Facile and Efficient Synthesis of Benzoxazoles and Benzimidazoles: The Application of Hantzsch Ester 1,4-Dihydropyridines in Reductive Cyclization Reactions

Both benzoxazole and benzimidazole are common heterocyclic scaffolds in biologically active and medicinally significant compounds. Reductive cyclization of ortho‐substituted nitrobenzene derivatives provides an attractive route to benzoxazole or benzimidazole ring formation. Unfortunately, only a few synthetic methods by reductive cyclization ofortho‐nitro compounds have been reported and the yields are rather low. In continuation of the development of biomimetic reductants in synthetically useful organic transformations, Hantzsch ester 1,4‐dihydropyridine (HEH), analogues of NAD(P)H, has attracted a considerable amount of attention. Hence, we wish to report that benzoxazoles and benzimidazoles can be efficiently synthesized by the reaction of ortho‐substituted nitrobenzene derivatives with HEH catalyzed by Pd/C. A range of functionalized ortho‐nitrophenyl esters or ortho‐nitrophenyl amides were efficiently reduced by HEH and cyclized to the corresponding benzoxazoles or benzimidazoles. Especially, working in the presence of the same substituents, benzimidazoles could be obtained in higher yields with respect to the corresponding benzoxazoles. Moreover, in the present work, the recycling of Pd/C was studied and was shown to maintain its high catalytic activity over five runs. On the basis of our experimental results and DFT calculations, a plausible reaction mechanism was proposed. An efficient reductive cyclization of ortho‐substituted nitrobenzenes was achieved by employing Hantzsch ester 1,4‐dihydropyridines as a biomimetic reducing agent inthe presence of catalytic Pd/C. This approach was applied with spectacular success to synthesize various benzoxazoles and benzimidazoles.