Oxidative Halogenation of Sydnones Mediated by KX–Oxone System under Mild Conditions

Abstract

A direct, straightforward, and convenient approach for the synthesis of halogenated sydnones using the potassium halide (KX)–Oxone system via oxidative halogenation is developed. Highlights of the strategy include readily available chemicals, mild reaction conditions, short reaction time, excellent yields, and aqueous medium. Additionally, the scale-up reaction of the present halogenation indicated the practical feasibility on a higher scale under mild conditions.

Keywords

Oxidative halogenation - Synthetic methods - C–H functionalization - Sydnones - Scale-up

• References

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• 22 General experimental procedure for the preparation of halogenated sydnones: To a 25-mL RB flask was added sydnone 1 (1.0 equiv 0.56 mmol), KX (1.1 equiv), oxone (1.1 equiv), and aq. acetonitrile (1:1, 2.0 mL). The reaction mixture was stirred at room temperature. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was quenched with water and extracted with dichloromethane (DCM). The combined organic layer was washed with water, saturated brine solution, and dried over sodium sulphate. The organic layer was concentrated under reduced pressure to obtain the crude product. The crude product was then washed with hexane to obtain the respective halogenated sydnone 2. 4-Bromo-3-phenyl-1,2,3-oxadiazol-3-ium-5-olate (2a): Off-white solid; Yield-96% (140 mg); m.p. 103–105 °C; R _f = (0.7 in 20% EtOAc/PET); ¹H NMR (400 MHz, DMSO-d ₆) δ = 7.83–7.81 (m, 2H), 7.80–7.77 (m, 1H), 7.76–7.72 (m, 2H); ¹³C NMR (101 MHz, DMSO- d ₆) δ = 165.3, 133.8, 132.7, 130.1, 125.5, 86.4; HRMS (ESI): m/z calcd for C₈H₅BrN₂O₂ [M+H] 240.9534, found 240.9538. 4-Bromo-3-(p-tolyl)-1,2,3-oxadiazol-3-ium-5-olate (2b): Off-white solid; Yield-98% (142 mg); m.p. 135–137 °C; R _f = (0.7 in 20% EtOAc/PET); ¹H NMR (400 MHz, DMSO-d ₆) δ = 7.67 (d, J = 8.6 Hz, 2H), 7.51 (d, J = 8.1 Hz, 2H), 2.43 (s, 3H); ¹³C NMR (101 MHz, DMSO-d ₆) δ = 165.4, 143.0, 131.3, 130.4, 125.2, 86.3, 20.9; HRMS (ESI): m/z calcd for C₉H₇BrN₂O₂ [M+H] 254.9691, found 254.9693. 4-Chloro-3-phenyl-1,2,3-oxadiazol-3-ium-5-olate (2o): Brown solid; Yield-95% (116 mg); m.p. 107–109 °C; R _f = (0.7 in 20% EtOAc/PET); ¹H NMR (400 MHz, DMSO-d ₆) δ = 7.85–7.82 (m, 2H), 7.80–7.76 (m, 1H), 7.76–7.71 (m, 2H); ¹³C NMR (101 MHz, DMSO-d₆) δ = 163.4, 132.8, 130.1, 125.3, 99.2; HRMS (ESI): m/z calcd for C₈H₅ClN₂O₂ [M+H] 197.0040, found 197.0042. 4-Chloro-3-(p-tolyl)-1,2,3-oxadiazol-3-ium-5-olate (2p): Pale brown solid; Yield-97% (116 mg); m.p. 124–126 °C; R _f = (0.7 in 20% EtOAc/PET); ¹H NMR (400 MHz, DMSO-d ₆) δ = 7.75–7.69 (m, 2H), 7.53 (d, J = 8.1 Hz, 2H), 2.44 (s, 3H); ¹³C NMR (101 MHz, DMSO-d ₆) δ = 163.4, 143.1, 130.4, 130.3, 125.0, 99.1, 20.9; HRMS (ESI): m/z calcd for C₉H₇ClN₂O₂ [M+H] 211.0196, found 211.0199. 4-Iodo-3-phenyl-1,2,3-oxadiazol-3-ium-5-olate (2w): Off-white solid; Yield-97% (172 mg); m.p. 172–174 °C; R _f = (0.7 in 20% EtOAc/PET); ¹H NMR (400 MHz, DMSO-d ₆) δ = 7.74–7.70 (m, 3H), 7.69–7.65 (m, 2H); ¹³C NMR (101 MHz, DMSO- d ₆) δ = 168.9, 135.3, 132.4, 129.9, 125.7, 57.8; HRMS (ESI): m/z calcd for C₈H₅IN₂O₂ [M+H] 288.9396, found 288.9398. 4-Iodo-3-(p-tolyl)-1,2,3-oxadiazol-3-ium-5-olate (2x): Off-white solid; Yield-98% (164 mg); m.p. 164–166 °C; R _f = (0.7 in 20% EtOAc/PET); ¹H NMR (400 MHz, DMSO-d ₆) δ = 7.53 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 8.1 Hz, 2H), 2.33 (s, 3H); ¹³C NMR (101 MHz, DMSO-d6) δ = 169.0, 142.7, 132.9, 130.3, 125.4, 57.7, 20.9; HRMS (ESI): m/z calcd for C₉H₇IN₂O₂ [M+H] 302.9552, found 302.9557.