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 pK_a, 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.