1,2-Disubstituted Benzimidazoles by the Iron Catalyzed Cross-Dehydrogenative Coupling of Isomeric o -Phenylenediamine Substrates.

Benzimidazoles are common in nature, medicines, and materials. Numerous strategies for preparing 2-arylbenzimidazoles exist. In this work, 1,2-disubstituted benzimidazoles were prepared from various mono- and disubstituted ortho -phenylenediamines (OPD) by iron-catalyzed oxidative coupling. Specifically, O ₂ and FeCl ₃ ·6H ₂ O catalyzed the cross-dehydrogenative coupling and aromatization of diarylmethyl and dialkyl benzimidazole precursors. N , N '-Disubstituted-OPD substrates were significantly more reactive than their N , N -disubstituted isomers, which appears to be relative to their propensity for complexation and charge transfer with Fe ³⁺ . The reaction also converted N-monosubstituted OPD substrates to 2-substituted benzimidazoles; however, electron-poor substrates produce 1,2-disubstituted benzimidazoles by intermolecular imino-transfer. Kinetic, reagent, and spectroscopic (UV-vis and EPR) studies suggest a mechanism involving metal-substrate complexation, charge transfer, and aerobic turnover, involving high-valent Fe(IV) intermediates. Overall, comparative strategies for the relatively sustainable and efficient synthesis of 1,2-disubstituted benzimidazoles are demonstrated.