Brønsted acid-catalyzed metal-free one-pot synthesis of benzimidazoles via [4+1] heteroannulation of ortho-phenylenediamines with β-oxodithioesters

Abstract

An operationally simple and user-friendly one-pot domino protocol for the synthesis of 2-aryl/hetaryl benzimidazoles has been devised from easily available and inexpensive 1,2-phenylenediamines and β-oxodithioesters. The strategic [4+1] heteroannulation initiated by Brønsted acid PTSA relies on remarkable domino sequence of condensation, cyclization, and elimination. The current approach enables N-H/N-H functionalization under solventless and metal-free conditions leading to diverse benzimidazoles. The reactions proceeded smoothly affording the desired products in good to excellent yields, exhibiting gram-scale ability and broad functional groups tolerance. Notably, the approach is highly chemo-and regioselective.

Recent Developments Towards Synthesis of (Het)arylbenzimidazoles

“…59 Scheme 13 2-(Het)arylbenzimidazoles from 1,2-DABs and (het)aryl methyl ketones Singh and co-workers developed a simple and easy-touse chemo-and regioselective one-pot method for the synthesis of 2-(het)arylbenzimidazoles from readily available and inexpensive 1,2-DABs 1 and -oxo dithioesters 55. 60 Ring closure initiated by Brönsted acid p-TsOH is based on the domino sequence of condensation, cyclization, and elimination. The reactions proceeded smoothly, giving the desired products in good to excellent yields and exhibiting gram scale-up ability and tolerance to a wide variety of functional groups (Scheme 14).…”

“…The reactions proceeded smoothly, giving the desired products in good to excellent yields and exhibiting gram scale-up ability and tolerance to a wide variety of functional groups (Scheme 14). 60…”

A decade update on the application of β-oxodithioesters in heterocyclic synthesis

“…This journal is © The Royal Society of Chemistry 2023 (Scheme 40), 63 which is similar to the transformation of synthesizing 2-substituted benzothiazoles 27-3 in Scheme 27.…”

“…In 2018, one-pot domino heteroannulation of β-oxodithioesters 40-1 and 1,2-phenylenediamines 40-2 to synthesize C-2 substituted benzimidazoles 40-3 under metal- and solvent-free conditions was demonstrated by Singh's group (Scheme 40), 63 which is similar to the transformation of synthesizing 2-substituted benzothiazoles 27-3 in Scheme 27. PTSA as a Brønsted acid played a vital role in the condensation reaction of β-oxodithioesters with 1,2-phenylenediamines to generate ketimines and subsequent N -cyclization.…”