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

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.

Automated summary

This paper describes an efficient and convenient method for the synthesis of 2-trifluoromethyl benzimidazoles. The cyclization reaction of various o-phenylenediamines with hexafluoroacetylacetone in the presence of Cu2O catalyst resulted in the formation of 2-trifluoromethyl benzimidazoles with high yields. Hexafluoroacetylacetone acted as both a cyclization partner and a ligand for the Cu catalyst, and various useful functional groups remained intact during the reaction.