A Versatile Method for the Synthesis of Benzimidazoles from o-Nitroanilines and Aldehydes in One Step via a Reductive Cyclization

Abstract

A highly efficient and versatile method for the synthesis of benzimidazoles was achieved in one step via the Na₂S₂O₄ reduction of o-nitroanilines in the presence of aldehydes. Heating a solution of o-nitroaniline (1c) and an aldehyde in EtOH or another appropriate solvent, in the presence of aqueous or solid Na₂S₂O₄, provided facile access to a series of 2-substituted N-H benzimidazoles 5a-m containing a wide range of functional groups not always compatible with the existing synthetic methods. This methodology has also been applied to the regioselective synthesis of N-alkyl and N-aryl benzimidazoles 6a-f via the cyclization of the corresponding N-substituted nitroanilines 13a-e, respectively. In addition, the method was applied successfully to the synthesis of other imidazole containing heterocyclic ring systems such as 1H-imidazo[4,5-b]pyridines 14a,b and 1H-imidazo[4,5-f]quinoline 15.

benzimidazoles - reductive cyclization - sodium dithionite - imidazopyridines - imidazoquinolines

References

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Current address: Donglai Yang, SSCI, Inc., 3065 Kent Avenue, West Lafayette, IN 47906, USA. E-mail: [e-mail].

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We observed that the presence of the aldehyde had a dramatic effect on the reduction of the starting o-nitroaniline as shown in Scheme [3] .
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This method has been routinely applied in our AMAP^TM (Automated Molecular Assembly Plant) for the high throughput solution phase synthesis of benzimidazole containing structures. More details will be communicated in due course.

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