C(115) 0.6917(1) 0.1621(1) 0.9406(2) 0.0569(5) C(116) 0.7644(2) 0.1525(1) 0.9531(2) 0.0758(7) C(117) 0.8198(2) 0.1902(2) 1.0589(4) 0.112(1) C(118) 0.7910(3) 0.1832(2) 1.1539(3) 0.117(1) C(119) 0.8400(4) 0.1977(2) 1.2554(5) 0.185(3) C(120) 0.8142(8) 0.1901(5) 1.3442(7) 0.301(9) C(121) 0.7441(7) 0.1694(4) 1.3342(4) 0.251(7) C(122) 0.6902(4) 0.1542(2) 1.2346(3) 0.164(2) C(123) 0.7168(3) 0.1626(1) 1.1421(2) 0.096(1) C(124) 0.6606(2) 0.1473(1) 1.0349(2) 0.0685(7) C(125) 0.5866(2) 0.1526(1) 1.0377(3) 0.101(1) C(126) 0.5910(2) 0.0921(1) 1.0104(3) 0.095 (1) C(127) 0.5538(2) 0.0534(1) 0.8971(3) 0.101(1) C(128) 0.4889(2) 0.0678(2) 0.8414(5) 0.160(2) C(129) 0.5183(2) 0.1337(2) 0.8397(4) 0.134(2) C(130) 0.5798(2) 0.1461(2) 0.7839(3) 0.111(1) C(131) 0.6411(2) 0.1255(1) 0.8283(2) 0.0733(7) C(132) 0.6081(2) 0.0602(1) 0.8284(2) 0.0836(8) C(133) 0.5420(2) 0.1726(2) 0.9548(4) 0.122(1) C(134) 0.6937(1) -0.0989(1) 0.7192(2) 0.0638(6) C(135) 0.7524(2) -0.0387(1) 0.7266(2) 0.0803(8) C(136) 0.8088(2) -0.0140(1) 0.8342(3) 0.0849(8) C(137) 0.7733(1) -0.0112(1) 0.9251(2) 0.0659(6) C(138) 0.8139(2) 0.0295(1) 1.0248(3) 0.0882(9) C(139) 0.7829(2) 0.0351(1) 1.1100(3) 0.010(1) C(140) 0.7110(2) 0.0006(1) 1.0964(2) 0.0910(9) C(141) 0.6705(2) -0.0401(1) 0.9997(2) 0.0748(7) C(142) 0.7004(1) -0.0475(1) 0.9120(2) 0.0565(5) C(143) 0.6542(1) -0.0925(1) 0.8073(2) 0.0551(5) C(144) 0.5935(1) -0.1465(1) 0.8157(2) 0.0731(7) C(145) 0.5731(1) -0.0996(1) 0.7732(2) 0.0699(6) C(146) 0.5327(2) -0.1126(1) 0.6542(3) 0.093(1) C(147) 0.5876(2) -0.0913(2) 0.5884(2) 0.097(1) C(148) 0.6424(2) -0.1228(1) 0.6031(2) 0.0884(9) C(149) 0.6018(2) -0.1887(2) 0.5670(3) 0.111(1) C(150) 0.5400(2) -0.2120(1) 0.6199(3) 0.115(1) C(151) 0.5688(2) -0.2079(1) 0.7410(3) 0.010(1) C(152) 0.4870(2) -0.1790(2) 0.6090(3) 0.125(2) Table 7.48. Bond lengths (A) of VIII with estimated standard deviations. atom atom bond 0(1) C( l ) 1.448(2) 0(2) C(20) 1.448(2) 0(3) C(39) 1.447(2) 0(4) C(58) 1.441(2) 0(5) C(77) 1.446(2) atom atom bond C(72) C(73) 1.527(4) C(73) C(74) 1.525(3) C(74) C(75) 1.533(3) C(75) C(76) 1.527(3) C(77) C(78) 1.513(4) 267 Chapter 7 Experimental/Crystallography 0(6) C(96) 1.453(2) 0(7) C(115) 1.447(2) 0(8) C(134) 1.448(3) C( l ) C(10) 1.522(3) C( l ) C(2) 1.531(3) C( l ) C(14) 1.542(3) C(2) C(3) 1.502(4) C(3) C(4) 1.496(4) C(4) C(5) 1.394(4) C(4) C(9) 1.401(3) C(5) C(6) 1.362(4) C(6) C(7) 1.365(5) C(7) C(8) 1.389(4) C(8) C(9) 1.408(3) C(9) C(10) 1.502(3) C(10) C(19) 1.522(3) C(10) C ( l l ) 1.534(3) C ( l l ) C(19) 1.501(3) C ( l l ) C(12) 1.526(3) C(12) C(17) 1.515(4) C(12) C(13) 1.524(4) C(13) C(14) 1.529(3) C(14) C(15) 1.524(3) C(15) C(16) 1.525(4) C(16) C(17) 1.520(4) C(16) C(18) 1.533(3) C(18) C(19) 1.510(3) C(20) C(29) 1.526(3) C(20) C(21) 1.533(3) C(20) C(36) 1.538(3) C(21) C(22) 1.504(3) C(22) C(23) 1.505(3) C(23) C(24) 1.388(3) C(23) C(28) 1.401(3) C(24) C(25) 1.372(4) C(25) C(26) 1.373(4) C(26) C(27) 1.383(4) C(27) C(28) 1.401(3) C(28) C(29) 1.508(3) C(29) C(32) 1.515(3) C(29) C(31) 1.531(3) C(30) C(37) 1.518(3) C(30) C(31) 1.524(3) C(30) C(38) 1.532(3) C(31) C(32) 1.502(3) C(32) C(33) 1.515(3) C(33) C(34) 1.526(4) C(34) C(35) 1.515(3) C(34) C(38) 1.521(3) C(77) C(86) 1.521(3; C(77) C(93) 1.533(4; C(78) C(79) 1.507(4; C(79) C(80) 1.508(5; C(80) C(81) 1.384(5; C(80) C(85) 1.388(5; C(81) C(82) 1.402(8; C(82) C(83) 1.317(8; C(83) C(84) 1.380(7; C(84) C(85) 1.409(4; C(85) C(86) 1.491(4 C(86) C(87) 1.522(4 C(86) C(88) 1.529(4 C(87) C(88) 1.499(4 C(87) C(95) 1.507(5 C(88) C(89) 1.510(5 C(89) C(90) 1.524(6 C(89) C(94) 1.532(4 C(90) C(91) 1.518(5 C(91) C(95) 1.513(5 C(91) C(92) 1.524(5 C(92) C(93) 1.532(4 C(93) C(94) 1.544(4 C(96) C(97) 1.518(3 C(96) C(105) 1.522(3 C(96) C(110) 1.544(3 C(97) C(98) 1.508(4 C(98) C(99) 1.493(4 C(99) C(100) 1.398(4 C(99) C(104) 1.397(3 C(100) C(101) 1.373(4 C(101) C(102) 1.366(4 C(102) C(103) 1.373(3 C(103) C(104) 1.407(3 C(104) C(105) 1.504(3 C(105) C(106) 1.517(3 C(105) C(114) 1.533(3 C(106) C(114) 1.504(3 C(106) C(107) 1.507(3 C(107) C(108) 1.533(4 C(108) C(109) 1.510(4 C(108) C(113) 1.531(4 C(109) C(110) 1.516(4 C(110) C ( l l l ) 1.537(3 C ( l l l ) C(112) 1.516(4 C(112) C(113) 1.524(4 C(112) C(114) 1.534(3 C(115) C(116) 1.521(3 C(115) C(124) 1.523(3 268 Chapter 7 Experimental/Crystal lography C(35) C(36) 1.533(3) C(115) C(131) 1.530(3) C(36) C(37) 1.531(3) C(116) C(117) 1.507(4) C(39) C(48) 1.517(2) C(117) C(118) 1.471(6) C(39) C(40) 1.529(3) C(118) C(123) 1.361(5) C(39) C(55) 1.544(3) C(118) C(119) 1.389(6) C(40) C(41) 1.504(3) C(119) C(120) 1.37(1) C(41) C(42) 1.500(3) C(120) C(121) 1.29(2) C(42) C(47) 1.393(3) C(121) C(122) 1.412(9) C(42) C(43) 1.396(3) C(122) C(123) 1.424(5) C(43) C(44) 1.380(4) C(123) C(124) 1.506(4) C(44) C(45) 1.361(4) C(124) C(126) 1.523(4) C(45) C(46) 1.364(3) C(124) C(125) 1.525(4) C(46) C(47) 1.402(3) C(125) C(126) 1.510(4) C(47) C(48) 1.501(3) C(125) C(133) 1.513(5) C(48) C(49) 1.529(3) C(126) C(127) 1.503(5) C(48) C(50) 1.532(3) C(127) C(132) 1.515(4) C(49) C(57) 1.505(3) C(127) C(128) 1.530(5) C(49) C(50) 1.508(3) C(128) C(129) 1.543(5) C(50) C(51) 1.518(3) C(129) C(130) 1.512(6) C(51) C(56) 1.516(3) C(129) C(133) 1.523(6) C(51) C(52) 1.528(3) C(130) C(131) 1.522(4) C(52) C(53) 1.529(3) C(131) C(132) 1.526(3) C(53) C(54) 1.518(3) C(134) C(143) 1.523(3) C(53) C(57) 1.527(3) C(134) C(135) 1.532(4) C(54) C(55) 1.513(3) C(134) C(148) 1.538(3) C(55) C(56) 1.531(3) C(135) C(136) 1.496(4) C(58) C(59) 1.523(3) C(136) C(137) 1.493(4) C(58) C(67) 1.525(2) C(137) C(142) 1.389(3) C(58) C(75) 1.547(3) C(137) C(138) 1.397(4) C(59) C(60) 1.507(3) C(138) C(139) 1.376(5) C(60) C(61) 1.502(3) C(139) C(140) 1.360(5) C(61) C(66) 1.389(3) C(140) C(141) 1.371(4) C(61) C(62) 1.395(3) C(141) C(142) 1.396(3) C(62) C(63) 1.366(3) C(142) C(143) 1.502(3) C(63) C(64) 1.371(4) C(143) C(144) 1.514(3) C(64) C(65) 1.377(3) C(143) C(145) 1.529(3) C(65) C(66) 1.407(3) C(144) C(145) 1.501(3) C(66) C(67) 1.509(3) C(144) C(151) 1.517(4) C(67) C(69) 1.516(3) C(145) C(146) 1.523(4) C(67) C(68) 1.532(3) C(146) C(152) 1.528(4) C(68) C(69) 1.501(3) C(146) C(147) 1.530(5) C(68) C(73) 1.519(3) C(147) C(148) 1.533(4) C(69) C(70) 1.511(3) C(148) C(149) 1.500(5) C(70) C(71) 1.527(4) C(149) C(150) 1.520(5) C(71) C(76) 1.518(3) C(150) C(152) 1.528(4) C(71) C(72) 1:522(4) C(150) C(151) 1.541(5) 269 Chapter 7 Experimental/Crystallography Table 7.49. Bond angles (°) of VIII with estimated standard deviations. atom atom atom angle atom atom atom angle 0(1) C( l ) C(10) 105.7(2) 0(5) C(77) C(78) 108.3(2) 0(1) C( l ) C(2) 107.8(2) 0(5) C(77) C(86) 105.8(2) C(10) C(l) C(2) 109.7(2) C(78) C(77) C(86) 109.7(2) 0(1) C( l ) C(14) 111.1(2) 0(5) C(77) C(93) 110.2(2) C(10) C(l) C(14) 114.0(2) C(78) C(77) C(93) 108.7(2) C(2) C(l) C(14) 108.4(2) C(86) C(77) C(93) 114.0(2) C(3) C(2) C( l ) 112.2(2) C(79) C(78) C(77) 111.6(3) C(4) C(3) C(2) 112.2(2) C(78) C(79) C(80) 111.7(3) C(5) C(4) C(9) 119.5(3) C(81) C(80) C(85) 120.1(4) C(5) C(4) C(3) 119.9(3)' C(81) C(80) C(79) 119.5(4) C(9) C(4) C(3) 120.6(2) C(85) C(80) C(79) 120.3(3) C(6) C(5) C(4) 122.6(3) C(80) C(81) C(82) 121.2(5) C(5) C(6) C(7) 118.8(3) C(83) C(82) C(81) 118.4(6) C(6) C(7) C(8) 120.6(3) C(82) C(83) C(84) 122.3(6) C(7) C(8) C(9) 121.3(3) C(83) C(84) C(85) 120.9(5) C(4) C(9) C(8) 117.1(2) C(80) C(85) C(84) 116.9(4) C(4) C(9) C(10) 122.3(2) C(80) C(85) C(86) 121.9(3) C(8) C(9) C(10) 120.7(2) C(84) C(85) C(86) 121.1(3) C(9) C(10) C(19) 116.2(2) C(85) C(86) C(77) 116.7(2) C(9) C(10) C( l ) 115.8(2) C(85) C(86) C(87) 116.0(2) C(19) C(10) C(l) 118.8(2) C(77) C(86) C(87) 118.7(2) C(9) C(10) C ( l l ) 116.5(2) C(85) C(86) C(88) 115.7(2) C(19) C(10) C ( l l ) 58.8(1) C(77) C(86) C(88) 118.5(2) C( l ) C(10) C ( l l ) 118.7(2) C(87) C(86) C(88) 58.8(2) C(19) C ( l l ) C(12) 119.2(2) C(88) C(87) C(95) 119.8(3) C(19) C ( l l ) C(10) 60.2(1) C(88) C(87) C(86) 60.8(2) C(12) C ( l l ) C(10) 120.9(2) C(95) C(87) C(86) 124.7(2) C(17) C(12) C(13) 109.8(2) C(87) C(88) C(89) 118.8(3) C(17) C(12) C ( l l ) 110.8(2) C(87) C(88) C(86) 60.3(2) C(13) C(12) C ( l l ) 110.0(2) C(89) C(88) C(86) 121.8(2) C(12) C(13) C(14) 108.7(2) C(88) C(89) C(90) 112.0(3) C(15) C(14) C(13) 109.0(2) C(88) C(89) C(94) 108.8(3) C(15) C(14) C( l ) 115.9(2) C(90) C(89) C(94) 110.3(3) C(13) C(14) C( l ) 110.1(2) C(91) C(90) C(89) 108.6(3) C(14) C(15) C(16) 114.7(2) C(95) C(91) C(90) 109.5(3) C(17) C(16) C(15) 110.0(2) C(95) C(91) C(92) 112.6(3) C(17) C(16) C(18) 109.5(2) C(90) C(91) C(92) 110.5(3) C(15) C(16) C(18) 112.3(2) C(91) C(92) C(93) 114.1(3) C(12) C(17) C(16) 109.4(2) C(92) C(93) C(77) 116.2(2) C(19) C(18) C(16) 114.5(2) C(92) C(93) C(94) 109.5(3) C ( l l ) C(19) C(18) 120.2(2) C(77) C(93) C(94) 109.4(2) C ( l l ) C(19) C(10) 61.0(2) C(89) C(94) C(93) 108.2(2) C(18) C(19) C(10) 125.0(2) C(87) C(95) C(91) 115.4(3) 0(2) C(20) C(29) 105.8(2) 0(6) C(96) C(97) 108.2(2) 0(2) C(20) C(21) 108.0(2) 0(6) C(96) C(105) 105.4(2) C(29) C(20) C(21) 109.0(2) C(97) C(96) C(105) 110.1(2) 0(2) C(20) C(36) 111.3(2) 0(6) C(96) C(110) 110.3(2) 270 Chapter 7 Experimental/Crystallography C(29) C(20) C(36) 114.4(2) C(21) C(20) C(36) 108.1(2) C(22) C(21) C(20) 112.4(2) C(21) C(22) C(23) 111.7(2) C(24) C(23) C(28) 119.9(2) C(24) C(23) C(22) 119.3(2) C(28) C(23) C(22) 120.8(2) C(25) C(24) C(23) 121.6(3) C(24) C(25) C(26) 119.5(3) C(25) C(26) C(27) 119.9(3) C(26) C(27) C(28) 121.7(3) C(23) C(28) C(27) 117.4(2) C(23) C(28) C(29) 121.8(2) C(27) C(28) C(29) 120.8(2) C(28) C(29) C(32) 116.1(2) C(28) C(29) C(20) 116.3(2) C(32) C(29) C(20) 119.1(2) C(28) C(29) C(31) 115.9(2) C(32) C(29) C(31) 59.1(1) C(20) C(29) C(31) 118.3(2) C(37) C(30) C(31) 110.8(2) C(37) C(30) C(38) 108.7(2) C(31) C(30) C(38) 110.7(2) C(32) C(31) C(30) 119.3(2) C(32) C(31) C(29) 59.9(1) C(30) C(31) C(29) 121.1(2) C(31) C(32) C(33) 120.1(2) C(31) C(32) C(29) 61.0(1) C(33) C(32) C(29) 124.2(2) C(32) C(33) C(34) 114.6(2) C(35) C(34) C(38) 110.7(2) C(35) C(34) C(33) 112.3(2) C(38) C(34) C(33) 110.0(2) C(34) C(35) C(36) 114.1(2) C(37) C(36) C(35) 108.5(2) C(37) C(36) C(20) 110.4(2) C(35) C(36) C(20) 115.8(2) C(30) C(37) C(36) 109.2(2) C(34) C(38) C(30) 108.8(2) 0(3) C(39) C(48) 105.5(1) 0(3) C(39) C(40) 108.2(2) C(48) C(39) C(40) 109.7(2) 0(3) C(39) C(55) 111.6(2) C(48) C(39) C(55) 113.7(2) C(40) C(39) C(55) 108.0(2) C(41) C(40) C(39) 112.3(2) C(42) C(41) C(40) 111.8(2) C(47) C(42) C(43) 119.7(2) C(47) C(42) C(41) 121.1(2) C(97) C(96) C(110) 108.2(2) C(105) C(96) C(110) 114.4(2) C(98) C(97) C(96) 112.4(2) C(99) C(98) C(97) 111.9(2) C(100) C(99) C(104) 119.4(2) C(100) C(99) C(98) 119.1(2) C(104) C(99) C(98) 121.5(2) C(101) C(100) C(99) 121.6(3) C(102) C(101) C(100) 119.6(3) C(101) C(102) C(103) 119.9(3) C(102) C(103) C(104) 122.2(2) C(99) C(104) C(103) 117.2(2) C(99) C(104) C(105) 121.8(2) C(103) C(104) C(105) 120.9(2) C(104) C(105) C(106) 116.0(2) C(104) C(105) C(96) 115.4(2) C(106) C(105) C(96) 119.7(2) C(104) C(105) C(114) 116.9(2) C(106) C(105) C(114) 59.1(1) C(96) C(105) C(114) 118.3(2) C(114) C(106) C(107) 120.4(2) C(114) C(106) C(105) 61.0(1) C(107) C(106) C(105) 125.1(2) C(106) C(107) C(108) 114.6(2) C(109) C(108) C(113) 111.3(2) C(109) C(108) C(107) 112.3(2) C(113) C(108) C(107) 108.9(2) C(108) C(109) C(110) 114.6(2) C(109) C(110) C ( l l l ) 109.7(2) C(109) C(110) C(96) 115.8(2) C ( l l l ) C(110) C(96) 109.5(2) C(112) C ( l l l ) C(110) 108.8(2) C ( l l l ) C(112) C(113) 109.3(2) C ( l l l ) C(112) C(114) 110.5(2) C(113) C(112) C(114) 110.9(2) C(112) C(113) C(108) 108.7(2) C(106) C(114) C(105) 59.9(1) C(106) C(114) C(112) 118.7(2) C(105) C(114) C(112) 120.8(2) 0(7) C(115) C(116) 108.5(2) 0(7) C(115) C(124) 105.4(2) C(116) C(115) C(124) 108.8(2) 0(7) C(115) C(131) 111.1(2) C(116) C(115) C(131) 108.0(2) C(124) C(115) C(131) 114.9(2) C(117) C(116) C(115) 111.7(2) C(118) C(117) C(116) 113.4(3) C(123) C(118) C(119) 120.4(6) C(123) C(118) C(117) 120.0(3) 271 Chapter 7 Experimental/Crystallography C(43) C(42) C(41) 119.2(2) C(119) C(118) C(117) 119.6(6) C(44) C(43) C(42) 121.0(2) C(120) C(119) C(118) 120.4(8) C(45) C(44) C(43) 119.6(2) C(121) C(120) C(119) 120.2(8) C(44) C(45) C(46) 120.1(2) C(120) C(121) C(122) 123.4(7) C(45) C(46) C(47) 122.3(2) C(121) C(122) C(123) 116.7(6) C(42) C(47) C(46) 117.3(2) C(118) C(123) C(122) 119.0(4) C(42) C(47) C(48) 122.0(2) C(118) C(123) C(124) 123.1(3) C(46) C(47) C(48) 120.7(2) C(122) C(123) C(124) 117.9(4) C(47) C(48) C(39) 115.9(2) C(123) C(124) C(115) 115.9(2) C(47) C(48) C(49) 116.1(2) C(123) C(124) C(126) 117.0(2) C(39) C(48) C(49) 118.8(2) C(115) C(124) C(126) 117.7(2) C(47) C(48) C(50) 116.2(2) C(123) C(124) C(125) 117.2(3) C(39) C(48) C(50) 119.1(2) C(115) C(124) C(125) 117.9(2) C(49) C(48) C(50) 59.0(1) C(126) C(124) C(125) 59.4(2) C(57) C(49) C(50) 120.8(2) C(126) C(125) C(133) 120.7(3) C(57) C(49) C(48) 124.6(2) C(126) C(125) C(124) 60.2(2) C(50) C(49) C(48) 60.6(1) C(133) C(125) C(124) 125.0(3) C(49) C(50) C(51) 118.3(2) C(127) C(126) C(125) 118.7(3) C(49) C(50) C(48) 60.4(1) C(127) C(126) C(124) 121.3(2) C(51) C(50) C(48) 120.7(2) C(125) C(126) C(124) 60.4(2) C(56) C(51) C(50) 110.4(2) C(126) C(127) C(132) 111.0(2) C(56) C(51) C(52) 109.5(2) C(126) C(127) C(128) 112.0(3) C(50) C(51) C(52) 111.0(2) C(132) C(127) C(128) 108.5(3) C(51) C(52) C(53) 108.9(2) C(127) C(128) C(129) 108.2(3) C(54) C(53) C(57) 112.2(2) C(130) C(129) C(133) 112.9(3) C(54) C(53) C(52) 110.9(2) C(130) C(129) C(128) 110.3(3) C(57) C(53) C(52) 108.7(2) C(133) C(129) C(128) 109.6(4) C(55) C(54) C(53) 114.5(2) C(129) C(130) C(131) 114.1(3) C(54) C(55) C(56) 109.5(2) C(130) C(131) C(132) 109.8(3) C(54) C(55) C(39) 116.0(2) C(130) C(131) C(115) 115.3(2) C(56) C(55) C(39) 109.9(2) C(132) C(131) C(115) 110.0(2) C(51) C(56) C(55) 108.9(2) C(127) C(132) C(131) 108.5(2) C(49) C(57) C(53) 114.8(2) C(125) C(133) C(129) 114.3(3) 0(4) C(58) C(59) 107.8(2) 0(8) C(134) C(143) 105.4(2) 0(4) C(58) C(67) 106.2(1) 0(8) C(134) C(135) 108.4(2) C(59) C(58) C(67) 109.4(2) C(143) C(134) C(135) 109.7(2) 0(4) C(58) C(75) 110.7(2) 0(8) C(134) C(148) 110.8(2) C(59) C(58) C(75) 108.7(2) C(143) C(134) C(148) 114.4(2) C(67) C(58) C(75) 113.9(2) C(135) C(134) C(148) 108.1(2) C(60) C(59) C(58) 112.3(2) C(136) C(135) C(134) 112.2(2) C(61) C(60) C(59) 111.4(2) C(137) C(136) C(135) 111.4(2) C(66) C(61) C(62) 120.0(2) C(142) C(137) C(138) 119.5(3) C(66) C(61) C(60) 120.7(2) C(142) C(137) C(136) 121.2(2) C(62) C(61) C(60) 119.3(2) C(138) C(137) C(136) 119.3(3) C(63) C(62) C(61) 121.5(2) C(139) C(138) C(137) 121.5(3) C(62) C(63) C(64) 119.3(2) C(140) C(139) C(138) 119.1(3) C(63) C(64) C(65) 120.3(2) C(139) C(140) C(141) 120.4(3) C(64) C(65) C(66) 121.5(2) C(140) C(141) C(142) 122.1(3) C(61) C(66) C(65) 117.3(2) C(137) C(142) C(141) 117.5(2) 272 Chapter 7 Experimental/Crystallography C(61) C(66) C(67) 122.2(2) C(137) C(142) C(143) 122.0(2) C(65) C(66) C(67) 120.5(2) C(141) C(142) C(143) 120.5(2) C(66) C(67) C(69) 116.2(2) C(142) C(143) C(144) 116.3(2) C(66) C(67) C(58) 116.2(2) C(142) C(143) C(134) 115.9(2) C(69) C(67) C(58) 118.7(2) C(144) C(143) C(134) 119.1(2) C(66) C(67) C(68) 115.9(2) C(142) C(143) C(145) 116.1(2) C(69) C(67) C(68) 59.0(1) C(144) C(143) C(145) 59.1(2) C(58) C(67) C(68) 118.7(2) C(134) C(143) C(145) 118.3(2) C(69) C(68) C(73) 119.3(2) C(145) C(144) C(143) 60.9(2) C(69) C(68) C(67) 60.0(1) C(145) C(144) C(151) 119.3(2) C(73) C(68) C(67) 121.1(2) C(143) C(144) C(151) 123.9(3) C(68) C(69) C(70) 120.4(2) C(144) C(145) C(146) 119.8(2) C(68) C(69) C(67) 61.0(1) C(144) C(145) C(143) 60.0(2) C(70) C(69) C(67) 124.2(2) C(146) C(145) C(143) 120.9(2) C(69) C(70) C(71) 114.5(2) C(145) C(146) C(152) 110.3(3) C(76) C(71) C(72) 110.1(2) C(145) C(146) C(147) 110.5(2) C(76) C(71) C(70) 113.0(2) C(152) C(146) C(147) 110.6(3) C(72) C(71) C(70) 109.7(2) C(146) C(147) C(148) 107.7(3) C(71) C(72) C(73) 109.1(2) C(149) C(148) C(147) 110.2(3) C(68) C(73) C(74) 110.2(2) C(149) C(148) C(134) 115.4(2) C(68) C(73) C(72) 110.6(2) C(147) C(148) C(134) 110.2(2) C(74) C(73) C(72) 109.7(2) C(148) C(149) C(150) 114.2(3) C(73) C(74) C(75) 108.5(2) C(149) C(150) C(152) 111.6(3) C(76) C(75) C(74) 109.3(2) C(149) C(150) C(151) 112.9(3) C(76) C(75) C(58) 115.9(2) C(152) C(150) C(151) 108.3(3) C(74) C(75) C(58) 110.1(2) C(144) C(151) C(150) 114.7(3) C(71) C(76) C(75) 114.0(2) C(150) C(152) C(146) 108.0(3) 7.2.15. (7a5/?,7bS/?,9/?S,llS^,lla^,llb5/?,13/?>S)-6,7,7b,8,9,10,ll,lla-octahydro-9,7a,ll-[l,2,3]Propanetriyl-7aH-benzo[a]benzo[3,4]cyclobuta[l,2-c]cyclohepten-llb(5fl)-ol (IX) A crystal of approximate dimensions of 0.25 x 0.10 x 0.10 mm size was chosen for data collection. Crystallographic data of IX appear in Table 7.46. A monoclinic cell with Z = 4 (the calculated density was 1.27 gcnr 3 ) was indicated by preliminary measurements. Of the 3312 reflections collected, 3118 were unique and 1930 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 22 carefully centred reflections in the range 55.41 273 Chapter 7 Experimental/Crystallography < 20 < 106.22°. The data for IX were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.72 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed minimal decay. The space group was assigned as P 2 i / c based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. The hydrogen atom on the hydroxyl oxygen was located from a Fourier difference map and refined isotropically. The remaining hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bonded atom. A secondary extinction correction was applied (final coefficient = 1.0 x 10"^). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.045, Rw = 0.049 for 195 variables (GOF = 2.64; including zeros: R = 0.089, Rw = 0.053), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.18 and 0.17 eA"3. This structure is almost identical to that of its homologue X. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.50 - 7.52, respectively. 274 Chapter 7 Experimental/Crystallography Table 7.50. Final atomic coordinates (fractional) and B(eq) (A 2) of IX. atom X y z B(eq) 0(1) 0.1456(2) 0.3927(1) 0.1684(2) 4.10(4) C( l ) 0.2578(2) 0.3296(1) 0.2197(2) 3.08(5) cm 0.3855(2) 0.3936(1) 0.2723(2) 3.09(5) C(3) 0.4400(3) 0.4069(2) 0.1487(2) 3.74(5) C(4) 0.3795(2) 0.3036(2) 0.1296(2) 3.42(5) C(5) 0.4986(3) 0.2304(2) 0.1724(2) 3.70(5) C(6) 0.4997(3) 0.2295(2) 0.3005(2) 3.63(5) C(7) 0.5077(3) 0.3333(2) 0.3364(2) 3.40(5) C(8) 0.6700(3) 0.3671(2) 0.3087(2) 4.28(6) C(9) 0.7030(3) 0.3562(2) 0.1833(2) 4.52(6) C(10) 0.6608(3) 0.2579(2) 0.1364(2) 4.60(6) C ( l l ) 0.6045(3) 0.4286(2) 0.1228(2) 4.76(6) C(12) 0.3314(3) 0.4774(2) 0.3413(2) 4.22(6) C(13) 0.2396(3) 0.4483(2) 0.4441(2) 4.60(6) C(14) 0.0887(3) 0.3965(2) 0.4215(2) 4.29(6) C(15) 0.0903(2) 0.2932(2) 0.3844(2) 3.45(5) C(16) 0.0003(3) 0.2288(2) 0.4433(2) 4.40(6) C(17) -0.0189(3) 0.1361(2) 0.4078(3) 5.00(7) C(18) 0.0524(3) 0.1053(2) 0.3118(3) 4.86(7) C(19) 0.1433(3) 0.1679(2) 0.2527(2) 4.16(6) C(20) 0.1655(2) 0.2611(2) 0.2883(2) 3.16(5) H(23) 0.112(5) 0.362(3) 0.105(4) 12(1) Table 7.51. Bond lengths (A) of IX with estimated standard deviations. atom atom distance atom atom distance 0(1) C( l ) 1.454(3) C(7) C(8) 1.538(3) 0(1) H(23) 0.92(4) C(8) C(9) 1.529(4) C( l ) C(2) 1.562(3) C(9) C(10) 1.535(4) C( l ) C(4) 1.562(3) C(9) C ( l l ) 1.513(4) C( l ) C(20) 1.504(3) C(12) C(13) 1.525(4) C(2) C(3) 1.560(3) C(13) C(14) 1.531(4) C(2) C(7) 1.560(3) C(14) C(15) 1.518(3) C(2) C(12) 1.514(3) C(15) C(16) 1.394(3) C(3) C(4) 1.562(3) C(15) C(20) 1.399(3) C(3) C ( l l ) 1.509(3) C(16) C(17) 1.381(4) C(4) C(5) 1.550(3) C(17) C(18) 1.376(4) C(5) C(6) 1.523(3) C(18) C(19) 1.384(3) C(5) C(10) 1.538(3) C(19) C(20) 1.390(3) C(6) C(7) 1.522(3) 275 Chapter 7 Experimental/Crystallography Table 7.52. Bond angles (°) of I X with estimated standard deviations. atom atom atom angle atom atom atom angle 0(1) C( l ) C(2) 107.2(2) C(2) C(7) C(6) 110.8(2) 0(1) C( l ) C(4) 108.5(2) C(2) C(7) C(8) 111.1(2) 0(1) C( l ) C(20) 104.7(2) C(6) C(7) C(8) 106.0(2) C(2) C( l ) C(4) 85.3(2) C(7) C(8) C(9) 111.2(2) C(2) C( l ) C(20) 122.6(2) C(8) C(9) C(10) 113.4(2) C(4) C( l ) C(20) 126.6(2) C(8) C(9) C ( l l ) 106.5(2) C( l ) C(2) C(3) 85.2(2) C(10) C(9) C ( l l ) 107.4(2) C( l ) C(2) C(7) 111.6(2) C(5) C(10) C(9) 110.2(2) C( l ) C(2) C(12) 116.0(2) C(3) C ( l l ) C(9) 108.0(2) C(3) C(2) C(7) 108.1(2) C(2) C(12) C(13) 113.3(2) C(3) C(2) C(12) 121.1(2) C(12) C(13) C(14) 116.6(2) C(7) C(2) C(12) 112.0(2) C(13) C(14) C(15) 119.7(2) C(2) C(3) C(4) 85.4(2) C(14) C(15) C(16) 117.9(2) C(2) C(3) C ( l l ) 121.2(2) C(14) C(15) C(20) 123.5(2) C(4) C(3) C ( l l ) 118.8(2) C(16) C(15) C(20) 118.3(2) C( l ) C(4) C(3) 85.1(2) C(15) C(16) C(17) 121.8(2) C ( l ) C(4) C(5) 113.1(2) C(16) C(17) C(18) 119.7(2) C(3) C(4) C(5) 110.1(2) C(17) C(18) C(19) 119.3(2) C(4) C(5) C(6) 109.4(2) C(18) C(19) C(20) 121.6(2) C(4) C(5) C(10) 111.3(2) C( l ) C(20) C(15) 119.7(2) C(6) C(5) C(10) 106.4(2) C ( l ) C(20) C(19) 120.9(2) C(5) C(6) C(7) 105.8(2) C(15) C(20) C(19) 119.2(2) 7.2.16. (8a5,8b5,9 /e ,115,l la^,l lb5,13 /f)-6,7,7b,8,9,10,l l , l la-decahydro-9,ll-[l,2]Propanediyl-7a-buytl-(7a^)-benzo[a]benzo[3,4]cyclobuta[l,2-c]cycloocten-ll-b(5//)-ol (X) A crystal of approximate dimensions of 0.30 x 0.25 x 0.20 mm size was chosen for data collection. Crystallographic data of X appear in Table 7.46. A monoclinic cell with Z = 4 (the calculated density was 1.25 gem"3) was indicated by preliminary measurements after twin deconvolution. Of the 3468 reflections collected, 3259 were unique and 2129 observed (> 2rj(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 25 carefully centred reflections in the 276 Chapter 7 Experimental/Crystallography range 75.80 < 28 < 105.04°. The data for X were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.39 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as Pl^lc based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. The hydrogen atom on the oxygen atom was located from a Fourier difference map and refined isotropically. The remaining hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. A secondary extinction correction was applied (final coefficient = 1.45 x IO"2). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.054, Rw = 0.150 for 202 variables (GOF = 1.066; including zeros: R = 0.098, Rw = 0.185), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.21 and 0.23 eA"3. The unit cell is almost identical to that of the homologue IX. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.53 - 7.55, respectively. 277 Chapter 7 Experimental/Crystallography Table 7.53. Final atomic coordinates (fractional) and U(eq) (A 2) of X. atom X y z U(eq) 0(1) 0.1347(2) 0.3807(1) 0.1509(1) 0.0567(5) C(l) 0.2495(2) 0.3292(2) 0.2116(2) 0.0443(5) C(2) 0.3742(2) 0.4024(2) 0.2491(2) 0.0436(5) C(3) 0.4255(3) 0.3964(2) 0.1259(2) 0.0492(5) C(4) 0.3729(3) 0.2962(2) 0.1293(2) 0.0482(5) C(5) 0.4960(3) 0.2363(2) 0.1858(2) 0.0536(6) C(6) 0.4980(3) 0.2551(2) 0.3103(2) 0.0507(6) C(7) 0.5010(2) 0.3575(2) 0.3230(2) 0.0464(5) C(8) 0.6601(3) 6.3884(2) 0.2887(2) 0.0599(7) C(9) 0.6906(3) 0.3613(2) 0.1685(2) 0.0642(7) C(10) 0.6545(3) 0.2610(2) 0.1448(2) 0.0647(7) C ( l l ) 0.5866(3) 0.4182(2) 0.0959(2) 0.0620(7) C(12) 0.1611(2) 0.2646(2) 0.2843(2) 0.0464(5) C(13) 0.1561(3) 0.1726(2) 0.2581(2) 0.0593(6) C(14) 0.0676(3) 0.1110(2) 0.3150(2) 0.0673(7) C(15) -0.0205(3) 0.1419(2) 0.4000(2) 0.0639(7) C(16) -0.0187(3) 0.2338(2) 0.4262(2) 0.0585(6) C(17) 0.0696(2) 0.2968(2) 0.3704(2) 0.0487(5) C(18) 0.0630(3) 0.3961(2) 0.4012(2) 0.0545(6) C(19) 0.2047(3) 0.4306(2) 0.4643(2) 0.0548(6) C(20) 0.2884(3) 0.5090(2) 0.4100(2) 0.0587(6) C(21) 0.3240(3) 0.4960(2) 0.2871(2) 0.0521(6) H(l) 0.099(2) 0.339(2) 0.100(3) 0.148(18) e 7.54. Bond lengths (A) of X with estimated standard deviations. atom atom distance atom atom distance 0(1) C( l ) 1.452(3) C(8) C(9) 1.531(4) C(l) C(12) 1.516(3) C(9) C ( l l ) 1.509(4) C( l ) C(4) 1.564(3) C(9) C(10) 1.530(4) C( l ) C(2) 1.596(3) C(12) C(13) 1.384(3) C(2) C(21) 1.514(3) C(12) C(17) 1.409(3) C(2) C(3) 1.564(3) C(13) C(14) 1.383(4) C(2) C(7) 1.565(3) C(14) C(15) 1.374(4) C(3) C ( l l ) 1.509(3) C(15) C(16) 1.384(4) C(3) C(4) 1.540(3) C(16) C(17) 1.390(3) C(4) C(5) 1.547(3) C(17) C(18) 1.502(3) C(5) C(6) 1.528(3) C(18) C(19) 1.539(4) C(5) C(10) 1.536(3) C(19) C(20) 1.521(4) C(6) C(7) 1.508(3) C(20) C(21) 1.533(3) C(7) C(8) 1.539(3) 278 Chapter 7 Experimental/Crystallography Table 7.55. Bond angles (°) of X with estimated standard deviations. atom atom atom angle atom atom atom angle 0(1) C( l ) C(12) 104.7(2) C(6) C(7) C(2) 110.4(2) O(l) C( l ) C(4) 109.1(2) C(8) C(7) C(2) 111.8(2) C(12) C( l ) C(4) 123.1(2) C(9) C(8) C(7) 110.7(2) 0(1) C( l ) C(2) 105.5(2) C ( l l ) C(9) C(10) 107.4(2) C(12) C( l ) • C(2) 127.9(2) C ( l l ) C(9) C(8) 107.0(2) C(4) C( l ) C(2) 84.4(2) C(10) C(9) C(8) 112.8(2) C(21) C(2) C(3) 115.4(2) C(9) C(10) C(5) 110.7(2) C(21) C(2) C(7) 114.8(2) C(3) C ( l l ) C(9) 108.1(2) C(3) C(2) C(7) 107.6(2) C(13) C(12) C(17) 118.6(2) C(21) C(2) C( l ) 119.3(2) C(13) C(12). C( l ) 119.4(2) C(3) C(2) C( l ) 84.4(2) C(17) C(12) C( l ) 121.6(2) C(7) C(2) C( l ) 111.3(2) C(14) C(13) C(12) 122.5(2) C ( l l ) C(3) C(4) 119.6(2) C(15) C(14) C ( l 3) 119.2(3) C ( l l ) C(3) C(2) 120.3(2) C(14) C(15) C(16) 119.1(2) G(4) C(3) C(2) 86.3(2) C(15) C(16) C(17) 122.7(2) C(3) C(4) C(5) 110.0(2) C(16) C(17) C(12) 117.9(2) C(3) C(4) C( l ) 86.3(2) C(16) C(17) C(18) 119.9(2) C(5) C(4) C( l ) 112.8(2) C(12) C(17) C(18) 122.2(2) C(6) C(5) C(10) 106.2(2) C(17) C(18) C(19) 113.9(2) C(6) C(5) C(4) 109.2(2) C(20) C(19) C(18) 115.6(2) C(10) C(5) C(4) 111.2(2) C(19) C(20) C(21) 115.6(2) C(7) C(6) C(5) 106.2(2) C(2) C(21) C(20) 118.1(2) C(6) C(7) C(8) 106.3(2) 7.2.17. (cis-Octahydronaphthalen-4a-yl)phenylmethanone (XIa) A crystal of approximate dimensions of 0.80 x 0.40 x 0.40 mm size was chosen for data collection. Crystallographic data of XIa appear in Table 7.56. A monoclinic cell with Z = 4 (the calculated density was 1.18 gem-3) was indicated by preliminary measurements. Of the 3067 collected, 2842 were unique and 2111 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles of 25 carefully centred reflections in the range 102.61 < 29 < 114.78°. The data for XIa were processed,3 and corrected for Lorentz and polarization effects. An 279 Chapter 7 Experimental/Crystallography absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.91 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as Plfc based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR92).6 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. Hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. A secondary extinction correction was applied (final coefficient = 3.8 x 10"^). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.049, Rw = 0.057 forl64 variables (GOF = 4.34; including zeros: R = 0.075, Rw = 0.074), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.17 and 0.18 eA"3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Table 7.57 -7.59, respectively. 280 Chapter 7 Experimental/Crystallography Table 7.56. Crystallographic data of XIa and Xlb. — — Formula C ^ . O F fw 242.36 260.35 Color, habit colourless, block colourless, block Crystal size, mm 0.80 x 0.40 x 0.40 0.75 x 0.50 x 0.50 Crystal system monoclinic monoclinic Space group Pljc P2Ja a, A 7.3068(6) 13.952(2) b,A 19.757(2) 6.4153(9) c,A 9.958(1) 16.271(1) a ( ° ) 90 90 P(°) 108.452(7) 109.170(9) Y(°) 90 90 V 1363.7(3) 1375.6(3) Z 4 4 Dcalc, g/cm3 1.18 1.26 F(000) 528 560 Radiation Cu- K a Cu- K a ja, mm'1 0.542 0.682 Transmission factors 0.91-1.00 0.77-1.00 Scan type co - 29 co-29 Scan range, ° in co 1.10 + 0.20 tanO 1.37 + 0.20 tan9 Scan speed, 7min 32.0 32.0 Data collected +h, +k, ±1 +h, +k, ±1 20max, ° 155 155 Crystal decay, % -1.24 -0.47 Data collection temperature (K) 293 293 Total reflections 3067 3550 Total unique reflections 2842 3020 0.04 0.05 merge No. of reflections with I > 3a(I) 2111 2073 No. of variables 164 257 p-factor 0.003 0.003 R 0.049 0.054 Rw 0.057 0.061 Goodness of fit (GOF) 4.34 5.08 Max A /a (final cycle) 0.00 0.00 Residual density e/A3 -0.17,0.18 -0.20, 0.27 281 Chapter 7 Experimental/Crystallography ° 2 Table 7.57. Final atomic coordinates (fractional) and B(eq) (A ) of XIa. atom X y z B(eq) 0(1) 0.5519(2) 0.18081(8) 0.9279(2) 6.63(4) C( l ) 0.4543(2) 0.0959(1) 0.7029(2) 4.94(4) C(2) 0.4038(3) 0.0391(1) 0.7878(3) 6.09(5) C(3) 0.5403(3) -0.0205(1) 0.8064(2) 5.85(5) C(4) 0.7497(3) 0.00254(9) 0.8698(2) 4.61(4) C(5) 0.8038(2) 0.05793(8) 0.7830(2) 3.66(3) C(6) 0.8139(3) 0.0318(1) 0.6405(2) 4.69(4) C(7) 0.8661(3) 0.0870(1) 0.5532(2) 5.66(5) C(8) 0.7215(3) 0.1444(1) 0.5257(2) 5.62(5) C(9) 0.7073(3) 0.17340(9) 0.6633(2) 4.73(4) C(10) 0.6661(2) 0.11958(8) 0.7637(2) 3.82(3) C ( l l ) 0.6908(2) 0.15564(9) 0.9042(2) 4.20(4) C(12) 0.8832(2) 0.16374(8) 1.0186(2) 3.83(4) C(13) 0.8846(3) 0.1591(1) 1.1577(2) 4.66(4) C(14) 1.0510(3) 0.1709(1) 1.2691(2) 5.37(5) C(15) 1.2181(3) 0.1897(1) 1.2422(2) 5.48(5) C(16) 1.2205(3) 0.1934(1) 1.1057(2) 5.07(5) C(17) 1.0552(3) 0.17989(9) 0.9934(2) 4.30(4) Table 7.58. Bond lengths (A) of XIa with estimated standard deviations. atom atom distance atom atom distance 0(1) C ( l l ) 1.218(3) C(8) C(9) 1.518(3) C( l ) C(2) 1.518(3) C(9) C(10) 1.553(3) C( l ) C(10) 1.545(2) C(10) C ( l l ) 1.529(3) C(2) C(3) 1.516(3) C ( l l ) C(12) 1.512(2) C(3) C(4) 1.528(3) C(12) C(13) 1.386(3) C(4) C(5) 1.522(3) C(12) C(17) 1.394(3) C(5) C(6) 1.534(3) C(13) C(14) 1.382(3) C(5) C(10) 1.553(2) C(14) C(15) 1.381(4) C(6) C(7) 1.516(3) C(15) C(16) 1.367(4) C(7) C(8) 1.515(3) C(16) C(17) 1.388(2) Table 7.59. Bond angles (°) of XIa with estimated standard deviations. atom atom atom angle atom atom atom angle C(2) C( l ) C(10) 113.3(1) C(5) C(10) C(9) 111.5(2) C( l ) C(2) C(3) 112.0(2) C(5) C(10) C ( l l ) 111.6(1) C(2) C(3) C(4) 110.7(2) C(9) C(10) C ( l l ) 106.2(1) C(3) C(4) C(5) 112.7(1) 0(1) C ( l l ) C(10) 120.2(1) C(4) C(5) C(6) 112.4(1) 0(1) C ( l l ) C(12) 116.4(2) C(4) C(5) C(10) 111.1(2) C(10) C ( l l ) C(12) 123.4(2) 282 Chapter 7 Experimental/Crystallography C(6) C(5) C(6) C(7) C(8) C( l ) C( l ) C( l ) C(5) C(6) C(7) C(8) C(9) C(10) C(10) C(10) C(10) C(7) C(8) C(9) C(10) C(5) C(9) C ( l l ) 111.6(1) 112.6(2) 110.7(2) 111.2(2) 113.9(2) 109.9(1) 109.2(1) 108.3(2) C ( l l ) C ( l l ) C(13) C(12) C(13) C(14) C(15) C(12) C(12) C(12) C(12) C(13) C(14) C(15) C(16) C(17) C(13) C(17) C(17) C(14) C(15) C(16) C(17) C(16) 117.2(2) 124.4(2) 118.2(1) 121.2(2) 119.8(2) 119.9(2) 120.6(2) 120.2(2) 7.2.18. (4-Fluorophenyl)-(a's-octahydro-naphthalen-4a-yl)rnethanone (Xlb) A crystal of approximate dimensions of 0.75 x 0.50 x 0.50 mm size was chosen for data collection. Crystallographic data of Xlb appear in Table 7.56. A monoclinic cell with Z = 4 (the calculated density was 1.26 gcirr 3) was indicated by preliminary measurements. Of the 3550 reflections collected, 3020 were unique and 2073 observed (> 3o~(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles of 25 carefully centred reflections in the range 106.16 < 20 < 113.71°. The data for Xlb were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.77 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as P2i/a based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR92).6 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic 283 Chapter 7 Experimental/Crystallography thermal parameters. Hydrogen atoms were located from difference Fourier syntheses and refined isotropically. A secondary extinction correction was applied (final coefficient = 5.5 x 10"^). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.054, Rw = 0.061 for 257 variables (GOF = 5.08; including zeros: R = 0.054, Rw = 0.061), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.20 and 0.27 eA"3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Table 7.60 - 7.62, respectively. T a b l e 7.60. Final atomic coordinates (fractional) and B(eq) (A 2) of X l b . atom X y z B(eq) F( l ) 0.5461(1) 0.2783(3) 0.4794(1) 7.26(5) 0(1) 0.8025(1) -0.2955(3) 0.3249(1) 5.31(4) C( l ) 0.7205(2) 0.1141(3) 0.1682(1) 3.46(4) C(2) 0.6267(2) -0.0131(4) 0.1205(2) 4.14(5) C(3) 0.6514(2) -0.1853(4) 0.0664(2) 4.26(5) C(4) 0.7373(2) -0.3209(3) 0.1224(2) 4.08(5) C(5) 0.8327(2) -0.1982(3) 0.1718(1) 3.53(4) C(6) 0.8875(2) -0.1187(4) 0.1099(2) 4.26(5) C(7) 0.9818(2) 0.0070(5) 0.1559(2) 4.90(6) C(8) 0.9560(2) 0.1875(4) 0.2049(2) 4.76(6) C(9) 0.9047(2) 0.1130(4) 0.2688(2) 4.29(5) C(10) 0.8081(1) -0.0203(3) 0.2263(1) 3.21(4) C ( l l ) 0.7786(2) -0.1180(3) 0.3018(1) 3.62(4) C(12) 0.7180(2) 0.0016(3) 0.3477(1) 3.76(4) C(13) 0.7373(2) 0.2045(4) 0.3776(2) 4.30(5) C(14) 0.6805(2) 0.2965(5) 0.4238(2) 4.90(6) C(15) 0.6038(2) 0.1860(5) 0.4372(2) 5.02(6) C(16) 0.5805(2) -0.0145(5) 0.4074(2) 5.38(7) C(17) 0.6394(2) -0.1061(4) 0.3640(2) 4.56(6) H( l ) 0.701(2) 0.221(4) 0.199(2) 4.6(6) H(2) 0.744(2) 0.183(4) 0.125(2) 4.2(5) H(3) 0.598(2) -0.074(4) 0.163(2) 5.0(6) 284 Chapter 7 Experimental/Crystallography H(4) 0.575(2) 0.080(4) 0.082(2; 5.0(6) H(5) 0.592(2) -0.278(4) 0.038(2; 5.0(6) H(6) 0.669(2) -0.118(4) 0.023(2; 4.1(5) H(7) 0.755(2) -0.423(4) 0.083(1; 4.6(5) H(8) 0.711(2) -0.395(4) 0.159(1; 4.0(5) H(9) 0.880(2) -0.294(3) 0.215(1; 3.6(5) H(10) 0.840(2) -0.027(4) o.o6i(i; 4.1(5) H ( l l ) 0.908(2) -0.242(4) 0.084(2; 5.2(6) H(12) 1.014(2) 0.060(4) 0.113(2; 5.5(6) H(13) 1.030(2) -0.081(4) 0.200(2; 5.3(6) H(14) 1.017(2) 0.274(4) 0.237(2; 5.8(6) H(15) 0.912(2) 0.293(4) 0.163(2; 4.5(5) H(16) 0.953(2) 0.020(4) 0.317(1; 4.1(5) H(17) 0.885(2) 0.233(4) 0.298(2; 4.7(6) H(18) 0.791(2) 0.282(3) 0.372(1; 3.9(5) H(19) 0.696(2) 0.435(5) 0.447(2; 6.8(7) H(20) 0.528(2) -0.083(4) 0.421(2; 6.2(7) H(21) 0.629(2) -0.247(4) 0.346(2; 4.5(6) Table 7.61. Bond lengths (A) of Xlb with estimated standard deviations. atom atom distance atom atom distance F(l) C(15) 1.354(3) C(8) C(9) 1.520(3) 0(1) C ( l l ) 1.211(3) C(9) C(10) 1.554(3) C( l ) C(2) 1.521(3) C(10) C ( l l ) 1.550(3) C( l ) C(10) 1.539(3) C ( l l ) C(12) 1.509(3) C(2) C(3) 1.520(3) C(12) C(13) 1.385(3) C(3) C(4) 1.519(3) C(12) C(17) 1.394(3) C(4) C(5) 1.528(3) C(13) C(14) 1.390(4) C(5) C(6) 1.539(3) C(14) C(15) 1.360(4) C(5) C(10) 1.552(3) C(15) C(16) 1.375(4) C(6) C(7) 1.515(3) C(16) C(17) 1.378(4) C(7) C(8) 1.514(4) Table 7.62. Bond angles (°) of Xlb with estimated standard deviations. atom atom atom angle atom atom atom angle C(2) C( l ) C(10) 112.9(2) C(5) C(10) C ( l l ) 108.7(2) C( l ) C(2) C(3) 111.4(2) C(9) C(10) C ( l l ) 106.7(2) C(2) C(3) C(4) 110.7(2) O(l) C ( l l ) C(10) 120.6(2) C(3) C(4) C(5) 113.6(2) 0(1) C ( l l ) C(12) 117.8(2) C(4) C(5) C(6) 111.1(2) C(10) C ( l l ) C(12) 121.6(2) C(4) C(5) C(10) 111.2(2) C ( l l ) C(12) C(13) 125.2(2) C(6) C(5) C(10) 112.4(2) C ( l l ) C(12) C(17) 116.5(2) 285 Chapter 7 Experimental/Crystallography C(5) C(6) C(7) C(8) C( l ) C( l ) C( l ) C(5) C(6) C(7) C(8) C(9) C(10) C(10) C(10) C(10) C(7) C(8) C(9) C(10) C(5) C(9) C ( l l ) C(9) 112.9(2) 110.5(2) 111.5(2) 113.8(2) 110.0(2) 111.3(2) 110.4(2) 109.7(2) C(13) C(12) C(13) F( l ) F( l ) C(14) C(15) C(12) C(12) C(13) C(14) C(15) C(15) C(15) C(16) C(17) C(17) C(14) C(15) C(14) C(16) C(16) C(17) C(16) 118.2(2) 120.6(2) 118.9(3) 118.9(3) 118.5(3) 122.6(3) 117.9(3) 121.7(3) 7.2.19. 4-[(ci's-octahydro-4a-(2//)-naphthalenyl)carbonyl]benzoic acid methyl ester (XIc) Repeated attempts at crystallization of XIc failed to yield good quality crystals for X-ray diffraction. A crystal of approximate dimensions of 0.25 x 0.25 x 0.25 mm size was chosen for data collection. Crystallographic data of XIc appear in Table 7.63. A monoclinic cell with Z = 4 (the calculated density was 1.25 gcnr^) was indicated by preliminary measurements. Of the 2611 reflections collected, 2503 were unique and 880 observed (> 2o(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles of 9 carefully centred reflections in the range 11.80 < 29 < 20.00°. The data for XIc were processed,3 and corrected for Lorentz and polarization effects. An absorption correction was applied (transmission factors: 0.95 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as Plfa based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR92).6 The non-hydrogen atoms were determined from E-maps or 286 Chapter 7 Experimental/Crystallography from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. The hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. A secondary extinction correction was applied (final coefficient = 1.5 x 10~2). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.062, Rw = 0.173 for 201 variables (GOF = 1.024; including zeros: R = 0.202, Rw = 0.216), with the largest parameter shift in the final cycle being O.OOrj. The final difference map showed electron density between -0.15 and 0.14 eA"3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.64 - 7.66, respectively. Table 7.63. Crystallographic data of XIc, XIIc, and XIVc. XIc XIIc XIVc Formula C19H24O3 C19H24O3 C19H22O3 fw 300.4 300.4 298.38 Colour, habit colourless, cube colourless, prism colourless, prism Crystal size, mm 0.25 x 0.25 x0.25 0.50 x 0.40 x 0.40 0.50 x 0.50 x 0.25 Crystal system monoclinic triclinic monoclinic Space group Plila P-l P2{ a, A 13.881(5) 8.8083(3) 11.209(1) b,A 6.362(2) 17.365(7) 10.149(1) c A 18.197(8) 6.182(2) '7.5641(8) a(° ) 90 90.99(3) 90 PC) 97.77(4) 109.53(3) 70.368(9) Y(°) 90 79.04(3) 90 v, A3 1591(1) 801.9(5) 810.5(2) z 4 2 2 Dcalc, g/cm3 1.25 1.24 1.22 F(000) 648 324 320 Radiation Mo- K a Cu- K a Cu- K a p., mm"1 0.083 0.659 0.651 Transmission factors 0.95-1.00 0.89-1.00 0.79-1.00 Scan type to - 20 to - 20 to-29 287 Chapter 7 Experimental/Crystallography Scan range, ° in to 1.26 + 0.35 tanO 1.42 + 0.20 tanO 1.10 + 0.20 tanO Scan speed, 7min 16.0 32.0 32.0 Data collected +h, +k, ±1 +h, ±k, ±1 +h, +k, ±1 29max, ° 55 155 155 Crystal decay, % 0.63 -0.27 1.74 Data collection temperature (K) 293 293 293 Total reflections 2611 3515 1884 Total unique reflections 2503 3263 1805 ^merge 0.03 0.02 0.05 No. of reflections with I > 3o(I) 880 > 2 a 2814 1465 No. of variables 201 200 199 p-factor n/a 0.01 0.003 R 0.062 0.060 0.041 Rw 0.173 0.060 0.044 Goodness of fit (GOF) 1.02 3.39 2.76 Max A /a (final cycle) 0.00 0.00 0.00 Residual density e/A"3 -0.15,0.14 -0.24, 0.25 -0.13,0.16 Table 7.64. Final atomic coordinates (fractional) and B(eq) (A 2) of XIc. atom X y z TJ(eq) 0(1) 0.7705(3) 0.1873(6) 0.2226(3) 0 163(2) 0(2) 1.1511(5) 0.5504(8) 0.0514(3) 0 188(3) 0(3) 1.0956(4) 0.8736(7) 0.0645(2) 0 151(2) C( l ) 0.8343(3) 0.6038(6) 0.3523(3) 0 089(2) C(2) 0.9139(3) 0.4638(7) 0.3932(3) 0 103(2) C(3) 0.8704(3) 0.3014(7) 0.4410(4) 0 110(2) C(4) 0.7926(3) 0.1733(6) 0.3944(4) 0 106(2) C(5) 0.7122(3) 0.3077(7) 0.3529(4) 0 102(2) C(6) 0.6460(3) 0.4039(7) 0.4036(4) 0 113(2) C(7) 0.5644(3) 0.5353(7) 0.3634(4) 0 119(2) C(8) 0.6081(3) 0.7119(7) 0.3218(4) 0 120(2) C(9) 0.6729(4) 0.6215(7) 0.2688(4) 0 118(2) C(10) 0.7551(3) 0.4767(7) 0.3043(3) 0 .094(2) C ( l l ) 0.7977(4) 0.3652(8) 0.2415(4) 0 .117(2) C(12) 0.8738(5) 0.4599(7) 0.2005(4) 0 .112(2) C(13) 0.8772(5) 0.6681(8) 0.1775(4) 0 .121(2) C(14) 0.9473(6) 0.7370(8) 0.1370(4) 0 .127(2) C(15) 1.0176(6) 0.6002(9) 0.1179(4) 0 .119(2) C(16) 1.0164(5) 0.3934(8) 0.1412(4) 0 .127(2) C(17) 0.9450(5) 0.3258(8) 0.1810(4) 0 .115(2) C(18) 1.0946(7) 0.667(1) 0.0738(4) 0 .145(3) C(19) 1.1707(6) 0.954(1) 0.0231(4) 0 .163(3) 288 Chapter 7 Experimental/Crystallography Table 7.65. Bond lengths (A) of XIc with estimated standard deviations. atom atom bond atom atom bond 0(1) C(l l) 1.228(5) C(7) C(8) 1.526(6) 0(2) C(18) 1.192(8) C(8) C(9) 1.517(7) 0(3) C(18) 1.324(7) C(9) C(10) 1.538(7) 0(3) C(19) 1.458(7) C(10) C(l l) 1.529(7) C(l) C(2) 1.531(6) C(ll) C(12) 1.499(7) C(l) C(10) 1.538(6) C(12) C(17) 1.388(7) C(2) C(3) 1.527(6) C(12) C(13) 1.392(7) C(3) C(4) 1.517(6) C(13) C(14) 1.370(7) C(4) C(5) 1.522(6) C(14) C(15) 1.386(8) C(5) C(6) 1.517(7) C(15) C(16) 1.383(7) C(5) C(10) 1.560(7) C(15) C(18) 1.483(9) C(6) C(7) 1.513(6) C(16) C(17) 1.373(7) Table 7.66. Bond angles (°) of XIc with estimated standard deviations. atom atom atom angle atom atom atom angle C(18) 0(3) C(19) 115.6(6) C(9) C(10) C(5) 109.4(4) C(2) C(l) C(10) 112.5(4) O(l) C(l l) C(12) 116.2(6) C(3) C(2) C(l) 110.8(4) O(l) C(l l) C(10) 120.1(6) C(4) C(3) C(2) 110.6(5) C(12) C(l l) C(10) 123.7(4) C(3) C(4) C(5) 113.2(4) C(17) C(12) C(13) 117.0(6) C(6) C(5) C(4) 112.9(5) C(17) C(12) C( l l ) 117.0(5) C(6) C(5) C(10) 112.0(4) C(13) C(12) C( l l ) 125.9(5) C(4) C(5) C(10) 111.0(4) C(14) C(13) C(12) 121.4(6) C(7) C(6) C(5) 113.9(5) C(13) C(14) C(15) 120.6(5) C(6) C(7) C(8) 108.9(4) C(16) C(15) C(14) 118.9(6) C(9) C(8) C(7) 110.2(4) C(16) C(15) C(18) 118.6(6) C(8) C(9) C(10) 115.5(5) C(14) C(15) C(18) 122.5(6) C(ll) C(10) C(l) 110.4(4) C(17) C(16) C(15) 119.9(6) C(ll) C(10) C(9) 107.8(5) C(16) C(17) C(12) 122.2(5) C(l) C(10) C(9) 110.8(4) 0(2) C(18) 0(3) 123.8(8) C(l l) C(10) C(5) 108.6(4) 0(2) C(18) C(15) 124.1(6) C(l) C(10) C(5) 109.8(5) 0(3) C(18) C(15) 112.0(7) 289 Chapter 7 Experimental/Crystallography 7.2.20. 4-[(4a/?,85,8a/?,95)-octahydro-9-hydroxy-2//-4a,8-methanonaphthalen-9-yl]benzoic acid methyl ester (XIIc) A crystal of approximate dimensions of 0.50 x 0.40 x 0.40 mm size was chosen for data collection. Crystallographic data of XIIc appear in Table 7.63. A triclinic cell with Z = 2 (the calculated density was 1.24 gcm"3) was indicated by preliminary measurements. Of the 3515 reflections collected, 3263 were unique and 2814 observed (> 3rj(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles of 15 carefully centred reflections in the range 113.20 < 20 < 114.60°. The data for XIIc were processed,3 and corrected for Lorentz and polarization effects. An absorption correction was applied (transmission factors: 0.89 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as PI based on E-statistics, no systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. The hydrogen atoms were fixed o in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. A secondary extinction correction was applied (final coefficient = 4.8 x 10"^). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-290 Chapter 7 Experimental/Crystallography hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.060, Rw = 0.060 for 200 variables (GOF = 3.39; including zeros: R = 0.071, Rw = 0.069), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.24 and 0.25 eA 3 . Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.67 -7.69, respectively. ° 2 Table 7.67. Final atomic coordinates (fractional) and B(eq) (A ) of XIIc. atom X y z B(eq) 0(1) 0.1746(2) 0.3040(1) 0.4029(3) 4.36(4) 0(2) 0.8690(3) 0.4201(1) 0.1251(4) 6.15(6) 0(3) 0.6485(3) 0.4481(1) -0.2102(3) 5.13(5) C( l ) -0.0458(4) 0.2144(2) -0.0018(4) 4.24(6) C(2) -0.1246(4) 0.1392(2) -0.0291(5) 4.92(7) C(3) -0.0787(4) 0.0897(2) 0.1926(6) 5.28(8) C(4) 0.1225(4) 0.0711(2) 0.3408(5) 4.72(7) C(5) 0.1757(3) 0.1502(2) 0.3688(4) 3.76(6) C(6) 0.3604(3) 0.1752(2) 0.4656(4) 3.69(5) C(7) 0.5033(4) 0.1187(2) 0.4039(5) 4.41(6) C(8) 0.4564(4) 0.1133(2) 0.1432(6) 5.58(8) C(9) 0.2584(4) 0.1417(2) 0.0082(4) 4.00(6) C(10) 0.1522(3) 0.1923(1) 0.1401(4) 3.33(5) C ( l l ) 0.2723(3) 0.2485(1) 0.2948(4) 3.39(5) C(12) 0.3850(3) 0.2900(1) 0.2082(4) 3.55(5) C(13) 0.3314(3) 0.3219(2) -0.0143(4) 3.94(6) C(14) 0.4348(4) 0.3631(2) -0.0856(4) 4.04(6) C(15) 0.6002(3) 0.3738(1) 0.0687(4) 3.77(6) C(16) 0.6558(4) 0.3418(2) 0.2912(4) 4.02(6) C(17) 0.5509(4) 0.3017(2) 0.3614(4) 4.03(6) C(18) 0.7189(4) 0.4155(2) 0.0004(5) 4.22(6) C(19) 0.7575(5) 0.4902(2) -0.2875(6) 5.98(9) 291 Chapter 7 Experimental/Crystallography Table 7.68. Bond lengths (A) of XIIc with estimated standard deviations. atom atom distance atom atom distance 0(1) C ( l l ) 1.428(3) C(7) C(8) 1.533(4) 0(2) C(18) 1.217(3) C(8) C(9) 1.524(4) 0(3) C(18) 1.322(3) C(9) C(10) 1.527(4) 0(3) C(19) 1.441(4) C(10) C ( l l ) 1.586(3) C( l ) C(2) 1.542(4) C ( l l ) C(12) 1.492(4) C( l ) C(10) 1.522(3) C(12) C(13) 1.387(3) C(2) C(3) 1.528(4) C(12) C(17) 1.408(3) C(3) C(4) 1.551(4) C(13) C(14) 1.375(4) C(4) C(5) 1.505(4) C(14) C(15) 1.402(4) C(5) C(6) 1.554(3) C(15) C(16) 1.386(4) C(5) C(10) 1.541(3) C(15) C(18) 1.473(4) C(6) C(7) 1.515(4) C(16) C(17) 1.369(4) C(6) C ( l l ) 1.562(3) Table 7.69. Bond angles (°) of XIIc with estimated standard deviations. atom atom atom angle atom atom atom angle C(18) 0(3) C(19) 117.0(2) 0(1) C ( l l ) C(6) 106.8(2) C(2) C( l ) C(10) 107.9(2) 0(1) C ( l l ) C(10) 112.1(2) C ( l ) C(2) C(3) 115.4(2) 0(1) C ( l l ) C(12) 108.3(2) C(2) C(3) C(4) 115.2(2) C(6) C ( l l ) C(10) 85.2(2) C(3) C(4) C(5) 104.1(2) C(6) C ( l l ) C(12) 120.3(2) C(4) C(5) C(6) 132.5(2) C(10) C ( l l ) C(12) 122.1(2) C(4) C(5) C(10) 113.7(2) C ( l l ) C(12) C(13) 123.5(2) C(6) C(5) C(10) 87.0(2) C ( l l ) C(12) C(17) 119.1(2) C(5) C(6) C(7) 111.4(2) C(13) C(12) C(17) 117.3(2) C(5) C(6) C ( l l ) 85.8(2) C(12) C(13) C(14) 122.0(2) C(7) C(6) C ( l l ) 113.6(2) C(13) C(14) C(15) 119.9(2) C(6) C(7) C(8) 111.9(2) C(14) C(15) C(16) 118.7(2) C(7) C(8) C(9) 113.8(2) C(14) C(15) C(18) 122.3(2) C(8) C(9) C(10) 114.9(2) C(16) C(15) C(18) 119.0(2) C ( l ) C(10) C(5) 109.9(2) C(15) C(16) C(17) 121.0(2) C( l ) C(10) C(9) 111.7(2) C(12) C(17) C(16) 121.1(2) C( l ) C(10) C ( l l ) 126.6(2) 0(2) C(18) 0(3) 122.2(3) C(5) C(10) C(9) 110.9(2) 0(2) C(18) C(15) 123.6(3) C(5) C(10) C ( l l ) 85.5(2) 0(3) C(18) C(15) 114.1(2) C(9) C(10) C ( l l ) 109.0(2) 292 Chapter 7 Experimental/Crystallography 7.2.21. l,2,3,4-Tetrahydro-9-oxo-4a,9a-butano-9H-fluorene-6-carboxylic acid methyl ester (XIVc) A crystal of approximate dimensions of 0.50 x 0.50 x 0.25 mm size was chosen for data collection. Crystallographic data of XIVc appear in Table 7.63. A monoclinic cell with Z = 2 (the calculated density was 1.22 gcnr 3 ) was indicated by preliminary measurements. Of the 1884 reflections collected, 1805 were unique and 1465 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles of 25 carefully centred reflections in the range 75.12 < 20 < 85.19°. The data for XIVc were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.79 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. Based on E-statistics, systematic absences, and subsequent successful structure solution and refinement, the space group was determined as P2\. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. Hydrogen atoms were fixed in idealized positions with C-H = 0.98 A and B H = 1.2 Bbonded atom. A secondary extinction correction was applied (final coefficient = 4.12 x 10"^). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the 293 Chapter 7 Experimental/Crystallography non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.1 2 1 3 The refinement converged at R = 0.041, Rw = 0.044 forl99 variables (GOF = 2.76; including zeros: R = 0.062, Rw = 0.046), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.13 and 0.16 eA"3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.70 -7.72, respectively. Table 7.70. Final atomic coordinates (fractional) and B(eq) (A 2) of XIVc. atom X y z B(eq) 0(1) 0.8247(3) 0.5166 -0.0463(3) 6.62(8) 0(2) 0.5890(3) 0.7932(4) 0.9118(3) 5.72(7) 0(3) 0.5860(2) 0.9581(4) 0.7225(3) 5.06(6) C( l ) 1.0127(3) 0.4511(5) 0.1703(5) 5.25(9) C(2) 1.0745(3) 0.3926(6) 0.3003(6) 6.6(1) C(3) 0.9944(4) 0.4197(6) 0.5040(7) 6.2(1) C(4) 0.8644(3) 0.3634(5) 0.5466(5) 4.66(8) C(5) 0.7947(3) 0.4106(4) 0.4169(4) 3.41(6) C(6) 0.6699(3) 0.3325(4) 0.4554(6) 4.79(9) C(7) 0.6873(4) 0.1948(5) 0.3704(7) 6.3(1) C(8) 0.7501(5) 0.2025(5) 0.1623(8) 7.0(1) C(9) 0.8795(4) 0.2671(5) 0.1123(5) 5.6(1) C(10) 0.8764(3) 0.4023(5) 0.2023(4) 3.93(7) C ( l l ) 0.8194(3) 0.5096(5) 0.1159(5) 4.24(8) C(12) 0.7633(3) 0.6077(4) 0.2647(4) 3.46(7) C(13) 0.7224(3) 0.7340(5) 0.2466(4) 3.99(8) C(14) 0.6734(3) 0.8092(4) 0.4072(4) 3.68(7) C(15) 0.6653(3) 0.7569(4) 0.5808(4) 3.20(6) C(16) 0.7072(3) 0.6301(4) 0.5976(4) 3.31(6) C(17) 0.7571(3) 0.5554(4) 0.4367(4) 3.17(6) C(18) 0.6098(3) 0.8345(4) 0.7574(5) 3.64(7) C(19) 0.5322(4) 1.0432(5) 0.8817(6) 6.2(1) 294 Chapter 7 Experimental/Crystallography Table 7.71. Bond lengths (A) of XIVc with estimated standard deviations. atom atom distance atom atom distance 0(1) C(l l) 1.210(4) C(7) C(8) 1.495(7) 0(2) C(18) 1.188(4) C(8) C(9) 1.519(6) 0(3) C(18) 1.328(4) C(9) C(10) 1.528(5) 0(3) C(19) 1.439(4) C(10) C ( l l ) 1.517(5) C( l ) C(2) 1.502(5) C ( l l ) C(12) 1.476(5) C(l) C(10) 1.546(5) C(12) C(13) 1.384(4) C(2) C(3) 1.525(6) C(12) C(17) 1.385(4) C(3) C(4) 1.496(6) C(13) C(14) 1.382(5) C(4) C(5) 1.522(4) C(14) C(15) 1.391(4) C(5) C(6) 1.549(5) C(15) C(16) 1.391(4) C(5) C(10) 1.575(4) C(15) C(18) 1.494(4) C(5) C(17) 1.522(4) C(16) C(17) 1.382(4) C(6) C(7) 1.522(5) Table 7.72. Bond angles (°) of XIVc with estimated standard deviations. atom atom atom angle atom atom atom angle C(18) 0(3) C(19) 117.2(3) C(9) C(10) C ( l l ) 113.8(3) C(2) C( l ) C(10) 114.8(3) 0(1) C ( l l ) C(10) 126.5(3) C( l ) C(2) C(3) 110.3(3) 0(1) C ( l l ) C(12) 126.6(3) C(2) C(3) C(4) 110.4(4) C(10) C ( l l ) C(12) 106.8(3) C(3) C(4) C(5) 114.5(3) C ( l l ) C(12) C(13) 128.3(3) C(4) C(5) C(6) 110.2(3) C ( l l ) C(12) C(17) 109.4(3) C(4) C(5) C(10) 113.6(2) C(13) C(12) C(17) 122.3(3) C(4) C(5) C(17) 115.2(3) C(12) C(13) C(14) 118.1(3) C(6) C(5) C(10) 110.0(3) C(13) C(14) C(15) 120.0(3) C(6) C(5) C(17) 105.8(2) C(14) C(15) C(16) 121.5(3) C(10) C(5) C(17) 101.5(3) C(14) C(15) C(18) 121.3(3) C(5) C(6) C(7) 114.3(3) C(16) C(15) C(18) 117.3(3) C(6) C(7) C(8) 110.2(4) C(15) C(16) C(17) 118.4(3) C(7) C(8) C(9) 110.9(3) C(5) C(17) C(12) 110.6(3) C(8) C(9) C(10) 113.5(3) C(5) C(17) C(16) 129.3(3) C( l ) C(10) C(5) 110.2(2) C(12) C(17) C(16) 119.7(3) C ( l ) C(10) C(9) 110.1(3) 0(2) C(18) 0(3) 122.9(3) C( l ) C(10) C ( l l ) 103.9(3) 0(2) C(18) C(15) 125.3(3) C(5) C(10) C(9) 115.2(3) 0(3) C(18) C(15) 111.8(3) C(5) C(10) C ( l l ) 102.9(2) 2 9 5 Chapter 7 Experimental/Crystallography 7.2.22. 4-[(cis-octahydro-4a-(2//)-naphthalenyl)carbonyl]benzoic acid (1R,2S)-(-)-norephedrine salt (SI) A crystal of approximate dimensions of 0.45 x 0.15 x 0.10 mm size was chosen for data collection. Crystallographic data of SI appear in Table 7.73. A monoclinic cell with Z = 4 (the calculated density was 1.23 gcnr^) was indicated by preliminary measurements. Of the 5510 reflections collected, 5299 were unique and 3627 observed (> 3o(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles of 19 carefully centred reflections in the range 76.26 < 20 < 91.89°. The data for SI were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.78 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as P2i based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97) and expanded using Fourier techniques. The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. Hydrogen atoms involved in hydrogen bonding were located from a Fourier difference map and refined isotropically. The remaining hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. Allthough Z = 2, the structure is not 296 Chapter 7 Experimental/Crystallography pseudosyrnrnetric. A secondary extinction correction was applied (final coefficient = 1.69 x 10~6). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12,13 The refinement converged at R = 0.043, Rw = 0.045 for 633 variables (GOF = 2.53; including zeros: R = 0.083, Rw = 0.047), with the largest parameter shift in the final cycle being 0.02a. The final difference map showed electron density between -0.14 and 0.18 eA~3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Table 7.74 -Table 7.76, respectively. Table 7 . 7 3 . Crystallographic data of Sl and S 2 . si s i Formula C 2 7 H 3 5 N 0 4 C 2 6 H 3 3 N 0 3 fw 437.58 407.55 Colour, habit colourless, prism colourless, prism Crystal size, mm 0.45 x 0.15 x 0.10 0.50x0.20x0.15 Crystal system monoclinic orthorhombic Space group P2i P2,2,2 1 a, A 13.959(2) 6.5004(5) b,A 6.396(2) 14.947(1) c, A 26.705(5) 23.025(2) a ( ° ) 90 90 PC) 97.58(2) 90 YC) 90 90 v,A 3 2363.5(9) 2237.2(3) z 4 4 Dcalc, g/cm3 1.23 1.21 F(000) 944 880 Radiation Cu- K a Mo- K a p., mm"1 0.651 0.078 Transmission factors 0.78-1.00 0.66-1.00 Scan type co - 20 0 and co Scan range, ° in co 1.00 + 0.20 tanO - 1 9 - 2 3 f , 0 - 190* Scan speed, 7min 16.0 12s* Data collected +h, +k, ±1 ±ll, ±k, ±1 20max, ° 155 56 297 Chapter 7 Experimental/Crystallography Crystal decay, % -0.02 0.00 Data collection temperature (K) 293 173 Total reflections 5510 18173 Total unique reflections 5299 4764 ^merge 0.03 0.13 No. of reflections with I > 3a(I) 3627 2320 No. of variables 633 284 p-factor 0.006 0.00 R 0.043 0.046 Rw 0.045 0.053 Goodness of fit (GOF) 2.53 1.61 Max A /a (final cycle) 0.02 0.00 Residual density e/A3 -0.14, 0.18 -0.47, 0.42 C C D data; this is the co scan range (°). C C D data; this is the (|> scan range (°). * C C D data; exposure time per frame. Table 7.74. Final atomic coordinates (fractional) and B(eq) (A 2) of SI. atom X y z B(eq) O(l) 0.1095(2) -0.6114 -0.3054(1) 4.49(9) 0(2) 0.5425(2) -0.1567(8) -0.2054(1) 4.39(8) 0(3) 0.4694(2) 0.1494(9) -0.2178(1) 4.68(8) 0(4) -0.3864(2) 0.4220(5) -0.3082(1) 3.96(8) 0(5) 0.0418(2) -0.0435(8) -0.2047(1) 4.63(9) 0(6) -0.0417(3) -0.3401(8) -0.2035(1) 5.13(9) 0(7) 0.2024(2) -0.2670(8) -0.1755(1) 4.35(8) 0(8) -0.3419(2) 0.0648(8) -0.1352(1) 4.94(9) N( l ) 0.1062(3) -0.629(1) -0.1887(2) 4.0(1) N(2) -0.3901(3) 0.442(1) -0.1976(2) 3.7(1) C( l ) 0.1159(3) -0.234(1) -0.4057(1) 3.1(1) C(2) 0.1845(3) -0.368(1) -0.4315(2) 3.7(1) C(3) 0.1304(3) -0.545(1) -0.4608(2) 4.0(1) C(4) 0.0747(3) -0.673(1) -0.4263(2) 3.8(1) C(5) 0.0054(3) -0.542(1) -0.3993(1) 3.2(1) C(6) -0.0824(3) -0.467(1) -0.4360(2) 3-7(1) C(7) -0.1513(3) -0.334(1) -0.4098(2) 4.1(1) C(8) -0.0991(3) -0.148(1) -0.3839(2) 4.1(1) C(9) -0.0139(3) -0.219(1) -0.3463(2) 3.6(1) C(10) 0.0596(3) -0.3587(9) -0.3698(1) 2.9(1) C ( l l ) 0.1269(3) -0.4463(9) -0.3247(2) 3.0(1) C(12) 0.2154(3) -0.329(1) -0.3019(1) 2.8(1) C(13) 0.2182(3) -0.1190(9) -0.2888(2) 3.2(1) C(14) 0.3002(3) -0.031(1) -0.2632(2) 3.2(1) C(15) 0.3834(3) -0.148(1) -0.2502(2) 3.0(1) C(16) 0.3826(3) -0.355(1) -0.2644(2) 3.6(1) C(17) 0.2994(3) -0.445(1) -0.2895(2) 3.4(1) C(18) 0.4709(4) -0.043(1) -0.2223(2) 3.4(1) 298 Chapter 7 Experimental/Crystallography C(19) -0.3790(3) 0.035(1) -0.4054(1) 3.0(1) C(20) -0.3105(3) 0.171(1) -0.4315(2) 3.7(1) C(21) -0.3654(3) 0.346(1) -0.4615(2) 3.7(1) C(22) -0.4222(3) 0.474(1) -0.4276(2) 3.6(1) C(23) -0.4915(3) 0.3442(9) -0.4003(1) 3 .KD C(24) -0.5782(3) 0.270(1) -0.4372(2) 3.7(1) C(25) -0.6480(3) 0.139(1) -0.4118(2) 4.3(1) C(26) -0.5963(3) -0.049(1) -0.3859(2) 3.8(1) C(27) -0.5109(3) 0.023(1) -0.3480(2) 3.5(1) C(28) -0.4372(3) 0.1618(9) -0.3708(1) 2.69(9) C(29) -0.3704(3) 0.250(1) -0.3255(2) 3.0(1) C(30) -0.2844(3) 0.133(1) -0.2994(1) 3.0(1) C(31) -0.2873(3) -0.073(1) -0.2838(2) 3.4(1) C(32) -0.2062(3) -0.163(1) -0.2554(2) 3.5(1) C(33) -0.1211(3) -0.047(1) -0.2440(1) 3.0(1) C(34) -0.1181(3) 0.157(1) -0.2610(2) 3.5(1) C(35) -0.1993(3) 0.249(1) -0.2875(2) 3.4(1) C(36) -0.0331(4) -0.152(1) -0.2149(2) 3.5(1) C(37) 0.2607(3) -0.392(1) -0.0403(2) 5.8(1) C(38) 0.3362(5) -0.366(1) -0.0015(2) 7.2(2) C(39) 0.4206(4) -0.274(1) -0.0126(2) 7-4(2) C(40) 0.4299(4) -0.217(1) -0.0601(2) 6.6(2) C(41) 0.3553(3) -0.244(1) -0.0987(2) 4.9(1) C(42) 0.2690(3) -0.3347(9) -0.0886(2) 3.9(1) C(43) 0.1887(3) -0.3741(9) -0.1310(2) 3.7(1) C(44) 0.1795(3) -0.607(1) -0.1433(2) 3.8(1) C(45) 0.2733(4) -0.710(1) -0.1535(2) 5.2(1) C(46) -0.1539(4) -0.017(1) -0.0965(2) 7.0(2) C(47) -0.0668(5) -0.051(1) -0.0657(3) 8.5(2) C(48) -0.0030(4) 0.109(1) -0.0553(2) 7.2(2) C(49) -0.0253(4) 0.298(1) -0.0746(2) 6.9(2) C(50) -0.1116(3) 0.334(1) -0.1060(2) 5.6(1) C(51) -0.1771(3) 0.177(1) -0.1167(2) 4.0(1) C(52) -0.2727(3) 0.2022(9) -0.1519(1) 3.7(1) C(53) -0.3113(3) 0.427(1) -0.1537(2) 3.5(1) C(54) -0.3486(5) 0.494(1) -0.1059(2) 5.4(2) H(50) 0.307(3) -0.61(1) -0.177(2) 7(1) H(51) 0.319(3) -0.710(9) -0.116(2) 6(1) H(52) 0.264(3) -0.84(1) -0.162(2) 6(1) H(53) 0.041(4) -0.50(1) -0.191(2) 10(2) H(54) 0.080(3) -0.748(7) -0.195(1) 1-4(8) H(55) 0.126(3) -0.610(8) -0.220(1) 4(1) H(56) 0.161(7) -0.25(3) -0.191(4) 26(2) H(64) -0.364(4) 0.61(1) -0.109(2) 6(2) H(65) -0.408(3) 0.39(1) -0.100(2) 8(2) H(66) -0.300(3) 0.490(9) -0.071(2) 7(1) H(67) -0.376(3) 0.44(1) -0.236(2) 8(2) H(68) -0.428(5) 0.58(1) -0.185(2) 11(2) H(69) -0.434(3) 0.340(8) -0.196(1) 3d) 299 Chapter 7 Experimental/Crystallography H(70) -0.370(3) 0.007(8) -0.169(2) 5(1) T a b l e 7.75. Bond lengths (A) of Sl with estimated standard deviations. atom atom distance atom atom distance 0(1) C ( l l ) 1.214(6) C(23) C(24) 1.531(5) 0(2) C(18) 1.271(6) C(23) C(28) 1.550(6) 0(3) C(18) 1.235(6) C(24) C(25) 1.514(7) 0(4) C(29) 1.227(6) C(25) C(26) 1.521(7) 0(5) C(36) 1.253(6) C(26) C(27) 1.530(6) 0(6) C(36) 1.253(6) C(27) C(28) 1.545(6) 0(7) C(43) 1.408(5) C(28) C(29) 1.532(6) 0(7) H(56) 0.68(9) C(29) C(30) 1.505(6) 0(8) C(52) 1.422(5) C(30) C(31) 1.382(7) 0(8) H(70) 1.00(5) C(30) C(35) 1.401(6) N( l ) C(44) 1.486(6) C(31) C(32) 1.400(6) N( l ) H(53) 1.22(7) C(32) C(33) 1.398(6) N( l ) H(54) 0.85(4) C(33) C(34) 1.382(7) N( l ) H(55) 0.92(4) C(33) C(36) 1.519(6) N(2) C(53) 1.501(6) C(34) C(35) 1.385(6) N(2) H(67) 1.08(5) C(37) C(38) 1.388(6) N(2) H(68) 1.09(8) C(37) C(42) 1.362(6) N(2) H(69) 0.90(4) C(38) C(39) 1.382(8) C( l ) C(2) 1.517(6) C(39) C(40) 1.342(8) C(l) C(10) 1.542(6) C(40) C(41) 1.376(7) C(2) C(3) 1.519(7) C(41) C(42) 1.394(6) C(3) C(4) 1.519(6) C(42) C(43) 1.504(5) C(4) C(5) 1.529(6) C(43) C(44) 1.529(7) C(5) C(6) 1.541(5) C(44) C(45) 1.521(7) C(5) C(10) 1.554(6) C(45) H(50) 1.05(5) C(6) C(7) 1.524(7) C(45) H(51) 1.12(4) C(7) C(8) 1.512(7) C(45) H(52) 0.86(6) C(8) C(9) 1.520(6) C(46) C(47) 1.391(8) C(9) C(10) 1.555(6) C(46) C(51) 1.374(8) C(10) C ( l l ) 1.531(6) C(47) C(48) 1.36(1) C ( l l ) C(12) 1.503(6) C(48) C(49) 1.335(9) C(12) C(13) 1.389(7) C(49) C(50) 1.394(7) C(12) C(17) 1.391(6) C(50) C(51) 1.364(7) C(13) C(14) 1.374(6) C(51) C(52) 1.537(5) C(14) C(15) 1.384(6) C(52) C(53) 1.534(7) C(15) C(16) 1.380(7) C(53) C(54) 1.502(8) C(15) C(18) 1.501(6) C(54) H(64) 0.77(6) C(16) C(17) 1.389(6) C(54) H(65) 1.09(5) C(19) C(20) 1.526(6) C(54) H(66) 1.07(4) C(19) C(28) 1.539(6) C(34) H(41) 1.134 C(20) C(21) 1.524(7) C(35) H(42) 1.02 C(21) C(22) 1.519(6) C(31) H(39) 1.114 C(22) C(23) 1.530(6) 300 Chapter 7 Experimental/Crystallography Table 7.76. Bond angles (°) of S l with estimated standard deviations. atom atom atom angle atom atom atom angle C(2) C( l ) C(10) 113.1(4) C(23) C(28) C(27) 109.2(3) C( l ) C(2) C(3) 110.8(3) C(23) C(28) C(29) 109.4(4) C(2) C(3) C(4) 110.4(4) C(27) C(28) C(29) 105.6(3) C(3) C(4) C(5) 113.5(4) 0(4) C(29) C(28) 120.3(4) C(4) C(5) C(6) 111.6(3) 0(4) C(29) C(30) 116.4(4) C(4) C(5) C(10) 110.8(3) C(28) C(29) C(30) 123.3(4) C(6) C(5) C(10) 112.4(4) C(29) C(30) C(31) 124.0(5) C(5) C(6) C(7) 112.2(3) C(29) C(30) C(35) 116.4(4) C(6) C(7) C(8) 110.8(3) C(31) C(30) C(35) 119.4(4) C(7) C(8) C(9) 110.9(5) C(30) C(31) C(32) 120.0(5) C(8) C(9) C(10) 113.8(4) C(31) C(32) C(33) 120.2(5) C( l ) C(10) C(5) 109.3(3) C(32) C(33) C(34) 119.3(4) C( l ) C(10) C(9) 111.7(4) C(32) C(33) C(36) 119.0(5) C( l ) C(10) C ( l l ) 111.6(3) C(34) C(33) C(36) 121.7(5) C(5) C(10) C(9) 109.7(3) C(33) C(34) C(35) 120.6(5) C(5) C(10) C ( l l ) 109.2(4) C(30) C(35) C(34) 120.3(5) C(9) C(10) C ( l l ) 105.3(3) 0(5) C(36) 0(6) 125.5(5) 0(1) C ( l l ) C(10) 121.1(4) 0(5) C(36) C(33) 117.6(5) 0(1) C ( l l ) C(12) 117.4(4) 0(6) C(36) C(33) 116.9(5) C(10) C ( l l ) C(12) 121.5(4) C(38) C(37) C(42) 121.6(5) C ( l l ) C(12) C(13) 125.4(5) C(37) C(38) C(39) 118.4(5) C ( l l ) C(12) C(17) 116.9(4) C(38) C(39) C(40) 120.7(5) C(13) C(12) C(17) 117.6(5) C(39) C(40) C(41) 121.0(6) C(12) C(13) C(14) 121.0(5) C(40) C(41) C(42) 119.7(5) C(13) C(14) C(15) 121.5(5) C(37) C(42) C(41) 118.5(4) C(14) C(15) C(16) 118.1(4) C(37) C(42) C(43) 121.3(4) C(14) C(15) C(18) 119.0(5) C(41) C(42) C(43) 120.2(4) C(16) C(15) C(18) 122.9(5) 0(7) C(43) C(42) 112.5(4) C(15) C(16) C(17) 120.7(5) 0(7) C(43) C(44) 108.0(4) C(12) C(17) C(16) 121.1(5) C(42) C(43) C(44) 111.0(4) 0(2) C(18) 0(3) 124.0(5) N( l ) C(44) C(43) 107.3(4) 0(2) C(18) C(15) 118.0(5) N( l ) C(44) C(45) 109.3(4) 0(3) C(18) C(15) 118.0(5) C(43) C(44) C(45) 114.2(5) C(20) C(19) C(28) 112.8(4) C(47) C(46) C(51) 120.8(6) C(19) C(20) C(21) 110.8(3) C(46) C(47) C(48) 120.2(7) C(20) C(21) C(22) 110.4(3) C(47) C(48) C(49) 119.3(5) C(21) C(22) C(23) 113.9(4) C(48) C(49) C(50) 121.2(6) C(22) C(23) C(24) 111.0(3) C(49) C(50) C(51) 120.6(6) C(22) C(23) C(28) 110.6(3) C(46) C(51) C(50) 117.8(4) C(24) C(23) C(28) 112.7(4) C(46) C(51) C(52) 118.5(5) C(23) C(24) C(25) 112.6(3) C(50) C(51) C(52) 123.6(5) C(24) C(25) C(26) 110.3(4) 0(8) C(52) C(51) 108.2(4) C(25) C(26) C(27) 110.2(4) 0(8) C(52) C(53) 109.8(4) C(26) C(27) C(28) 114.4(3) C(51) C(52) C(53) 113.1(4) 301 Chapter 7 Experimental/Crystallography C(19) C(19) C(19) C(28) C(28) C(28) C(23) C(27) C(29) 110.6(3) 111.4(4) 110.6(3) N(2) N(2) C(52) C(53) C(53) C(53) C(52) C(54) C(54) 107.5(4) 110.2(5) 113.5(4) 7.2.23. 4-[(cw-octahydro-4a-(2H)-naphthalenyl)carbonyl]benzoic acid (S')-(-)-A crystal of approximate dimensions of 0.50 x 0.20 x 0.15 mm size was chosen for data collection. Crystallographic data of S2 appear in Table 7.73. An orthorhombic cell with Z = 4 (the calculated density was 1.21 gem"3) was indicated by preliminary measurements. Of the 18173 reflections collected, 4764 were unique and 2320 observed (> 3o~(I)). The final unit-cell parameters were obtained by least-squares on the setting angles for 18173 reflections in the range 2.989 < 0 < 28.01°. The data for S2 were processed3. An absorption correction (empirical, based on a three-dimensional analysis of symmetry-equivalent data using 4 t h order spherical harmonics) was applied (transmission factors: 0.66 to 1.00). The space group was assigned as P2{1{1\ based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. Hydrogen atoms involved in hydrogen bonding were located from difference Fourier maps and refined isotropically. The remaining hydrogen atoms were fixed in idealized positions with C - H = 0.98 A a-methylbenzylamine salt (S2) 302 Chapter 7 Experimental/Crystallography and B H = 1.2 Bbonded atom. Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.046, Rw = 0.053 for 284 variables (GOF =1.61; including zeros: R = 0.093, Rw = 0.129), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.47 and 0.42 eA"3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.77 - 7.79, respectively. Table 7.77. Final atomic coordinates (fractional) and B(eq) (A 2) of S 2 . atom X y z B(eq) 0(1) 0.4712(3) 0.2726(2) 0.63351(9) 3.45(6) 0(2) 0.0261(3) 0.6609(1) 0.5416(1) 2.79(5) 0(3) -0.2837(3) 0.6127(1) 0.56914(9) 2.66(5) N(l) 0.4154(4) 0.6715(2) 0.4946(1) 1.84(6) C( l ) 0.1144(5) 0.2787(2) 0.7519(1) 2.24(7) C(2) 0.2576(6) 0.3415(2) 0.7836(1) 2.98(8) C(3) 0.4354(6) 0.2910(3) 0.8120(1) 3.51(9) C(4) 0.5494(5) 0.2372(2) 0.7669(2) 3.34(8) C(5) 0.4087(5) 0.1729(2) 0.7321(1) 2.62(7) C(6) 0.3462(6) 0.0929(2) 0.7692(1) 3.56(9) C(7) 0.2064(7) 0.0287(2) 0.7363(2) 4.4(1) C(8) 0.0193(7) 0.0763(2) 0.7141(2) 4.6(1) C(9) 0.0799(6) 0.1558(2) 0.6754(1) 3.54(8) C(10) . 0.2264(5) 0.2229(2) 0.7052(1) 2.08(7) C ( l l ) 0.3041(5) 0.2856(2) 0.6572(1) 2.22(7) C(12) 0.1869(5) 0.3674(2) 0.6375(1) 1.86(6) C(13) -0.0213(4) 0.3679(2) 0.6226(1) 2.20(7) C(14) -0.1071(4) 0.4456(2) 0.6003(1) 2.23(7) C(15) 0.0060(4) 0.5234(2) 0.5929(1) 1.71(6) C(16) 0.2133(4) 0.5230(2) 0.6094(1) 2.03(7) C(17) 0.3006(4) 0.4454(2) 0.6310(1) 2.10(7) C(18) -0.0923(5) 0.6045(2) 0.5664(1) 1.90(6) C(19) 0.1752(6) 0.4931(3) 0.4292(2) 4.8(1) C(20) 0.128(1) 0.4063(5) 0.4389(3) 8.9(2) C(21) 0.249(2) 0.3490(4) 0.4666(3) 9.0(2) C(22) 0.434(1) 0.3791(3) 0.4862(2) 8.3(2) C(23) 0.4947(8) 0.4671(3) 0.4766(2) 5.1(1) 303 Chapter 7 Experimental/Crystallography C(24) 0.3681(5) 0.5249(2) 0.4482(1) 2.85(8) C(25) 0.4228(5) 0.6206(2) 0.4384(1) 2.20(7) C(26) 0.6340(5) 0.6345(2) 0.4104(1) 3.30(8) H( l ) 0.432(5) 0.731(2) 0.483(1) 2.4(6) H(2) 0.250(7) 0.656(3) 0.523(2) 7.3(8) H(25) 0.512(6) 0.656(3) 0.517(2) 5.4(8) Table 7.78. Bond lengths (A) of S2 with estimated standard deviations. atom atom distance atom atom distance 0(1) C ( l l ) 1.231(4) C ( l l ) C(12) 1.510(4) 0(2) C(18) 1.276(4) C(12) C(13) 1.397(4) 0(3) C(18) 1.252(3) C(12) C(17) 1.388(4) N( l ) C(25) 1.501(4) C(13) C(14) 1.386(4) C( l ) C(2) 1.511(5) C(14) C(15) 1.387(4) C( l ) C(10) 1.543(4) C(15) C(16) 1.400(4) C(2) C(3) 1.527(5) C(15) C(18) 1.500(4) C(3) C(4) 1.508(5) C(16) C(17) 1.384(4) C(4) C(5) 1.550(5) C(19) C(20) 1.353(7) C(5) C(6) 1.524(4) C(19) C(24) 1.410(5) C(5) C(10) 1.532(4) C(20) C(21) 1.33(1) C(6) C(7) 1.524(5) C(21) C(22) 1.36(1) C(7) C(8) 1.499(6) C(22) C(23) 1.391(6) C(8) C(9) 1.535(5) C(23) C(24) 1.360(5) C(9) C(10) 1.544(4) C(24) C(25) 1.491(5) C(10) C ( l l ) 1.535(4) C(25) C(26) 1.531(4) Table 7.79. Bond angles (°) of S2 with estimated standard deviations. atom atom atom angle atom atom atom angle C(2) C( l ) C(10) 112.5(3) C(13) C(12) C(17) 119.0(3) C( l ) C(2) C(3) 111.5(3) C(12) C(13) C(14) 119.1(3) C(2) C(3) C(4) 109.9(3) C(13) C(14) C(15) 122.3(3) C(3) C(4) C(5) 113.4(3) C(14) C(15) C(16) 118.3(3) C(4) C(5) C(6) 110.7(3) C(14) C(15) C(18) 120.2(3) C(4) C(5) C(10) 111.2(3) C(16) C(15) C(18) 121.6(3) C(6) C(5) C(10) 113.8(3) C(15) C(16) C(17) 119.7(3) C(5) C(6) C(7) 112.0(3) C(12) C(17) C(16) 121.6(3) C(6) C(7) C(8) 110.7(3) 0(2) C(18) 0(3) 123.9(3) C(7) C(8) C(9) 110.9(4) 0(2) C(18) C(15) 117.3(2) C(8) C(9) C(10) 113.8(3) 0(3) C(18) C(15) 118.8(3) C( l ) C(10) C(5) 110.3(2) C(20) C(19) C(24) 118.3(5) C( l ) C(10) C(9) 111.7(3) C(19) C(20) C(21) 124.3(6) C( l ) C(10) C ( l l ) 109.1(2) C(20) C(21) C(22) 118.0(5) C(5) C(10) C(9) 109.8(3) C(21) C(22) C(23) 120.7(6) C(5) C(10) C ( l l ) 109.6(3) C(22) C(23) C(24) 120.3(5) 304 Chapter 7 Experimental/Crystallography C(9) C(10) C ( l l ) 106.3(2) C(19) C(24) C(23) 118.3(4) 0(1) C ( l l ) C(10) 120.8(3) C(19) C(24) C(25) 119.2(3) 0(1) C ( l l ) C(12) 116.1(3) C(23) C(24) C(25) 122.5(3) C(10) C ( l l ) C(12) 123.0(3) N( l ) C(25) C(24) 110.4(2) C ( l l ) C(12) C(13) 124.6(3) N( l ) C(25) C(26) 108.8(2) C ( l l ) C(12) C(17) 116.3(3) C(24) C(25) C(26) 114.0(3) 7.2.24. l-(4-Fluorophenyl)-2-(2,4,6-trimethylphenyl)ethanone (XVIa) A crystal of approximate dimensions of 0.50 x 0.25 x 0.10 mm size was chosen for data collection. Crystallographic data of XVIa appear in Table 7.80. A monoclinic cell with Z = 4 (the calculated density was 1.19 gcm~3) was indicated by preliminary measurements. Of the 3275 reflections collected, 3094 were unique and 1716 observed (> 3o~(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 21 carefully centred reflections in the range 70.31 < 20 < 86.19°. The data for XVIa were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.90 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as P2fa based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR92).6 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. Hydrogen atoms on the methyl carbons were found from a 305 Chapter 7 Experimental/Crystallography Fourier difference map and fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. The remaining hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. A secondary extinction correction was applied (final coefficient = 1.2 x 10"^ ). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.043, Rw = 0.047 for 173 variables (GOF = 2.56; including zeros: R = 0.089, Rw = 0-051), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.14 and 0.16 eA . Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.81 - 7.83, respectively. Table 7.80. Crystallographic data of X V I a and XVIb . XVIa XVIb Formula C 1 7 H l 7 FO C 1 8 H l 7 NO fw 256.32 263.34 Colour, habit colourless, plate yellow, prism Crystal size, mm 0.50x0.25 x 0.10 1.00 x 1.00x0.50 Crystal system monoclinic monoclinic Space group P2/a PIJa a, A 10.151(3) 10.586(1) b,A 8.687(4) 8.377(2) c A 16.802(4) 17.539(2) a(° ) 90 90 p n 104.99(2) 107.325(8) Y(°) 90 90 v, A3 1431.1(7) 1484.9(4) z 4 4 Dcalc, g/cm3 1.19 1.18 F(000) 544 560 Radiation Cu- K a Cu- K a fx, mm"1 0.655 0.568 Transmission factors 0.90-1.00 0.98-1.00 Scan type co - 20 co - 29 306 Chapter 7 Experimental/Crystallography Scan range, ° in co 0.94 + 0.20 tanO 1.31 + 0.20 tanO Scan speed, 7min 32.0 32.0 Data collected +h, +k, ±1 +h, +k, ±1 29max, ° 155 155 Crystal decay, % 1.37 0.31 Data collection temperature (K) 293 293 Total reflections 3275 3437 Total unique reflections 3094 3255 merge 0.02 0.06 No. of reflections with I > 3o(I) 1716 2299 No. of variables 173 182 p-factor 0.008 0.004 R 0.043 0.045 Rw 0.047 0.063 Goodness of fit (GOF) 2.56 4.18 Max A /a (final cycle) 0.00 0.00 Residual density e/A3 -0.14, 0.16 -0.13,0.15 Table 7.81. Final atomic coordinates (fractional) and B(eq) (A 2) of XVIa . atom X y z B(eq) F( l ) 0.4713(1) 0.8060(2) -0.0030(1) 6.95(4) 0(1) 0.8891(2) 0.3052(2) 0.1725(1) 6.78(5) C( l ) • 0.5466(2) 0.6945(3) 0.0446(2) 4.90(6) C(2) 0.6671(2) 0.6525(3) 0.0288(2) 4.99(6) C(3) 0.7431(2) 0.5401(3) 0.0773(1) 4.66(6) C(4) 0.6991(2) 0.4696(3) 0.1401(1) 4.15(5) C(5) 0.5749(2) 0.5162(3) 0.1534(1) 4.76(6) C(6) 0.4984(2) 0.6292(3) 0.1057(2) 5.17(6) C(7) 0.7846(2) 0.3468(3) 0.1889(1) 4.64(6) C(8) 0.7408(2) 0.2733(3) 0.2600(1) 5.16(6) C(9) 0.8388(2) 0.1530(3) 0.3052(1) 4.58(6) C(10) 0.8196(2) -0.0018(3) 0.2843(2) 5.27(6) C ( l l ) 0.9152(3) -0.1086(3) 0.3247(2) 6.10(7) C(12) 1.0289(3) -0.0679(4) 0.3853(2) 6.09(8) C(13) 1.0466(3) 0.0859(4) 0.4057(2) 6.10(7) C(14) 0.9538(2) 0.1977(3) 0.3659(1) 5.29(6) C(15) 0.9824(3) 0.3649(3) 0.3894(2) 7.56(9) C(16) 0.6994(3) -0.0561(4) 0.2170(2) 8.03(9) C(17) 1.1335(3) -0.1855(4) 0.4275(2) 9.3(1) 82. Bond lengths (A) of X V I a with estimated standard deviations. atom atom distance atom atom distance F( l ) C( l ) 1.358(3) C(8) C(9) 1.506(3) 0(1) C(7) 1.218(2) C(9) C(10) 1.391(3) C( l ) C(2) 1.367(3) C(9) C(14) 1.392(3) C( l ) C(6) 1.369(3) C(10) C ( l l ) 1.387(3) C(2) C(3) 1.373(3) C(10) C(16) 1.508(4) 307 Chapter 7 Experimental/Crystallography C(3) C(4) 1.391(3) C ( l l ) C(12) 1.373(4) C(4) C(5) 1.396(3) C(12) C(13) 1.379(4) C(4) C(7) 1.481(3) C(12) C(17) 1.511(4) C(5) C(6) 1.374(3) C(13) C(14) 1.397(3) C(7) C(8) 1.519(3) C(14) C(15) 1.514(4) Table 7.83. Bond angles (°) of XVIa with estimated standard deviations. atom atom atom angle atom atom atom angle F( l ) C( l ) C(2) 118.1(2) C(8) C(9) C(10) 120.8(2) F( l ) C( l ) C(6) 118.8(2) C(8) C(9) C(14) 119.7(2) C(2) C( l ) C(6) 123.1(2) C(10) C(9) C(14) 119.4(2) C( l ) C(2) C(3) 117.9(2) C(9) C(10) C ( l l ) 119.2(2) C(2) C(3) C(4) 121.5(2) C(9) C(10) C(16) 121.7(3) C(3) C(4) C(5) 118.3(2) C ( l l ) C(10) C(16) 119.1(3) C(3) C(4) C(7) 118.7(2) C(10) C ( l l ) C(12) 122.6(3) C(5) C(4) C(7) 123.0(2) C ( l l ) C(12) C(13) 117.6(2) C(4) C(5) C(6) 120.7(2) C ( l l ) C(12) C(17) 121.8(3) C( l ) C(6) C(5) 118.4(2) C(13) C(12) C(17) 120.5(3) 0(1) C(7) C(4) 120.6(2) C(12) C(13) C(14) 121.8(2) 0(1) C(7) C(8) 120.1(2) C(9) C(14) C(13) 119.4(2) C(4) C(7) C(8) 119.3(2) C(9) C(14) C(15) 121.8(2) C(7) C(8) C(9) 113.6(2) C(13) C(14) C(15) 118.9(2) 7.2.25. 4-[2-(2,4,6-trimethylphenyl)acetyl]benzonitrile (XVIb) A crystal of approximate dimensions of 1.00 x 1.00 x 0.50 mm size was chosen for data collection. Crystallographic data of XVIb appear in Table 7.80. A monoclinic cell with Z = 4 (the calculated density was 1.18 gcnr-^) was indicated by preliminary measurements. Of the 3437 reflections collected, 3255 were unique and 2299 observed (> 3o~(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 21 carefully centred reflections in the range 105.41 < 20 < 114.32°. The data for XVIb were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.98 to 1.00). The intensities of 308 Chapter 7 Experimental/Crystallography three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as P2Ja based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR92).6 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. Hydrogen atoms on the methyl carbons were found from a Fourier difference map and fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. The remaining hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. A secondary extinction correction was applied (final coefficient = 3.3 x 10"^). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.045, Rw = 0.063 for 182 variables (GOF = 4.18; including zeros: R = 0.075, Rw = 0.084), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.13 and 0.15 eA"3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.84 - 7.86, respectively. Table 7.84. Final atomic coordinates (fractional) and B(eq) (A2) of X V I b . atom x y z B(eq) 0(1) N(l) C(l) 0.8750(1) 0.3635(2) 0.4283(2) 0.3255(2) 0.8881(2) 0.8001(2)-0.1932(1) -0.0467(1) -0.0019(1) 6.55(4) 5.74(4) 4.38(4) 309 Chapter 7 Experimental/Crystallography C(2) 0.5114(2) 0.6890(2) 0.0531(1) 3.94(3) C(3) 0.4672(2) 0.6070(2) 0.1089(1) 4.68(4) C(4) 0.5491(2) 0.4977(2) 0.1593(1) 4.51(4) C(5) 0.6754(2) 0.4693(2) 0.1539(1) 3.89(3) C(6) 0.7181(2) 0.5526(2) 0.0975(1) 4.62(4) C(7) 0.6375(2) 0.6613(2) 0.0475(1) 4.57(4) C(8) 0.7684(2) 0.3493(2) 0.2042(1) 4.36(4) C(9) 0.7277(2) 0.2610(2) 0.2682(1) 4.77(4) C(10) 0.8317(2) 0.1450(2) 0.3145(1) 4.24(4) C(ll) 0.8172(2) -0.0188(2) 0.2989(1) 4.55(4) C(12) 0.9176(2) -0.1213(2) 0.3390(1) 5.31(5) C(13) 1.0325(2) -0.0685(3) 0.3947(1) 5.39(5) C(14) 1.0431(2) 0.0934(3) 0.4098(1) 5.56(5) C(15) 0.9459(2) 0.2011(2) 0.3711(1) 4.98(4) C(16) 0.6960(2) -0.0867(3) 0.2389(1) 6.52(6) C(17) 0.9673(3) 0.3767(3) 0.3902(2) 7.22(6) C(18) 1.1413(3) -0.1817(3) 0.4364(2) 7.87(7) Table 7.85. Bond lengths (A) of X V I b with estimated standard deviations. atom atom distance atom atom distance O(l) C(8) 1.217(2) C(9) C(10) 1.511(2) N( l ) C( l ) 1.144(2) C(10) C ( l l ) 1.399(2) C( l ) C(2) 1.437(2) C(10) C(15) 1.397(2) C(2) C(3) 1.387(2) C ( l l ) C(12) 1.384(3) C(2) C(7) 1.387(2) C ( l l ) C(16) 1.507(3) C(3) C(4) 1.384(2) C(12) C(13) 1.386(3) C(4) C(5) 1.389(2) C(13) C(14) 1.380(3) C(5) C(6) 1.392(2) C(13) C(18) 1.504(3) C(5) C(8) 1.496(2) C(14) C(15) 1.385(3) C(6) C(7) 1.371(2) C(15) C(17) 1.510(3) C(8) C(9) 1.510(3) Table 7.86. Bond angles (°) of XVIb with estimated standard deviations. atom atom atom angle atom atom atom angle N(l) C(l ) C(2) 178.7(2) C(9) C(10) C ( l l ) 120.4(2) C( l ) C(2) C(3) 121.8(1) C(9) C(10) C(15) 120.2(2) C( l ) C(2) C(7) 118.1(2) C ( l l ) C(10) C(15) 119.4(2) C(3) C(2) C(7) 120.1(2) C(10) C ( l l ) C(12) 119.1(2) C(2) C(3) C(4) 119.9(2) C(10) C ( l l ) C(16) 121.9(2) C(3) C(4) C(5) 120.2(2) C(12) C ( l l ) C(16) 119.1(2) C(4) C(5) C(6) 119.0(2) C ( l l ) C(12) C(13) 122.7(2) C(4) C(5) C(8) 123.5(2) C(12) C(13) C(14) 116.9(2) C(6) C(5) C(8) 117.4(1) C(12) C(13) C(18) 121.8(2) C(5) C(6) C(7) 121.0(2) C(14) C(13) C(18) 121.3(2) C(2) C(7) C(6) 119.7(2) C(13) C(14) C(15) 122.7(2) 310 Chapter 7 Experimental/Crystallography O(l) C(8) C(5) 119.7(2) C(10) C(15) C(14) 119.2(2) 0(1) C(8) C(9) 121.4(2) C(10) C(15) C(17) 121.7(2) C(5) C(8) C(9) 119.0(1) C(14) C(15) C(17) 119.1(2) C(8) C(9) C(10) 113.1(2) 7.2.26. l-(3-fluorophenyI)-2-[(2,4,6-trimethylphenyl)ethanone (XVIc) A crystal of approximate dimensions of 0.25 x 0.25 x 0.25 mm size was chosen for data collection. Crystallographic data of XVIc appear in Table 7.87. An orthorhombic cell with Z = 8 (the calculated density was 1.20 gcm~3) was indicated by preliminary measurements. Of the 2951 reflections collected, 2951 were unique and 1372 observed (> 2o(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 18 carefully centred reflections in the range 88.00 < 20 < 132.00°. The data for XVIc were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.70 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as Pbca based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. A Fourier difference map showed that the fluorine atom was disordered, and the occupancies of F l and FT were 311 Chapter 7 Experimental/Crystallography refined to a ratio of 71:29. The occupancies of the corresponding HI and HI ' were restrained to this ratio. Hydrogen atoms on the methyl carbons were found from a Fourier difference map and fixed in idealized positions with C - H = 0.98 A and B J J = 1.5 Bbonded atom- The methyl hydrogens on C15, C16, and C17 were found to be disordered from the Fourier difference map, and their occupancies were refined until they converged with ratios of 23:77, 23:77, and 2:3, respectively. The remaining hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and Bpj =1.2 bonded atom- A secondary extinction correction was applied (final coefficient = 1.4 x 10"3). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.049, Rw = 0.150 for 186 variables (GOF = 1.02; including zeros: R = 0.133, Rw = 0.183), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.15 and 0.15 eA"3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.88 -7.90, respectively. Table 7.87. Crystallographic data of XVIc , X V I d , and XVIe. XVIc X V I d XVIe Formula C 1 7 H 1 7 O F C n H 1 7 O C l C i 7 H 1 7 O B r fw 256.32 272.77 317.22 Colour, habit colourless, cube colourless, prism colourless, block Crystal size, mm 0.25 x 0.25 x 0.25 0.25 x 0.25 0.20 0.25 x 0.20x0.10 Crystal system orthorhombic monoclinic monoclinic Space group Pbca P2i/a P2l/a a, A 9.985(3) 7.984(5) 7.996(2) b, A 33.586(7) 15.621(3) 15.755(3) c ,A 8.457(4) 11.770(1) 11.843(1) 312 Chapter 7 Experimental/Crystallography a(° ) 90 90 90 p n 90 100.68(2) 101.06(1) Y(°) 90 90 90 v, A 3 2836(1) 1443(1) 1464.1(5) z 8 4 4 Dcalc, g/cm3 1.20 1.26 1.44 F(000) 1088 576 648 Radiation Cu- K a Cu- K a Cu- K a p., mm"1 0.661 2.26 3.747 Transmission factors 0.70-1.00 0.94-1.00 0.68-1.00 Scan type to-20 to - 20 to-20 Scan range, ° in to 1.00 + 0.20 tanO 1.10 + 0.20 tanO 1.05 + 0.20 tan0 Scan speed, 7min 16.0 32.0 32.0 Data collected +h, +k, +1 +h, +k, ±1 +h, +k, ±1 20max, ° 155 155 155 Crystal decay, % -0.74 -0.23 0.02 Data collection temperature (K) 293 293 293 Total reflections 2951 3825 3453 Total unique reflections 2951 3040 3226 0.00 0.02 0.03 merge No. of reflections with I > 3a(I) 1372 f 2066 2293 No. of variables 186 173 173 p-factor n/a 0.004 0.005 R 0.049 0.041 0.051 Rw 0.150 0.044 0.064 Goodness of fit (GOF) 1.02 2.81 4.37 Max A /a (final cycle) 0.00 0.00 0.00 Residual density e/A3 -0.15,0.15 -0.28,0.17 -0.65, 0.55 fno. reflections > 2a(I) Table 7.88. Final atomic coordinates (fractional) and U(eq) (A 2) of XVIc . atom X y z U(eq) 0(1) 0.4647(2) 0.1578(1) 0.8246(3) 0.0971(7) C( l ) 0.6445(3) 0.2384(1) 1.1211(3) 0.0836(8) F( l ) 0.5777(3) 0.2701(1) 1.1696(3) 0.1151(9) C(2) 0.5820(3) 0.2121(1) 1.0231(3) 0.0741(7) C(3) 0.6527(2) 0.1798(1) 0.9636(3) 0.0616(6) C(4) 0.7845(2) 0.1746(1) 1.0081(3) 0.0763(7) C(5) 0.8422(3) 0.2017(1) 1.1104(4) 0.0905(9) F(l ') 0.9628(6) 0.1987(3) 1.1517(10) 0.145(3) C(6) 0.7746(3) 0.2338(1) 1.1679(4) 0.0904(9) C(7) 0.5824(2) 0.1527(1) 0.8522(3) 0.0659(6) C(8) 0.6589(2) 0.1193(1) 0.7755(3) 0.0711(7) C(9) 0.5784(2) 0.0962(1) 0.6561(3) 0.0663(6) C(10) 0.5881(3) 0.1053(1) 0.4943(3) 0.0742(7) C ( l l ) 0.5079(3) 0.0847(1) 0.3882(3) 0.0799(8) C(12) 0.4203(3) 0.0554(1) 0.4344(4) 0.0808(8) 3 1 3 Chapter 7 Experimental/Crystallography C(13) 0.4142(3) 0.0467(1) 0.5925(4) 0.0783(7) C(14) 0.4905(3) 0.0666(1) 0.7048(3) 0.0700(7) C(15) 0.4744(3) 0.0561(1) 0.8762(4) 0.0960(9) C(16) 0.6800(3) 0.1374(1) 0.4337(4) 0.1024(10) C(17) 0.3335(4) 0.0337(1) 0.3165(4) 0.1098(11) Table 7.89. Bond lengths (A) of XVIc with estimated standard deviations. atom atom distance atom . atom distance O(l) C(7) 1.211(3) C(8) C(9) 1.507(3) C( l ) F( l ) 1.323(3) C(9) C(14) 1.387(3) C( l ) C(2) 1.363(4) C(9) C(10) 1.405(4) C( l ) C(6) 1.366(4) C(10) C ( l l ) 1.387(4) C(2) C(3) 1.388(3) C(10) C(16) 1.508(4) C(3) C(4) 1.379(3) C ( l l ) C(12) 1.374(4) C(3) C(7) 1.486(3) C(12) C(13) 1.370(4) C(4) C(5) 1.382(4) C(12) C(17) 1.509(4) C(5) F(l ' ) 1.258(6) C(13) C(14) 1.389(4) C(5) C(6) 1.361(4) C(14) C(15) 1.501(4) C(7) C(8) 1.504(3) Table 7.90. Bond angles (°) of XVIc with estimated standard deviations. atom atom atom angle atom atom atom angle F(l) C(l) C(2) 118.7(3) C(7) C(8) C(9) 113.8(2) F( l ) C( l ) C(6) 118.6(3) C(14) C(9) C(10) 119.2(2) C(2) C( l ) C(6) 122.6(3) C(14) C(9) C(8) 120.5(2) C( l ) C(2) C(3) 119.6(3) C(10) C(9) C(8) 120.2(2) C(4) C(3) C(2) 118.9(2) C ( l l ) C(10) C(9) 118.8(3) C(4) C(3) C(7) 123.2(2) C ( l l ) C(10) C(16) 119.2(3) C(2) C(3) C(7) 117.9(2) C(9) C(10) C(16) 121.9(3) C(3) C(4) C(5) 119.1(3) C(12) C ( l l ) C(10) 122.7(3) F(l ') C(5) C(6) 116.1(4) C(13) C(12) C ( l l ) 117.3(3) F(l ') C(5) C(4) 121.3(5) C(13) C(12) C(17) 121.1(3) C(6) C(5) C(4) 122.5(3) C ( l l ) C(12) C(17) 121.6(3) C(5) C(6) C(l) 117.1(3) C(12) C(13) C(14) 122.7(3) 0(1) C(7) C(3) 119.6(2) C(9) C(14) C(13) 119.3(3) 0(1) C(7) C(8) 121.0(2) C(9) C(14) C(15) 121.6(2) C(3) C(7) C(8) 119.3(2) C(13) C(14) C(15) 119.2(2) 314 Chapter 7 Experimental/Crystallography 7.2.27. l-(3-chlorophenyl)-2-[(2,4,6-trimethylphenyl)ethanone (XVId) A crystal of approximate dimensions of 0.25 x 0.25 x 0.20 mm size was chosen for data collection. Crystallographic data of XVId appear in Table 7.87. A monoclinic cell with Z = 4 (the calculated density was 1.26 gem - 3) was indicated by preliminary measurements. Of the 3825 reflections, collected 3040 were unique and 2066 observed (> 3o~(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 23 carefully centred reflections in the range 87.57 < 20 < 106.40°. The data for XVId were processed, and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.94 to 1.00). The intensities of three standard reflections measured every 400 reflections throughout the data collection showed no decay. The space group was assigned as Pl^la based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by 7 10 direct methods (SIR97) and expanded using Fourier techniques. The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. Electron density peaks representing hydrogen atoms on the methyl carbons C16 and C17 were located using a Fourier difference map. The peaks indicated disorder among the methyl hydrogens, and these hydrogen atoms were modelled as disordered. Their populations refined to a 1:1 ratio, and then they were fixed in their final positions with C - H = 0.98 A and B H = 315 Chapter 7 Experimental/Crystallography 1.2 Bbonded atom. The remaining hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. A secondary extinction correction was applied (final coefficient = 7.56 x 10"^). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the 12 13 International Tables for X-ray Crystallography. ' The refinement converged at R = 0.041, Rw = 0.044 for 173 variables (GOF = 2.81; including zeros: R = 0.067, Rw = 0.045), with the largest parameter shift in the final cycle being O.OOo. The final O -3 difference map showed electron density between -0.28 and 0.17 eA . Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.91 - 7.93, respectively. Table 7.91. Final atomic coordinates (fractional) and B(eq) (A 2) of X V I d . atom X y z B(eq) Cl( l ) 0.3879(1) 0.12505(5) 0.40380(6) 7.07(2) 0(1) 0.3136(2) -0.0726(1) 0.7513(1) 6.34(5) C( l ) 0.2366(3) 0.1100(1) 0.4913(2) 4.73(5) C(2) 0.2696(3) 0.0514(1) 0.5805(2) 4.41(5) C(3) 0.1482(3) 0.0372(1) 0.6487(2) 3.89(4) C(4) -0.0047(3) 0.0816(1) 0.6259(2) 4.38(5) C(5) -0.0337(3) 0.1402(1) 0.5357(2) 5.05(6) C(6) 0.0878(3) 0.1549(1) 0.4692(2) 5.09(6) C(7) 0.1891(3) -0.0274(1) 0.7447(2) 4.27(5) C(8) 0.0715(3) -0.0332(1) 0.8309(2) 4.57(5) C(9) 0.1447(3) -0.0811(1) 0.9406(2) 3.99(5) C(10) 0.2527(3) -0.0378(1) 1.0287(2) 4.20(5) C ( l l ) 0.3178(3) -0.0808(2) 1.1310(2) 4.63(5) C(12) 0.2774(3) -0.1654(2) 1.1474(2) 4.69(5) C(13) 0.1707(3) -0.2071(1) 1.0593(2) 4.72(5) C(14) 0.1045(3) -0.1669(1) 0.9550(2) 4.27(5) C(15) -0.0061(3) -0.2178(2) 0.8619(2) 6.04(7) C(16) 0.3030(3) 0.0541(1) 1.0165(2) 5.56(6) C(17) 0.3523(3) -0.2118(2) 1.2578(2) 6.80(7) 316 Chapter 7 Experimental/Crystallography Table 7.92. Bond lengths (A) of XVId with estimated standard deviations. atom atom distance atom atom distance Cl( l ) C( l ) 1.742(3) C(8) C(9) 1.513(3) 0(1) C(7) 1.211(3) C(9) C(10) 1.395(3) C( l ) C(2) 1.382(3) C(9) C(14) 1.397(3) C( l ) C(6) 1.362(3) C(10) C ( l l ) 1.394(3) C(2) C(3) 1.386(3) C(10) C(16) 1.504(3) C(3) C(4) 1.386(3) C ( l l ) C(12) 1.381(3) C(3) C(7) 1.505(3) C(12) C(13) 1.378(3) C(4) C(5) 1.388(3) C(12) C(17) 1.512(3) C(5) C(6) 1.374(3) C(13) C(14) 1.393(3) C(7) C(8) 1.507(3) C(14) C(15) 1.501(3) Table 7.93. Bond angles (°) of XVId with estimated standard deviations. atom atom atom angle atom atom atom angle Cl( l ) C( l ) C(2) 118.9(2) C(8) C(9) C(10) 118.8(2) Cl( l ) C( l ) C(6) 119.6(2) C(8) C(9) C(14) 121.2(2) C(2) C( l ) C(6) 121.5(2) C(10) C(9) C(14) 120.0(2) C( l ) C(2) C(3) 119.4(2) C(9) C(10) C ( l l ) 119.2(2) C(2) C(3) C(4) 119.5(2) C(9) C(10) C(16) 122.1(2) C(2) C(3) C(7) 117.7(2) C ( l l ) C(10) C(16) 118.7(2) C(4) C(3) C(7) 122.8(2) C(10) C ( l l ) C(12) 121.5(2) C(3) C(4) C(5) 119.6(2) C ( l l ) C(12) C(13) 118.4(2) C(4) C(5) C(6) 120.7(2) C ( l l ) C(12) C(17) 120.9(2) C( l ) C(6) C(5) 119.2(2) C(13) C(12) C(17) 120.7(2) 0(1) C(7) C(3) 120.0(2) C(12) C(13) C(14) 122.1(2) O(l) C(7) C(8) 121.9(2) C(9) C(14) C(13) 118.8(2) C(3) C(7) C(8) 118.1(2) C(9) C(14) C(15) 122.5(2) C(7) C(8) C(9) 114.4(2) C(13) C(14) C(15) 118.7(2) 7.2.28. l-(3-bromophenyl)-2-[(2,4,6-trimethylphenyl)ethanone (XVIe) A crystal of approximate dimensions of 0.25 x 0.20 x 0.10 mm size was chosen for data collection. Crystallographic data of XVIe appear in Table 7.87. A monoclinic cell with Z = 4 (the calculated density was 1.44 gem - 3) was indicated by preliminary measurements. Of the 3453 reflections collected, 3226 were unique and 317 Chapter 7 Experimental/Crystallography 2293 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 23 carefully centred reflections in the range 95.24 < 20 < 110.84°. The data for XVIe were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.68 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The structure was solved by conventional heavy atom methods (DIRDIF P A T T Y ) . 1 0 Structure analysis was initiated in the centrosymmetric space group P2\/a on the basis of the F-statistics and the appearance of the Patterson function. The coordinates of the bromine atom were determined from the Patterson function and those of the remaining non-hydrogen atoms from subsequent difference Fourier syntheses. This choice was confirmed by subsequent calculations. Hydrogen atoms were found from a Fourier difference map and fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. A secondary extinction correction was applied (final coefficient = 4.3 x 10~6). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.051, Rw = 0.064 for 173 variables (GOF = 4.37; including zeros: R = 0.078, Rw = 0.063), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.65 and 0.55 eA"3. Final atomic coordinates and 318 Chapter 7 Experimental/Crystallography equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.94 - 7.96, respectively. Table 7.94. Final atomic coordinates (fractional) and B(eq) (A 2) of XVIe. atom x y_ z B(eq) Br(l) 0.38776(8) 0.12337(4) 0.39648(5) 6.02(2) 0(1) 0.3108(4) -0.0713(2) 0.7531(3) 6.01(9) C(l) 0.2271(6) 0.1083(3) 0.4936(4) 4.3(1) C(2) 0.2620(6) 0.0511(3) 0.5834(4) 4.2(1) C(3) 0.1428(5) 0.0375(3) 0.6523(3) 3.75(9) C(4) -0.0110(5) 0.0808(3) 0.6297(4) 4.1(1) C(5) -0!0425(7) 0.1386(3) 0.5408(4) 5.0(1) C(6) 0.0759(7) 0.1532(3) 0.4717(4) 4.7(1) C(7) 0.1852(5) -0.0268(3) 0.7474(4) 4.1(1) C(8) 0.0709(6) -0.0339(3) 0.8337(4) 4.4(1) C(9) 0.1467(5) -0.0807(3) 0.9421(4) 3.99(9) C(10) 0.1089(6) -0.1665(3) 0.9564(4) 4.3(1) C(ll) 0.1783(6) -0.2059(3) 1.0596(4) 4.7(1) C(12) 0.2849(6) -0.1645(3) 1.1472(4) 4.6(1) C(13) 0.3222(6) -0.0807(3) 1.1312(4) 4.6(1) C(14) 0.2553(5) -0.0384(3) 1.0306(4) 4.1(1) C(15) -0.0009(7) -0.2172(3) 0.8635(5) 6.0(1) C(16) 0.3022(6) 0.0537(3) 1.0182(5) 5.5(1) C(17) 0.3616(7) -0.2106(4) 1.2567(5) 6.6(2) Table 7.95. Bond lengths (A) of XVIe with estimated standard deviations, atom atom distance atom atom distance Br(l) C( l ) 1.897(5) C(8) C(9) 1.504(6) 0(1) C(7) 1.215(5) C(9) C(10) 1.403(6) C( l ) C(2) 1.381(6) C(9) C(14) 1.394(6) C( l ) C(6) 1.381(7) C(10) C ( l l ) 1.388(6) C(2) C(3) 1.385(6) C(10) C(15) 1.500(7) C(3) C(4) 1.387(6) C ( l l ) C(12) 1.375(7) C(3) C(7) 1.504(6) C(12) C(13) 1.375(7) C(4) C(5) 1.377(6) C(12) C(17) 1.510(7) 319 Chapter 7 Experimental/Crystallography C(5) C(6) 1.384(6) C(13) C(14) 1.380(6) C(7) C(8) 1.500(5) C(14) C(16) 1.514(6) Table 7.96. Bond angles (°) of XVIe with estimated standard deviations. atom atom atom angle atom atom atom angle Br(l) C( l ) C(2) 119.2(4) C(8) C(9) C(10) 120.9(4) Br( l) C( l ) C(6) 119.5(3) C(8) C(9) C(14) 119.9(4) C(2) C( l ) C(6) 121.3(4) C(10) C(9) C(14) 119.1(4) C(l) C(2) C(3) 119.7(4) C(9) C(10) C ( l l ) 118.5(4) C(2) C(3) C(4) 119.6(4) C(9) C(10) C(15) 122.4(4) C(2) C(3) C(7) 117.6(4) C ( l l ) C(10) C(15) 119.1(4) C(4) C(3) C(7) 122.7(4) C(10) C ( l l ) C(12) 122.5(4) C(3) C(4) C(5) 119.9(4) C ( l l ) C(12) C(13) 118.1(4) C(4) C(5) C(6) 121.1(4) C ( l l ) C(12) C(17) 120.7(5) C( l ) C(6) C(5) 118.5(4) C(13) C(12) C(17) 121.2(5) 0(1) C(7) C(3) 119.7(4) C(12) C(13) C(14) 121.6(5) O(l) C(7) C(8) 121.6(4) C(9) C(14) C(13) 120.1(4) C(3) C(7) C(8) 118.7(4) C(9) C(14) C(16) 121.0(4) C(7) C(8) C(9) 114.8(4) C(13) C(14) C(16) 118.9(5) 7.2.29. 3-[2-(2,4,6-trimethylphenyl)acetyl]benzonitrile (XVIf) A crystal of approximate dimensions of 0.40 x 0.25 x 0.15 mm size was chosen for data collection. Crystallographic data of X V I f appear in Table 7.97. A monoclinic cell with Z = 4 (the calculated density was 1.20 gcm~3) was indicated by preliminary measurements. Of the 3294 reflections collected, 3081 were unique and 2533 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 22 carefully centred reflections in the range 111.67 < 20 < 114.26°. The data for X V I f were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.95 to 1.00). The intensities of 320 Chapter 7 Experimental/Crystallography three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as P2\la based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. Hydrogen atoms on the methyl carbons were found from a Fourier difference map and fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. The remaining hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. A secondary extinction correction was applied (final coefficient = 4.57 x 10~5). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.049, Rw = 0.071 for 182 variables (GOF = 4.05; including zeros: R = 0.058, Rw = 0.072), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.15 and 0.24 eA"3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.98 -7.100, respectively. Table 7.97 Crystallographic data of X V I f and XVIg . XVIf XVIg Formula fw C 1 8 H 1 7 N O 263.34 C 1 8 H 1 8 O 3 282.34 321 Chapter 7 Experimental/Crystallography Colour, habit colourless, prism yellow, prism Crystal size, mm 0.40x0.25x0.15 0.30 x 0.25 x 0.20 Crystal system monoclinic monoclinic Space group P2J a P2,/c a, A 7.962(1) 12.590(1) b, A 15.840(3) 9.201(1) c A 12.119(3) 52.865(4) a(°) 90 90 PC) 107.40(1) 94.451(8) Y C ) 90 90 v, A 3 1458.5(5) 6102(1) z 4 16 Dcalc, g/cm3 1.20 1.23 F(000) 560 2400 Radiation Cu- K a Cu- K a p., mm"1 0.578 0.668 Transmission factors 0.95-1.00 0.95-1.00 Scan type co-20 co - 20 Scan range, ° in co 1.21+0.20 tan 9 0.92 + 0.20 tan 9 Scan speed, 7min 32.0 32.0 Data collected +h, +k, ±1 +h, +k, ±1 29max, ° 155 155 Crystal decay, % 0.34 -0.51 Data collection temperature (K) 293 293 Total reflections 3294 13816 Total unique reflections 3081 13223 ^merge 0.02 0.05 No. of reflections with I > 3o(I) 2533 4075 No. of variables 182 758 p-factor 0.03 0.005 R 0.049 0.046 Rw 0.071 0.044 Goodness of fit (GOF) 4.05 2.16 Max A/a (final cycle) 0.00 0.01 Residual density e/A3 -0.15,0.24 -0.14, 0.14 Table 7.98. Final atomic coordinates (fractional) and B(eq) (A 2) of XVIf . atom x y z B(eq) 0(1) -0.0129(1) 0.03498(8) 0.7600(1) 5.03(3) N( l ) 0.4911(3) -0.1233(1) 0.4174(2) 7.19(5) C( l ) 0.3787(2) -0.1197(1) 0.4574(2) 5.04(4) C(2) 0.2368(2) -0.11300(9) 0.5077(1) 3.95(3) C(3) 0.2546(2) -0.06015(9) 0.6021(1) 3.85(3) C(4) 0.1131(2) -0.04891(8) 0.6451(1) 3.51(3) C(5) -0.0429(2) -0.0916(1) 0.5942(1) 3.93(3) C(6) -0.0578(2) -0.1468(1) 0.5029(1) 4.46(3) C(7) 0.0816(2) -0.1573(1) 0.4589(1) 4.38(3) 322 Chapter 7 Experimental/Crystallography C(8) 0.1219(2) 0.01033(9) 0.7436(1) 3.78(3) C(9) 0.3018(2) 0.0358(1) 0.8198(1) 4.58(4) C(10) 0.3044(2) 0.0866(1) 0.9253(1) 3.89(3) C ( l l ) 0.3438(2) 0.1728(1) 0.9308(1) 4.31(3) C(12) 0.3522(2) 0.2168(1) 1.0318(2) 4.84(4) C(13) 0.3193(2) 0.1784(1) 1.1256(2) 4.70(4) C(14) 0.2782(2) 0.0933(1) 1.1179(1) 4.40(3) C(15) 0.2708(2) 0.0469(1) 1.0196(1) 4.03(3) C(16) 0.2254(2) -0.0457(1) 1.0178(2) 5.08(4) C(17) 0.3791(3) 0.2200(1) 0.8322(2) 6.14(5) C(18) 0.3282(3) 0.2282(2) 1.2341(2) 7.02(6) Table 7.99. Bond lengths (A) of X V I f with estimated standard deviations. atom atom distance atom atom distance O(l) C(8) 1.214(2) C(9) C(10) 1.506(2) N( l ) C( l ) 1.139(2) C(10) C ( l l ) 1.398(2) C( l ) C(2) 1.440(2) C(10) C(15) 1.399(2) C(2) C(3) 1.390(2) C ( l l ) C(12) 1.393(2) C(2) C(7) 1.390(2) C ( l l ) C(17) 1.504(2) C(3) C(4) 1.387(2) C(12) C(13) 1.382(3) C(4) C(5) 1.386(2) C(13) C(14) 1.384(2) C(4) C(8) 1.503(2) C(13) C(18) 1.517(2) C(5) C(6) 1.387(2) C(14) C(15) 1.385(2) C(6) C(7) 1.378(2) C(15) C(16) 1.509(2) C(8) C(9) 1.509(2) Table 7.100. Bond angles (°) of X V I f with estimated standard deviations. atom atom atom angle atom atom atom angle N( l ) . C( l ) C(2) 178.7(2) C(9) C(10) C ( l l ) 120.5(1) C( l ) C(2) C(3) 119.5(1) C(9) C(10) C(15) 119.7(1) C( l ) C(2) C(7) 119.6(1) C ( l l ) C(10) C(15) 119.7(1) C(3) C(2) C(7) 120.9(1) C(10) C ( l l ) C(12) 118.8(1) C(2) C(3) C(4) 119.5(1) C(10) C ( l l ) C(17) 122.7(1) C(3) C(4) C(5) 119.4(1) C(12) C ( l l ) C(17) 118.5(2) C(3) C(4) C(8) 121.9(1) C ( l l ) C(12) C(13) 122.1(1) C(5) C(4) C(8) 118.7(1) C(12) C(13) C(14) 118.2(1) C(4) C(5) C(6) 120.9(1) C(12) C(13) C(18) 120.9(2) C(5) C(6) C(7) 119.9(1) C(14) C(13) C(18) 120.9(2) C(2) C(7) C(6) 119.4(1) C(13) C(14) C(15) 121.5(1) 0(1) C(8) C(4) 119.8(1) C(10) C(15) C(14) 119.6(1) 0(1) C(8) C(9) 122.6(1) C(10) C(15) C(16) 121.9(1) C(4) C(8) C(9) 117.6(1) C(14) C(15) C(16) 118.5(2) C(8) C(9) C(10) 115.6(1) 323 Chapter 7 Experimental/Crystallography 7.2.30. 4-[2-(2,4,6-Trimethylphenyl)acetyl]benzoic acid (XVIg) A crystal of approximate dimensions of 0.30 x 0.25 x 0.20 mm size was chosen for data collection. Crystallographic data of X V I g appear in Table 7.97. A monoclinic cell with Z = 16 (the calculated density was 1.23 gem - 3) was indicated by preliminary measurements. Of the 13816 reflections collected, 13223 were unique and 4075 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 25 carefully centred reflections in the range 51.58 < 20 < 87.43°. The data for X V I g were processed,3 and corrected for Lorentz and polarization effects. No absorption correction was required (transmission factors: 0.95 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as P2Jc based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (using the "hard run" phasing routine of SIR92).6 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. Hydrogen atoms on the methyl carbons were found from a Fourier difference map and restrained in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. Hydrogen atoms involved in hydrogen bonding were located from the Fourier difference map but not refined. The remaining hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. The four molecules in the asymmetric unit form two pairs of hydrogen 324 Chapter 7 Experimental/Crystallography bonded dimers with a false centre of symmetry (pseudosymmetry) between the molecules containing 09 and 012. A secondary extinction correction was applied (final coefficient = 7.0 x 10"'7). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.046, Rw = 0.044 for 758 variables (GOF = 2.16; including zeros: R = 0.212, Rw = 0.056), with the largest parameter shift in the final cycle being 0.01a. The final difference map showed electron density between -0.14 and 0.14 eA~3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.101 - 7.103, respectively. Table 7.101. Final atomic coordinates (fractional) and B(eq) (A2) of XVIg . atom X y z B(eq) 0(1) 0.8168(3) -0.6602(4) 0.56467(6) 7.2(1) 0(2) 0.7119(3) -0.8360(4) 0.57723(6) 7.8(1) 0(3) 0.9159(3) -0.4660(4) 0.69232(6) 7.2(1) 0(4) 0.6385(3) -0.4765(3) 0.51938(6) 7.5(1) 0(5) 0.5394(3) -0.6483(4) 0.53530(6) 7.8(1) 0(6) 0.5829(3) -0.0747(4) 0.62962(6) 6.8(1) 0(7) 0.4563(3) -0.1964(4) 0.50625(6) 7.5(1) 0(8) 0.3511(3) -0.3618(4) 0.52204(6) 7.7(1) 0(9) 0.3739(3) 0.2669(4) 0.60630(6) 8.0(1) 0(10) 0.2760(3) -1.0206(4) 0.46430(6) 8.7(1) 0(11) 0.1729(3) -1.1918(4) 0.47864(6) 8.3(1) 0(12) 0.0615(3) -0.7279(4) 0.57724(6) 8.3(1) C( l ) 0.7712(4) -0.7273(6) 0.5818(1) 5.6(2) C(2) 0.7887(3) -0.6793(5) 0.60849(8) 5.0(1) C(3) 0.7381(3) -0.7526(5) 0.62702(9) 6.0(1) C(4) 0.7568(3) -0.7123(5) 0.65221(9) 5.8(1) C(5) 0.8248(3) -0.5984(5) 0.65924(8) 4-7(1) C(6) 0.8745(3) -0.5250(5) 0.64034(9) 5.7(1) C(7) 0.8570(4) -0.5651(5) 0.61523(9) 5.9(1) C(8) 0.8475(4) -0.5539(5) 0.68623(9) 5.2(1) C(9) 0.7812(4) -0.6189(6) 0.70599(9) 8.2(2) C(10) 0.8221(4) -0.6088(6) 0.73342(9) 5.7(1) C ( l l ) 0.7801(4) -0.5077(6) 0.7496(1) 5-9(1) C(12) 0.8100(4) -0.5141(6) 0.7751(1) 6.0(1) C(13) 0.8828(4) -0.6151(6) 325 0.78545(9) 5.7(1) Chapter 7 Experimental/Crystallography C(14) 0.9273(3) -0.7091(5) 0.7690(1) 5.7(1) C(15) 0.8979(4) -0.7080(5) 0.7433(1) 5.5(1) C(16) 0.9516(4) -0.8172(6) 0.7271(1) 9.3(2) C(17) 0.7044(4) -0.3904(7) 0.7396(1) 11.0(2) C(18) 0.9117(4) -0.6198(6) 0.81355(9) 9.0(2) C(19) 0.5873(4) -0.5292(6) 0.53709(9) 5.8(2) C(20) 0.5862(3) -0.4466(5) 0.56136(9) 5.0(1) C(21) 0.5387(4) -0.5054(5) 0.5816(1) 6.2(1) C(22) 0.5390(4) -0.4308(6) 0.60431(9) 6.3(2) C(23) 0.5832(3) -0.2939(5) 0.60677(8) 4.6(1) C(24) 0.6284(3) -0.2337(5) 0.58612(9) 5.5(1) C(25) 0.6318(3) -0.3097(6) 0.56375(8) 5.9(1) C(26) 0.5830(3) -0.2067(6) 0.63049(9) 5.2(1) C(27) 0.5847(4) -0.2868(5) 0.65548(9) 6.5(1) C(28) 0.5827(4) -0.1901(5) 0.67845(8) 5.2(1) C(29) 0.4891(4) -0.1685(5) 0.69093(9) 5.7(1) C(30) 0.4906(4) -0.0751(6) 0.7114(1) 6.4(2) C(31) 0.5806(5) -0.0008(6) 0.72028(9) 6.4(2) C(32) 0.6722(4) -0.0250(6) 0.7081(1) 6.3(2) C(33) 0.6750(4) -0.1170(5) 0.68769(9) 5.8(1) C(34) 0.7796(4) -0.1333(6) 0.6756(1) 8.6(2) C(35) 0.3870(4) -0.2442(6) 0.6819(1) 8.9(2) C(36) 0.5778(4) 0.1074(7) 0.7421(1) 9.9(2) C(37) 0.3993(4) -0.2417(6) 0.52338(9) 5.5(1) C(38) 0.3896(4) -0.1465(5) 0.54565(8) 5.0(1) C(39) 0.3269(4) -0.1854(5) 0.5646(1) 6.8(2) C(40) 0.3169(4) -0.0970(6) 0.58512(9) 6.6(2) C(41) 0.3683(3) 0.0348(5) 0.58734(8) 4.9(1) C(42) 0.4311(4) 0.0737(5) 0.5681(1) 6.5(1) C(43) 0.4414(4) -0.0157(6) 0.54774(9) 6.5(2) C(44) 0.3567(3) 0.1384(6) 0.60887(9) 5.6(1) C(45) 0.3293(4) 0.0767(5) 0.63404(8) 6.2(1) C(46) 0.2944(4) 0.1843(5) 0.65332(8) 5.1(1) C(47) 0.1869(4) 0.2144(5) 0.65478(8) 5.3(1) C(48) 0.1556(3) 0.3059(6) 0.6739(1) 5.9(1) C(49) 0.2280(4) 0.3684(5) 0.6912(1) 6.0(1) C(50) 0.3352(4) 0.3408(5) 0.68906(9) 6.0(1) C(51) 0.3691(4) 0.2532(5) 0.67025(9) 5.4(1) C(52) 0.4876(4) 0.2354(5) 0.66790(9) 7.7(2) C(53) 0.1013(4) 0.1508(6) 0.63613(9) 8.1(2) C(54) 0.1919(4) 0.4618(6) 0.7125(1) 9.3(2) C(55) 0.2162(4) -1.0691(6) 0.4806(1) 6.2(2) C(56) 0.1956(4) -0.9729(6) 0.50200(8) 5.7(1) C(57) 0.1240(4) -1.0124(5) 0.5193(1) 7.0(2) C(58) 0.1032(4) -0.9199(6) 0.53878(9) 7.0(2) C(59) 0.1526(4) -0.7871(5) 0.54135(8) 5.3(1) C(60) 0.2271(4) -0.7510(5) 0.52443(9) 6.9(2) C(61) 0.2480(4) -0.8429(6) 0.50487(9) 7.2(2) C(62) 0.1236(4) -0.6883(6) 0.56243(9) 6.1(2) C(63) 0.1742(4) -0.5386(5) 0.56485(9) 6.9(2) C(64) 0.1039(4) -0.4237(5) 0.5756(1) 5-5(1) C(65) 0.1217(4) -0.3775(5) 0.60061(9) 5.4(1) C(66) 0.0571(4) -0.2682(6) 0.60920(9) 6.1(2) C(67) -0.0243(4) -0.2053(6) 0.5941(1) 7.0(2) 326 Chapter 7 Experimental/Crystallography C(68) C(69) C(70) C(71) C(72) -0.0407(4) 0.0209(5) 0.2090(4) -0.0030(5) -0.0923(4) -0.2548(6) -0.3635(6) -0.4389(5) -0.4143(6) -0.0857(7) 0.5696(1) 0.5601(1) 0.61869(9) 0.5329(1) 0.6038(1) 7.5(2) 6.6(2) 7.8(2) 10.2(2) 11.8(2) 7.102. Bond lengths (A) of XVIg with estimated standard deviations. atom atom distance atom atom distance 0(1) C( l ) 1.267(5) C(56) C(57) 1.383(6) 0(2) C( l ) 1.260(5) C(56) C(61) 1.369(6) 0(3) C(8) 1.206(4) C(57) C(58) 1.375(6) 0(4) C(19) 1.272(5) C(58) C(59) 1.374(6) 0(5) C(19) 1.251(5) C(59) C(60) 1.385(5) 0(6) C(26) 1.216(5) C(59) C(62) 1.504(6) 0(7) C(37) 1.269(5) C(60) C(61) 1.377(6) 0(8) C(37) 1.260(5) C(62) C(63) 1.519(6) 0(9) C(44) 1.212(5) C(12) C(13) 1.386(6) 0(10) C(55) 1.266(5) C(13) C(14) 1.374(6) 0(11) C(55) 1.255(5) C(13) C(18) 1.502(6) 0(12) C(62) 1.205(5) C(14) C(15) 1.379(5) C( l ) C(2) 1.480(6) C(15) C(16) 1.513(6) C(2) C(3) 1.384(5) C(19) C(20) 1.492(6) C(2) C(7) 1.387(5) C(20) C(21) 1.378(5) C(3) C(4) 1.384(5) C(20) C(25) 1.386(5) C(4) C(5) 1.386(5) C(21) C(22) 1.380(5) C(5) C(6) 1.393(5) C(22) C(23) 1.380(5) C(5) C(8) 1.490(5) C(23) C(24) 1.385(5) C(6) C(7) 1.378(5) C(23) C(26) 1.488(5) C(8) C(9) 1.509(6) C(24) C(25) 1.377(5) C(9) C(10) 1.503(6) C(26) C(27) 1.511(5) C(10) C ( l l ) 1.394(6) C(27) C(28) 1.506(5) C(10) C(15) 1.393(6) C(28) C(29) 1.409(5) C ( l l ) C(12) 1.376(6) C(28) C(33) 1.398(6) C ( l l ) C(17) 1.507(6) C(29) C(30) 1.381(6) C(38) C(43) 1.370(6) C(29) C(35) 1.507(6) C(39) C(40) 1.369(6) C(30) C(31) 1.373(6) C(40) C(41) 1.375(5) C(31) C(32) 1.382(6) C(41) C(42) 1.382(5) C(31) C(36) 1.527(6) C(41) C(44) 1.500(6) C(32) C(33) 1.374(6) C(42) C(43) 1.369(6) C(33) C(34) 1.515(6) C(44) C(45) 1.510(6) C(37) C(38) 1.479(6) C(45) C(46) 1.510(5) C(38) C(39) 1.370(5) C(46) C(47) 1.390(5) C(63) C(64) 1.516(6) C(46) C(51) 1.398(5) C(64) C(65) 1.392(6) C(47) C(48) 1.393(6) C(64) C(69) 1.391(6) C(47) C(53) 1.519(6) C(65) C(66) 1.392(6) C(48) C(49) 1.367(6) C(65) C(70) 1.509(6) C(49) C(50) 1.387(6) C(66) C(67) 1.376(6) C(49) C(54) 1.516(6) C(67) C(68) 1.372(6) C(50) C(51) 1.373(5) C(67) C(72) 1.508(7) 327 Chapter 7 Experimental/Crystallography C(51) C(52) 1.515(6) C(68) C(69) 1.385(6) C(55) C(56) 1.476(6) C(69) C(71) 1.521(6) Table 7.103. Bond angles (°) of X V I g with estimated standard deviations. atom atom atom angle atom atom atom angle 0(1) C( l ) 0(2) 123.0(4) 0(7) C(37) 0(8) 123.0(4) 0(1) C ( l ) C(2) 119.5(4) 0(7) C(37) C(38) 117.3(4) 0(2) C( l ) C(2) 117.3(4) 0(8) C(37) C(38) 119.6(4) C( l ) C(2) C(3) 119.1(4) C(37) C(38) C(39) 120.9(4) C( l ) C(2) C(7) 120.9(4) C(37) C(38) C(43) 121.0(4) C(3) C(2) C(7) 119.8(4) C(39) C(38) C(43) 117.9(4) C(2) C(3) C(4) 119.7(4) C(38) C(39) C(40) 121.1(4) C(3) C(4) C(5) 121.0(4) C(39) C(40) C(41) 121.3(4) C(4) C(5) C(6) 118.4(4) C(40) C(41) C(42) 117.2(4) C(4) C(5) C(8) 122.1(4) C(40) C(41) C(44) 123.5(4) C(6) C(5) C(8) 119.3(4) C(42) C(41) C(44) 119.2(4) C(5) C(6) C(7) 120.8(4) C(41) C(42) C(43) 121.1(4) C(2) C(7) C(6) 119.9(4) C(38) C(43) C(42) 121.1(4) 0(3) C(8) C(5) 121.2(4) 0(9) C(44) C(41) 120.4(4) 0(3) C(8) C(9) 120.1(4) 0(9) C(44) C(45) 121.3(4) C(5) C(8) C(9) 118.5(4) C(41) C(44) C(45) 118.1(4) C(8) C(9) C(10) 118.4(4) C(44) C(45) C(46) 116.4(3) C(9) C(10) C ( l l ) 120.8(5) C(45) C(46) C(47) 120.2(4) C(9) C(10) C(15) 119.7(5) C(45) C(46) C(51) 120.8(4) C ( l l ) C(10) C(15) 119.2(4) C(47) C(46) C(51) 118.9(4) C(10) C ( l l ) C(12) 118.9(4) C(46) C(47) C(48) 119.4(4) C(10) C ( l l ) C(17) 121.6(5) C(46) C(47) C(53) 122.1(4) C(12) C ( l l ) C(17) 119.4(5) C(48) C(47) C(53) 118.4(4) C(l l) C(12) C(13) 122.4(4) C(47) C(48) C(49) 121.8(4) C(12) C(13) C(14) 117.5(4) C(48) C(49) C(50) 118.0(4) C(12) C(13) C(18) 120.6(5) C(48) C(49) C(54) 120.9(4) C(14) C(13) C(18) 121.7(5) C(50) C(49) C(54) 120.9(5) C(13) C(14) C(15) 121.6(4) C(49) C(50) C(51) 121.6(4) C(10) C(15) C(14) 119.8(4) C(46) C(51) C(50) 119.8(4) C(10) C(15) C(16) 123.0(5) C(46) C(51) C(52) 121.0(4) C(14) C(15) C(16) 117.0(5) C(50) C(51) C(52) 119.0(4) 0(4) C(19) 0(5) 123.1(4) 0(10) C(55) 0(11) 122.6(5) 0(4) C(19) C(20) 118.5(4) 0(10) C(55) C(56) 117.3(5) 0(5) C(19) C(20) 118.3(4) 0(11) C(55) C(56) 119.9(5) C(19) C(20) C(21) 120.1(4) C(55) C(56) C(57) 120.8(5) C(19) C(20) C(25) 120.6(4) C(55) C(56) C(61) 119.7(5) C(21) C(20) C(25) 119.2(4) C(57) C(56) C(61) 119.3(4) C(20) C(21) C(22) 120.5(4) C(56) C(57) C(58) 120.2(4) C(21) C(22) C(23) 120.6(4) C(57) C(58) C(59) 120.8(4) C(22) C(23) C(24) 118.5(4) C(58) C(59) C(60) 118.2(4) C(22) C(23) C(26) 122.9(4) C(58) C(59) C(62) 118.4(4) C(24) C(23) C(26) 118.4(4) C(60) C(59) C(62) 123.2(4) C(23) C(24) C(25) 120.9(4) C(59) C(60) C(61) 121.0(4) C(20) C(25) C(24) 119.9(4) C(56) C(61) C(60) 120.0(4) 0(6) C(26) C(23) 120.4(4) 0(12) C(62) C(59) 120.3(4) 328 Chapter 7 Experimental/Crystallography 0(6) C(26) C(27) 121.3(4) 0(12) C(62) C(63) 120.5(4) C(23) C(26) C(27) 118.1(4) C(59) C(62) C(63) 119.0(4) C(26) C(27) C(28) 114.5(3) C(62) C(63) C(64) 114.2(4) C(27) C(28) C(29) 121.8(4) C(63) C(64) C(65) 120.8(5) C(27) C(28) C(33) 120.0(4) C(63) C(64) C(69) 119.4(5) C(29) C(28) C(33) 118.1(4) C(65) C(64) C(69) 119.6(4) C(28) C(29) C(30) 119.6(4) C(64) C(65) C(66) 118.4(4) C(28) C(29) C(35) 120.7(4) C(64) C(65) C(70) 122.9(4) C(30) C(29) C(35) 119.6(4) C(66) C(65) C(70) 118.6(4) C(29) C(30) C(31) 122.5(4) C(65) C(66) C(67) 122.9(4) C(30) C(31) C(32) 117.2(4) C(66) C(67) C(68) 117.2(5) C(30) C(31) C(36) 121.0(5) C(66) C(67) C(72) 121.8(5) C(32) C(31) C(36) 121.6(5) C(68) C(67) C(72) 120.9(6) C(31) C(32) C(33) 122.5(4) C(67) C(68) C(69) 122.3(5) C(28) C(33) C(32) 119.9(4) C(64) C(69) C(68) 119.3(5) C(28) C(33) C(34) 122.0(4) C(64) C(69) C(71) 121.2(5) C(32) C(33) C(34) 117.9(5) C(68) C(69) C(71) 119.4(6) 7.2.31. 4-[2-(2,4,6-Trimethyl-phenyl)acetyl]benzoic acid QS,2fl)-(+)-norephedrine salt (S3) A crystal of approximate dimensions of 0.35 x 0.10 x 0.05 mm size was chosen for data collection. Crystallographic data of S3 appear in Table 7.104. A monoclinic cell with Z = 4 (the calculated density was 1.19 gcm"3) was indicated by preliminary measurements. Of the 2841 reflections collected, 2747 were unique and 1996 observed (> 3o(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 23 carefully centred reflections in the range 50.87 < 26 < 83.89°. The data for S3 were processed,3 and corrected for Lorentz and polarization effects. No absoprtion correction was necessary. The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. 329 Chapter 7 Experimental/Crystallography The space group was assigned as C2 based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. Hydrogen atoms involved in hydrogen bonding were found from a Fourier difference map and refined isotropically. Hydrogen atoms on the methyl carbons were found from a Fourier difference map and o fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. The o remaining hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. A secondary extinction correction was applied (final coefficient = 2.23 x 10~6). Neutral atom scattering factors for all atoms and anomalous dispersion corrections" for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.045, Rw = 0.052 for 305 variables (GOF = 2.76; including zeros: R = 0.079, Rw = 0.054), with the largest parameter shift in the final cycle being 0.00a. The final difference map showed electron density between -0.17 and 0.15 e A 3 . Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.105 -7.107, respectively. Table 7.104. Crystallographic data for S3, S4, and S5. S3 S4 S5 Formula fw Colour, habit Crystal size, mm C 2 7 H 3 , N 0 4 433.55 C27H 3 1N0 3 417.55 C 2 7 H 3 1 N 0 3 417.55 colourless, prism colourless, plate colourless, prism 0.35 x 0.10x0.05 0.65 x 0.30x0.10 0.50 x 0.25 x 0.25 330 Chapter 7 Experimental/Crystallography Crystal system monoclinic monoclinic triclinic Space group C2 P2, PI a, A 17.732(5) 7.182(1) 10.519(3) b,A 5.612(2) 6.048(1) 13.927(5) c, A 25.720(4) 27.779(2) 9.501(3) a(° ) 90 90 99.57(3) PO 109.18(2) 97.094(9) 114.97(2) YO 90 90 101.68(3) v,A3 2417(1) 1197.4(2) 1184.9(8) z 4 2 2 Dcalc, g/cm3 1.19 1.16 1.17 F(000) 928 448 448 Radiation Cu- K a Cu- K a Cu- K a u,, mm"1 0.636 0.591 0.597 Transmission factors n/a 0.79-1.00 0.70-1.00 Scan type C O -20 co - 20 c o - 2 0 Scan range, 0 in co 0.94 + 0.20 tan0 1.10 + 0.20 tanO 1.21 +0.20 tan0 Scan speed, 7min 16.0 32.0 32.0 Data collected +h, +k, ±1 +h, +k, ±1 +h, ±k, ±1 20max, ° 155 155 155 Crystal decay, % -0.07 0.58 -1.28 Data collection temperature (K) 293 293 293 Total reflections 2841 2911 5103 Total unique reflections 2747 2707 4837 ^merge 0.04 0.04 0.04 No. of reflections with I > 3o(I) 1996 1973 3919 No. of variables 305 292 571 p-factor 0.011 0.009 0.03 R 0.045 0.044 0.062 Rw 0.052 0.049 0.083 Goodness of fit (GOF) 2.76 2.88 3.44 Max A/a (final cycle) 0.00 0.00 0.01 Residual density e/A3 -0.17,0.15 -0.14, 0.14 -0.18,0.20 Table 7.105. Final atomic coordinates (fractional) and B(eq) (A 2) of S3. atom x y z B(eq) 0(1) 0.0751(2) 0.5169 -0.0443(1) 5.18(7) 0(2) 0.1688(1) 0.2385(7) -0.02799(9) 4.10(6) 0(3) -0.0072(2) -0.2025(9) -0.2928(1) 9.0(1) 0(4) 0.1983(2) 0.3125(7) 0.0816(1) 4.89(7) N( l ) 0.1746(2) -0.1808(9) 0.0315(1) 3.69(7) C( l ) 0.1065(2) 0.3440(9) -0.0592(1) 3.54(8) C(2) 0.0713(2) 0.2524(9) -0.1168(1) 3.31(7) C(3) 0.0977(2) 0.0439(9) -0.1331(1) 4.00(8) C(4) 0.0651(2) -0.0377(9) -0.1866(1) 4.51(9) C(5) 0.0060(2) 0.090(1) -0.2250(1) 4.19(9) 331 Chapter 7 Experimental/Crystallography C(6) -0.0202(2) 0.302(1) -0.2089(1) 4.82(9) C(7) 0.0120(2) 0.3812(9) -0.1550(1) 4.24(8) C(8) -0.0266(3) -0.008(1) -0.2818(2) 5.5(1) C(9) -0.0877(3) 0.140(1) -0.3253(1) 5.5(1) C(10) -0.1076(2) 0.039(1) -0.3828(1) 4.8(1) C ( l l ) -0.1617(3) -0.145(1) -0.4001(2) 5.4(1) C(12) -0.1770(3) -0.245(1) -0.4518(2) 6.2(1) C(13) -0.1398(3) -0.159(1) -0.4876(2) 6.0(1) C(14) -0.0875(3) 0.027(1) -0.4704(2) 6.4(1) C(15) -0.0696(2) 0.131(1) -0.4183(2) 5.6(1) C(16) -0.0090(3) 0.330(2) -0.4020(2) 8.8(2) C(17) -0.2044(3) -0.254(1) -0.3628(2) 7.8(2) C(18) -0.1547(3) -0.274(1) -0.5435(2) 8.6(2) C(19) 0.2985(3) -0.026(1) 0.2059(2) 5.3(1) C(20) 0.3221(3) 0.009(1) 0.2620(2) 7.1(1) C(21) 0.2956(4) 0.199(1) 0.2829(2) 7.5(2) C(22) 0.2446(3) 0.361(1) 0.2477(2) 7.1(2) C(23) 0.2204(3) 0.323(1) 0.1913(2) 5.1(1) C(24) 0.2480(2) 0.1323(9) 0.1697(1) 3.60(8) C(25) 0.2286(2) 0.0971(9) 0.1085(1) 3.42(7) C(26) 0.1720(2) -0.1122(9) 0.0872(1) 3.44(8) C(27) 0.0870(2) -0.065(1) 0.0838(2) 6.0(1) Table 7.106. Bond lengths (A) of S3 with estimated standard deviations. atom atom distance atom atom distance 0(1) C( l ) 1.240(5) C(10) C ( l l ) 1.383(7) 0(2) C( l ) 1.277(4) C(22) C(23) 1.387(5) 0(3) C(8) 1.208(6) C(23) C(24) 1.370(6) 0(4) C(25) 1.409(5) C(24) C(25) 1.510(4) 0(4) H( l ) 0.89(6) C(25) C(26) 1.525(5) N( l ) C(26) 1.499(4) C(26) C(27) 1.504(5) N( l ) H(1A) 1.10(5) C(10) C(15) 1.398(6) N( l ) H(1B) 0.97(4) C ( l l ) C(12) 1.384(6) N( l ) H(1C) 0.86(5) C ( l l ) C(17) 1.531(6) C( l ) C(2) 1.497(4) C(12) C(13) 1.384(6) C(2) C(3) 1.377(5) C(13) C(14) 1.371(8) C(2) C(7) 1.384(5) C(13) C(18) 1.519(6) C(3) C(4) 1.382(5) C(14) C(15) 1.399(6) C(4) C(5) 1.380(5) C(15) C(16) 1.510(8) C(5) C(6) 1.389(6) C(19) C(20) 1.378(6) C(5) C(8) 1.488(5) C(19) C(24) 1.383(5) C(6) C(7) 1.388(5) C(20) C(21) 1.347(8) C(8) C(9) 1.523(6) C(21) C(22) 1.386(8) C(9) C(l6) 1.513(5) 332 Chapter 7 Experimental/Crystallography Table 7.107. Bond angles (°) of S3 with estimated standard deviations. atom atom atom angle atom atom atom angle O(l) C( l ) 0(2) 123.6(3) C ( l l ) C(12) C(13) 120.9(5) O(l) C( l ) C(2) 119.3(3) C(12) C(13) C(14) 118.1(4) 0(2) C( l ) C(2) 117.1(3) C(12) C(13) C(18) 120.7(5) C( l ) C(2) C(3) 121.4(3) C(14) C(13) C(18) 121.2(5) C( l ) C(2) C(7) 119.8(3) C(13) C(14) C(15) 122.8(4) C(3) C(2) C(7) 118.8(3) C(10) C(15) C(14) 117.8(5) C(2) C(3) C(4) 120.8(3) C(10) C(15) C(16) 122.8(4) C(3) C(4) C(5) 120.8(4) C(14) C(15) C(16) 119.3(4) C(4) C(5) C(6) 118.6(3) C(20) C(19) C(24) 121.2(5) C(4) C(5) C(8) 118.2(4) C(19) C(20) C(21) 120.4(5) C(6) C(5) C(8) 123.2(4) C(20) C(21) C(22) 119.8(4) C(5) C(6) C(7) 120.4(4) C(21) C(22) C(23) 119.6(5) C(2) C(7) C(6) 120.6(4) C(22) C(23) C(24) 120.9(4) 0(3) C(8) C(5) 120.9(4) C(19) C(24) C(23) 118.1(3) 0(3) C(8) C(9) 120.7(4) C(19) C(24) C(25) 119.5(3) C(5) C(8) C(9) 118.3(4) C(23) C(24) C(25) 122.3(4) C(8) C(9) C(10) 113.2(4) 0(4) C(25) C(24) 108.6(3) C(9) C(10) C( l l ) 120.7(4) 0(4) C(25) C(26) 112.6(3) C(9) C(10) C(15) 119.5(4) C(24) C(25) C(26) 111.9(3) C ( l l ) C(10) C(15) 119.8(4) N( l ) C(26) C(25) 108.5(3) C(10) C ( l l ) C(12) 120.5(4) N( l ) C(26) C(27) 109.5(3) C(10) C ( l l ) C(17) 122.1(4) C(25) C(26) C(27) 114.5(3) C(12) C ( l l ) C(17) 117.3(5) 7.2.32. 4-[2-(2,4,6-Trimethylphenyl)acetyl]benzoic acid (/?)-(+)-a,4-dimethyl-benzylamine salt (S4) A crystal of approximate dimensions of 0.65 x 0.30 x 0.10 mm size was chosen for data collection. Crystallographic data of S4 appear in Table 7.104. A monoclinic cell with Z = 2 (the calculated density was 1.16 gcnr^) was indicated by preliminary measurements. Of the 2911 reflections collected, 2707 were unique and 1973 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 24 carefully centred reflections in the range 77.38 333 Chapter 7 Experimental/Crystallography < 20 < 87.88°. The data for S4 were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.79 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as P2i based on E-statistics, systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. Hydrogen atoms involved in hydrogen bonding were found from a Fourier difference map and refined isotropically. Hydrogen atoms on the methyl carbons were found from a Fourier difference map and o fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. The remaining hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. A secondary extinction correction was applied (final coefficient = 1.39 x 10~5). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.12'13 The refinement converged at R = 0.044, Rw = 0.049 for 292 variables (GOF = 2.88; including zeros: R = 0.078, Rw = 0.053), with the largest parameter shift in the final cycle being O.OOo. The final difference map showed electron density between -0.14 and 0.14 eA"3. Final atomic coordinates and equivalent 334 Chapter 7 Experimental/Crystallography isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.108 -7.110, respectively. Table 7.108. Final atomic coordinates (fractional) and B(eq) (A2) of S4. atom X y z B(eq) 0(1) 0.7922(4) 0.5120 0.91965(8) 5.61(6) 0(2) 0.8800(4) 0.1749(6) 0.94234(8) 6.36(7) 0(3) 0.5570(6) -0.2028(8) 0.7107(1) 10.1(1) N( l ) 0.0704(4) 0.7789(7) 0.9605(1) 4.49(7) C( l ) 0.8136(4) 0.3116(7) 0.9110(1) 4.37(8) C(2) 0.7532(4) 0.2309(7) 0.8606(1) 3.85(7) C(3) 0.7709(4) 0.3683(7) 0.8215(1) 4.57(8) C(4) 0.7221(5) 0.2950(8) 0.7744(1) 5.07(8) C(5) 0.6545(4) 0.0823(7) 0.7657(1) 4.59(8) C(6) 0.6332(4) -0.0540(7) 0.8047(1) 4.52(8) C(7) 0.6855(4) 0.0177(8) 0.8516(1) 4.26(7) C(8) 0.6090(6) -0.012(1) 0.7160(1) 6.4(1) C(9) 0.6352(6) 0.129(1) 0.6718(1) 8.0(1) C(10) 0.5384(6) 0.034(1) 0.6256(1) 6.6(1) C ( l l ) 0.3635(7) 0.107(1) 0.6070(2) 8-1(1) C(12) 0.2698(7) 0.014(1) 0.5648(2) 9.1(2) C(13) 0.3450(7) -0.156(1) 0.5421(2) 8.4(1) C(14) 0.5200(7) -0.229(1) 0.5603(2) 8.6(1) C(15) 0.6166(6) -0.138(1) 0.6014(1) 7.7(1) C(16) 0.8096(8) -0.231(2) 0.6195(2) 12.1(2) C(17) 0.2685(9) 0.296(2) 0.6312(2) 13.1(2) C(18) 0.2379(8) -0.266(2) 0.4976(2) 12.9(2) C(19) 0.3901(6) 0.919(1) 0.9627(1) 8.7(1) C(20) 0.2580(5) 0.7372(8) 0.9440(1) 5.27(8) C(21) 0.2358(4) 0.7099(8) 0.8895(1) 4.89(8) C(22) 0.2941(5) 0.5170(9) 0.8695(2) 6.4(1) C(23) 0.2679(6) 0.487(1) 0.8198(2) 8.0(1) C(24) 0.1858(6) 0.647(1) 0.7893(1) 7.7(1) C(25) 0.1333(5) 0.841(1) 0.8094(1) 6.9(1) C(26) 0.1589(5) 0.8733(9) 0.8591(1) 5.43(9) C(27) 0.1536(7) 0.607(2) 0.7350(2) 13.6(2) .109. Bond lengths (A) of S4 with estimated standard deviations. atom atom distance atom atom distance 0(1) C( l ) 1.249(4) C ( l l ) C(12) 1.396(7) 0(2) C( l ) 1.251(4) C ( l l ) C(17) 1.528(9) 0(3) C(8) 1.215(6) C(12) C(13) 1.351(7) 335 Chapter 7 Experimental/Crystallography N(l) C(20) 1.497(4) C(13) C(14) 1.370(6) C( l ) C(2) 1.496(4) C(13) C(18) 1.526(6) C(2) C(3) 1.386(4) C(14) C(15) 1.376(6) C(2) C(7) 1.390(5) C(15) C(16) 1.523(7) C(3) C(4) 1.386(4) C(19) C(20) 1.502(6) C(4) C(5) 1.386(5) C(20) C(21)- 1.511(4) C(5) C(6) 1.385(4) C(21) C(22) 1.378(5) C(5) C(8) 1.492(5) C(21) C(26) 1.372(5) C(6) C(7) 1.381(4) C(22) C(23) 1.385(6) C(8) C(9) 1.524(6) C(23) C(24) 1.370(7) C(9) C(10) 1.498(5) C(24) C(25) 1.373(7) C(10) C ( l l ) 1.371(6) C(24) C(27) 1.516(5) C(10) C(15) 1.390(7) C(25) C(26) 1.383(5) Table 7.110. Bond angles (°) of S4 with estimated standard deviations. atom atom atom angle atom atom atom angle 0(1) C( l ) 0(2) 123.6(3) C(12) C ( l l ) C(17) 118.4(5) 0(1) C( l ) C(2) 117.9(3) C ( l l ) C(12) C(13) 121.2(5) 0(2) C( l ) C(2) 118.5(3) C(12) C(13) C(14) 118.3(5) C( l ) C(2) C(3) 119.6(3) C(12) C(13) C(18) 121.3(5) C( l ) C(2) C(7) 121.7(3) C(14) C(13) C(18) 120.4(6) C(3) C(2) C(7) 118.6(3) C(13) C(14) C(15) 121.5(5) C(2) C(3) C(4) 120.8(3) C(10) C(15) C(14) 120.5(4) C(3) C(4) C(5) 120.3(3) C(10) C(15) C(16) 121.4(4) C(4) C(5) C(6) 119.1(3) C(14) C(15) C(16) 118.1(5) C(4) C(5) C(8) 123.2(3) N( l ) C(20) C(19) 108.9(3) C(6) C(5) C(8) 117.6(3) N( l ) C(20) C(21) 109.7(2) C(5) C(6) C(7) 120.5(3) C(19) C(20) C(21) 114.3(3) C(2) C(7) C(6) 120.6(3) C(20) C(21) C(22) 119.7(3) 0(3) C(8) C(5) 120.3(4) C(20) C(21) C(26) 121.5(3) 0(3) C(8) C(9) 119.9(4) C(22) C(21) C(26) 118.8(3) C(5) C(8) C(9) 119.7(4) C(21) C(22) C(23) 120.2(4) C(8) C(9) C(10) 112.7(4) C(22) C(23) C(24) 121.3(5) C(9) C(10) C ( l l ) 120.4(5) C(23) C(24) C(25) 118.1(4) C(9) C(10) C(15) 121.9(4) C(23) C(24) C(27) 120.4(6) C ( l l ) C(10) C(15) 117.7(4) C(25) C(24) C(27) 121.6(6) C(10) C ( l l ) C(12) 120.7(5) C(24) C(25) C(26) 121.3(4) C(10) C ( l l ) C(17) 120.9(5) C(21) C(26) C(25) 120.3(4) 336 Chapter 7 Experimental/Crystallography 7.2.33. 4-[2-(2,4,6-Trimethylphenyl)acetyl]benzoic acid (R)-(+)-N,a-dimethylbenzylamine salt (S5) A crystal of approximate dimensions of 0.50 x 0.25 x 0.25 mm size was chosen for data collection. Crystallographic data of S5 appear in Table 7.104. A triclinic cell with Z = 2 (the calculated density was 1.17 gcnr^) was indicated by preliminary measurements. Of the 5103 reflections collected, 4837 were unique and 3919 observed (> 3a(I)). The final unit-cell parameters were obtained by least-squares refinement on the setting angles for 24 carefully centred reflections in the range 97.28 < 20 < 104.74°. The data for S5 were processed,3 and corrected for Lorentz and polarization effects. An absorption correction (empirical, based on azimuthal scans for three reflections) was applied (transmission factors: 0.70 to 1.00). The intensities of three standard reflections measured every 200 reflections throughout the data collection showed no decay. The space group was assigned as PI based on E-statistics, no systematic absences, and subsequent successful structure solution. The structure was solved by direct methods (SIR97)7 and expanded using Fourier techniques.10 The non-hydrogen atoms were determined from E-maps or from subsequent difference Fourier syntheses and were refined with anisotropic thermal parameters. Hydrogen atoms involved in hydrogen bonding were found from a Fourier difference map and refined isotropically. Hydrogen atoms on the methyl carbons were found from a Fourier difference map and fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. The 337 Chapter 7 Experimental/Crystallography remaining hydrogen atoms were fixed in idealized positions with C - H = 0.98 A and B H = 1.2 Bbonded atom. There are four molecules in the asymmetric unit, with the two achiral carboxylic acid moieties related to one another by a false centre of symmetry (pseudosymmetry). A secondary extinction correction was applied (final coefficient = 1.04 x 10-5). Neutral atom scattering factors for all atoms and anomalous dispersion corrections11 for the non-hydrogen atoms were taken from the International Tables for X-ray Crystallography.1 2 , 1 3 The refinement converged at R = 0.062, Rw = 0.083 for 571 variables (GOF = 3.44; including zeros: R = 0.084, Rw = 0.085), with the largest parameter shift in the final cycle being 0.01a. The final difference map showed electron density between -0.18 and 0.20 eA"3. Final atomic coordinates and equivalent isotropic thermal parameters, bond lengths, and bond angles appear in Tables 7.111 -7.113, respectively. Table 7.111. Final atomic coordinates (fractional) and B(eq) (A 2) of S5. atom X y z B(eq) 0(1) 0.1475 -0.5025 0.9258 5.3(1) 0(2) -0.0677(6) -0.4720(5) 0.8522(7) 6.1(1) 0(3) 0.1712(7) -0.0684(4) 0.5892(7) 5-9(1) 0(4) 0.0502(6) 0.1818(4) 0.0310(7) 5-9(1) 0(5) -0.1641(5) 0.2148(3) -0.0413(5) 5-4(1) 0(6) -0.1937(6) -0.2190(4) 0.2960(7) 6.0(1) N( l ) -0.1732(6) 0.4121(5) -0.0054(7) 4.4(1) N(2) 0.0909(7) 0.2885(5) 0.8405(7) 4.5(1) C( l ) 0.0589(8) -0.4562(5) 0.8648(8) 4.6(1) C(2) 0.1080(7) -0.3696(5) 0.8025(8) 4.1(1) C(3) 0.0106(7) -0.3187(5) 0.7230(8) 4.4(1) C(4) 0.0525(7) -0.2433(6) 0.6620(9) 4.9(1) C(5) 0.1944(7) -0.2149(5) 0.6790(8) 4.2(1) C(6) 0.2930(7) -0.2634(5) 0.7607(9) 4.6(1) C(7) 0.2478(7) -0.3407(5) 0.8223(9) 4.8(1) C(8) 0.2360(8) -0.1319(5) 0.6102(8) 4.5(1) C(9) 0.3578(8) -0.1317(6) 0.566(1) 6.1(2) C(10) 0.3425(7) -0.0873(5) 0.4281(8) 4.4(1) 338 Chapter 7 Experimental/Crystallography C ( l l ) 0.4278(8) 0.0116(5) 0.4549(8) 4.7(1) C(12) 0.4134(8) 0.0482(5) 0.3234(9) 4.7(1) C(13) 0.3214(8) -0.0098(6) 0.1672(9) 5.0(1) C(14) 0.2339(8) -0.1065(6) 0.1434(8) 5-4(1) C(15) 0.2424(8) -0.1446(5) 0.2698(9) 4.7(1) C(16) 0.140(1) -0.2498(6) 0.230(1) 7.9(2) C(17) 0.533(1) 0.0811(7) 0.623(1) 7.7(2) C(18) 0.307(1) 0.0326(8) 0.025(1) 7.7(2) C(19) -0.0747(7) 0.1671(5) 0.0218(8) 4.0(1) C(20) -0.1234(7) 0.0829(5) 0.0855(8) 3.8(1) C(21) -0.0289(7) 0.0312(5) 0.1622(8) 4.7(1) C(22) -0.0725(7) -0.0473(5) 0.2215(8) 4.4(1) C(23) -