The study is more specifically concerned with the reactions of aromatic sulfonic anhydrides. The study was carried out in order to gain more knowledge on the reactions and behaviour of aromatic sulfonic anhydrides, and the role they play in the formation of sulfones in the industrial sulfonation process. An introduction to industrial sulfonation as used in the detergent industry is included. It has been proposed that sulfones are formed in the sulfonation process, by reaction of sulfonic anhydrides with alkylbenzene (starting material). An initial study of the reactions of <i>p-</i>toluenesulfonic anhydride with toluene using different catalysts was carried out, providing background knowledge for the more detailed studies that followed. A number of competition reactions were completed, investigating the influence of substituents in a series of arenes on the relative rates of reaction of <i>p-</i>toluenesulfonic anhydride. Studies were carried out using nitromethane as solvent and AlCl₃ as catalyst. Included in the study is a review of the synthesis of diaryl sulfones, and the synthesis of a number of unsymmetrical sulfones. A new route to di-tolyl sulfone was identified from <i>intra</i>molecular reaction of <i>p-</i>toluenesulfonic anhydride catalysed by AlCl₃. The relative rate of formation of sulfones via this route compared to Friedel-Crafts type sulfonylation reactions and was studied. The relative rates were found to be very low. The synthesis of a series of aromatic sulfonic anhydrides was carried out using direct sulfonation with SO₃. The sulfonic anhydrides were then used to investigate the effect of substituents on the rates of reaction of substituted benzenesulfonic anhydrides reacting with toluene. The reactions were carried out in nitromethane using AlCl₃ as the catalyst.

It is well established that certain anthracene-9,10-diones such as Mitoxantrone (24b) and Amentantrone (24a) are potent anticancer drugs but suffer from the disadvantage that they are also cardiotoxic. Few suffer containing anthracene-9,10-diones have been researched for their biological activity, and the current studies were aimed to synthesise a series of anthracene-9,10-dione derivatives containing both as substituted and as part of the ring system in an endeavour to conserve their anticancer activity but reduce their cardiotoxicity. A series of twenty four anthracene-9,10-diones were synthesized, seventeen of which have not been previously reported. Twelve of those derivatives contained suffer and include the 1,4-bis(amino)-5,8-bis(sulfanyl)anthracene-9,10-diones, which were synthesised from the amination of 2,3-dihydro-9,10-dihydroxy-5,8-dichloroanthracene-1,4-dione with selected amines followed by the subsequent reaction with thiolates. A ring derivative was also synthesised, 7-(aminoalkyl)-14H-naptho[2,3-a]phenothiazine-8,13-dione from the reaction of l-(alkylamino)-4-hydroxyanthracene-9,10-dione and 2-aminothiophenol with boric acid. Semi-empirical molecular orbital methods were employed to model the anthracene-9,10-dione derivatives. To establish the most appropriate method for calculation a set of well known anthracene-9,10-diones were selected from the Cambridge crystallographic database and compared to computational data obtained using the AMI, PM3 and MNDO methods. All three methods give reasonable structures by comparison with the experimental data, when suitable constraints were applied to the optimisations. On balance the AMI method was selected to model the synthesized anthracene-9,10-dione derivatives in this work. AMI produced more accurate results for the nitrogen-carbon and oxygen carbon bond lengths. It also required no constraints when the simple suffer derivatives were optimised. A series of reference calculations at the ab initio 6-3IG** level were also carried out, to check veracity of the of the results obtained form the AMI method. The computational data highlighted two factors that may be significant in the biological activity of anthracene-9,10-diones. It appears that molecules that are biologically active contain alkylamino groups at the 1-and 4- position and have ionization potentials in the range of 7.7-7.9 eV. The computational data of the derivatives synthesized in this work shows many of them meet this criteria and therefore may possess anti-cancer activity, though this aspect of the research was not addressed in the current studies.

No description available.

Reaction of the beta-ketoesters namely methyl (and ethyl) 3,3a-dihydro-3a-hydroxy-2-oxo-2H-cyclopenta(l)phenantherene-1-carboxylate (primary-condensate), of methyl (and ethyl) 2,3-dihydro-1-hydroxy-2-oxo-1H-cyclopenta(l)phenanthrene-1-carboxylate (iso-compound), and of methyl (and ethyl) 2,3-dihydro-1-oxo-1H-cyclopenta(l)phenanthrene-1-carboxylate (hydriodic acid reduced product) with ammonia, hydrazine, acetylhydrazine, and ethyl carbazate are investigated and several novel compounds are described. Reactions of the iso-compound with hydrazine, acetylhydrazine, and ethyl carbazate give the expected hydrazones and a second molecular proportion of hydrazine also reacts to afford the hydrazide-hydrazone. Reaction with ammonia includes rearrangement and leads to 3,3a-dihydro-3-hydroxy-2-oxo-2H-cyclopenta-(1)phenanthrene-1-carboxamide. The hydriodic acid reduced product reacts analogously with acetylhydrazine, and ethyl carbazate (to give hydrazones) but with ammonia the pentacyclic ring is opened and the half ester-half amide (-half hydrazide in the case of hydrazine) corresponding to 9,10-phenanthrenediacetic acid is obtained. The primary-condensate forms hydrazones with acetylhydrazine, and ethyl carbazate in acidified methanol, but isomerisation of the olefinic bond occurs and a methoxy group is incorporated in the reaction products methyl 2-acetylhydrazono-2,3-dihydro-1-methoxy-2-oxo-1H-cyclopenta(1)phenanthrene-1-carboxylate and methyl 2-ethoxycarbonylhydrazono-2,3-dihydro-l-methoxy-1H-cyclopenta(I)phenanthrene-1-carboxylate, Hydrazine participates in a Michael type addition reaction and a heterocyclic product 1, 2, 3, 4, 4a, 12b-hexahydro-12b-acetic acid ethyl ester -4a-hydroxy-3-oxo-1,2-diazatriphenylene is formed. This diazatriphenylene gives the acetyl derivative and undergoes thermal elimination of ethyl acetate and water to form a dibenzocinnolone namely 2,3-dihydro-3-oxo-1,2-diazatriphenylene, A Michael type addition occurs between the primary-condensate and ammonia, leading to 9-amino-9-carbamoylmethyl-10(9H)phe-nanthryleneacetamide.

No description available.

No description available.

This thesis investigates the design, synthesis and binding properties of novel calix[4]arene based heteroditopic receptors and interlocked structures. <strong>Chapter 1</strong> introduces the field of supramolecular chemistry. The areas of host-guest chemistry and self-assembly are introduced, with a particular emphasis on strategies for designing receptors for ions and synthesising interlocked structures. <strong>Chapter 2</strong> details the synthesis and binding properties of calix[4]arene based ion-pair receptors. These receptors show cooperative AND ion-pair recognition, where the receptors show little affinity for the 'free' ions but enhanced binding of the ion-pair. The extension of this work to the synthesis of their cryptand analogues is also explored. Finally, efforts towards preparing calix[4]arene based zinc Schiff base anion receptors is reported. <strong>Chapter 3</strong> describes the synthesis of the first calix[4]arene based rotaxane host systems for anions using a new ion-pair templation strategy. NMR spectroscopy and X-ray crystallography demonstrate the successful interlocking of the macrocycle and axle components in the rotaxane structures. Anion binding studies reveal the importance of preorganisation of the host binding cavity on anion binding. The synthesis of rotaxanes using a stoppering approach and catenanes using a ring closing metathesis clipping strategy is also investigated. <strong>Chapter 4</strong> investigates the use of copper catalysed coupling reactions, such as Eglinton coupling and click chemistry, in the preparation of interlocked structures. The synthesis and anion binding properties of a novel catenane are described. Efforts towards the first anion templated synthesis of rotaxanes by slippage and kinetic slippage studies are also reported. <strong>Chapter 5</strong> reports the experimental procedures and characterisation details of the compounds synthesised in this thesis. <strong>Chapter 6</strong> gives supplementary information about titration protocols, kinetic experiments and X-ray crystal structures.

No description available.

Cholecystokinin (CCK) is a 33 amino acid peptide which acts as a digestive hormone in peripheral tissues and functions as a neurotransmitter, widely distributed throughout the brain and central nervous system. Two types of CCK receptors exist, those primanly located in peripheral tissues, CCK, receptors, and those primarily located in the brain and central nervous system, CCK2 receptors. Tetronothiodin 1 is a recently discovered potent CCK2 receptor antagonist Isolated from the culture Streptomyces sp NR0489 It consists of an oxaspirobicyclic unit and a functionalized tetrahydrothiophene moiety, linked by a macrocyclic framework. This thesis details the first studies towards the synthesis of the substituted tetrahydrothiophene moiety of tetronothiodm Four different approaches were attempted; a route in which the key step proceeded via a nitro-aldol reaction, a dicarboxylic acid cyclisation route, cyclisations of substituted butadlenes, and finally 1,3-dlpolar cycloaddition reactions of novel thiocarbonyl yhdes and dipolarophiles.

This thesis describes a modular diversity-oriented synthesis approach, which exploited a ‘build→couple→couple→pair’ reaction sequence, to generate a library of natural product-like macrocycles. The use of a fluorous−tagged building block allowed the expedient purification of the substrates between the ‘couple→couple’ stages of the sequence. Building blocks were iteratively linked onto the fluorous tagged building block to give linear substrates bearing two terminal alkenes. These substrates were subjected to ring-closing metathesis to yield diverse macrocyclic scaffolds. Subsequent, deprotection and diversification steps yielded natural product-like macrocycles. Using this approach, over 13 macrocyclic scaffolds were prepared which, in turn, after diversification, yielded over 55 diverse macrocycles, each with unique scaffolds. In addition this project also saw the synthesis of the corresponding linear compounds. Chapter 1 discusses the importance of macrocycles in nature, how this class of molecules have been poorly explored and methods that have been used to explore chemical space. Chapter 2 describes the synthesis of the building blocks and the proposed method to prepare the library of diverse macrocycles. Chapter 3 explores the reactivity of the building blocks and developments required to improve the efficiency of the library synthesis. Chapter 4 describes the final library synthesis from building blocks to final compounds. This work aims to prepare compounds with potential bioactivity; however, the biological evaluation of the compounds is beyond the remit of the study.