Reaction of azoles with ethyl bromopyruvate oxime: alkylation by substitution and by elimination–addition

Abstract

Ethyl bromopyruvate oxime (1a) reacts with imidazole, 1-methylimidazole, pyrazole, 3-methylpyrazole, 3,5-dimethylpyrazole, and 1,2,4-triazole to give products of N-alkylation of the azoles. The rates of reaction of (1a) with imidazole, 1-methylimidazole, and 3,5-dimethylpyrazole are much faster than with the other azoles. The O-alkylated oxime (1b) reacts much more slowly than (1a) with imidazole and with 3,5-dimethylpyrazole. Imidazole is shown to be a strong enough base to eliminate HBr from the bromo oxime (1a), and the reaction of pyrazole with (1a) is greatly accelerated when an external base (sodium carbonate) is added. As a result, it is concluded that the more basic azoles, with pKa, values above 4, react with (1a) by an elimination–addition mechanism whereas the others react by direct displacement of bromide. Related reactions of imidazole and of 1,2,4-triazole with ethyl chloro(hydroxyimino)acetate have also been carried out and the N-substituted azoles (12), (13), and (14) have been isolated.