Imidazol-5-yl radicals as reactive intermediates

Abstract

Imidazol-5-yl radicals have been generated as reactive intermediates in reduction reactions e.g. the reduction of 5-bromo-1,2-dimethylimidazole with Na/NH₃/Bu^tOH and the reduction of 5-iodo- and 5-bromo-imidazole with Bu₃SnH, to yield 1,2-dimethylimidazole. The imidazol-5-yl radical resulting from the Na/NH₃/Bu^tOH and Bu₃SnH reduction of 5-bromo-1 -(but-3-en-1-yl)-2-methylimidazole has been trapped by exo-radical cyclisation to yield the bicyclic imidazole (7). Attempted S_RN1 substitution reactions between nucleophiles and 5-bromo- and 5-iodo-1,2-dimethylimidazole were unsuccessful. The radical anions of 5-nitroimidazoles were shown not to dissociate to nitrite anions and the corresponding imidazol-5-yl radicals, thereby disproving a putative explanation for the generation of nitrite anions in the antimicrobial mode of action of 5-nitroimidazoles. A mechanism has been proposed to explain the release of nitrite in the mode of action of nitroimidazoles.¹³C NMR spectroscopy has been used to distinguish between 4- and 5-bromo- and -iodo-imidazoles.