Regioselective alkylation of 4(5)-nitro-1H-imidazoles in acidic media: study of temperature effects

Abstract

Alkylation of 4(5)-nitro-1H-imidazoles in acidic media with reactive alkylating agents such as benzyl chloride and allyl bromide resulted in the predominant formation of the 5-nitro isomers at lower temperatures (75 °C) and the 4-nitro isomers at higher temperatures (140 °C). With less reactive alkylating agents, only the 5-nitro isomers were produced irrespective of temperature. The mechanism was shown to involve quaternization of the initially formed 1-alkyl-5-nitro-1H-imidazoles followed by preferential dealkylation to yield the thermodynamically more stable 4-nitro1H-imidazoles.