Novel cyclisations of nitro-compounds for heterocyclic synthesis

The research described in this thesis is aimed at developing novel methods of synthesis for heterocyclic compounds, in particular cyclisation reactions involving the nitro functional group. The first chapter describes investigations into the Wallach imidazole synthesis. A number of chloroimidazoles were prepared, but the possible extension to highly functionalised imidazoles proved elusive. The second chapter describes studies on the successful conversion of nitroimidazolyl malonates 1 into imidazo[4,5-c]isoxazoles 2, Scheme 1. Related cyclisations are described in chapter three and the thiophene fused isoxazole 3 was successfully prepared. [Illustration omitted.] Chapter four investigates the reactivity of the strained imidazo[4,5-c]isoxazole heterocycles. Ring opening of the isoxazole occurred on reaction with phosphines to give iminophosphorane derivatives. Reactions with electron deficient acetylenes led to pyrrolyl imidazoles 4, and a novel [1,4]diazepino[2,3-c]isoxazole 5, Scheme 1, but no reaction was observed with alkenes. [Illustration omitted.] Chapter five entails synthesis of a series of 5-aryl-2H,1H-imidazo[4,5-d][1,2,3]triazole derivatives 7. Triethyl N-1-ethyl-2-methyl-4-nitro-1H-imidazol-5-yl phosphoramidate compound 6 was treated with a range of aryl isocyanates which gave imidazo[4,5-c]triazoles 7 in moderate to good yields. A mechanism involving carbodiimide formation was postulated and was supported using infra-red spectroscopy, Scheme 2. [Illustration omitted.] Chapter six reports a new synthesis of 5-aryl-2H indazole derivatives 9 by base catalysed reaction of 2-nitrobenzyl triphenylphosphonium bromide salts 8 with a range of aryl isocyanates. A mechanism of this reaction was proposed and investigated by infra-red spectroscopy, Scheme 3. [Illustration omitted.]