Hydrogen Peroxide Promoted Metal-Free Oxidation/Cyclization of α-Hydroxy N-Arylamides: A Facile One-Pot Synthesis of Isatins

Abstract

A novel, efficient, and environmentally friendly method was developed for converting α-hydroxy N-arylamides into isatins (1H-indole-2,3-diones) by using hydrogen peroxide as oxidant. The reactions proceeded smoothly under metal-free conditions and generated the corresponding products in good to excellent yields. This method has advantages of a broad substrate scope and simple operations.

Key words

hydrogen peroxide - hydroxy amides - isatins - cyclization - indoles

• References and Notes

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• 20 N-Methylisatin (2a); Typical Procedure A mixture of α-hydroxy amide 1a (152.2 mg, 1.0 mmol) and 30% aq H₂O₂ (0.68 g, 6.0 mmol, 0.61 mL) was added to DMSO (2 mL), and the mixture was stirred under air at 100 °C for 3 h. When the reaction was complete (TLC), the mixture was cooled to r.t., diluted with H₂O, and extracted with EtOAc (3 × 10 mL). The organic layer was washed with sat. brine, dried (Na₂SO₄), and evaporated to dryness. The crude residue was purified by flash chromatography [silica gel, PE–EtOAc (10:1)] to give a red solid; yield: 143.3 mg (0.89 mmol, 89%); mp 130–133 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.64–7.58 (m, 2 H), 7.15–7.11 (m, 1 H), 6.92 (d, J = 8.0 Hz, 1 H), 3.26 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 183.3, 158.1, 151.4, 138.4, 125.1, 123.8, 117.3, 109.9, 26.2. HRMS (ESI): m/z [M + Na⁺] calcd for C₉H₇NNaO₂: 184.0374; found: 184.0370.