A concise synthesis of 2-(2-aminothiophene)-benzimidazoles by one-pot multicomponent reaction

Abstract

A one-pot synthesis of 2-aminothiophene linked benzimidazoles was achieved by utilizing 2-cyanomethyl benzimidazoles in a modified Gewald multicomponent reaction. The synthetic strategy of the reaction involved treatment of 2-(cyanomethyl)-benzimdazole with aldehydes containing an active methylene group and sulfur powder under refluxing conditions. The multicomponent reaction proceeded via Knoevenagel condensation of 2-(cyanomethyl)-benzimdazole with aldehyde to generate an alpha,beta-unsaturated nitrile followed by cyclization with molecular sulfur under basic conditions to give biologically relevant 2-(2-aminothiophene)-benzimidazoles in good yields.