Studies of some fused imidazole derivatives
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The main synthetic routes to benzimidazole N-oxides are outlined and some indication is given as to the current and potential pharmacological usefulness of such materials. A claim that 4-methyl-2-nitrophenylglycine is cyclised in acetic anhydride to give either 5-methylbenzimidazole 3-oxide or the isomeric 5 methylbenzimidazolone was investigated. This work was found to be impossible to duplicate. It is established that, by employing flash vacuum pyrolysis, the claimed products can be obtained thermolytically from the starting glycine. This is the first recorded example of the formation of an isomerisable benzimidazole N – oxide by thermolytic cyclisation of an o- nitroaniline derivative, and provides a possible explanation for the published findings. Routes to some aminobenzimidazole N- oxide derivatives (potential analogues of natural purines) are explored. Although several approaches were investigated the most successful was that involving the preparation and cyclisation of (4-protected amino ) -N- cyanomethyl-2-nitroanilines. In this way a range of suitably functionalised N-oxides was obtained. The difficulties encountered in using a similar approach in the synthesis of the corresponding 4 and 7-amino derivatives are described and, in particular, the importance of substituent effects in the base-induced cyclisation of N-(activated alkyl)- 2-nitroanilines is established. The preparation of some nucleoside analogues was briefly undertaken. An attempt was made to increase the scope of the base induced cyclisation of o-nitroaniline derivatives to the preparation of novel tricyclic systems. Although this was for the most part unsuccessful one such system was prepared by cyclisation of a suitably functionalised alkoxybenzimidazole. A method of preparing a range of symmetrically and unsymmetrically substituted diamino-dinitrobenzenes is described. It was established that for the most part these compounds could not be cyclised in the presence of base. Finally, the reduction of some of these compounds was undertaken and a new route to some pyrazino- quinoxalines thus established.
Thesis, PhD Doctor of Philosophy
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