Metal-Free Oxidative Dimerization of Dithiocarbamates: Direct Access to 3,5-Bis-mercapto-1,2,4-thiadiazoles

Abstract

A facile and efficient protocol for the synthesis of 3,5-bis-mercapto-1,2,4-thiadiazoles by the oxidative dimerization of S-alkyl dithiocarbamates using periodic acid as an inexpensive and commercially available oxidant is reported. High to excellent yields and short reaction times are the main advantages of this procedure.

Key words

3,5-bismercaptoorganyl-1,2,4-thiadiazoles - dithiocarbamate - oxidative dimerization - hypervalent iodine - transition-metal-free

• References and Notes

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• 16 Synthesis of 3,5-(Bismercaptoorganyl)-1,2,4-thiadiazoles; General Procedure: To a solution of dithiocarbamate 1 (0.5 mmol) in CH₂Cl₂ (2 mL), periodic acid (0.5 mmol) was added. The resulting mixture was stirred at 0 °C for 15 minutes. After completion of the reaction, water (3 mL) was added and the mixture was extracted with CH₂Cl₂ (3 × 3 mL). The combined organic extracts were dried over Na₂SO₄, filtered and evaporated under reduced pressure. The desired product 2 was purified by column chromatography (silica gel; ethyl acetate/hexane, 1:10).Characterization Data for Selected Compounds
  3,5-Bis(benzylthio)-1,2,4-thiadiazole (2a): Yield: 70 mg (85%); yellow oil. IR (KBr): 1424, 1211, 1041, 699 cm^–1; ¹H NMR (300 MHz, CDCl₃): δ = 4.47 (s, 4 H), 7.27–7.45 (m, 10 H); ¹³C NMR (75 MHz, CDCl₃): δ = 36.4, 38.4, 127.4, 128.1, 128.5, 128.8, 129.0, 129.1, 135.0, 136.8, 170.2, 187.2; Anal. Calcd (%) for C₁₆H₁₄N₂S₃: C, 58.15; H, 4.27; N, 8.48; Found: C, 58.27; H, 4.17; N, 8.35.3,5-Bis(isopentylthio)-1,2,4-thiadiazole (2b): Yield: 65 mg (89%); yellow oil. IR (KBr): 1427, 1209, 1041 cm^–1; ¹H NMR (300 MHz, CDCl₃): δ = 0.93–0.96 (m, 12 H), 1.63–1.76 (m, 6 H), 3.19–3.25 (m, 4 H); ¹³C NMR (75 MHz, CDCl₃): δ = 22.1, 22.2, 27.4, 27.5, 30.2, 32.3, 37.5, 38.1, 171.1, 187.9; Anal. Calcd (%) for C₁₂H₂₂N₂S₃: C, 49.61; H, 7.63; N, 9.64; Found: C, 49.32; H, 7.55; N, 9.49.Dibutyl 3,3'-[(1,2,4-Thiadiazole-3,5-diyl)bis(sulfanediyl)]di­-propanoate (2k): Yield: 81 mg (80%); yellow oil. IR (KBr): 1735, 1465, 1430, 1350, 1213, 1063 cm^–1; ¹H NMR (300 MHz, CDCl₃): δ = 0.88–0.93 (m, 6 H), 1.31–1.39 (m, 4 H), 1.57–1.62 (m, 4 H), 2.78–2.85 (m 4 H), 3.40–3.50 (m, 4 H), 4.07–4.12 (m, 4 H); ¹³C NMR (75 MHz, CDCl₃): δ = 13.6, 19.0, 26.9, 29.0, 30.5, 33.1, 33.8, 34.0, 34.4, 34.7, 64.6, 64.8, 169.9, 171.1, 171.6, 187.2; Anal. Calcd (%) for C₁₆H₂₆N₂O₄S₃: C, 47.26; H, 6.45; N, 6.89; Found: C, 47.17; H, 6.32; N, 7.05