PART I A STUDY OF MECHANISTIC VARIATIONS IN THE BROMINATION AND CHLORINATION OF SOME ALKYL PHENOLS, PHENYL ETHERS AND PNENYL ESTERS. The brominations of some 2,6-dialkylphenyl acetates in nitro-methane and in acetic acid have been shown to give (a) products of substitution at both the C-3 and C-4 nuclear sites (b) products of substitution with rearrangement leading to the formation of various brominated alkylphenols and (c) uniquely in acetic acid, a product of alkyl side-chain substitution. The bromination of the corresponding benzoate derivatives realised only the products of 3- substitution. Various products of (a) substitution and (b) substitution with rearrangement were determined in the bromination of 3,4-dimethylphenyl acetate, phenyl acetate, and 2,3,5,6-tetramethylphenyl acetate. The bromination of 2,4,6-dimethylphenyl methyl ether gave only the expected product of nuclear substitution. Evidence for the likely involvement of addition-elimination sequences in the formation of products of substitution with rearrangement, has been adduced. The possible role of various other processes leading to the formation of deacylated products is discussed. The chlorination of 2,6-dimethylphenyl acetate, 2,6-dimethylphenyl benzoate and of 2,3,5,6-tetramethylphenyl acetate in both acetic acid and nitromethane gave only the expected product of nuclear substitution. The reaction of chlorine with 3,4-dimethylphenol, its acetate and methyl ether in acetic acid led to the formation of certain enone and dienone adduct derivatives which could be shown to rearrange under the conditions of the reaction to give (a) in the case of the phenol-products of substitution and (b) for the acetate and methyl ether derivatives, products of substitution with rearrangement. The structures of the intermediates were determined from their spectral properties. Various mechanisms likely to be involved in processes of chloro-deacylation and of chloro-demethylation are discussed; a consideration of certain structural features of the substrates studied led to the conclusion that chloro-deacylation and chloro-demethylation were essentially processes initiated by ortho- attack of the chlorine molecule. PART II REACTION PATHS IN THE BROMINATION OF CHOLEST-4-EN-3-ONE, CHOLEST-5-EN-3-ONE AND 3-ACETOXYCHOLESTA-3,5-DIENE The bromination of cholest-4-en-3-one can occur by a number of reaction paths. Conditions have been established under which reaction can be established as occurring in part by electrophilic attack on (a) 3-hydroxycholesta-4,6-diene (b) 3-hydroxycholesta-2,4-diene or its anion and (c) cholest-4-en-3-one; among the products can be included 2α-, 4-, 6β-, and 6α-bromocholest-4-en-3-one; 2α,6β-, 2α,6α-, and 4,6β-dibromocholest-4-en-3-one; and 2α,4,6β-tribromocholest-4-en-3-one. Unstable adducts involving the 4,5-double bond are implicated in a number of cases. The bromination of cholest-5-en-3-one is equally complicated, and can involve addition to the 5,6-double bond. Knowledge of the range of conditions and reagents through which 3-acetoxycholesta-3,5-diene is brominated to give 6β-bromocholest-4-en-3-one has been extended. Intermediate adducts involving the 5,6-double bond have been shown to be components of the reaction mixture from the acetoxydiene and bromine in acetic acid. Acid catalysed isomerisation and rearrangements of the kinetically controlled products, and dibromination, can be controlled by selective choice of the conditions of bromination and work-up. Complications associated with the reaction paths have been partly elucidated. The rates and mechanism of reversible isomerisation of 6β- to 6α-bromocholest-4-en-3-one, and of 2α,β- to 2α,6α-dibromocholest-4-en-3-one, have been studied and a proposed mechanism is outlined.

A study of the influence of several "soft donor" ligands on the cupric ion has been completed. Nitrogen and sulphur donors were chosen since these are considered to be present in "biological copper" situations, some of the conditions of which it was hoped to duplicate. Complicated reactions were found with several different types of ligands. Those containing imine functions, when complexed to copper(II), were invariably found to cleave due to the presence of external nucleophiles and it was considered that for such donors to be important in "biological" situations they would need to be shielded by bulky ligand systems. The cleavage reactions were found to have their origin in electronic mechanisms and earlier suggestions based on steric interactions were criticised. A study of sulphur donors showed that, whereas thioethers had a poor affinity for copper(II), thiols bonded very strongly. Reduction to copper(I) invariably took place, but with ligands containing TT-delocalised aromatic thiols as well as amine donors mixed-valent complexes of copper were formed. The properties of most of these complexes were unusual and one, especially, (N-(2-thiophenol) pyridine-2-aldiminato)copper(II) chloride, showed reactions and properties that suggested it may be a suitable model for cupro-enzymes. Complexes with thiol donors were termed "anomalous" in view of their complicated physical properties, whereas compounds with other donors showed "normal" behaviour. Absorption spectral studies were undertaken in an attempt to understand the electronic states of the "soft donor" complexes; at the same time an assessment of a recent scheme for assigning stereochemistries from visible spectra as applied to "soft donor" systems was possible. An X-ray structural determination of the complex μ-chloro-chlorobis(3,4-bis(3-amino-1-thiapropyl)toluene)dicopper(II) diperchlorate was undertaken, partly because of its unusual synthetic and physical characteristics. Two copper centres, one five- and the other six-co-ordinate, were found to be linked by a bridging chloride ion. The geometries about each copper ion were considerably distorted from square-pyramidal and octahedral respectively; the ligand systems also showed unusual electronic effects. Comparison with other recent structural investigations suggested that five-co-ordination is favoured by the copper ion in "soft donor" environments, and this was thought to be significant in terms of oxygen-carrying ability, where an increase in co-ordination number must occur. Several attempts to oxygenate prepared complexes were made, but no conclusive results were obtained, although several somewhat unstable crystalline products were produced.

This thesis is concerned with the synthesis and properties of fluorocarbene complexes of ruthenium and osmium. Chapter 1 is a review of transition metal CF3-complexes and illustrates a number of unusual features of these compounds which makes them suitable for modification into CF2-complexes. To place the fluorocarbene complexes into context, Chapter 2 contains a brief review of transition metal carbene complexes with the emphasis on other halocarbene species. As described in Chapter 3, CF3-complexes of ruthenium can be prepared by the addition of Hg(CF3)2 to Ru(CO)3(PPh3)2. The x-ray crystal structure of Ru(HgCF3)(CF3)(CO)2(PPh3)2 shows longer C-F bonds in the ruthenium bound CF3-group than in the mercury bound CF3-group. Reactions of fluorocarbon complexes with Lewis acids have been explored and RuCl(CF3)(CO)2(PPh3)2 reacts with BCl3 to form the known RuCl2(CO)(CCl2)(PPh3)2. Similarly OsCl(CF2H)(CO)2(PPh3)2 reacts with one equivalent of BCl3 to form initially a cationic carbene complex in which the carbene carbon atom substitutes first into a benzene ring of one PPh3-ligand and, through further reaction with BCl3, into a ring of the second PPh3-ligand. The x-ray crystal structures of OsCl(CO)2(PPh2C6H4CHCl)PPh3 and OsCl(CO)2(PPh2C6H4CH)(PPh2C6H4) are reported. RuCl(CF3)(CO)2(PPh3)2 in many of its reactions behaves as a CF2-complex precursor and Chapter 4 describes the reaction between the related RuCl(CF3)(CH3CN)(CO)(PPh3)2 and Me3SiCl to form the first isolable CF2-complex, RuCl2(CO)(CF2)(PPh3)2. RuCl2(CO)(CF2)(PPh3)2 contains an electrophilic carbene ligand and reacts rapidly with hard, oxygen and nitrogen containing nucleophiles. A comparison of the reactivity of RuCl2(CO)(CF2)(PPh3)2 and RuCl2(CO)(CCl2)(PPh3)2 is presented and reasons for the differing reactivities proposed. Chapter 5 shows that d8 CF2-complexes can be prepared directly from reaction between the more active CF3-transfer reagent, Cd(CF3)2-glyme, and various zerovalent complexes. The x-ray crystal structures of M(CO)2(CF2)(PPh3)2 M = Ru, Os and OsCl(NO)(CF2)(PPh3)2 are described and the bonding characteristics of the CF2-ligand discussed. The carbene ligand of M(CO)2(CF2)(PPh3)2 M = Ru, Os has some nucleophilic character and reacts readily with electrophiles, for example reaction with HC1 yields MCl(CF2H)(CO)2(PPh3)2 M = Ru, Os. A comparison between RuCl2(CO)(CF2)(PPh3)2 and Ru(CO)2(CF2)(PPh3)2 reveals that the reactivity of the carbene ligand is controlled by the electron density at the metal centre, i.e. is oxidation state dependent.

The synthesis and ozonolysis of the 6- and 7-substituted 12-hydroxypodocarpatrienes (26), (86), (90), and (98), as a possible route for the synthesis of drimanes from 12-hydroxypodocarpa-8,11,13-trien-19-oic acid (podocarpic acid) (9) has been investigated. Modification of the aromatic ring of (9) has given 11- and l4-hydroxypodocarpatrienes which were ozonised to give the congeners (31), (34), and (36) of the naturally occurring drimanes confertifolin (6), isodrimenin (7), and winterin (8). The oxidation of a 12,13-dihydroxypodocarpatriene (37) and its dimethyl ether (38) have also been investigated. Routes for the conversion of the enone (45) and oxime (230), derived from the ozonolysis products of methyl podocarpate (10), to drimanes have also been investigated.

The crystal and molecular structures of five binary complexes between transition-metal ions and 5'-ribonucleotides have been determined by X-ray crystallographic means. All data were collected by diffractometry and the structures refined by the full-matrix least-squares method. The complex Ni (C10H11N4O8P) (H2O) 5. 2H2O crystallizes in the orthorhombic space group P212121 with four molecules in a unit cell of dimensions a = 6.853(1), b = 10.812(2), c = 25.925 (3) Å. Refinement converged with R and Rw values of 0.054 and 0.059 respectively. The structure is monomeric with nickel octahedrally co-ordinated to N(7) of the base and to five water molecules. The monomer is stabilized by three intramolecular hydrogen bonds involving co-ordinated water molecules, phosphate oxygens, and the exocyclic O (6) atom of the base. The complex of empirical formula CO (C9H12N3O8P) (H2O) crystallizes in the monoclinic space group P21 with two formula units in a unit cell of dimensions a = 10.002(1), b = 7.459(2), c = 9.429(1) Å, β = 96.58(11°. The final R and Rw values were 0.073 and 0.063 respectively. The structure is polymeric in two dimensions. The cobalt is in a distorted tetrahedral environment, being co-ordinated to N (3) of the base, two oxygens of two different phosphate groups, and a water molecule. There is a weak interaction between the metal ion and the exocyclic 0 (2) atom of the base. The complex of empirical formula Cd(C9H12N3O8P) (H2O) .H2O crystallizes in the orthorhombic space group P212121 with four formula units in a unit cell of dimensions A = 5.294(1), b = 17.070(1), c = 16.371(1) Å. Final R and Rw values of 0.038 and 0.045 respectively were obtained. The structure is polymeric in three dimensions. The cadmium is in a distorted square-pyramidal environment, being co-ordinated to N (3) of the base, three oxygen atoms of three phosphate groups, and a water molecule, There is a weak interaction between the metal ion and the O (2) atom of the base. The complex of empirical formula Cu (C10H11N4O8P). H2O crystallizes in the orthorhombic space group P212121 with four formula units in a unit cell of dimensions a = 17.412 (3), b = 15.772(3), c = 5.077(1) Å. Refinement returned R and Rw values of 0.083 and 0.061 respectively. The structure is polymeric in one dimension. The copper is co-ordinated to N (7) of the base and three oxygens of three phosphate groups. Weak axial bonds to a further phosphate oxygen and the exocyclic O(6) atom of the base complete the pseudo octahedral co-ordination geometry (4 + 1 + 1). The complex of empirical formula Cu3(C10H12N5O8P)3- (H2O)8.4H2O crystallizes in the orthorhombic space group P21212 with four formula units in a unit cell of dimensions a = 20.813(4), b = 23.356(3), c = 11.392(1) Å. The final R and Rw values were 0.11 and 0.09 respectively. The structure consists of irregular helical chains. Each of the tree independent coppers is in a square-pyramidal environment, with N (7) of the bases occupying the axial positions. Whereas the square-planes of two of the coppers each consists of one phosphate oxygen and three water molecules, that of the third consists of two oxygens from two phosphates, and two water molecules. The structure is stabilized by intramolecular hydrogen bonds involving co-ordinated water molecules, phosphate oxygens, and the exocyclic O(6) atoms of the bases. A system has been devised for classifying the structures of binary metal/ribonucleotide complexes.

The reaction of chloranil with various substituted phenols under basic conditions has been studied. It has been found that the yields of benzobisbenzofuranquinonoid (1) derivatives are greater when after initial nucleophilic attack on the ketoenoid system by the oxygen atom of the phenoxide ion, the carbon atom ortho to the vinyl-aryl ether linkage is activated towards further nucleophilic attack by the presence of a suitably orientated electron releasing substituent. The other products of the reaction mixture have been isolated and characterised, and the spectral data discussed for the derivatives of 2,3-diethoxydi-benzofuran-1,4-quinone which were obtained in this way. The mass spectra of benzobisbenzofuranquinones and the corresponding quinol acetates have been examined. Facile loss methyl radicals from aromatic methoxy groups and ketene from the acetate derivatives was observed. Decarbonylation and fragmentation involving the heterocyclic ring system resulted in peaks of only minor intensity. The ready loss of substituents as described above is explained by the resulting formation of resonance stabilized quinonoid ions. Some chemical constituents of Peniophora gigantea have been isolated and characterised. 2',3',6'-Trimethoxy-p-terphenyl (25) was obtained which represents the first methoxylated p-terphenyl isolated from a fungus. Also obtained was a mixture comprising two compounds, C30H48 and C30H50. On mass spectral grounds these are proposed to be the pentacyclic triterpenes, lupa-15,19(22)-diene (33) and lup-19(22)-ene (34) respectively. 14,15-Epoxy-2-ketomanoyl oxide (44) has been microbiologically hydroxylated by Calonectria decora to form 1β,7α-dihydroxy-14,15-epoxy-2-ketomanoyl oxide (45). The positions of the hydroxyl groups were determined from the peaks arising from fragmentations in rings A and B in the mass spectrum. Strong intramolecular hydrogen bonding observed in the i.r. spectrum supported the equatorial conformation of the hydroxy group at Cl whilst the facile loss of water upon electron impact and the presence of a signal corresponding to an equatorial carbinol proton in the n.m.r. infers that at C7 is axial. Finally, it has been proposed that the structures of the blue pigments, corticins A and B, isolated from Corticium caeruleum by Dean are 2,6,9-trihydroxy-3,8,12-trimethoxybenzo[1,2-b:4,5-b']bisbenzofuran and 2,3,8,9-tetramethoxybenzo[1,2-b:4,5-b']bisbenzofuran-6,12-dione respectively. The n.m.r. spectrum of corticin A triacetate and comparison of the mass spectra of these compounds and those authentic samples prepared synthetically support these structures. Erratum p105 para 1: Should read (R=Ac).

The metal ion catalysed aquation of the trisoxalatochromium(III) ion has been studied in the presence and absence of added electrolytes with emphasis on the copper(II) ion catalysed aquation. The interpretation of the observed catalytic effects of the copper(II) ion, has been attempted in terms of ion association. The proposed scheme, for the aquation, involves metallation of the CrOX33- species to account for the promoting effect of the copper(II) ions. The specific rates of aquation and formation constants of the various species formed between the copper(II) ion and the CrOX33- ion have been obtained using curve fitting techniques. Further, the dependence of the formation constants and the specific rates of aquation on temperature has been shown to yield realistic thermodynamic and activation parameters for the proposed model. Increasing the pH was found to have an accelerating affect on the aquation of the trisoxalatochromium(III) ion at constant copper ion concentration. This has been discussed, using ion association, in terms of catalysis of the aquation reaction by hydrolysis products of the copper(II) ion, in particular the CuOH+ ion. The catalysed and uncatalysed isomeristion of the bisoxalatochromium(III) ion has been investigated in the presence and absence of various electrolytes and the kinetic data has been rationalized in terms of an ion association model. It has also been proposed, from comparisons of studies on the copper(II) ion catalyes aquation and racemisation of the trisoxalatochromium(III) ion, that a copper(II) ion associates with the CrOX33- ion through three carboxyl oxygen atoms, one from each oxalate group to form a monometallated species. Further comparison of these studies has led us to postulate, in the aquation, that a second copper(II) ion, proposed to associate with the monometallated species, associates with two carbonyl oxygen atoms of one of the oxalate groups of the CrOX33- ion. This, and the comparison of the specific rates of aquation of the monometallated and bimetallated species, led us to the conclusion that aquation occurs by a rapid one ended dissociation of an oxalate ligand followed by a rate determining loss of the oxalate group. A number of other results of relevance to the substitution and rearrangement reactions of chromium(III)-oxalate complexes, have also been included.

The triterpene precursor, 12-methoxypodocarpa-8,11,13-trien-3-one (46)*, has been prepared via the 3a-alcohol (48) formed by opening of the 3a,4a-epoxide (13) with lithium diethylamide. The total synthesis of the methyl ether of the natural product, (+)-hinokione, has been achieved by a similar sequence involving prior addition of an isopropyl group at C 13 of the methoxy acid (4) ( Scheme 1 ) . A study of the boron trifluoride rearrangements of the three epoxides (12), (13), and (14), has been made using benzene and dimethyl sulphoxide as solvents. The stereochemistry of a series of 6-bromo-7-oxo derivatives of diterpenoids possessing an aromatic ring-C is discussed and the assignment of configuration of the 6-bromo substituents from n.m.r. and n.0.e. data is examined. A preliminary investigation into the possibility of preparing a 9a-methyl steroidal analogue by addition of a cyclopentatone ring across positions 3 and 4 of ring-A of the podocarpic system is also reported.

The radiation chemistry of cysteamine and of cysteamine-S- phosphoric acid in oxygen-free and oxygenated solution has been studied at acidic and near-neutral pH. In oxygen-free solution and in oxygenated solution above pH 5 the mechanism of cysteamine radiolysis appears similar to that of cysteine. From measurements of the dependence of G(-RSH), G(RSSR), and G(H2O2) upon pH and cysteamine concentration, suggestions regarding the stoichiometry of the chain reaction occurring at higher pH and the mechanistic implications have been made. The dependence of the rate of oxidation of cysteamine by hydrogen peroxide upon pH has been studied, second-order kinetics being observed over the pH range 6.5 to 10.9, and the rate has been found to depend in a simple manner upon ionisation of the thiol. The rate constant of the reaction of aquated electrons with cysteamine-S-phosphoric acid has been measured as about 5 x 109 M-1 sec-1 by competition with cysteamine at pH 4.2, and measurements have indicated the formation of orthophosphate, inorganic phosphorothioate, and an aldehyde as products of the reaction of hydroxyl radicals with cysteamine-S-phosphoric acid at pH 8.6.

This thesis is concerned with the solvent extraction of ternary complexes of cobalt(II) and nickel(II). In a preliminary survey, the extraction of nickel(II) by a variety of systems containing carboxylic acids in the presence of 1,2-diaminoethanes was investigated in order to determine the extent to which these complexes extract into different solvents. The aromatic carboxylic acids studied were benzoic, p-toluic, phenylacetic, cinnamic, anthranilic and salicylic acid while the aliphatic acids studied were butanoic, hexanoic, octanoic, decanoic, dodecanoic, 2-bromohexanoic, 2-bromöoctanoic, chloroacetic and 2-chloropropanoic acid. The 1,2-diaminoethane used in conjunction with these acids were ethylenediamine, 1,2-diaminopropane, 1,2-diamino-2-methylpropane, 1,2-diaminocyclohexane, N,N'-diaminoethylenediamine, N,N-diaminoethylenediamine and N,N,N',N'-tetramethylethylenediamine. Of the aromatic ternary systems studied, salicylic acid with either 1,2-diaminocyclohexane or a N-substituted diamine were found to give the highest extraction. These were then investigated in depth to determine the number and nature of the extracted species. Unlike the aromatic acids, the longer chain n-carboxylic acids are capable of quantitative extraction in the absence of a diamine. During the course of this part of the project it therefore became necessary to investigate the extraction of nickel(II) both by the acids alone and by the acids in combination with a diamine. It was found that the inclusion of a diamine had little influence on the pH of extraction. Finally, the extraction of cobalt(II) by combination of salicylic acid and N,N'-dimethylethylenediamine and N,N,N',N'-tetramethylethylenediamine and by decanoic acid alone were investigated. The behaviour of cobalt(II) and nickel(II) in equivalent systems were compared in order to assess the degree of separation obtainable.