On the mechanism of benzimidazole synthesis via copper-catalysed intramolecular N-arylation

Abstract

Copper(I)-catalysed intramolecular Ullmann N-arylation has been widely used to synthesise benzimidazoles. However, the possible intermediates on the catalytic pathway and the role of the ancillary ligands in these systems have been seldom studied and are currently not fully understood, especially when compared to comparable intermolecular Ullmann reactions. Accordingly, this work explores the copper(I)-intramolecular N-arylation of 1,2-dimethylbenzimidazole, reporting on the solid-state structures of several copper(I) species with the reaction substrate and product. In addition, kinetic profiling using bis(tetra-n-butylphosphonium) malonate as a soluble base has been carried out, notably revealing negligible catalyst deactivation but significant catalyst inhibition. Based on these results an improved catalytic protocol using sub-mol% catalyst loading has been developed.