Facile One-Pot Synthesis of Benzimidazole and Quinoxalin-2(1H)-one Scaffolds via Two-Component Coupling Reaction, Deprotection, and Intermolecular Cyclization

Abstract

Two scaffolds, namely benzimidazole and quinoxalin-2(1H)-one, were synthesized by treating 2-(N-Boc-amino)phenyl­isocyanide (Boc: tert-butoxycarbonyl) with carboxylic acids and glyoxylic acids, respectively. The target compounds were generated directly after two-component coupling, deprotection, and intermolecular cyclization.

Key words

benzimidazole - quinoxaline-2(1H)-one - two-component coupling - one-pot synthesis - intermolecular cyclization

• References and Notes

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• 17 General Procedure for the Synthesis of Compound 14 A solution of 2-(N-Boc-amino)phenylisocyanide (0.50 mmol) and carboxylic acid (0.50 mmol) in DCE (2 mL) was subjected to microwave irradiation at 150 °C for 10 min. After the microwave vial was cooled to r.t., TFA (0.20 mL) was added to the mixture and treated in microwave again at 100 °C for 10 min. Then, the solvent was removed, and the residue was diluted with EtOAc (15 mL) and washed with sat. Na₂CO₃ (15 mL) and brine (10 mL). The organic layer was dried over MgSO₄ and concentrated. The residue was purified by silica gel column chromatography using a gradient of EtOAc–hexane (10–80%) to afford the relative benzimidazole products. Compound 14a: yield 82%. ¹H NMR (400 MHz, DMSO-d ₆): δ = 12.59 (s, 1 H), 8.40–8.21 (m, 2 H), 7.85 (dd, J = 8.0, 1.4 Hz, 1 H), 7.63–7.44 (m, 4 H), 7.41–7.27 (m, 2 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 155.0, 154.6, 136.1, 132.5, 130.8, 130.6, 129.7, 129.2, 128.3, 123.8, 115.5. HRMS: m/z calcd for C₁₄H₁₀N₂O [M + H]⁺: 222.0793; found: 222.0796.