Part I: The Methyl trans-Methyleneoctadecanoates. The sixteen isomeric methyl trans-methyleneoctadecanoates have been synthesised from the corresponding methyl trans alkenoates by the Simmons-Smith reaction, and some of their physical properties examined. Only one isomer (methyl trans-9,10-methyleneoctadecanoates) has previously been reported. The gas liquid chromatographic data are interesting in that on both polar and non-polar columns the cis and trans isomers are well separated. The methyl trans-methyleneoctadecanoates show diagnostic nuclear magnetic resonance signals around 9.8 to 9.6r. The 2,3-; 3,4-; 5,6-; 16,17-; and 17,18- isomers differ from one another, but the remainder are very similar to each other. The mass spectra of some of the isomers were examined but they do not provide much useful information. Our data, along with that previously reported for the corresponding cis isomers (see ref 21), should assist in the recognition of these compounds. For complete identification, however it may be necessary, in addition to examine the mass spectrum of the hydrogenated ester. Part II: Halogenation of Unsaturated Long-chain Hydroxy Compounds. Neighbouring group participation in unsaturated hydroxy compounds occurring during reaction at the unsaturated centre has already been observed in appropriate long-chain compounds during various oxidation reactions and during oxymercuration. The halogenation of certain hydroxyalkenoates, octadecenols and octadecenoic acids has now been examined with a view to finding out if neighbouring group participation occurs during these reactions. The halogenating agents employed were iodine monochloride, bromine and chlorine giving rise to the electrophilic reagents I+, Br+ and C1+ respectively. In most reactions only the simple addition products (vic-dihalides) were observed and these were converted into ene-halides by dehydro- halogenation since the latter have been reported previously in only a few cases. The hydroxyl group was involved in halogenation in only a few instances - mainly in iodochlorination - to give substituted tetrahydrofurans (1,4-epoxides). Lactones were obtained during the halogenation of some unsaturated acids. Attempts to obtain N-heterocyclic compounds by the reaction of long-chain amines were less successful but the conversion of methyl ricinoleate to methyl 12-amino-oleate was satisfactorily achieved.

The pK values for xanthone protonation in the S0, S1 and T1 states have been determined by direct measurement and by Forster Cycle calculation. Both methods for determining pK give the order for xanthone of pK(T1) > pK(S1) > pK(S0). A study of benzophenones and acetophenones showed this pK order to be a common one for aromatic carbonyl compounds. The pK order for these compounds has been explained in terms of the type of transitions involved and the S1-T1 splitting of these transitions. In the case of substituted aromatic carbonyl compounds the pK order reflects the effect of substitution on the lowest S0-S1 and transitions. Results are also presented on the effect of inorganic anions solvenli and temperature on xanthone fluorescence. Spectral details are reported for several xanthones, benzophenones, acetophenones, and anthraquinones.

A study of the historical and more recent work on rotation about carbon-carbon and carbon-nitrogen bonds was the basis for the further investigation of three series of compounds: 1. 2,2'-disubstituted biphenyls, 2. N-benzyl-N-tosyl substituted anilines, 3. substituted quinone-anils. From this work it was established that, in certain compounds, the free energy (ΔG*) for hindered rotation cannot be discussed solely in steric terms but that electronic influences should also be considered. In. the substituted aniline series, it was concluded that a Hammett type correlation existed between the electronegativity of the substituents para to the amino group and the value of ΔG*. This correlation was extrapolated to explain the electronic influence of the substituents ortho to the amino group. Consideration was paid to the possibility that, for the ortho substituents, steric factors may outweigh electronic factors. An attempt was made to extend this correlation to explain the electronic influence of 2'- and 4'-substituents upon the ΔG* values and rates of racemization of-substituted biphenyls. However, it was found that the simple Hammett correlation was not followed and that, for the racemization studies, the entropy of activation (ΔS*) became a significant factor. The values of ΔG* for hindered rotation were obtained from the analysis of 100MHz n.m.r. spectra. The validity of these ΔG* values was discussed with respect to their accuracy and with respect to the effect of entropy. The synthetic routes used to obtain the three series of compounds were also discussed. The discussion of the synthetic routes includes the attempted preparations of a number of quinone-anils via the condensation of 2,6-di-t-butyl-l,4-benzoquinone with 4-substituted 2-benaylanilines. This was complicated by the production of impure samples of 2-benzylaniline and 2-benayl-4-chloroaniline. The synthesis of 2-benzyl-4-nitroaniline was not reproducible. The condensation reaction resulted in a number of products. These were separated by crystallization techniques and identified by high pressure liquid chromatography, I.R. spectroscopy, -13C and proton n.m.r. The structure of a new compound based on a dihydroindole containing one spiro carbon joined to a substituted quinone ring is proposed.

The reaction of a series of 2,6-dimethylaryl halides with strong base has been investigated. Debromination to give polymethylbenzenes has been found to occur in all the systems studied and varying amounts of higher-boiling products, mainly polymethyl-bibenzyls, have also been obtained. Various mechanisms for these new reactions are discussed and the participation of an unusual triplet carbene intermediate is suggested. The related thermal decomposition of sodium o-halophenates has also been investigated. The participation of a similar carbene intermediate in this reaction appears to be unlikely. Possible mechanisms for the formation of diphenylmethanes obtained in the decomposition of sodium pentachlorophenate in methylbenzenes, are discussed.

One of the main objectives of this Thesis was to explore the use of thiophenes to synthesize several more complex aromatic systems. Thus starting from 2,4-dimethyl 5- amino-3-methylthiophene-2,4-dicarboxylate 115, the synthesis of the first cis-thia[ 13]annulene, 4-bromo-cis-9b,9c-dimethyl-9b,9c-dihydrophenyleno[1,9-bc]thiophene 116a, as well as the trans-isomer, 116b have been achieved in 11 steps. Introduction of a bromo-substituent at an early stage, facilitated rearrangement of the thiacyclophanes 119a and 119b to permit easier isolation of the product annulenes. Both the cis-thia[ 13]annulene 116a and the trans-thia[ 13]annulene 116b were found to be diatropic on the basis of their 1H NMR chemical shifts. Using thiophene dioxide 150 and 152 as key intermediates to generate multifunctional azulenes, the novel azulene containing thiacyclophane 105 has been synthesized in 9 steps. Even though this was not able to be converted to the [18]annulene 100, discovery of a new route to thiacyclophanes from thiolacetates was achieved. This has been tested successfully on a variety of other examples, including the unusual bis thiophene containing cyclophanes 194 and 195, as well as the unsymmetrical 191 which was subsequently converted to the dihydropyrene 236a and 236b. During the course of this work, we discovered a new mild method to electrophilically brominate reactive aromatics using NBS in [special characters omitted] at room temperature. This reagent was investigated for several thiophenes, azulenes and dihydropyrenes. The products from the latter were successfully coupled using Ni(0) catalysis to generate 28% of the first unsymmetrically connected dimer of DMDHP, 249, as well as 33% of the symmetrical dimer 102. Unlike 102, the bi-annulenyl 249 has a significant barrier to rotation, which is estimated as 11.0 kcal/mole from [special characters omitted] measurement, compared to a PCMODEL calculated barrier of 12 kcal/mole. This is the first measurement of the barrier to rotation in a 1,2'-binaphthyl type system. Electrophilic substitution in DMDHP using the diazonium salts 277 and 283 was also studied, and several novel cross-coupling products have been synthesized and isolated, such as 278 from 279 and 280. As well the very unusual isomeric quinones, 7-(10b, 10c-dimethyl-7-oxo- 2,7,10b, 10c-tetrahydro-2-pyrenyliden)-10b, 10c-dimethyl-2,7-10b, 10c-tetrahydro-2- pyrenone 263 and 264 have been successfully prepared by reacting 102 with NBS or PDC. Compounds 263 and 264 have highly extended conjugated systems. / Graduate

The synthesis of trans-11b,11c-dimethyl-11b,11c-dihydro-7H-cyclopent [a] pyrene, 109, from trans-10b,10c-dimethyl-10b,10c-dihydropyrene, 32, was achieved in six steps in an overall yield of 29%. Deprotonation of 109 gave the first annuleno-fused cyclopentadienide, trans-11b,11c-dimethyl-11b,11c-dihydrocyclopent[a] pyrene, ion(1-), 101. Experimental and theoretical proton NMR results for the anion in the presence and absence of the counter cation were analysed. The cyclopentadienyl anion, when fused to 32, has 53% of the effective bond-fixing ability of benzene fused to the same system. In terms of benzene resonance energy units, cyclopentadienyl anion has an effective resonance energy of 0.53. Metal complexation of the cyclopent[a]dihydropyrene, 101, was investigated, and gave the first two cyclopent-fused large annulene metal complexes, (6a,7,8,9,9a- μ5]-trans-11b,11c-dimethyl-11b,11c-dihydrocyclopent[a] pyrene-pentamethylcyclopentadienylruthenium(II), 139, and (6a,7,8,9,9a- μ5) trans-11b,11c-dimethyl-11b,11c-dihydrocyclopent[a] pyrene-tricarbonylmanganese (I), 141. Experimental and theoretical 1H NMR results for the two complexes were analysed. Ruthenocene, when fused to 32, was found to be 1.38 times more bond-fixing than benzene itself. Similarly, cyclopentadienylmanganesetricarbonyl is 1.33 times more bond-fixing than benzene. In terms of benzene resonance energy units, the two complexes have effective experimental resonance energies of 1.42 and 1.36, respectively. The diamagnetic susceptibility, X, of a cyclopentadienylruthenium moiety, with the center of anisotropy located at the metal atom, was calculated as -330x10-36 m3 per molecule. The same parameter for a manganese tricarbonyl moiety, with the center of anisotropy being located at 3.2 A° down from the manganese atom, was calculated as -635x10-36 m3 per molecule. An X-ray structure determination of 32 was finally achieved some 25 years after its first synthesis. The structural data confirm the planarity and lack of bond alternation in the bridged annulene, indicating that it is aromatic. / Graduate

The electrochemical hydroxylation of aromatic substrates was investigated in some detail, with the view to develop a method, which could produce dihydroxybenzenes in acceptable yields. Of particular interest was the selectivity and yield of the 1,4-dihydroxybenzenes. Two distinctly different methods were investigated in order to achieve this goal, acyloxylation and direct electrochemical hydroxylation. Acyloxylation is the process where radical cations generated at the anode undergoes nucleophilic attack by acetate anions. The resulting aromatic acetates so produced can then be hydrolysed to the phenolic compounds. Two nucleophile systems were considered in the investigation, acetates (acetoxylation) and trifluoro-acetates (trifluoro-acetoxylation). These investigations were conducted under a variety of conditions using phenol and phenyl acetate as starting materials. From the results it was, however, concluded that the acetoxylation of these aromatic compounds occurs in unacceptable product and current yields. Trifluoro-acetoxylation on the other hand showed promise, but due to the nature and cost of the reagents it was deemed to be an impractical process. Direct electrochemical hydroxylation: in which the radical cations produced at the anode undergoes nucleophilic attack by water producing the corresponding dihydroxybenzenes. These dihydroxybenzenes are then further oxidised to the benzoquinones, which then undergo reduction at the cathode in order to produce the corresponding dihydroxybenzene. In this process phenol, 2-tert-butylphenol and 2,6-di-tert-butylphenol were investigated as substrates. The results indicated that the yield towards the 1,4-dihdroxybenzenes increased as the degree of substitution on the ring increased.

A metabolite of a widely used pesticide, paraoxon, exerted a dramatic mutagenic synergistic effect in Salmonella typhimurium with a number of mammalian-activated or plant-activated aromatic amines and heterocyclic amines. The mutagenic synergy required an activated an aromatic amine, and was not attributable to the generation of new mutagenic products or to the modification of the stability of the activated aromatic amine products. Paraoxon modulated the genotoxic potency of dietaiy heterocyclic amines in human cells. The results of this study raise the concern of the environmental effects of organophosphorus ester insecticides. A clone of the Chinese hamster ovary cell line, AS52, was isolated, characterised and analysed under identical treatment conditions with the mutagens 2-acetoxy-acetylaminofluorene (2AAAF), ethyl methanesulphonate (EMS), and UV radiation. The genetic endpoints included acute DNA damage detected in the alkaline single cell gel electrophoresis (SCGE) assay, whole cell clastogenicity detected with laser beam flow cytometry and forward mutation at a target gene. There were statistically significant increases in DNA damage and forward mutation with all three mutagens. Statistically significant increases in chromosome damage were observed with 2AAAF and EMS but not with UV. A non-uniform distribution of DNA damage throughout the genome was indicated with the chemical mutagens in the SCGE assay. Another type of modulation in genotoxic response was investigated whereby numerous commercial soybean processing products and by-products were analysed for their antimutagenic and antigenotoxic activities. Antimutagenic activity was detected in a soybean processing by-product, soybean molasses and in an ethanol extract, fraction PCC. PCC protected mammalian cells against direct DNA damage, clastogenic damage and point mutation induced by 2AAAF. A fraction of PCC, PCC100 was an effective antimutagen in mammalian cells and in human lymphocytes. Analytical chemical studies identified the compounds responsible for the antimutagenic activity as the soyasaponins I, III and V.

No description available.

No description available.