This thesis discusses the synthesis of new organic, heterocyclic materials for potential application as pigments. Chapter 1 comprises an introduction to the field of pigment and dye chemistry, discussing the rudimentary elements of colour theory, before advancing to a review of the pertinent literature regarding high performance organic pigments. In particular, the development of 1,4-diketopyrrolo[3,4-c]pyrrole (DPP) pigments is described and the central objective of synthesising alkenyl-DPPs is outlined. Chapters 2 and 3 describe synthetic efforts towards alkenyl-DPPs, employing retro Diels-Alder methodology. The reactions involving the furan-acrylonitrile adduct as the nitrile component in the standard DPP synthesis led mainly to aromatisation of the bicyclic system and the cyclopentadiene-acrylonitrile adduct failed to react altogether. The explanation for this failure has been investigated. In the course of this these studies, several DPPs incorporating a secondary alkyl substituent were prepared, not least a novel cyclohexenyl-DPP. Chapter 4 describes the use of α β-unsaturated nitriles in the standard DPP synthesis. These behaved as Michael acceptors and in the case of cinnamonitriles led to a new family of coloured materials, namely substituted 4-hydroxy-2/7- cyclopenta[c]pyrrol-1-one-5-carbonitriles. Chapter 5 describes the corresponding reaction of cinnamate esters, but in these cases bicyclic systems were not formed. The reactions are analogous to Claisen acylations and the stereochemistry of the products varied according to the substituents. Chapter 6 contains the detailed experimental work for these investigations and concludes with a portfolio of X-ray structural data.

With the intention of preparing long chain esters containing a carbocyclic system, methyl linoleate and related esters were subjected to strongly acidic reaction conditions. The major product of the reaction, however, was shown to be a mixture of isomeric 1,4-epoxidea (tetrahydrofurans) and for comparison, a mixture of the cis and trans 9,12-epoxidos was prepared by an unambiguous synthesis. The discovery of those hotorocyclic fatty esters prompted further investigations into their methods of preparation. The cyclodehydration of some trihydroxyacids containing a 1,4-diol system was examined and the mechanism of the reaction elucidated. Those studies led to the formulation of the absolute configurations of the 9,12,13-tri-hydroxystearic acids. Methyl ricinoleate and methyl 9-hydroxyoctadec-cis-12- enoate were found to give different types of product when epexidised, The former yielded the expected 1,2-epoxide, whilst the latter furnished a mixture of hydroxytetrahydrofurans (90%). Since it was evident that the second reaction involved participation by the hydroxyl function, other epoxidation Reactions of various hydroxy, oxo and acetylenic ostors were investigated. The results indicated that oxo and hydroxy functions can interact with a proformed epoxide to yield cyclic products. Finally, various unsubstiuted 1,4-opoxidos were prepared by free radical oxidations of some hydroxyostors. Both load totraacotate and metal oxido-halogon mixtures were used as oxidising agents.

Twelve heterocyclic ring compounds have been prepared and a high resolution Nuclear Magnetic Resonance study of each carried out. In particular, solvent effects and coupling constants have been studied. Some axial and equatorial shifts of methylene protons were found to be reversed compared to the predicted situation, Observed coupling constants have been found to be slightly solvent dependent. Some interesting values of coupling constants prompted a full X-ray crystal analysis of two of the compounds. This has been done, yielding bond lengths, bond angles, configuration around the phosphorus atom and conformation of the heterocyclic ring, all in the solid state. Dihedral angles for P-O-C-H systems have been calculated and an attempt has been made to correlate observed coupling constants with dihedral angles and electronegativity of substituents.

Various rules which have been used to rationalise molecular geometries are discussed. After this the results from MNDO calculations on simple carbenes, ethers and amines are presented, and these were designed to test the hypothesis that in the presence of ligands of low electronegativity lone pairs would not fulfil their stereochemical role assigned to them in the VSEPR model. Following on are MNDO calculations on cyclic molecules: the cyclopentadiene ring is planar in silylcyclopentadiene and non-planar in trimethylsilylcyclopentadiene. The calculations attempt to resolve this and in addition the nature of the fluxional exchange. The intermediates which are formed by diazepinium salts when they are protodebrominated are then discussed in the light of MNDO calculations. Single crystal x-ray work was carried out for four heterocyclic molecules. The compounds reported are: 4-phenyl-3-phenylamino-1,2,4-thiadiazolin-5-one; 5-(N-methylthiocarbamoylimino)-4-phenyl-3-phenylamino-4H-l,2,4-thiadiazoline; N,N-bis[2-(5-t-butyl-3H-1,2-dithiol-3-ylidene)ethylidene]hydrazine and N,N-dimethyl-N-[2-(5-t-butyl-3H-1,2-dithiol-3-ylidene)ethylidene]hydrazine. Details of MNDO calculations which were undertaken on molecules related to the x-ray work are then presented, and in the final chapter a discussion of the heterocyclic crystal structures appears. The first appendix reports the structure of a macrocyclic ligand, the second provides a list of publications and the third appendix is a list of the structure factors, least-squares planes and anisotropic temperature parameters for the crystal structure determinations.

The original aim of this project was to investigate the possibility of synthesising a novel polymer system combining the best features of cyanate ester resins and epoxy resins. Chapter 1 presents the historical background for both types of resin. The remaining three chapters describe attempts to achieve this aim by a) finding a cyanate ester that cures at a lower temperature than those in current commercial use (Chapter 2); b) using mixed epoxy and cyanate ester resins (Chapter 3); and c) designing chemically completely novel polymers from knowledge of the existing ones (Chapter 4). In Chapter 2 it was revealed that different cyanate esters cure at different temperatures, but that no obvious correlation exists between curing temperature and either steric or electronic effects of the ring substituents. The mixing of two dicyanate esters, one of which cures at a lower temperature than the other, leads to some reduction in the overall curing temperature required, but not sufficient to warrant further study at this stage. In Chapter 3 the usefulness of a previously proposed co-reaction between cyanate esters and epoxides was examined. Previous work in this area is full of inconsistencies that put many of the proposed conclusions in doubt. Further examination of the alleged co-reaction reveals that any such co-reaction is unpredictable, can vary significantly with reaction conditions and is in any case a minor reaction pathway by comparison with the self-reactions of the two individual reactants. It was therefore decided that further pursuit of this strategy was also likely to prove unrewarding in the short term. In Chapter 4 a study was made into the effects of including novel monomers in a standard epoxy resin system. These novel monomers had a cyanurate backbone with epoxide functionality, and can be cured at the lower temperatures of epoxy resins. Tests on the properties (mechanical, dielectric, water absorption, fracture toughness etc.) of these polymers were of a preliminary "scouting" nature, but are sufficiently promising to encourage further study.

The thermal decomposition of 2,3,4,5-tetraphenyldiazocyclopentadiene in the presence of carbene acceptors having Group V and VI elements to give 2,3,4,5-tetraphenylcyclopentadienylides has been extended and the first example of a telluronium ylide has been prepared by this method. The procedure has also been extended to other substituted diazo-cyclopentadienes and various new phosphonium, arsonium and sulphonium ylides have been prepared. The reaction of diazocyclopentadienes with triphenylphosphine to give either phosphazines or phosphonium ylides has been studied and the reasons for the difference in reactivity of these diazo-compounds has been clarified to some extent. It has been shown that for phosphazine formation both lack of steric hindrance and the absence of an electron- donating group on the cyclopentadiene ring are required. The thermal reaction of diazocyclopentadienes is assumed to proceed via a carbene-type intermediate which is then attacked by the reagent present to give an ylide. This reaction can be catalysed by the presence of copper-bronze and, in this case, can be effected either under melt conditions or in solution. The stability of the carbenoid intermediate is demonstrated by its preferential reaction with triphenylarsine rather than with benzene, which is present as the solvent. The reaction of 2,5-diphenyldiazocyclopentadiene with triphenylarsine gives a rearranged 2,4-disubstituted product. The carbene-type intermediate in this case is presumed to rearrange before reaction with the triphenylarsine. Some cyclopentadienylidene triphenylphosphazines have been shown to decompose thermally in the presence of triphenylphosphine to give the related triphenylphosphonium ylides. Diazocyclopentadienes have been found to react with either hydrochloric or hydrobromic acid to give the monochloro or monobromo cyclopentadienes. The parent, unsubstituted triphenylarsonium cyclopentadienylide has been prepared by the reaction of triphenylarsine with dibromocyclopentene and basification of the bis-arsonium salt so formed. Its properties and reactions have been studied and are found to be similar to the analogous triphenylphosphonium ylide. The salt method for the preparation of cyclopentadienylides has also been investigated. Triphenylarsine has been shown to react with 5-bromo-1,2,3-triphenylcyclopentadiene in solution at room temperature to give the hydrobromide salt of the ylide. Various sulphides also reacted with the bromo-compound to give, in most cases, unexpected products. The reactions of the cyclopentadienylides prepared with aldehydes have been investigated and the results are in line with previous findings. The cyclopentadienylides also readily undergo electrophilic substitution on the five-membered ring. The reaction proceeds preferentially at the 2(5)-position.

The reaction of specially prepared salicylaldehyde benzyl ethers with the activated alkenes, methyl acrylate or acrylonitrile, in the presence of the catalyst, DABCO, has afforded Baylis-Hillman products, which have been subjected to conjugate addition with either piperidine or benzylamine. Hydrogenolysis of these conjugate addition products in the presence of a palladium-on-carbon catalyst has been shown to afford the corresponding 3-substituted coumarins, while treatment of O-benzylated Baylis-Hillman adducts with HCl or HI afforded the corresponding 3-(halomethyl)coumarins directly, in up to 94%. The 3-(halomethyl)coumarins have also been obtained in excellent yields (up to 98%) and even more conveniently, by treating the unprotected Baylis-Hillman products with HCl in a mixture of AcOH and Ac₂O, obtained from tert-butyl acrylate and various salicylaldehydes. The generality of an established route to the synthesis of coumarins via an intramolecular Baylis-Hillman reaction, involving the use of salicylaldehyde acrylate esters in the presence of DABCO, has also been demonstrated. Reactions between the 3-(halomethyl)coumarins and various nitrogen and carbon nucleophiles have been shown to proceed with a high degree of regioselectivity at the exocyclic allylic centre to afford 3-substituted coumarin products. The electronimpact mass spectra of selected coumarin derivatives have been investigated using high-resolution and B/E linked scan data. Fragmentation pathways have been proposed and fragmentation modes associated with different coumarin-containing analogues have been compared. A series of coumarin-containing analogues of ritonavir (a clinically useful HIV-1 protease inhibitor) have been prepared and characterized. The synthetic approach has involved the coupling of coumarin derivatives with a hydroxyethylene dipeptide isostere to afford ritonavir analogues containing coumarin termini. An interactive docking procedure has been used to explore the docking of ritonavir and a coumarincontaining analogue into the enzyme active site.

The reaction of various 2-nitrobenzaldehyde derivatives with methyl vinyl ketone (MVK) in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) has afforded the Baylis-Hillman adducts in moderate to good yield. Dissolution of the catalyst in the solvent before the addition of the aldehyde was observed to improve the yield. Reduction of the Baylis-Hillman adducts was effected by catalytic hydrogenation using a 10% palladium-on- carbon catalyst in ethanol to give quinoline and quinoline-N-oxide derivatives and, in some cases, acyclic reduction products. All products were characterised using NMR and, where appropriate, HRMS methods. Selected quinoline-N-oxides were successfully converted to their corresponding quinoline derivatives using phosphorus tribromide (PBr₃) and DMF as solvent. Conjugate addition of the benzylamine and piperidine nucleophiles to the Baylis-Hillman adducts was also investigated but proved problematic, with one of the substrates undergoing a retro-Baylis-Hillman reaction to afford the aldehyde in ca. 40% yield, but seemingly only traces of the required product. Perkin-type coupling of two 2-methylquinolines with benzaldehyde was successfully effected to afford the desired styrylquinoline derivatives confirming the potential of the Baylis-Hillman approach to the construction of the analogues of known HIV-1 integrase inhibitors. Three ¹³C NMR chemical shift prediction programmes, viz., Chem Window, neural network and HOSE (hierarchically ordered spherical description of environment) methods were applied to selected representative compounds prepared in the project. The results from the three programmes correlated reasonably well with the experimental carbon-13 chemical shift data for each of the selected compounds.

Baylis-Hillman reactions of 2,2’-dithiodibenzaldehyde with the acyclic alkenes, methyl vinyl ketone (MVK) and methyl acrylate have afforded the thiochromene derivatives in moderate yields, and this approach has been extended to the use of the cyclic alkenes, 2-cyclohexenone and 2-cyclopentenone to afford the tricyclic analogues. In all cases, reduction of the disulphide link and intramolecular cyclisation occurred in situ, and a preliminary kinetic study of this reaction using the acyclic substrates MVK and methyl acrylate was undertaken with the aim of elucidating the mechanism involved. The results obtained showed that the consumption of both 2,2’-dithiodibenzaldehyde and MVK and/or methyl acrylate followed 1st-order kinetics during the initial stages of the reaction, but then deviated from 1st-order linearity. The reaction with methyl acrylate was much slower than with MVK, and the kinetic data indicates the mechanism to be more complex than anticipated. Conjugate addition reactions of methyl acrylate-derived 2-nitrobenzaldehyde Baylis-Hillman adducts with the amines, piperidine and benzylamine, afforded a range of conjugate addition products as diastereomeric mixtures in excellent yield (80-100%). Catalytic hydrogenation of the conjugate addition products using a Pd-C catalyst in ethanol, has afforded the corresponding, novel 3-amino-2-quinolone derivatives in lower yield (22-37%).The application of [superscript 13]C NMR prediction programmes to selected compounds synthesized in this study has revealed reasonable correlations between the experimental and predicted values.

Complexes formed between heterocyclic compounds and polynitro benzene derivatives have been examined spectroscopically. It has been found that many complexes, when irradiated in the region of their charge-transfer absorption emit a short-lived radiation in the region of the heterocyclic triplet. There is some evidence for a radiationless transition from an excited, bonding charge-transfer state to the excited triplet level of the heterocyclic component. / Science, Faculty of / Chemistry, Department of / Graduate