UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

The solution and solid state photochemistry of some substituted acetophenones Harkness, Brian Robert 1986

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata

Download

Media
831-UBC_1986_A6_7 H37.pdf [ 6.05MB ]
Metadata
JSON: 831-1.0060531.json
JSON-LD: 831-1.0060531-ld.json
RDF/XML (Pretty): 831-1.0060531-rdf.xml
RDF/JSON: 831-1.0060531-rdf.json
Turtle: 831-1.0060531-turtle.txt
N-Triples: 831-1.0060531-rdf-ntriples.txt
Original Record: 831-1.0060531-source.json
Full Text
831-1.0060531-fulltext.txt
Citation
831-1.0060531.ris

Full Text

THE SOLUTION AND SOLID STATE PHOTOCHEMISTRY OF SOME SUBSTITUTED ACETOPHENONES by BRIAN ROBERT HARKNESS c., (Hons), University of British Columbia, 1984 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE i n THE FACULTY OF GRADUATE STUDIES DEPARTMENT OF CHEMISTRY We accept this thesis as conforming to the requi red_standard They'll ni versity of British Columbia August, 1986 © Brian Robert Harkness, 1986 I n p r e s e n t i n g t h i s t h e s i s i n p a r t i a l f u l f i l m e n t o f t h e r e q u i r e m e n t s f o r an advanced degree a t t h e U n i v e r s i t y o f B r i t i s h C o l u m b i a , I agree t h a t t h e L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r r e f e r e n c e and s t u d y . I f u r t h e r agree t h a t p e r m i s s i o n f o r e x t e n s i v e c o p y i n g o f t h i s t h e s i s f o r s c h o l a r l y purposes may be g r a n t e d by t h e head o f my department o r by h i s o r h e r r e p r e s e n t a t i v e s . I t i s u n d e r s t o o d t h a t c o p y i n g o r p u b l i c a t i o n o f t h i s t h e s i s f o r f i n a n c i a l g a i n s h a l l n o t be a l l o w e d w i t h o u t my w r i t t e n p e r m i s s i o n . Department o f The U n i v e r s i t y o f B r i t i s h Columbia 1956 Main Mall Vancouver, Canada V6T 1Y3 Date A t / v ^ - f r r 3 ) ^ , i i ABSTRACT A series of a-methyl-a-cycloalkyl- and a-cycloalkyl-para-substituted acetophenones have been synthesized. These compounds were found to react photochemically in the solid state to give cycl ization and cleavage products as expected for a Norrish Type II reaction. It has been found that a-methyl substitution of a-cycloalkyl-para-carboxyacetophenones (cyclohexyl and cyclooctyl) results in changing the hydrogen abstraction transition state from boatlike to chair l ike. This result is based on the assumption that the abstraction geometry is similar to the geometry of the ground state ketone as determined by X-ray crystallography. The differences in the ratios of cycl ization to cleavage in the sol id state as compared to solution wer found to be no greater than 10% for most of the ketones studied. This suggests that formation of cycl izat ion and cleavage products are topochemically allowed in the solid state. Alternatively, the reaction may not be under topochemical control, however, the high melting points of the compounds studied tend to support the f i r s t poss ib i l i ty . a-Methylation of a-cyclopentyl-para-carboxyacetophenone decreased the percent cleavage from 100% to 45%. This result is l ikely due to a change in the geometry of the starting ketone which occurs upon a-methylat ion. Solid state photolysis of a-cycloalkyl-para-substituted acetophenones (cyclooctyl and cycloheptyl) results in almost exclusive formation of the trans-cyclobutanol. This result has been attributed to a restr ict ion of the motions required for cis-cyclobutanol formation in the solid state. i i i TABLE OF CONTENTS Page ABSTRACT ii TABLE OF CONTENTS i i i LIST OF FIGURES iv-ix LIST OF TABLES x,ix LIST OF ABBREVIATIONS xii ACKNOWLEDGEMENTS xiii INTRODUCTION 1 RESEARCH OBJECTIVES 35 DISCUSSION 41 Synthesis 41 Identification of Photoproducts 52 Geometry of Hydrogen Abstraction 74 Ratios of Cyclization to Cleavage 79 The Effect of Different Media on 99 the Cyclobutanol Ratios Quantum Yields and Rate Studies 106 EXPERIMENTAL 114 General 114 Synthesis of Starting Materials 116 Photochemical Studies 134 BIBLIOGRAPHY 161 APPENDIX 166 i v LIST OF FIGURES F igure T i t l e Page 1 I r r a d i a t i o n of 2-hexanone 1 2 Type I e l im i n a t i o n from simple ketones 2 3 Pho t o l y s i s of 2-pentanone 2 4 Formation of a 1,4 b i r a d i c a l 3 5 Formation of propene-2-ol from 2-pentanone 4 6 Photochemical e x c i t a t i o n of a carbonyl group 5 7 Phys i ca l d e s c r i p t i o n of an n , n e x c i t ed s ta te 6 8 Energy diagram fo r s i n g l e t and t r i p l e t 7 n , n e x c i t e d s t a t e s 9 T r a n s i t i o n s ta tes fo r hydrogen ab s t r a c t i o n 9 by an a lkoxy r ad i c a l and ketone t r i p l e t 10 Parameters d e f i n i ng s p a t i a l r e l a t i o n s h i p 11 of the "n " o r b i t a l to the abs t r a c t ab l e hydrogen atom 11 McLa f fe r ty rearrangement in s t e r o i d s 12 12 McLa f fe r ty rearrangements of ketones 13 13 Photoreac t ions of valerophenone 14 14 So lvent e f f e c t s on the behavior of 15 the 1,4 b i r a d i c a l of valerophenone 15 Photochemical racemiza t ion of (4S) - 17 (+)-4-methy l -1-phenyl hexanone 16 p -Orb i t a l geometries cons idered idea l 21 f o r c leavage 17 P ho t o l y s i s of 1-adamantyl acetone 22 18 Suggested conformat ion of the 1,4 23 b i r a d i c a l of a s imple a l k y l phenyl ketone V Figure T i t l e Page 19 Suggested geometry for cyclobutanol 24 formation 20 S tereose lect iv i ty of cyclobutanol 25 formation 21 Two d i f ferent conformers of a molecule 26 giving r i se to d i f ferent photoproducts 22 The photochemistry of a-methyl-cyclopentyl 28 phenyl ketone 23 The photochemistry of a-methyl-cyclohexyl 29 phenyl ketone 24 The photochemistry of ene-dione 1 32 25 p-hydrogen abstract ion geometry for 33 ene-diones 26 The photochemistry of a-cyclohexyl- 35 p-chloroacetophenone 27 The photochemistry of 7-tridecanone 37 28 a-Cycloalkyl-para-subst i tuted acetophenones 38 with avai lable y-hydrogen 29 Design of the a-methyl ketones 39 30 Design of the ketones lacking an 39 a-methyl substituent 31 Design of the ketones bearing 40 var iable para-substituents 32 Synthesis of cyclooctyl acet ic acid 41 33 Synthesis of cycloheptyl acet ic acid 42 34 Synthetic routes towards the synthesis 44 of a-and para-substituted-a-cycloalkyl acetophenones 35 Products of Fr iede l -Craf ts acylat ion of 45 subst ituted benzenes using cycloocty l acetyl chlor ide and aluminum t r i ch l o r i de as cata lys t vi Figure Tit l e Page 36 McLafferty rearrangement of 46 a-cyclooctyl-para-substituted acetophenones 37 The synthesis of a-cyclooctyl-para- 48 cyano and para-carboxyacetophenones 38 a-Cycloalkyl-para-cyanoacetophenone 49 derivatives and their melting points 39 a-Cycloalkyl-para-carboxyacetophenone 49 derivatives and their melting points 40 a-Cycloalkyl-para-carbomethoxy- 51 acetophenone derivatives and their melting points 41 Products from the photolysis of 53 a-cycloalkyl-para-chloroacetophenones 42 I.U.P.A.C. numbering scheme for 54 bicyclo [n.2.0] alkanols 43 The photolysis of some a-cyclooctyl- 55 para-substituted acetophenones 44 Experimental and literature melting 56 points of para-substituted acetophenones 45 Retro 2+2 fragmentation pattern observed 57 for [6.2.0] cyclobutanols 46 400 MHz XH nmr spectra of the cis- and 59 trans-cyclobutanols derived from a-cycloocty1-para-cyanoacetophenone 47 *H nmr spectrum of the cis-cyclobutanol 61 decoupled at 0.38 ppm 48 Photolysis of a-methyl-a-cyclooctyl-para- 64 carboxyacetophenone 49 l H nmr of the major cyclobutanol isolated 66 from photolysis of a-methyl-a-cyclooctyl-para-carboxyacetophenone vi i Figure T i t l e Page 50 LH N.O.E. difference spectra of the 67 cyclobutanol shown in f igure 49 51 LH nmr of the second cyclobutanol 68 i so lated from photolysis of a-methyl-a-cycl ooctyl-para-carboxyacetophenone 52 1H N.O.E. difference spectra of the 69 second cyclobutanol derived from a-methyl-a-cyclooctyl-para-carboxyacetophenone 53 l H nmr spectrum of the major cyclobutanol 71 derived from photolysis of a-methyl-a-cycl ohexyl -para-carboxyacetophenone 54 1H nmr spectrum of the major cyclobutanol 73 derived from a-methy 1 -a-cyc lopentyl-para-carboxyacetophenone 55 Boat l ike and cha i r l i ke abstract ion geometries 77 56 Stereodiagrams fo r boatl ike and cha i r l i ke 79 abstract ion geometries 57 Photoproducts derived from a-methyl-a- 80 cycl oalkyl -para- carboxyacetophe nones 58 % Cleavage from the photolysis of 81 a-methyl-a-cycloalkyl acetophenones in benzene, a ce ton i t r i l e , and the so l i d state 59 The photochemistry of ene-dione 1 in 82 benzene and the so l id state 60 % Cleavage from the photolysis of 83 a -cyc l oal kyl-pa ra-carboxy acetophenones in polar solvent, benzene and the so l i d state 61 % Cleavage vs para-substituent in various 84 media for the a-cyc loocty l acetophenones 62 % Cleavage in the so l i d state as compared ' 86 to the values of 91 and 02 f ° r several a -cyc l oalkyl -para-chloroacetophenones vi i i Figure T i t l e Page 63 Magnitude of the angle n as the cyc loa lky l 88 r ing size increases from 4 to 8 for the a-cycloalkyl-para-chloroacetophenones 64 Bond rotat ions required for the formation 89 of the trans-cyclobutanol 65 Calculated s t ra in energies for some 92 b icyc lo [n.2.0] alkanes 66 Photolysis of cyclobutyl phenyl ketone 93 67 % Cleavage recorded for non-methylated 95 and a-methyl-a-cyclopentyl phenyl ketones 68 The b i rad ica l generated from a-methyl- 96 a-cyclopentyl-para-carboxyacetophenone as viewed down the a-p carbon bond 69 Two conformers of the b i rad ica l generated 98 from a-cyclopentyl-para-carboxyacetophenone 70 The ra t io of trans- to c is-cyclobutanols 100 formed from the photolysis of a - cyc looc ty l -para-chloroacetophehone in d i f fe rent media 71 Geometries of the c i s - and trans-cyclobutanols 101 72 Packing diagram of a - cyc looc ty l - 102 para-chloroacetophenone 73 Percentage of the major cyclobutanol as a 104 function of the total cyclobutanol produced from photolysis of a-methyl-a-cyc loalky l-para-carboxyacetophenones in various media 74 X-ray crysta l structure of a-methyl-a- 106 cyclooctyl-para-carboxyacetophenone 75 Total product quantum y ie lds for 107 several substituted acetophenones in benzene 76 Y-Hydrogen and P-hydrogen abstract ion 109 distances and angles for a-methyl-a-cyclooctyl and a-methyl-a-cyclohexyl-para-carboxyacetophenones i x Figure T i t l e Page 77 Stern-Volmer plots for a -cyc loocty l -para- 111 cyanoacetophenone and a-cycloheptyl-para-cyanoacetophenone 78 Hydrogen abstract ion rate constants 113 for valerophenone and a r i g i d b i c yc l i c ketone X LIST OF TABLES Table T i t l e Page I The photochemistry of a-subst i tuted 18 valerophenones in benzene II The photochemistry of p-substituted 19 butyrophenones in benzene III The photochemistry of y -subst i tuted 20 butyrophenones in benzene IV Hydrogen abstract ion geometries for 75 several substituted acetophenones V The st ra in energies for some cycloalkanes 91 and the calculated s t ra in energies for some cycloalkenes VI Product rat ios from the photolysis of 138 ketone (9) VII Product rat ios from the photolysis of 140 ketone (20) VIII Product rat ios from the photolysis of 142 ketone (21) IX Product rat ios from the photolysis of 145 keto-acid (26) X Product rat ios from the photolysis of 146 keto-acid (27) XI Product rat ios from the photolysis of 149 keto-acid (28) XII Product rat ios from the photolysis of 151 keto-acid (29) XIII Product rat ios from the photolysis of 153 keto-acid (30) XIV Product rat ios from the photolysis of 155 keto-acid (31) XV Product rat ios from the photolysis of 155 keto-ester (32) xi T i t l e Product rat ios from the photolysis of keto-ester (33) Product rat ios from the photolysis of keto-ester (34) Product rat ios from the photolysis of keto-ester (35) Product ra t ios from the photolysis of keto-ester (36) Product ra t ios from the photolysis of keto-ester (37) Quantum y ie lds for ketones 20, 21, 33-37, in benzene Values of $ 0 /$ and quencher concentrations for ketones 20 and 21 xi i LIST OF ABBREVIATIONS Anal. micro analysis °C degrees celc ius cone. concent rat i on gc gas l i qu id chromatography 1 H nmr proton nuclear magnetic resonance i r infrared spectroscopy l i t . l i t e ra tu re m+ parent ion max maximum m/e mass/charge rat io mi n mi nute(s) mp melting point ms mass spectroscopy NOE Nuclear Overhauser Effect rt retention time s seconds uv u l t r av i o l e t spectroscopy 0 phenyl group abbreviations for mu l t i p l i c i t i e s of 1H nmr signals s s ing let d doublet t t r i p l e t q quartet dd doublet of doublets m mult ip let xi i i ACKNOWLEDGEMENTS I wish to express my sincere thanks to Professor John Scheffer f o r his excel lent guidance and helpful suggestions throughout the course of my research and the preparation of th is thes i s . I also thank Stephen Evans and Professor J . Trot ter , without whom th is work would not be possible. I thank Omkaram Nalamasu fo r al lowing me to quote some of his experimental resu l ts . I also wish to thank a l l of the members of Dr. Scheffer 's and Dr. Tro t te r ' s research group, past and present, who have made the last two years very enjoyable ones. F i na l l y , the assistance of the elemental analys is , nmr, and mass spectroscopy s taf f is appreciated. To rty Parents 1 INTRODUCTION One of the more s ign i f i can t events in photochemical h istory occurred during the early 1930's. At th is time, a group headed by R. Norrish i r rad iated a sample of 2-hexanone with u l t r av i o l e t l ight and unexpectedly obtained propene and acetone as products (f igure l ) 1 . Figure 1: I r rad ia t ion of 2-hexanone This pa r t i cu la r photochemical transformation has become known as the Norrish Type II reaction. P r i o r to the photolysis of 2-hexanone, by Norr ish, i t was known that i r r ad ia t i on of simpler ketones resulted in the extrusion of carbon monoxide and the formation of an alkane from the alkyl radicals (f igure 2) . The photochemical transformation result ing in homolysis of the bond between the carbonyl-carbon and an a-carbon atom 2 0 h v > CO + «CH, + RCH0« R Figure 2: Type I e l iminat ion from simple ketones has become known as the Norrish Type I react ion. Early studies of the Norrish Type II reaction found that simple a l i pha t i c ketones bearing y-hydrogen atoms formed a ketone and an o l e f i n as the products of u l t r a v i o l e t i r r ad i a t i on . The l i s t of products grew in 1958 when N.C. Yang discovered that i r r ad ia t i on of 2-pentanone resul ts in the formation of three products, these being acetone, an o le f i n and a cyclobutanol (f igure 3 ) 2 . As the resu l t of his studies of 2-pentanone, CH Figure 3: Photolysis of 2-pentanone 3 Yang proposed that the Norrish Type II process involved an i n i t i a l 1,5 hydrogen atom transfer resu l t ing in the formation of a 1,4 b i rad ica l ( f igure 4). This b i rad ica l could close to form a cyclobutanol or cleave Figure 4: Formation of a 1,4 b i rad ica l to form an o l e f i n and an enol . The enol could rapidly tautomerize to form the observed ketone. To ver i fy the hypothetical enol intermediate, J .N . P i t t s monitored the infrared spectra of concurrently photolyzed 2-pentanone gas 3 . Infrared analysis was able to detect propene-2-ol which slowly tautomerized to acetone (f igure 5) . Evidence for the involvement of a y-hydrogen was obtained when the photolysis of 2-hexanone-5-d 2 resulted in the formation of acetone-d^. Yang also noticed a large isotope ef fect on the rate of y-hydrogen abstract ion by the carbonyl Hi OH 4 tautermerize 0 + other products Figure 5: Formation of propene-2-ol from 2-pentanone oxygen atom5. With all of the prior data in mind, the definition of the Norrish Type II reaction was expanded to describe a process by which a ketone, containing an abstractable y-hydrogen atom, undergoes, upon electronic excitation, a 1,5 hydrogen transfer to yield both bond cleavage and cyclization products. The photochemical abstraction of a y-hydrogen atom is believed to transition involves the excitation of an electron from the doubly occupied n-orbital to the n -orbital. This transition can be achieved using ultraviolet radiation with a wavelength of 270-350 nm. It has been occur from the n,n excited state of the carbonyl group (figure 6) 6. This * 5 fx n 2 * y * ( o o r b i t a l ) Figure 6: Atomic orbital diagram for the excitation of a carbonyl group * postulated that the n,n excitation of carbonyl compounds produces an alkoxy radical-like excited state in which an electron deficiency on the oxygen atom induces diradical character on the carbonyl group (figure 7) 7> 8. 6 to* — ** 11 1 E ±± > JL_n R R R R i £ d l r a d l c a l Figure 7: Valence bond diagram for the n,n excited state * The n,n excited state diradical can exist in either of two mul t ip l i c i t ies . The radical electrons can have the same spin to produce the t r ip le t excited state or can have opposite spins to produce the singlet excited state. When an electron is excited from the n 2 orbital to * the n,n excited state i t wil l i n i t i a l l y exist in the singlet configuration. The singlet excited state can then undergo one of several possible transformations (figure 8 ) 6 . 7 c c K C . r c JC -M w T3 V M o w u Singlet 01 configuri _5 "St C - Singlet i E «J w. e £-f c I I ! i i c 4- { • i - i * J r-c o Z K V r-i l J£ ~ S 5 S o ' i i c .£ i i «• S 5 c o I 8 c t I o 9 5 w 5 u-"5c, "SI c > c c w c c c I e .£ c i t c t t c £ .£• * c I -C Mi C S t E Figure 8: Energy diagram for s ing let and t r i p l e t n,n excited s ta tes 6 1. The s ing let can intersystem cross to the t r i p l e t state. 2. The molecule can undergo a photochemical reaction from the s ing let s tate. 8 3. The excited s ing let can revert back to the ground state by e i ther a non-radiative decay t rans i t ion or by emitting l i gh t in the form of f luorescence. I f the s ing let does intersystem cross to the t r i p l e t excited state i t can undergo one of two possible transformations. 1. The molecule can undergo a photochemical reaction from the t r i p l e t state. 2. The excited t r i p l e t can revert back to the ground state by ei ther a non-radiative decay t rans i t ion or by emitt ing l i gh t in the form of phosphorescence. • It has been well establ ished that both s ing let and t r i p l e t n,n states of a l i pha t i c ketones can undergo Type II e l i m i n t a i o n 9 _ 1 2 » 1 3 . Cyclobutanol formation from a l iphat i c ketones occurs mostly from the t r i p l e t s t a t e 1 4 . Wagner studied the ef fects of piperylene (1,3 pentadiene) on the type II photoreactions of a l i phat i c ketones in s o l u t i o n 1 4 . Piperylene i s an e f f i c i en t quencher which accepts energy from t r i p l e t excited ketones 1 3 . The excited t r i p l e t ketones transfer the i r excited state energy to the diene and revert back to the ground state without forming products. Wagner found that the Stern-Volmer p lot (see appendix 1) of ®Q/$, where $ Q i s the quantum y i e l d in benzene and $ i s the quantum y i e l d in benzene at a par t i cu la r quencher concentration, against the concentration of piperylene was non-l inear for a l iphat i c ketones as even high concentrations of quencher f a i l ed to t o t a l l y quench the photoelimination react ion. The most obvious explanation for th is resu l t is that the el iminat ion reaction proceeds from both the s ing let and t r i p l e t excited states. 9 The behavior of aromatic ketones is s l i gh t l y d i f ferent from that of a l i pha t i c ketones in that intersystem crossing from the s inglet to the t r i p l e t state is 100% e f f i c i en t , and both e l iminat ion and cyc l i za t i on occur only from the t r i p l e t state 1 1*. Wagner found that at even high concentrations of quencher the Stern-Volmer plot is s t i l l l i n e a r 1 5 . The rapid rate of intersystem crossing fo r a lkyl phenyl ketones is ref lected in the lack of any observable s ing let state reac t i v i t y . * The geometry of hydrogen abstract ion by the t r i p l e t n,n excited state is of par t i cu la r importance in deciding whether a y-hydrogen atom can be abstracted by the electron def ic ient n-orbital of the carbonyl oxygen. Wagner has suggested that 1,5 hydrogen transfers in acyc l i c systems ref lect a tors ion f ree, cha i r l i k e , six-membered cyc l i c t r ans i t i on state (f igure 9 ) 1 7 . alkoxy r a d i c a l ketone t r i p l e t Figure 9: Trans i t ion states fo r hydrogen abstract ion by an alkoxy radical and ketone t r i p l e t 10 Hesse has shown that the C-H-0 angle must be cons ide rab l y l e s s than 180° f o r hydrogen t r a n s f e r s by a lkoxy r a d i c a l s 1 8 . S t r a i n present i n the cyc loheptane- and cyc l open tane -1 i ke t r a n s i t i o n s t a te s f o r 1,6 and 1,4 hydrogen t r a n s f e r s has been used as an exp lanat ion f o r the r a r i t y of 6 and 0 hydrogen ab s t r a c t i o n by the exc i t ed ketone. Th i s r e s u l t i s i n accordance w i th the we l l known order 1,5 > 1,6 » 1,4 i n the ra tes of i n t r amo l e cu l a r hydrogen t r a n s f e r s i n a c y c l i c s y s t e m s 1 8 * 1 9 . The involvement of a c h a i r l i k e a b s t r a c t i o n geometry i s however not an abso lu te requirement f o r v-hydrogen a b s t r a c t i o n . S che f f e r and T r o t t e r have r e cen t l y shown tha t 1,5 hydrogen t r a n s f e r s can a l so occur from a b o a t l i k e reac tan t geomet r y 2 0 . Furthermore, Sche f fe r and T r o t t e r have attempted to c o r r e l a t e the a b s t r a c t a b i l i t y of a v-hydrogen atom w i th the s p a t i a l r e l a t i o n s h i p of the carbony l "n" o r b i t a l to the v - h yd r ogen 2 1 . Three geometr ic parameters have been de f ined and these desc r i be the s pa t i a l r e l a t i o n s h i p of the "n " o r b i t a l to the hydrogen atom being abs t r a c t ed . They are de f ined as f o l l ows ( f i g u r e 10): •A , the d i s t ance between the ab s t r a c t i n g oxygen atom and the ab s t r a c t ab l e hydrogen atom; T_ , the angle de f ined by the o x ygen*hyd r ogen vec to r and i t s p r o j e c t i o n on the mean p lane of the carbonyl group which conta ins the oxygen n - o r b i t a l ) ; A_ , the angle between the carbonyl carbon, the carbonyl oxygen and ab s t r a c t ab l e hydrogen atom. 11 Figure 10: Parameters def ining spat ia l re lat ionship of the "n" orb i ta l to the abstractable hydrogen atom Scheffer and Trotter have suggested that the ideal geometry for hydrogen abstract ion occurs when -c i s 0° and A i s 90-120°. The least favourable geometry occurs when T approaches 90° and A approaches 0° or 180°. Scheffer and Trotter have also suggested that the distance for hydrogen abstract ion by oxygen has an upper l im i t of approximately 2.7 A, which i s the sum of the Van der Waals rad i i of the oxygen and hydrogen a t oms 2 1 > 2 2 . The mass spectroscopy analogue of the Norrish type II react ion, the McLafferty rearrangement, also involves a 1,5 hydrogen transfer to the rad ica l -cat ion of the carbonyl group. Through the use of r i g i d steroidal ketones and molecular models, Djerassi has determined an upper l im i t of 1.8 A for the distance between the abstract ing oxygen and abstractable hydrogen atoms (f igure l l ) 2 3 . The magnitude of the angle t has also been 12 m/e 259 F i g u r e 11: M c L a f f e r t y rearrangement i n s t e r o i d s i m p l i c a t e d i n the a b i l i t y of the c a r b o n y l oxygen ,to a b s t r a c t a y-hydrogen i n t h e M c L a f f e r t y rearrangement. Ketone (1) ( f i g u r e 12) d i d not undergo M c L a f f e r t y rearrangement whereas ketone (2) was observed t o r e a r r a n g e . T h i s r e s u l t was e x p l a i n e d on the b a s i s of an u n f a v o u r a b l e t a n g l e of 80° i n ketone (1) as opposed t o the more f a v o u r e d T angle of 50° i n ketone (2). From m o l e c u l a r models, the d i s t a n c e d f o r both ketones (1) and (2) was e s t i m a t e d t o be 1.6 A 2 1 + . The a n g l e x was a l s o o b t a i n e d from m o l e c u l a r models of the a c t u a l systems. 13 Ketone 1 Figure 12: Ketone (1) does not undergo McLafferty rearrangement whereas ketone (2) does Following the abstract ion of a y-hydrogen atom, the 1,4 b i rad ica l intermediate can undergo three d i f ferent chemical transformations (f igure 1 3 ) 2 5 . 1. The y-carbon radical can reabstract the hydrogen on the hydroxy radical and revert back to the ground state ketone. 2. The a-p carbon bond can cleave to form an alkene and an enol . The enol can tautomerize to form the observed ketone. 3. The 1,4 b i rad ica l can undergo a r ing closure reaction to form a cyclobutanol. 14 0 Figure 13: Photoreactions of valerophenone Wagner has studied the effects of polar and non-polar solvents on the behavior of the 1,4 b i rad ica l generated by photolysis of valerophenone. It was found that the quantum y i e l d fo r to ta l photoreacti on rose from 0.45 in non-polar solvents to unity in alcohols and a c e t o n i t r i l e 1 6 . The polar solvent effect is not due to a change in the excited state of the ketone since the n,n t r i p l e t has a sharply decreased dipole moment and only weak dipole interact ions are expected 2 6 * 2 7 . Rather, the increased quantum y i e l d observed in polar solvent has been attr ibuted to strong hydrogen bonding between the solvent and the hydroxyl group of the 1,4 b i r ad i ca l . The hydrogen bonding 15 s tab i l i z e s the hydroxy radical impeding reverse hydrogen abstract ion by the y-carbon r ad i ca l . The net resu l t is that a l l of the 1,4 b i rad i ca l s in polar solvent y i e l d photoproducts. This i s in contrast to the resu l ts obtained from photolysis in non-polar solvents where the majority of the b i rad ica l s revert back to the ground state ketone (f igure 14). Photolysis in polar solvents also has an ef fect on the rat ios of c i s - and trans-l-phenyl-2-methylcyclobutanol. In a non-polar solvent, such as hexane, a 5:1 t rans:c i s ra t io of cyclobutanols i s observed. In Non-Polar S o l v e n t P o l a r S o l v e n t Figure 14: Solvent ef fects on the behavior of the 1,4 b i rad ica l of valerophenone 16 a polar solvent, such as ter t -butano l , the t rans:c i s rat io f a l l s to 2 : 1 1 6 . This effect has been explained in terms of an increase in the s te r i c bulk of the hydroxy group due to hydrogen bonded solvent molecules. The s t e r i c interference between the hydrogen bonded hydroxyl group and the 2-methyl group in the t rans i t i on state fo r the formation of the trans-isomer results in an increase in the cis- isomer product. Further evidence fo r the involvement of a reverse hydrogen abstract ion step was obtained from the study of a lky l phenyl ketones containing a ch i ra l y-carbon atom. Wagner found that i r r ad ia t i on of (4s)-(+)-4-methyl-l-phenyl-l-hexanone, in benzene, results in a rapid loss of opt ical a c t i v i t y . The sample was i r rad iated to a conversion of 16% and the iso lated unreacted ketone was found to have undergone 31% racemizat ion 2 8 . A s im i l a r photochemical racemization of (4s)-(+)-5-methyl-2-heptanone was also observed by Yang 1 1 . The racemization of the y-carbon was postulated to occur in the fo l lowing sequence of events (f igure 15). 1. Formation of a 1,4 b i r ad i ca l . 2. Racemization of the y-carbon. 3. Reverse hydrogen abstract ion by the y-carbon forming the ground state ketone. 17 ]. Rotation * 0 2. Rever»e Abstraction F igu re 15: Photochemical racemiza t ion of (4 s ) - (+) -4 -me thy l - l - pheny l In a dd i t i o n to reverse hydrogen a b s t r a c t i o n , the 1,4 b i r a d i c a l i n te rmed ia te can a l so g ive r i s e to e l im i n a t i o n and c y c l i z a t i o n p roduc t s . To date , l i t t l e i s known about the nature of the 1,4 b i r a d i c a l i n te rmed ia te and the f a c t o r s c o n t r o l l i n g the r a t i o of c y c l i z a t i o n to c l eavage . Stephenson and Brauman have suggested tha t the s te reochemis t ry of product format ion i s determined by how wel l c y c l i z a t i o n and cleavage compete wi th bond r o t a t i o n s 2 9 . W a g n e r 2 5 » 3 0 » 3 1 and L e w i s 3 2 * 3 3 have made ex tens i ve i n v e s t i g a t i o n s i n to the e f f e c t s of a, p and y s ub s t i t uen t s on the photochemistry of s imple a l k y l phenyl ketones . I t was hoped tha t the study of these systems would b r ing to l i g h t the p r i n c i p l e s which govern the r a t i o of c y c l i z a t i o n to c leavage , the ra tes of hydrogen ab s t r a c t i o n and the s te reochemis t ry of the products . Lewis has shown tha t a-methyl subs t i t uen t s can g rea t l y increase the percentage of c y c l i z a t i o n products from the pho t o l y s i s of v a l e r ophenone 3 3 . For example, a-methyl and a,a-dimethyl s u b s t i t u t i o n of valerophenone inc reases the percentage of c y c l i z a t i o n from 22 to 43 and hexanone 18 71% respectively (table I ) . P-Substituents have been observed to have a variable effect on the photochemistry of butyrophenone (table I I ) . For example, photolysis of buty rophenone results in 10% cyc l i za t i on which Ketone 7. Cyclization (J> Total lc^ X 108 sec" 1 22 (18) 0.42 1.4 4 3 0.29 1.3 71 0.074 I.I Table I: The photochemistry of a-substituted valerophenones in benzene3 (brackets indicate results obtained by Wagner 2 5) increases to 15% fo r P-methyl butyrophenone but decreases to 3% f o r P,p-dimethyl buty rophenone. The effects of y-substituents on the percentage of cyc l i za t i on fo r y-subst i tuted butyrophenones can also be var iab le, with the changes being less dramatic than those observed for a and p subst i tut ion (table I I I ) 2 5 . 3 5 . 19 Ketone % C y c l i z a t i o n Cj> T o t a l . X 10 8 s e c " 1 10 0.40 0.076 15 0.31 0.20 0^C 3 0.18 0.54 Table I I : The photochemistry of p-substituted butyrophenones in benzene 3 3 20 Ketone % C y c l i z a t i o n T o t a l kjj X 1 0 8 s e c " 1 0 0 0 0 12 (10) 18 (22) 0.38 0.40 0.28 0.076 1.25 5.0 Table I I I : The photochemistry of y -subst i tuted butyrophenones in benzene 2 5 (brackets indicate results obtained by Lew is 3 3 ) Wagner has suggested that cleavage of a 1,4 bi radical intermediate can occur most e f f i c i en t l y when the molecule is in a conformation in which the two "p" orb i ta ls are para l le l to the C-C o-bond being broken (f igure 1 6 ) 2 5 » 3 1 . 21 0 Transoid Gauche Cisoid Figure 16: p-Orbital geometries considered ideal for cleavage For example, i t has been suggested that the lack of type II cleavage from 1-adamantyl acetone may be the resu l t of an unfavourable or ientat ion of the radical "p" o rb i ta l s with the a-p carbon bond being cleaved (f igure 1 7 ) 3 6 . A l te rna t i ve ly , the lack of cleavage products may also re f l e c t the high s t ra in energy involved in the formation of adamantene i f cleavage were to occur. 22 Figure 17: Photolysis of 1-adamantyl acetone Wagner has postulated that the bi radical intermediate, formed from the photolysis of alkyl phenyl ketones, exists in the conformation shown in f igure 18. In th is model the "p" orb i ta l on the y-carbon is para l l e l to , and the benzyl ic "p" orb i ta l perpendicular to the a,p C-C bond 2 5 . In order fo r cleavage to occur there must be a 90° rotat ion of the bond between the carbonyl carbon and the a-carbon. If such a rotat ion was to 23 OH H 90° rotat ion for cleavage R a - H . H, CH, F igure 18: Suggested conformat ion of the 1,4 b i r a d i c a l of a s imple a l k y l phenyl ketone occur , a-methyl subs t i t uen t s would create a s t e r i c b a r r i e r t o t h i s r o t a t i o n and thus impede the a b i l i t y of the molecule to a t t a i n the cleavage geometry. The s t e r i c h inderance would lower the rate constant f o r cleavage (kcA) i n r e l a t i o n t o the rate constant f o r c y c l i z a t i o n (key) . The t r a n s i t i o n s ta te f o r c y c l i z a t i o n requ i res the over lap of the "p" o r b i t a l s on the Y-carbon and the hydroxy-carbon. S ince over lap of the "p" o r b i t a l s w i th the a,P bond i s not requ i red , Lewis has pos tu la ted that the t r a n s i t i o n s ta te f o r c y c l i z a t i o n i s non-p lanar so as t o minimize 1,2 e c l i p s i n g i n t e r a c t i o n s ( f i gu re 1 9 ) 3 2 > 3 3 . Lewis has suggested that the 24 Figure 19: Suggested geometry fo r cyclobutanol formation decrease in the amount of cyc l i za t i on f o r p,P-dimethyl subst ituted butyrophenone is due to the introduct ion of a 1,3 d iax ia l interact ion which destab i l i zes the t r ans i t i on state fo r c y c l i z a t i o n 3 3 . The importance of s te r i c interact ions on the behavior of 1,4 b i rad ica ls is also evident in the stereochemistry of the cyc l i za t i on products. As shown in f igure 20, photolysis of a-methyl buty rophenone gives exc lus ive ly the trans-isomer of the cyc l i za t ion product 3 3 . This 25 0 Figure 20: S tereose lec t iv i ty of the cyclobutanol formed upon photolys is of a-methyl buty rophenone high degree of s te reose lec t i v i t y has been attr ibuted to a repulsive in teract ion between the aromatic ortho-hydrogens and the a-methyl group of the 1,4 bi radical forc ing the bi radical to form the more favoured trans -cycl obutanol. Although y-subst i tu t ion has only a small effect on the competition between cyc l i za t i on and cleavage, i t does have a tremendous impact on the rates of hydrogen abstract ion by the e lectron-def ic ient oxygen atom. The reac t i v i t i e s are of the order 200:25:1 for the formation of a tert iary-secondary-primary y-carbon rad ica l , which ref lects the dependance of on the y C-H bond d issoc ia t ion energy 1 4 » 3 5 » 3 7 . The addit ion of a, p and y substituents has been observed to lower the quantum y i e l d for the formation of products from alkyl phenyl ketones. 26 Lewis has suggested that th is decrease i s due to s te r i c interact ions which increase the energy of the t rans i t i on states for cyc l i za t i on and cleavage and make return of the b i rad ica l to the ground state, by reverse hydrogen abstract ion, more favourable. The substituent ef fects on the behavior of 1,4 b i rad ica l intermediates c lea r l y show that the ground state geometry of the s tar t ing ketone may be very important in determining the product s e l e c t i v i t y . Lewis has stated that ground state molecular conformations can inf luence photochemical behaviour when the excited state reactions are more rapid than conformational i s o m e r i s m 3 7 ' 3 8 . This i s pa r t i cu la r l y evident when the two conformers can give r i se to d i f ferent photoproducts (f igure 21). AB B hv AB hv ± B Figure 21: Two d i f fe rent conformers of a molecule giving r ise to d i f fe rent photoproducts Lewis has proposed two l im i t i ng cases which may influence the rat ios of the products formed 4 0 . Case I: The energy barr ier for conformational isomerism is lower than 27 the act ivat ion energies fo r the formation of X or Y * (k^B » k^.kg) and the product ratios w i l l depend on the act ivat ion energies of the t rans i t i on states leading to products A and B Case I I : The energy bar r ie r fo r excited state conformational isomerism is higher than the act ivat ion energy fo r the formation of X or Y * ( k A B « k A > kg) and the product rat io depends on the re lat ive * * population of A and B , which are in turn dependent on the re lat ive populations of A and B. The photochemical behavior of a-methyl cycl opentyl phenyl ketone has been observed to exhib i t case I behavior. The pseudorotation of the cyclopentane ring is more rapid than a-cleavage or y-hydrogen abstract ion * (k^g > k a , ky), and is attr ibuted to a low energy bar r ie r fo r alkane bond rotations in cyclopentane. Although y-hydrogen abstraction can only occur from the axia l conformation A (f igure 2 2 ) 5 1 » 5 2 , the l i fet imes of the two conformers must be the same since i t was found that the rates of formation of benzaldehyde and the cyclobutanol were i den t i ca l , thus implying a rapidly equ i l i b ra t ing cyclopentane r ing. The photochemistry of a-methyl cycl ohexyl phenyl ketone (figure 23) has been shown to be an example of case II behavior. The formation of benzaldehyde and the cyclobutanol 28 Figure 22: The photochemistry of a-methylcyclopentyl phenyl ketone product has been observed to occur at d i f ferent rates which are dependent on the conformer l i fe t imes t A and - C g 3 8 ' 4 0 . If the rate constant * k A B << k a , k^ , then the product quantum y ie lds should depend on the ground state populations for the d i f ferent conformers as well as the e f f i c iency of product formation from the radical pair and b i rad ica l intermediates. The quantum y ie lds for the formation of benzaldehyde and the cyclobutanol 29 were found to agree well with the conformational populations of the s ta r t ing ketone in so lut ion. This result is in agreement with the Figure 23: The photochemistry of a-methylcyclohexyl phenyl ketone existence of a large rotat ional energy bar r ie r preventing rapid i nterconversion of the cyclohexane ring of the s tar t ing ketone. Many organic molecules have been observed to exist as rapidly equ i l i b ra t ing conformational isomers of s im i la r energy in so lut ion. This 30 fact makes i t d i f f i c u l t to obtain single products from a reactant which may give several products from more than one conformational isomer. Attempts have been made to control the geometry of the reactant species so as to obtain a more selective conversion to products. These attempts have involved the use of organized media which may limit the available geometries of the reactant species and thus alter the ratios and number of products formed. These organized media often consist of: 1. Micellar systems 2. Monolayer assemblies 3. Inclusion complexes 4. Liquid crystals 5. Glassy matrixes 6. Crystalline state The use of highly structured media, such as the crystalline state, to control photochemical reactions, has received considerable attention in recent years1*1 >42 >1+3 >44. In contrast to solution state reactions, the reactants in the solid state are usually locked in a fixed orientation with this orientation being the minimum energy state of the molecule. In 1918, Kohlschutter proposed that reactions in crystals proceed with a minimum of atomic and molecular movement1*5. The topochemical postulate originating at this time suggests that the nature and properties of the products from a solid state reaction are governed by the crystalline influence of the three dimensionally periodic environment. Schmidt refined the definition of the topochemical postulate by suggesting that solid-state reactions are controlled by the relatively fixed distances and 31 orientat ions of the molecule, as determined by the crystal l a t t i c e , between potent ia l l y reactive centers. What is implied is that fo r a par t i cu la r reaction type, there should ex ist geometries and distances beyond which a reaction cannot occur. Furthermore, the molecular structure of the products may be a function of the geometry of the reactant in the c r y s t a l 4 6 . What is pa r t i cu la r l y advantageous about studying chemical reactions in the c rys ta l l i ne state is that the geometry and atomic distances of the reactant species may be obtained from X-ray crystal lography. So l id state magic angle spinning N.M.R. spectroscopy also lends i t s e l f quite well to the study of organic so l ids . These two techniques may be used to draw s t ruc ture- reac t i v i ty correlat ions f o r photochemical transformations in the so l id state. Scheffer and Trotter have used the techniques of X-ray crystal lography and so l i d state magic angle spinning N.M.R. spectroscopy to determine the so l i d state geometry of ene-dione 1 (f igure 24). In so lu t ion , th is ene-dione can exist in conformations A or B. Conformation 32 1 (R.'CHfrRfCtH,) Figure 24: The photochemistry of ene-dione 1 A gives photoproducts 2 and 3, whereas conformation B gives photoproducts 2'and 3 ' . Solut ion state photolysis of ene-dione 1 produces a mixture of 2, 2 ' , 3 and 3 ' , the rat io of which is dependent on the extent of conversion. In the so l id state ene-dione 1 has been shown to exist sole ly in conformation A and gave only the enone-alcohol 2 as the product. The cyclobutanone 3 was not formed in the so l id state. Scheffer and Trot ter at t r ibute th is result to an unfavourable so l i d state s te r i c ef fect 33 accompanying cyclobutanone formation but not enone-alcohol formation. The formation of products 2 and 2' has been found to occur via a H 5 abstract ion by 0 4 followed by C 2 - C 8 bonding. The formation of 3 and 3' is brought about by a t ransfer of H 8 to C 3 followed by C 2 - C 8 bonding. Scheffer and Trot ter have studied the geometric requirements f o r P- hydrogen abstract ion by the carbonyl oxygen of ene-diones (f igure 25). It was found that the abstract ion distances varied between 2.26 and 2.58 A and that t and A were close to ideal (0° to 8° fo r t and 81° to 86° f o r A ) 4 8 . Scheffer and Trot ter have extended the study of hydrogen abstract ion distances and angles to the Norrish Type II react ion. The Figure 25: p-Hydrogen abstract ion geometry fo r ene-diones study involved the photolysis of a series of a-cycl oalky l-p-chl oroacetophenone der ivat ives (cyc lobuty l , cycl opentyl, cycl ohexyl, cyc loheptyl , exo-2-norbornyl and 1-adamantyl). A l l s ix ketones were reported to undergo the Norrish Type II process in the so l id s t a t e 2 1 . It was found that the distance fo r y-hydrogen abstract ion by the 34 carbonyl oxygen could be much larger than 1.8 A and s t i l l occur. An abstract ion distance of 3.1 A for the abstract ion of a y-hydrogen from a-cyclobutyl-p-chloroacetophenone was reported. The angles A and T were also observed to deviate considerably from the theoret i ca l l y ideal values of 90°-120° and 0° respect ively. In an extreme case the value of x was found to be 62° fo r the abstract ion of a y-hydrogen from a-1-adamantyl-p-chloroacetophenone. The so l i d state geometry of the six-membered t rans i t i on state for y-hydrogen abstract ion was found to vary from boat to twist boat to cha i r l i ke depending on the a-cyc loalky l moiety. Scheffer and Trot ter have also studied the effect of l a t t i c e control on the par t i t ion ing of the 1,4 bi radical intermediate. Most of the ketones studied show very s im i l a r rat ios of cyc l i za t i on to cleavage in so lut ion and the so l i d state. Only the cyclohexyl compound (f igure 26) was observed to show a s i gn i f i c an t l y d i f ferent cyc l i za t i on to cleavage ra t io in the so l i d state compared to the solut ion state. For th is compound, a s l i gh t increase in the amount of cleavage was observed in the so l i d state, and th i s was explained in terms of a topochemical r es t r i c t i on of the motions required fo r cyc l i z a t i on . 35 0 CI T / Figure 26: The photochemistry of a-cycl ohexyl-p-chloroacetophenone Research Objectives The objective of th is research is to study the effects of a-cycl oal kyl ring size (cyc loocty l , cycloheptyl , cycl ohexyl and cyclopentyl) as well as the effect of a-methyl substituents on the photochemistry of para-substituted acetophenones. It is hoped that four important questions may be answered from th is work. 1. The effect of a-methyl substituents and cycloalkyl ring size on the geometry for hydrogen abstract ion by the oxygen "n" o rb i t a l . 2. The effect of a-methyl substituents and cycloalkyl ring size on the competition between cyc l i za t ion and cleavage. It is known that a-methyl substituents increase the amount of cyc l i za t ion product upon photolysis of simple alkyl phenyl ketones in s o l u t i o n 3 3 . Perhaps 36 th i s trend may also be true for a-methyl-a-cycloalkyl-para-subst ituted acetophenones. I f th is i s the case, i t may be possible to corre late the geometry of the s tar t ing ketone, as determined by X-ray crystal lography, to the observed rat ios of cyc l i za t i on to cleavage. Likewise, s imi lar corre lat ions may be made for the ef fects of cyc loa lky l r ing size on the rat io of cyc l i za t ion to cleavage. 3. The ef fect of a-methyl substituents and cyc loa lky l r ing size on the stereochemistry of the photoproducts and how the stereochemistry may be related to the geometry of the s tar t ing ketone. 4. The ef fect of a-methyl substituents and cyc loalky l r ing size on the quantum y ie lds for product formation can be observed. The design of the ketones involved in th is study i s of par t i cu lar importance. The two most important design features are the fo l lowing: 1. The molecules must be c r y s t a l l i ne such that X-ray analysis i s poss ib le. I t would be benef ic ia l to study a molecule which has a high melting point in order to minimize melting during photo lys is . 2. The molecule must have an avai lab le y-hydrogen atom when photolyzed in the so l i d s tate. I t has been shown that 7-tridecanone does not react in the so l i d state but does react in the melt (f igure 27). 37 hv 10* N o R e a c t i o n H H >33,* T y p e I I (melt) , y Figure 27: The photochemistry of 7-tridecanone This behavior i s believed to be the resu l t of the molecule ex i s t ing in an extended conformation in the so l i d , thus making the y-hydrogen inaccessib le to the abstract ing ke tone 4 9 . Scheffer and Trotter have shown that the y-hydrogens of a-cyc loa lky l -para-subst i tuted acetophenones can be within the abstract ing distance of the carbonyl oxygen(figure 2 8 ) 2 0 . 2 1 . 8 0 . 38 Figure 28: <x-Cycloalkyl-para-substituted acetophenones with ava i lab le Y-hydrogen The molecules involved in th is study w i l l be very s im i l a r to those already studied by Scheffer and T r o t t e r 2 0 ' 2 1 . In th is case an a-methyl group w i l l be attached to the s tar t ing ketone. The para-substituent w i l l be a carboxyl ic acid functional group to ensure that the molecules w i l l be high melting so l i d s . The size of the cycloalkyl ring w i l l be varied from cyclopentyl to cyclooctyl (f igure 29). 39 y n - 5 , 6 , 7 , 8 Figure 29: Design of the a-methyl ketones To better understand the effects of a-methyl subst i tu t ion, another ser ies of compounds analogous to those in f igure 29 but lacking an a-methyl substituent w i l l also be studied (f igure 3 0 ) 5 0 . 5 3 . n - 5 , 6 , 7 , 8 Figure 30: Design of the ketones lacking an a-methyl substituent F i na l l y , the effects of larger r ing ketones with varying para-substituents w i l l also be studied. In this case the packing of the 40 molecules in the crysta l l a t t i c e may influence the behavior of these ketones when photolyzed in the so l i d state (f igure 31). X - CI, CN, COOH n - 7,8 Figure 31: Design of the ketones bearing var iable para-substituents 41 RESULTS AND DISCUSSION Synthesis The synthesis of the a-cycloalkyl-para-substituted-acetophenones required for th is study has centered on the a va i l a b i l i t y of cyc loalky l acet ic acids as s tar t ing mater ia ls . Cyclohexyl and cyclopentyl acet ic acids are both commercially ava i lab le , however, cycloheptyl and cycloocty l acet ic acids are not. Fortunately, synthetic routes for cycloocty l and cycloheptyl acet ic acids have been reported in the l i t e r a t u r e . The synthesis of cyclooctyl acet ic acid has been accomplished by Bl icke and Johnson 5 5 using the sequence of reactions out l ined in f igure 32. The f i r s t step involves the conversion of cyclooctene ( la) to Figure 32: Synthesis of cyclooctyl acet ic acid 42 cycloocty l bromide (1), using hydrobromic acid dissolved in g lac ia l acet ic acid as the brominating reagent. Reaction of cyclooctyl bromide with the sodium enolate of diethyl malonate resul ts in a nucleophi l ic displacement of the bromine atom by the carbanion resul t ing in the formation of the diester (2a). Hydrolysis in a solut ion of potassium hydroxide, followed by decarboxylation y i e lds cyclooctyl acetic acid (2). The synthesis of cycloheptenyl acet ic acid (3) has been accomplished by McCarthy and Brown 5 6 using the sequence of reactions out l ined in f igure 33. Cata ly t i c hydrogenation of cycloheptenyl acet ic acid using a method developed by J . F . Sauvage et a l . 5 7 generates cycloheptyl acet ic acid (5). Figure 33: Synthesis of cycloheptyl acet ic acid 43 The f i r s t step of th i s reaction sequence involves the reaction of cycloheptanone with cyanoacetic acid in the presence of a small amount of ammonium acetate. Under these condit ions, small quant i t ies of the enolate of cyanoacetic acid are generated and th is attacks the carbonyl carbon of cycloheptanone. Removal of water from the ref lux ing reaction as an azeotrope with benzene drives the reaction to completion. Decarboxylation of the resultant product y ie lds cycloheptenyl a ce ton i t r i l e . This compound was converted to cycloheptenyl acet ic acid upon ref lux ing in a solut ion of potassium hydroxide dissolved in water and ethanol. Cata ly t i c hydrogenation of cycloheptenyl acet ic acid using hydrogen gas at a pressure of 500 l b s / i n 2 and 10% palladium on charcoal as cata lys t y i e l d s cycloheptyl acet ic acid (5). With the a v a i l a b i l i t y of the four cyc loalky l acet ic acids (cyc looc ty l , cyc lohepty l , cyc lohexyl , and cyclopentyl) as s tar t ing mater ia ls , i t was possible to develop a synthetic strategy towards the synthesis of the a and para-substituted a-cycloalkyl acetophenones required for th is study. The strategy follows the sequence of steps out l ined in f igure 34. 44 X • OMe, M e , CI Figure 34: Synthetic routes towards the synthesis of a and para-subst i tuted-a-cycloalkyl acetophenones The f i r s t step in the synthesis involves the conversion of the cycl oalkyl acet ic acid to the corresponding acetyl chloride using a modified version of a procedure u t i l i z ed by Bl icke et a l . 5 5 . The cyc loa lky l acetyl chloride was reacted with a mono-substituted benzene der ivat ive , in a Fr iede l -Craf ts acylat ion reaction catalyzed by aluminum 45 t r i c h l o r i d e , to form an a-cyc loa lky l -para-subst i tuted acetophenone. The same procedure was used by Wagner58 to synthesize several d i f fe rent para-substi tuted valerophenones. The reaction of cyclooctyl acetyl chlor ide with e i ther chlorobenzene, toluene, anisole or fluorobenzene in the presence of aluminum t r i ch l o r i de y ie lds the compounds shown in f igure 35. X=CA : m.p. = 48-49°C X=0Me : o i l at 22°C X=Me : o i l at 22°C X=F : o i l at 22°C Figure 35: Products of Fr iede l -Craf ts acylat ion of substituted benzenes using cyclooctyl acetyl chlor ide and aluminum t r i ch l o r i de as a cata lys t The fol lowing spectroscopic data supports the proposed structures. 1. The infrared spectra of these compounds show a strong carbonyl absorption at 1675-1685 cm - 1 which is ind icat ive of an alkyl phenyl ketone. 2. The 400 MHz XH nmr spectra show two d i s t i n c t signals in the aromatic region, each of which integrates for two protons. This evidence 46 suggests that para-subst i tut ion had occurred. In addi t ion, the two a-hydrogen atoms appear as doublets at 2.8-3.0 ppm; the a-hydrogen to 6-hydrogen coupling constant measures 8 Hz. 3. The mass spectra of these compounds exhibi t the correct parent ion mass. In addi t ion, the base peaks in the spectra correspond to a McLafferty rearrangement of the parent ion (f igure 36). 4. The structure of a-cyclooctyl-para-chloroacetophenone was ver i f i ed by X-ray c rys ta l l ography 6 2 . The R factor for th is determination was calculated to be 4.4%. Figure 36: McLafferty rearrangement of a-cycloocty l-para-subst i tuted acetophenones 47 The para-methoxy and para-methyl-a-cyclooctyl-acetophenones were found to be l iqu ids at room temperature and as a result were of l i t t l e use to th i s study. The para-f luoro der ivat ive is also a l i qu i d , but as shown in f igure 34 i t can serve as a valuable synthetic intermediate fo r the synthesis of other para-subst ituted-a-cycloalkyl acetophenones. The remaining cycl oal kyl acetyl chlorides (cycloheptyl , cycl ohexyl, and cycl opentyl) were reacted with f luorobenzene in the presence of aluminum t r i c h l o r i de , producing the corresponding a -cyc l oal ky l -para-f luoroacetophenones 6 0. Two aromatic signals in the XH nmr spectra at approximately 7.1 and 8.0 ppm, integrat ing fo r two protons each, are observed fo r a l l the para-f luoro der ivat ives . This pattern suggests that para-subst i tut ion of fluorobenzene had occurred. The mass spectra of each compound exhib i ts the correct parent ion mass and the base peak corresponds to a McLafferty rearrangement of the parent ion. Infrared analysis shows a strong alkyl phenyl ketone stretching band at 1684 c m - 1 . A l l of the compounds in th is series are o i l s at room temperature. At th is stage of the synthesis the a-cycl oal ky l-para-fluoroacetophenones could be methylated in the a -pos i t ion leading to the formation of the a-methyl ketone ser ies . Omitting the methylating step would lead to the synthesis of a number of d i f ferent a-cycl oal ky l-para-subst i tuted acetophenones (figure 37). The a-methylation was accomplished by reaction of the a-cycloalkyl-para-fluoroacetophenone with l i th ium di isopropyl amide at 0°C to generate the corresponding enolate. 4 8 n - 7,8 Figure 37: The synthesis of a-cyclooctyl-para-cyano and para-carboxy acetophenones The enolate was then allowed to react with methyl iodide generating the a-methyl analogue of the s tar t ing ketone. This a lky la t ion step was conducted using a modified version of an a lky la t ion procedure developed by P.L. C reger 5 9 . The 1H nmr of the a-methyl-a-cycl oalkyl-pa ra-fluoroacetophenones exhibi t a methyl doublet at approximately 1.1 ppm. The coupling constant between the a-methyl group and the a-hydrogen measures 7 Hz. The next step in the synthesis involved the reaction of the para-f luoro alkyl phenyl ketones with sodium cyanide in dimethyl sulphoxide at 110-120°C for two days. The cyanide ion displaces the para-f luoro substituent to form the a-cycloalkyl-para-cyanoacetophenone compounds. The same method was used by Wagner58 to synthesize para-cyanovalerophenone from para-fluorovalerophenone. The fo l lowing spectroscopic data supports the proposed structures. 49 1. The XH nmr spectra exh ib i t two signals in the aromatic region, each of which integrates for two protons. This suggests that subst i tut ion had occurred in the para-pos i t ion. 2. The mass spectra of these compounds exhib i t the correct parent ion mass. In addi t ion, the base peak in the spectra corresponds to a McLafferty rearrangement of the parent ion. 3. The infrared spectra of these compounds exh ib i t a strong n i t r i l e stretching band in the 2225 cm - 1 region. In addi t ion, the alkyl phenyl ketone band i s observed at 1687 c m - 1 . These compounds and the i r respective melting points are shown in f igure 38. In th is ser ies only the a - cyc looc ty l - and a-cyc lohepty l-para-cyanoacetophenones are so l ids at room temperature. CN n R melting point (°C) 8 H 62-63°C 7 H 41-42°C 8 CH3 o i l at 22°C 7 CH3 o i l at 22°C 6 CH3 o i l at 22°C 5 CH3 o i l at 22°C Figure 38: a-Cycloalkyl-para-cyanoacetophenone der ivat ives and the i r melting points To obtain so l ids of the a-methyl analogues, i t was necessary to convert the para-cyano functional group to the carboxyl ic ac id. The para-cyano compounds were added to a ref lux ing mixture of water, potassium 50 hydroxide and ethanol. These hydrolysis conditions were employed by Wagner58 to hydrolyze para-cyanovalerophenone to para-carboxyvalerophenone. The resultant a-methyl-a-cycloalkyl-para-carboxyacetophenones are a l l so l ids at room temperature. The non-methylated a -cyc l oalkyl-para-carboxyacetophenones are also so l ids . AIT of the para-carboxy compounds have been found to have melting points greater than 100°C (f igure 39.) . 0^ COOH n R melting point (°C) 8 H 188-189°C 7 H 183-184°C 8 CH3 137-138°C 7 CH3 152-153°C 6 CH3 157-158°C 5 CH3 140-141°C Figure 39: a-Cycloalkyl-para-carboxyacetophenone der ivat ives and t h e i r melting points The fo l lowing spectroscopic data supports the proposed structures. 1. The mass spectra of these compounds exhibi t the correct parent ion mass. In addi t ion, the base peak in the spectra corresponds to a McLafferty rearrangement of the parent ion. 2. A low f i e l d acid proton is observed in the lH nmr. 3. Infrared analysis reveals a broad 0-H stretching band around 2900 cm - 1 . In addit ion, two carbonyl peaks are observed in the regions 1683 cm - 1 and 1700 c m - 1 , these correspond to the keto and acid carbonyl stretching bands respect ively. 51 4. X-ray crystal lography has ve r i f i ed the structures of a-cyclooctyl-para-carboxyacetophenone 6 2 , a-methyl-a-cyclooctyl-para-carboxyacetophenone 6 2 , a-methyl-a-cyclohexyl -para-carboxyacetophenone 6 0 » 6 1 , and a-methyl-a-cyclopentyl-para-carboxyacetophenone 6 3. The calculated R factors have been found to be 4.2, 4.6, 5.8% and 6.5% respect ively. The f i na l step in the synthesis involved the conversion of the para-carboxy compounds to the corresponding carbomethoxy der ivat ives. This conversion was accomplished by reacting diazomethane with the a -cyc l oal kyl-para-carboxyacetophenone precurser, dissolved in ether. Diazomethane was prepared using a method developed by Th. J . DeBoer and H.J. Becker 6 4 . The carbomethoxy der ivat ives are so l ids with the majority of these having low melting points (f igure 40). COOCH. n R melting point (°C) 8 H 40-41°C 7 H 54-55°C 8 CH3 39-40°C 7 CH3 59-60°C 6 CH3 82-83°C 5 CH3 38-39°C Figure 40: a-Cycloalkyl-para-carbomethoxyacetophenone derivat ives and thei r melti ng poi nts The fol lowing spectroscopic data supports the proposed structures. 52 1. The mass spectra of these compounds exh ib i t the correct parent ion mass. In addi t ion, the base peak in the spectra corresponds to a McLafferty rearrangement of the parent ion. 2. The l H nmr spectra exhib i ts a sharp s ing let at approximately 4.0 ppm which integrates for the three protons of the methyl ester . 3. Infrared analysis reveals two carbonyl stretching bands at approximately 1680 cm - 1 and 1720 cm - 1 which correspond to the keto and ester carbonyl stretching bands respect ive ly . 4. A l l of the keto-esters showed acceptable elemental ana lys i s . I d e n t i f i c a t i o n o f the Photoproducts Scheffer and Trotter have shown that a -cyc loa lky l -para-chloroacetophenones (cyc lohepty l , cyc lohexyl , cyclopentyl and cyc lobuty l) undergo the Norrish Type II reaction when photolyzed in the so l i d and solut ion s t a t e s 2 0 * 2 1 . Photolysis of these compounds was found to give r i se to four products, these being an alkene, para-chloroacetophenone and two isomeric cyclobutanols (f igure 41). The two cyclobutanols have been 53 0 trans-cyclobutanol cis-cyclobutanol Figure 41: Products from the photolysis of a-cyc loa lky l -para-chl oroacetophenones designated c is and trans. In the case of the c i s - isomer, the hydroxyl group is cis to the nearest bridgehead hydrogen atom and in the trans-isomer the hydroxyl group is trans to the nearest bridgehead hydrogen. Iden t i f i ca t i on of the c i s - and trans-isomers has been made possible through the use of XH nmr spectroscopy. The cis-cyclobutanols have been observed to show a low f i e l d doublet of doublets at 2.8 ppm (J=6.5 and 4 Hz). This signal integrates fo r one proton and has been assigned to H (f igure 41). The assignment has been based on H^  ly ing within the deshielding region of the rotat iona l ly hindered aryl group. 54 Scheffer and Trot ter have also found that trans-cyclobutanols have shorter g.c. retention times than the corresponding c is isomers. A s im i l a r observation was also noted by Wagner fo r the retention times of the c i s - and trans-cyclobutanols derived from substituted valerophenones 2 5. To aid in the assignment of the structure and stereochemistry of these b i c y c l i c [n.2.0] alkanols the fol lowing I.U.P.A.C. numbering scheme has been used (figure 42). Figure 42: I.U.P.A.C. numbering scheme fo r b icyc lo [n.2.0] alkanols Photolysis of a series of a -cyc loocty l -para-subst i tuted acetophenones (para-chl oro, para-cyano and para-carboxy) in ace ton i t r i l e results in the conversion of the s tar t ing ketones into four photoproducts (f igure 43). 55 0 Figure 43: The photolysis of some a-cyc loocty l-para-subst i tuted acetophenones G.C. analysis of the resultant product mixtures showed three major product peaks. The retention time of cyclooctene was too short to be detected under normal g.c. condit ions. The second cleavage product, a para-substituted acetophenone, was observed to have a short g.c. retention time as compared to the retention times recorded fo r the cyclobutanols. The cleavage product and the isomeric cycl obutanol s were iso lated using column chromatography. The photoproducts derived from the para-carboxy ketone were e s t e r i f i ed , using diazomethane, p r io r to column chromatography and g.c. analys is . 56 The iso lated cleavage products were ident i f i ed by the fo l lowing spectral and physical charac te r i s t i c s . 1. The mass spectra of the para-substituted acetophenones exhib i t the correct parent ion mass. 2. 1H nmr shows a sharp s ing let peak at 2.7 ppm which integrates fo r the three protons of the a-methyl group. Two signals in the aromatic region of the spectra account fo r the four aromatic protons. An addit ional signal is observed fo r para-carbomethoxyacetophenone at 4.0 ppm. This peak integrates fo r three protons and accounts fo r the methyl ester hydrogens. 3. The infrared spectra of these compounds show a strong alkyl phenyl ketone stretching band at approximately 1675 cm - 1 . Para-cyanoacetophenone shows a strong n i t r i l e stretching band at 2230 cm - 1 and para-carbomethoxyacetophenone shows a strong ester carbonyl stretching band at 1723 cm - 1 . 4. The melting points of the para-substituted acetophenones also agree quite well with the recorded l i t e ra tu re values shown in f igure 44. X Obs. m.p. (°C) l i t . m.p. (°C) -CA -CN -COOMe o i l (a 22° 60-61° 93-94° 20 ° 6 5 60-61° 6 6 0,2 ° 66 Figure 44: Experimental and l i t e ra tu re melting points of para-substituted acetophenones 57 The two isomeric cycl obutanol s, from each s tar t ing ketone, were iso lated and ident i f i ed from the fol lowing spectroscopic data. 1. Infrared spectra of these compounds show a strong, broad, hydroxyl stretching band around 3440 cm - 1 . The absence of any bands in the region 1600-1800 cm - 1 ve r i f i e s the lack of a carbonyl group in the products. The para-carbomethoxy cycl obutanol s do show an ester carbonyl stetching band at 1724 cm - 1 . 2. The mass spectra of the cycl obutanols exhibi t the correct parent ion masses. In addi t ion, these compounds were also found to undergo a mass spectral retro 2+2 fragmentation producing the observed base peak (f igure 45). Herzschuh and Epsch have also observed that X - C l , COOMe, CN Figure 45: Retro 2+2 fragmentation pattern observed for [6.2.0] cycl obutanol s 58 b i c y c l i c [n.2.0] alkanes undergo an e f f i c i en t retro 2+2 mass spectral fragmentation as the major fragmentation pattern observed 7 8 . 3. The d i s t i n c t i on between c i s - and trans-cyclobutanols has been made using l H nrnr spectroscopy. The 400 MHz lH nmr spectra for the c i s -and the trans-para-cyano [6.2.0] cyclobutanols are shown in f igure 46. The l t i nmr spectrum of the trans-cyclobutanol is very 46a: Trans-cyclobutanol 59 5 ppm it ppm 3 ppm 2 ppm 1 ppm 46b: C is -cyc l obutanol Figure 46: 400 MHz XH nmr spectra of the c i s - and trans-cyclobutanols derived from a-cycl ooctyl-para-cyanoacetophenone complicated, making i t d i f f i c u l t to draw any structural corre la t ions . Only the four aromatic protons resonating at 8.0 and 8.1 ppm are d is t inguishable. The l H nmr of the cis- isomer on the other hand is more revealing, showing the fol lowing charac ter i s t i cs : i ) a doublet of doublets is observed at 2.8 ppm (J=8 and 4 Hz) which is in the exact region of the spectrum in which H^  was observed in the cis-cyclobutanols ident i f i ed by Scheffer and T r o t t e r 2 0 . 2 1 ; 60 i i ) a signal is observed at 0.38 ppm. The fact that th i s s i gna l , which integrates for one proton, i s located at such a high f i e l d suggests that i t must be located in the shie ld ing region of n electron density above and below the plane of the aryl group. I t was thought that the shielded hydrogen atom would most l i k e l y be one of the hydrogen atoms bonded to C 7 . To provide more conclusive proof, a series of decoupling experiments was carr ied out. I t was found that decoupling the signal at 0.38 ppm s imp l i f i e s the signal at 2.29 from a mul t ip let to a doublet (J=8 Hz), as shown in f igure 47. Such a simple s p l i t t i n g 61 Figure 47: 1H nmr spectrum of the cis-cyclobutanol decoupled at 0.38 ppm pattern can only be accounted fo r by e i ther of the two ring junct ion hydrogen atoms or Hg of the cyclobutanol r ing. Hydrogen atoms H^  and Hx can be eliminated as po s s i b i l i t i e s since decoupling of the signal at 2.80 ppm (H )^ has no effect on the signal at 2.29 ppm. Thus, the signal at 2.29 can be assigned to bridgehead hydrogen H 8 . The coupling constant of 8 Hz is due to coupling with H x . A small coupling of H 8 with the second H 7 may also be present but is so small that i t cannot be detected, and results in the signal at 2.29 appearing as a doublet. 62 The assignment of a c is or trans ring junct ion cannot be deduced from the XH nmr spectra. It has been shown 6 7 that the differences between the cis and trans proton coupling constants fo r substituted cyclobutanes is often smal l , however, the c is coupling constant was always found to be greater than the trans coupling constant. The ranges of magnitude fo r the coupling constants were found to be 8-12 Hz and 8-10 Hz fo r the c is and trans geometries r e spec t i ve l y 6 7 . For the c is-cyc lobutanol , the coupling constant between H : and H 8 (J=8 Hz) is with in the range expected fo r a c is or trans arrangement. Scheffer and Trot ter have suggested that the cyclobutanols formed upon photolysis of a-cyc l oal ky l-para-chl oroacetophe nones (cycloheptyl , cycl ohexyl, cycl opentyl and cyclobutyl) contain cis fused r i n g s 2 0 . 2 1 . Since only two major cyclobutanol products are observed in the photolysis of a-cyc l ooctyl-para-subst i tuted acetophenones, i t is un l ike ly that the b i c y c l i c rings are trans fused. If in fact the crossover point from cis to trans fused rings has been reached, then we would expect to observe more than two cyclobutanols. In addi t ion, the proton H^  appears in a pos i t ion expected fo r the c is product as determined by Scheffer and Trot ter for the c i s -cyc l obutanol derived from photolysis of a -cyc l ohexyl-para-substituted acetophenones. If in the case of the a -cyc l ooctyl ketones the ring junct ion was to become trans, then the chemical sh i f t of th i s signal would be expected to change due to a change in the posi t ion of the aryl group. In spite of th is evidence, the assignment of a c is ring junct ion must remain tentat ive since the bridgehead geometry cannot be absolutely determined. 63 Photolysis of the a-cycloheptyl-para-subst i tuted acetophenones also gave r ise to the formation of cleavage and cyc l i za t i on products. The para-cyano and para-carboxyacetophenone cleavage products, derived from the photolysis of the corresponding a-cycloheptyl-para-subst i tuted acetophenones were ident i f i ed by comparing the i r physical and spectral properties with samples iso lated from the photolysis of the cyclooctyl der ivat ives and with the l i t e ra tu re values. Two cyclobutanols (c is and trans) were also iso lated as products. These exhibi t the spectroscopic character i s t i cs expected fo r cycl obutanols. Infrared analysis shows a strong 0-H stretching band around 3440 c m - 1 . Mass spectroscopy exhib i ts the correct parent ion mass and also records a base peak molcular ion which corresponds to a retro 2+2 fragmentation of the parent ion. i H nmr of the cis- isomer shows a doublet of doublets at approximately 2.85 ppm (J =7.75 and 4.5 Hz) accounting for H .^ The cis- isomer also produces a high f i e l d signal at approximately 0.44 ppm accounting for proton H 6 . The signal fo r the bridgehead hydrogen H 7 is found at 2.3 ppm. Photolysis of a-methyl-a-cyclooctyl-para-carboxyacetophenone in ace ton i t r i l e resulted in the formation of several products as shown in f igure 48. P r i o r to analysis and i so l a t i on , the products were converted to t he i r methyl esters using diazomethane. The product with the 64 0 t h r e e i s o m e r s Figure 48: Photolysis of a-methyl-a-cyclooctyl-para-carboxyacetophenone shortest g.c. retent ion time was iso lated and found to be para-carbomethoxypropiophenone. The structure of th is compound was ve r i f i ed by the fol lowing spectroscopic charac te r i s t i c s : 1. The mass spectrum shows the correct parent ion mass. 2. The presence of the a- and e-hydrogens i s ve r i f i ed by a t r i p l e t at 1.2 ppm (3H, J=8 Hz) and a quartet at 3.0 ppm (2H, J=8 Hz). A sharp s ing let at 3.9 ppm integrates for the three protons of the methyl ester and a mult ip let at 8.1 ppm accounts for the four remaining aromatic hydrogens. 65 3. The infrared spectrum reveals two carbonyl stretching bands at 1680 crn-1 and 1723 cm - 1 , accounting fo r the presence of the ketone and ester functional groups. Three other photolysis products were also observed having retention times in the region expected fo r cycl obutanols. Two of these were iso lated using column chromatography. The f i r s t of these had the shortest cyclobutanol retention time and was found to comprise 70% of the tota l cyclobutanol product in ace ton i t r i l e . The second cyclobutanol had a retention time close to that observed fo r the para-carbomethoxy-trans [6.2.0] cyclobutanol and was found to comprise 19% of the tota l cyclobutanol product in a ce ton i t r i l e . These two cycl obutanols showed the fo l lowing spectroscopic charac ter i s t i cs . 1. The infrared spectra of these compounds show a strong 0-H stretch at approximately 3400 cm - 1 . 2. Mass spectroscopy exhib i ts the correct parent ion mass as well as a base peak ion which corresponds to a retro 2+2 fragmentation of the parent ion. 3. The 1H nmr of the cycl obutanols gives some clues as to t he i r stereochemistry. The XH nmr of the major cyclobutanol formed in ace ton i t r i l e is shown in f igure 49. The methyl group on C 1 0 i s 66 Figure 49: lti nmr of the major cyclobutanol iso lated from photolysis of a-methyl-a-cyclooctyl-para-carboxyacetophenone c lea r l y v i s i b l e , appearing as a doublet at 1.08 ppm (J=7.5 Hz). Decoupling the signal at 1.08 ppm resul ts in the mult ip let observed at 2.11 s impl i fy ing to a doublet (J=9 Hz). Decoupling at 2.11 ppm has no ef fect on the mul t ip le t at 2.24 ppm. Based on these resu l t s , the signal at 2.11 can be assigned to proton H 1 0 . The signal at 2.24 can not be assigned to proton H x , since i t does not couple to proton H 1 0 . The s p l i t t i n g pattern of the signal at 2.24 does resemble the s p l i t t i n g pattern of H 8 for the cis-cyclobutanol shown in f igure 46, 67 thus the signal at 2.24 was tentat ive ly assigned to proton H 8 . This assignment was ve r i f i ed by an N.O.E. difference experiment. I r rad iat ion of the aromatic protons Hm resul ts in the enhancements shown in f igure 50. The endo assignment of the C 1 0 methyl group *H nmr spectrum • 9 T- j -T • 1 1 1 r- , 7 6 5 4 3 2 1 0 *_ . i . Jl W I. " " I T / \ " 1 H H H N . O . E . d i f f e r e n c e spectrum 8 1 0 J 1 1 1 • . Figure 50: 1H N.O.E. difference spectra of the cyclobutanol shown in f igure 49 i s based on the observation that no enhancement of the C 1 0 methyl group i s observed, whereas proton H 1 0 does exh ib i t a strong enhancement. Lewis has observed that the cyclobutanol derived from the photolysis of a-methylbutyrophenone strongly prefers the geometry in which the methyl group and the aryl group are in a trans o r i e n t a t i o n 3 7 * 3 8 . I r rad iat ion of Hm also resu l ts in the enhancement of H 8 ind icat ing that the cyclobutanol i s in fact trans. 68 The second cyclobutanol iso lated produces the XH nmr shown in f igure 51. The methyl group on C 1 0 is c lear ly v i s i b l e in the *H nmr, ~—• ~< —i -i -i - i — 5 ppm 4 p p m 3 ppm 2 ppm 1 ppm 0 — Figure 51: lH nmr of the second cyclobutanol iso lated from photolysis of a-methyl-a-cyclooctyl-para-carboxyacetophenone appearing as a doublet at 1.07 ppm (J=6.5 Hz). Decoupling the signal at 1.07 ppm results in the mult ip let observed at 2.51 s impl i fy ing to a doublet (J=9.5 Hz). Hence, the signal at 2.51 ppm can be assigned to H 1 0 . Decoupling the signal at 2.19 ppm results in the s imp l i f i ca t i on of the mult ip let at 2.51 ppm to a quartet (J=6.5 Hz) and s imp l i f i ca t i on of the mult ip let at 2.37 ppm to a doublet (J =11 Hz). Hence, the signal at 2.19 ppm can be assigned to H L since i t couples to H 1 0 . The signal at 69 2.37 ppm also couples to and thus, th is signal can be assigned to H 8 . The doublet s p l i t t i n g of H 8 i s due to a strong coupling of H 8 to one of the C7 hydrogens. It is worth noting that decoupling of the H 7 high f i e l d proton of the para-cyano-cis [6.2.0] cyclobutanol also results in the collapse of H8 from a mult ip let to a doublet. Again the observation of a doublet s p l i t t i n g pattern is most l i k e l y due to the fact that coupling of H8 to the second C 7 hydrogen is too weak to be detected. In an N.O.E. difference experiment (f igure 52), i r rad ia t i on of 1 *H nmr spectrum • —1 8 i i - i T - i - — i • 1 r — 7 6 5 4 3 2 | 0 N . O . E . d i f fe rence spectrum Hg n i 1 / *. ' • * -T Figure 52: lH N.O.E. difference spectra of the second cyclobutanol derived from a-methyl-a-cyclooctyl-para-carboxyacetophenone the aromatic protons Hm results in a strong enhancement of the signal due to H 1 0 . C lear ly the methyl group at C 1 0 is trans to the aryl group. A 70 weak enhancement of the signal fo r H 8 is also observed. This observation suggests that H8 is c is to the aryl group. The rationale fo r the weak enhancement of H 8 re lat ive to H 1 0 is not known. In th i s case the assignment of the ring junct ion stereochemistry re lat ive to the aryl group cannot be pos i t i ve ly determined. The th i rd cyclobutanol could not be iso lated from the product mixture. It accounted f o r 11% of the tota l cyclobutanol products formed in ace ton i t r i l e . Ident i f i ca t i on was made using combined gas chromatography-mass spectroscopy (g.c .m.s.) . The g.c.m.s. does not show a parent ion fo r the cyclobutanol. This can be accounted fo r by the lowered sens i t i v i t y of the g.c.m.s. system used fo r th is ana lys is . The mass spectrum does exhibi t a base peak ion corresponding to a retro 2+2 fragmentation of the parent ion. Photolysis of a-methyl-a-cycloheptyl-para-carboxyacetophenone resulted in the formation of cycl oheptene, para-carboxypropiophenone and three isomeric cyclobutanols. It was found that cleavage of the 1,4 b i rad ica l generated from the a-cycl oheptyl ketone is the predominant process in acetoni t r i l e . Cyclobutanols were found to comprise 30% of the photolysis mixture. These were iden t i f i ed as t he i r methyl esters and have been observed to exhibi t base peaks which correspond to a retro 2+2 fragmentation of the parent ions in t he i r g.c.m.s. Photolysis of a-methyl-a-cycl ohexyl-para-carboxyacetophenone in ace ton i t r i l e resulted in the formation of cyclohexene, para-carboxy-propi ophenone and four isomeric cyclobutanols. The major cyclobutanol product, iso lated as i t s methyl ester, was found to comprise 56% of the tota l cyclobutanol product formed in ace ton i t r i l e . It was isolated using 71 column chromatography and analyzed spectroscopica l ly . The in f rared spectrum of the cyclobutanol exhib i ts a broad 0-H stretching band at 3497 c m - 1 . Mass spectroscopy exhib i ts the correct parent ion mass and a base peak corresponding to a retro 2+2 fragmentation of the parent ion is observed. The 400 MHz lH nmr spectrum of the major cyclobutanol is shown in f igure 53. The methyl group on C 8 i s c lear l y v i s i b l e as a doublet 5 ppm k ppm 3 ppm 2 ppm l ppm Figure 53: l H nmr spectrum of the major cyclobutanol derived from photolysis of a-methyl-a-cyclohexyl-para-carboxyacetophenone at 1.11 ppm. Decoupling of the signal at 1.11 ppm resul ts in the mul t ip le t observed at 2.31 ppm s impl i fy ing to a doublet (J=10 Hz). The signal at 2.31 can therefore be assigned to proton H 8 . In an N.O.E. di f ference experiment, i r r ad ia t i on of Hm resul ts in the enhancement of H 8 and in addi t ion, the bridgehead hydrogen H6 i s resolved from the 72 mul t ip le t signal at 1.7 ppm. The fact that the signal due to the C 1 0 methyl group i s not enhanced c lea r l y indicates that the methyl group i s s i tuated trans to the aryl group. Enhancement of the bridgehead proton H 6 indicates that the system is a trans-cyclobutanol. The three minor cyclobutanol isomers observed from the photolysis of a-methyl-a-cyclohexyl-para-carboxyacetophenone were i den t i f i ed by the presence of a base peak in the i r g.c.m.s. which corresponds to a retro 2+2 fragmentation of the parent ion. Photolysis of a-methyl-a-cyclopentyl-para-carboxyacetophenone, in a ce ton i t r i l e , resulted in the formation of cyclopentene, para-carboxypropiophenone and two isomeric cyclobutanols. The major cyclobutanol was found to comprise 11% of the tota l cyclobutanol formed. This cyclobutanol was i so la ted , as i t s methyl ester, using column chromatography and studied spectroscopica l ly . The infrared spectrum of the cyclobutanol shows a broad 0-H stretching band at 3466 c m - 1 . Mass spectroscopy exh ib i ts the correct parent ion mass and in addit ion a base peak corresponding to a retro 2+2 fragmentation of the parent ion is observed. The 400 MHz lW nmr spectrum of the major cyclobutanol is shown in f igure 54. The methyl group on C 7 i s c lear l y v i s i b l e as a doublet 73 5 ppm A ppm 3 ppm 2 PPm 1 PPm 0 Figure 54: 1 H nmr spectrum of the major cyclobutanol derived from photolysis of a-methyl-a-cyclopentyl-para-carboxyaceto-phenone at 1.15 ppm (J=7 Hz). The mul t ip le t observed at 2.53 ppm integrates for two protons and the mul t ip let at 2.79 ppm integrates for one proton. Decoupling the signal at 2.53 ppm resu l ts in the col lapse of the methyl signal at 1.15 ppm (J=7 Hz) from a doublet to a s ing le t . Clear ly one of the protons resonating at 2.53 ppm must be proton H 7 . Decoupling the signal at 2.53 ppm also s imp l i f i es the mult ip let at 2.79 ppm from a mul t ip le t to a doublet (J=2.1 Hz). Hence, the signal at 2.79 ppm may be assigned to e i ther Hx or H 5 . In an N.O.E. difference experiment, i r r ad i a t i on of Hm resu l ts in a strong enhancement of the signal at 2.53 ppm and a weak enhancement of the signal at 2.79 ppm. Since both of 74 the proton signals at 2.53 ppm are enhanced and the methyl group on C 7 not enhanced suggests that the C7 methyl group i s trans to the aryl group. The two remaining protons on the cyclobutane r ing are also enhanced ind icat ing that the aryl group is c i s to the bridgehead hydrogen H 5 in the trans-cyclobutanol . The minor cyclobutanol isomer observed from the photolysis of a-methyl-a-cyclopentyl-para-carboxyacetophenone was i den t i f i ed by the presence of a base peak in i t s g.c.m.s. which corresponds to a retro 2+2 fragmentation of the parent ion. Geometry of Hydrogen a b s t r a c t i o n Of the f i f teen substituted acetophenones photolyzed in th is study, f i ve have had the i r structure determined by X-ray crystal lography. For these f i ve cases, the geometry of the i n i t i a l hydrogen abstract ion step can be observed. The geometry of hydrogen abstract ion by the carbonyl oxygen has been analyzed with respect to the previously defined parameters d, x and A (f igure 10). In addi t ion, the overal l geometry of the six-membered t rans i t i on states for abstract ion have also been observed. These resul ts are shown in table IV. As seen in table IV, the distance 75 ketone d(A) * ( ° ) M ° ) Abstract ion geometry 2.7 46 77 boa t 6 2 2.7 49 77 boa t 6 2 2.6 50 79 chai r 6 2 2.6 44 90 b o a t 5 0 . 5 3 2.7 61 73 chai r 6 1 3.1* 3.5 50 56 58 73 boat 6 3 Table IV: Hydrogen abstract ion geometries fo r several subst ituted acetophenones; (*) t w 0 conformations in the so l i d state between the carbonyl oxygen atom and the y-hydrogen atom can be as great as 3.1 A and s t i l l react photochemically in the so l id state. C lear ly , most of the abstract ing distances shown in table IV f a l l wi th in the 76 hydrogen abstract ion l im i t of approximately 2.7 A , as suggested by Scheffer and T r o t t e r 2 0 * 2 1 . The a-methyl-a-cyclopentyl ketone was observed to have an abstract ing distance of 3.1 A . Scheffer and Trot ter have also observed an abstaction distance of 3.1 A fo r a-cyclobutyl-pa ra-chloroacetophenone 2 1. This result suggests that 2.7 A may not be the upper l im i t fo r hydrogen abstaction. A l te rnat i ve ly , i t is possible that bond rotations in the crystal may lead to a more favorable abstract ion geometry. The value of t has been observed to range from 44° to a maximum of 61°, yet hydrogen abstract ion is s t i l l observed. This data suggests that abstract ion may occur from geometries in which the angle T has deviated substant ia l ly from the ideal value of 0°. The observed values of A are quite close to the ideal value of 90-120° as suggested by Scheffer and T r o t t e r 2 0 * 2 1 . The geometry of the six-membered t rans i t i on state fo r hydrogen abstract ion has been observed to vary from a chair to a boat conf igurat ion. It can be seen that fo r the a-cyc loa lky l -para-carboxyacetophenones (cyclohexyl and cyc loocty l ) , the s ix membered t r ans i t i on state adopts a boatl ike geometry. This result is in agreement with the boatl ike abstract ion geometries observed fo r the series of a - cyc l oalkyl-para-chl oroacetophenones reported by Scheffer and T r o t t e r 2 0 * 2 1 . The introduct ion of an a-methyl substituent into these compounds changes the geometry fo r hydrogen abstract ion such that abstract ion of a Y-hydrogen atom by the carbonyl oxygen of an a-methyl-a-cycloalkyl-para-carboxyacetophenone (cyclohexyl and cyc loocty l) occurs 77 X boat-like transition state c h a i r - l i k e transition state Figure 55: Boat l ike and cha i r l i ke abstract ion geometries through a cha i r l i ke t r ans i t i on state. This change in the abstract ion geometry of the six-membered t rans i t i on state is the result of a rotat ion about the a-carbon-carbonyl carbon bond which occurs with the addit ion of an a-methyl subst i tuent. For example, the addit ion of an a-methyl group onto a -cyc l ooctyl-para-carboxyacetophenone results in a 91° rotat ion about the a-carbon-carbonyl carbon bond as shown in f igure 55. The geometric change is induced by a s te r i c repulsion between the a-methyl group and the aromatic r ing. Stereodiagrams for the boat and chair abstract ion geometries are shown in f igure 56. Unlike the a-methyl-a-cycl ooctyl and a-methyl-a-cyclohexyl-para-carboxyacetophenones, a-methyl-a-cyclopentyl-para-carboxyacetophenone assumes a boatl ike hydrogen abstract ion geometry. 78 C(U) C(li) Figure 56a: a-Cyclooctyl-para-carboxyacetophenone, with a boat l ike abstract ion geometry 79 Figure 56b: a-Methyl-a-cyclooctyl-para-carboxyacetophenone, with a chairlike abstraction geometry Ra t i o s o f c y c l i z a t i o n to c leavage The 1,4 biradical generated from photolysis of a-methyl-a-cycloalkyl-para-carboxyacetophenones can undergo three possible transformations. The biradical can fragment to form cleavage products, close to form cyclobutanol products or revert to the ground state ketone by reverse hydrogen abstraction (figure 57). The percentage of cleavage 80 Figure 57: Photoproducts derived from a-methyl -a-cyc loalky l-para-carboxyacetophenones products from the b i rad ica l generated in benzene, ace ton i t r i l e and the so l i d state are shown in f igure 58. As shown in the diagram, the rat io of cyc l i za t ion to cleavage in the so l i d state i s not substant ia l ly d i f fe rent from that observed in so lu t ion . This resu l t suggests that the motions required for the formation of cleavage and cyc l i za t ion products 81 Ring Size (n) Figure 58: % cleavage from the photolysis of a-methyl-a-cycloalkyl acetophenones in benzene, ace ton i t r i l e and the so l i d state are topochemically permitted in the so l id state. Scheffer has shown that photolys is of ene-dione 1 (f igure 59) also gives the same photoproduct rat ios in the so l id state and benzene 4 8 . This resu l t i s due to the fact 82 Benzene S o l u t i o n l S o l i d s t a t e 1 Figure 59: The photochemistry of ene-dione 1 in benzene and the so l i d state that the molecular motions leading to the two photoproducts are topochemically allowed in the so l id state. It i s also possible that the s im i l a r i t y between the solut ion and so l i d state resul ts may be due to crysta l melting during photo lys is . The percentage of cleavage products from the photolysis of a ser ies of a-cycloalkyl-para-carboxyacetophenones (cyc loocty l , cyc lohepty l , cyclohexyl and cyclopentyl) in polar solvents (ace ton i t r i l e and t-BuOH 5 0) , benzene and the so l id state are shown in f igure 6 0 5 0 . From th is p lo t , i t can be seen that the rat io of cyc l i za t i on to cleavage is s l i gh t l y 83 8. 8-*> 8 c e s R-A Benzene • l Acetonitrile •2t-BuOH O Solid State O 5.0 e.o — i — 7.0 - 1 — e.o Ring Size (n) Figure 60: % cleavage from the photolysis of a -cyc loa lky l -para-carboxyacetophenones in polar solvent, benzene and the so l i d s t a t e 5 5 d i f fe rent in the so l i d state as compared to so lu t ion . The most dramatic ef fect is an increase in the amount of cyc l i za t ion observed when a-cyclooctyl-para-carboxyacetophenone is photolyzed in the so l id state. I t has been observed that a l l of the cyclooctyl der ivat ives exh ib i t higher 84 ratios of cyc l i za t i on in the so l id than in so lut ion. The percent cleavage from the photolysis of several a-cyc loocty l-para-subst i tuted acetophenones is shown in f igure 61. In the case of the a-cyc loocty l-para-subst i tuted co • CD CP C o O Benzene ^ A c e t o n i t r i l e • Sol id State X - CI X - CN p a r a - s u b s t i t u e n t — i r X - COOH Figure 61: % cleavage vs para-substituent in various media for the a-cyc loocty l acetophenones 85 acetophenones i t appears that the crysta l l a t t i c e s l i gh t l y impedes the rotat ions required for cleavage, thus favouring cy c l i z a t i on . The nature of these motions w i l l be discussed l a t e r . Referring back to f igures 58 and 60, i t i s apparent that there is no corre la t ion between the cycloalkane r ing size and the cyc l i za t i on to cleavage r a t i o . I t is also evident that the cyclohexyl and the cyclooctyl der ivat ives give the highest amount of cyc l i z a t i on , whereas the cyclopentyl and cycloheptyl der ivat ives tend to favour cleavage. This trend was also observed by Scheffer and Trotter for the photolysis of a series of a -cyc loa lky l -para-ch loroacetophenones 2 0 » 2 1 . I t was o r i g i na l l y thought that the se l e c t i v i t y between cyc l i za t i on and cleavage i s due to whether the "p" o rb i ta l s of the b i rad ica l were in a favourable geometry for cleavage, keeping in mind that cleavage i s considered to be most favourable when the two "p" o rb i ta l s are coplanar with the a-p a-bond being cleaved. The calculated geometry of the "p" o rb i ta l s for the b i rad ica l s generated from the a-cycloalkyl-para-chloroacetophenones (cyc looc ty l , cyc lohepty l , cyclohexyl,. cyclopentyl and cyclobutyl) are shown in f igure 62 along with the rat io of cyc l i za t ion to cleavage in the so l i d state. The geometry of the radical "p" orb i ta l on the carbonyl carbon i s assumed to be orthoganol to the plane consist ing of the carbonyl carbon atom, the oxygen atom and the two carbon atoms alpha to the carbonyl carbon. The geometry of the radical "p" orb i ta l on the y-carbon i s assumed to be orthoganol to the plane of the p, y and 6 carbon atoms. I t is c lear from f igure 62 that the calculated b i rad ica l "p" orb i ta l 86 Ring Size 0! (°) 02 (°) % cleavage 4 90 129 9 2 2 1 5 90 112 9 2 2 1 6 95 88 4 5 2 1 7 94 99 69 2 1 8 96 132 4 Figure 62: % cleavage in the so l id state as compared to the values of 0X and 02 f ° r several a-cycloalkyl-para-chloroacetophenones geometries do not corre late with the observed rat io of cyc l i za t i on to cleavage. If th is was the case then these b i rad ica ls would be expected to give mostly cyc l i za t i on products, since the b i rad ica l "p" o rb i ta l s are essent ia l l y orthoganol to the o-bond being cleaved. 87 In l i gh t of th is resul t we must look at other factors which may govern the rat io of cyc l i za t i on to cleavage. These may be the fo l lowing: 1. the nature of the molecular motions required for product formation and; 2. the thermodynamic s t a b i l i t i e s of the products formed. Referring to f igure 60, there appears to be a trend toward an increase in the rat io of cyc l i za t i on to cleavage as the cyc loa lky l r ing s i ze increases. The most obvious geometric change observed i s an increase in the magnitude of the intraannular tors ion angle n , accompanying an increase in r ing s i ze ( f igure 63). The values of n recorded in f igure 63 88 I Ring Size n ( ° ) 4 14 5 30 6 55 7 67 8 104 Figure 63: Magnitude of the angle n as the cyc loa lky l r ing size increases from 4 to 8 for the a-cycloalkyl-para-chloroacetophenones have been obtained from crystal !ographic studies of a-cyc loa lky l -para-chl oroacetophenones. If cleavage of the a-cyc loa lky l ketones is to occur, then the intraannular tors ion angle fl must approach a value of 0° to at ta in the syn-pariplanar geometry required for alkene formation. S ign i f i cant deviations of n away from th is geometry should favour c y c l i z a t i on , since cyc l i za t i on does not require a planar t rans i t ion geometry. In addi t ion, 89 when the value of n becomes much greater than 0°, a large motion i s required to at ta in the planar geometry required for cleavage. Thus, the rate of motion of the r ing towards the cleavage geometry may be slow compared to the rotat ions that bring the molecule into the geometry for cyc l i za t i on (f igure 64). For example, photolysis of a-cyc lopentyl-para-carboxyacetophenone resulted in 100% cleavage. In th is case, the intraannular tors ion angle n i s approximately 30° and thus only a small amount of motion i s required for cleavage. On the other hand, the value of n for a-cyclooctyl-para-carboxyacetophenone i s 99° and as a resu l t , a large motion i s required to at ta in the geometry required for cycloalkene formation. Perhaps the increase in the amount of cyc l i za t i on in the Figure 64: Bond rotat ions required for the formation of the trans-cyclobutanol 90 so l i d state photolysis of a-cyc loocty l -para-subst i tuted acetophenones (f igure 60) may be due to a l a t t i c e res t r i c t i on which impedes n rotat ion to the extent that the rotations required for cyc l i za t i on are favoured. If we assume that the rat io of cyc l i za t ion to cleavage for the a-cycloalkyl-para-carboxyacetophenones is so le ly a function of the cycl oalkyl intraannular tors ion angle n , then we would expect the amount of cyc l i za t i on to increase as the intraannular tors ion angle increases. This is not the case and i t is obvious that there are other factors in addit ion to the intraannular tors ion angle which are inf luencing the ra t io of cyc l i za t ion to cleavage. One of these factors may be the thermodynamic s t a b i l i t i e s of the photolysis products. The s t ra in energies of the cycl oalkanes 6 9 (cyc loocty l , cycloheptyl , cycl ohexyl and cycl opentyl) as well as the calculated s t ra in energies fo r the c y c l o a l k ene s 7 0 » 7 1 > 7 2 (c is-cyclooctene, cis-cycloheptene, cyclohexene and cyclopentene) are shown in table V. It can be seen that the s t ra in energy of 91 Ring Size (n) 5 6 7 8 Strain Energies (kcal/mole) cycloalkane 6.5 0.0 6.3 9.6 cycloalkene 6 . 8 7 0 ; 6 . 9 7 1 2 . 5 7 0 ; 2 . 6 7 2 6 . 7 7 0 ; 7 . 2 5 7 2 7 . 4 7 0 ; 8 . 8 7 2 Table V: The s t ra in energies for some cycloalkanes and the ca lcu lated s t ra in energies for some cycloalkenes cyclopentane i s very close to that for cylopentene, whereas the s t ra in energy of cyclohexene is approximately 2.5 kcal/mole higher than cyclohexane. This may be a factor in the large amount of cyc l i z a t i on observed from oc-cyclohexyl-para-carboxyacetophenone as compared to a-cyclopentyl-para-carboxyacetophenone. Likewise, the s t ra in energy difference between cycloheptane and cycloheptene i s also very small which may be a factor in the increase in the amount of cleavage observed in going from the cyclohexyl to the cycloheptyl ketone. According to table V, cyclooctene should be more stable than cyclooctane. This resu l t does not corre late with the photochemical data which shows a large decrease in the amount of cleavage for the a-cyc loocty l -para-subst i tuted acetophenones. The thermodynamic s t ab i l i t y of the cyclobutanol products may also influence the rat ios of cyc l i za t i on to cleavage. It is very d i f f i c u l t to make any corre lat ion between the s t a b i l i t i e s of the bicyclo [n.2.0] 92 alkanols and the observed rat io of cyc l i za t i on to cleavage simply because the thermodynamic data avai lable fo r these systems is quite l im i ted . Some data is avai lable f o r the b icyc lo [n.2.0] alkanes (n=3,4,5,6), but these have been found to vary in the l i t e r a tu re . The calculated s t ra in energies of some bicyc lo [n.2.0] alkanes are shown in f igure 65. The s t ra in ( C Vn n ring s t ra in (kcal/mole) 3 4 5 6 3 0 . 5 1 7 ; 3 4 . 4 7 4 28 .2 7 5 ;32 .0 7 1 4 - 3 2 . 0 7 8 - 3 6 . 8 7 8 Figure 65: Calculated s t ra in energies fo r some bicyc lo [n.2.0] alkanes energies reported fo r the b i c y c l i c [5.2.0] and [6.2.0] systems have not been calculated d i rec t l y but are reported in the l i t e ra tu re as approximations based on b icyc lo [n.1.0] alkane s t a b i l i t e s . It is c lear that the rat ios of cyc l i za t ion to cleavage do not correlate well with the reported s t ra in energies fo r b i c y c l i c [n.2.0] alkanes. This is evident when we observe that the b i c y c l i c [6.2.0] alkane system has been reported to have the highest s t ra in energy, yet the bicyc lo [6.2.0] alkanols are the major products from photolysis of a-cyc loocty l -para-subst i tuted acetophenones. There are two problems associated with comparing the s t ra in energies encountered in the formation of the b i cyc l i c [n.2.0] alkanols with the corresponding b i c y c l i c [n.2.0] alkanes. F i r s t l y , in 93 forming the b icyc lo [n.2.0] alkanols we are only interested in the s t ra in energy of forming the cyclobutane r ing. The second ring has al ready been formed. Secondly, the ec l ips ing interact ions involv ing the ring substituents has not been taken into account. In l ight of th is reasoning, ec l ips ing and ring s t ra in cannot be ruled out as factors inf luencing the ra t io of cyc l i za t i on to cleavage. It is possible that the reduced y ie lds of cyc l i za t i on products from the a-cycl oheptyl and a-cycl opentyl ketones may be due to s te r i c and s t ra in factors involved in cyclobutanol formati on. It is also worth noting that the s t ra in energies of the photoproducts often do not correlate with the photoproduct ra t io . Photolysis of cyclobutyl phenyl ketone results in a preference fo r the ring closure product over B e l im ina t i on 7 6 (f igure 66). This result has m i n o r p r o d u c t Figure 66: Photolysis of cyclobutyl phenyl ketone 94 been explained in terms of the radical "p" o rb i ta l s being unable to overlap with the a - p carbon bond as is required for cleavage to occur. The percent cleavage observed in the photolysis of the a-methyl-a-cycloalkyl-para-carboxyacetophenone series ( f igure 58) shows some s im i l a r i t i e s with the percent cleavage observed for the a - cyc loa l ky l -para-carboxyacetophenone series (f igure 60). In both cases the cyc loocty l and cyclohexyl phenyl ketones have been shown to exh ib i t the highest ra t ios of cyc l i za t i on to cleavage with respect to the cyclopentyl and cycloheptyl phenyl ketones. The most dramatic difference between the non-methylated and a-methyl ketones was observed for the a-cyclopentyl ketone der ivat ives . a-Cyclopentyl-para-carboxyacetophenone produces only cleavage products upon photolys is , whereas, for the a-methyl analogue, a-methyl-a-cyclopentyl-para-carboxyacetophenone, cyc l i za t i on accounts for 55% of the tota l products (f igure 67). The difference observed in the 95 ketone % cleavage 45% 100%50 Figure 67: % cleavage recorded fo r non methylated and a-methyl-a-cyclopentyl phenyl ketones ra t io of cyc l i za t i on to cleavage is not due to a change in the intraannular tors ion angle n since a-methyl subst i tut ion does not s i gn i f i c an t l y change the cycloalkyl ring geometry. However, a-methyl subst i tut ion does change the geometry of the ketone. The X-ray crystal structure has indicated that the conformation of the b i rad ica l from a-methyl-a-cyclopentyl-para-carboxyacetophenone ex is ts as shown in f igure 68. The conformation of the a-methyl-a-cyclopentyl ketone as 96 Figure 68: The b i rad ica l generated from a-methyl-a-cyclopentyl-para-carboxyacetophenone as viewed down the a-6 carbon bond viewed down the a-B carbon bond (f igure 68) appears to be in a geometry which very c losely resembles the geometry required fo r cyc l i za t i on . Thus, only a minimum amount of motion is required fo r cyc l i za t i on allowing cyc l i za t i on to compete with cleavage. The motion required for cyc l i za t ion of a-cyc l opentyl - para-chl oroacet ophenone is shown in f igure 69. In th is case, the rate of cleavage is greater than the rate of the bond rotations 97 Figure 69: The b i rad ica l generated from a-cycl opentyl-para-chloroacetophenone as viewed down the a-p carbon bond required fo r c yc l i z a t i on , hence, cleavage is the predominant process. There i s , however, a problem with th is explanation. This problem l i es in the fact that a -cyc l opentyl-para-carboxyacetophenone ex is ts in two lowest energy conformations in the c ry s ta l . One of these conformations resembles the conformation of a -cyc l opentyl-para-chl oroacetophenone as shown in f igure 69, whereas the second resembles the geometry observed fo r a-methyl-a-cycl opentyl-para-carboxyacetophenone as shown in f igure 68. According to the theory just presented, both cyc l i za t ion and cleavage should be observed from the photolysis of a-cycl opentyl-para-carboxyacetophenone. Since only cleavage is observed, th is suggests that 98 e i ther the theory is incorrect or only one of the conformations of a-cycl opentyl- para-carboxyacetophenone is reacting. The hydrogen abstract ion distances (d) and the angles x and A fo r these two conformers are given in f igure 70. Conformer I, which is expected to give mostly Conformer I Conformer II d=2.9A T=48° A=77° Figure 70: Two conformers of the b i rad ica l generated from a-cycl opentyl-para-carboxyacetophenone cleavage products, has a favourable hydrogen abstract ion distance which is within the abstract ion distance of approximately 2.7 A suggested by Scheffer and Trot ter . The values of x and A, 17° and 80°, do not deviate much from the i r ideal values of 0° and 90-120° respect ively. The second conformer, which is expected to produce more cyc l i za t i on products, has a larger hydrogen abstract ion distance of 2.9 A. In addit ion the angle x of 48° deviates considerably from the ideal value of 0°. These angles and distances suggest that conformer I may be reacting more rapidly i f not exc lus ive ly with respect to conformer I I . This may explain why only 99 cleavage is observed fo r the photolysis of a-cycl opentyl-para-ca rboxyacet ophe none. The effect of a-methyl substituents on the rat io of cyc l i za t i on to cleavage for the larger ring a-cyc loa lky l phenyl ketones (cyc loocty l , cycloheptyl and cyclohexyl) appears to be less dramatic than the ef fect produced upon a-methylation of a-cyclopentyl-para-carboxyacetophenone. The rat io of cyc l i za t i on to cleavage fo r a-methy 1-a-cyclohexyl-para-carboxyacetophenone is essent ia l l y the same as observed fo r the non-methylated analogue. For the a-methy1-a-cyclooctyl and a-methyl-a-cycloheptyl acetophenones the amount of cyc l i za t ion is decreased by approximately 15% with respect to the non-a-methylated analogues (see f igures 58 and 60). The reason for th is decrease is not obvious looking at the geometry of the s tar t ing ketone. It may be possible that the a-methyl group may destab i l i ze the t rans i t i on state required f o r cyc l i za t i on via ec l ips ing interact ions with other ring substituents in the formation of the b icyc lo [n.2.0] alkanols (n=5,6). The E f f e c t of D i f f e r e n t Media on the Cyc lobutano l Ra t i o s The rat ios of the cycl obutanols formed from the photolysis of a -cyc loa lky l -para-subst i tuted acetophenones was observed to d i f f e r in d i f ferent media. For example, the ratios of trans- to c is-cyc lobutanols formed from the photolysis of a-cyclooctyl-para-chloroacetophenone in benzene, ace ton i t r i l e and the so l id state are shown in f igure 71. 100 CI Sol vent trans: c is Benzene Aceton i t r i le So l id State 77:23 56:44 96:4 CI 6 t r a n s OH H O - h - V ~ ~ \ hv u ' I J H H c i s CI Figure 71: The rat io of trans- to cis-cyclobutanols formed from the photolysis of a-cycl ooctyl-para-chl oroacetophenone in d i f ferent media In benzene and the so l i d state, formation of the trans-cyclobutanol is favoured. Thus, in these two media, the less hindered cyclobutanol is formed. Photolysis of a-cyclooctyl-para-chloroacetophenone in ace ton i t r i l e resulted in more of the c i s -cyc l obutanol being formed. This result can be explained in terms of hydrogen bonding which increases the s te r i c bulk of the hydroxy radical to the extent that i t becomes able to 101 compete with the aryl group fo r the more stable c is pos i t ion with respect to the nearest bridgehead hydrogen atom in the cyclobutanol. The almost exclusive formation of the trans-cyclobutanol from the so l i d state photolysis of a-cyc loocty l and a-cycloheptyl-para-subst i tuted acetophenones can be attr ibuted to a topochemical r e s t r i c t i on preventing the formation of the cis- isomer. The predicted geometry of the b i rad ica l generated from a-cyclooctyl-para-chloroacetophenone is shown in f igure 72. It should be noted that only one of the two possible disrotatory or conrotatory motions lead to the formation of cyclobutanols with c is-fused r ings. t r a n s - c y c l o b u t a n o l c i s - c y c l o b u t a n o l Figure 72: Geometries of the c i s - and trans-cyclobutanols 102 Formation of the c i s - cyc l obutanol requires a 90° rotat ion of the aryl group. This rotat ion i s topochemically disallowed since i t would resu l t in the aromatic system bumping into the adjacent aryl group. The packing arrangement of the ketone molecules in the crysta l l a t t i c e results in a 3.5 A interplanar distance between the aryl groups. This separation i s not large enough to accommodate the motions required for the formation of the c i s -cyc lobutano l . The packing diagram for a-cyc loocty l -para-chl oroacetophenone is shown in f igure 73. Formation of the Figure 73: Packing diagram of a-cyclooctyl-para-chloroacetophenone trans-cyclobutanol is topochemically allowed since the 90° aryl group rotat ion is not necessary for i t s formation. Model studies also suggest that the trans-cyclobutanol may be much better suited to f i t into the i n i t i a l reactant cavity than the c is -cyc lobutano l . To further ver i fy th is 103 pos s i b i l i t y i t would be benef ic ia l to know the exact product geometries; however, X-ray crysta l structures of the cyclobutanol products are unavai lable. Experimentally, i t was also found that a small amount of the topochemically disfavoured cis-cyclobutanol was formed. This resu l t may be due to a par t ia l melting of the sample during photolys is . The product mixtures obtained from the photolysis of the a-methyl-a-cycloalkyl-para-carboxyacetophenones resul ts in the formation of one major cyclobutanol and one, two or three addit ional minor cyclobutanol products. The major cyclobutanol has the stereochemistry as shown in f igure 74. The methyl group in th is case is trans to the aryl 104 " major " + other c y c l o b u t a n o l s r ing size (n) benzene {%) Ace ton i t r i l e {%) Sol id State (%) 5 76 77 100 6 48 56 49 7 60 54 63 8 76 70 31 Figure 74: Percentage of the major cyclobutanol as a function of the tota l cyclobutanol produced from photolysis of a-methyl - a -cycloalkyl-para-carboxyacetophenones in various media group which i s also the case for the major cyclobutanol derived from a-methylvalerophenone in benzene 3 2 * 3 3 . The aryl group is in the more stable pos i t ion c i s to the nearest bridgehead hydrogen. For most of the a-methyl-a-cycloalkyl-para-carboxyacetophenones, the cyclobutanol ra t io changes very l i t t l e in going from benzene to ace ton i t r i l e to the so l id state. A possible explanation for th is result could be that these compounds are conformational^ r i g i d ex is t ing in the same conformations in the so l i d state and so lut ion. Photolysis of 105 a-methyl-a-cyclooctyl-para-carboxyacetophenone in the so l id state, however, resul ts in a very d i f ferent cyclobutanol ra t io than that observed in so lu t ion . In th i s case the minor cyclobutanol in solut ion has become the major cyclobutanol in the so l i d state. The stereochemistry of th is cyclobutanol is not known since i t was formed in only 6% total y i e l d in ace ton i t r i l e and i so la t ion was not poss ib le. The X-ray crysta l structure of the s tar t ing ketone i s shown in f igure 75. Looking at the geometry of the s tar t ing ketone, i t appears that the 1,4 b i rad ica l "p" o rb i ta l s could close to form a c i s -cyc lobutano l . Further evidence for th is was obtained when i t was found that the cyclobutanol has a s imi lar retention time to the cis-cyclobutanol derived from a-cyclooctyl-para-carboxyacetophenone. 106 Figure 75: X-ray crysta l structure of a-methyl -a-cyc loocty l-para-carboxyacetophenone Unfortunately, without any other structural evidence i t i s impossible to draw any structure, reac t i v i t y cor re la t ions . Quantum Yields and Rate Studies The quantum y ie lds for product formation from the photolysis of several a -cyc loa lky l -para-subst i tuted acetophenones is shown in f igure 76. The quantum y ie lds for these ketones, as determined in benzene so lut ion, 107 n » 6 Ring Size (n) Figure 76: Total product quantum y ie lds fo r several substituted acetophenones in benzene are considerably less than unity. This ine f f i c iency , as suggested by Wagner, can be accounted fo r by reverse hydrogen abstract ion from the hydroxy-radical to the y-carbon rad ica l . The quantum y ie lds for product formation from a-cyclooctyl and a-cycl oheptyl-para-cyanoacetophenones as well as a-cycl oheptyl-para-108 carbomethoxyacetophenone was observed to be approximately 0.17. Wagner has determined that the quantum y ie lds for type II e l iminat ion from para-cyano and para-carbomethoxyvalerophenones are both 0.19 in benzene s o l v en t 5 8 . The quantum y ie lds for tota l product formation from a ser ies of a-methyl-a-cycloalkyl-para-carbomethoxyacetophenones has been observed to be quite low in benzene solvent. I t has been found that the tota l quantum y i e l d for product formation from a-cycloheptyl-para-carboxy-acetophenone is almost three times as large as i t s corresponding a-methyl analogue. Lewis has suggested that the lowering of quantum y ie lds upon a-methyl subst i tut ion may be due to s ter i c interact ions involv ing the a-methyl group which increase the energy of the t rans i t i on states required for cyc l i za t i on and cleavage, making return of the b i rad ica l to the ground state, by reverse hydrogen abstract ion, more f a vou r ab l e 3 2 * 3 3 . I t has been determined by X-ray crystal lography that the B-hydrogen atoms on the a-methyl group may be in a better hydrogen abstract ion geometry than the y-hydrogen atoms on a-methyl-a-cyclooctyl and a-methyl-cyclohexyl-para-carboxyacetophenone, as shown in f igure 77. 109 n Y--hydrogen p-hydrogen d(A) *(°) M°) d(A) M°) 6 2.7 61 73 2.6 6 84 8 2.6 50 79 2.5 32 83 Figure 77: y-Hydrogen and P-hydrogen abstract ion distances and angles fo r a-methyl-a-cyclooctyl and a-methyl-a-cyclohexyl-para-ca rboxyacet ophe nones The data c lear ly indicate that fo r these ketones, the p hydrogen atoms are more favourably oriented fo r abstaction than the y-hydrogen atoms. If we assume that the para-carbomethoxy ketones have a s im i l a r geometry to the para-carboxy ketones in benzene, then the low quantum y ie lds observed fo r the a-methyl ketones may also be due to a reversible p abstract ion. However, i t should be pointed out that the P-hydrogen is primary whereas the y-hydrogen is secondary, thus, the rate of y-hydrogen abstract ion may be much larger than the rate of P-hydrogen abstract ion. For example, i t is known that the rate of y-hydrogen abstract ion i s 25x fas te r fo r valerophenone as compared toibutyrophenone 2 5 . The t e r t i a r y p-met pyre hydrogen has also been observed to be close to the abstract ing carbonyl oxygen. The distance between the P-methine hydrogen has been observed to range from 2.5 A fo r a-cyclooctyl-para-chloroacetophenone, to 3.5 A for a-methyl-a-cyclooctyl-para-no carboxyacetophenone. This data suggests that the low quantum y i e l d s , in benzene, may also be the result of a reversible B-methine hydrogen abst racton. The Stern-Volmer plots for the quenching of a-cycl ooctyl and a-cyc l oheptyl-para-cyanoacetophenone t r i p l e t s in benzene are shown in f igure 78. In both cases, the plots of * /* against quencher in eg in d - t - | | 1 1 1 0.0 0.04 0.08 0.12 Quencher Concentration (M) Figure 78a Ill Figure 78b Figure 78: Stern-Volmer plots for a-cyc l ooctyl-para-cyano-acetophenone (a) and a -cyc l oheptyl-para-cyano-acetophenone (b) concentration (2,5-dimethyl-2,4-hexadiene) are l inear with slopes of 9.11 M"1 and 6.78 M - 1 fo r the a-cyc loocty l and a-cycl oheptyl ketones respect ively. According to the Stern-Volmer relat ionship (appendix I ) , 112 the slope of the plot a>0/* against quencher concentration is equal to kqx where x is the tr i p l e t lifetime and kq is the rate of quenching by 2,5-dimethyl-2,4-hexadiene. The value of kq has been determined to be 5 x 109 M"1 s"1 in benzene, i f i t is assumed that the rate of quenching is diffusion controlled 1 1*, the values of % can be calculated to be 1.82 x 10"9 s and 1.36 x 10 - 9 s for the a-cyclooctyl and a-cycloheptyl-para-cyanoacetophenone triplets respectively. The lifetime T is equal to the inverse of the sum of the rate constants which deactivate the ketone t r i p l e t . If i t is assumed that hydrogen abstraction is the major pathway for deactivation of the ketone t r i p l e t , then x is equal to the inverse of the hydrogen rate constant k^. Thus, the hydrogen abstraction rate constants k H can be calculated to be 5.5 x 108 s - 1 and 7.4 x 108 s" 1 for the a-cyclooctyl and a-cycloheptyl ketones respectively. These rates are similar in magnitude to the rate of hydrogen abstraction of 5.7 x 108 s _ 1 and 6.7 x 108 s" 1 for a-cycloheptyl and a-cyclooctyl-para-chloroacetophenones r e s p e c t i v e l y 2 1 * 7 9 . Wagner has found the rates of y-hydrogen abstraction for para-cyanovalerophenone to be 6.89 x 107 s - 1 as compared to 3.7 x 10 7 s _ 1 for para-chlorovalerophenone 5 8. It is interesting to note that the rate of hydrogen abstraction by the a-cyclooctyl and a-cycloheptyl-para-substituted acetophenones (para-chloro and para-cyano) are approximately lOx faster than the corresponding para-substituted valerophenones. This result is likely due to the fact that the v-hydrogen in the a-cycloalkyl acetophenones is in a 113 better geometry for abstract ion than the corresponding para-substituted valerophenones. Another example of th i s i s shown in f igure 79. The b i c y c l i c ketone undergoes hydrogen abstract ion nearly lOOx faster than Figure 79: Hydrogen abstract ion rate constants for valerophenone and a r i g i d b i c y c l i c ketone valerophenone. This resu l t has been attr ibuted to the fact that the Y-hydrogen atom and the carbonyl oxygen of the b i cyc l i c ketone are locked in a conformation par t i cu la r l y favourable for hydrogen abstraction whereas valerophenone must form a six-membered t rans i t ion state for abstraction to o c cu r 7 7 . 114 EXPERIMENTAL General Melting points (mp_) were determined on a Fisher-Johns hot stage apparatus and are uncorrected. Infrared spectra (i_r) were recorded on a Perkin-Elmer model 710 B spectrometer or a Perkin-Elmer model 1710 Four ier transform spectrometer. Infrared spectra recorded on the Perkin-Elmer model 710 B spectrometer were ca l ibrated using the 1601 cm - 1 band of polystyrene. The posi t ion of absorption maxima are given in cm - 1 . Neat infrared spectra were obtained fo r a l l o i l s and the spectra of so l ids were obtained in KBr pe l l e t s . U l t rav io le t spectra (uv) were obtained in ace ton i t r i l e or MeOH and recorded on a Pye Unicam Ph 880 UV/Vis spectrophotometer. The proton nuclear magnetic resonance spectra (XH nmr) were observed in deuterochloroform and recorded at 80 MHz on a BrCfker WP-80 spectrometer, at 270 MHz using an Oxford instrument with a 63.4 KG superconducting magnet, a Nickolet 32 K computer and Broker TT-23 console, at 300 MHz on a Varian XL-300 spectrometer or at 400 MHz on a BrUker WH-400 spectrometer. Signal posit ions are given in ppm with tetramethylsi 1 ane as the reference. Signal mu l t i p l i c i t i e s and coupling constants are l i s t ed in brackets. Low and high resolut ion mass spectra (ms) were recorded on a Kratos model MS 50 mass spectrometer. Combined gas chromatography-mass spectroscopy was performed on a Kratos MS 80 mass spectrometer coupled to a Karlo-Erba gas chromatograph. Gas chromatography fo r the product rat io studies was performed on a Hewlett-Packard 5890 A gas chromatograph coupled to a Hewlett-Packard 115 3392 A integrator. The ca r r i e r gas was helium and the mode of detection was flame ion i za t ion . The column head pressure was 20 p s i . Retention times (rt) are recorded in minutes and the fol lowing column and programs were used: .210° Program 1: i ^ L . ' 20°C/min 1 min Column A: Carbowax 12m (0.25n) .200° Program 2: I1°L.-" 2 0 ° C / m i n 1 min A l l reactions involv ing water-sensit ive reagents were carr ied out under dry nitrogen using oven-dried glassware. The solvents and reagents were pur i f ied as fo l lows: tetrahydrofuran was d i s t i l l e d from l i th ium aluminum hydride; benzene, di i s op ropy 1 amine, dimethyl sulphoxide and ethanol were d i s t i l l e d from calcium hydride. Benzene used in photochemical quenching and rate studies was washed with sulphuric ac id, water, d i lute sodium hydroxide and water. It was then dried over phosphorous pentoxide and d i s t i l l e d . Spectral grade benzene and ace ton i t r i l e were used fo r product rat io determinations. Photolysis was performed using a 450 W medium pressure Hanovia lamp placed in a water-cooled Pyrex immersion well (X > 290 nm) or a Molectron UV 22 pulsed nitrogen laser (A. = 337 nm). Microanalysis was performed by Peter Borda of the U.B.C. Chemistry Department. The X-ray crysta l structure of compound 30 was determined by 116 Dr. Sara A r i e l , and a l l the remaining X-ray structures were determined by Stephen Evans. Synthes i s o f S t a r t i n g M a t e r i a l s Cy c l oo c t y l Bromide (1) Following the procedure of W i l l s ta t te r and Waser 5 4 , 274 g (2.5 moles) of cyclooctene was added to 400 mi of g lac ia l acet ic ac id . This solut ion was s t i r r ed at room temperature while hydrobromic acid was slowly bubbled through i t . The hydrobromic acid addit ion was maintained for 5 hours, af ter which time the addit ion was stopped and the solut ion s t i r r ed for twelve addit ional hours. The mixture was taken up in 500 mi of water and the organic layer was extracted three times with 200 ml of d iethyl ether. The combined ether extracts were washed twice with 100 mil of water followed by 100 ml of aqueous sodium bicarbonate solut ion and f i n a l l y with a further 100 ma of water. The organic layer was dried over anhydrous sodium sulphate and f i l t e r e d . The product was concentrated by rotary evaporation followed by vacuum pumping. D i s t i l l a t i o n at 83°C (0.5 mm Hg) y ie lded 337 g (1.8 moles, 71% y ie ld ) of the c lear o i l product ( l i t 5 4 : b.p. 90.5-91.5°C (10 mm Hg); y i e l d , 93%): lH nmr (CDCA3, 80 MHz) 1.1-1.9 (10H, m), 2.0-2.5 (4H, m), 4.4 (IH, m); m/e ( re la t i ve intens i ty) 111 (52.6), 69 (100). 117 Cyclooctyl Acetic Acid (2) Following the procedure of Bl icke and Johnson 5 5 , 19.8 g (0.79 moles) of sodium metal was slowly added to 460 mSL of dry ethanol which was s t i r r i ng under a nitrogen atmosphere. When a l l of the sodium metal had dissolved, 160 g (0.86 moles) of diethyl malonate was added dropwise, over 10 minutes, to the s t i r r i n g solut ion of sodium ethoxide. The reaction was s t i r r ed at room temperature for two hours. Next, 150 g (0.79 moles) of cycloocty l bromide (1) was added to the reaction mixture, dropwise over a period of 15 minutes. The reaction was brought to ref lux and s t i r r ed for 3.5 days. I t was then cooled to 0°C and the prec ip i tated sodium bromide sa l t was removed by suction f i l t r a t i o n . The ethanol solvent was removed by rotary evaporation to y i e l d a dark o i l . The o i l was added to a rapidly s t i r r i ng solut ion of 300 mJl water, 89 g of potassium hydroxide and 40 ml of ethanol. The reaction was heated to ref lux for a period of 3.5 hours. The solut ion was cooled to room temperature, a c i d i f i ed with 160 ml of concentrated hydrochloric ac id , and s t i r r ed for 24 hours. The resultant o i l y layer was removed and the remaining aqueous phase was extracted twice with 100 ml of diethyl ether. The o i l y layer and organic extracts were combined, washed with 100m£ of water and dried over anhydrous magnesium sulphate. The solut ion was f i l t e r e d and concentrated by rotary evaporation. The resultant o i l was transferred to a round bottom f lask containing 1 g of copper-bronze and heated to approximately 100°C under vacuum (35 mm Hg) for 4 days. The resultant product d i s t i l l e d at 168-172°C (0.5 mm Hg) to y i e l d 61.7 g (0.36 moles, 46% y i e l d ) of the product ( l i t 5 5 : y i e l d 42.5%): i r (neat) 118 1708 cm-1 (broad, OO) , 3000 cm"1 (broad, OH); XH nmr (CDCi 3 , 80 MHz) 1.0-1.9 (15H, m), 2.3 (2H, s ) , 10.84 (IH, s) ; m/e ( re la t ive intens i ty) 170 (m+, 1.7), 152 (0.82), 111 (100), 69 (91.3). Cycloheptenyl Acet ic Acid (3) Following the procedure of McCarthy et a l . 5 6 , 100 g (0.89 moles) of cycloheptanone was added to 150 ml of dry benzene. Cyanoacetic acid (76 g, 0.89 moles) and 3.0g (50 mmoles) of ammonium acetate were added to the f lask , and the reaction was brought to re f lux . The reaction was maintained at ref lux for 2.5 days while water was continuously being removed from the react ion. When no more water was being evolved the reaction was stopped and the benzene solvent was removed by rotary evaporation to y i e l d an o i l . The o i l was decarboxylated by heating i t at approximately 100°C at reduced pressure (30 mm Hg) for a period of 1 day. The o i l was cooled and taken up in 100 ml of diethyl ether. The organic phase was washed with 50 ml of water, 50 ml of a saturated sodium bicarbonate solut ion and 50 ml of water. The ether layer was dried over anhydrous sodium sulphate and f i l t e r e d . The ether was removed by rotary evaporation and the o i l d i s t i l l e d at 128-134°C (26-30 mm Hg): ir_ (neat) 2280 cm - 1 (C^N). The resultant o i l was added to a s t i r r i n g solut ion of 250 ml water, 80 g of sodium hydroxide and 30 mi of water. The mixture was brought to ref lux and allowed to react for 3 days. The reaction was cooled to room temperature and ac i d i f i ed with 170 ml of concentrated hydrochloric ac id . The reaction was s t i r r ed at room temperature for 1 day. The o i l y layer was separated from the aqueous layer and the aqueous layer extracted twice with 150 ml of diethyl ether. The ether 119 extracts and the o i l y layer were combined, dried over anhydrous sodium sulphate, and f i l t e r e d . The ether solvent was removed by rotary evaporation to y i e l d a yel low o i l . The o i l was d i s t i l l e d at 150-160°C (15 mm Hg) to y i e l d 72.1 g (0.47 moles, 53% y i e l d ) of a c lear o i l ( l i t 5 6 : b.p. 155-160 (15 mm Hg); y i e l d 75%): l r (neat) 1635 cm- 1 (C=C), 1704 cm" 1 (broad, C=0), 2900 cm"1 (broad, OH); ^ nmr (CDCi 3, 400 MHz) 1.45-1.6 (4H, m), 1.6-1.8 (4H, m), 2.11 (2H, m), 2.20 (2H, m), 5.71 (IH, m), 10.4 (IH, s, broad); m/e ( re la t i ve intens i ty) 154 (m+, 42.6) 136 (14.7), 94 (100). Cyc lohepty l A c e t i c A c i d (4) Following a modified procedure of Sauvage et a l . 5 7 , 27.2 g (0.177 moles) of cycloheptenyl acet ic acid (3) was dissolved in 75 ml of dry methanol and placed in a bomb hydrogenation apparatus. To th is was added 2 g of 10% palladium on charcoal. The reaction was s t i r r ed at room temperature for two days under 500 l b s / i n 2 of hydrogen gas. The mixture was f i l t e r ed and the methanol removed by rotary evaporation to y i e l d an o i l as product: j_r (neat) 1708 cm"1 (broad, C=0), 2930 cm- 1 (broad, OH); LH nmr (CDC*3, 80 MHz) 0.7-2.0 (13H, m), 2.3 (2H, d, J=7 Hz), 10.7 (IH, s, broad); m/e ( re la t i ve intens i ty) 156 (m+, 2.1), 138 (2.3), 97 (100). Cyc l oo c t y l Ace ty l Ch l o r i d e (5) Following a modified procedure of Bl icke and Johnson 5 5 , 3.4 g 120 (0.020 moles) of cycloocty l acet ic acid (2) was placed in a dry round bottom f lask . To th is was added 3 mi (0.042 moles) of thionyl ch lor ide, and the reaction was s t i r r ed at room temperature for 45 minutes. The excess thionyl chlor ide was removed by vacuum pumping and the resultant o i l was d i s t i l l e d at 122°C (0.6 mm Hg) to y i e l d 3.43 g (0.018 moles, 91% y i e l d ) of the product. The cyclooctyl acetyl chlor ide was immediately u t i l i z e d in Fr iede l -Craf ts acylat ion reactions and no spectroscopic data was obtained. Cyc lohepty l Ace ty l Ch l o r i d e (6) Acid chlor ide (6) was prepared from cycloheptyl acet ic acid (4) in the same sequence of steps as in the synthesis of cyclooctyl acetyl chlor ide (5). The product was d i s t i l l e d at 102°C (0.5 mm Hg) to y i e l d an o i l in 93% y i e l d . The cycloheptyl acetyl chlor ide was immediately used in Fr iede l -Craf ts acylat ion reactions and no spectroscopic data was obtained. Cyc lohexy l Ace ty l Ch l o r i d e (7) Acid chlor ide (7) was prepared from cyclohexyl acetic acid (Aldr ich) in the same sequence of steps as in the synthesis of (5). The product was d i s t i l l e d at 62°C (0.5 mm Hg) to y i e l d a c lear l i qu id in 94% y i e l d . The cyclohexyl acetyl chlor ide was immediately used in Fr iede l -Craf ts acylat ion reactions and no spectroscopic data was obtained. 121 Cyc lopenty l Ace ty l Ch l o r i d e (8) Acid Chloride (8) was prepared from cyclopentyl acet ic acid (Aldr ich) in the same sequence of steps as in the synthesis of (5). The product was d i s t i l l e d at 36°C (0.5 mm Hg) to y i e l d a c lear l i qu i d in 95% y i e l d . The cyclopentyl acetyl chlor ide was immediately used in Fr iede l -Craf ts acy lat ion reactions and no spectroscopic data was obtained. 2-cyc looc ty l - l - ( 4 - ch1oropheny1 )-ethanone ( 9 ) 6 2 a-Cyclooctyl-para-chloroacetophenone (9) was prepared fol lowing a modified procedure of Wagner et a l . 5 8 ; 3.43 g (18 mmoles) of cyclooctyl acetyl chlor ide (5) was added to 2.4 g (18 mmoles) of aluminum t r i c h l o r i d e . To th is mixture was added 5.5 mi (54 mmoles) of chlorobenzene and the reaction was s t i r red under dry condit ions. Bubbles of hydrochloric acid were observed to be evolved. The mixture was allowed to s t i r at room temperature for 24 hours. The reaction was cooled to 0°C and quenched with ice cold water. The organic phase was extracted twice with 100 ml of diethyl ether. The combined organic extracts were washed with 50 mi of an aqueous sodium bicarbonate solut ion and twice with 50 mi of water. The organic phase was dried over anhydrous sodium sulphate and f i l t e r e d . The diethyl ether was removed by rotary evaporation and vacuum pumping to y i e l d a yellow o i l . The o i l was d i s t i l l e d and the higher bo i l i ng f ract ion was co l lected at 219°C (0.3 mm Hg) to y i e l d a c lear o i l which immediately c r y s t a l l i z ed to y i e l d 3.55 g (13 mmoles, 75% y ie ld ) of the product. Rec rys ta l l i za t ion from ethanol y ie lded white c rys ta l s , mp_ 122 48-49°C: vr (KBr) 1681 cm"1 (C=0); XH nmr (CDCA3, 400 MHz) 1.38 (2H, m), 1.45-1.80 (12H, m), 2.26 (IH, m), 2.84 (2H, d, J=8 Hz), 7.42 (2H, d, J=8.8 Hz), 7.88 (2H, d, J=8.8Hz); m/e ( re la t i ve in tens i ty) 264/266 (m+, 0.45/0.13), 154/156 (100/35.9), 139/141 (56.4/19.3); ca lculated  mass, C 1 6 H 2 1 0 C i 3 5 / C 1 6 H 2 1 0 C X 3 7 : 264.1281/266.1281, Found: 264.1269/266.1255; Ana l . , ca lculated for C 1 6 H 2 i0CA: C, 72.56; H, 8.00, Found: C, 72.69; H, 8.00; uv Umax, n , n * , MeOH) 316 nm, emax=40 l i t r e s • moles - 1 • c m - 1 . 2-cyclooctyl-l-(4-methoxypheny1)-ethanone (10) a-Cyclooctyl-para-methoxyacetophenone (10) was prepared from anisole and cyclooctyl acetyl chlor ide in the same sequence of steps as in the synthesis of (9). The o i l recovered was d i s t i l l e d at 195-200°C (0.5 mm Hg) to y i e l d a c lear o i l . The o i l was recrysta l1 ized 4 times from petroleum ether at approximately -70° to y i e l d an o i l at room temperature as the f ina l product in 47% y i e l d : j_r (neat) 1676 cm - 1 (C=0); lH nmr (CDCJI3, 400 MHz) 0.85 (IH, m), 1.2-1.8 (13H, m), 2.24 (IH, m), 2.98 (2H, d, J=8Hz), 3.82 (3H, s) , 6.89 (2H, d, J=8.8 Hz), 7.90 (2H, d, J=8.8 Hz); m/e ( re la t i ve in tens i ty) 260 (m+, 0.10), 150 (100), 135 (65.7). 2-cyclooctyl-l-(4-methy!phenyl)-ethanone (11) a-Cyclooctyl-para-methylacetophenone (11) was prepared from toluene and cyclooctyl acetyl chlor ide in the same sequence of steps as in the synthesis of (9). The o i l recovered was d i s t i l l e d at 190-200°C (0.5 mm Hg) to y i e l d a c lear o i l as product in 66% y i e l d : ir^  (neat) 123 1685 cm-1 (C=0); 1H nmr (CDCi 3 , 400 MHz) 1.3-1.7 (14H, m), 2.27 (1H, m), 2.39 (3H, s ) , 2.82 (2H, d, J=7.6 Hz), 7.23 (2H, d, J=8.4 Hz), 7.84 (2H, d, J=8.4 Hz); m/e ( re la t i ve intens i ty) 244 (m+, 0.10), 134 (100), 119 (30.7); ca lculated mass, C 1 7 H 2 4 0 : 244.1827, Found: 244.1831. 2-cyclooctyl-l-(4-f1uoropheny1)-ethanone (12) a-Cyclooctyl-para-fluoroacetophenone (12) was prepared from fluorobenzene and cyclooctyl acetyl chlor ide in the same sequence of steps as in the synthesis of (9). The o i l recovered was d i s t i l l e d at 196-198°C (0.5 mm Hg) to y i e l d a c lear o i l as product in 83% y i e l d : ir_ (neat) 1682 cm"1 (C=0); lH nmr (CDCi 3 , 400 MHz) 1.3-1.8 (14H, m), 2.27 (IH, m), 2.84 (2H, d, J=7.6 Hz), 7.1 (2H, m), 7.9 (2H, m); m/e ( re la t i ve in tens i ty) 248 (m+, 2.20), 138 (100), 123 (40.7). 2-cycloheptyl-l-(4-f1uoropheny1)-ethanone (13) a-Cycloheptyl-para-fluoroacetophenone (13) was prepared from fluorobenzene and cycloheptyl acetyl chlor ide (6) in the same sequence of steps as in the synthesis of (9). The o i l recovered was d i s t i l l e d at 159°C (0.5 mm Hg) to y i e l d a c lear o i l as product in 80% y i e l d : ir^  (neat) 1686 cm"1 (C=0); XH nmr (CDCi 3 , 400 MHz) 1.26 (2H, m), 1.38-1.85 (10H, m), 2.22 (IH, m), 2.85 (2H, d, J=7.6 Hz), 7.10 (2H, m), 7.98 (2H, m); m/e ( re la t i ve intens i ty) 234 (m+, 1.9), 138 (100), 123 (70.0), 95 (35.8). 2-cyclohexyl-l-(4-fluorophenyl)-ethanone (14) 6 0 a-Cyclohexyl-para-fluoroacetophenone (14) was prepared from 124 fluorobenzene and cyclohexyl acetyl chloride (7) in the same sequence of steps as in the synthesis of (9). The o i l recovered was d i s t i l l e d at 138°C (0.5 mm Hg) to y i e l d a c lear o i l in 87% y i e l d : j_r (neat) 1686 cm"1 (OO): lH nmr (CDCi3 , 300 MHz) 0.85-1.4 (5H, m), 1.5-1.85 (5H, m), 2.09 (IH, m), 2.79 (2H, d, J=7.5 Hz), 7.11 (2H, m), 7.97 (2H, m); m/e (re lat ive in tens i ty) 220 (m+, 3.0), 138 (100), 123 (58.9), 95 (20.3); calculated  mass, C 1 H H 1 7 0F : 220.1263, Found: 220.1264. 2 - cy c1open t y l - l - ( 4 - f l uo ropheny l ) - e thanone ( 1 5 ) 6 0 a-Cyclopentyl-para-fluoroacetophenone (15) was prepared from fluorobenzene and cycl opentyl acetyl chloride (8) in the same sequence of steps as in the synthesis of (9). The o i l recovered was d i s t i l l e d at 129°C (0.7 mm Hg) to y i e l d a c lear o i l product in 88% y i e l d : j! (neat) 1687 cm"1 ( 0 0 ) , XH nmr (CDCi3 , 300 MHz) 1.13 (2H, m), 1.56 (4H, m), 1.85 (2H, m), 2.33 (IH, m), 3.92 (2H, d, J=7.5 Hz), 7.09 (2H, m), 7.95 (2H, m), m/e (re lat ive in tens i ty) 206 (m+, 3.5), 138 (45.0), 123 (54.3), 95 (100). 2 - cy c l ooc t y l - 2 -me thy l - l - ( 4 - f 1uo ropheny l ) - e t hanone (16) a-Methyl-a-cyclooctyl-para-fluoroacetophenone (16) was prepared fo l lowing a modified procedure of Creger et a l . 5 9 , in which 100 mi of dry tetrahydrofuran was added to 5.1 mi (36 mmoles) of diisopropylamine. This mixture was s t i r r ed under a nitrogen atmosphere and cooled to 0°C fo r a period of 5 minutes. A solut ion of 23.4 mi of 1.55 M n-butyl l i th ium in hexanes was slowly added to the f lask and the resultant so lut ion was 125 s t i r r ed at 0°C for 20 minutes. Ketone (12) (7.5 g, 30 mmoles) was dissolved in 20 ml of dry tetrahydrofuran and th is solut ion was added dropwise over 10 minutes to the s t i r r i n g solut ion of l i th ium di isopropyl amide. The reaction was s t i r r ed at 0°C for 2 hours. The generation of the enolate could be monitored by the formation of a deep red colored solut ion in the reaction f lask . Methyl iodide (2.3 ml, 36 mmoles) was added to the reaction and the solut ion was allowed to slowly warm to room temperature. The reaction was s t i r red at room temperature for two days. The reaction of the enolate with the methyl iodide could be monitored by observing the loss of the deep red color in the so lut ion. The reaction was quenched with 50 ml of water. The organic phase was extracted twice with 100 ml of diethyl ether. The combined extracts were washed with 50 ml of an aqueous brine solut ion and then twice with 50 ml of water. The organic phase was dried over anhydrous sodium sulphate and f i l t e r e d . The diethyl ether solvent was removed by rotary evaporation and vacuum pumping to leave 7.5 g (28 mmoles, 93% y i e l d ) of an o i l . The o i l was analyzed by gas chromatography and found to contain 10% star t ing material and 90% product: rr (neat) 1682 cnr 1 (C=0); lH nmr (CDCi 3, 300 MHz) 1.13 (3H, d, J=7.0 Hz), 1.20-1.80 (14H, m), 2.03 (IH, m), 3.33 (IH, m), 7.31 (2H, m), 7.96 (2H, m); m/e ( re la t ive intens i ty) 262 (m+, 0.8), 152 (100), 123 (74.0), 95 (38.0). 2-cycloheptyl-2-methyl-l-(4-f1uoropheny1)-ethanone (17) a-Methyl-a-cycloheptyl-para-fluoroacetophenone (17) was prepared 126 from (13) in the same sequence of steps as in the synthesis of (17). An o i l was iso lated in 93% y i e l d . The o i l was analyzed by g.c. and found to contain 13% star t ing material and 87% product: ir_ (neat) 1682 cm - 1 (C=0); XH nmr (CDCA3, 300 MHz) 1.10 (3H, d, J=7.0 Hz), 1.1-1.8 (12H, m), 1.9 (IH, m), 3.32 (IH, m), 7.09 (2H, m), 7.93 (2H, m); m/e ( re la t i ve in tens i ty) 248 (m+, 0.7), 152 (100), 123 (77.1), 95 (25.8). 2-cyclohexyl-2-methy1-l-(4-fluorophenyl)-ethanone (18) a-Methyl-a-cyclohexyl-para-fluoroacetophenone (18) was prepared from (14) in the same sequence of steps as in the synthesis of (17). An o i l was iso lated in 85% y i e l d . The o i l was analyzed by g.c. and found to contain 10% star t ing material and 90% product: jjr (neat) 1681 cn r 1 (C=0); lH nmr (CDCA3, 300 MHz) 0.8-1.3 (4H, m), 1.1 (3H, d, J=7 Hz), 1.5-1.8 (7H, m), 3.24 (IH, m), 7.09 (2H, m), 7.95 (2H, m); m/e ( re la t i ve in tens i ty) 234 (m+, 0.5), 152 (100), 123 (54.3), 95 (15.2); ca lculated mass, C 1 5 H 1 9 0F : 234.1420, Found: 234.1428. 2-cyclopentyl-2-methy1-l-(4-fluorophenyl)-ethanone (19) a-Methyl-a-cyclopentyl-para-fluoroacetophenone (19) was prepared from (15) in the same sequence of steps as in the synthesis of (17). A yel low o i l was iso lated in 90% y i e l d . The o i l was analyzed by g.c. and found to contain 8% s tar t ing material and 92% product: ir. (neat) 1681 cm"1 (C=0); lH nmr (CDW 3, 300 MHz) 0.90-1.90 (10H, m), 1.18 (3H, d, J=7 Hz), 3.22 (IH, m), 7.05 (2H, m), 7.95 (2H, m); m/e ( re la t ive in tens i ty) 220 (m+, 0.5), 152 (48.9), 123 (100), 95 (35.2). 127 2-cyc looc ty l - l - (4 - cyanopheny1) -e thanone (20) a-Cycl ooctyl-para-cyanoacetophenone (20) was prepared fol lowing a modified procedure of Wagner and S i ebe r t 5 8 in which 6.67 g (27 mmoles) of (12) was dissolved in 50 mi of dry dimethyl sulphoxide to which was added 4.3 g (89 mmoles) of sodium cyanide. The reaction was heated to 110-120°C and s t i r r ed fo r 2 days under anhydrous condit ions. The reaction was cooled to room temperature and quenched with 50 mi of water. The organic phase was extracted twice with 75 mi of diethyl ether. The ether extracts were combined, washed twice with 50 mi of water and dried over anhydrous sodium sulphate. The so lut ion was f i l t e r ed and the diethyl ether removed by rotary evaporation and vacuum pumping to y i e l d a reddish colored so l i d . The so l i d was chromatographed on a column (2.5 cm x 20 cm) of s i l i c a gel 60 (230-400 mesh) using a step gradient of 0-5% ethyl acetate in petroleum ether as the eluent. The combined fract ions containing the product were concentrated giving 5.5 g (22 mmoles, 76% y i e l d ) of a white so l i d product. Recrysta l1 izat ion from ethanol gave white c rys ta l s , mp_ 62-63°C: j_r (KBr) 1687 cm"1 (C=0), 2230 cm- 1 (C=N), nmr (CDCi 3 , 300 MHz) 1.2-1.8 (14H, m), 2.28 (IH, m), 2.87 (IH, d, J=7.5 Hz), 7.77 (2H, d, J=8.5 Hz), 8.03 (2H, d, J=8.5 Hz); m/e ( re la t ive in tens i ty) 255 (m+, 2.7), 145 (100), 130 (29.2); calculated mass, C 1 7 H 2 1 0N: 255.1623, Found: 255.1623; Ana l . , calculated fo r C 1 7 H 2 1 0N: C, 79.96, H, 8.29, Found: C, 79.89; H, 8.49; uv (\ max, n , n * , MeOH) 324 nm, emax=123 l i t r e s • moles - 1 • cm - 1 . 128 2-cycloheptyl-l-(4-cyanopheny1)-ethanone (21) a-Cycloheptyl-para-cyanoacetophenone (21) was prepared from (13) in the same sequence of steps as in the synthesis of (20). Following column chromatography, a white so l i d was iso lated in 71% y i e l d . The so l i d was rec rys ta l l i zed from ethanol to y i e l d white c rys ta l s , mp_ 41-42°C: vr_ (KBr) 1692 cm- 1 (C=0), 2224 cm- 1 (C=N); lU nmr (CDCi 3, 400 MHz) 1.26 (2H, m), 1.4-1.8 (10H, m), 2.19 (IH, m), 2.89 (2H, d, J=7.5 Hz), 7.76 (2H, d, J=8.5 Hz), 8.03 (2H, d, J=8.5 Hz); m/e ( re la t i ve in tens i ty) 241 (m+, 6.9), 145 (100), 130 (67.8); ca lculated mass, C 1 6 H 1 9 0N: 241.1466, Found: 241.1466; Ana l . , ca lcualted for C 1 6 H 1 9 0N: C, 79.63; H, 7.94, Found: C, 79.46, H, 7.96; uv Umax, n , n * , MeOH) 324 nm, emax=101 l i t e r s • moles - 1 • c m - 1 . 2-cyclooctyl-2-methy1-l-(4-cyanophenyl)-ethanone (22) a-Methyl-a-cyclooctyl-para-cyanoacetophenone (22) was prepared from (16) using the same sequence of steps as in the synthesis of (20). Following column chromatography, a c lear o i l was iso lated in 83% y i e l d : vr_ (neat) 1687 cm - 1 (C=0), 2230 cm - 1 (C=N); XH nmr (CDCi 3, 300 MHz) 1.15 (3H, d, J=7 Hz), 1.2-1.85 (14H, m), 2.03 (IH, m), 3.35 (IH, m), 7.79 (2H, d, J=8.5 Hz), 8.00 (2H, d, J=8.5 Hz); m/e ( re la t ive intens i ty) 260 (m+, 0.3), 159 (100), 130 (23.0). 2-cycloheptyl-2-methyl-l-(4-cyanophenyl)-ethanone (23) a-Methyl-a-cycloheptyl-para-cyanoacetophenone (23) was prepared 129 from (17) using the same sequence of steps as in the synthesis of (20). Following column chromatography, a c lear o i l was iso lated in 80% y i e l d : ir (neat) 1692 cm"1 (OO), 2224 cm"1 (C=N); *H nmr (CDC*3, 300 MHz) 1.13 (3H, d, J=7 Hz), 1.2-1.8 (12H, m), 1.95 (IH, m), 3.38 (IH, m), 7.75 (2H, d, J=8.5 Hz), 8.00 (2H, d, J=8.5 Hz); m/e ( re la t ive in tens i ty) 255 (m+, 0.23), 159 (100), 130 (29.3). 2 -cyc lohexy l -2 -methy1- l - (4 -cyanopheny l ) -e thanone ( 2 4 ) 6 0 a-Methyl-a-cyclohexyl-para-cyanoacetophenone (24) was prepared from (18) using the same sequence of steps as in the synthesis of (20). Following column chromatography, a c lear o i l was iso lated in 60% y i e l d : ir (neat) 1687 cm"1 ( 0 0 ) , 2232 cm"1 (C=N)i XH nmr (CDCA3, 300 MHz) 0.8-1.3 (4H, m), 1.17 (3H, d, J=7 Hz), 1.5-1.9 (7H, m), 3.30 (IH, m) 7.77 (2H, d, J=8.5 Hz), 8.01 (2H, d, J=8.5 Hz); m/e ( re la t ive intens i ty) 241 (m+, 1.1), 159 (100), 130 (30.9); calculated mass fo r C 1 A H 1 Q 0N: 241.1467, Found: 241.1473. 2 - cyc l open ty l -2 -methy l - l - (4 - cyanopheny l ) - e thanone (25) a-Methyl-a-cyclopentyl-para-cyanoacetophenone (25) was prepared from (19) using the same sequence of steps as in the synthesis of (20). Following column chromatography, a c lear o i l was isolated in 84% y i e l d : ir (neat) 1686 cm"1 ( 0 0 ) , 2232 cm"1 (C=N); lH nmr (CDW 3, 300 MHz) 1.0 (2H, m), 1.20 (3H, d, J=7 Hz), 1.2-2.0 (6H, m), 2.15 (IH, m), 3.28 (IH, m), 7.74 (2H, d, J=8 Hz), 8.00 (2H, d, J=8.5 Hz), m/e ( re la t ive intens i ty) 227 (m+, 0.90), 212 (3.1), 159 (100), 130 (67.7). 130 2-cyclooctyl-l-(4-carboxypheny1)-ethanone (26) 6 2 ' a-Cyclooctyl-para-carboxyacetophenone (26) was prepared fol lowing a modified procedure of Wagner and S i ebe r t 5 8 in which 5.5 g (22 mmoles) of (20) was added to a s t i r r i n g solut ion of 10 ml ethanol and 40 ml of a 30% solut ion of potassium hydroxide in water. The reaction was brought to ref lux and s t i r r ed at ref lux for 1 day. The reaction was cooled to room temperature and ac i d i f i ed with concentrated hydrochloric ac id. The organic layer was extracted twice with 100 ml of diethyl ether. The combined extracts were washed twice with 50 ml of water and dried over anhydrous sodium sulphate. The solut ion was f i l t e r ed and the ether solvent removed by rotary evaporation to y i e l d 4.24 g (15 mmoles, 71% y ie ld ) of a white s o l i d . The so l i d was recrysta l1 ized from ethanol to y i e l d c lear c rys ta l s , mp_ 188-192°C: ir_ (KBr) 1688 cm" 1 (broad, C=0), 2900 cm"1 (broad, OH); lH nmr (CDCA3, 400 MHz) 1.4 (2H, m), 1.45-1.8 (12H, m), 2.29 (IH, m), 2.91 (2H, d, J=7 Hz), 8.02 (2H, d, J=8.4 Hz), 8.20 (2H, d, J=8.4 Hz), 9.9 (IH, s, broad); m/e ( re la t ive intens i ty) 274 (m+, 1.7), 164 (100), 149 (48.8); ca lculated mass for C 1 7 H 2 2 0 3 : 274.1569, Found: 274.1574; Ana l . , calculated for C 1 7 H 2 2 0 3 : C, 74.42; H, 8.08, Found: C, 74.60; H, 7.98. 2-cycloheptyl-l-(4-carboxypheny1)-ethanone (27) a-Cycloheptyl-para-carboxyacetophenone (27) was prepared from (21) using the same sequence of steps as in the synthesis of (26). A white so l i d product was iso lated in 80% y i e l d . The so l id was recrysta l1 ized from ethanol to y i e l d c lear c rys ta l s , mp_ 183-184°C: vr. (KBr) 1 6 8 7 c m _ 1 131 (C=0), 2900 cm"1 (broad, OH); lH nmr (CDCJc3, 400 MHz) 1.25 (2H, m) 1.4-1.8 (10H, m), 2.2 (IH, m), 2.92 (2H, d, J=7 Hz), 8.04 (2H, d, J=8.4 Hz), 8.20 (2H, d, J=8.4 Hz), 10.0 (IH, s, broad); m/e ( re la t ive in tens i ty) 260 (m+, 3.5), 164 (100), 149 (45.9), calculated mass f o r C| f t H , n0^: 260.1412, Found: 260.1412; Ana l . , calculated fo r C 1 6 H 2 0 0 3 : C, 73.82; H, 7.74; • Found: C, 73.65, H, 7.85; uv (kmax, n ,n , ace ton i t r i l e ) 325 nm. 2-cyclooctyl-2-methyl-l-(4-carboxyphenyl)-ethanone (28) 6 2 a-Methyl-a-cyclooctyl-para-carboxyacetophenone (28) was prepared from (22) using the same sequence of steps as in the synthesis of (26). A white so l id product was iso lated in 71% y i e l d . The so l i d was rec rys ta l l i zed in g lac ia l acet ic acid and yie lded c lear crysta ls of a 1:1 mixed dimer of acet ic acid and (28), as determined by nmr and and X-ray crystal lography, mp_ 137-138°C: ir (KBr) 1683 cm"1 (OO), 1700 cm" 1 ( 0 0 ) , 2900 cm"1 (broad, OH); lH nmr (CDCi 3 , 400 MHz) 1.16 (3H, d, J=7 Hz), 1.2-1.7 (14H, m), 2.05 (IH, m), 3.38 (IH, m), 8.00 (2H, d, J=8.4 Hz), 8.21 (2H, d, J=8.4 Hz), 9.9 (IH, s, broad); m/e ( re la t ive intens i ty) 288 (m+, 0.8), 178 (100), 149 (36.0); calculated mass fo r CmH^O,: 288.1725, Found: 288.1730. 2-cycloheptyl-2-methyl-l-(4-carboxyphenyl)-ethanone (29) 6 8 a-Methyl-a-cycloheptyl-para-carboxyacetophenone (29) was prepared from (23) using the same sequence of steps as in the synthesis of (26). A white so l i d product was isolated in 82% y i e l d . The so l id was recrys ta l l ized in g lac ia l acet ic acid to y i e l d c lear c rys ta l s , mp_ 132 152-153°C: j_r (KBr) 1679 cm' 1 (C=0), 1694 cm'1 (C=0), 2900 cm"1 (broad, OH); XH nmr (CDC*3, 400 MHz) 1.17 (3H, d, J=7 Hz), 1.2-1.8 (12H, m), 1.95 (IH, m), 3.44 (IH, m), 8.01 (2H, d, J=8.4 Hz), 8.22 (2H, d, J=8.4 Hz), 10.0 (IH, s, broad); m/e (re lat ive intens i ty) 274 (m+, 0.3), 178 (100), 149 (54.5), calculated mass fo r C 1 7HooQ,: 274.1569, Found: 274.1571, Ana l . , calculated f o r C 1 7 H 2 2 0 3 : C, 74.42; H, 8.10, Found: C, 74.20; H, 8.10. 2-cyc lohexy1-2-methy l - l - (4 -carboxypheny1)-e thanone ( 3 0 ) 6 Q » 6 1 a-Methyl-a-cyclohexyl-para-carboxyacetophenone (30) was prepared from (24) using the same sequence of steps as in the synthesis of (26). A white so l id product was iso lated in 72% y i e l d . The so l id was recrystal 1 ized from acet ic acid to y i e l d c lear c rys ta l s , mp_ 157-158°C: j_r (KBr) 1678 cm"1 (C=0), 1693 an" 1 (C=0), 2900 cm"1 (broad, OH), lH nmr (CDCi 3, 400 MHz) 0.9-1.3 (4H, m), 1.17 (3H, d, J=7 Hz), 1.6-1.8 (7H, m), 3.35 (IH, m), 8.02 (2H, d, J=8.4 Hz), 8.22 (2H, d, J=8.4 Hz), 9.8 (IH, s, broad); m/e ( re la t ive intens i ty) 260 (m+, 0.9), 178 (100), 149 (54.2); calculated mass f o r C 1 5 H 2 0 0 3 : 260.1412, Found: 260.1407. 2 - cyc l openty l -2 -methy l - l - (4 -carboxypheny1) -e thanone (31 ) 6 3 a-Methyl-a-cycl opentyl-para-carboxyacetophenone (31) was prepared from (25) using the same sequence of steps as in the synthesis of (26). A white so l id product was iso lated in 75% y i e l d . The so l id was recrystal 1 ized in g lac ia l acet ic acid to y i e l d c lear c rys ta l s , mp_ 140-141°C: 21 ( K B r ) 1 6 8 0 c m _ 1 ( c =°)> 1 6 9 1 c m _ 1 ( c =°)> 2 9 0 0 c m _ 1 (broad, 133 OH); XH nmr (CDCi 3, 400 MHz) 1.06 (IH, m), 1.23 (3H, d, J=7 Hz), 1.45-1.65 (5H, m), 1.72 (IH, m), 1.84 (IH, m), 2.20 (IH, m), 3.35 (IH, m), 8.02 (2H, d, J=8.4 Hz), 8.21 (2H, m, J=8.4 Hz), 10.0 (IH, s, broad); m/e ( re la t i ve intens i ty) 246 (m+, 1.2), 178 (84.9), 149 (100); calculated  mass for C 1 5 H 1 8 0 3 : 246.1256, Found: 246.1253; Ana l . , calculated for C 1 5 H 1 8 0 3 : C, 73.15; H, 7.37, Found: C, 73.08; H, 7.40. 2-cyc1ooctyl-l-(4-carbomethoxyphenyl)-ethanone (32) Following the procedure of DeBoer and Backer6 1*, a 100 ml long-necked d i s t i l l a t i o n f lask was equipped with a condenser and dropping funnel, and f i l l e d with a solut ion of 3 g of potassium hydroxide, 10 mi of water and 40 mi of 2-ethoxyethanol. The mixture was heated in an o i l bath to 70-75°C. A solut ion consist ing of 3 g (15 mmoles) of N-methyl-N-nitrosotoluene-4-sulphonamide dissolved in 50 mi of d iethyl ether was added to the d i s t i l l a t i o n f lask dropwise over 5 minutes. During the d i s t i l l a t i o n the solut ion was s t i r r ed vigorously. The d i s t i l l i n g diazomethane solut ion was immediately added to a f lask containing keto-acid (26). The addit ion of diazomethane was allowed to proceed unt i l the solut ion retained the yel low color of diazomethane and the evolution of nitrogen gas ceased. The excess diazomethane and diethyl ether were allowed to evaporate y ie ld ing a white so l i d , mp_ 40-41 °C: jjr (KBr) 1677 cm-1 (C=0), 1723 cm"1 (C=0); l H nmr (CDCi 3, 300 MHz) 1.2-1.7 (14H, m), 2.28 (IH, m), 2.89 (2H, d, J=7 Hz), 3.95 (3H, s ) , 7.99 (2H, d, J=8.3 Hz), 8.12 (2H, d, J=8.3 Hz); m/e ( re la t ive intens i ty) 288 (m+, 5.3), 257 (10.7), 178 (100), 163 (48.7), 135 (19.6); Ana l . , calculated for 134 C 1 8 H 2 1 t 0 3 : C, 74.97, H, 8.38, Found: C, 75.12; H, 8.48; uv (\max, n , n * , MeOH) 327, emax = 92 l i t r e s • moles" 1 • cm" 1. 2-cyc l ohepty l - l - (4-car tomethoxypheny1)-ethanone (33) a-Cycl oheptyl-para-carbomethoxyacetophenone (33) was prepared from (27) using the same sequence of steps as in the synthesis of (32). A white so l i d was iso lated as product, mp_ 54-55°C: j j r (KBr) 1676 cm - 1 ( O O ) , 1723 cm"1 (C=0); lH nmr (CDCX3, 300 MHz) 1.25 (2H, m), 1.4-1.8 (10H, m), 2.21 (IH, m), 2.90 (2H, d, J=7 Hz), 3.96 (3H, s ) , 7.99 (2H, d, J=8.3 Hz), 8.12 (2H, d, J=8.3 Hz), m/e (re lat ive intens i ty) 274 (m+, 1.8), 243 (4.9), 178 (100), 163 (55.7), 147 (35.8); Ana l . , calculated fo r C 1 7 H 2 2 0 3 : C, 74.42, H, 8.08, Found: C, 74.68, H, 8.08; uv (\max, n , n * . MeOH) 327, emax = 158 l i t r e s • moles" 1 • cm" 1 . 2-cyc loocty l -2-methy1- l - (4-carbomethoxypheny1)-ethanone ( 3 4 ) 3 3 a-Methyl-a-cyclooctyl-para-carbomethoxyacetophenone (34) was prepared from (28) using the same sequence of steps as in the synthesis of (32). A white so l i d was iso lated as the product, mp_ 39-40°C: v r (KBr) 1677 cm-1 (C=0), 1725 cm"1 (C=0); l H nmr (CDW 3, 270 MHz) 1.14 (2H, d, J=7 Hz), 1.2-1.7 (14H, m), 2.1 (IH, m), 3.7 (IH, m), 3.95 (3H, s ) , 7.96 (2H, d, J=8.4 Hz), 8.13 (2H, d, J=8.4 Hz), m/e ( re la t ive intens i ty) 302 (m+, 0.4), 192 (100), 163 (46.9), 133 (28.0), Ana l . , calculated fo r C 1 9 H 2 6 0 3 : C, 75.46, H, 8.67, Found: C, 75.66, H, 8.76; uv (Xmax, n . n * . MeOH) 327, emax = 176 l i t r e s • moles - 1 • cm - 1 . 135 2-cycloheptyl-2-methyl-l-(4-carbomethoxyphenyl)-ethanone (35) a-Methyl-a-cycloheptyl-para-carbomethoxyacetophenone (35) was prepared from (29) using the same sequence of steps as in the synthesis of (32). A white so l i d was iso lated as the product, mp_ 59-60°C: i £ (KBr) 1672 cm-1 (C=0), 1722 cm- 1 (OO); XH nmr (CDCi 3, 270 MHz) 1.15 (3H, d, J=7 Hz), 1.2-1.7 (12H, m), 1.91 (IH, m), 3.40 (IH, ra), 3.96 (3H, s ) , 7.97 (2H, d, J=8.4 Hz), 8.12 (2H, d, J=8.4 Hz); m/e ( re la t i ve intens i ty) 288 (m+, 0.1), 192 (100), 163 (59.0), 133 (31.8); Ana l . , ca lculated for c i 8 H 2 t ° 3 : c» 74.97; H, 8.39, Found: C, 74.76; H, 8.41; uv (Xmax, n , n * , MeOH) 372, emax = 100 l i t r e s • moles - 1 • c m - 1 . 2-cyclohexyl-2-methyl-l-(4-carbomethoxyphenyl)-ethanone (36) a-Methyl-a-cyclohexyl-para-carbomethoxyacetophenone (36) was prepared from (30) using the same sequence of steps as in the synthesis of (32). A white so l i d was iso lated as product, mp_ 82-83°C: ir_ (KBr) 1672 cm-1 ( 0 0 ) , 1724 cm"1 (C=0); 1H nmr (CDU 3 , 300 MHz) 0.9-1.3 (4H, m), 1.15 (3H, d, J=7 Hz), 1.5-1.8 (7H, m), 3.33 (IH, m), 3.95 (3H, s ) , 7.97 (2H, d, J=8.3 Hz), 8.12 (2H, d, J=8.3 Hz); m/e ( re la t i ve in tens i ty) 274 (m+, 0.8), 243 (1.1), 215 (6.8), 192 (100), 163 (73.7), 133 (31.0); Ana l . , calculated for C 1 7 H 2 2 0 3 : C, 74.42; H, 8.08, Found: C, 74.40; H, 8.06; uv (A.max, n,n*, MeOH) 327 nm, emax = 157 l i t r e s • moles - 1 • c m - 1 . 2-cyclopentyl-2-methyl-l-(4-carbomethoxyphenyl)-ethanone (37) a-Methyl-a-cyclopentyl-para-carbomethoxyacetophenone (37) was 136 prepared from (31) using the same sequence of steps as in the synthesis of (32). A white so l i d was iso lated as product, mp_ 38-39°C: jjr (KBr) 1674 cm-1 (OO), 1724 cm- 1 (OO); XH nmr (CDC*3, 270 MHz) 1.05 (IH, m), 1.20 (3H, d, J=7 Hz), 1.4-1.9 (9H, m), 2.19 (IH, m), 3.33 (IH, m), 3.95 (3H, s ) , 7.98 (2H, d, J=8.4 Hz), 8.01 (2H, d, J=8.4 Hz); m/e ( re la t i ve in tens i ty) 260 (m+, 0.9), 192 (71.0), 163 (100); Ana l . , calculated for C 1 6 H 2 0 ° 3 : c» 7 3.82; H, 7.47, Found: C, 73.75; H, 7.61; uv (Xmax, n , n * , MeOH) 327 nm, emax = 124 l i t r e s • moles - 1 • c m - 1 . Photochemical Studies Photolysis of 2-cyclooctyl-1-(4-chlorophenyl)-ethanone (9) a-Cyclooctyl-para-chloroacetophenone (800 mg) was dissolved in 250 ml of ace ton i t r i l e and placed in a 250 ml Pyrex immersion well (x > 290 nm). The sample was deoxygenated for 45 minutes pr ior to i r r ad ia t i on using a steady flow of nitrogen gas through the s t i r r i n g so lu t ion . The nitrogen flow was continued while the sample was being i r rad ia ted , at room temperature, using a 450 watt medium pressure Hanovia lamp. Following a 3 hour i r r ad ia t i on time, the ace ton i t r i l e solvent was removed by rotary evaporation to y i e l d a yellow o i l . This o i l was analyzed by g.c. (column A, program 1) and found to contain 3 major products: 9a ( r t 1.59), 9b ( r t 7.51) and 9c ( r t 8.9). The products were separated using a column (2.0 cm x 30 cm) of s i l i c a gel 60 (230-400 mesh) and a 0-4% ethyl acetate in petroleum ether solvent as the step gradient 137 eluent. The products were separated and only the purest f ract ions (>90%) were iso lated and characterized. l - (4 -Ch lo ropheny l ) -e thanone (9a) Para-chloroacetophenone (9a) was isolated as a s l i gh t l y yel low o i l : j r (neat) 1687 cm"1 (C=0); XH nmr (CDCA3, 80 MHz) 2.8 (3H, s ) , 7.45 (2H, d, J=8.4 Hz), 7.95 (2H, d, J=8.4 Hz); m/e (re lat ive intens i ty) 154 (m+, 56.5), 139 (100); ( l i t 6 5 : mp 20°C). 9 - ( l a t 8a, 9B ) - ( 4 - ch l o ropheny l ) - b i c y c l o [ 6 . 2 . 0 ] decan-9-o l (9b) Trans-cyclobutanol (9b) was isolated as a yellow o i l : j_r (neat) 3440 cm-1 (broad, OH); l » nmr (CDW 3, 400 MHz) 1.15-1.4 (5H, m), 1.52-1.63 (2H, m), 1.65-1.95 (6H, m), 2.2-2.4 (4H, m), 7.95 (4H, m); m/e ( re la t ive intens i ty) 264/266 (m+, 0.7/0.2), 154/156 (100/38.4), 139/141 (55.6/21.8), calculated mass f o r C,^H 9 1 0CX 3 5 /C,^H 9 iOCA 3 7 : 264.1281/266.1281, Found: 264.1272/266.1260. 9 - ( l a , 8a, 9 a ) - ( 4 - ch lo ropheny l ) -b i cyc lo [ 6 . 2 . 0 ] decan-9-ol (9c) Cis-cyclobutanol (9c) was isolated as a yellow o i l : j_r (neat) 3440 cm-1 (broad, OH); LH nmr (CDC*3, 400 MHz) 0.47 (IH, m), 1.02 (IH, rn), 1.1-1.45 (6H, m), 1.56 (IH, m), 1.65-2.0 (5H, m), 2.26 (IH, m), 2.48 (IH, s, broad, exchanges with D 2 0), 2.80 (IH, dd, J=7.5 and 4 Hz), 7.32 (2H, d, J=8.3 Hz), 7.40 (2H, d, J=8.3 Hz), proton decoupling of the signal at 0.47 results in the s imp l i f i ca t i on of the mult ip let at 1.56 and causes the mult ip let at 2.26 to collapse to a doublet of doublets (J =9.5 138 and 3 Hz); m/e ( re la t i ve in tens i ty) 264/266 (m+, 0.6/0.1), 154/156 (100/37.4), 139/141 (46.1/19.1); ca lcu lated mass for C 1 6 H 2 1 0 a 3 5 / C 1 6 H 2 1 0 a 3 7 : 263.1281/266.1281, Found: 264.1285/266.1257. Product Ra t i o Study Three 0.4 mi Pyrex tubes were f i l l e d with a 0.10 M solut ion of (9) in benzene. Three tubes were f i l l e d with a 0.10 M solut ion of (9) in a ce ton i t r i l e . Three tubes were f i l l e d with a 0.01 M solut ion of (9) i n ace ton i t r i l e and a further three tubes f i l l e d with 2 mg of crushed c rys ta l s of (9). The solut ion samples were deoxygenated by subjecting the tubes to three freeze-pump-thaw cycles under a nitrogen atmosphere. The so l i d samples were pumped and placed under a nitrogen atmosphere. The so l i d samples and the 0.01 M solut ion of (9) in ace ton i t r i l e were cooled to -32°C and photolyzed at 337 nm. The 0.1 M solutions were photolyzed at room temperature at 337 nm. Solut ion state conversions were l im i ted to 10%, whereas the so l i d state conversions were l imi ted to 2%. A l l of the samples were analyzed by g.c. and the rat ios of (9b + 9c):9a and 9b:9c are shown in table VI: SOLVENT cone. (M) temp.°C (9b+9c):9a 9b :9c Ace ton i t r i l e Ace ton i t r i l e Benzene So l id State 0.01 M 0.10 M 0.10 M -32 ± 2 22 ± 2 22 ± 2 -32 ± 2 85:15 ± 3 73:27 ± 1 70:30 ± 2 96:4 ± 1 51:49 ± 1 56.44 ± 1 77:23 ± 1 96:4 ± 1 Table VI: Product rat ios from the photolysis of ketone (9) 139 Pho t o l y s i s of 2 - c y c l ooc t y l - 1 - ( 4 cyanophenyl)-ethanone (20) a-Cyclooctyl-para-cyanoacetophenone (750 mg) was i r rad iated fol lowing the same procedure used in the i r r ad ia t i on of (9). The resultant o i l was analyzed by g.c. (column A, program 1) and found to contain three major products; 20a (rt 1.57), 20b (rt 9.22) and 20c (rt 10.86). The products were separated using a column (2.0 cm x 30 cm) of s i l i c a gel 60 (230-400 mesh) and a 0-7% ethyl acetate in petroleum ether solvent as the step gradient eluent. The products were separated and only the purest f ract ions (>90%) were iso lated and characterized: l - (4-cyanopheny l ) -e thanone (20a) Para-cyanoacetophenone (20a) was iso lated as a white s o l i d , mp_ 60-61°C ( l i t 6 6 : mp 60-61°C): j_r (KBr) 1689 cm"1 (C=0), 2230 cm" 1 (C=N); 1ti nmr (CDU 3 , 80 MHz) 2.7 (3H, s ) , 7.8 (2H, d, J=8.5 Hz), 8.1 (2H, d, J=8.5 Hz), m/e ( re la t ive intens i ty) 145 (m+, 12.4), 130 (100), 102 (44.0). 9-(la , pa , 9B) - (4 -Cyanopheny l ) -b i cyc lo [6.2.0] decan -9-ol (20b) Trans-cyclobutanol (20b) was isolated as a yel lowish o i l : J_r (neat) 2229 cm"1 (C=N), 3470 cm"1 (broad, OH); l H nmr (CDC*3, 400 MHz) 1.15-1.45 (5H, m), 1.5-1.6 (2H, m), 1.65-2.0 (6H, m), 2.2-2.5 (4H, m), 8.0 (2H, d, J=8.5 Hz), 8.10 (2H, d, J=8.5 Hz); m/e ( re la t ive intens i ty) 255 (m+, 2.3), 145 (100), 130 (83.2); calculated mass fo r C 1 7 H 2 1 0N: 255.1623, Found 255.1626. 140 9-(la, 8a, 9a)-(4-cyanopheny1 ) - b i c y c l o [ 6 . 2 . 0 ] decan -9-o l (20c) Cis-cyclobutanol (20c) was isolated as a yel lowish o i l : j_r (neat) 2229 cm"1 (C=N), 3428 cm"1 (broad, OH); IH nmr (CDCA3, 400 MHz) 0.38 (IH, m), 1.0 (IH, m), 1.05-1.45 (6H, m), 1.53 (IH, m), 1.63-1.82 (3H, m), 1.84-1.95 (2H, m), 2.24 (IH, s, broad, exchanges with D 2 0), 2.29 (IH, m), 2.80 (IH, dd, J=8 Hz and 4 Hz), 8.07 (4H, m), proton decoupling of the signal at 0.38 results in the signal at 2.29 col lapsing to a doublet (J=8.0 Hz), proton decoupling of the signal at 2.29 results in the collapse of the mult ip let at 0.38 to a t r i p l e t of doublets (J=2.5 and 0.9 Hz), proton decoupling of the signal at 2.80 results in no observable change in the spectrum; m/e ( re la t ive intens i ty) 255 (m+, 0.4), 145 (100), 130 (68.4); calculated mass f o r CwH^ON: 255.1623, Found: 255.1627. Product R a t i o Study The product rat io study fo r ketone (20) was conducted in the same fashion as the product study fo r (9). A l l of the samples were analyzed by g.c. and the rat ios of (20b+20c):20a and 20b:20c are shown in table VII . SOLVENT cone. (M) temp.°C (20b+20c):20a 20b:20c Ace ton i t r i l e Ace ton i t r i l e Benzene So l id State 0.01 M 0.10 M 0.10 M -32 ± 2 22 ± 2 22 ± 2 -32 ± 2 82:18 ± 2 72:28 ± 3 72:28 ± 1 87:13 ±2 51:49 ± 1 56.44 ± 1 75:25 ± 1 83:17 ± 1 Table VII: Product rat ios from the photolysis of ketone (20) 141 Photolysis of 2-cycloheptyl-l-(4-cyanopheny1)-ethanone (21) a-Cycloheptyl-para-cyanoacetophenone (800 mg) was i r rad iated fol lowing the same procedure used in the i r rad ia t ion of (9). The resultant o i l was analyzed by g.c. (column A, program 1) and found to contain three major products; 20a ( r t 1.59), 21b ( r t 7.10), and 21c ( r t 8.11). The products were separated using a column (2.0 cm x 30 cm) of s i l i c a gel 60 (230-400 mesh) and a 0-7% ethyl acetate in petroleum ether solvent as the step gradient eluent. The products were separated and only the purest f ract ions (>90%) were iso lated and character ized: l-(4-cyanopheny1)-ethanone (20a) Para-cyanoacetophenone was iden t i f i ed by i t s g.c. retention time, physical and spectral charac ter i s t i cs as compared to an authentic sample. 8-(la, 7a, 86)-(4-cyanophenyl)-bicyclo [5.2.0] nonan-8-ol (21b) Trans-cyclobutanol (21b) was iso lated as a s l i gh t l y yel low o i l : ijr (neat) 2229 cm"1 (C=N), 3402 cnr 1 (broad, OH); XH nmr (CDCi 3, 400 MHz) 1.24 (IH, m), 1.32-1.50 (2H, m), 1.53-1.82 (5H, m), 1.89-2.10 (3H, m), 2.23-2.50 (4H, m), 7.48 (2H, m), 7.61 (2H, m); m/e ( re la t ive intens i ty) 241 (m+, 3.3), 145 (100), 130 (69.4); calculated mass for C 1 6 H 1 9 0N: 241.1467, Found: 241.1466. 8-(la, 7a, 8a)-(4-cyanophenyl)-bicyclo [5.2.0] nonan-8-ol (21c) Cis-cyclobutanol (21c) was iso lated as a s l i gh t l y yellow o i l : _ir (neat) 2229 cm"1 (C=N), 3402 (broad, OH); XH nmr (CDCA3, 400 MHz) 0.43 142 (IH, m), 0.89 (IH, m), 1.05 (1H, m), 1.15-1.55 (5H, m), 1.68-1.8 (2H, m), 1.9-2.0 (2H, m), 2.37 (1H, m), 2.66 (1H, s, broad, exchanges with D 2 0), 2.84 (IH, dd, J=7.5 and 4.5) , 7.57 (2H, m), 7.64 (2H, m), m/e ( re la t ive in tens i ty) 241 (m+, 3.9), 145 (100), 130 (62.1); calculated mass f o r C 1 6 H 1 9 0N: 241.1467, Found: 241.1467. Product R a t i o Study The product ra t io study fo r ketone (21) was conducted in the same fashion as the product study fo r (9). A l l of the samples were analyzed by g.c. and the rat ios of (21b+21c):20a and 21b:21c are shown in table V I I I . SOLVENT cone. (M) temp.°C (21b+21c):20a 21b:21c Aceton i t r i le Aceton i t r i le Benzene So l id State Sol id State 0.01 M 0.10 M 0.10 M -32 ± 2 22 ± 2 22 ± 2 0 + 2 -32 ± 2 75:25 ± 4 65:35 ± 5 47:53 ± 3 37:63 ± 1 36.64 ± 1 65:35 ± 1 66.34 ± 1 85:15 ± 1 72:28 ± 2 76:24 ± 1 Table VII I : Product rat ios from the photolysis of ketone (21) Pho t o l y s i s of 2 -cyc looc ty l - 1 - ( 4 - ca rboxypheny l ) -e thanone (26) a-Cycl ooctyl-para-carboxyacetophenone (800 mg) was i r rad iated fol lowing the same procedure used in the i r rad ia t i on of (9). A yel lowish so l i d remained fol lowing the removal of the ace ton i t r i l e solvent. To this was added diazomethane, using the same es t e r i f i c a t i on procedure used in the synthesis of (32). The diethyl ether and excess diazomethane was allowed to evaporate to y i e l d a yel lowish o i l . The o i l was analyzed by g.c. 143 (column A, program 1) and found to contain three major products; 26a (rt 1.67), 26b (rt 9.20) and 26c (rt 10.71). The products were separated using a column (2.0 cm x 30 cm) of s i l i c a gel 60 (230-400 mesh) with a 0- 9% ethyl acetate in petroleum ether solvent as the step gradient eluent. The products were separated and only the purest f ract ions (>90%) were iso lated and characterized: 1- (4-carbomethoxyphenyl)-ethanone (26a) Para-carbomethoxyacetophenone (26a) was iso lated as a white s o l i d , mp_ 93-94°C ( l i t 6 6 : mp 92°C): j_r (KBr) 1678 cm"1 (OO), 1722 cm" 1 ( 0 0 ) ; lH nmr (CDC*3, 80 MHz) 2.7 (3H, s ) , 4.0 (3H, s ) , 8.1 (4H, m); m/e ( re la t ive intens i ty) 178 (m+, 21.3), 163 (100). 9-(la, 8a, 9B) - (4-carbomethoxypheny l ) -b i cyc lo [ 6 . 2 . 0 ] decan-9-ol (26b) Trans-cyclobutanol (26b) was iso lated as a s l i gh t l y yel low o i l : j_r (neat) 1724 cm"1 ( 0 0 ) , 3490 cm"1 (broad, OH); lH nmr (CDCJt 3 , 400 MHz) 0.86 (IH, m), 1.15-1.4 (5H, m), 1.55-1.65 (2H, m), 1.68-1.90 (4H, m), 1.97 (IH, m), 2.11 (IH, s, broad, exchanges with D 2 0), 2.25-2.45 (3H, m), 3.90 (3H, s ) , 7.44 (2H, d, J=8 Hz), 7.98 (2H, d, J=8 Hz); m/e ( re la t ive in tens i ty) 288 (m+, 0.9), 178 (100), 163 (48.3); calculated mass f o r C 1 8 H 2 4 0 3 : 288.1726, Found: 288.1723. 9-(la, 8a, 9a) - (4-carbomethoxypheny l) -b icyc lo [ 6 . 2 . 0 ] decan-9-ol (26c) Cis-cyclobutanol (26c) was iso lated as a yel lowish o i l : _ir (neat) 1724 cm"1 ( 0 0 ) , 3469 cm"1 (broad, OH); XH nmr (CDCA3, 400 MHz) 0.45 144 (1H, m), 1.04 (IH, m), 1.1-1.49 (6H, m), 1.55 (IH, m), 1.65-2.0 (5H, m), 2.32 (IH, m), 2.50 (1H, s, broad, exchanges with D 20), 2.88 (IH, dd, J=7.5 and 4 Hz), 3.90 (3H, s ) , 7.53 (2H, d, J=8 Hz), 8.0 (2H, d, J=8 Hz); m/e ( re la t i ve intens i ty) 288 (m+, 0.8), 178 (100), 163 (40.3); ca lculated mas£ for C 1 8 H 2 4 0 3 : 288.1726, Found: 288.1729. Product Ratio Study The product ra t io study for keto-acid (26) was conducted in a modified version of the product study for (9). Due to a lower so l ub i l i t y of keto-acid (26) in both benzene and ace ton i t r i l e , the concentration of a l l the solut ion samples was reduced to 0.01 M. The so l i d and solut ion samples were i r rad ia ted at room temperature. Following i r r ad i a t i on , the samples were transferred to 3 ml sample v ia l s where the photolysis solvents were allowed to evaporate. To each sample v ia l was added an excess of diazomethane in diethyl ether. The v i a l s were sealed for approximately 3 hours fol lowing which the excess diazomethane and ether were allowed to evaporate. A l l of the resultant samples were analyzed by g.c. and the rat ios of (26b+26c):26a and 26b:26c are shown in table IX: 145 SOLVENT cone. (M) temp.°C (26b+26c):26a 26b:26c Ace ton i t r i l e Benzene Sol id State 0.01 M 0.01 M 22 + 2 22 ± 2 22 ± 2 69:31 ± 5 64:36 ± 4 85:15 ± 5 53:47 ± 1 72:28 ± 4 92:8 ± 4 Table IX: Product rat ios from the photolysis of keto-acid (26) Photolysis of 2-cyc1ohepty1-l-(4-carboxypheny1)-ethanone (27) a-Cycloheptyl-para-carboxyacetophenone (800 mg) was i r rad iated fol lowing the same procedure used in the i r rad ia t i on of keto-acid (26). The resultant o i l was analyzed by g.c. (column A, program 1) and found to contain three major products; 26a ( r t 1.68), 27b ( r t 7.35), 27c ( r t 8.31). The products were separated in the same manner used in the i so la t ion of products from keto-acid (26): l-(4-carbomethoxypheny1)-ethanone (26a) Para-carbomethoxyacetophenone was iden t i f i ed by i t s g.c. retention time, physical and spectral charac ter i s t i cs as compared to an authentic sample. 8 - ( l a , 7a, 8p)-(4-carbomethoxyphenyl)-bicyclo [5.2.0] nonan-8-ol (27b) Trans-cyclobutanol (26b) was iso lated as a s l i gh t l y yellow o i l : 2r (neat) 1724 cm"1 (C=0), 3423 cm" 1 (broad, OH); XH nmr (CDCJlg, 400 MHz) 1.23 (2H, m), 1.35-1.85 (8H, m), 1.87-2.03 (2H, m), 2.1 (IH, s, broad, exchanges with D 2 0), 2.24-2.47 (2H, m), 3.94 (3H, s ) , 7.41 (2H, m), 7.98 (2H, m); m/e ( re la t ive intens i ty) 274 (m+, 1.1), 178 (100), 163 (51.8). 146 8- ( l a , 7a, 8a)-(4-carbomethoxyphenyl)-bicyclo [5.2.0] nonan-8-ol (27c) Cis-cyclobutanol (27c) was iso lated as a s l i gh t l y yel low o i l : j_r (neat) 1725 cm"1 (C=0), 3424 cm"1 (broad OH); XH nmr (CDCA3, 400 MHz) 0.46 (1H, m), 0.87 (1H, m), 1.08 (IH, m), 1.17-1.85 (7H, m), 1.85-2.03 (2H, m), 2.16 (1H, s, broad, exchanges with D 2 0), 2.37 (IH, m), 2.89 (IH, dd, J=7.5 and 4.5 Hz), 3.91 (3H, s ) , 7.53 (2H, d, J=8 Hz), 8.03 (2H, d, J=8 Hz); m/e ( re la t ive intens i ty) 274 (m+, 1.2), 178 (100), 163 (44.3), 147 (43.2). Product Rat io Study The product rat io study fo r keto-acid (27) was conducted in the same fashion as the product study fo r keto-acid (26). A l l of the samples were analyzed by g.c. and the rat ios of 26a: (27b+27c) and 27b:27c are shown in table X: SOLVENT cone. (M) temp.°C 26a:(27b+27c) 27b:27c Aceton i t r i le Benzene So l id State 0.01 M 0.01 M 22 ± 2 22 ± 2 22 ± 2 36:64 ± 3 50:50 ± 6 56:44 ± 5 69:31 ± 1 87:13 ± 1 96:4 ±2 Table X: Product ratios from the photolysis of keto-acid (27) Photolysis of 2-cyclooctyl-2-methyl-1-(4-carboxyphenyl)-ethanone (28) a-Methyl-a-cyclooctyl-para-carboxyacetophenone (1.2 g) was i r rad iated fol lowing the same procedure used in the i r r ad i a t i on of keto-acid (26). The resultant o i l was analyzed by g.c. (column A, program 1) and found to contain four major products, 28a (rt 1.92), 28b 147 (rt 7.74), 28c (r t 8.76), 28d (rt 11.46). Cleavage product 28a and cyclobutanol 28b were iso lated using a column (2.0 cm x 30 cm) of s i l i c a gel 60 (230-400 mesh) with a 0-9% ethyl acetate in petroleum ether solvent as the step gradient eluent. The second cyclobutanol 28c was iso lated using f i ve separate columns of the type used in the i so la t i on of 28a and 28b. The forth product 28d was ident i f i ed by i t s g.c.-mass spectrum: 2-methy l - l - (4 -carbomethoxyphenyl) -ethanone (28a) Para-carbomethoxypropiophenone (28a) was isolated as a white s o l i d , mp_ 77-78°C: I r (KBr) 1680 cm"1 (C=0), 1723 cm"1 (C=0); lH nmr (CDC£3, 80 MHz) 1.2 (3H, t , J=8 Hz), 3.0 (2H, q, J=8 Hz), 3.9 (3H, s ) , 8.1 (4H, m); m/e ( re la t ive in tens i ty) 192 (m+, 3.3), 163 (100). 9-(la , 8a, 96, 10a)-(4-carbomethoxyphenyl ) -10-methyl-bicyc lo [6.2 .0]  decan -9-o l (28b) Cyclobutanol 28b was iso lated as a c lear o i l : jjr (neat) 1724 cm - 1 (C=0), 3495 cm"1 (broad, OH); XH nmr (CDCi 3, 400 MHz) 1.08 (3H, d, J=7.5 Hz), 1.15-1.40 (5H, m), 1.50-1.60 (2H, m), 1.60-2.0 (7H, m), 2.11 (IH, m), 2.24 (IH, m), 3.92 (3H, s ) , 7.49 (2H, d, J=8 Hz), 8.00 (2H, d, J=8 Hz), proton decoupling of the signal at 2.11 results in the doublet at 1.08 col laps ing to a s ing le t ; proton decoupling the signal at 2.24 had no effect on the signals at 1.08 and 2.11, in an N.O.E. difference experiment, i r r ad ia t i on of the doublet at 7.47 results in equal enhancement of the signals at 2.24 and 2.11; enhancement is also observed 148 for the signal at 8.00; m/e ( re la t i ve intens i ty) 302 (m+, 1.2), 192 (100), 163 (78.4); ca lcu lated mass for C 1 9 H 2 6 0 3 : 302.1882, Found: 302.1890. 9-(4-carbomethoxypheny l ) -10-methy l -b icyc1o [ 6 . 2 . 0 ] decan-9-o l (28c) - s te reochemis t ry unknown Cyclobutanol (28c) was iso lated as a c lear o i l : j l ( n e a t ) 1725 cm-1 (C=0), 3494 cm"1 (broad, OH); XH nmr (CDCl 3 , 400 MHz) 0.90 (IH, m), 1.07 (3H, d, J=6.5 Hz), 1.1-1.8 (11H, m), 1.94 (IH, s, broad, exchanges with D 2 0), 2.19 (IH, m), 2.37 (IH, m), 2.51 (IH, m), 3.91 (3H, s ) , 7.42 (2H, d, J=8 Hz), 8.01 (2H, d, J=8 Hz), proton decoupling of the signal at 1.07 resul ts in the mul t ip le t at 2.51 col laps ing to a doublet (J=9.5 Hz); proton decoupling of the signal at 2.51 resu l ts in the mul t ip le t at 2.37 col laps ing to a doublet (J =11 Hz) and the mul t ip le t at 2.51 co l laps ing to a quartet (J=6.5 Hz); proton decoupling of the signal at 2.37 resul ts in the s imp l i f i ca t i on of the signal at 2.19; in an N.O.E. difference experiment i r r ad ia t i on of the doublet at 7.42 resu l ts in enhancement of the mul t ip le t at 2.51 and a weak enhancement of the mul t ip le t at 2.37, enhancement was also observed for the doublet at 8.01; m/e ( re la t i ve in tens i ty) 302 (m+, 0.3), 192 (100); ca lculated mass for C 1 9 H 2 6 0 3 : 302.1882, Found: 302.1886. 9-(4-carbomethoxypheny1)-10-methy1-bicyc1o [ 6 . 2 . 0 ] decan-9-o l (28d) - s te reochemis t ry unknown Cyclobutanol (28d) was not i so la ted . I t was tentat ive ly 149 iden t i f i ed by i t s g.c.-mass spectrum. Its absolute stereochemistry is not known: m/e (re lat ive intens i ty) 192 (100), 178 (8.8), 163 (16.8), 133 (18.4). Product R a t i o Study The product rat io study for keto-acid (28) was conducted in the same fashion as the study fo r keto-acid (26). A l l of the samples were analyzed by g.c. and the ratios of (28b+28c+28d):28a and 28b:28c:28d are shown in table XI. Keto-acid (28) was photolyzed in the so l i d state as a 1:1 mixed dimer with acet ic ac id. SOLVENT cone. (M) temp.°C (28b+28c+28d):28a 28b:28c:28d Aceton i t r i le Benzene So l id State 0.01 M 0.01 M 22 ± 2 22 ± 2 22 ± 2 57:43 ± 5 66:34 ± 2 70:30 ± 2 70:19:11 ± 2 76:17:7 ± 2 31:14:55 ± 2 Table XI: Product ratios from the photolysis of keto-acid (28) Pho t o l y s i s of 2 -cyc lohepty l -2 -methy l -1 - ( 4 -carboxypheny l ) -e thanone (29) Prel iminary photolysis of keto-acid (29) indicated that para-carboxypropiophenone (28a) was the predominant product formed upon photolysis of (29) in benzene and ace ton i t r i l e . The photoproducts were ident i f i ed as t he i r methyl esters. Para-carbomethoxypropiophenone was i den t i f i ed by i t s g.c. retention time and mass spectra as compared to an authentic sample. Three cycl obutanols were also formed as indicated by g.c. analysis (column A, program 2): 29b (rt 6.85), 29c (rt 7.30), and 29d (rt 9.23). The cycl obutanols were not iso lated and have been 150 tentat ive ly ident i f i ed by the i r g.c.-mass spectra. The absolute stereochemistry of the cycl obutanols is not known. 8-(4-carbomethoxyphenyl)-9-methyl-bicyclo [5.2.0] nonan-8-ol (29b) - stereochemistry unknown m/e (re la t ive intens i ty) 229 (23.9), 192 (100), 178 (18.2), 163 (40.9), 133 (25.0). 8-(4-carbomethoxyphenyl)-9-methyl-bicyclo [5.2.0] nonan-8-ol (29c) - stereochemistry unknown m/e (re lat ive intens i ty) 229 (4.23), 192 (100), 177 (12.7), 163 (23.9), 133 (25.4). 8-(4-carbomethoxyphenyl)9-methyl-bicyclo [5.2.0] nonane-8-ol (29d) - stereochemistry unknown m/e (re lat ive intens i ty) 192 (100), 177 (6.7), 163 (16.7), 133 (16.7). Product Ratio Study The product rat io study fo r keto-acid (29) was conducted in the same fashion as the product study fo r keto-acid (26). A l l of the samples were analyzed by g.c. and the ratios of (29b+29c+29d):28a and 29b:29c:29d 151 are shown in table XII: SOLVENT cone. (M) temp.°C (29b+29c+29d):28a 29b:29c:29d Ace ton i t r i l e Benzene So l id State 0.01 M 0.01 M 22 + 2 22 + 2 22 ± 2 31:69 ± 2 32:68 ± 2 27:73 ± 1 54:32:14 ± 2 60:28:12 ± 1 63:13:24 ± 1 Table XII: Product rat ios from the photolysis of keto-acid (29) Photolysis of 2-cyclohexyl-2-methyl-l-(4-carboxypheny1)-ethanone (30) a-Methyl-a-cyclohexyl-para-carboxyacetophenone (1.0 g) was i r rad ia ted fol lowing the same procedure used in the i r rad ia t i on of keto-acid (26). The resultant o i l was analyzed by g.c. (column A, program 2) and found to contain f i ve products; para-carbomethoxypropiophenone 28a ( r t 2.34) and four cyclobutanols; 30b ( r t 5.75), 30c ( r t 6.24), 30d ( r t 6.72), and 30e ( r t 7.05). The two major components, 28a and 30b were iso lated using a column (2.0 cm x 30 cm) of s i l i c a gel 60 (230-400 mesh) with a 0-9% ethyl acetate in petroleum ether solvent as the step gradient eluent. Para-carbomethoxypropiophenone (28a) was i den t i f i ed by i t s g.c. retention time and mass spectra as compared to an authentic sample. The cyclobutanols which were not iso lated have been tentat ive ly i den t i f i ed by the i r g.c.-mass spectra. The stereochemistry of these cyclobutanols i s not known. 7-(la, 6a, 76, 8a)-(4-carbomethoxyphenyl)-8-methyl-bicyclo [4.2.0]  octan-7-ol (30b) Cyclobutanol (30b) was iso lated as a yel lowish o i l : jhr (neat) 152 1724 cm"1 (C=0), 3497 cm"1 (broad, OH); lH nmr (CDCI 3, 400 MHz) 1.11 (3H, d, J=7.5 Hz), 1.2-1.45 (3H, m), 1.57 (IH, m), 1.62-1.95 (6H, m), 2.31 (IH, m), 3.90 (3H, s ) , 7.43 (2H, d, J=9 Hz), 7.99 (2H, d, J=9 Hz), proton decoupling of the signal at 1.11 results in the mult iplet at 2.31 col laps ing to a doublet (J=10 Hz); in an N.O.E. difference experiment; i r r ad i a t i on of the doublet at 7.43 results in the enhancement of the signal at 2.31 and in addit ion a signal is enhanced at 1.7 ppm; m/e ( re la t ive intens i ty) 274 (m+, 0.1), 215 (60.4), 192 (100), 178 (43.6), 163 (93.4); calculated mass fo r C 1 7 H 9 O 0 q : 274.1569, Found: 274.1538. 7- (4 -carbomethoxypheny l ) -8 -methy l -b i cyc lo [4 .2 .0 ] oc tan-7 -o l (30c) - s te reochemis t ry unknown m/e ( re la t ive intens i ty) 215 (11.1), 192 (100), 177 (5.6), 163 (22.2), 133 (20.8). 7 - (4 -carbomethoxypheny l ) -8 -methy l -b i cyc lo [4 .2 .0 ] oc tan-7 -o l (30c) - s te reochemis t ry unknown m/e ( re la t ive intens i ty) 215 (33.9), 192 (100), 163 (32.2), 133 (23.7). 7 - (4 -carbomethoxypheny l ) -8 -methy l -b i cyc lo [4 .2 .0 ] oc tan -7 -o l (30d) - s te reochemis t ry unknown m/e (re lat ive intens i ty) 215 (19.3), 192 (100), 177 (9.2), 163 (42.9), 133 (27.7). 153 Product Rat io Study The product ra t io study f o r keto-acid (30) was conducted in the same fashion as the product study fo r keto-acid (26). A l l of the samples were analyzed by g.c. and the rat ios of (30b+30c+30d+30e):28a and 30b:30c:30d:30e are shown in table XI I I : SOLVENT cone. (M) temp.°C (30b+30c+30d+30e):28a 30b:30c:30d:30e Aceton i t r i le Benzene Sol id State 0.01 M 0.01 M 22 + 2 22 ± 2 22 ± 2 75:25 ± 3 61:39 ± 3 68:32 ± 2 56:11:11:22±1 48:17:15:20+1 49:3:6:42 ±2 Table XIII : Product rat ios from the photolysis of keto-acid (30) Photolys is of 2-cyclopentyl-2-methyl-1-(4-carboxyphenyl)-l-ethanone(31) a-Methyl-a-cyclopentyl-para-carboxyacetophenone (1.0 g) was i r rad iated fol lowing the same procedure used in the i r r ad ia t i on of keto-acid (26). The resultant o i l was analyzed by g.c. (column A, program 2) and found to contain 3 products, para-carbomethoxypropi ophenone 28a (rt 2.34), and two cyclobutanols, 31b (rt 6.22) and 31c (r t 6.54). The two major components 28a and 31b were isolated using a column (2.0 cm x 30 crn) of s i l i c a gel 60 (230-400 mesh) with a 0-9% ethyl acetate in petroleum ether solvent as the step gradient eluent. The minor cyclobutanol 31c was tentat ive ly i den t i f i ed by i t s g.c.-mass spectrum. The stereochemistry of cyclobutanol 31c is not known. Para-carbomethoxypropi ophenone was ident i f i ed by comparison of i t s g.c. retention time and mass spectrum with an authentic sample. 154 6-(la, 5a, 66, 7a)-(4-carbomethoxypheny1)-7-methyl-bicyclo [3.2.0]  heptan-6-ol (31b) Cyclobutanol (31b) was iso lated as a s l i gh t l y yellow o i l : _ir (neat) 1726 cm"1 (C=0), 3466 cm"1 (broad, OH); XH nmr (CDU 3 , 400 MHz) 1.15 (3H, d, J=7 Hz), 1.3-1.65 (6H, m), 1.92 (IH, s, broad, exchanges with D 20), 2.53 (2H, m), 2.79 (IH, m), 3.92 (3H, s ) , 7.33 (2H, d, J=8 Hz), 8.01 (2H, d, J=8 Hz), proton decoupling of the signal at 1.15 results in a s imp l i f i ca t i on of the s p l i t t i n g pattern fo r the mult ip let at 2.53; proton decoupling of the signal at 2.53 results in the doublet at 1.15 co l laps ing to a s ing let and the mult ip let at 2.79 to col lapsing to a broad doublet (J=2.1 Hz); proton decoupling the signal at 2.79 results in a s imp l i f i c a t i on of the s p l i t t i n g pattern fo r the mult ip let at 2.53; in an N.O.E. difference experiment, i r r ad ia t i on of the signal at 7.33 results in an enhancement of the signal at 2.53 and a weaker enhancement at 2.79, the signal at 8.01 is also enhanced; m/e (re lat ive intens i ty) 260 (m+, 0.1), 192 (100), 163 (51.6); calculated mass fo r C 1 A H ? n 0^: 260.1412, Found: 260.1409. 6-(4-carboroethoxyphenyl)-7-methyl-bicyclo [3.2.0] heptan-6-ol (31c) - stereochemistry unknown m/e (re lat ive intens i ty) 192 (100), 177 (16.2), 163 (40.0), 133 (27.0). Product Rat io Study The product rat io study fo r keto-acid (31) was conducted in the 155 same fashion as the product rat io study fo r keto-acid (26). A l l of the samples were analyzed by g.c. and the ratios of (31b+31c):28a and 31b:31c are shown in table XIV: SOLVENT cone. (M) temp.°C (31b+31c):28a 31b:31c Ace ton i t r i l e Benzene Sol id State 0.01 M 0.01 M 22 ± 2 22 ± 2 22 ± 2 68:32 ± 4 53:47 ± 2 55:45 ± 3 77:23 ± 2 76:24 ± 1 100:0 Table XIV: Product rat ios from the photolysis of keto-acid (31) In order to perform quantum y i e l d studies, the keto-acids were converted to t he i r corresponding methyl esters. Photolysis of the keto-esters y ie lded the same products as were obtained by e s t e r i f i c a t i on of the photoproducts from the keto-acids. The product ratios from the photolysis of the keto-esters were obtained in ace ton i t r i l e and benzene solvents in the same fashion as the product rat io study for ketone (9). Photolysis of 2-cyclooctyl-l-(4-carbomethoxyphenyl)-ethanone (32) SOLVENT cone. (M) temp.°C (26b+26c):26a 26b:26c Ace ton i t r i l e Benzene 0.10 M 0.10 M 22 ± 2 22 + 2 68:32 ± 1 65:35 + 1 52:48 ± 1 75:25 ± 1 Table XV: Product rat ios from the photolysis of keto-ester (32) 156 Pho t o l y s i s of 2-cyc lohepty l-1-(4-carbomethoxyphenyl)-ethanone (33) SOLVENT cone. (M) temp.°C (27b+27c):26a 27b:27c Ace ton i t r i l e Benzene 0.10 M 0.10 M 22 ± 2 22 ± 2 38:62 ± 1 46:54 ± 1 65.35 ± 1 84:16 ± 1 Table XVI: Product rat ios from the photolysis of keto-ester (33) Pho t o l y s i s of 2 -cyc loocty l-2 -methy l-1-(4 -carbomethoxyphenyl)- ethanone (34) SOLVENT cone. (M) temp.°C (28b+28c+28d):28a 28b:28c:28d Ace ton i t r i l e Benzene 0.10 M 0.10 M 22 ± 2 22 ± 2 50:50 ± 3 57:43 ± 2 66:19:15 ± 1 75:19:6 ± 1 Table XVII: Product rat ios from the photolysis of keto-ester (34) Pho t o l y s i s of 2-cyc lohepty l-2-methyl-1-(4-carbomethoxyphenyl)- ethanone (35) SOLVENT cone. (M) temp.°C (29b+29c+29d):28a 29b:29c:29d Ace ton i t r i l e Benzene 0.10 M 0.10 M 22 ± 2 22 ± 2 30:70 ± 2 29:71 ± 3 52:29:19 ± 1 59:27:14 ± 2 Table XVIII: Product rat ios from the photolysis of keto-ester (35) 157 Photolysis of 2-cyclohexyl-2-methyl-1-(4-carbomethoxyphenyl)- ethanone (36) SOLVENT cone. (M) temp.°C (30b+30c+30d+30e):28a 30b:30c:30d:30e Aceton i t r i le Benzene 0.10 M 0.10 M 22 ± 2 22 + 2 48:52 ± 2 47:53 ± 2 58:7:9:26 ± 1 57:10:13:20± 2 Table XIX: Product rat ios from the photolysis of keto-ester (36) Pho t o l y s i s of 2 -cyc lopenty l-2 -methy l -1-(4-carbomethoxypheny1)- ethanone (37) SOLVENT cone. (M) temp.°C (31b+31c):28a 31b:31c Aceton i t r i le Benzene 0.10 M 0.10 M 22 ± 2 22 ± 2 45:55 ± 2 61:39 ± 2 79:21 ± 2 72:28 ± 1 Table XX: Product rat ios from the photolysis of keto-ester (37) Quantum Y i e l d s $ Quantum y ie lds were determined fol lowing the procedure of Lewis 3 Three Pyrex tubes were f i l l e d with 3 ml of benzene containing the ketone (0.10 M) and an alkane internal standard. Three d i s t i n c t standards were used at a concentration of 1 mg/ml: 1. Tetradecane (C 1 1 +) , Valerophenone standard •2. Docosane (C 2 2 ) 3. Tetracosane (C 2 4 ) 158 P r io r to quantum y i e l d determinations, the accuracy of the g.c. detector response to the standard and photoproducts was accurately determined. These were found not to deviate substant ia l ly from the response factor of 1:1 fo r a 1:1 mass rat io of photoproduct to standard. The samples were degassed using three freeze-pump-thaw cycles and i r rad ia ted using a 450-W, medium pressure mercury lamp with a f i l t e r so lut ion of potassium chromate to i so la te the 313 nm l i ne . The amount of l i gh t absorbed was measured by simultaneous i r rad ia t i on of the tubes containing the ketone, with three tubes containing a 0.10 M solut ion of valerophenone and 1 mg/m! standard as the actinometer so lut ion. The i r r ad i a t i on was conducted on a merry-go-round apparatus, and product y i e lds were determined by g . c , fo r conversions up to 4%. The y i e l d of acetophenone from valerophenone was calculated knowing the exact concentration of the internal standard, the detector response factor (1:1) and the rat io of acetophenone to internal standard, as determined by g.c. analys is . The quantum y i e l d of acetophenone from valerophenone is known to be 0 .33 3 5 and thus, the amount of l i gh t absorbed by the samples was determined. From the y ie lds of the photoproducts and knowledge of the amount of l i gh t absorbed by the samples, the quantum y ie lds of the fol lowing ketones were determined. These are shown in table XXI. An accumulated er ror of ±15% in the quantum y ie lds has been calculated from the standard deviations observed fol lowing mult iple g.c. analys is . The ketone concentrations of 0.1 M ensured that the samples were 159 opt i ca l l y opaque at 313 nm. KETONE STANDARD $ CLEAVAGE $ CYCLIZATION $ TOTAL 20 C 22 0.11 0.06 0.17 21 C 22 0.074 0.108 0.18 33 c 2 H 0.11 0.064 0.174 34 C2L> 0.0665 0.056 0.123 35 C2L> 0.046 0.013 0.059 36 C 2 4 0.022 0.013 0.035 37 C 2 4 0.027 0.016 0.043 Table XXI: Quantum y ie lds fo r ketones 20, 21, 33-37, in benzene Rate Studies Rate studies were performed fol lowing the same i r r ad i a t i on and degassing techniques u t i l i z ed in the quantum y i e l d studies. Several Pyrex tubes containing 3 ml of a 0.1 M solut ion of ketone and 1 mg/ml of standard, in benzene, were prepared with several concentrations of 2,5-dimethyl-2,4-hexadiene. The amount of l ight absorbed was calculated using valerophenone as the actinometer. The absolute y i e l d of the photoproducts was determined and converted to quantum y ie lds fo r each quencher concentration. The quantum y i e l d f o r each ketone in the absence of quencher was divided by the quantum y ie lds ($) determined at each quencher concentration. These values are shown in table XXII. For a t r i p l e t state photoreacti on, a plot of § Q /§ against quencher concentration w i l l y i e l d a stra ight l ine with a slope equal to K i and an intercept 160 of 1. The value T i s the t r i p l e t l i f e t ime and is the rate of t r i p l e t quenching by the quencher. KETONE Cone. Quencher (M) » 0/» 20 0.0 0.17 1.0 0.022 0.14 1.21 0.056 0.112 1.52 0.108 0.092 1.85 0.155 0.083 2.05 0.212 0.068 2.50 21 0.0 0.18 1.0 0.022 0.154 1.17 0.0564 0.123 1.46 0.108 0.091 1.98 Table XXII: Values of $0/<£> and quencher concentrations for ketones 20 and 21 161 BIBLIOGRAPHY 1. Norr ish, R., and Appleyard, M., J . Chem. S o c , 874 (1934). 2. Yang, N .C , and Yang, D.H., J . Am. Chem. S o c , 80, 2913 (1958). 3. McMil lan, G.R., Calvert , J .G . , and P i t t s , J . N . , J . Am. Chem. Soc. 3602 (1964). 4. Sr in ivasan, R., J . Am. Chem. S o c , 81, 5061 (1959). 5. Coulson, D.R., and Yang, N.C., J . Am. Chem. S o c , 88, 4511 (1966). 6. For a review of photochemical excited states see: Turro, N.J . , Modern Molecular Photochemistry, Columbia: Benjamin/Cummings, 1978. 7. Rauh, R.D., and Leermakers, P.A., J . Am. Chem. S o c , 90, 2246 (1968). 8. Hochstrasser, R.M., and Marzacco, C , J . Chem. Phys., 49, 971 (1968) . 9. Yang, N .C , E l l i o t , S.P., and Kim, B., J . Am. Chem. S o c , 91, 7551 (1969) . 10. Dougherty, T . J . , J . Am. Chem. S o c , 87, 4011 (1967). 11. Yang, N .C , and E l l i o t , S.P. , J . Am. Chem. S o c , 91, 7550 (1969). 12. Wagner, P . J . , and Hammond, G.S., J . Am. Chem. S o c , 87, 4009 (1965). 13. Hammond, G.S., Leermakers, P.A., and Turro, N.J . , J . Am. Chem. S o c , 83, 2396 (1961). 14. Wagner, P . J . , and Hammond, G.S., J . Am. Chem. Soc. 88, 1245 (1966). 15. Wagner, P . J . , and Kochevar, I . , J . Am. Chem. S o c , 90, 2232 (1968). 16. Wagner, P . J . , J . Am. Chem. S o c , 89, 5898 (1967). 17. Wagner, P . J . , Kelso, P.A., Kemppainen, A .E . , and Zepp, R.G., J . Am. Chem. S o c , 94, 7500 (1972). 18. Hesse, R.H., Advanced Free Rad. Chem., 1, 83, (1969). 19. Corey, E . J . , and Hert ler , W.R., J . Am. Chem. S o c , 82, 1657 (1960). 162 20. A r i e l , S., Ramamurty, V., Scheffer, J .R . , and Trotter, J . , J . Am. Chem. S o c , 105, 6959 (1983). 21. Scheffer, J .R . , Trot ter , J . , Omkaram, N., Evans, S., and A r i e l , S., Mol. Cryst. L i q . Cryst. Vol 134, 169 (1986). 22. Appel, W.K., J iang, Z.Q., Scheffer, J .R . , and Walsh, L., J . Am. Chem. S o c , 105, 5354 (1983). 23. Djerass i , C D . , Pure Appl. Chem., 9, 159 (1964). 24. Henion, J .D . , and Kingston, D.G.I., J . Am. Chem. S o c , 96, 2532 (1974). 25. Wagner, P .J . Kelso, P.A., Kemppainen, A.E. , McGrath, J .M . , Schott, H.N., and Zepp, R.G., J . Am. Chem. S o c , 94, 7506 (1972). 26. Krishna, V.G., and Goodman, L., J . Am. Chem. S o c , 83, 2042 (1961). 27. Wal l ing, C , and Gibian, J .M . , J . Am. Chem. S o c , 87, 3361 (1965). 28. Wagner, P . J . , Kelso, P.A., and Zepp, R.G., J . Am. Chem. S o c , 94, 7480 (1972). 29. Stephenson, L.M., and Brauman, J . I . , J . Am. Chem. S o c , 93, 1988 (1971) . 30. Wagner, P . J . , and Kemppainen, A.E. , J . Am. Chem. S o c , 90, 5896 (1968). 31. Wagner, P . J . , Accounts Chem. Res., 4, 168 (1971). 32. Lewis, F.D., and H i l l i a r d , T.A., J . Am. Chem. S o c , 92, 6672 (1970). 33. Lewis, F.D., and H i l l i a r d , T.A., J . Am. Chem. S o c , 94, 3852 (1972). 34. Wagner, P . J . , and McGrath, J .M . , J . Am. Chem. S o c , 94, 3849 (1972). 35. Wagner, P . J . , and Kemppainen, A.E. , J . Am. Chem. S o c , 94, 7495 (1972) . 36. Gagosian, R.B., Dalton, J . C . , and Turro, N.J . , J . Am. Chem. S o c , 92, 4752 (1970). 37. Lewis, F.D., and Johnson, R.W., Tetrahedron Le t t . , No. 27, 2557 (1973) . 163 38. Lewis, F.D., and Johnson, R.W., J . Am. Chem. S o c , 96, 6090 (1974). 39. E l i e l , E.L., Stereochemistry of Carbon Compounds, pp 157, 237, New York, N.Y.: McGraw H i l l , 1962. 40. Lewis, F.D., Johnson, R.W., and Johnson, D.E., J . Am. Chem. S o c , 96, 6096 (1974). 41. Schmidt, G.M., Pure Appl. Chem., 27, 647 (1971). 42. Thomas, J .M . , Pure Appl. Chem., 51, 1065 (1979). 43. Scheffer, J .R . , Acc. Chem. Res., 13, 283 (1980). 44. Ramamurty, V., and Venkatesan, K., in preparation (1986). 45. Kohlshutter, H.W., Z. Anorg. A l l g . Chem., 105, 121 (1918). 46. Cohen, M.D., and Schmidt, G.M., J . Chem. S o c , 1996 (1964). 47. A r i e l , S., Evans, S., Hwang, C , Jay, J . , Scheffer, J .R . , Trot ter , J . , and Wong, V., Tetrahedron Le t t . , vo l . 26, No. 8, 965 (1985). 48. Scheffer, J .R . , And Dzakpasu, A.A., J . Am. Chem. S o c , 100, 2163 (1978). 49. S l i v inskas , J .A . , and Gu i l l e t , J . E . , J . Polym. S c i . , Polym Chem. Ed., 11, 3043 (1973). 50. The a-cyclohexyl and a-cyclopentyl-para-carboxyacetophenones have been prepared and studied by N. Omkaram; unpublished resu l t s . The X-ray structure of a-cyclopentyl-para-carboxyacetophenone has been determined; Evans, S., and Trotter , J . , unpublished resu l t s . 51. Lewis, F.D., Johnson, R.W., and Ruden, R.A., J . Am. Chem. S o c , 94, 4292 (1972). 52. Padawa, A., and Eastman, D., J . Am. Chem. S o c , 91, 462 (1969). 53. The X-ray structure of a-cyclohexyl-para-carboxyacetophenone has been determined; A r i e l , S., and Trot ter , J . , Acta Crys t . , C41, 446 (1985). 54. W i l l s t a t t e r and Waser, E. Ber., 43, 1176 (1910). 55. B l i cke , F.F., and Johnson, W.K., J . Am. Pharm. Assn., vo l . XLV, No. 7, 443 (1956). 164 56. McCarthy and Brown, J . Am. Pharm. Assn., vo l . XLIII , No. 11, 661 (1954). 57. Sauvage, J . F . , et a l . , J . Am. Chem. S o c , 83, 3874 (1961). 58. Wagner, P . J . , and Siebert, E . J . , J . Am. Chem. S o c , 103, 7329 (1981). 59. Creger, P.L., Organic Synthesis, vo l . 50, p. 58: John Wiley and Sons, 1970. 60. The fol lowing compounds have been previously synthesized; Scheffer, J .R . , and Omkaram, N., unpublished resu l ts : i ) a-cyclohexyl and a-cyclopentyl-para-fluoroacetophenone, i i ) a-methyl-a-cyclohexyl-para-cyanoacetophenone, i i i ) a-methyl-a-cyclohexyl-para-carboxyacetophenone. 61. The crysta l structure for a-methyl-a-cyclohexyl-para-carboxyacetophenone has been determined; A r i e l , S., and Trot ter , J . , Acta. Cryst . , C42, 71 (1986). 62. The crysta l structure has been determined; Evans, S., and Trot ter , J . , unpublished resu l t s . 63. The x-ray crysta l structure of a-methyl-a-cyclopentyl-para-carboxyacetophenone has been determined. Disorder in the crysta l structure may resu l t in s l i gh t deviations of the quoted angles and distances from the actual values. Evans, S., and Trot ter , J . , unpublished resu l t s . 64. De Boer, Th. J . , and Backer, H.J . , Recuei des Traveaux Chimiques, 73, 229 (1954). 65. Nol ler and Adams, J . Am. Chem. S o c , 46, 1889 (1924). 66. Meyer, Ann., 219, 260 (1883). 67. Weitkamp, H., and Korte, F., Tetrahedron Supp. 7., 75 (1966). 68. Preliminary X-ray analysis performed by S. Evans; Evans, S., and Trot ter , J . , unpublished resu l t s . 69. E l i e l , A l l i nge r , Angyal and Morrison, Conformational Analys is , p 193, New York, N.Y.: Interscience Publ ishers, 1965. 70. Schleyer, P. von R., Wil l iams, J . E . , and Blanchard, K.R., J . Am. Chem. S o c , 92, 2377 (1970). 71. A l l i nge r , N.L., and Sprague, J .T . , J . Am. Chem. S o c , 94, 5734 (1972). 165 72. Baird, N.C., and Dewar, M.J.S., J . Chem. Phys., 50, 1262 (1969). 73. Euler, E.M., Andose, J .D . , Schleyer, u.P.von., J . Am. Chem. S o c , 95, 8008 (1973). 74. A l l i nge r , N.L., J . Am. Chem. S o c , 93, 1637 (1971). 75. Chang, S . J . , McNally, C , Tehrany, S., Hickey, M.I., and Boyd, u.R., J . Am. Chem. S o c , 92, 3109 (1970). 76. Padawa, A., Alexander, E., and Niemcyzk, M., J . Am. Chem. S o c , 91, 456 (1969). 77. Reference 6, p. 237. 78. Herzschuch, R., and Epsch, K., J . Prakt. Chemie., 1, 37 (1986). 79. Scheffer, J .R . , and Omkaram, N., unpublished resu l t s . 80. The p-Me and p-OMe ketones excluding the a-cyclohexyl ser ies have been studied by N. Omkaram: Omkaram, N., and Scheffer, J .R . , unpublished resu l t s . 166 APPENDIX Quantum Y ie ld : From the t r i p l e t state $ = §CT ——— sal H LKd § n = quantum y i e l d of type II products 5>^ y = quantum y i e l d for s ing let to t r i p l e t intersystem crossing kH = di radical formation from T. kH + Ik d 0p = e f f i c i ency of d i rad ica l to Type II products kH = rate of hydrogen abstract ion k n = rate of t r i p l e t deact ivat ion by radiat ive and non-radiative decay Rate Study: Stern-Volmer Analysis — = 1 + k x [Q] $ = quantum y i e l d in the presence of quencher $° = quantum y i e l d in the absence of quencher kq = bimolecular quenching rate constant x = t r i p l e t l i f e t ime [Q] = quencher concentration 

Cite

Citation Scheme:

        

Citations by CSL (citeproc-js)

Usage Statistics

Share

Embed

Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                        
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            src="{[{embed.src}]}"
                            data-item="{[{embed.item}]}"
                            data-collection="{[{embed.collection}]}"
                            data-metadata="{[{embed.showMetadata}]}"
                            data-width="{[{embed.width}]}"
                            async >
                            </script>
                            </div>
                        
                    
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:
https://iiif.library.ubc.ca/presentation/dsp.831.1-0060531/manifest

Comment

Related Items