Dimerization of 3-Chlorooxindoles Mediated by Potassium Ethyl­xanthate: Synthesis of Isoindigos

Abstract

A novel dimerization of 3-chlorooxindoles promoted by potassium ethylxanthate to access isoindigo derivatives is described. The reactions proceeded readily at room temperature in short reaction times. A mechanistic study revealed that the 3-chlorooxindole is initially converted into O-ethyl S-(2-oxo-2,3-dihydro-1H-indol-3-yl) dithiocarbonate, which subsequently undergoes dimerization with elimination of carbon disulfide. In almost all cases, analytically pure isoindigos were isolated in moderate to good yields without a requirement for chromatographic purification.

Key words

isoindigos - potassium ethylxanthate - dimerization - chlorooxindoles - carbon disulfide

• References and Notes

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• 14 Compounds 2a–g; General Procedure Potassium ethylxanthate (1.0 mmol, 2 equiv) was added to a solution of the appropriate 3-chlorooxindole 1 (0.5 mmol) in acetone (2 mL), and the reaction was stirred at RT for 4 h until the reaction as complete. The solvent was removed in a rotary evaporator and the residue was diluted with H₂O (20 mL) and filtered. The residue was washed with Et₂O (20 mL) to give the analytically pure product. (3E)-3,3′-Biindole-2,2′(1H,1′H)-dione (2a)¹¹ Red solid; yield: 58.4 mg, (89%); mp >300 °C. ¹H NMR (500 MHz, DMSO-d₆ ): δ = 10.89 (s, 2 H), 9.05 (d, J = 6.4 Hz, 2 H), 7.33 (td, J = 6.1, 0.8 Hz, 2 H), 7.01–6.90 (m, 2 H), 6.83 (d, J = 6.1 Hz, 2 H). ¹³C NMR (126 MHz, DMSO-d₆ ): δ = 169.5, 144.6, 133.9, 133.3, 129.8, 122.2, 121.7, 110.1. HRMS (ESI): m/z [M – H]⁺ calcd for C₁₆H₉N₂O₂: 261.0664; found: 261.0655.
• 15 Compounds 2j–l; General Procedure Potassium ethylxanthate (1.0 mmol, 2 equiv) was added to a solution of the appropriate 3-chlorooxindole 1 (0.5 mmol) in acetone (2 mL), and the mixture was stirred at RT for 4 h. The solvent was then removed in a rotary evaporator and the residue was extracted with EtOAc (2 × 20 mL) and H₂O (20 mL). The organic layers were combined, dried (Na₂SO₄), and concentrated, and the residue was purified by column chromatography [silica gel, CH₂Cl₂–hexane (1:1)]. (3E)-1,1′-Dibenzyl-3,3′-biindole-2,2′(1H,1′H)-dione (2j)^11,13a Red solid; yield: 80.8 mg (73%); mp 223–224 °C. ¹H NMR (500 MHz, CDCl₃): δ = 9.23 (d, J = 5.9 Hz, 2 H), 7.46–7.11 (m, 12 H), 7.05 (td, J = 6.3, 0.8 Hz, 2 H), 6.72 (d, J = 6.1 Hz, 2 H), 5.02 (s, 4 H). ¹³C NMR (126 MHz, CDCl₃): δ = 168.0, 144.5, 135.7, 133.5, 132.5, 130.0, 128.8, 127.7, 127.2, 122.5, 121.7, 108.6, 43.7. HRMS (ESI): m/z [M + H]⁺ calcd for C₃₀H₂₃N₂O₂: 443.1760; found: 443.1759.
• 16 Compounds 2m–o; General Procedure K₂CO₃ (0.5 mmol, 1 equiv) was added to a solution of O-ethyl S-(2-oxo-2,3-dihydro-1H-indol-3-yl) dithiocarbonate (3a; 0.5 mmol) and N-alkyl-3-chlorooxindole 1 (0.5 mmol, 1 equiv) in acetone (2 mL), and the mixture was stirred at RT for 4 h. The solvent was then removed in a rotary evaporator and the mixture was extracted with EtOAc (2 × 20 mL) and H₂O (20 mL). The organic layers were combined, dried (Na₂SO₄), and concentrated, and the residue was purified by column chromatography [silica gel, EtOAc–CH₂Cl₂ (1:9)]. (3E)-1-Benzyl-3,3′-biindole-2,2′(1H,1′H)-dione (2m)^5b Red solid; yield: 66.9 mg (38%); mp 230–232 °C. ¹H NMR (500 MHz, DMSO-d₆ ): δ = 10.94 (s, 1 H), 9.25–8.78 (m, 2 H), 7.42–7.29 (m, 6 H), 7.27 (dt, J = 7.4, 3.4 Hz, 1 H), 7.08–6.92 (m, 3 H), 6.86 (d, J = 6.3 Hz, 1 H), 5.02 (s, 2 H). ¹³C NMR (126 MHz, DMSO-d ₆): δ = 169.4, 167.9, 144.9, 144.5, 136.8, 134.9, 133.6, 133.0, 132.4, 130.1, 129.7, 129.3, 128.0, 127.8, 122.5, 122.2, 121.8, 121.5, 110.2, 109.5, 43.3. HRMS (ESI): m/z [M – H]⁺ calcd for C₂₃H₁₅N₂O₂: 351.1134; found: 351.1130.