Cu-catalyzed convenient synthesis of 2-trifluoromethyl benzimidazoles via cyclization of o-phenylenediamines with hexafluoroacetylacetone

Abstract

An efficient and convenient method for the synthesis of 2-trifluoromethyl benzimidazoles is described in this paper. The cyclization reaction of various o-phenylenediamines with hexafluoroacetylacetone proceeded smoothly in the presence of Cu₂O as the catalyst to produce 2-trifluoromethyl benzimidazoles in satisfactory to excellent yields (up to >99% yield). The CF₃ source, hexafluoroacetylacetone, acted not only as cyclization partner, but also acted as a ligand for the Cu catalyst. Various synthetically useful functional groups, such as halogen atoms, cyano, and methoxycarbonyl groups, remained intact during the cyclization reactions. The reaction mechanism was thoroughly investigated and was determined to involve a seven-membered cyclic diimine intermediate.