Practicable syntheses of 2-hydroxymethyl-substituted benzimidazoles and 2-formylbenzimidazole

Abstract

N-Protection of benzimidazole by a diethoxymethyl group, as in [3; R²= H, R¹= CH(OEt)₂], allows exclusive lithiation at the 2-position. This protected anion can be made to react with various electrophiles (e.g. ketones, aldehydes) to yield the corresponding 2-hydroxymethylbenzimidazoles (1). Facile deprotection occurs with acid. Two practicable syntheses of 2-formylbenzimidazole are also described and an indirect route to benzimidazole-2-alcohols is discussed.