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Towards liquid crystalline [3 + 3] Schiff-base macrocycles Edwards, David Ryan 2007

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TOWARDS LIQUID CRYSTALLINE [3+3] SCHIFF-BASE MACROCYCLES  by David Ryan Edwards B.Sc. (Hons.), University of Victoria, 2004  A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE  in THE FACULTY OF GRADUATE STUDIES (Chemistry)  THE UNIVERSITY OF BRITISH COLUMBIA September 2007  © David Ryan Edwards, 2007  Abstract Conjugated Schiff-base macrocycles are interesting compounds of interest as platforms for catalysis, the preparation of novel synthetic ion channels and potentially as porous or tubular discotic liquid crystals. The preparation of organic macrocycles is typically low yielding, with polymerization competing with cyclization; the use of imines derived from the condensation of an aldehyde and an amine provides a means by which to conduct cyclizations under thermodynamic control and thereby improve yields. The use of difunctional aldehydes and amines allows for the formation of macrocycles in high yields without the need for high-dilution conditions. Two highly substituted dialdehydes also bearing phenolic and aikyl functionalities were prepared by several routes in an effort to obtain macrocycle precursors. These precursors were characterized and subsequently employed to prepare [3+3] Schiff-base macrocycles with a large number of appended aikyl and alkoxy substituents in hopes that they would display discotic liquid crystallinity.  A series of highly substituted [3+3] Schiff-base macrocycles was prepared and characterized by 'H NMR, C NMR, UV-Vis, and IR spectroscopies in addition to MALDI- ~ 13  TOF mass spectrometry. The thermal properties of these macrocycles were also examined, and they were not found to display liquid crystalline mesophases either by differential scanning calorimetry or polarizing optical microscopy. A crystal structure of one of the macrocycles was obtained and was found to display structural features not previously observed in related macrocycles.  Table of Contents  Abstract Table of Contents....:  ii iii  List o f Tables  v  List o f Figures  vi  List of Schemes  viii  List o f Symbols and Abbreviations  ix  Acknowledgements  xi  Chapter 1: Introduction  1  1.1 Schiff Bases  1  1.2 Schiff Base Macrocycles  2  1.3 Liquid Crystals  8  1.3.1 A Historical Perspective  8  1.3.2 A B r i e f Primer on Liquid Crystallinity  9  1.3.3 Discotic L i q u i d Crystals  12  1.4 Objectives  16  Chapter 2: Hexasubstituted Benzenes as Macrocycle Precursors  17  2.1 Background  17  2.2 In Pursuit o f dialkyldihydroxybenzenedialdehydes  19  2.3 A Brief Discussion o f Synthetic Methodologies  32  2.4 Properties o f the dialkyldihydroxybenzenedialdehydes  33  2.5 Conclusions and Recommendations  39  2.6 Experimental  40 iii  Chapter 3: [3+3] Macrocycles  53  3.1 Background  53  3.2 Discussion  :  56  3.2.1 Synthetic Aspects  56  3.2.2 Characterization  58  3.2.3 Thermal Properties o f the Macrocycles  66  3.2.4 Crystallography o f Macrocycle 19a...  68  3.3 Conclusions and Recommendations 3.4 Experimental  Chapter 4: Conclusions and Future Work  71 •  72  81  4.1 Conclusions  81  4.2 Future W o r k  82  References  84  Appendix 1: Crystallographic Data for Compounds 31a and 19a  90  iv  List of Tables Table 2.1: Optimization o f Lithiation/Formylation Conditions  25  Table A l . 1: Crystallographic Data for Compound 31a  90  Table A1.2: Crystallographic Data for Macrocycle 19a  92  V ,  List of Figures  Figure 1.1: Early Polyheterodentate Schiff Base Macrocycles  4  Figure 1.2: Porphine and Some Related Expanded Porphyrin Schiff Base Macrocycles  5  Figure 1.3: A [6+6] Schiff Base Macrocycle  6  Figure 1.4: Schematic Representations of a) Nematic Calamitic, b) Smectic-A,  11  and c) Smectic-C Mesophases Figure 1.5: Schematic Representation of a Chiral Nematic Mesophase  11  Figure 1.6: Prototypical Calamitic and Cholesteric Mesogens  11  Figure 1.7: Widely Investigated Planar Discotic Molecules That Exhibit L i q u i d  13  Crystallinity; a) hexa-n-alkanoates of benzene; b) hexa-n-alkyl, hexa-n-alkoxy, and hexa-n-alkanoate derivatives of triphenylene; c) octasubstituted phthalocyanines; d) hexasubstituted hexa-pen-hexabenzocoronenes ( H B C s ) Figure 1.8: Schematic Representation of Nematic and Columnar Discotic Mesophases  13  Figure 1.9: Pyramidal or B o w l i c Mesogens  15  Figure 1.10: Target [3+3] Schiff Base Macrocycles  16  Figure 2.1: [3+3] Schiff Base Macrocycles Bearing Six A l k o x y Substituents  17  Figure 2.2: 400 M H z *H N M R of the Crude Product of the Lithiation and  26  Formylation o f 25b Figure 2.3: Determination o f Product Distribution by N M R Integration  ,  26  Figure 2.4: 400 M H z ' H N M R Spectrum of Compound 31a  33  Figure 2.5: 100 M H z C N M R Spectrum of Compound 31a  34  Figure 2.6: IR Spectrum of Compound 31a  34  Figure 2.7: O R T E P Diagram of the Assymetric Unit Cell of a Single Crystal of  36  1 3  Compound 31a Figure 2.8: V i e w A l o n g the a A x i s for a Single Crystal of 31a  37  Figure 2.9: V i e w A l o n g the b A x i s for a Single Crystal o f 31a  37  Figure 2.10: V i e w A l o n g the c A x i s for a Single Crystal of 31a  38 vi  Figure 2.11: Possible Quinoidal Tautomers for 2,3-dialkyl-5,6-dihydroxybenzene-  38  1,4-dialdehydes Figure 3.1: Structures o f the [3+3] Macrocycles Prepared in this Work  55  Figure 3.2: Structures o f Some o f the [1+2] Fragments Obtained  55  Figure 3.3: 400 M H z *H N M R Spectrum of Macrocycle 19a  59  Figure 3.4: 100 M H z C N M R Spectrum of Macrocycle 19a  60  Figure 3.5: 400 M H z *H N M R Spectrum of Macrocycle 20e  60  Figure 3.6: IR Spectrum of Macrocycle 19a  61  Figure 3.7: IR Spectrum of Macrocycle 20e  61  Figure 3.8: M A L D I - T O F Mass Spectrum of 19a  62  Figure 3.9: M A L D I - T O F Mass Spectrum of 20e  63  Figure 3.10: Normalized Absorption Spectra of Macrocycles 19a, 19b and 19f  64  Figure 3.11: 400 M H z H N M R Spectrum of the [1+2] Compound 32a  65  Figure 3.12:IR Spectrum of the [1+2] Compound 32b  65  1 3  ]  Figure 3.13: D S C Trace for Macrocycle 19b  ".  67  Figure 3.14: D S C Trace for Macrocycle 19f...  67  Figure 3.15: Top V i e w o f Macrocycle 19a as Determined by S C X R D  68  Figure 3.16: Side V i e w o f Macrocycle 19a as Determined by S C X R D . .  69  Figure 3.17: Packing V i e w of Macrocycle 19a A l o n g the a - A x i s  70  Figure 3.18: Packing V i e w of Macrocycle 19a A l o n g the c-Axis  70  vii  List of Schemes Scheme 1.1: General Schiff Base Condensation  2  Scheme 1.2: Structual Diversity from the Condensation o f Diftinctional Amines and Carbonyls  3  Scheme 1.3: Formation o f [3+3] Schiff Base Macrocycles  7  Scheme 2.1: Some Routes Employed to Prepare the Target Compounds  18  Scheme 2.2: Kumada Coupling  19  Scheme 2.3: Bromination o f 1,2-dialkylbenzenes  21  Scheme 2.4: Methoxylation o f l,2-dibromo-4,5-dialkylbenzenes  21  Scheme 2.5: Direct Formylation o f 1,2-dimethoxybenzene  23  Scheme 2.6: Bromination o f l,2-dimethoxy-4,5-dialkylbenzenes  24  Scheme 2.7: Lithiation/Formylation o f l,4-dibromo-2,3-dialkyl-5,6-  25  dimethoxybenzenes Scheme 2.8: Lithiation/Acylation o f l,4-dibromo-2,3-dialkyl-5,6-dimethoxybenzenes  27  Scheme 2.9: Reduction o f Crowded Benzoate Esters with L1AIH4  28  Scheme 2.10: Reduction with D I B A L - H  .29  Scheme 2.11: Cyanation o f A r y l Bromides  29  Scheme 2.12: Proposed General Mechanism for Formylation with H M T A  31  Scheme 2.13: Possible Route to Longer Chain Analogues o f 30a and 30b  39  Scheme 3.1: Possible Mechanism for Piperidine-Catalyzed Imine Formation via an Iminium Intermediate  58  List of Symbols and Abbreviations A  angstroms (1 A = 10" m)  a.m.u.  atomic mass units  br  broad ( N M R , IR)  ca.  circa (about)  , 3  8  C NMR  carbon-13 nuclear magnetic resonance  d  deuterium ( N M R )  d  doublet ( N M R )  5  chemical shift  dec.  decomposes  DCM  dichloromethane  DIBAL-H  diisobutylaluminum hydride  dppp  l,3-bis(diphenylphosphino)propane  DSC  differential scanning calorimetry  8  molar extinction coefficient exempli gratia (for example)  equiv.  equivalents  ESI  electrospray ionization  h  hours  HMTA  hexamethylenetetramine  'HNMR  proton nuclear magnetic resonance  HR-EI-MS  high resolution electron impact mass spectrometry  Hz  Hertz  /'. e.  id est (that is)  IR  infrared  J  coupling constant ( N M R )  M  moles/L  MALDI-TOF-MS  matrix-assisted laser desorption/ionization time-of-flight mass spectrometry  m.p.  melting point  m  multiplet ( N M R )  Me  methyl group  MeO  methoxy group  MeOH  methanol  min  minutes  mol  moles  m/z  mass to charge ratio  NMR  nuclear magnetic resonance  ORTEP  Oak Ridge thermal ellipsoid plot  PCC  pyridinium chlorochromate  ppm  parts per million ( N M R )  q  quartet ( N M R )  R  alkyl group  s  singlet ( N M R )  SCXRD  single crystal x-ray diffraction  t  triplet ( N M R )  TMEDA  tetramethyleneethylenediamine  THF  tetrahydrofuran  UV-Vis  ultraviolet-visible  Acknowledgements  I would like to take the opportunity to thank Dr. Mark MacLachlan for his support and patience when times were trying. I know I can be difficult and for your tolerance I have the utmost gratitude. I would also like to thank Jon Chong for his assistance with the crystallography, Joseph Hui for his assistance with the MALDI and Alfred Leung for useful discussions on thefineart of chromatography. I am grateful to the MacLachlan group as a  whole for their good humour and acceptance; you are a solid bunch and I wish you luck in life, love, and lit. preps. May all your reactions be high yielding and all your crystals be single. I would also like to thank the various support staff associated with the Department of Chemistry; your tirelessness and dedication keep the pursuit of knowledge on track. My sincere thanks go out to the staff of the NMR facilities, the Mass Spec, and Microanalysis lab, and the Crystallography labs. My apologies to anyone I may have forgotten. Finally, I would like to thank my family; your love and support are worth more to me than I can ever hope to express.  xi  Chapter 1: Introduction 1.1-Schiff Bases Ever since the discovery of the condensation between primary amines and carbonyl compounds (see Scheme 1.1) by Hugo Schiff in 1864, chemists have used this reaction to generate a staggering array o f compounds. Examples o f these so-called Schiff bases (also known as imines or azomethines) are legion in the literature owing to their ease o f synthesis as well as their versatility in binding metals. The ease with which these compounds can be prepared has much to do with the reversibility o f all the steps in the condensation reaction as well as the extrusion o f water; these features allow the reactions to be conducted under thermodynamic conditions in which water can be removed by a variety o f means, thereby allowing them be driven effectively to completion. Schiff bases have been demonstrated to play a role in biochemical processes, adding to their appeal as targets o f investigation for 1  mechanistic elucidation o f enzymatic processes and as structural models for metalloenzymes as well as for the design o f new catalysts. '  2 3  The imines derived from the condensation of mono-  functional carbonyl compounds and amines (and their metal complexes) are o f interest not only as models for biochemical processes and metalloproteins but also for use as liquid crystals (vide 4  infra). Another interesting application of Schiff base chemistry, at least from the standpoint o f materials chemistry, is the condensation o f polyfunctional amines and carbonyl compounds to generate linear polymers and cyclic oligomers. The preparation and characterization o f some of these cyclic oligomers, in the form o f macrocycles, forms the basis o f this thesis.  1  -OH  -OH R"'  "  H R"  H  R +H  R N=<  R'  R  R'  R"  ®> =< H R"  +H 0 2  =  N  -H 0 2  R  +  R' H  N+P® H  R"  H  Scheme 1.1: General Schiff Base Condensation  1.2 - Schiff Base Macrocycles Schiff base macrocycles have the distinction of being some of the earliest known and most thoroughly investigated (non-naturally occurring) cyclic, polydentate ligands. Although the earliest work in the field involved the condensation of bifunctional monomers (i.e. those in which amine and aldehyde functionalities are present on the same molecule), a huge array of 5  possible macrocyclic structures can be imagined arising from the condensation of a difunctional carbonyl unit and a diamine unit. Based on the number and structural diversity of these building blocks, a massive library of macrocyclic ligands can be envisioned. The choice of possible constituent diamine and dicarbonyl moieties is huge; a range of aliphatic and aromatic compounds have been employed to generate a wealth of novel macrocyclic species. In general, 6  the condensation of a difunctional amine and a difunctional carbonyl unit will result in the formation of a number of compounds (see Scheme  1.2),  6,7  in effect generating a dynamic  combinatorial library ranging from discrete mono-condensation products to oligomers and polymers. Through judicious choice of structural features in the building blocks, such as the geometry of the functional groups, macrocycles can be constructed preferentially in relatively high yields.  2  N-  H  2  N .  Y  , N ^ X ^ N . H  Y  , N H  H  A A X  +  N- H N " " N H Y  H  2  2  2  H H N  [1+2]  0  2  y—H  Y-N  H  H O  A  H  X  ^  N  ^  N  ^  X  A  n  [1+1]  0  H  linear oligomers and polymers  H  [2+1]  >t  N  N=  )=N  N:=<  Y  H  <  [2+2], [3+3]  J H n  [N+N]  X, Y = aliphatic, aromatic or some combination thereof  Scheme 1.2: Structual Diversity from the Condensation o f Difunctional Amines and Carbonyls (in this case, aldehydes)  Extensive research in the field has produced a diverse collection o f macrocycles, ranging from relatively small [2+2] species to very large [6+6] cycles incorporating a huge array o f different spacers.  6  The smallest macrocycles possible arising from the condensation of  difunctional building blocks are o f the [2+2] variety; some o f the most widely examined compounds o f this class are the so-called Robson and M c K e e macrocycles, the prototypes o f 8  9  which are illustrated in Figure 1.1 as structures 1 and 2, respectively. These were some o f the first Schiff base macrocycles to incorporate heterodentate binding sites; the early Robson macrocycles were shown to coordinate up to two metal atoms in the two N 2 O 2 compartments or pockets while M c K e e macrocycles can coordinate as many as four.  10  A number of homo and  heterometallic complexes have been prepared and investigated and several o f the homometallic tetrametallated, mixed-valence compounds display cooperative redox behaviour attributable to their geometrically-constrained coordination environments.  11  Structural diversification o f these  types o f macrocycles is an active area o f research, with a number o f different modifications reported in the literature including the use o f thiophenolate donors' and the expansion o f the 2  diamine or dialdehyde 13  14  linkers to name just a few.  Figure 1.1: Early Polyheterodentate Schiff Base Macrocycles  Another interesting class o f Schiff base macrocycles is that consisting o f dicarbonyl units which include one or more pyrrole units ("expanded porphyrins").  Porphyrins and other  15  structurally related polypyrrolic compounds are naturally occurring macrocyclic ligands that are present in a number o f important biological systems; these extremely versatile and varied molecules are central to biochemical processes such as photosynthesis (as chlorophylls) and in oxygen fixation and aerobic respiration (as hemes). Elaboration o f these types o f macrocycles has been the topic o f significant investigation in efforts to design artificial mimics o f these natural systems as well as to probe their properties. Expanded porphyrins incorporating Schiff bases are often obtained by polycondensation o f dicarbonyl units on pyrroles or oligopyrroles, the diamine moieties consisting o f phenylene diamine derivatives ' 16  17  or even small molecules  18  like hydrazine.  A n example o f the prototypical porphyrin, 3 ( also known as porphine), along  with an expanded porphyrin (4) are illustrated in Figure I.2.- Intriguingly, some o f these planar, rigid core, expanded porphyrins (5, with n = 6, 10 and 14) have been shown to display discotic liquid crystalline properties (vide infra)}* 4  Needless to say, there is a huge array of Schiff base macrocycles represented in the chemical literature, the diversity of which is limited only by the imaginations of chemists and the synthetic accessibility of the building blocks. Much work in the MacLachlan group has focused on the construction of new dialdehyde units for incorporation into novel cycles. A significant body of work has been established in particular in the construction of [3+3] species, along with larger [6+6] cycles (e.g. 6; see Figure 1.3).  19  Further elaboration of these types of macrocycles  through thoughtful variation of the constituent synthons and the investigation of their properties as ligands, small-molecule and ion sensors, and components in supramolecular assemblies are active areas of ongoing research.  5  OC Hi 6  0CgHi3  3  6  Figure 1.3: A [6+6] Schiff Base Macrocycle  The specific work undertaken in this project is related to the structural elaboration of a class of [3+3] macrocycles (9a), originally reported in the literature by Akine and coworkers,  20  which are derived from the polycondensation of three equivalents of 3,6-diformylcatechol (7) and three equivalents of 1,2-phenylenediamine (8a; see Scheme 1.3); subsequent work in the MacLachlan group expanded on this macrocyclic core by the incorporation of alkoxy substituents on the diamine moiety, significantly improving the solubility of these species (9bm) and reducing the required reaction time from weeks at room temperature to hours at reflux in a mixture of chloroform and acetonitrile. The resulting soluble macrocycles were shown to display a high affinity for small alkali metal cations resulting in their aggregation into dimeric and trimeric assemblies as evidenced by mass spectrometry and through the use of UV-Vis and N M R spectroscopies.  19d  6  e R = OC H fR = O C H 4  5  | R = OC, H mR = OC H  9  6  n  3 3  1 8  3 7  Scheme 1.3: Formation of [3+3] Schiff Base Macrocycles Fully conjugated macrocycles based on this type of structure have several distinct features that make them desirable synthetic targets for materials chemistry applications. One is their remarkable ease of synthesis; the combination of stoichiometric amounts of an aromatic diamine and an aromatic dialdehyde with the appropriate patterns of substitution, in particular those bearing phenolic groups adjacent to the aldehydes, almost invariably results in the formation of at least some [3+3] macrocycle. This propensity to form macrocyclic products has been attributed to the presence of strong hydrogen-bonding in both the intermediate condensation products and in the final cycles themselves. ' ' ' In a sense, these types of 6 19 20 21  structures can be regarded as self-templating, whereas a number of other classes of Schiff base macrocycles (such as those of the Robson or McKee variety) typically require the presence of metal ions to guide the cyclization process to the desired products in preference to linear oligomers and polymers. Indeed, the versatility of this type of core has also been demonstrated through the use of aliphatic diamine linkers (specifically l,2-bis(aminooxy)ethane) with 3,6diformyl catechol to produce an analogous [3+3] hexaoxime macrocycle in the absence of a metal template, albeit in low yields. Another feature that makes these types-of structures 22  attractive from a materials standpoint is the aforementioned affinity for small metal cations and the possible tubular assemblies which can be produced; these assemblies may constitute a new 19d  class of synthetic ion channels. 7  1.3 — Liquid Crystals 1.3.1 A Historical Perspective  23  It was long believed that matter existed in only three states: solid, liquid and vapour; In the mid to late 1800s, scientists working with biologically derived molecules such as stearic acid (octadecanoic acid) and its salts observed strange optical behaviour as these materials neared their melting points. Stearic acid, for example, was observed to undergo several visibly distinct transitions when heated from the solid state, namely from a waxy solid to a cloudy liquid, then to an opaque liquid and finally to an isotropic liquid (i.e. one in which the properties are independent of direction). In 1888, the Austrian botanist Friedrich Reinitzer observed that the benzoate ester of cholesterol melted initially to a cloudy liquid at 146 °C and to an isotropic liquid at 179 °C. On cooling back to the solid state, the sample briefly displayed a blue colour at the isotropic transition temperature (the clearing point) and a violet colour just prior to crystallization. At the time these observations were inexplicable, however the scientific community rose to the challenge and proposed the existence of intermediate states between liquid and solid. Recognition of these intermediate, liquid crystalline states (dubbed mesophases from the Greek meso, or middle) sparked a great deal of interest in the topic at the time.  Despite early interest in thefield,work on liquid crystals seemed to flounder for several decades in the mid 20 century. In spite of pioneering early work by scientists like Walter th  Nernst (who proposed and later retracted the idea that the observed optical phenomena occurred as a result of emulsions or tautomerization rather than mesomorphism) and F.C. Frank (who developed the continuum theory of liquid crystallinity), the field grew largely quiescent between about 1925 and 1960. In 1957, an excellent comprehensive review on the topic was published  24  helping to prompt a resurgence of research interest in the field. As new characterization 8  techniques became available, the understanding of the mesomorphic state grew and in the ensuing years the field of liquid crystals flourished in both academic and industrial circles culminating in the pioneering use of liquid crystals in optical sensors, optoelectronic devices and display technologies. In more recent history, the discovery by Chandrasekhar in 1977 that hexaesters of benzene exhibited mesophase behaviour introduced to the world to a new class of 25  mesogens: discotic liquid crystals. At present, liquid crystals represent some of the most commercially successful advanced materials and dominate the electronic display industry with sales on the order of tens to hundreds of billions of dollars per year. In addition, these materials furnish a rich field of study; the sheer number and structural diversity of compounds which display liquid crystallinity presents an opportunity for chemists to investigate fundamental structure-property relationships for materials with significant commercial applications.  1.3.2 A Brief Primer on Liquid Crystallinity Although lacking the positional order of solids, liquid crystalline phases display some degree of orientational order intermediate between that of crystalline solids and isotropic liquids, the degree of which can vary with temperature and concentration. Several broad classes of liquid crystals are known, and their mesophase behaviour can largely be correlated with their molecular structure. For these types of materials (i.e. mesogens), structural anisotropy on the molecular scale can be paralleled in an emergent fashion by anisotropy on significantly larger length scales. Amphiphilic molecules, most commonly encountered in everyday life as surfactants and soaps, will often form concentration-dependant mesophases when solvated. The micellar, lamellar, and hexagonal columnar arrangements typical of these lyotropic mesogens can be regarded as occurring as a result of the phase segregation of incompatible components on a molecular scale resulting in assemblies which can cooperatively associate into structures possessing micro or even macroscopic dimensions. While lyotropic liquid crystals comprise one 9  broad class o f mesogens, another class is the thermotropic mesogens in which temperature most strongly affects mesophase formation and structure. In these types o f compounds (like cholesteryl benzoate) within a certain temperature range there is sufficient thermal energy to disrupt crystal packing but insufficient energy to overcome certain non-covalent interactions between nearby molecules. This results in the formation o f assemblies or ensembles of molecules that, while lacking long-range positional periodicity, do maintain a degree o f orientational order with respect to one another.  A s mentioned, molecular structure often correlates well with the mesophase behaviours observed in liquid crystals. Rod-like (or calamitic) molecules typically display so called nematic mesophases, in which the molecules lose all long-range positional order but maintain a certain degree o f orientational order. For these types o f molecules, the long axis o f the molecule generally defines the director, n, along which they align. The nematic calamitic is the least ordered mesophase observed (see Figure 1.4a). Other arrangements are possible for calamitic mesogens, including a number o f smectic phases. In these types o f phases, the molecules maintain orientational order (once again with respect to the director, n, usually the long molecular axis), but also gain some positional order relative to a nematic calamitic arrangement. Two examples o f smectic calamitic mesophases are illustrated i n Figure 1.4b and c; in the Smectic-A phase, the director is perpendicular to the planes o f the layers, while in the Smectic-C phase, the molecules are tilted with respect to the plane. When chirality is present in the molecules it can be reflected in the mesophases they display. The so-called chiral nematic (or cholesteric) phase, first observed for the esters of cholesterol, is illustrated in Figure 1.5. In this type o f mesophase the molecules are still aligned into layers, however successive layers are twisted with respect to one another. Prototypical examples o f calamitic and cholesteric mesogens are illustrated i n Figure 1.6 as structures 11 and 12, respectively. A number of other 10  types of mesophase structures have been observed and are generally classified according to variations in the structure of their interlayer arrangements.  Figure 1.5: Schematic Representation of a Chiral Nematic Mesophase  11 calamitic  12 cholesteric  Figure 1.6: Prototypical Calamitic and Cholesteric Mesogens  11  1.3.3 Discotic Liquid Crystals As mentioned, a relatively recent discovery in the field of liquid crystals was that not only can rod-shaped molecules display mesomorphism, but those with disc-like cores can do so as well. This discovery has prompted researchers to investigate a wide variety of disc-like molecules as potential mesogens; some of the most thoroughly examined discotic mesogenic cores are illustrated in Figure 1.7. While these molecules display the same general sort of mesophase behaviours as their thermotropic rod-like cousins (such as birefringence of the mesophase), they differ in several obvious respects. One difference is the dimensionality of the systems; rod-like mesogens can be effectively considered one-dimensional, while discotic mesogens can be considered to extend into two dimensions. This increased dimensionality has an effect on the structures of the mesophases that these materials tend to display. In particular, discotic mesogens, in addition to displaying nematic phases analogous to those of calamitic mesogens (albeit with the director, n, perpendicular to the plane of the cores), most commonly arrange themselves into columnar arrays (see Figure 1.8). ' 26  27  These columnar discotic  mesophases display a number of interesting properties including highly anisotropic charge transport. Hexa-peri-hexabenzocoronene (HBC) derivatives (16, Figure 1.7d), for example, show remarkably high charge carrier mobilities parallel to the columns, comparable to those found for graphite or single crystal organic semiconductors, ' raising the intriguing possibility 27  28  of using these types of materials as molecular wires or interconnects.  Early studies on these types of mesogens typically focused on the smallest possible aromatic core demonstrated to display mesomorphism, namely benzene, however researchers rapidly realized that larger cores might prove advantageous in maximizing the intermolecular, cofacial n-n interactions that have been shown to play a role not only in the charge transport  12  c)  R  R  R  16  Figure 1.7: Widely Investigated Planar Discotic Molecules That Exhibit L i q u i d Crystallinity; a) hexa-n-alkanoates o f benzene; b) hexa-n-alkyl, hexa-n-alkoxy, and hexa-n-alkanoate derivatives of triphenylene; c) octasubstituted phthalocyanines; d) hexasubstituted hexa-perihexabenzocoronenes ( H B C s )  Figure 1.8: Schematic Representation of Nematic and Columnar Discotic Mesophases  •  <  •  properties but also in stabilizing the mesophase.  *  28  A number o f other interesting structure-  property relationships have been established for the rigid, aromatic core discotics in which strong correlations have been observed between the nature o f the substituents and the connecting 77  groups and the temperature o f the mesophase and melting transitions.  In general, it has been  observed that for a series o f rigid discotics with a common core, increasing the length o f the  13  substituents decreases the temperature at which the phase transitions occur. Similarly, the use o f alkoxy linkers to the core reduces the phase transition temperatures relative to aikyl substituents 29  of the same length.  The opposite effect is observed when esters or amides are used as linkers;  typically this type o f substitution results in an increase in the phase transition temperatures, typically attributed to the increased dipole-dipole interactions between the molecules. Although these sorts o f general trends have been observed, there are significant variations between systems based on different cores and in many cases the formation o f a mesophase has been shown to be extremely sensitive to small changes in the structure o f the pendant groups.  For example, for a  series o f ester substituted triphenylene derivatives it was observed that inclusion o f a single bromine atom on the substituent groups was sufficient to completely inhibit mesophase formation.  30  Although rigid core discotic molecules are by far the most commonly reported discotic mesogens represented in the literature, examples exist where molecules with flexible cores can display columnar discotic mesophases. Two examples o f such rare, flexible core mesogens (referred to as pyramidic or bowlic)  are illustrated in Figure 1.9. Certain calix[4]arenes (17,  Figure 1.9a) with pendant alkoxy or ester groups have been shown to form columnar arrays in the mesophase; these molecules also have a sizeable net dipole moment, giving rise to potentially ferri- or antiferrielectric mesophases whose orientation can readily be changed by application o f an external field.  In these species, although inversion o f the cone is rapid for  isolated molecules i n isotropic solutions at the temperatures at which mesophase ordering is observed, cooperativity is believed to slow this process in columnar aggregates. Another example o f a bowlic mesogen is that based on hexaacylated azacrown[18]-N6 (Figure 1.9b). In this type o f compound, the columnar stacks produced in the mesophase have been described as tubular discotic, with evidence suggesting that the columns retain a hollow space in the m i d d l e .  32  14  Variation o f the substituents appended to the nitrogen atoms indicated that these tubular mesophases were somewhat difficult to induce; only those possessing the long chain alkyl benzamide moieties exhibited mesomorphism (18a and 18b).  In analogous compounds with  straight chain amides or amides in which aromatic groups were separated from the core by one or more methylene groups, all mesophase behaviour was absent.  33  Nonetheless, despite the  relative rarity o f this type o f mesogen and the sensitivity o f the observed mesophase behaviour to the substitution, these materials offer the intriguing possibility o f creating persistent hollow columns that are not only interesting from a fundamental standpoint but also as potential for ion transport media or for the preparation o f novel inclusion complexes.  a)  R  R  b)  R  R  R = alkoxy, alkanoate  R  O  18a R = C H OC H. 18b R = CehUOC-nH; 6  4  12  17  Figure 1.9: Pyramidal or B o w l i c Mesogens  15  1.4 - Objectives The goal o f the work undertaken in this project was to develop new, highly soluble macrocycles in the [3+3] Schiff base family incorporating a large number o f appended aikyl and alkoxy groups (see Figure 1.10) in the hopes that these species might be induced to display porous or tubular discotic liquid crystalline mesophases. Although previous attempts to impart liquid crystallinity to these types o f macrocycles through the incorporation o f six peripheral alkoxy substituents were unsuccessful, it was thought that the inclusion o f a larger number o f appended groups (in this case aikyl as in  19c-f and 20c-e) might induce liquid crystallinity. This  thesis w i l l describe the synthesis o f highly substituted dialdehyde units required to for these cycles in Chapter 2 and their subsequent use in the preparation o f [3+3] macrocycles and related compounds in Chapter 3. Characterization and the thermal behaviour o f these macrocycles w i l l also be discussed along as the crystal structure o f 19a.  R  R  R  R= H R = OMe 19c R = OC H 19d R = OC H 19e R = OC H 19f R = OC H 19a 19b  6  R= H R = OMe 20c R = OC H 20d R = OC H 20e R = OC H 20a 20b  13  14  29  16  33  18  R  6  13  16  3  18  3  37  Figure 1.10: Target [3+3] Schiff Base Macrocycles  16  Chapter 2: Hexasubstituted Benzenes as Macrocycle Precursors 2.1 - Background C o n s t r u c t i o n o f the target [ 3 + 3 ] S c h i f f base m a c r o c y c l e s requires b o t h a d i f u n c t i o n a l a m i n e a n d a d i f u n c t i o n a l aldehyde. S o m e o f the p r e v i o u s w o r k i n the M a c L a c h l a n group focused o n v a r i a t i o n o f the d i a m i n e components, i n particular the use o f 4 , 5 - d i a l k o x y phenylenediamine derivatives  (8b-I), and their c o n d e n s a t i o n w i t h 3 , 6 - d i f o r m y l c a t e c h o l (7) to  produce a l i b r a r y o f m a c r o c y c l e s b e a r i n g s i x s o l u b i l i z i n g a l k o x y groups  (9b-l, see F i g u r e 2.1).  A l t h o u g h these m a c r o c y c l e s have been investigated w i t h regards to p o s s i b l e m e s o g e n i c i t y , were observed to be l i q u i d c r y s t a l l i n e either as metal free o r as metallated s p e c i e s . ' 2  3  1  none  It w a s  thought that i n c o r p o r a t i o n o f m o r e pendant groups, i n this case o n the d i a l d e h y d e , m i g h t lead to mesogenic [3+3] macrocycles.  R  R  9a-l  F i g u r e 2.1: [ 3 + 3 ] S c h i f f B a s e M a c r o c y c l e s B e a r i n g S i x A l k o x y Substituents  W i t h s u c h goals i n m i n d , a n d g i v e n the relative f a c i l i t y i n c o n s t r u c t i n g the [ 3 + 3 ] core w i t h the appropriate starting materials and w i t h the synthesis o f the d i a m i n e moieties already b e i n g w e l l e s t a b l i s h e d , the c r u x o f this project c a n essentially be v i e w e d as the synthesis a n d 4  p u r i f i c a t i o n o f the d i o l / d i a l d e h y d e species (31)  r e q u i r e d for the p r e p a r a t i o n o f the m a c r o c y c l e s ,  17  A s such, attempts were made to find a general method to produce these deceptively simple looking molecules. A variety o f methods were employed in attempts to find a general route to these compounds, the majority o f which are summarized in Scheme 2.1.  Scheme 2.1: Some Routes Employed to Prepare the Target Compounds a) Ni(dppp)Cl ; b) B r ; c) NaOMe/MeOH, CuBr, EtOAc; d) B B r ; e) B r , FeCl ; f). Vilsmeyer-Haack (and modifications); g) SnCl , C 1 C H 0 C H ; h) T i C l , C l C H O C H ; i) H-BuLi, D M F ; j) CuCN, D M F ; k) «-BuLi, C l C 0 E t ; 1) D I B A L - H ; m) H M T A , TFA; n) M n 0 ; o) PCC. 2  2  3  4  2  2  3  4  2  2  3  2  3  2.2 - In Pursuit of dialkyldihydroxybenzenedialdehydes The first step in the syntheses employed a Kumada coupling in which the appropriate Grignard reagent was reacted with 1,2-dichlorobenzene (21) in the presence o f a nickel (II) 5  7  *  *  catalyst (see Scheme 2.2). " This reaction is known to be fairly broad i n scope, however certain complications arose for alkyl chains longer than hexyl. The rate o f the reaction appeared to be directly related to the length o f the alkyl chains employed in preparing the Grignard reagent; the longer the chain, the greater the viscosity o f the solution and the slower the reaction. It is a known drawback o f the Grignard that long reaction times promote the formation o f the homocoupling product, with the presence o f the nickel catalyst presumably exacerbating this tendency. Indeed, related catalyst systems have been employed to cross-couple aliphatic Grignards and halides, often resulting in complex product mixtures. This homocoupling 6  reaction was observed to be particularly evident for reactions with R=octyl, decyl and dodecyl, with a large proportion o f the isolated products on workup appearing to being hexadecane, dodecane and tetracosane, respectively, based on ' H N M R integration. The reactions employing octyl- and decyl- magnesium bromide were particularly problematic inasmuch as the homocoupled product distilled in the same temperature range as the desired product, namely the 1,2-dialkylbenzene. Although easier to purify by distillation, further complications arose with the subsequent functionalization of the didodecyl derivative  C l  (vide infra).  Ni(dppp)CI •<2 2  Cl  + 2.5BrMgR  Et 0, N , A 2  2  21  22a-c Scheme 2.2: Kumada Coupling  The next step was the fairly straightforward dibromination o f the 1,2-dialkylbenzenes (see Scheme 2.3).  8 ( R = b u t y l )  '  9 ( R = h e x y l )  Typically, the distilled dialkylbenzene was treated with a 19  slight excess o f elemental bromine in the presence o f h and in the dark. This was followed by quenching with an aqueous solution o f sodium sulfite and sodium hydroxide. Although the literature reports suggest that the dibromo derivative o f 1,2-dibutylbenzene can be obtained as a solid directly from the bromination, it was found in practice that the crude materials obtained 8  were viscous oils from which the l,2-dibromo-4,5-dibutylbenzene would very slowly crystallize on storage at -11 °C. The dibromodibutylbenzene was by far the most easily isolated being a solid (mp = 33-35 °C, lit. 34-35 ° C ) ; the dihexyl analogue, when pure, was a low.melting solid 8  (mp ~18 °C; reported in the literature as an o i l at room temperature) which was prone to melt 9  during filtration. Fortunately, the somewhat more pure solids/oils, which were obtained by filtration, could be recrystallized from 2-propanol affording materials o f high purity in synthetically useful yields for R=butyl and hexyl (-15-20% yield over two steps). Unfortunately, for the dioctyl and didecyl species the distillation o f the dialkylbenzenes proved particularly problematic given the co-distillation of the homocoupled alkanes. For these derivatives the bromination o f the crude mixture of dialkylbenzene and alkane was undertaken, but the products appeared to be themselves viscous oils which made product isolation problematic. Purification o f these oils by distillation required high temperatures (typically >250 °C at <0.1. m m Hg) that resulted in significant decomposition. It was possible to purify the 1,2didodecylbenzene prepared from the Kumada coupling by distillation, however bromination of this material by the method employed for the shorter chain analogues was not effective. Once again, the longer the chain, the longer the reaction times required and the more likely it was to observe products arising from the competitive bromination o f benzyllic positions rather than direct bromination o f the ring. In fact, the bromination o f 1,2-didodecylbenzene with either L or FeCl3 as catalyst seemed to only afford the mono-brominated product, and even that only after long reaction times and i n very low yields (<10%) after chromatographic separation. Other authors have reported the preparation of the target compound by bromination in CCI4; given the 20  relative scarcity o f this solvent and the somewhat unsatisfactory characterization presented,  this  method was not attempted.  R ~  1) X S Br , cat. I , 0°C->RT 2  B  2  2) aq. 5% N a S 0 , 5% N a O H  R  2  2  \  r  r  ^  5  ^  R  B r ^ ^ ^ R  3  22a, b  23a, b  Scheme 2.3: Bromination o f 1,2-dialkylbenzenes  Reaction o f an aryl bromide with sodium methoxide in methanol in the presence o f a catalytic amount o f copper (I) bromide and ethyl acetate affords arylmethoxy ethers in high yields.  11  This reaction was employed on the dibromodialkyl substrates affording the desired  products in good yields for the dibromodibutyl- and dibromodihexylbenzenes (see Scheme 2.4). The products were typically obtained as viscous, water-white oils. Attempts were made to use this reaction to prepare the (mono)methoxy ether o f the chromatographically purified 1-bromo3,4-bisdodecylbenzene in the hopes that the product could be further brominated and resubjected to the methoxylation conditions to afford the desired l,2-dimethoxy-4,5-didodecylbenzene, but the substrate appeared to be incompatible with the conditions and none o f the desired methoxylated product was observed spectroscopically. This is likely attributable to the immiscibility o f the long-chain dialkyls with the extremely polar solvent conditions and their consequent reduced reactive cross section.  B  r  V V  25 wt.% N a O M e in M e O H cat. EtOAc, CuBr  R  B r - ^ ^ R ' 2 3 a  b  N ,A 2  „  rt  M e O ^ ^ R M e O ^ ^ R 24a, b  Scheme 2.4: Methoxylation of l,2-dibromo-4,5-dialkylbenzenes  With the dimethoxydibutyl- and dimethoxydihexyl-benzenes in hand, a general method for introducing formyl groups to the aromatic core was sought. Initial attempts involved use o f '  12 13  Vilsmeyer-Haack conditions '  in hopes that the system would be sufficiently activated towards 21  formylation by the presence o f four electron donating groups on the ring. Attempts were made using the standard conditions, namely the formation o f the complex o f D M F and P O C I 3 followed by addition o f the substrate at 0 °C followed by heating, ' 14  15  however no formylated product was  observed on workup. Complexes o f D M F and other Lewis acids were also employed (namely anhydrides o f acetic-, trifluoroacetic-, methanesulfonic-, and trifluoromethanesulfonic acids) with no success. It is interesting to note that authors have reported the monoformylation o f 1,3,5-trimethylbenzene in 60% yield and o f anisole in 80% yield (-1:4 o/p) using trifluoromethanesulfonic a c i d / D M F .  16  Attempts were also made to formylate or chloromethylate  these substrates (compounds 24a and 24b) through use o f tin tetrachloride/chloromethyl methyl ether and titanium tetrachloride/ dichloromethyl methyl ether, respectively. The substrates were completely unreactive to the former, while the latter only afforded only mono-formylated product after acidic hydrolysis, and that only in low yield (-20-80%) and after long reaction times (~3 days at reflux in D C M ) . Presumably the failure o f these methods is attributable to the hindered nature o f the substrates; the hexasubstitution o f benzene is known to be somewhat difficult.  The second general method attempted to diformylate these substrates consisted broadly of attempts to lithiate the remaining positions on the ring followed by quenching with an electrophile. Direct lithiation o f the ring was possible through the use o f «-BuLi (ortholithiation), however quenching with D M F afforded predominantly the mono-formylated species. The use of T M E D A and a sizeable excess o f «-BuLi was no more effective. This is in contrast to the preparation unhindered analogues (see Scheme 2.5), in which direct lithiation and formylation with D M F (followed by deprotection) affords the desired pyrocatechol derivatives in low to moderate yields.  17  22  CHO OMe \ ^ ^ O M e  OMe  1) nBuLi, T M E D A , E t 0 2  2) D M F then H 0 2  ^ \ ) M e CHO  32  33, - 3 0 % yield  Scheme 2.5: Direct Formylation o f 1,2-dimethoxybenzene  Although direct or/Zzo-lithiation o f aryl ethers is a well known method for further functionalization o f aromatic compounds,  18  it was clearly not adequate to prepare the desired  diformyl compounds required for the synthesis o f the target macrocycles. One method which has been employed successfully to increase the reactivity o f aromatics towards lithiation and subsequent structural elaboration is through the use o f bromine-lithium exchange, at low temperatures.  19  18  particularly  Indeed, the use o f this methodology has been applied to similar (albeit  generally somewhat less hindered) substrates, in which bromine-lithium exchange followed by quenching with D M F or N-methylformanilide has been used to formylate aromatics.  20  A s such,  the l,2-dimethoxy-3,4-dialkylbenzenes (24a, b) were subjected to bromination conditions in an effort to obtain more reactive substrates.  It was found that several different methods could be employed to introduce bromine onto the remaining unsubstituted ring positions o f these compounds. The use o f N B S in D C M was adequate to introduce a single bromine atom-in good yields, however dibromination with this reagent was not feasible even using a large excess o f N B S . This was observed using both the longer chain compounds (R=butyl, hexyl) as well as with dimethylveratrole. Presumably the introduction o f a single bromine atom onto the ring (in addition to the inherent steric congestion of these compounds) is sufficient to deactivate it towards further bromination. That being said, the use o f elemental bromine in the presence o f a Lewis acid catalyst (FeCU) in dichloromethane remarkably afforded the dibromo derivatives in reasonable yields and purities (see Scheme 2.6).  23  Care had to be taken however to not "overbrominate" the compounds, the benzyllic positions being activated towards radical bromination.  MeO 3  Br  Br "Y^Y'  R  M e O ^ ^ ^ R  XS NBS, CH CN 3  0°C->RT  MeO^/L,R MeO  ^  1.2 Br , cat. FeCI , CH CI  MeO  0°C->RT  MeO'  2  R  3  2  25a, b ^R Br  24a, b  A XS Br , cat. FeCI , CH CI 2  3  2  2  0°CH>RT  Scheme 2.6: Bromination o f l,2-dimethoxy-4,5-dialkylbenzenes  With l,4-dibromo-2,3-dibutyl-5,6-dimethoxybenzene and l,4-dibromo-2,3-dihexyl-5,6dimethoxybenzene in hand, attempts were made to apply the bromine-lithium exchange protocol followed by quenching with formylating agents. A number o f different conditions were employed in attempts to optimize this method; typically the concentrations were held constant while conditions like temperature and the electrophile were varied. Initial attempts focused on the use o f conditions analogous to those applied to the dihydro- analogues, namely lithiation followed by quenching with anhydrous D M F . Although a distribution o f products was always observed, some o f the diformylated species was obtained on workup along with monoformylated and regenerated dihydro- compounds (see Scheme 2.7). N o brominated starting material was generally observed spectroscopically after application o f this protocol. A typical ' H N M R spectrum o f the crude material obtained from this method is illustrated in Figure 2.2.  Different  conditions and formylating agents were employed in an attempt to maximize the yield of the desired product (see Table 2.1); however, regardless o f the conditions employed, the proportion of the diformylated compounds never exceeded - 5 0 % as determined by N M R integration, the methoxy signals being diagnostic (see Figure 2.3). Chromatography on the crude material also 24  proved problematic; despite numerous attempts it was extremely difficult to find conditions that would separate all three components. Typically, it was found that conditions that would separate the formylated products from the dihydro species were inadequate to resolve mono- and diformylated species. After many attempts at method optimization and given the somewhat capricious chromatography and relative lack of scalability, it was concluded that this method was not suitable for the preparation o f the target compounds in the quantities required for the ultimate synthesis of the target macrocycles.  25a, b  26a, b  24a, b  a, R = butyl b, R = hexyl  Scheme 2.7: Lithiation/Formylation of l,4-dibromo-2,3-dialkyl-5,6-dimethoxybenzenes  Table 2.1 - Optimization of Lithiation/Formylation Conditions Approximate Product Distribution Substrate Conditions (diformylated  (26a,b):monoformylated:dihydro (24a,b))  24b 24b 25b 25b 25b 25b 25b 25a 25a  4 equiv. rc-BuLi, 2.5 equiv. T M E D A , room temp., 10 equiv. D M F 4 equiv. «-BuLi, 2.5 equiv. T M E D A , reflux prior to quench, 10 equiv. D M F 4 equiv. rc-BuLi, room temp, 10 equiv. D M F 4 equiv. rc-BuLi, 0 °C, 10 equiv. D M F 4 equiv. «-BuLi, -78 °C, 10 equiv. D M F 6 eq. w-BuLi, -78 °C, 10 eq. D M F 4 equiv. «-BuLi, 2.5 equiv. T M E D A -78 °C, 10 equiv. D M F 4 equiv. n B u L i , room temp., 10 equiv. trimethyl orthoformate 4 equiv. «-BuLi, -78 °C, 10 equiv. methyl formate  1 0 % : 6 5 % : 25% 15% : 60% : 25% 20% : 50% : 30% 35% : 45% : 20% 50% : 45% : 5% 4 5 % : 4 5 % : 10% 30% : 50% : 20% 0% : 0% : 100% 40% : 50% : 10%  25  Chloroform-d  11.5  11.0  10.5  10,0  9.5  9.0  8.5  8.0  7.5  7.0  6,5  6.0 ppm  5.5  5.0  4.5  4.0  3.5  3.0  2.5  2.0  1.5  1.0  0.5  0.0  Figure 2.2: 400 M H z ' H N M R o f the Crude Product o f the Lithiation and Formylation o f 25b  3.93 ppm  4.15  4.10  4.05  4,00  3 90 ppm  3 85  3.88, 3.87 ppm  3,75  3.84 ppm  3.70  Figure 2.3: Determination o f Product Distribution by N M R Integration (indicated chemical shifts are for the methoxy protons)  26  Thus, with substrates active towards lithiation but not particularly suited for direct formylation in high yields, other routes to the target 2,3-dialkyl-5,6-dihydroxybenzene-l,4dialdehydes were sought. It was found that quenching o f the dilithiated species with the more reactive ethyl chloroformate afforded the 1,4-diesters 27a and 27b in reasonable yields (-80%) and with a higher proportion o f disubstituted relative to monosubstituted product (usually > 2:1; see Scheme 2.8). Chromatographic separation o f these compounds was also easier given the almost complete absence o f regenerated dihydro- species. That being said, the functionality o f these materials was in the wrong oxidation state, necessitating their net reduction to aldehydes for subsequent macrocyclization.  Br  Br  C0 Et 2  25a, b  27a, b  Scheme 2.8: Lithiation/Acylation o f l,4-dibromo-2,3-dialkyl-5,6-dimethoxybenzenes  Interestingly, it was found that these esters were completely inert to reduction with lithium aluminum hydride even after treatment with a large molar excess (> 1 Ox) and at reflux in dry T H F or 1,4-dioxane under nitrogen for three days. This is i n contrast to the reduction o f similar compounds reported in the literature in which LiAlH4 reductions o f crowded benzoate esters have been reported to afford the benzyl a l c o h o l s ' under the appropriate conditions in 21  22  >75% yields (-4 and < 1 equivalents LiAlH4 respectively and < 3 hours at reflux in dry diethyl ether or T H F ; see Scheme 2.9). Given the relatively mild conditions reported for these reductions o f related compounds, one must conclude that the steric congestion present in the compounds prepared in this work can once again be implicated in their lack o f reactivity.  27  C0 Et  HO.  2  MeO. MeO  OMe  +  UAIH4 0.16 mmol  THF, A, N  MeO.  2  45 minutes  MeO'  34 0.04 mmol  OMe  35, 87% yield  C0 Me  HO  2  +  - 0 . 7 UAIH4  E t 0 , A, N 2  2  2hrs  36  37, 75% yield  Scheme 2.9: Reduction o f Crowded Benzoate Esters with L i A l F L ; (see references 21 and 22)  Despite the failure o f L i A I H 4 to reduce the diesters, other reducing agents were sought in hopes o f ultimately obtaining a synthetically useful route to the target compounds. It is known that stoichiometric amounts o f neutral aluminum hydrides (e.g. diisobutyl aluminum hydride, or D I B A L - H ) can be used to selectively reduce esters to aldehydes at l o w temperature.  23  In spite o f  the relative bulk o f the isobutyl groups present and the previous issues o f steric crowding in the substrates, it was found that the reaction of stoichiometric amounts o f D I B A L - H with the esters did, in fact, reduce the compounds however the results were not exactly as anticipated. Use o f two equivalents o f D I B A L - H at -78 °C instead seemed to reduce some o f the material entirely to benzyl alcohol while leaving some unchanged. Unfortunately, the selectivity o f D I B A L - H decreases with increasing temperature; '  23 24  use of stoichiometric amounts o f this reagent at  ambient temperature also did not appear to yield any aldehyde but instead only partial conversion directly to the benzyl alcohol. Use o f an excess o f this reagent at reduced or at ambient temperature afforded the bis-benzylalcohol (28) i n l o w yields (<20%) after purification (see Scheme 2.10). Subsequent attempts to oxidize these compounds back to aldehydes were unsuccessful; they were found to be completely unreactive towards MnC»2 oxidation while  28  oxidation with P C C in dichloromethane gave a distribution o f products, only a very small proportion o f which was the desired dialdehyde.  Scheme 2.10: Reduction with D I B A L - H  A r y l bromides are versatile substrates for carbon-carbon bond forming reactions. A number o f modern reactions employing these compounds as substrates have been developed including palladium catalyzed reactions like the Heck and Sonogashira couplings. A classical reaction employing these types o f reagents is the Rosenmund-von Braun reaction in which an aryl bromide is converted into an aromatic nitrile by the action o f a stoichiometric amount o f copper (I) cyanide.  Although the original conditions call for the reaction do be done in the  absence o f solvent, it has been found that the use o f high boiling, coordinating solvents (such as pyridine, A^-methylpyrrolidone or D M F ) greatly simplify the workup and do not adversely affect the yields. " 263  0  A p p l y i n g this reaction to compounds 25a and 25b remarkably afforded the  dinitrile species 29a and 29b in high yields (>85%; see Scheme 2.11). Subsequent reduction o f 29a with a stoichiometric amount o f D I B A L - H ' 2 4  corresponding dialdehyde (26a)  25a, b  2 7  followed by acidic hydrolysis afforded the  in - 5 0 % yield after chromatography.  2 9 a  -  b  Scheme 2.11: Cyanation o f A r y l Bromides 29  Considering the large number of steps and resulting less than satisfactory yields and difficult chromatography associated with the lithiation/formylation and cyanation methods, yet another different route to the target 2,3-dialkyl-5,6-dihydroxybenzene-l,4-dialdehydes was sought. Phenols are generally quite reactive substrates for electrophilic.aromatic substitution and, as such, reactions were sought in which the 1,2-dihydroxy-4,5-dialkylbenzenes might be formylated directly, hopefully minimizing the number o f steps and improving the yields. One such reaction that has been used to formylate activated aromatics is the D u f f reaction, in which a phenol is reacted with hexamethylenetetramine ( H M T A ) i n an acidic medium usually affording formylated products in low to moderate yields (see Scheme 2.12).  28  More recent examples o f  this reaction in the literature using trifluoroacetic acid as the solvent indicate improvements in yields  and also, fairly remarkably, the triformylation o f a hindered aromatic system (albeit in  low yields).  30  A l o n g those lines, this reaction was applied to l,2-dihydroxy-4,5-dialkylbenzenes  (30a and 30b) prepared by deprotection o f compounds 24a and 24b with boron tribromide. The initial results o f this method were promising, with spectra indicating the presence o f the desired products in the crude reaction mixture after hydrolysis and extraction. Although the chromatography seemed initially intractable given the marked tendency o f the products to tail on the column (presumably owing to their high polarity), suitable conditions were eventually discovered allowing the isolation o f the target compounds in synthetically useful yields and high purities.  30  CF C0 H 3  Nl  -N  2  -N  Scheme 2.12: Proposed General Mechanism for Formylation with HMTA (adapted from reference 31)  2.3 - A Brief Discussion of Synthetic Methodologies In synthesis, unless some new, specific methodology is being devised and explored, it seems evident that a key factor in the choice of synthetic routes is economy o f effort; it is often advantageous to minimize the number o f steps required to obtain any given target compound in order to maximize yields. A number o f different avenues were explored in an effort to devise a general method to obtain 2,3-dialkyl-5,6-dihydroxybenzene-l,4-dialdehydes (31a,b) for use in the preparation o f novel Schiff base macrocycles. Although three different general routes were successful in producing the target compounds for relatively short butyl and hexyl chains (namely the lithiation/formylation approach, the cyanation/reduction approach and the direct formylation approach), the efficiency o f these methods differ markedly in terms o f the number of steps required as well as the ease o f purification o f the intermediates and products.  From a yield standpoint, the Duff route is certainly the preferred method; overall yields for this route were on the order o f 25-30% from the known compounds 23a and 23b over three steps. B y contrast, the lithiation/formylation and cyanation/reduction routes had yields on the order o f 10-15% over four steps and 20-25% over five steps, respectively. In addition, although chromatography is required at (at least) the final stage for all three routes, that for the Duff formylation is by far the most forgiving and most easily executed. It seems unfortunate in hindsight that in terms o f ease and yields the routes were explored chronologically from hardest to easiest; however this would seem to be the nature o f devising routes to new compounds. Everything is easy once you know what w i l l and w i l l not work, figuring out which is which is the challenge o f synthesis.  32  2.4 - Properties of the dialkyldihydroxybenzenedialdehydes Although seemingly simple compounds, the 2,3-dialkyl-5,6-dihydroxybenzene-l,4dialdehydes (31a,b) present some interesting spectral and structural features which seem worthy of mention. While the ' f f N M R and  1 3  C N M R spectra o f the dibutyl compound (31a,  see  Figures 2.4 and 2.5, respectively) are in accord with what one might expect for, this sort of symmetrically substituted aromatic core, the IR spectrum presents some interesting features (see Figure 2.6). In particular, the C = 0 stretching mode is observed at ca. 1650 cm" , which is quite 1  low for an aromatic aldehyde, but not entirely unexpected given the presumed strong hydrogen bonding present owing to the adjacent phenol. Similarly, the band at 1294 cm" , which can 1  tentatively be assigned to the phenolic C - 0 stretching mode, is somewhat higher that that typically observed for unsubstituted phenols. This may indicate some strengthening/shortening of the C - 0 bond possibly signifying some quinoidal character to the bonding (vide infra).  Chlorolorm-d  water  T  1.89  2.03  y 1  3  1  2  a 1  1  '  "  4 00  '  6.05  y  • •  1  0  9  8 ppm  7  6  '  5  4  y 3  2  1  0  Figure 2.4: 400 M H z H N M R Spectrum o f Compound 31a [  33  5 ^  <N  I  •uinininn4ii««»tmi»iii iiwinin  Figure 2.5: 100 M H z  1 3  C N M R Spectrum o f Compound 31a  It was possible to grow single crystals o f compound 31a by slow evaporation o f a concentrated hexanes solution. Two distinct conformers are present within the asymmetric unit 34  cell o f 31a (see Figure 2.7), one in which the aldehyde groups point towards the phenolic groups and are apparently engaged in strong intramolecular hydrogen bonding. In the other conformer, one aldehyde points towards the phenols, the other towards the (disordered) aikyl chains; in both conformers the aldehydes lie in approximately the same plane as the ring. Packing views along the a, b, and c crystallographic axes are illustrated in Figures 2.8, 2.9, and 2.10, respectively. The view along the a axis suggests that the molecules pack "head to head," forming an interdigitated, lamellar type arrangement in which the polar head groups are, at least to some extent, segregated from the aikyl chains. For a table o f the crystallographic parameters as well as selected bond lengths and angles see Appendix 1, Table 1.  Closer examination o f the bond lengths in the higher symmetry conformer reveals, in general, a slight expansion o f the bonds in the aromatic core from those typically observed (ca. 1.38-1.43 A observed vs. 1.37-1.40 A for typical aromatic C - C bonds).  32  Although some degree  of bond alternation seems evident, it is not particularly pronounced and by no means dramatic. The aldehyde C = 0 bonds also seem to be slightly elongated relative to related compounds (ca. 1.21-1.22 A observed vs. 1.19-1.20 A for typical aromatic aldehydes). The phenolic C - 0 bonds are somewhat shortened relative to that o f a typical phenol, for example (ca. 1.35 A observed vs. 1.36 A for phenols), however this difference is admittedly quite small. Taken together, these trends in bond lengths would seem to suggest possible contributions from a quinoidal tautomer (see Figure 2.11), however the contribution is likely minimal considering the only slight observed bond alternation. The expansion o f the aromatic C - C bonds could readily be attributed to the high degree o f substitution o f the system and the consequent strain induced.  The thermal behaviour o f these compounds was also investigated, both by differential scanning calorimetry ( D S C ) and by polarizing optical microscopy ( P O M ) . Although both 31a 35  and b both exhibited well defined melting transitions by D S C (at 54 °C and 41 °C, respectively), the dibutyl analogue (31a)  was also observed on occasion to display an endothermic transition at  - 5 0 °C. The possibility that this transition corresponded to the formation o f a mesophase was investigated through the use o f P O M , however no textures that might be attributed to liquid crystallinity were observed. Although conceivably an artifact, it is also possible that this transition represents a transformation from one crystalline polymorph to another prior to melting. N o analogous transition was observed for the hexyl analogue  31b.  Figure 2.7: O R T E P Diagram o f the Assymetric Unit C e l l o f a Single Crystal o f Compound 31a  36  37  Figure 2.10: V i e w A l o n g the c A x i s for a Single Crystal o f 31a  R  R  R  R  R  R  Figure 2.11: Possible Quinoidal Tautomers for 2,3-dialkyl-5,6-dihydroxybenzene-l,4-dialdehydes  38  2.5 - Conclusions and Recommendations Three different routes to the highly substituted, target 2,3-dialkyl-5,6-dihydroxybenzene1,4-dialdehydes (31a and 31b) were explored. These routes can broadly be classified as the lithiation/formylation route, the cyanation/reduction route and the direct formylation route. Yields for these different routes were on the order o f 10-15%, 20-25%) and 25-30% from known compounds, respectively. In terms o f ease o f synthesis, yield, and minimization o f the steps required, the direct formylation route was found to be preferable. Although all three methods were successful for relatively short alkyl chains (butyl and hexyl), the preparation o f longer chain analogues was hampered at an early stage by difficulties in purification and functionalization by the methods employed (namely Kumada coupling followed by electrophilic bromination). A recently reported synthesis o f the di dodecyl analogue o f compounds 30a and 30b using sequential Friedel-Crafts acylations and reductions o f 1,2-dimethoxybenzene followed by deprotection (see Scheme 2.13)  33  may provide a viable alternative route to the longer chain  analogues o f compounds 31a and 31b, as well as to possible asymmetric dialdehydes, however compatability with'the direct formylation conditions remains to be seen.  O  Scheme 2.13: Possible Route to Longer Chain Analogues o f 30a and 30b  39  2.6 - Experimental Materials. o-Dichlorobenzene, 1-bromoalkanes, nickel (II) chloride hexahydrate, bromine, iodine, N-bromosuccinimide, iron (III) chloride, copper (I) bromide, copper (I) cyanide, 25 wt.% N a O M e in M e O H , anhydrous N,N-dimethylformamide, M-butyllithium (1.6M in hexanes), methyl formate, tetramethyleneethylenediamine ( T M E D A ) , ethyl chloroformate, lithium aluminum hydride, calcium hydride, diisobutyl aluminum hydride ( D I B A L - H , 1 .OM in hexanes), boron tribromide, trifluoroacetic acid, and hexamethylene tetraamine ( H M T A ) were obtained from A l d r i c h or Fisher Scientific. Diethyl ether and T H F were distilled from sodium/benzophenone ketyl under nitrogen. Methyl formate and D M F were distilled from calcium hydride under nitrogen. Hexanes was dried by passage through a column of activated alumina. Deuterated solvents were obtained from Cambridge Isotope Laboratories, Inc. Dichloro[l,3-bis(diphenylphosphino)propane] nickel (II) was prepared according to the literature method using l,3-bis(diphenylphosphino)propane obtained from Strem Chemical Company. 6  Equipment. A l l reactions were carried out under nitrogen unless otherwise noted. 300 M H z *H N M R spectra and 75.5 M H z C N M R spectra and 400 M H z *H N M R spectra and 100 M H z 1 3  1 3  C  N M R spectra were recorded on Bruker A V - 3 0 0 and A V - 4 0 0 spectrometers respectively. ' H N M R spectra were calibrated to residual protonated solvent while  1 3  C N M R spectra were  calibrated to deuterated solvent. U V - V i s spectra were obtained on a Varian Cary 5000 U V vis/near-IR spectrophotometer using a 1 cm quartz cuvette. IR spectra were obtained from K B r pellets or as neat or drop cast films on N a C l plates using a B o m e m MB-series spectrometer. Electron impact (EI) and electrospray ionization (ESI) mass spectra as well as elemental analyses were performed at the U B C Microanalytical Services Laboratory. Differential scanning calorimetry ( D S C ) thermograms were obtained using a Perkin Elmer Diamond D S C . A n  40  Olympus B X 4 1 polarizing optical microscope ( P O M ) equipped with a variable temperature hot stage was employed to look for liquid crystalline textures. Melting points were determined by D S C , P O M , or on a Fisher-Johns melting point apparatus. S C X R D data was collected on a Bruker X 8 A P E X diffractometer with graphite monochromated M o - K a radiation.  Synthesis of l,2-dibromo-4,5-dibutylbenzene (23a):" 5  9  To a I L 3-neck round bottom flask under nitrogen was added 22.10g (0.853 moles) magnesium turnings and ca. 300 m L dry diethyl ether. 1-Bromobutane (100 m L , 0.853 moles) was added by addition funnel over 2 h at a rate sufficient to maintain the solution at reflux. After the addition was complete, the solution was heated to reflux for one hour then chilled to 0 °C on ice. The chilled solution was transferred by syringe to 0 °C solution o f 30 m L 1,2-dichlorobenzene (0.284 moles) in 100 m L dry diethyl ether containing 231 mg Ni(dppp)Cl2 (0.428 mmol, 1.5 m o l % with respect to dichlorobenzene). The resulting green/black suspension was heated to reflux for 48 h after which it was cooled on ice and an additional 230 mg Ni(dppp)Cl2 added. Over the course of another 16h at reflux, large amounts o f grey/green salt precipitated; N M R at this time indicated only traces o f starting materials. The reaction was quenched by careful addition to 300 m L ice-cold 0 . 5 M H C I then extracted with diethyl ether (3x80 m L ) . The organic fractions were dried over MgS04, filtered and the solvent removed by rotary evaporation to afford 44.35g o f a thin yellow oil. Distillation at reduced pressure (b.p.=58-64 °C at -0.1 m m Hg) afforded 18.68g (98.2 mmol, 35% yield) o f 1,2-dibutylbenzene as a thin, colourless liquid. To 15.03g (79.0 mmol) o f the distilled 1,2-dibutylbenzene was added ca. 20 mg iodine followed by 8.3 m L Br2 (-160 mmol) i n the dark at 0 °C vented through a concentrated aqueous N a O H solution until the cessation o f H B r evolution (typically - 4 8 h). When no residual starting material was observed by N M R , the solution was diluted with 100 m L dichloromethane and  41  quenched by careful addition o f an aqueous 5% K O H / 5 % Na2S03 solution. The organic fraction was dried over MgS04, filtered, and the solvent removed by rotary evaporation.  Storage at  -11 °C over a week afforded large, pale yellow crystals. The crude solid was filtered and recrystallized from 2-propanol yielding 11.63g l,2-dibromo-4,5-dibutylbenzene as water-white crystals over two crops (33.4 mmol, 42% yield from 1,2-dibutylbenzene). The characterization of this compound conformed to that reported in reference 6. *H N M R (300 M H z , C D C 1 ) : 8 7.36 (s, 2 H , Ar-H), 2.51 (t, 4 H , A r - C / / ) , 1.3-1.6 (m, 8H), 0.93 3  2  (t, 6 H , terminal CH ). 3  Synthesis of l,2-dibromo-4,5-dihexylbenzene (23b): Conditions analogous to those for the preparation o f l,2-dibromo-4,5-dibutylbenzene were employed. 1,2-Dihexylbenzene was obtained as a thin, colourless o i l (b.p. ~ 135-145 °C at -0.1 m m H g , 50% yield). Bromination afforded l,2-dibromo-4,5-dihexylbenzene as a low melting solid (m.p. = 18-22 °C) after four rounds of recrystallization from 2-propanol (30% yield from 1,2-dihexylbenzene). The characterization o f this compound conformed to that reported i n reference 7. !  H N M R (300 M H z , C D C 1 ) : 8 7.35 (s, 2 H , Ax-H), 2.50 (t, 4 H , Ar-C#2), 1.3-1.6 (m, 16H), 0.89 3  (t, 6 H , terminal CHj).  Synthesis of l,2-dimethoxy-4,5-dibutylbenzene (24a): To 3.042g (8.74 mmols) 1,2-dibromo-4,5-dibutylbenzene was added 100 m L o f 25 wt. % N a O M e i n M e O H , 3 drops o f ethyl acetate and 27 mg C u B r (0.19 mmols, 2 mol %). This produced a dark blue suspension which was kept at reflux overnight under nitrogen. The reaction was cooled, checked by N M R to ensure completion, and then poured quickly into 100 m L ice-cold water. The resulting pale blue suspension was extracted with 3x60 m L diethyl 42  ether. The organic layer was rinsed with 50 m L dilute (-0.1 M ) N H O H ( ) then 2x50 m L water, 4  aq  dried over M g S 0 4 and filtered. The solvent was removed in vacuo affording 1.948g (7.78 mmol, 89% yield) l,2-dimethoxy-4,5-dibutylbenzene as a thin, colourless o i l . ' H N M R (400 M H z , CDC1 ): 5 6.62 (s, 2 H , Ai-H), 3.84 (s, 6 H , OCH ), 3  Ax-CH ),  3  2.53 (t, J=7.6Hz, 4 H ,  1.53 (m, 4 H , A r - C H C / / ) , 1.39 (m, 4H), 0.94 (t, J - 7 . 2 H z , 6 H , terminal CH );  2  2  2  1 3  3  N M R (100 M H z , CDCI3): 5 146.8 (Ar-OCK ), 3  C  132.6, 112.6, 55.9 ( A r - O C H ) , 33.9, 32.1, 22.8, 3  14.0; U V - V i s (CH2CI2): km,* (e) 284 n m (430 L-mof'-cm" ); IR (neat): v = 2957, 2930, 2860, 1  1609, 1598, 1578, 1495, 1460, 1394, 1260, 1200, 1051, 875, 750 cm" ; A n a l . C a l c ' d for 1  C, H260 : C , 76.75; H , 10.47; O, 12.78. Found: C , 76.59; H , 10.44. 6  2  Synthesis of l,2-dimethoxy-4,5-dihexylbenzene (24b): Conditions analogous to those for the preparation o f l,2-dimethoxy-4,5-dibutylbenzene were employed. l,2-Dimethoxy-4,5-dihexylbenzene was obtained as a thin, colourless oil (91% yield). ' H N M R (400 M H z , C D C 1 ) : 5 6.64 (s, 2 H , Ar-H), 3.84 (s, 6 H , OCH ), 3  3  A1-CH2), 1.3-1.6 (m, 16H), 0.89 (t, J=7.2 H z , 6 H , terminal CfY ); 3  1 3  2.52 (t, J=7.6Hz, 4 H ,  C N M R (100 M H z , CDC1 ): 3  8 146.8 0 4 r - O C H ) , 132.5, 112.6,55.9 ( A r - O C H ) , 33.9, 32.1,31.6, 29.8,22.8, 14.0 3  UV-Vis  (CH2CI2): l  3  (e) 282 nm (380 L-mof'-cm" ); IR (neat): u = 2956, 2928, 2856, 1610, 1  max  1519, 1465, 1266, 1224, 1115, 1036, 1006, 859, 742cm" ; A n a l . C a l c ' d for 1  C20H34O2:  C , 78.38;  H , 11.18; O, 10.44. Found: C , 78.03; H , 11.00.  Synthesis of l,4-dibromo-2,3-dibutyl-5,6-dimethoxybenzene (25a): To 1.948g (7.78 mmol) l,2-dimethoxy-4,5-dibutylbenzene was added 50 m L dichloromethane and - 1 0 m g F e C ^ and the resulting solution chilled to 0 °C on ice. To this solution -1 m L Br2 (-19 mmol) was added slowly by pipette and the mixture left to warm to room temperature with  stirring overnight. The resulting orange solution was quenched by addition o f 40 m L o f an aqueous 5% N a O H / 5 % Na2S03 solution followed by extraction with 3x40 m L dichloromethane. The organic fraction was dried over M g S 0 4 , filtered, and the solvent removed in vacuo. The resulting crude, pale yellow o i l was separated chromatographically on silica using 3:1 hexanes:DCM as the eluent affording 2.361g (5.78 mmol, 74% yield) l,4-dibromo-2,3-dibutyl5,6-dimethoxybenzene as a viscous, pale yellow o i l (>95% pure by N M R integration). *H N M R (400 M H z , C D C 1 ) : 5 3.86 (s, 6 H , OCH ), 2.78 (t, J=7.9Hz, 4 H , Ar-CH ), 3  3  2  1.3-1.6 (m,  8H), 0.97 (t, .7=7.0 H z , 6 H , terminal CH ); C N M R (100 M H z , C D C 1 ) : 5 149.0, 137.5, 120.1, 1 3  3  3  60.6, 33.6, 31.8, 23.1, 13.8; H R - E I - M S : m/z = 408.01226 (calc), 408.01208 (found); U V - V i s (CH2CI2): W  (e) 290 n m (540 L - m o l ' W ) ; I R (neat): v = 2956, 2928, 2872, 2860, 1596, 1  1556,,1527, 1458, 1405, 1384, 1298, 1265, 1166, 1087, 1029, 976, 764, 740 cm" . 1  Synthesis of l,4-dibromo-2,3-dibutyl-5,6-dimethoxybenzene (25b): Conditions analogous to those for the preparation o f l,4-dibromo-2,3-dimethoxy-5,6dibutylbenzene were employed. l,4-dibromo-2,3-dimethoxy-5,6-dihexylbenzene was obtained as a viscous, pale yellow oil (73% yield and >95% pure by N M R integration after chromatography). ' H N M R (400 M H z , CDCI3): 5 3.86 (s, 6 H , OCH ), 2.77 (t, J=7.8Hz, 4 H , Ar-CfY ), 1.3-1.6 (m, 3  16H), 0.90 (t, J=7.2 H z , 6 H , terminal C / / ) ; 3  1 3  2  C N M R (100 M H z , CDC1 ): 5 149.0, 137.5, 120.1, 3  60.6, 33.9, 31.5, 29.7, 29.6, 22.6, 14.1; H R - E I - M S : m/z = 464.07486 (calc), 464.07501 (found); U V - V i s (CH2CI2):  l x ma  (e) 291 nm (480 L-mof'-cm" ); IR (neat): u = 2957, 2928, 2857, 1528, 1  1458, 1405, 1384, 1301, 1214, 1164, 1091, 1033, 974, 766 cm" . 1  44  Synthesis of 2,3-dibutyl-5,6-dimethoxybenzene-l,4-dialdehyde (26a) via dibromo 25a: Although several sets o f conditions were employed, an optimized reaction was as follows: to an oven-dried 100 m L Schlenk was added 0.707 g (1.73 mmol) l,4-dibromo-2,3-dimethoxy-5,6r  dibutylbenzene which was dried under vacuum for ~1 h. To this was added - 3 0 m L dry, freshly distilled diethyl ether and the solution cooled to -78 °C with an acetone/dry ice bath under nitrogen. /7-BuLi i n hexanes (4.3mL, 1.6M, -6.9 mmols, - 2 equiv.) was slowly added resulting in a bright yellow/orange solution. The solution was stirred at -78 °C for 5 min and quenched by addition o f 1.3 m L dry, distilled D M F (-17 mmol, - 5 equiv.). The resulting solution was allowed to warm to room temperature under nitrogen over 1-2 h and the resulting cloudy, yellow solution treated with 80 m L distilled water followed by extraction with 3x30 m L diethyl ether. The organic fraction was dried over MgSCM, filtered, and the solvent removed in vacuo affording a yellow/orange o i l consisting of regenerated l,2-dimethoxy-4,5-dibutylbenzene, mono- and diformylated compounds. Chromatography on silica first with toluene as eluent then again with 1:3 hexanes:DCM afforded the dialdehyde as a thin yellow o i l (0.176g, 0.57 mmol, 33% yield, >95% pure by N M R integration). ' H N M R (400 M H z , C D C 1 ) : 5 10:52 (s, 2 H , aldehyde CH), 3.93 (s, 6 H , O M e ) , 2.80 (t, J=7.6 3  H z , 4 H , Ax-CH ), 1.3-1.6 (m, 8H), 0.89 (t, J=7.3 H z , 6 H , terminal CH ); 2  3  1 3  C N M R (100 M H z ,  CDC1 ): 8 192.8, 153.8, 139.1, 132.9, 62.0,31.7, 29.7,22.6, 14.0; IR (neat): u = 2956, 2934, 3  2872,2866, 2752, 1708 (vs, aldehyde C = 0 ) , 1596, 1565, 1442, 1411, 1373, 1262, 1158, 1128, 1042, 862, 794, 744, 667 cm" ; U V - V i s ( C H C 1 ) : 1  2  2  l  (s)'298 nm (5.6 x 10 L - m o l " W ) . 3  max  Synthesis of 2,3-dihexyl-5,6-dimethoxybenzene-l,4-dialdehyde (26b) via dibromo 25b: Conditions analogous to those for the preparation of 2,3-dibutyl-5,6-dimethoxybenzene-l,4dialdehyde were employed. 2,3-Dihexyl-5,6-dimethoxybenzene-l,4-dialdehyde was obtained as a thin yellow o i l (31% yield and >95% pure by N M R integration after chromatography). 45  ' H N M R (400 M H z , CDCI3): 5 10.52 (s, 2 H , aldehyde CH), 3.93 (s, 6 H , O M e ) , 2.81 (t, J=7.6 Hz, 4 H , Ar-Cr7 ), 1.3-1.6 (m, 16H), 0.90 (t, J=7.3 H z , 6 H , terminal CH ); 2  3  1 3  C N M R (100 M H z ,  CDCI3): 5 192.9, 153.9, 139.2, 133.1,62.0,31.7,31.5,29.8,27.9, 22.6, 14.0; IR (neat): v = 2956, 2933, 2872, 2861, 2754, 1706 (vs, aldehyde C = 0 ) , 1598, 1566, 1443, 1412, 1375, 1260, 1156, 1128, 1042, 895, 862, 794, 738, 668 c m ' ; U V - V i s ( C H C 1 ) : l 1  2  2  00 302 nm (5.4 x 10 L-mol" 3  max  '•cm" ). 1  Synthesis of 2,3-dihexyl-5,6-dihydroxybenzene-l,4-dialdehyde (31b) via dibromo 25b: To 0.186g (0.556 mmol) 2,3-dihexyl-5,6-dimethoxybenzene-l,4-dialdehyde was added 30 m L dicholoromethane and the resulting solution cooled to 0 °C under nitrogen. To this solution was added 0.5 m L (~5.3 m m o l , ~5 equiv.) boron tribromide by syringe. The solution was stirred under nitrogen overnight warming to room temperature then quenched by addition o f 50 m L distilled water followed by three drops o f concentrated H C I . The aqueous layer was extracted with 2x30 m L D C M and the organic fractions dried over M g S 0 4 , filtered, and the solvent removed in vacuo ultimately affording 2,3-dihexyl-5,6-dihydroxybenzene-l,4-dialdehyde as a waxy orange solid (0.139g, 0.416 mmol, 75% yield; see 31b v i a 30b for complete characterization). ' H N M R (400 M H z , CDCI3): 5 11.96 (s, 2 H , Ar-OH), 10.34 (s, 2 H , Ar-CrYO), 2.85 (t, 4 H , A r CH ), 1.50 (m, 4H), 1.30-1.35 (m, 12H), 0.98 (t, 6 H , terminal CH ). 2  3  Synthesis of diethyl 2,3-dibutyl-5,6-dimethoxybenzene-l,4-dioate (27a): To an oven dried 250 m L Schlenk was added 1.958g (4.80 mmol) l,4-dibromo-2,3-dimethoxy5,6-dibutylbenzene which was dried under vacuum on for ~1 h. T o this was added - 5 0 m L dry, freshly distilled diethyl ether (~50 m L ) was added and the solution cooled to -78 °C with an acetone/dry ice bath while flushing the reaction with nitrogen. To this solution was slowly 46  added 12 mL of 1.6 Mrc-BuLiin hexanes (-19.2 mmols, -2 equiv.) resulting in a bright yellow solution. The.solution was stirred at -78 °C for 5 minutes and quenched by addition of 4.6 mL ethyl chloroformate (-48 mmol, -5 equiv.). The resulting solution was warmed to room temperature under nitrogen over the course of 1 h and the resulting cloudy, yellow solution treated with 100 mL distilled water followed by extraction with 3x50 mL diethyl ether. The organic fraction was dried over MgSCv, filtered, and the solvent removed in vacuo affording a yellow/orange oil consisting of a mixture of mono- and diester. Chromatography on silica with 3:1 hexanes:DCM afforded the diester as a thin, pale yellow oil (1.195g, 3.02 mmol, 63% yield, >95% pure by NMR integration). 'H NMR (400 MHz, CDC1): 8 4.39 (q, 4H, OC/7CH), 3.85 (s, 6H, Ar-OC/7), 2.47 (t, 4H, Ar3  2  3  3  CH ), 1.74-1.82 (m, 4H), 1.38 (t, 6H, OCH C// ), 1.24-1.30 (m, 4H), 0.89 (t, 6H, terminal CH ); 2  2  3  3  EI-MS: m/z = 394 (M , 35%), 348 (M-EtOH, 100%). +  +  Synthesis of diethyl 2,3-dihexyl-5,6-dimethoxybenzene-l,4-dioate (27b):  Conditions analogous to those for the preparation of diethyl 2,3-dibutyl-5,6-dimethoxybenzene1,4-dioate were employed. Diethyl 2,3-dihexyl-5,6-dimethoxybenzene-l,4-dioate was obtained as a thin, pale yellow oil (55% yield and >95% pure by NMR integration after chromatography). 'H NMR (300 MHz, CDC1): 8 4.39 (q, 4H, OC// CH ), 3.84 (s, 6H, Ar-OC// ), 2.47 (t, 4H, Ar3  2  3  3  CH ), 1.74-1.82 (m, 4H), 1.38 (t, 6H, OCHC/7), 1.25-1.35 (m, 12H), 0.89 (t, 6H, terminal 2  2  3  CH ); CNMR(100 MHz, CDC1): 8 167.7, 153.1, 134.1, 122.2, 62.8,61.2,39.0, 34.8,31.4, 13  3  3  25.4, 23.0, 14.2, 14.0; EI-MS: m/z = 450 (M , 20%), 404 (M -EtOH, 100%); IR (neat): v = 2958, +  +  2932,2872, 2861, 1759 (sh), 1736 (vs, ester C=0), 1596, 1560, 1459, 1413, 1368, 1265, 1154, 1099, 1044, 895, 864, 794, 738 cm". 1  47  Synthesis of l,2-dibutyl-3,6-bis(hydroxymethyl)-4,5-dimethoxybenzene (28): To an oven dried 100 m L Schlenk was added 0.686g (1.52 mmol) diethyl 2,3-dihexyl-5,6dimethoxybenzene-l,4-dioate which was dried under vacuum for - 3 0 min. To this was added - 5 0 m L dry hexanes and the solution cooled to -78 °C with an acetone/dry ice bath under nitrogen. A 1.0 M D I B A L - H solution in hexanes (10 m L , -19.2 mmols, - 6 equiv.) was slowly added by syringe resulting in a clear, pale yellow solution. The solution was stirred at -78 °C for 5 m i n then warmed to room temperature. The resulting clear and colourless solution was quenched by slow addition o f 30 m L 10% K O H ( ) , then extracted with 3x30 m L diethyl ether. aq  The organic fraction was dried over M g S 0 4 , filtered, and the solvent removed in vacuo affording a waxy ivory-coloured solid. Recrystallization from acetone afforded a white solid (0.094g, 0.26 mmol, 17% yield, >95% pure by N M R integration). ' H N M R (400 M H z , C D C 1 ) : 5 4.69 (d, J=6.3 H z , 4 H , A r C / / O H ) , 3.89 (s, 6 H , A r - O C t f ) , 2.63 3  2  3  (t, 4 H , A r - C 7 / ) , 2.23 (t, J=6.3 H z , 2 H , OH), 1.42-1.48 (m, 4H),T.26-1.30 (m, 4H), 0.96 (t, 6 H , 2  terminal CH );  1 3  3  C N M R (100 M H z , CDC1 ): 8 149.6, 136.1, 133.0, 60.8, 58.0, 34.4, 28.9, 23.3, 3  13.9; E I - M S : m/z = 310 ( M , 20%), 292 ( M - H 0 , 100%); IR (thin film): u = 3381 (br, O H ) , +  +  2  3310 (sh), 2296, 2931, 2871, 2859, 1458, 1418, 1338, 1310, 1263, 1095, 999, 745 cm" ; mp = 1  78-80 °C (dec).  Synthesis of 2,3-dibutyl-5,6-dimethoxybenzene-l,4-dinitrile (29a): Into a 50 m L round bottom flask was weighed 1.013g (2.48 mmol) l,4-dibromo-2,3-dimethoxy5,6-dibutylbenzene. This was dissolved in 20 m L dry D M F followed by addition o f 0.672g C u C N (7.50 mmol, - 3 equiv.). The resulting orange, turbid solution was heated to reflux for 3 h then poured hot into a solution o f 2.15g F e C l in 75 m L water and 20 m L cone. H C I . After 3  stirring for 30 min, this solution was then extracted with toluene (3x40 m L ) ; the organic extracts were rinsed with 2x20 m L water then dried over M g S 0 4 , filtered, and the solvent removed in 48  vacuo. The resulting viscous green oil was flushed through silica with D C M ultimately affording 0.715g o f 2,3-dibutyl-5,6-dimethoxybenzene-l,4-dinitrile as a viscous, pungent orange oil (2.38 mmol, 96% yield, >90% pure by N M R integration). ' H N M R (400 M H z , C D C 1 ) : 5 4.01 (s, 6 H , O M e ) , 2.77 (t, 4 H , A r - C i / ) , 1.46-1.50 (m, 8H), 0.97 3  2  (t, 6 H , terminal CH ); C N M R ( 1 0 0 M H z , CDC1 ): 5 152.8, 141.1, 128.9, 114.2,61.8,32.9, 1 3  3  3  29.4, 22.4, 13.9; H R - E I - M S : m/z = 300.18378 (calc), 300.18426 (found); I R (neat): u = 2957, 2932,2875,2859, 2228, 1575, 1555, 1467, 1416, 1378, 1321, 1257, 1189, 1108, 1092, 1069, 1032, 1012, 967, 863, 794, 746, 593 c m ' . 1  Synthesis of 2,3-dihexyl-5,6-dimethoxybenzene-l,4-dinitrile (29b): Conditions analogous to those for the preparation o f 2,3-dibutyl-5,6-dimethoxybenzene-l,4dinitrile were employed. 2,3-Dihexyl-5,6-dimethoxybenzene-l,4-dinitrile was obtained as a viscous, pungent orange o i l (89% yield, >90% pure by N M R integration). ' H N M R (400 M H z , CDCI3): 5 4.02 (s, 6 H , O M e ) , 2.77 (t, 4 H , A r - C i / ) , 1.42-1.48 (m, 16H), 2  0.97 (t, 6 H , terminal CH ); C N M R ( 1 0 0 M H z , CDC1 ): 5 152.8, 141.3, 128.9, 114.2,61.8, 1 3  3  3  33.0, 31.3, 30.9, 29.4, 22.4, 13.9; H R - E I - M S : m/z = 356.24638 (calc), 356.24710 (found); I R (neat): u = 2986, 2928,2860, 2228, 1608, 1576, 1556, 1467, 1416, 1323, 1266, 1101, 1070, 1 0 4 0 , 9 7 1 , 7 9 8 , 7 3 0 , 6 6 9 cm" . 1  Synthesis of 2,3-dibutyl-5,6-dimethoxybenzene-l,4-dialdehyde (26a) via nitrile 29a: To an oven-dried 100 m L Schlenk flask was added 0.409g (1.36 mmol) 2,3-dibutyl-5,6dimethoxybenzene-l,4-dinitrile. To this was added - 2 0 m L dry, distilled diethyl ether by syringe under N . The resulting yellow solution was cooled to -78 °C i n an acetone/dry ice bath; 2  once cooled, 3.4 m L 1.0 M D I B A L - H i n hexanes (3.4 mmol, - 1 . 2 equiv.) was added slowly. The solution was then warmed to room temperature with stirring. After stirring at room 49  temperature for - 3 0 min, 40 m L 10% H S04( ) was carefully added and the solution stirred at 2  aq  ambient temperature for another 30 min. This solution was diluted with 20 m L water and extracted with diethyl ether (3x25 m L ) . The organic layer was dried over M g S 0 , filtered and 4  the solvent removed in vacuo. The resulting yellow/orange o i l was chromatographed on silica with toluene as the eluent affording 0.2lOg (0.69 mmol, 50% yield) 2,3-dibutyl-5,6dimethoxybenzene-l,4-dialdehyde as a thin, pale yellow o i l (>95% pure by N M R integration). ' H N M R (400 M H z , CDC1 ): 5 10.52 (s, 2 H , CHO), 3.93 (s, 6 H , O C / / ) , 2.81 (t, 4 H , A r - C / / ) , 3  3  2  1.45 (m, 8H), 0.97 (t, 6 H , terminal CH ). 2  Synthesis of 2,3-dibutyl-5,6-dihydroxybenzene-l,4-dialdehyde (31a) via catechol 30a: To 2.332g (9.31 mmol) l,2-dimethoxy-4,5-dibutylbenzene was added 100 m L dicholoromethane and the resulting solution chilled to 0 °C under nitrogen. To this solution was added 3.8 m L (-40 mmol, - 2 equiv.) boron tribromide by syringe. The solution was stirred under nitrogen overnight warming to room temperature then quenched by addition o f 150 m L distilled water followed by three drops o f concentrated H C I . The aqueous layer was extracted with 3x50 m L D C M and the organic fractions dried over Na S04, filtered, and the solvent removed in vacuo 2  affording l,2-dihydroxy-4,5-dibutylbenzene as a tan solid; this material was found to slowly degrade on standing in air and was not isolated ( H N M R (400 M H z , C D C 1 ) : 5 6.65 (s, 2 H , A r !  3  H), 5.27 (br s, 2 H , ArOH), 2.46 (t, 4 H , A r - C / / ) , 1.48-1.52 (m, 4H), 1.25-1.35 (m, 4H), 0.88 (t, 2  6 H , terminal CH3)). The solid was dissolved in 75 m L trifluoroacetic acid under nitrogen. To the resulting pink solution was added 5.430g H M T A (38.7 mmol, - 2 equiv. relative to 1,2dimethoxy-4,5-dibutylbenzene), and the solution heated to reflux for 3 h under nitrogen. O n heating, the solution changed from pink to orange to dark red. After 3 h at reflux the solution was cooled to room temperature and 100 m L - 4 M HCl( ) was added. This solution was then aq  held at reflux overnight under nitrogen. The resulting orange/red solution was cooled to room 50  temperature, transferred to a separatory funnel and diluted with 100 m L distilled water. A suspension formed and was extracted with D C M (4x60 m L ) . The pooled organic extracts were rinsed with 60 m L distilled water, 80 m L 1% NaHC03( ), and another 60 m L distilled water aq  then dried over N a S 0 4 , filtered, and the solvent removed by rotary evaporation. The crude 2  material was obtained as a viscous orange/red tar and was purified by chromatography on silica using 0.5% acetone i n D C M as the eluent. The desired product eluted first, with subsequent fractions containing a sizeable proportion o f the product along with impurities. Later fractions were retained and resubjected to the column conditions. The product 2,3-dibutyl-5,6dihydroxybenzene-l,4-dialdehyde was obtained as a waxy, bright orange solid (0.899g, 3.23 mmol, 35% yield after three column passes). Crystals suitable for x-ray diffraction were grown by slow evaporation o f a hexanes solution. ' H N M R (400 M H z , CDC1 ): 5 11.95 (s, 2 H , Ai-OH), 10.35 (s, 2 H , A r - C / / 0 ) , 2.86 (t, 4 H , A r 3  CH ), 1.44-1.56 (m, 8 H , A r - C H C / / C i / ) , 0.98 (t, 6 H , terminal CH ); 2  2  2  2  3  1 3  C N M R (100 M H z ,  CDCI3): 5 196.60 ( A r - C H O ) , 151.17 (Ar-OU), 132.4, 120.9, 35.5, 26.2, 22.9, 13.8; U V - V i s (CH C1 ): 2  2  l  (s) 304 nm (1.5 x 10 L-mof'-cm" ), 441 nm (3.5 x 10 L-mof'-cm" ); IR (thin 4  max  1  3  1  film): i) = 3388 (br, O H ) , 3085 (br, O H ) , 2959, 2929, 1646 (vs, C = 0 ) , 1554, 1439, 1397, 1294, 1247, 1195, 929, 758 c m T ; A n a l . C a l c ' d for C i H 0 : C , 69.04; H , 7.97; O, 22.99. Found: C , 6  2 2  4  69.07; H , 7.99. M . p . = 54 °C.  51  Synthesis of 2,3-dihexyl-5,6-dihydroxybenzene-l,4-dialdehyde (31b) via catechol 30b: Conditions analogous to those for the preparation o f 2,3-dibutyl-5,6-dihydroxybenzene-l,4dialdehyde were employed. 2,3-dihexyl-5,6-dihydroxybenzene-l,4-dialdehyde was obtained as a waxy, bright orange solid (31% yield after 3 column passes). ' H N M R (400 M H z , CDCI3): 5 5 11.96 (s, 2 H , A r - O / f ) , 10.34 (s, 2 H , A r - C M ) ) , 2.85 (t, 4 H , A r CH ), 1.50 (m, 4 H ) , 1.30 (m, 12H), 0.98 (t, 6 H , terminal CH ); 2  1 3  C N M R (100 M H z , CDC1 ): 8 3  3  196.6 ( A r - C H O ) , 151.2 (Ar-Orl), 132.4, 120.9, 35.5, 32.6, 29.6, 26.2, 22.9, 13.8; U V - V i s (CH2CI2): ^  (e) 299 nm (1.4 x 10 L-mor'-cm-'), 436 nm (3.1 x 10 L - m o r ' - c m ) ; 4  m a x  3  -1  IR (neat): v = 3387 (br, O H ) , 3085 (br, O H ) , 2956, 2856, 1645 (vs, C = 0 ) , 1555, 1440, 1397, 1296, 1236, 1117, 1094, 936, 764 cm" ; A n a l . C a l c ' d for C o H o 0 : C , 71.82; H , 9.04; O, 19.14. 1  2  3  4  Found: C , 72.02; H , 9.11. M . p . = 41 °C.  52  Chapter 3: [3+3] Macrocycles 3.1 - Background The formation o f Schiff bases is the relatively straightforward condensation o f an aldehyde and a primary or secondary amine (vide supra). Preparation o f macrocyclic Schiff base compounds requires difunctional amines and aldehydes; condensation o f these types of precursors have yielded a diverse array of macrocyclic products ranging from those of the Robson and M c K e e families, expanded porphyrins, as well as much larger cycles. Although so-called [2+2] macrocycles are fairly common in the literature (e.g. the aforementioned Robson and M c K e e cycles), those derived from the condensation o f three equivalents o f dialdehyde and diamine, namely [3+3] macrocycles are rarer. While reports exist i n which condensation o f aliphatic but structurally constrained stereogenic diamines such as trans-\,2diaminocyclohexane or l,2-diamino-l,2-diphenylethane derivatives with aromatic dialdehydes yields [3+3] species (dubbed trianglimines), ' the stability o f these species appears to be highly 4 5  dependant not only on the geometry of the functional groups but also on the presence o f functionality that enables strong intramolecular hydrogen bonding within the core.  6  Even less well represented i n the literature are [3+3] Schiff base macrocycles in which conjugation exists around the periphery o f the core. The earliest reported compounds o f this type, derived from the condensation o f 3,6-diformylcatechol (7) and 1,2-phenylenediamine (8a; see Scheme 1.3), were found to be quite insoluble in common organic solvents.  7  Subsequent  work i n which 4,5-diamino-l,2-dialkoxybenzenes were used in the cyclocondensation afforded soluble [3+3] macrocycles with a number o f interesting properties including small cation induced aggregation as well as the templation o f heptametallic zinc-oxo clusters.  These  macrocycles have also been found to be versatile ligands for polymetallation; the formation o f 53  heptanuclear manganese complexes as well as trimetallated nickel, copper, and cobalt species have recently been reported.  10  In addition to improving the solubility o f these shape-persistent, conjugated [3+3] macrocycles, the appending o f six alkoxy substituents was undertaken in an effort to explore the possibility that these materials might display liquid crystallinity. Although none was observed for any o f the resulting macrocycles nor for the metallated analogues,  11  the intriguing possibility  that the sort o f tubular arrangement proposed for the cation-induced aggregates believed to exist in solution might be displayed in the bulk materials by the formation o f tubular, columnar discotic mesophases prompted further investigation. Indeed, the possibility that by appending a larger number o f substituents to the periphery o f these relatively small macrocyclic cores that these materials would display discotic liquid crystalline behaviour was the principal rationale for the work undertaken i n this project.  This chapter w i l l describe the synthesis and characterization o f a series o f highly substituted [3+3] Schiff base macrocycles (see Figure 3.1) as well as certain smaller [1+2] condensation products that were isolable and are presumed intermediates in the cyclocondensation (see Figure 3.2). The crystal structure obtained for macrocycle 19a w i l l also be discussed.  54  H9C4  Hi3C  C4H9  -i  N  —*  >-N  ° \U/ 6  Hi C 3  19a R = 19b R = 19c R = 19d R = 19eR = 19f R =  H OMe OC H OC H OC H OC H 6  2 9  1 6  3 3  1 8  >=<  OH  0H  20a 20b 20c 20d 20e  1  N ^>  HO Ho  \=N  6  1 3  1 4  HO  R  OH  V Hi3  1 3  J M !  R  R  CsH  6  ^fV"  N=/  R R R R R  = = = = =  C6Hi3  C H 6  H OMe OC H OC H OC H 6  1 3  1 3  1 6  3 3  1 8  3 7  3 7  Figure 3.1: Structures of the [3+3] Macrocycles Prepared in this Work  HgC  4  OH NH  P4H9 R OH "  N  ^ J—? /  NH  2  32aR = O C H 32b R = O C H 6  1 2  R  2  1 3 2 5  Figure 3.2: Structures of Some of the [1+2] Fragments Obtained  55  3.2 - Discussion 3.2.1: Synthetic Aspects With the appropriate "starting materials, namely aromatic diamines and aromatic dialdehydes, the construction o f [3+3] macrocycles  19a-f and 20a-e proved to be quite facile.  Combination o f stoichiometric amounts o f reagents in a suitable solvent system was sufficient to generate the target macrocycles in yields ranging from 25% to 65% however certain details o f these systems deserve mention. Macrocycles derived from phenylenediamine (19a and 20a) would readily precipitate from solution on cooling after several hours at reflux, whereas those bearing six relatively short alkoxy chains  (19b-c and 20b-c) were found to be extremely soluble  in the reaction medium (namely a 2:1 mixture o f acetonitrile and choloroform) even after cooling or reduction o f the solvent volume. This enhanced solubility was much more pronounced for macrocycles bearing longer alkoxy chains; these compounds were found not only to be soluble in very small volumes o f chlorinated solvents but also, quite remarkably, i n alkanes such as petroleum ether and hexanes as well as aromatic solvents such as toluene. This made purification o f these species by precipitation virtually impossible; despite being insoluble in acetonitrile, addition o f concentrated solutions o f macrocycle in chloroform or D C M to acetonitrile (or conversely, addition of acetonitrile to concentrated solutions o f macrocycle) would not induce precipitation. Attempts at varying the solvent conditions o f the reaction were attempted, namely increasing the proportion o f acetonitrile relative to chloroform, however use of 5:1 and 10:1 ratios seemed simply to induce precipitation o f oligomers and fragments during the course o f the reaction. This is in marked contrast to the related macrocycles without aikyl substitution on the dialdehyde moieties (9a-m), which could all be isolated and purified by precipitation.  Indeed, it would seem that incorporation o f aikyl substituents on the dialdehydes  in addition to alkoxy substituents on the diamines produces macrocycles that are the most  56  soluble species present in the reaction medium, the smaller fragments being somewhat less soluble. This poses a challenge for the purification o f these macrocycles, the strategy employed being to remove the insoluble materials (typically fragments and oligomers as determined by N M R and M A L D I ) by filtration followed by removal o f the solvent. Although this was adequate to obtain the macrocycles in acceptable purities (ca. 85-95% pure by N M R integration), analytically pure samples o f these materials are likely unattainable by this method. Further attempts at purification by conventional chromatography were unsuccessful given the apparent lability o f the imine bonds, the end result being decomposition on the column yielding only fragments on elution. This tendency to decompose on silica has been observed by other researchers for similar [3+3] Schiff base macrocycles necessitating reduction o f the imines to amines with sodium borohydride for successful chromatographic resolution.  4  Another interesting feature in the preparation o f these compounds was the apparent need to include a catalytic amount o f piperidine in the reaction mixture to generate macrocycles in a practical length o f time. In the absence o f piperidine, refluxing for up to three days would afford predominantly [1+2] condensation products (e.g. 32a-b), with only traces o f macrocycle evident by N M R . Previous work on the related macrocycles produced similar [1+2] condensation products by careful control o f the stoichiometry.  12  It is known that the nucleophilicity o f the  second amine in aromatic diamines (such as 1,2-phenylenediamine) dramatically drops after the formation o f a first i m i n e . ' 13  14  This is supported by the observation that the isolable [1+2]  condensation products prepared in the absence o f piperidine consist o f diamine-capped dialdehydes. Although the exact mechanism of the catalysis is unknown, it seems reasonable to assume that the intermediacy o f a relatively more reactive intermediate derived from the dialdehyde and piperidine is significant. In particular, it seems likely that an iminium from the  57  condensation these two species would be quite labile  15  and consequently more reactive to  subsequent displacement by an aromatic amine (see Scheme 3.1).  Scheme 3.1: Possible Mechanism for Piperidine-Catalyzed Imine Formation via an Iminium Intermediate  3.2.2: Characterization Standard techniques were employed for the characterization o f the [3+3] macrocycles and [1+2] fragments prepared in this work including N M R , IR and U V - V i s spectroscopies as well as M A L D I - T O F mass spectrometry. O n the whole, proton and carbon N M R for the various species conformed to what was anticipated. The ' H and  1 3  C N M R spectra for macrocycle 19a  are presented in Figures 3.3 and 3.4, respectively, along with the ' H N M R spectrum o f macrocycle 20e in Figure 3.5. The appearance o f the spectra suggest an overall Dih symmetry for these species in solution due to fluxionality and signal averaging on the N M R timescale; this symmetry does not exist in the solid state, however, with crystallographic evidence indicating much lower symmetry (vide infra). This apparent high symmetry in solution is consistent with previously reported related macrocycles.  12  The (averaged) phenolic resonance for these  macrocycles tends to appear far downfield (ca. 14.0-14.7 ppm), consistent with the associated protons being strongly hydrogen-bonded within the macrocyclic core. The sharpness of these resonances suggests that the protons are not undergoing significant exchange with any water  58  present in the deuterated solvent. The chemical shifts for these phenolic protons seem to vary not only between different macrocycles but also from sample to sample o f the same compound, presumably owing to different degrees o f hydration (i.e. how wet the N M R solvent is). The  1 3  C  N M R spectra present the number o f signals expected for systems o f this (apparent) symmetry, with the imine carbon resonances appearing in the range o f ca. 160-165 ppm. N o resonances around 195 ppm attributable to residual aldehyde were observed (see Figure 2.5 for example). For the macrocycles with long alkoxy chains (19d-f and 20d-e), not all o f the carbon signals between about 20 and 35 ppm could be resolved, however they all displayed the requisite number o f signals in the aromatic and imine regions.  6.03 U 15  14  6.49 13  12  11  12.19 1=1  24.56 18.00 t=J U  10  Figure 3.3: 400 M H z ' H N M R Spectrum o f Macrocycle 19a  59  Chloroform-d  190  180 • I"  'I  i' 170  i" P i  160  150  140  130  120  110  100  90 ppm  80  70  60  50  40  30  20  10  Figure 3.4: 100 MHz C NMR Spectrum of Macrocycle 19a 13  6.00 U 16  15  14  13  12  5.60 U  12.25  12.41  11  Figure 3.5: 400 MHz 'H NMR Spectrum of Macrocycle 20e 60  Infrared spectra for the macrocycles (see Figures 3.6 and 3.7) were also consistent with the absence o f residual aldehyde. The carbonyl bands observed for the 2,3-dialkyl-5,6dihydroxybenzene-l,4-dialdehydes at -1650 cm" were noticeably absent, being replaced with 1  C = N stretching bands o f low to medium intensity ranging between 1605 and 1620 cm" . 1  Although seemingly quite low, these bands fall within the range o f those previously reported for aromatic Schiff bases.  16  N o bands attributable to residual diamine were observed.  Wavenumber (cm-1)  Figure 3.6: IR Spectrum of Macrocycle 19a  s  Wavenumber (cm-1)  Figure 3.7: IR Spectrum o f Macrocycle 20e 61  The macrocycles were also characterized by mass spectrometry, specifically by matrix assisted laser desorption/ionization time-of-flight ( M A L D I - T O F ) mass spectrometry. Although somewhat limited i n terms o f resolution, M A L D I is ideal for the characterization o f these relatively fragile macrocycles for which other methods o f ionization result in extensive fragmentation.  11  The correct molecular weights ( M + l ) were observed for all the synthesized  macrocycles (see Figures 3.8 and 3.9); the mass spectra typically also displayed peaks corresponding to the macrocycles plus a sodium ion (M+23 a.m.u.) as well as macrocycle plus a sodium ion plus water (M+41 a.m.u.). Occasionally, multiply hydrated species were also observed. The affinity o f these macrocycles for sodium ions has been previously reported, but 8  the appearance o f multiple hydrates is o f some interest. Although often shown to crystallize with at least one water molecule present, the observation o f water i n the mass spectra o f these types 7  of macrocycles would seem to suggest that the cores remain hydrated even under the high vacuum conditions o f a M A L D I experiment (ca.-10" torr). 7  1060  1110  1160  m/z  Figure 3.8: M A L D I - T O F Mass Spectrum o f I9a 62  SM  U  SM  L Figure 3.9: M A L D I - T O F Mass Spectrum o f 20e  The macrocycles were also characterized by U V - V i s spectroscopy (see Figure 3.10). Macrocycles 19a and 20a both exhibited a single broad absorption feature centered at about 370 nm with extinction coefficients o f 1.58xl0 M"'-cm' and 1.56xl0 M " •cm" respectively. The 5  1  5  1  hexaalkoxy substituted macrocycles (19b-f and 20b-e) were remarkable only in the similarity o f their absorption spectra; all were virtually superimposable and exhibited peak maxima  (Xmax)  in  the range o f 414-420 n m along with a smaller shouldering peak centered i n the range of 350-355 nm. The slight red shift observed seemed to correlate with the length o f the alkoxy groups, possibly indicating some degree o f aggregation even in very dilute solution (ca. 10" M ) , 5  however this is by no means definitive. N o significant differences in the absorption o f macrocycles derived from dibutyl- and dihexyl- substituted dialdehydes (31a and 31b) were observed.  63  1.2  Macrocycle 19a Macrocycle 19b Macrocycle 19f  300  400  500  600  700  800  Wavelength /nm  Figure 3.10: Normalized Absorption Spectra of Macrocycles 19a, 19b and 19f  Characterization of the [1+2] fragments was also conducted using NMR, IR and UV-Vis spectroscopies. The ' H N M R spectrum of the [1+2] compound 32a is presented in Figure 3.11. The spectrum is consistent with a C2 symmetric species and displays a single sharp phenolic V  resonance at 14.43 ppm, a single imine peak at 8.87 ppm and two aromatic peaks corresponding to the two chemically distinct protons present on the flanking diamines. Signals attributable to the amines are not immediately apparent, however two broad resonances on either side of the multiplet at 3.95 ppm (OCH ) can likely be assigned to them. The IR spectrum of the [1+2] 2  compound 32b is presented in Figure 3.12. Noticeably absent is the carbonyl band of the starting dialdehyde while the relatively sharp band at 3373 cm" which can be assigned to an N-H 1  stretching mode. MALDI-TOF mass spectra of these compounds were also consistent, often  64  displaying strong peaks corresponding to (M+2H20+Na ) in addition to the parent ion peaks +  corresponding to ( M + l ) .  3.2.3: Thermal Properties of the Macrocycles  The primary motivation for the work undertaken was to generate a series of highly substituted [3+3] Schiff base macrocycles in hopes that they would display thermotropic liquid crystallinity. As such, the thermal properties of these materials were of significant interest. The target macrocycles were examined by differential scanning calorimetry (DSC) as well as by polarizing optical microscopy (POM) to ascertain whether or not they would, in fact, from mesophases. A typical temperature program consisted of holding the sample at -20 °C for 10 min followed by heating at 5 °C/min to 190 °C. The sample was held at 190 °C for 10 minutes then cooled back to -20 °C at 5 °C/min. The maximum temperature of 190 °C was chosen based on the observation that macrocycles 19b and 20b displayed broad, shallow exotherms above this temperature likely indicating decomposition (see Figure 3.13). Examination of these macrocycles by POM above -190 °C confirmed this, with samples changing from dark orange/red to brown and then black. Although sharp endotherms were observed for two of the macrocycles with long alkoxy chains (e.g. 19e at 111 °C and 19f at 123 °C, see Figure 3.14), for the remainder of the macrocycles no transitions were observed in the temperature range employed. In addition, for those compounds where endotherms were observed, no exotherms were observed on cooling, nor were endotherms observed when reheating the same samples. This suggests that the melting transitions are monotropic, which is to say that they are only observable in one direction, and that the amorphous/melted state is metastable even on holding at -20 °C for prolonged periods.  Polarizing optical microscopy confirmed the observations made by DSC. Compounds 19e and 19f melted from seemingly amorphous solids to isotropic liquids at approximately the same temperatures as the transitions observed by DSC. It is conceivable that the observed  66  endotherms for these two compounds occurred as a result of water loss but the absence of sharp transitions in the DSC traces and the P O M observations of the other macrocycles would seem to suggest otherwise. A l l the other macrocycles seemed to smoothly transition from amorphous red/black solids to dark red/orange isotropic liquids at temperatures between 60-80 °C. On heating above -200 °C, all the samples examined changed from dark red/orange to brown then to black. This irreversible decomposition has been observed previously for the related macrocycles 8jand81  n  Peak = 203.77 °C  A r e a = 0.624 mJ Delta H = 0.223 J/g  160 165 170 175 180 185 1 90 1 95 200 205 210 215 220 Temperau tre CC ') Figure 3.13: DSC Trace for Macrocycle 19b  Peak = 122.58 °C  A r e a = 6.945 mJ Delta H = 5.B90 J/g  90  100 10 120 Temperau tre C "(O  140 150  Figure 3.14: DSC Trace for Macrocycle 19f 67  3.2.4: Crystallography of Macrocycle 19a Although the long-chain hexaalkoxy substituted macrocycles were isolated as amorphous solids, it was possible to grow single crystals of macrocycle 19a suitable for x-ray diffraction. ORTEP diagrams for the structure obtained are illustrated in Figure 3.15 and 3.16. Although quite similar to crystal structures reported for the parent macrocycle 9a and the related 7  macrocycle 9c,  12  the structure presents some unique features. In particular, although the phenyl  rings associated with the diamine moieties are approximately coplanar, the catechol moieties are all twisted in one direction relative to the plane derived from the phenylenediamine rings and are pointed towards a water molecule nestled in the center of the cycle. This is in contrast to the previously reported related structures in which two of the catechol moieties point to one side of the plane, with the third approximately in the plane. This produces a bowl shape in the solid state, which has previously been reported for macrocycles of this type only after polymetallation with zinc acetate.  9  <y-c. ...  9  X  0  Jk  I  J.  \> o  o'"'7'b\  Figure 3.15: Top View of Macrocycle 19a as Determined by S C X R D 68  Figure 3.16: Side View of Macrocycle 19a as Determined by S C X R D (butyl groups omitted for clarity)  The packing of this macrocycle shows that the macrocycles orient themselves with adjacent "bowls" adopting an up-down (or concave-convex) arrangement. This is most clearly seen when viewed along the a crystallographic axis (see Figure 3.17). There also appear to be channels or pores when the structure is viewed along the c-axis (see Figure 3.18);however the separation of the macrocycles is quite large (ca. 17 A ) , corresponding to the length of the unit cell along c. The convex faces of the bowls are capped by a water molecule while interstitial spaces are filled with several molecules of acetonitrile. For a table of the crystallographic parameters as well as selected bond lengths and angles, see Appendix 1, Table 2.  69  Figure 3.17: Packing View of Macrocycle 19a Along the a-Axis (acetonitrile molecules omitted for clarity)  Figure 3.18: Packing View of Macrocycle 19a Along the c-Axis  3.3 - Conclusions and Recommendations A series of [3+3] Schiff base macrocycles bearing six alkoxy and six aikyl groups appended to their peripheries was synthesized. These compounds were characterized by ' H and 13  C N M R , IR, and U V - V i s spectroscopies as well as by MALDI-TOF mass spectrometry. As  previously reported, the synthesis of these macrocycles is extremely facile; combination of stoichiometric amounts of dialdehyde and diamine in an appropriate solvent system and in the presence of a catalytic amount of piperidine afforded the desired [3+3] cycles in good yields and purities with only a very small proportion of oligomers or fragments observed.  The thermal properties of these macrocycles were investigated by differential scanning calorimetry and by polarizing optical microscopy. Although sharp melting transitions were observed for some of the target long-chain alkoxy macrocycles they were, for the most part, amorphous and the melting transitions, when observed, were irreversible. No indication of liquid crystallinity in any these macrocycles was observed.  Although it is conceivable that further structural modification of this type of macrocycle might lead to novel discotic liquid crystals, certain features of these systems differentiate them from typical discotic mesogens. In particular, they lack the planarity and structural rigidity of conventional compounds which display discotic liquid crystallinity; they are neither planar in the solid state (as evidenced by the crystal structure of 19a), nor are they particularly rigid. Although appearing to have high symmetry in solution by N M R , this occurs as a result of fluxionality within the macrocyclic core. This does not preclude the possibility that macrocycles based on this core could be liquid crystalline, however examples of bowlic or pyramidal discotic liquid crystals are quite rare in the literature. Perhaps a telling example of the fragility of the 71  mesophase for atypical discotics is the story of those based on hexaacylated azacrown[18]-N6; tubular discotic liquid crystallinity was observed for two of these compounds by Lehn and coworkers.  Subsequent systematic variation of the substitution on azacrown[l 8]-N6 core by  Idziak and coworkers failed to generate any other related compounds that displayed liquid 18  crystallinity.  It may be that examples of this class of liquid crystals (i.e. bowlic mesogens)  does not lend themselves to rational design but instead require serendipity for their discovery.  3.4 — Experimental Materials. Solvents were degassed by sparging with nitrogen for ~1 h prior to use. Deuterated solvents were obtained from Cambridge Isotope Laboratories, Inc. 4,5-diamino-l,2dialkoxybenzenes (8b-m) were prepared by methods previously reported in the literature.  19  Equipment. A l l reactions were carried out under nitrogen unless otherwise noted. 300 M H z *H N M R spectra and 75.5 M H z  1 3  C N M R spectra and 400 M H z H N M R spectra and 100 M H z C !  1 3  N M R spectra were recorded on Bruker AV-300 and AV-400 spectrometers respectively and were calibrated to residual protonated solvent. UV-Vis spectra were obtained on a Varian Cary 5000 UV-vis/near-IR spectrophotometer using a 1 cm quartz cuvette. IR spectra were obtained from neat or drop cast films on NaCl plates using a Bomem MB-series spectrometer. Matrix assisted laser desorption and ionization - time-of-flight (MALDI-TOF) mass spectra as well as elemental analyses were performed at the U B C Microanalytical Services Laboratory. M A L D I mass spectra were obtained from a dithranol matrix on a Micromass L C T time-of-flight mass spectrometer. Differential scanning calorimetry (DSC) thermograms were obtained using a Perkin Elmer Diamond DSC. A n Olympus BX41 polarizing optical microscope (POM) equipped with a variable temperature hot stage was employed to look for liquid crystalline  72  textures. Melting points were obtained by DSC and/or by P O M . S C X R D data was collected on a Bruker X8 A P E X diffractometer with graphite monochromated M o - K a radiation.  Synthesis of Macrocycle 19a: Into a 100 mL round bottom flask 2,3-dibutyl-5,6-dihydroxybenzene-l,4-dialdehyde (31a; 0.359 g, 1.29 mmol) was dissolved in 50 mL acetonitrile and 10 mL chloroform. Phenylenediamine (8a; 0.142 g, 1.35 mmol) was added and the resulting yellow solution stirred briefly under nitrogen for 5 minutes. A drop of piperidine was added immediately turning the solution dark pink/red. This solution heated at reflux overnight under nitrogen, then cooled to room temperature at which point a fine precipitate formed. The solid was filtered on a Buchner funnel rinsing with a small volume of ice-cold acetonitrile. After air drying, the product 19a was obtained as an orange/brown powder (0.108 g, 0.103 mmol, 24% yield, >95% pure by N M R integration). Slow diffusion of acetontrile into a concentrated dichloromethane solution afforded single crystals suitable for x-ray diffraction. ' H N M R (400 M H z , CDC1 ): 5 14.00 (s, 6H, OH), 8.92 (s, 6H, C=NH), 7.36 (br d, 6H, Ar-H), 3  7.16 (br d, 6H, Ar-H), 2.79 (m, 12H, Ar-CH ), 1.49 (br m, 24H), 0.97 (m, 18H, terminal CH ); 2  13  3  C N M R ( 1 0 0 M H z , CDC1 ): 5 162.02 (C=N), 151.9, 143.6, 129.4, 127.6, 119.6, 118.5,35.0, 3  27.6, 23.0, 13.9; MALDI-TOF: m/z =1051.3 ((M+H) , 100%); IR (thin film): v = 3339, 3198, +  2955,2924, 2856, 1618, 1556, 1493, 1465, 1383, 1327, 1215, 1140, 1101, 827, 748 cm" . U V 1  Vis (CH C1 ): ^max (e) 370 nm (1.58 x 10 L-mof'-cm" ); Anal. Calc'd for CeeHygNeOe: C, 75.40; 5  2  1  2  H, 7.48; N , 7.99; O, 9.13. Found: C, 75.09; H , 8.19; N , 7.17; m.p. = 202 °C.  73  Synthesis of Macrocycle 20a: Conditions analogous to those used for the preparation of macrocycle 19a were employed. Compound 20a was obtained as an orange/brown powder (28% yield, >95% pure by N M R integration). *H N M R (400 M H z , CDC1 ): 8 14.00 (s, 6H, OH), 8.91 (s, 6H, C=NH), 7.36 (br d, 6H, Ar-H), 3  7.16 (br d, 6H, Ar-H), 2.78 (m, 12H, Ar-Cr7 ), 1.49 (br m, 24H), 0.97 (m, 18H, terminal Cf7 ); 2  13  3  C N M R (100 M H z , CDC1 ): 8 163.19 (C=N), 152.64, 144.58, 130.40, 128.75, 120.39, 119.41, 3  34.58, 29.64, 27.57, 26.18, 22.98, 13.86; MALDI-TOF: m/z = 1219.9 ((M+H) , 100%); IR(thin +  film): n = 3340, 3194, 2956, 2922,2855, 1619, 1556, 1494, 1466, 1382, 1324, 1216, 1149, 1096, 828, 743 cm" . U V - V i s (CH C1 ): X 1  2  2  (e) 371 nm (1.56 x 10 L-mor'-cm" ); m.p. = 205 °C. 5  m a x  1  Synthesis of Macrocycle 19b: Under nitrogen, 2,3-dibutyl-5,6-dihydroxybenzene-l,4-dialdehyde (31a; 86 mg, 0.31 mmol) and 4,5-diamino-l,2-dimethoxybenzene (8b; 52 mg, 0.31 mmol) were weighed into a 100 mL Shlenk flask. Still under nitrogen, 5 mL of degassed chloroform and 10 mL degassed acetonitrile were added by syringe. A drop of piperidine was added and the solution heated to reflux for approximately 24 hours. On cooling, a fine sediment appeared to form. The solution was filtered and the filtrate concentrated in vacuo affording 19b as a red/black solid (88 mg, 0.071 mmol, 69%) yield, ca. 90%) pure.by N M R integration). ' H N M R (400 M H z , CDCI3): 8 14.64 (br s, 6H, OH), 8.96 (s, 6H, C=NH), 6.84 (s, 6H, Ar-H), 3.99 (s, 18H, Ar-OC/fc), 2.83 (m, 12H, Ar-CH ), 1.50 (br m, 24H), 1.00 (m, 18H, terminal CH ); 2  1 3  3  C N M R ( 1 0 0 M H z , CDC1 ): 8 163.0 ( O N ) , 152.4, 148.6, 137.4, 122.8, 120.4, 114.4, 70.2 3  (OCH3), 34.4, 29.6, 27.6, 26.2, 23.1, 13.9; MALDI-TOF: m/z = 1232.2 ((M+H) , 10%), 1253.9 +  ((M+Na ), 100%), 1270.0 ((M+H 0+Na ), 30%); IR (thin film): u = 3419 (br), 2955, 2929, +  +  2  2856, 1605, 1513, 1463, 1385, 1322, 1261, 1219, 1194, 1008, 842, 669 cm"'. UV-Vis (CH C1 ): 2  2  74  Imz* (s): 352 nm (7.64 x IO L-mol"'-cm"'), 414 nm (8.53 x 10 L-mof'-cm"'); m.p. ~ 195 °C 5  5  (dec).  Synthesis of Macrocycle 20b: Conditions analogous to those used for the preparation of macrocycle 19b were employed. Compound 20b was obtained as a red/black solid (65% yield, ca. 90% pure by N M R integration). ' H N M R (400 MHz, CDC1 ): 5 14.56 (br s, 6H, OH), 8.94 (s, 6H, C=NH), 6.82 (s, 6H, Ar-H), 3  3.99 (s, 18H, Ar-OC// ), 2.81 (m, 12H, Ar-CH ), 1.46 (br m, 48H), 1.00 (m, 18H, terminal CH ); 3  13  2  3  C N M R ( 1 0 0 M H z , CDC1 ): 8 164.1 (C=N), 152.0, 146.5, 139.0, 121.8, 120.3, 115.3,71.0 3  (OCH3), 34.3, 28.0, 27.7, 26.3, 23.0, 13.9; MALDI-TOF: m/z = 1399.5 ((M+H) , 100%), 1422.6 +  ((M+Na ), 100%), 1438.7 ((M+H 0+Na ), 25%); IR (thin film): v = 3422 (br), 2955, 2926, +  +  2  2855, 1605, 1513, 1464, 1386, 1322, 1261, 1220, 1195, 1008, 841,669 cm ; UV-Vis (CH C1 ): -1  2  W  2  (£): 350 nm (7.81 x 10 L-mof'-cm" ), 415 nm (8.64 x 10 L-mof'-cm"'); m.p. ~ 195 °C 5  1  5  (dec).  Synthesis of Macrocycle 19c: Conditions analogous to those used for the preparation of macrocycle 19b were employed but using 4,5-diamino-l,2-dihexyloxybenzene (8g). Compound 20b was obtained as red/black solid (50% yield, ca. 85% pure by N M R integration). ' H N M R (400 M H z , CDC1 ): 5 14.71 (br s, 6H, OH), 8.91 (s, 6H, C=N#), 6.82 (s, 6H, Ar-H), 3  4.10 (m, 12H, Ar-OC// ), 2.81 (m, 12H, Ax-CH ), 1.88 (br m, 12H), 1.44 (br m, 48H), 0.90 (m, 2  36H, terminal CH ); 3  I 3  2  C N M R (100 MHz, CDC1 ): 5 162.38 ( O N ) , 152.5, 146.6, 137.9, 121.9, 3  120.3, 115.4, 70.8 (OCH ), 34.3, 31.4, 31.1, 31.0, 28.0, 27.7, 26.3, 23.0, 15.5, 13.9; M A L D I 3  TOF: m/z= 1653.4 ((M+H) , 100%), 1675.2 ((M+Na ), 50%), 1693.3 ((M+H 0+Na ), 50%); IR +  +  +  2  75  (thin film): u = -3200 (v br), 2956, 2926, 2857, 1604, 1509, 1466, 1385, 1322, 1264, 1193, 1093, 1017, 740 cm" ; U V - V i s (CH C1 ): ^ 1  2  2  (e): 353 nm (6.44 x 10 L-mof'-cm-'), 415 nm 5  m a x  (7.99 x 10 L-mof'-cm"'); m.p. ~ 195 °C (dec). 5  Synthesis of Macrocycle 20c: Conditions analogous to those used for the preparation of macrocycle 19b were employed but using 4,5-diamino-l,2-dihexyloxybenzene (8g) and 2,3-dihexyl-5,6-dihydroxybenzene-l,4dialdehyde (31b). Compound 20b was obtained as a red/black solid (50% yield, ca. 85% pure by N M R integration). ' H N M R (400 M H z , CDC1 ): 5 14.71 (s, 6H, OH), 8.92 (s, 6H, C=NH), 6.83 (s, 6H, Ax-H), 4.10 3  (m, 12H, Ar-OC# ), 2.82 (m, 12H, Ax-CH ), 1.87 (br m, 12H), 1.48 (br m, 72H), 0.92 (m, 36H, 2  2  terminal CH ); C N M R ( 1 0 0 MHz, CDC1 ): 5 163.1 (C=N), 152.0, 146.6, 137.9, 121.8, 120.2, 1 3  3  3  115.4,71.0 (OCH ), 34.3, 31.4, 31.1, 31.0, 28.0, 27.7, 26.3, 23.3, 23.0, 15.5, 13.9; MALDI-TOF: 3  m/z= 1821.5 ((M+H) , 100%), 1843.5 ((M+Na ), 50%), 1859.6 ((M+H 0+Na ), 40%),1877.6 +  +  +  2  ((M+2H 0+Na ), 10%); IR (thin film): n = -3200 (v br), 2956, 2927, 2856, 1606, 1510, 1466, +  2  1386, 1322, 1265, 1193, 1092, 1017, 739 cm"'. UV-Vis (CH C1 ): X 2  2  max  (s): 354 nm (6.48 x 10  5  L-mof'-cm"'), 413 nm (8.03 x 10 L-mof'-cm"'); m.p. - 195 °C (dec). 5  Synthesis of [1+2] Fragment 32a: Conditions analogous to those used for the preparation of macrocycle 19b were employed using 4,5-diamino-l,2-dihexyloxybenzene (8g) and 2,3-dibutyl-5,6-dihydroxybenzene-l,4-dialdehyde (31a), however no piperidine was added as catalyst. Compound 32a was obtained as a pink/orange solid (28% yield, > 90% pure by N M R integration). ' H N M R (400 M H z , CDC1 ): 8 14.43 (s, 2H, OH), 8.37 (s, 2H, C=N//), 6.75 (s, 2H, Ar-H), 6.36 3  (s, 2H, Ar-H), 3.95 (m, 8H, Ar-OC// ), 3.90 (s, v br, - 4 H , N / / ) , 2.80 (t, 8H, Ax-CH ), 1.80 (m, 2  2  2  76  8H, O C H C / / ) , 1-40 (br m, 32H), 0.92 (m, 18H, terminal CH ); 2  2  3  I 3  C N M R (100 MHz, CDC1 ): 8 3  156.6, 151.1, 149.4, 142.2, 136.8, 130.1, 126.8, 118.6, .106.2, 102.3, 71.3, 69.3, 32.7, 31.7, 31.6, 29.7, 29.5, 29.2, 27.9, 25. 8, 25.7, 22.7, 22.6, 14.0; IR (thin film): u = 3373 (NH stretch), 3152 (br), 2955, 2925, 2852, 1609, 1586, 1522, 1465, 1432, 1385, 1263, 1207, 1158, 839 cm" ; U V 1  Vis (CH C1 ): X 2  2  (s): 315 nm (2.82 x 10 L-mof'-cm" ), 473 nm (4.70 x 10 L-mof'-cm" ); 5  m a x  1  5  1  Anal. Calc'd for C 5 H N 0 : C, 72.69; H , 9.62; N , 6.52; O, 11.17. Found: C, 72.46; H , 9.69; N,' 2  8 2  4  6  5.92; m.p. = 228-232 °C.  Synthesis of Macrocycle 19d: Conditions analogous to those used for the preparation of macrocycle 19b were employed but using 4,5-diamino-l,2-bis(tetradecyloxy)benzene (8k). Compound 19d was obtained as a waxy, amorphous orange/black solid (30% yield, ca. 85% pure by N M R integration). ' H N M R (400 M H z , CDCI3): 8 14.10 (br s, 6H, OH), 8.89 (s, 6H, C=N//), 6.78 (s, 6H, Ar-//), 4.07 (m, 12H, A r - O C / / ) , 2.76 (m, 12H, Ar-C/Z ), 1.88 (br m, 12H), 1.40 (br m, 156H), 0.87 (m, 2  36H, terminal C// ); 3  l 3  2  C N M R (100 MHz, CDC1 ): 8 164.2 ( O N ) , 152.6, 146.4, 137.8, 122.6, 3  121.4, 116.9, 70.7 (OCH3), 34.3,31.2,31.1,30.9, 28.0, 27.7, 26.3,23.0, 16.8, 15.5, 13.9; MALDI-TOF: m/z = 2326.2 ((M+H) , 10%), 2348.2 ((M+Na ), 100%), 2364.3 ((M+H 0+Na ), +  +  +  2  60%); IR (thin film): u = 2955, 2922, 2852, 1604, 1511, 1466, 1385, 1322, 1260, 1214, 1015, 838, 721, 668 cm" ; U V - V i s (CH C1 ): X 1  2  2  (e): 355 nm (3.94 x 10 L-mof'-cm" ), 417 nm (4.92 5  max  1  x 10 L-mof'-cm" ); m.p. ~ 195 °C (dec). 5  1  77  Synthesis of [1+2] Fragment 32b: Conditions analogous to those used for the preparation of macrocycle 19b were employed using 4,5-diamino-l,2-bis(tetradecyloxy)benzene (8k) and 2,3-dibutyl-5,6-dihydroxybenzene-l,4dialdehyde (31a), however no piperidine was added as catalyst. Compound 32a was obtained as a waxy orange solid (35% yield, > 90% pure by N M R integration). ' H N M R (400 MHz, CDC1 ): 6 14.43 (s, 2H, OH), 8.86 (s, 2H, C=NH), 6.75 (s, 2H, Ar-H), 6.36 3  (s, 2H, Ai-H), 3.95 (m, 8H, Ar-OC// ), 2.78 (brt, 8H, Ar-C/7 ), 1.55 (br m, 56H), 0.92 (m, 18H, 2  terminal CH );  1 3  3  2  C N M R (100 MHz, CDC1 ): 8 157.1, 151.1, 149.5, 144.2, 136.7, 129.8, 126.5, 3  118.5, 106.3, 103.1, 71.3, 69.6, 32.0, 31.7, 31.5, 29.7, 29.6, 29.2, 27.9, 25.8, 25.7, 22.7, 22.6, 14.02, 13.98; MALDI-TOF: m/z = 1308.5 ((M+H) , 5%), ((M+2H 0+Na ), 100%); IR (thin +  +  2  film): u = 3375 (NH stretch), 3145 (br), 2956, 2917, 2849, 1611, 1585, 1522, 1466, 1432, 1386, 1262, 1207, 839 cm" ; UV-Vis (CH C1 ): lmax (e): 315 nm (1.40 x 10 L-mof'-cm" ), 469 nm 1  5  2  1  2  (2.27 x 10 L-mof'-cm" ); m.p. = 206-209 °C. 5  1  Synthesis of Macrocycle 19e: Conditions analogous to those used for the preparation of macrocycle 19b were employed but using 4,5-diamino-l,2-bis(hexadecyloxy)benzene (81). Compound 19e was obtained as a waxy, amorphous orange/black solid (45% yield, ca. 85% pure by N M R integration). ' H N M R (400 MHz, CDCI3): 8 14.03 (s, 6H, OH), 8.89 (s, 6H, C=N/f), 6.77 (s, 6H, Ar-H), 4.06 (m, 12H, Ar-OC// ), 2.76 (m, 12H, Ar-C# ), 1.86 (br m, 12H), 1.40 (br m, 180H), 0.87 (m, 36H, 2  2  terminal CH ); C N M R ( 1 0 0 MHz, CDCI3): 8 163.1 (C=N), 153.8, 147.0, 138.1, 122.7, 121.3, 1 3  3  117.0, 70.6 (OCH3), 34.2, 31.4, 31.1, 30.7, 28.1, 27.7, 26.4, 23.0, 16.7, 15.5, 13.9; MALDI-TOF: m/z = 2326.2 ((M+H) , 10%), 2348.2 ((M+Na ), 100%), 2364.3 ((M+H 0+Na ), 60%); IR (thin +  +  +  2  film): u = 2955, 2922, 2852, 1604, 1511, 1466, 1385, 1322, 1260, 1214, 1015,838, 721,668  78  cm . U V - V i s (CH C1 ): X -1  2  cm ); -1  2  (s): 354 nm (3.88 x IO L-mor'-cm" ), 419 nm (4.83 x 10 L-mol"'5  max  1  5  m.p. ~ 195 °C (dec).  Synthesis of Macrocycle 20d: Conditions analogous to those used for the preparation of macrocycle 19b were employed but using 4,5-diamino-l,2-bis(hexadecyloxy)benzene (81) and 2,3-dihexyl-5,6-dihydroxybenzene1,4-dialdehyde (31b). Compound 19e was obtained as an amorphous orange/black solid (40% yield, ca. 85% pure by N M R integration). ' H N M R (400 M H z , CDCI3): 8 14.73 (s, 6H, OH), 8.91 (s, 6H, C=N#), 6.82 (s, 6H, Ar-H), 4.09 (m, 12H, Ar-OC# ), 2.81 (m, 12H, Ar-CH ), 1.87 (br m, 12H), 1.40 (br m, 204H), 0.86 (m, 36H, 2  terminal CH );  1 3  2  C N M R ( 1 0 0 M H z , CDC1 ): 8 162.14 (C=N), 153.0, 146.8, 138.4, 122.0, 121.4, 3  3  116.9, 70.6 (OCH3), 34.2,31.5,31.2,30.9, 28.2, 27.6, 26.4, 23.0, 16.8, 15.5, 13.9; MALDI-TOF: m/z = 2662.7 ((M+H) , 50%), 2684.9 ((M+Na ), 100%), 2701.3 ((M+H 0+Na ), 80%); IR (thin +  +  +  2  film): n = 2955, 2922, 2852, 1604, 1511, 1466, 1385, 1322, 1260, 1214, 1092, 1015, 838, 721, 668-cm"' . U V - V i s (CH C1 ): W (e): 352 nm (3.81 x 10 L-mor'-cm"'), 414 nm (4.88 x 10 1  5  2  5  2  L-mor'-cm" ); m.p. I l l °C. 1  Synthesis of Macrocycle 19f: Conditions analogous to those used for the preparation of macrocycle 19b were employed but using 4,5-diamino-l,2-bis(octadecyloxy)benzene (8m).  Compound 19f was obtained as an  amorphous orange/black solid (30% yield, ca. 90% pure by N M R integration). ' H N M R (400 M H z , CDC1 ): 8 14.73 (s, 6H, OH), 8.91 (s, 6H, C=NH), 6.82 (s, 6H, Ar-H), 4.09 3  (m, 12H, A r - O C / / ) , 2.81 (m, 12H, Ar-CH ), 1.88 (br m, 12H), 1.40 (br m, 204H), 0.87 (m, 36H, 2  terminal CH ); 3  1 3  2  C N M R (100 MHz, CDC1 ): 8 163.2 (C=N), 153.1, 146.8, 138.4, 121.9, 121.5, 3  116.8, 70.6 (OCH3), 34.2, 31.5, 31,2, 30.9, 28.2, 27.6, 26.4, 23.0, 16.8, 15.5, 13.9; MALDI-TOF: 79  m/z = 2662.4 ((M+H) , 100%), 2684.8 ((M+Na ), 90%), 2702.3 ((M+H 0+Na ), 70%); IR (thin +  +  +  2  film): u = 2954, 2921, 2851, 1604, 1510, 1465, 1385, 1321, 1260, 1208, 1093, 1014, 838, 721, 669 cm ; U V - V i s (CH C1 ): W -1  2  2  (s): 356 nm (3.92 x 10 L-mof'-cm" ), 417 nm (4.89 x 10 5  1  5  L-mol"'-cm"'); m.p. 123 °C.  Synthesis of Macrocycle 20e:  Conditions analogous to those used for the preparation of macrocycle 19b were employed but using 4,5-diamino-l,2-bis(octadecyloxy)benzene (8m) and 2,3-dihexyl-5,6-dihydroxybenzene1,4-dialdehyde  (31b).  Compound 20e was obtained as an amorphous orange/black solid (35%  yield, ca. 85% pure by N M R integration). ' H N M R (400 M H z , CDC1 ): 5 14.54 (br s, 6H, OH), 8.91 (s, 6H, C=HH), 6.81 (s, 6H, Ax-H), 3  4.08 (m, 12H, Ar-OCfY ), 2.80 (m, 12H, Ax-CH ), 2  1.87 (br m, 12H), 1.40 (br m, 228H), 0.87 (m,  2  36H, terminal CrY ); C N M R (100 MHz, CDC1 ): 5 163.2 (C=N), 153.0, 146. 8, 138.4, 121.9, 1 3  3  3  121.5, 116.8, 70.6 (OCH ), 34.2, 31.4, 31.3, 30.9, 28.2, 27.5, 26.4, 23.1, 16.8, 15.6, 13.9; 3  MALDI-TOF: m/z = 2830.9 ((M+H) , 100%), 2852.7 ((M+Na ), 80%), 2868.8 ((M+H 0+Na ), +  +  +  2  60%); IR (thin film): u = 2954, 2921, 2851, 1604, 1510, 1465, 1385, 1321, 1260, 1208, 1093, 1014, 838, 721, 669 cm' ; U V - V i s (CH C1 ): l 1  2  2  (e): 351 nm (3.15 x 10 L-mof'-cm' ), 416 nm 5  max  1  (4.24 x 10 L-mol' •cm' ); m.p. ~ 195 °C (dec). 5  1  1  80  Chapter 4: Conclusions and Future Work 4.1 - Conclusions A number of synthetic routes were investigated in an effort to obtain the highly substituted aromatic dialdehydes 31a and 31b. These compounds were successfully obtained by three different methods that can be categorized as the lithiation/formylation route, the cyanation/reduction route and the direct formylation route. Of the three, the latter was found to be preferable in terms of minimization of the steps required and yields obtained. Although successful for relatively short aikyl chains (i.e. butyl and hexyl), the methods employed were unsuitable for the preparation of longer-chain analogues. A n alternative method for the preparation of the related longer-chain compounds was suggested. Compounds 31a and 31b were characterized by ' H N M R ,  1 3  C N M R , IR and UV-Vis spectroscopies, as well as by high  resolution mass spectrometry. Satisfactory elemental analyses were obtained. In addition, a crystal structure for compound 31a was obtained by single-crystal x-ray diffraction (SCXRD) and was discussed.  Compounds 31a and 31b were subsequently used to prepare a series [3+3] Schiff base macrocycles incorporating six alkoxy substituents and six aikyl substituents around their peripheries (19c-f and 20c-e) in hopes that they might form discotic liquid crystalline mesophases. Characterization of these macrocycles by *H N M R ,  1 3  C N M R , IR and UV-Vis  spectroscopies, as well as by MALDI-TOF mass spectrometry was undertaken. The characterization was consistent with the successful preparation of these compounds, however their extreme solubility in common organic solvents and relative hydrolytic sensitivity made their purification problematic. In addition, the thermal properties of these macrocycles were  81  investigated by differential scanning calorimetry (DSC) and by polarizing optical microscopy (POM). Although sharp endotherms were observed by DSC for two of the macrocycles prepared as were well-defined melting transitions by P O M they were, for the most part, amorphous solids which melted directly to isotropic liquids with no indications of mesophase formation. A crystal structure of the related macrocycle 19a was obtained by S C X R D and was discussed.  4.2 - Future Work  A number of possible options for further exploration of these types of macrocycles exist. One avenue for future work would be to attempt to further purify the macrocycles; as prepared the purities were typically only on the order of 80-90% by N M R integration. The presence of impurities such as fragments and oligomers may inhibit the formation of mesophases, but the sharp melting transitions observed for some of the prepared macrocycles would seem to suggest (at least circumstantially) a reasonable degree of purity. Unfortunately, the hydrolytic sensitivity of the imine bonds makes purification of these compounds by conventional chromatography quite difficult; attempts to chromatograph these macrocycles on silica afforded only fragments on elution. Gel permeation chromatography may provide a feasible means of purification, or at least provide a better gauge of their purities, assuming the macrocycles are sufficiently robust. For the macrocycles bearing long alkoxy chains (i.e. hexyloxy and longer), purification by precipitation did not seem to be a viable option. The extreme solubility of these compounds in virtually every organic solvent employed (with the exception of acetonitrile) makes this method impractical. In addition, and once again as a result of the hydrolytic sensitivity of the imine bonds, the purity of the compounds seemed to decrease on attempts at purification by precipitation. Nonetheless, it seems likely that some method for obtaining these macrocycles in  82  higher purities, whether through judicious choice of reaction conditions or through some means of post-reaction purification, is possible given further investigation.  Another obvious possibility for future investigation is to complex these macrocycles to metals. Although preliminary attempts to incorporate metals in the macrocycles prepared in this work with nickel and zinc were undertaken, they did not seem to appreciably modify their bulk physical properties. On treatment with metal salts, the macrocycles retained their extreme solubility in common organic solvents. That being said, metallation may improve the structural rigidity of the macrocycles making them more likely to form discotic mesophases. In addition, the incorporation of metals may lead to stronger interactions in the solid state, possibly promoting the formation of a tubular mesophase.  One of the crowning virtues of these types of [3+3] macrocycles is the variety and structural diversity of the diamine and dialdehyde components from which they can be prepared. The possibilities for structural variation seem almost limitless and, as such, the avenues for the construction of novel macrocycles that might display interesting structural features and physical properties is limited only by one's imagination and synthetic acumen.  83  References  Chapter 1 1 - Choi, K . H . ; Lai, V.; Foster, C.E.; Morris, A.J.; Tolan, D.R.; Allen, K . N . Biochemistry 2006, 45,8546. 2 - O'Donnell, M.J. Ace. Chem. Res. 2004, 57, 506. 3 - For some examples of the use of Schiff base complexes as catalysts, see: DiMauro, E.F.; Kozlowski, M . C . J. Am. Chem. Soc. 2002,124, 12668. Jacobsen, E.N. Acc. Chem. Res. 2000, 55,421. 4 - For examples of some Schiff base derived liquid crystals, see: Warm, M . A . ; Harbison, G.S. J. Am. Chem. Soc. 1989, 111, 7273. Marcos, M . ; Romero, P.; Serrano, J.L. Chem. Mater. 1990, 2, 495. Marcos, M . ; Serrano, J.L.; Sierra, T.; Gimenez, M.J. Chem. Mater. 1993, 5, 1332. Hudson, S.A.; Maitlis, P . M . Chem. Rev. 1993, 93, 861 (and references cited therein). Binnemans, K.; Gorller-Walrand, C. Chem. Rev. 2002, 102, 2303 (and references cited therein). 5 - Melsen, G.A.; Busch, D.H. J. Am. Chem. Soc. 1964, 86, 4834. Melsen, G.A.; Busch, D.H. J. Am. Chem. Soc. 1965, 87, 1706. 6 - Borisova, N.E.; Reshetova, M.D.; Ustynyuk, Y A . Chem. Rev. 2007,107, 46 (and references cited therein). 7 - Failla, S.; Finocchiaro, P. J. Chem. Soc, Perkin Trans. 1992, 701. 8 - Pilkington, N . H . ; Robson, R. Aust. J. Chem. 1970, 25, 2225. 9 - Tandon, S.S.; McKee, V . J. Chem. Soc, Dalton Trans. 1989, 19. 10-Kruger, P.E.; McKee, V . Chem. Commun. 1997, 1341. 11 - McCrea, J.; McKee, V.; Metcalfe, T.; Tandon, S.S.; Wikaira, J. Inorg. Chim. Acta 2000, 297,220. 12 - Brooker, S. Coord. Chem. Rev. 2001, 222, 33. 84  13 - Dutta, B.; Bag, P.; Adhikary, B.; Florke, U . ; Nag, K. J. Org. Chem. 2004, 69, 5419. 14 - Fontecha, J.B.; Goetz, S.; McKee, V. Angew. Chem. Int. Ed. 2002, 41, 4553. 15 - Jasat, A.; Dolphin, D. Chem. Rev. 1997, 97, 2267. 16 - Meyer, S.; Andrioletti, B.; Sessler, J.L.; Lynch, V . J. Org. Chem. 1998, 63, 6752. 17 - Sessler, J.L.; Mody, T.D.; Lynch, V . J. Am. Chem. Soc. 1993,115, 3346. 18 - Sessler, J.L.; Callaway, W.; Dudek, S.P.; Date, R.W.; Lynch, V . ; Bruce, D.W. Chem. Commun.  2003, 2422.  19 - For some examples of Schiff Base macrocycles developed by the MacLachlan group, see: a) Hui, J.K.-H.; MacLachlan, M.J. Chem. Commun. 2006, 2480. b) Gallant, A.J.; Hui, J.K.H.; Zahariev, F.; Wang, Y . A . ; MacLachlan, M.J. J. Org. Chem. 2005, 70 , 7936. c) Ma, C ; Lo, A.; Abdolmaleki, A.; MacLachlan, M.J. Org. Lett. 2004, 6, 3841. d) Gallant, A.J.; MacLachlan, M.J. Angew. Chem. Int. Ed. 2003, 42, 5307. 20 - Akine, S.; Taniguchi, T.; Nabeshima, T. Tetrahdron Lett. 2001, 8861. 21 - Akine, S.; Hashimoto, D.; Saiki, T.; Nabeshima, T. Tetrahedron Lett. 2004, 4225. 22 - Akine, S.;Sunaga, S.; Taniguchi, T.; Miyazaki, H.; Nabeshima, T. Inorg. Chem. 2007, 46, 2959. 23 - For a more comprehensive recounting of the history of this fascinating field of study, see: Gray, G.W. In Handbook of Liquid Crystals; Demus, D., Goodby, J.W., Gray, G.W., Spiess, H.W., V i l l , V., Eds.; Wiley V C H : New York, 1998; Volume 1, pp.1-16. 24 - Brown, G.H.; Shaw, W.G. Chem. Rev. 1957, 57, 1049. 25 - Chandrasekhar, S.; Sadashiva, B.K.; Suresh, K . A . Pramana 1977, 9, All. 26 - Chandrasekhar, S.; Ranganath, G.S. Rep: Prog. Phys. 1990, 53, 57. 27 - Sergeyev, S.; Pisula, W.; Geerts, Y . H . Chem. Soc. Rev. 2007, ASAP, DOI: 10.1039/b417320c (and references cited therein)  85  28 - Debije, M . G . ; Piris, J.; de Haas, M.P.; Warman, J.M.; Tomovic, Z.; Simpson, C D . ; Watson, M.D.; Mullen, K . J. Am. Chem. Soc. 2004,126, 4641. 29 - Cammidge, A . N . ; Bushby, R.J. In Handbook of Liquid Crystals; Demus, D., Goodby, J.W., Gray, G.W., Spiess, H.W., V i l l , V., Eds.; Wiley V C H : New York, 1998; Volume 2, pp. 693-748. 30 - Lillya, C P . ; Collard, D . M . Mol. Cryst. Liq. Cryst. 1990,182B, 201. 31 - Baron, M . ; Stepto, R.F.T. Pure Appl. Chem. 2002, 74, 493. 32 - Lehn, J.M.; Malthete, J.; Levelut, A . M . Chem. Commun. 1985, 1794. 33 - Idziak, S.H.J.; Maliszewskyj, N . C ; Heiney, P A . ; McCauley, J.P.; Sprengeler, P A . ; Smith, A . B . J. Am. Chem. Soc. 1991,113,1666.  Chapter 2 1 - Gallant, A.J.; Hui, J.K.H.; Zahariev, F.; Wang, Y . A . ; MacLachlan, M.J. J. Org. Chem. 2005, 70, 7936. 2 -Nabeshima, T.; Miyazaki, H.; Iwasaki, A.; Akine, S.; Saiki, T.; Ikeda, C. Tetrahedron 2007, 63,3328.  •'  ,  3 - Hui, J. M.S. Thesis, The University of British Columbia, 2004. 4 - Antonisse, M . M . G . ; Snellink-Ruel, B.H.M.; Yigit, I.; Engberson, J.F.J.; Reinhoudt, D.N. J. Org. Chem. 1997, 62, 9034. (for compound 8j, for example) 5 - Tamao, K.; Sumitani, K.; Kumada, M . J. Am. Chem. Soc. 1972, 94, 4374. 6 - Kumada, M . ; Tamao, K.; Sumitani, K . Org. Syn. 1978, 58, Ul. Van Hecke, G.R.; Horrocks, W.D. Inorg. Chem. 1966, 5, 1968.  7 - Zhou, Q.; Carroll, P.J.; Swager, T.M. J. Org. Chem. 1994, 59, 1294. 8 - Cuellar, E.A.; Marks, T.J. Inorg. Chem. 1981, 20, 3766. 9 - Hanack, M . ; Haisch, P.; Lehmann, H.; Subramanian, L.R. Synthesis, 1993, 387. 10 - Ohta, K.; Jacquemin, L.; Sirlin, C ; Bosio, L.; Simon, J. New. J. Chem. 1988,12, 751. 86  11 - a) Aalten, H.L.; van Koten, G.; Grove, D.M.; Kuilman, T.; Piekstra, O.G.; Hulshof, L.A.; Sheldon, R.A. Tetrahedron, 1989, 45, 5565. b) Capdevielle, P.; Maumy, M . Tetrahedron Lett., 1993,34,1007. 12 - Vilsmeyer, A . ; Haack, A . Ber. Dtsch. Chem. Ges. 1927, 60, 119. 13 - Martinez, A . G . ; Alvarez, R . M . ; Barcina, J.O.; de la Moya Cerero, S.; Vilar, E.T.; Fraile, A.G.; Hanack, M . ; Subramanian, L.R. Chem. Commun. 1990, 1571. 14 - Campaigne, E.; Archer, W.L. Org. Syn. 1953, 33, 27. 15 - Makara, G.M.; Anderson, W.K. J. Org. Chem. 1995, 60, 5717.  ;  16 - Akine, S.; Taniguchi, T.; Nabeshima, T. Tetrahedron Lett. 2001, 42, 8861. 17 - Crowther, G.P.; Sundberg, R.J.; Sarpeshkar, A . M . J. Org. Chem. 1984, 49, 4657. 18 - Gilman, H.; Jacoby, A . L . J. Org. Chem. 1938, 3, 108. 19 - Parham, W.E.; Bradsher, C.K. Acc. Chem. Res. 1982, 15, 300. (and references cited therein) 20 - Worden, L.R.; Kaufman, K.D.; Smith, P.J.; Widiger, G.N. J. Chem. Soc. (C) 1970, 227. 21 - Iyer, S.; Liebeskind, L.S. J. Am. Chem. Soc. 1987,109, 2759. 22 - Weissensteiner, W.; Scharf, J.; Schlogl, K. J. Org. Chem. 1987, 52, 1210. 23 - Carey, F.A.; Sundberg, R.J. Avanced Organic Chemistry, Part B: Reactions and Synthesis,  3 ed.; Plenum: New York, 1990; pp. 232-237. rd  24 - Miller, A.E.G.; Biss, J.W.; Schwartzman, L.H. J. Org. Chem. 1959, 24, 627. 25 - M o w r y , D.T. Chem. Rev. 1948, 42, 189. (  26 - a) Newman, M.S. Org. Syn. 1941, 21, 89. b) Friedman, L ; Shechter, H. J. Org. Chem. 1961, 26, 2522. c) Newman, M . ; Boden, H. J. Org. Chem. 1961, 26, 2525. 27 - Trofimenko, S. J. Org. Chem. 1964, 29, 3046. 28 - Duff, J.C.; Bills, E.J. J. Chem. Soc. 1934, 1305. Duff, J.C. J. Chem. Soc. 1941, 547.  87  29 - Smith, W.E. J. Org. Chem. 1972, 37, 3972. Larrow, J.F.; Jacobsen, E.N.; Gao, Y.; Hong, Y.; Nie, X . ; Zepp, C M . J. Org. Chem. 1994, 59, 1939. 30 - Chong, J.H.; Sauer, M . ; Patrick, B.O.; MacLachlan, M.J. Org. Lett. 2003, 5, 3823. 31 - Ogata, Y . ; Kawasaki, A . ; Sugiura, F. Tetrahedron 1968, 24, 5001. 32 - CRC Handbook of Chemistry and Physics, 78 ed. Lide, D.R., Ed.; C R C Press: New York, th  1997. 33 - Grenier, C.R.G.; Pisula, W.; Joncheray, T.J.; Mullen, K.; Reynolds, J.R. Angew. Chem. Int. Ed. 2007, 46, 714.  Chapter 3 I - Pilkington, N . H . ; Robson, R. Aust. J. Chem. 1970, 23, 2225. , 2 - Tandon, S.S.; McKee, V . J. Chem. Soc, Dalton Trans. 1989, 19. 3 - Jasat, A.; Dolphin, D. Chem. Rev. 1997, 97, 2267. 4 - Kuhnert, N . ; Lopez-Periago, A . M . Tetrahedron Lett. 2002, 43, 3329. 5 - Kuhnert, N . ; Lopez-Periago, A . M . ; Rossignolo, G . M . Org. Biomol. Chem. 2005, 3, 524. 6 - Gao, J.; Reibenspies, J.H.; Zingaro, R.A.; Woolley, F.R.; Martell, A . E . ; Clearfield, A . Inorg. Chem. 2005, 44,232. 7 - Akine, S.; Taniguchi, T.; Nabeshima, T. Tetrahdron Lett. 2001, 8861. 8 - Gallant, A.J.; MacLachlan, M.J. Angew. Chem. Int. Ed. 2003, 42, 5307. 9 - Gallant, A.J.; Chong, J.H.; MacLachlan, M.J. Inorg. Chem. 2006, 45, 5248. 10 - Nabeshima, T.; Miyazaki, H.; Iwasaki, A.; Akine, S.; Saiki, T.; Ikeda, C. Tetrahedron 2007, 63, 3328. II - Hui, J. M.Sc Thesis, The University of British Columbia, 2004. 12 - Gallant, A.J.; Hui, J.K.H.; Zahariev, F.; Wang, Y . A . ; MacLachlan, M.J. J. Org. Chem. 2005, 70 , 7936. 88  13 - Borisova, N.E.; Reshetova, M.D.; Ustynyuk, Y.A. Chem. Rev. 2007,107, 46. 14 - Benetollo, F.; Bombieri, G.; De Cola, L.; Polo, A.; Smailes, D.L.; Vallarino, L.M. Inorg. Chem. 1989, 28, 3447. 15 - Carey, F.A.; Sundberg, R.J. Avanced Organic Chemistry, Part A: Structure and  Mechanisms, 4 ed.; Plenum: New York, 2000; pp. 449-495. rd  16 - Clougherty, L.E.; Sousa, J.A.; Wyman, G.M. J. Org. Chem. 1957, 22, 462. 17-Lehn, J.M.; Malthete, J.; Levelut, A.M. Chem. Commun. 1985, 1794. 18 - Idziak, S.H.J.; Maliszewskyj, N.C.; Heiney, P.A.; McCauley, J.P.; Sprengeler, PA.; Smith, A.B. J. Am. Chem. Soc. 1991,113, 7666. 19 - Zhou, Z.L.; Weber, E.; Keana, F.W. Tetrahdron Lett. 1995, 36, 7583. Forget, S.; Veber, M. New J. Chem. 1997, 21, 409.  89  Appendix 1: Crystallographic Data for Compounds 31a and 19a Table A l . 1: X-Ray Diffraction Data for Compound 31a A. Crystal Data Empirical Formula Formula Weight Crystal Color, Habit Crystal Dimensions Crystal System Lattice Type Lattice Parameters  C16H22O4  278.34 orange, blade 0.05 X 1.20 X 1.40 mm primitive Monoclinic a = 18.1497(16) A b = 7.2908(7) A c = 24.030(2) A a = 90° p = 109.146(5)° y = 90°  Dcalc FOOO  V = 3003.8(5) A P2,/a(#14) 8 1.231 g/cm 1200  u(MoKa)  0.87 cm"  Space Group Z value  3  3  1  B. Intensity Measurements Diffractometer Radiation Data Images Detector Position 29max No. of Reflections Measured  Bruker X8 A P E X MoKoc (k = 0.71073 A ) graphite monochromated 2349 exposures @ 10.0 seconds 35.99 mm 54.46° Total: 56005 Unique: 6689 (Ri t = 0.0528) Absorption ( T = 0.778, T = 0.996) Lorentz-polarization n  min  Corrections  max  C. Structure Solution and Refinement Structure Solution  Direct Methods (SIR92)  Refinement  Full-matrix least-squares on F  Function Minimized  I w (Fo - F c )  Least Squares Weights Anomalous Dispersion  w=l/(a (Fo )+(0.0805P) +4.3362P) A l l non-hydrogen atoms  2  2  2  2  2  2  2  90  C. Structure Solution and Refinement (continued) No. Observations (I>0.00a(I)) No. Variables Reflection/Parameter Ratio  6689 414 16.16  Residuals (refined on F , all data): R l ; wR2 Goodness of Fit Indicator No. Observations (I>2.00a(I)) Residuals (refined on F): R l ; w R 2 Max Shift/Error in Final Cycle Maximum peak in Final Diff. Map  0.1052; 0.2001 0.991 4348 0.0632; 0.1605 -0.001 0.948 e'/A^  Minimum peak in Final Diff. Map  -0.416 e"/A^  2  D. Selected Bond Lengths and Angles 0 ( 7 ) - C (20) 1 1 0 ( 6 ) - C(19) 1 0 ( 1 ) - C(7) C(18) - C ( 2 3 ) 1 C ( 5 ) - C(8) 1 C(2)- C(l) 1 C (20) - C ( 2 1 ) 1 C(15) -C(16) 1 C (22) - C (29) 1 1 C ( D - C(9) C(14) - C ( 1 3 ) 1 C (25) - C ( 1 7 ) 1 C (29) - C ( 3 0 ) 1 C (26) - C ( 2 7 ) 1 C(27B)-C(28B)  342(3) 0(8)344(3) 0(2)222(3) C(18) 488 (4 ) C(5)C(4)466(3) 418(3) C(2)C(21) 396(3) 512 (4) C(15) 519 (4) C(6)509(3) C(10) 529(3) C (23) 494 (4) C (25) 533(6) C (30) C(27) 488 (7) 1. 5 3 7 ( 9 )  C ( 1 9 ) - C ( 1 8 ) - C (17) C(17)-C(18)-C(23) C(4)-C(5)-C(8)  120.9(2) 125.1(2) 117.4(2)  C(24) C(3) -C(19) C(4) C(3) C(7) - C (22) -C(14) C(l) -C(ll) -0(5) -C(26) -C(31) -C(28) C (27B)  1 217 (3) 1 356(3) 1' 388 (4) 1 401(3) 1 403(3) 1 466(3) 1 416(4) 1 514(3) 1 391(3) 1 511 (4) 1 191(4) 1 623 (7) 1 510 (5) 1 531(9) -C(26B)  C(19)-C(18)-C(23) C(4)-C(5)-C(6) C(6)-C(5)-C(8)  0 ( 3 ) - C(4) 0 ( 4 ) - C(8) C(18) - C ( 1 7 )  C(5)C(2)C (20) C(21) C (22) C(6)C(10) C (25) C(ll) C(31)  1 1 1 1 C(6) 1 C(3) -C(19) 1 -C(24) 1 -C(17) 1 1 C(13) 1 -C(9) -C(26B)1 -C(12) 1 -C(32) 1  1. 5 4 6 ( 9 ) 114.1(2) 120.9(2) 121.6(2)  337(3) 218(3) 415 (4) 416 (3) 387(3) 403(3) 461 (4) 397 (4)' 512(3) 529 (4) 456(8) 493 (5) 521 (10)  D. Selected Bond Lengths and Angles (continued) 116 . 8 2) 119 . 2 2) 117 . 7 2)  0(3)- C(4)-C(5)  121  0 (2)  115 . 9 2) 119 . 4 2)  0(7)- C (20)-C(21)  124  7 (2)  0(6)- C(19)-C(18)  119  1 (2)  120 . 6 2) 120 . 5 2)  C(18) - C ( 1 9 ) - C ( 2 0 ) C (20) - C ( 2 1 ) - C (24)  120  3 (2)  117  6 (2)  1 2 1 . 9 2) 116 .5 2)  0(2)- C(3)-C(2) C ( 2 ) - C(3)-C(4)  123  6 (2)  119  9 (2)  114 .2  C(17) -C(22)-C(21)  119  9 (2)  C(21) - C ( 2 2 ) - C ( 2 9 ) C(D- C ( 6 ) - C ( 1 3 )  119  1 (2)  120  4 (2)  C(6)- C(l)-C(2) C(2)- C(l)-C(9)  119  1 (2)  119  8 (2)  C-(ll) - C ( 1 0 ) - C ( 9 ) 0(8)- C(24)-C(21)  113  6 (2) 3 (2)  1 2 3 . 9 3) 0(1)- C(7)-C(2) 113 . 2 2) C(6)- C ( 1 3 ) - C (14) C ( 2 6 B ) - C ( 2 5 ) - C ( 1 7 ) 1 2 3 . 6 6) C ( 2 2 ) - C ( 1 7 ) - C ( 1 8 ) 119 . 0 2)  C(D-  113  6 (2)  C(18) - C ( 1 7 ) - C ( 2 5 ) C(31) - C ( 3 0 ) - C ( 2 9 ) C (27) - C ( 2 6 ) - C ( 2 5 )  0(3)- C(4)-C(3) C(3)- C(4)-C(5)  .  C(3)- C(2)-C(7) 0(7)- C(20)-C(19) C(19) - C ( 2 0 ) - C (21) 0(6)- C(19)-C(20) C (20) - C ( 2 1 ) - C ( 2 2 ) C (22) - C ( 2 1 ) - C ( 2 4 ) 0(2)  -C(3)-C'(4)  C(16) - C ( 1 5 ) - C (14) C (17) - C ( 2 2 ) - C ( 2 9 )  edi-  C(6)-C(5) cts) -C ( 6 ) - C ( 1 3 ) C(6)- C(l)-C(9)  2) 120 . 9 3) 119 . 5 2) 120 . 1 2)  0(4)- C(8)-C(5)  1 2 1 . 1 2) 124 . 4 2)  C(15) -C(14)-C(13)  113 . 8  2)  119 . 9 3) 113 . 0 5)  114 . 0 6) C(28B)-C(27B)-C(26B) L10.2 (8)  C(3)- G(2)-C(l) C ( l ) - C(2)-C(7)  .  C(9)-C(10)  124  1 (2)  121  2 (2)  124  0(5)- C(23)-C(18) C(12) -C(11)-C(10)  128  3 (3)  113  3 (3)  C (22) - C ( 1 7 ) - C ( 2 5 )  121  0 (3)  C (22) - C ( 2 9 ) - C ( 3 0 )  112  0 (3)  C (30) - C ( 3 1 ) - C ( 3 2 )  112  5 (6)  C (26) - C ( 2 7 ) - C ( 2 8 )  112  8  C (25) - C ( 2 6 B ) - C ( 2 7 B )  108  .  8) 1(7)  Table A l .2: X-Ray Diffraction Data for Compound 19a A. Crystal Data • Empirical Formula Formula Weight Crystal Color, Habit Crystal Dimensions Crystal System Lattice Type Lattice Parameters  C68H83N7O7  1110.41 red, blade 0 . 5 0 X 0 . 1 0 X 0 . 0 5 mm primitive triclinic a = 13.284(6) A b = 16.492(7) A c = 16.775(7) A a = 61.51(2)° (3 = 68.97(2) ° y = 80.20(3) °  Space Group . Z value  V = 3014.7(3) A P-l (#2) 2  Dcalc F000  1.223 g/cm 2224  u(MoKoc)  0.80 cm"  B. Intensity Measurements  1  3  3  Diffractometer Radiation  Bruker X8 A P E X M o K a (A, = 0.71073 A ) graphite monochromated 1901 exposures @ 25.0 seconds 36.01 mm  Data Images Detector Position 29max No. of Reflections Measured  45.10° Total: 34824 Unique: 7883 (Rim = 0.0305) Absorption ( T = 0.089, T = 0.961) Lorentz-polarization min  Corrections  max  C. Structure Solution and Refinement Structure Solution  Direct Methods (SIR2002)  Refinement  Full-matrix least-squares on F  Function Minimized  E w (Fo - F c )  Least Squares Weights Anomalous Dispersion No. Observations (I>0.00a(I)) No. Variables Reflection/Parameter Ratio  w=l/(a (Fo )+(0.1165P) +6.1219P) A l l non-hydrogen atoms 7883 771 10.22  Residuals (refined on F , all data): R l ; wR2 Goodness of Fit Indicator No. Observations (I>2.00cj(I)) Residuals (refined on F): R l ; wR2 Max Shift/Error in Final Cycle  0.1088; 0.2419 1.027 5757 0.0810; 0.2140 0.003  Maximum peak in Final Diff. Map  1.089 e " / A  Minimum peak in Final Diff. Map  -0.690 e - / A  2  2  2  2  2  2  2  2  3  3  93  D. Selected Bond Lengths and Angles C ( l ) -C(6) C(2) -C(3) C(5) - C ( 6 ) c m -G(8) C(9) -0(1) C (10 )-C(43) . C(12 )-C(13) C (14 )-N(3) C (15 )-N(3) C (18')-C(19) C (21 )-N(4) C(22 )-C (24) C (24 )-C(26) C (25 )-C(27) C (27 )-C(28) C (29 )-C(34) C (31 )-C(32) C (34 ) - N ( 6 ) C (36 )-C(37) C (37 )-C(39) C (39 ) - 0 ( 6 ) C (40 )-C(63) C (43 )-C(44) C (47 )-C(48) C (51 )-C(52)  1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1  391 370 391 453 352 527 430 296 418 374 283 422 385 394 449 406 380 419 399 390 359 523 529 414 544  (7) (7) (6) (7) (6) (6) (6) (5) (6) (6) 5) (6) 6) 6) 6) 6) (7) (5) (6) 6) 6) 7) 7) 10) 8) .  C (1) - C(2) C (3)- C(4) C (6)- N(2) c 8 ) - C(9) c 9 ) - C(l-l) c 11) -0(2) c 12) -C(47) c 15) -C(20) c 16) -C(17) c 19) -C(20) c 21) -C(22) c 23) -0(3) c 24) -C(51) c 26) -C(27) c 28) -N(5) c 29) -N(5) c 32) -C(33) c 35) - N ( 6 ) c 36) -C(38) c 38) -C(40) c 39) -C(41) c 41) -C(42) c 44) -C(45) c 48) -C(4 9) c 52) -C(53)  1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1  401 365 415 388 408 348 520 395 375 397 455 346 510 426 292 418 378 281 420 389 388 481 517 395 483  (7) (7) (6) (6) (7) 5) (7) (6) (6) 6) 6) 5) 6) 6) 5) 5) 6) 5) 6) 6) . 6) 7) 7) 8) 9)  C (1) - N ( l ) C (4) -C(5.) C (7) -N(2) C (8) -C(10)C (10 )-C(12) C (11 )-C(13) C (13 )-C(14) C 15 )-C(16) C (17 )-C(18) C 20 )-N(4) C (22 )-C(23) C 23 )-C(25) c 25 )-0(4) c 26 )-C(55) c 29 )-C(30) c 30 )-C(31) c 33 )-C(34) C- 35 )-C(36) c 37 )-0(5) c 38 )-C(59) c 40 )-C(41) c 42 ) - N ( l ) c 45 )-C(46) c 49 )-C(50) c 53 )-C(54)  1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1  411 371 290 409 380 387 449 396 371 418 397 389 359 519 386 372 388 461 350 517 409 221 499 445 545  (6) (7) (6) (7) (7) (6) (6) (6) (7) (5) (6) (6) (5) 6) 6) 6) 6) 6) 5) 6) 7) 6) 9) 11) 14)  D. Selected Bond Lengths and Angles (contined) c (55) c (59) c (63)  -C(56)  1.519(7)  C  56) -C (57)  1.601  (7)  C(57)-C(58)  1.483(9)  -C(60)  1.529(7)  1.510  (8)  C(61)-C(62)  1.502(11)  -C(64)  1.511(7)  c c  60) -C (61) 64) -C (65)  1.530  (8)  C(65)-C(66)  1.483(8)  c(6)- C(l)-C(2) c(2)- C(l)-N(l) c (4)- C(3)-C(2) c (4)- C(5)-C(6) c (1) - C ( 6 ) - N ( 2 )  C(D-  118  8 (4 )  C (6)-  N(l)  118  122  7 (4)  C (3)- C(2)- C(l)  120  8 (5  120  1 (5)  C (3)- C ( 4 ) - C(5)  120  3 (5  120  8 (5)  2 (4  8 (4)  C (1) - C ( 6 ) - C ( 5 ) C (5)- C ( 6 ) - N(2)  119  117  123  0 (4  N (2)- C(7)-C(8)  123  7 (4)  C (9)- C ( 8 ) - C(10)  120  5 (4  C (9)- C(8)-C(7) 0 (1) - C ( 9 ) - C ( 8 )  118  7 (4)  120  6 (4  123  9 (4)  C (10) - C ( 8 ) - C ( 7 ) 0 (1) - C ( 9 ) - C ( l l )  116  4 (4  c(8)c (12)  C ( 9 ) - C ( l l )  119  7 (4)  C (12) - C ( 1 0 ) - C  120  1 (4  -C(10)-C(43)  122  6 (4)  117  3 (4  0 (2)- C(11)-C(13)  123  5 (4 )  C (8)- C(10) -C(43) 0 (2)- C(ll) -C(9)  116  5 (4  c (13) c (10) c (11) c (12) c (20) c (16) c (18) c (18) c (15)  -C(11)-C(9)  120  0 (4)  -C (12 ) - C ( 1 3  119  3 (4  -C(12)-C(47)  121  1 (4 )  -C (12 ) - C ( 4 7  119  6 (4  -C(13)-C(12)  120  1 (4)  c (10) c (13) c (11)  -C (13 ) - C ( 1 4  119  0 (4  - C ( 1 3 ) - C ( 1 4 ).  120  9 (4)  N (3)- C(14) -C(13)  122  4 (4  -C(15)-C(16)  119  1 (4 )  C (20) -C (15 ) - N ( 3 )  118  7 (4  121  0 (4  120  5 (4  118  9 (4  122  6 (4  120  1 (4  119  8 (4  (8)  5 (4  119  0 (4 )  0 (3)- C(23)-C(25)  116  8 (4 )  c (25) c 26)  -C(23)-C(22)  120  0 (4)  -C(24)-C(51)  120  6 (4)  c (17) -C (16 ) - C ( 1 5 c (17) -C (18 ) - C ( 1 9 c (15) -C (20 ) - C ( 1 9 c (19) -C (20 ) - N ( 4 ) c (23) - C (22 ) - C (24 c (24 ) - C (22 ) - C ( 2 1 c ( 3 ) - C (23) - C ( 2 2 ) c (26) - C (24 ) - C ( 2 2 c (22) - C (24 ) - C ( 5 1  116  7 (4)  0 (4)- C(25) -C(27)  122  5 (4  24) -C (26 ) - C ( 2 7  120  2 (4  27) -C (26 ) - C ( 5 5  118  9 (4  25) -C (27 ) - C  119  6  -C (15) - N (3)'  122  1 (4)  -C(17)-C(16)  119  7 (4)  -C(19)-C(20)  120  7 (4)  -C(20)-N(4)  118  4 (4)  N (4)- C(21)-C(22)  122  4 (4 )  c (23)  -C(22)-C  (21)  120  9 (4  123  2 (4  119  5 (4  0  4)- C(25)-C(23)  c c c c c c c c c  23) - C ( 2 5 ) - C ( 2 7 )  120  8 (4)  24) - C ( 2 6 ) - C ( 5 5 )  120  8 (4)  25) - C ( 2 7 ) - C ( 2 6 )  119  3 (4)  c c c  26) - C ( 2 7 ) - C ( 2 8 )  121  1 (4)  N  5 ) - C (28) - C ( 2 7 )  122  8 (4  30) - C ( 2 9 ) - C ( 3 4 )  118  4 (4 )  123  7  4  117  8  3)  31) -C (30 ) - C  (29  121  5  4  30) - C ( 3 1 ) - C ( 3 2 )  119  8  4)  3 3 ) - C ('32 ) - C ( 3 1  120  1  4  32) - C ( 3 3 ) - C ( 3 4 )  120  4  4)  33) - C (34 ) - C ( 2 9  119  7  4  33) - C ( 3 4 ) - N ( 6 )  122  3  4)  29) - C (34 ) - N ( 6 )  117  9  4  N  6)- C(35)-C(36)  121  9  4)  37) -C (36 ) - C ( 3 8  119  5  4  c  37) - C ( 3 6 ) - C ( 3 5 )  119  2  4)  c c c c c c c  30) -C (29 ) - N ( 5 )  34) - C ( 2 9 ) - N  38) -C (36 ) - C ( 3 5  121  2  4  0  5)- C(37)-C(39)  117  1  4)  0  5 ) - C(37) -C(36)  122  2  4  c c  39) - C ( 3 7 ) - C ( 3 6 )  120  7  4)  40) -C (38 ) - C  119  2  4  40) - C ( 3 8 ) - C ( 5 9 )  120  4  4)  c c  36) -C (38 ) - C ( 5 9  120  4  4  0  6)- C(39)-C(41)  120  5  4)  0  6 ) - C(39) -C (37)  119  5  4  c c c c c c c c c c c c  41) - C ( 3 9 ) - C ( 3 7 )  119  9  4)  38) -C (40 ) - C  120  4  4  38) - C ( 4 0 ) - C ( 6 3 )  120  4  4)  39) - C ( 4 1 ) - C  (40)  120  1  4)  c c c  40) - C ( 4 1 ) - C  (42)  121  7  5)  N  10) - C ( 4 3 ) - C ( 4 4 )  112  7  4)  46) - C ( 4 5 ) - C ( 4 4 )  114 . 0  5)  49) - C ( 4 8 ) - C  c c c c c c c c  (5)  (47)  130. 1  7)  24) - C ( 5 1 ) - C ( 5 2 )  112 . 3  4)  52) - C ( 5 3 ) - C ( 5 4 )  110. 5  9)  55) - C ( 5 6 ) - C  110. 1  4)  38) - C ( 5 9 ) - C ( 6 0 )  113. 1  4)  62) - C ( 6 1 ) - C ( 6 0 )  112 . 9  6)  (57)  (28  (36  (41  4  41) -C (40 ) - C ( 6 3  119  1  4  39) -C (41)-C  (42  118  2  5  1) -C ( 4 2 ) - C ( 4 1 ) 45) -C (44 ) - C ( 4 3  125  5  5  112  9  4  48) -C (47 ) - C ( 1 2  116  8  7  48) -C (49 ) - C ( 5 0  131. 5  9  53) -C (52 ) - C ( 5 1  115. 1  7  56) -C (55 ) - C ( 2 6  113. 3  4  58) - C ( 5 7 ) - C ( 5 6  109. 6  8  61) - C ( 6 0 ) - C ( 5 9 64) -C (63 ) - C ( 4 0  114 . 6  5  113. 4  4  D. Selected Bond Lengths and Angles (contined) C(63)-C(64)-C(65) C(42)-N(1)-C(1) C(14)-N(3)-C(15) C(28)-N(5)-C(29)  111.8(5) 121.5(5) 119.7(4) 120.0(3)  C(66)-C(65)-C(64) C(7)-N(2)-C(6) C(21)-N(4)-C(20) C(35)-N(6)-C(34)  114.3(5) 119.9(4) 120.8(4) 121.4(4)  

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