First Report on the Synthesis of Isatins via Pyridinium Chlorochromate Catalyzed Intramolecular Cyclization Reactions

Abstract

A new and useful strategy to synthesize isatins from α-formyl amides has been developed via one-pot intramolecular cyclization–oxidation reaction with the present of pyridinium chlorochromate (PCC). The reaction proceeded smoothly under air and has good yields of the corresponding products. Also, this methodology has a broad substrate scope, and is operationally simple and atom economic.

Key words

isatins - PCC-catalyzed - one-pot - intramolecular cyclization

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• 18 General Procedure for the Synthesis of 2 (2a as an Example) A mixture of N-methyl-2-oxo-N-phenylacetamide (1a, 0.5 mmol) and PCC (0.5 mmol) were added in DMSO (2 mL) with a condenser and then heating for 3 h under air at 100 °C. After the completion of the reaction (monitored by TLC), the reaction mixture was cooled to r.t., diluted with H₂O and extracted with EtOAc. The organic layer was washed with sat. brine, dried over anhydrous Na₂SO₄ and the solvent was evaporated to dryness. The crude residue was purified by flash chromatography on silica (PE–EtOAc, 10:1) to afford pure 1-methylindoline-2,3-dione (2a) as a red solid (66 mg, 82% yield). 1-Methylindoline-2,3-dione (2a) Yield 82%; red solid; mp 130–133 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.64–7.58 (m, 2 H), 7.14 (t, J = 7.6 Hz, 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. ESI-HRMS: m/z [M + Na⁺] calcd for C₉H₇NO₂ + Na⁺: 184.0369; found: 184.0370.