Multigram Synthesis of 1-(Difluoromethyl)imidazoles and -benzimidazoles

Abstract

An expedient approach to the difluoromethylation of imidazoles­ and benzimidazoles has been developed. The key feature of the procedure is the gradual generation of the difluoromethylation reagent in the reaction mixture, which is achieved by the simultaneous addition of chlorodifluoromethane and alkali. The method is applicable to functionalized substrates and allows the corresponding 1-(difluoromethyl)imidazoles and -benzimidazoles to be prepared in 60-95% yield on a hundred-gram scale.

Key words

fluorine compounds - heterocycles - imidazoles - benzimidazoles - difluoromethylation

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23

We did not consider the NaH-THF system used in one of the reports (see ref.^¹5) due to the high flammability of the reagent, especially on a multigram scale.