Rate and equilibrium constants for chemical systems involving two- stage processes in aqueous media have been measured and analysed. The major part of this thesis discusses the effect of added organic cosolvents or salts on the reaction kinetics of transition metal complexes in solution. The thesis also includes an analysis of published rate and equilibrium data in order to derive thermodynamic activation and reaction parameters. The oxidation of iodide by the 12-tungstocobaltate(III) anion by an outer-sphere process, of iron (II) by the chloropentammine cobalt (III) cation by an inner-sphere process, and the mercury(II)-catalysed aquation of seme rhodium (III) and chramium(III) chloro-ccmplexes have been studied in binary aqueous mixtures. The aquation of the N,N,N",N" tetraethyldiethylenetriamine-chloro palladium (II) cation and the reaction of cis-bis-(4-cyanopyridine) dichloro platinum (II) with thiourea have been studied in aqueous salt solutions. For the above reactions, it has been possible to dissect the effects of solvent variation or added salt on the rate constants into their initial state and transition state contributions. This has been done by estimating the change in the chanical potential of the initial state from appropriate solubility measurements. The results obtained are discussed in terms of the solvation characteristics of the species involved. The reactions of two anionic iron(II) tris-diimine ccmplexes with hydroxide and cyanide in aqueous media have been studied. Kinetic and spectroscopic evidence for intermediates is reported. With regard to computer-based studies, the tamperature dependence of the rate constant for solvolysis of t-butyl chloride in binary aqueous mixtures has been analysed in terms of the two-stage Albery-Robinson mechanism. The derived enthalpies and heat capacities of activation are examined. The temperature dependence of acid dissociation constants has been analysed using the Gurney equation and the two-stage Eigen mechanism.

The thermolysis and photolysis of a number of cyclic sulphones has been studied, with a view to developing these reactions as possible synthetic processes. Some substituted dihydronaphthothiophene sulphones were prepared and those containing a pent-4-ene sidechain successfully underwent intramolecular Diels-Alder cyclisations. 2-Phenylthietan was prepared by a new route and the preparation and pyrolysis of some 2-phenylthietan 1,1-dioxide derivatives was studied. Some 2-(alkan-1-o1) 3,3-dimethylthietan sulphones were prepared and the dehydration of these, with a view to preparing alk-1-ene derivatives, was studied. Phosphorus oxychloride in pyridine was the most successful of those reagents tried. The alk-1-ene derivatives were shown to have unusual thermal behaviour, when they ring-expanded to their respective sultines under flash vacuum thermolysis conditions. The use of 3,3-dimethylthietan 1,1-dioxide as a starting material for a new route to chrysanthemates has been studied. Methyl-trans-chrysanthemate was eventually identified as one of the products after a 4-step synthesis from this sulphone. A number of cyclic sulphides were prepared using phase transfer catalysis.

An evaluation is made of ethyl (diethoxyphosphino)-acetate as a common intermediate for the synthesis of various phosphinoline and isophosphinoline systems. Two syntheses of 2-hydroxy-l,2,3,4-tetrahydroisophosphinoline 2,4-dioxide from [special character omitted]-bromotoluene and 2-(bromomethyl)benzoic acid are described. Attempts to induce cyclisation of 3-(hydroxyphenyl-phosphinyl)propanoic acid with polyphosphoric acid, and the corresponding bis-acid chloride with aluminium chloride, prove unsuccessful, due to deactivation of the ring towards electrophilic attack. Three 1-substituted-1,2-dihydrophosphinoline 1-oxides are synthesised, which when photolysed in a nucleophilic solvent give the three double-bond isomers of l-(2- phosphorylphenyl)propene derivatives. This is rationalised in terms of solvent trapping of a phospha-quinoidal intermediate, obtained by electrocyclic ring-opening of the phosphinoline. The Lewis acid catalysed cyclisation of 2- biphenylylphosphorodichloridothioate to 6-chloro-6H-dibenz (c,e)(1,2)oxaphosphorin 6-sulphide is investigated under a variety of conditions, leading to the identification of the optimum procedure as a neat reaction at 200 C for Ih, in the presence of 0.1 equivalent of aluminium chloride. Esterification of the resultant heterocycle, followed by photolysis of a methanolic solution gives three unidentified products. The complete absence of any photolytic reaction of the analogous 9,10-dihydro-9-methoxyphosphaphen anthrene leads to the conclusion that reaction is not by a concerted, electrocyclic pathway. t-Butylamine is found to selectively monodemethylate phosphorus esters in the presence of carboxylate esters in a side-chain. Marked preference for removal of a methyl over benzyl or higher alkyl groups is demonstrated by reactions with mixed esters. Treatment of dimethyl 2-bromoethylphosphonate with t-butylamine, however, gives dimethyl vinylphosphonate, while dimethyl 3-bromopropyl-phosphonate undergoes nucleophilic substitution. The mildness of conditions required to demethylate a phosphorus ester leads to the suggestion of using methyl as phosphate protecting-group in nucleotide synthesis.

No description available.

The phosphonamidic chlorides ArP(0)(Cl)NMe2 and ArP(0)(Cl)NHBut (Ar = phenyl, o-tolyl, mesityl, 2,4,6-triisopropylphenyl) have been synthesised and characterised. Both types react cleanly with t-butylamine, isopropylamine, and other primary amines in aprotic solvents to give the expected phosphonic diamides, but from the results of rate studies (steric retardation or acceleration) and competitive experiments (high or low discrimination between competing amines) it is clear that the mechanisms differ. For ArP(0)(Cl)NMe2 reaction is always associative SN2(P) but base-induced dissociative elimination-addition processes are important for ArP(0)(Cl )NHBut, especially at higher concentrations of amine. These give rise to reactive metaphosphon- imidate intermediates that display little discrimination and phosphorylate even such poor nucleophiles as diisopropylamine and t-butanol. The results of stereochemical studies with optically active PhP(0)(Cl)NHBut (partially resolved) and ButP(0)(Cl)NHCHMePh (pure diastereoisomers) confirm that while elimination-addition usually proceeds by a preassociation mechanism, the planar metaphosphonimidate intermediate is produced as a free species at low amine concentrations. Part B Reactivity of Phosphinoyl Aminimides The principal photochemical reaction of the phosphinoyl aminimide Ph2P(0)N--+NMe3 in dimethyl sulphoxide or methanol is rearrangement to the aminal Ph2P(0)NHCH2NMe2 which subsequently decomposes to give Ph2P(0)NH2. The phosphinoyl hydrazinium salt Ph2P(0)NMe+NMe3 undergoes a formally similar rearrangement with base to give the aminal Ph2p(0)NMeCH2NMe2. The corresponding benzoyl substrates undergo comparable reactions. To explore the scope and mechanism of these aminal forming rearrangements, the substrates where one or more of the N-methyl groups is replaced by an ethyl group have been synthesised and their reactions examined. For the base-induced 1,2 sigmatropic rearrangement of the hydrazinium salts, insertion into a methyl group, with formation of a methylene aminal, is preferred whereas for the photochemical rearrangement, insertion into an ethyl group, with formation of an ethylidene aminal, is preferred. In the light of these results the mechanisms of the rearrangement are discussed.

No description available.

In a series of synthetic studies towards the taxane group of natural products, we have developed a synthesis of 2-lithio-1, 3-butadiene from 3-buten-2-one-2',4',6'-tri-iso-propylbenzenesulphonyl hydrazone using the Shapiro reaction. The reaction of 2-lithio-1,3-butadiene with a series of aldehydes and other electrophiles was then studied. In contrast to the corresponding Grignard, the major isolated products from the reaction of 2-lithio-1,3-butadiene with aliphatic aldehydes were 2-substituted dienyl alcohols, whilst with aromatic and some a,b-unsaturated aldehydes varying amounts of the regioisomeric allenic alcohols were also formed. Two of the dienyl alcohols were shown to undergo the amide acetal Claisen rearrangement. 2-Lithio-1,3- butadiene was then used in an attempt to synthesise a taxane model compound. In an alternative approach to a different taxane model compound, we developed a stereocontrolled route to a trisubstituted cyclohexane derivative. The cyclohexane was then converted into a Diels-Alder substrate using a stepwise diene synthesis which employed silicon as a control element. Lewis acid catalysed cyclisation of the Diels-Alder substrate gave stereospecifically a tricyclo [9. 3.1.03,8] pentadecane taxane model compound, which had the same relative configuration about its chiral centres as the taxane natural products. Attempts were then made to extend the synthesis to incorporate the C-14-gem-dimethyl groups.

No description available.

In the early 1990s, enzymatic polymerization studies on an unactivated adipic acid (A) / butane-1,4-diol (B) system in anhydrous organic media suggested that in solvent-free conditions a step-growth mechanism operates involving the effective sequential addition of an 'AB' unit. Subsequent optimisation work led to development of an efficient solvent-free process using lipase B from Candida antarctica as catalyst at temperatures of around 60°C, producing polyesters with unique properties compared to their counterparts synthesised using conventional high temperature processes. The present work describes the synthesis and unambiguous characterisation by GPC of a series of key oligomers formed during the enzymatic process, enabling a clearer understanding of the polymer assembly route. Use of semi-quantitative methods to compare the reactivity of these oligomeric species along the proposed enzymatic reaction pathway further clarifies the polymerisation mechanism and explains the differences between the final products of conventional and enzymatic polymerisations. Comparison of polyesterifications performed in solvent-free and toluene-based media reveals a change in lipase specificity from a simple esterification to an esterification! transesterification mode. Addition of a variety of compounds to the enzymatic polyesterification process led to an enhancement of lipase activity and sometimes enabled recovery of lipase from the system with no loss in activity. Explanations for these effects are proffered with supporting experimental evidence. A variety of studies on the effect of changing the polarity of reaction medium have been performed, an apparent trend of decreasing lipase activity with increasing solvent polarity having been noted. The low temperatures employed in the enzymatic polymerisations enable access to a range of polyesters precluded by harsh conventional conditions. Studies on the polymerisation of novel polymers possessing unsaturation, labile groups such as epoxides and chirality are detailed, giving an indication of one of the potential advantages of an enzymatic system. In addition, studies on the more conventional uses of enzymes in organic synthesis are included, where an apparent switch in lipase stereoselectivity occurs, in line with the findings of other workers in the field.

The exploration of possible routes towards the synthesis of alkylated oxathiane and oxathianone systems are presented in this research thesis. The ultimate objective of these studies was the synthesis of dihydrofurans and dihydrofuranones via the Ramberg-Backlund rearrangement. Initially, studies were carried out on the alkylation of the cyclic ether, 1,4-oxathiane S.S-dioxide. It was during investigations with the readily available cyclic ether that several ring-opened novel compounds were synthesised. Subsequently, an alkylated epoxide was prepared and two pathways from this epoxide to the synthesis of an alkylated 1,4-oxathiane S.S-dioxide were examined. The first involved an examination influencing the regioselectivity of the epoxide and consequent ring-opening to yield the corresponding hydroxy sulfide. Further studies explored the possibility of either ring closure of the sulfide followed by oxidation to the sulfone or oxidation to the sulfone followed by cyclization. However, these routes were to prove unsuccessful. The second pathway involved the use of a readily available epoxide for the afore mentioned cyclizationloxidations. The preparation of oxathianones was the second part of these studies and involved the synthesis of the lactone 1,4-oxathian-3-one S.S-dioxide again with the aim of alkylating this sulfone for use as the precursor required in the Ramberg- Backlund reaction. Investigations included acid/alcohol cyclizations and catalytic oligomerizationldepolymerization methods. Another sequence of reactions available to us was the direct oxidation of a hydroxy diol and/or lactol oxidation to the lactone. However, it was during this research towards the synthesis of the sulfone lactone that four unexpected and novel compounds were synthesised. The latter part of our studies took us to the preparation of an alkylated oxotetrahydrothiophene S.S-dioxide with the intention of performing the Baeyer- Villiger oxidation to the requisite lactone. However, success came with the double alkylation of the system rather than the mono-alkylation.