Synthesis of Disulfanes from Organic Thiocyanates Mediated by Sodium in Silica Gel

Abstract

We report an efficient procedure for the synthesis of symmetrical disulfanes from organic thiocyanates in the presence of sodium in silica gel at room temperature. By avoiding the use of foul-smelling thiols, the present protocol provides an attractive alternative to existing methods for the preparation of symmetrical disulfanes.

Key words

disulfides - reduction - thiocyanates - coupling - sodium

• References and Notes

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• 16 Disulfanes (Table 2; Entries 1–14); General Procedure An oven-dried three-neck flask, cooled under a flow of N₂, was charged with Na_SG (Stage 1, Sigma–Aldrich, Catalogue No. 660167; 4 mmol, 306 mg), and a solution of the appropriate thiocyanate (1 mmol) in dry THF (5 mL) was added via syringe. The solution was magnetically stirred until the starting material was completely consumed. The reaction was then quenched by careful addition of H₂O (10 mL), and the mixture was filtered and extracted with EtOAc (3 × 10 mL). The organic phases were combined, dried (Na₂SO₄), filtered, and concentrated under reduced pressure to give a crude product that was purified by flash chromatography (silica gel; hexane–EtOAc). (CAUTION! The reaction involves liberation of toxic cyanide ion. The aqueous phase must be carefully treated with NaOCl solution before disposal.).
• 17 Bis(3-phenoxypropyl) Disulfide (Table 2, Entry 4) Oil; yield: 132 mg (79%). ¹H NMR (400 MHz, CDCl₃): δ = 2.18 (quin, J = 12 Hz, 4 H), 2.87 (t, J = 12 Hz, 4 H), 4.04 (t, J = 12 Hz, 4 H), 6.87–6.95 (m, 5 H), 7.25–7.29 (m, 5 H). ¹³C NMR (100 MHz, CDCl₃): δ = 28.76, 35.07, 65.65, 114.45, 120.71, 120.78, 129.40, 158.73. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₈H₂₂NaO₂S₂: 357.1061; found: 357.1063. Bis[2-(phenylsulfanyl)ethyl] Disulfide (Table 2, Entry 5) Oil; yield: 147 mg (87%). ¹H NMR (400 MHz, CDCl₃): δ = 2.75 (t, J = 12 Hz, 4 H), 3.10 (t, J = 12 Hz, 4 H), 7.15–7.19 (m, 2 H), 7.21–7.23 (m, 4 H), 7.27–7.29 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 33.13, 37.61, 126.54, 129.03, 129.86, 134.75. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₈NaS₄: 361.0291; found: 361.0289. Disulfanediylbis(ethane-2,1-diyl) Dibenzoate (Table 2, Entry 6) Oil; yield: 141 mg (78%). ¹H NMR (400 MHz, CDCl₃): δ = 3.09 (t, J = 6 Hz, 4 H), 4.60 (t, J = 6 Hz, 4 H), 7.43 (t, J = 6 Hz, 4 H), 7.55–7.56 (d, J = 6 Hz, 2 H), 8.05 (t, J = 6 Hz, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 37.42, 62.77, 128.41, 129.69, 129.87, 133.14, 166.35. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₈H₁₈NaO₄S₂: 385.0647; found: 385.0645. Bis(4-methoxybenzyl) Disulfide (Table 2, Entry 10) Oil; yield: 127 mg (83%). ¹H NMR (400 MHz, CDCl₃): δ = 3.63 (s, 4 H), 3.83 (s, 6 H), 6.89 (d, J = 6 Hz, 4 H), 7.20 (d, J = 6 Hz, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 42.75, 55.25, 113.87, 129.38, 130.49, 159.00. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₈NaO₂S₂: 329.0748; found: 329.0745. Bis(2-phenylethyl) Disulfide (Table 2, Entry 11) Oil; yield: 112 mg (82%). ¹H NMR (400 MHz, CDCl₃): δ = 2.88 (dd, J = 6, 12 Hz, 4 H), 2.90 (dd, J = 6, 12 Hz, 4 H), 7.10–7.14 (m, 6 H), 7.20–7.23 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 35.68, 40.16, 126.36, 128.47, 128.57, 139.98. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₈NaS₂: 297.0850; found: 297.0852. Bis(3-fluorobenzyl) Disulfide (Table 2, Entry 12) Oil; yield: 124 mg (88%). ¹H NMR (400 MHz, CDCl₃): δ = 3.52 (s, 4 H), 6.89 (t, J = 6 Hz, 6 H), 6.94 (d, J = 12 Hz, 1 H), 7.1–7.23 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 42.73, 114.37, 116.29, 125.01, 129.95, 130.00 139.80. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₄H₁₂F₂NaS₂: 305.0348; found: 305.0349. Bis(but-3-yn-1-yl) Disulfide (13) Oil; yield: 66 mg (78%). ¹H NMR (400 MHz, CDCl₃): δ = 2.04 (s, 2 H), 2.60–2.63 (m, 4 H), 2.85 (t, J = 6 Hz, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 18.98, 37.21, 69.87, 82.04. HRMS (ESI): m/z [M + Na]⁺ calcd for C₈H₁₀NaS₂: 193.0224; found: 193.0223.
• 18 Hamed EM, Doai H, McLaughlin CK, Houmam A. J. Am. Chem. Soc. 2006; 128: 6595