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

 

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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.

• References and Notes

• 1a Jocelyn PC. Biochemistry of the SH Group: The Occurrence, Chemical Properties, Metabolism and Biological Function of Thiols and Disulphides. Academic Press; London: 1972
  Google Scholar
• 1b Bodzansky M. Principles of Peptide Synthesis. Springer; Berlin: 1984
  Google Scholar
• 1c Capozzi G, Madona G In The Chemistry of the Thiol Group. Vol. II. Patai S. Chap. 17 Wiley; Chichester: 1974: 785
  Google Scholar
• 2a Ramadas K, Srinivasan N. Synth. Commun. 1995; 25: 227
  Crossref
• 2b Fisher HL. Ind. Eng. Chem. 1950; 42: 1978
  Crossref
• 3a Kishi Y, Nakatsuga S, Fukuyama T, Havel M. J. Am. Chem. Soc. 1973; 95: 6493
  CrossrefPubMed
• 3b Ito S, Ota A, Suhara H, Tabashi K, Kawashima Y. Chem. Pharm. Bull. 1993; 41: 1066
  Crossref
• 4a Tazaki M, Tagaki M. Chem. Lett. 1979; 767
• 4b Caserio MC, Fisher CL, Kim JK. J. Org. Chem. 1985; 50: 4390
  Crossref
• 4c Koval IV. Russ. Chem. Rev. 1994; 63: 735
  Crossref
• 4d Billard T, Langlois BR. Tetrahedron Lett. 1996; 37: 6865
  Crossref
• 5a Nuzzo RG, Allara DL. J. Am. Chem. Soc. 1983; 105: 4481
  Crossref
• 5b Biebuyck HA, Bain CD, Whitesides GM. Langmuir 1994; 10: 1825
  Crossref
• 6a Witt D. Synthesis 2008; 2491
  Article in Thieme Connect
• 6b Mandal B, Basu B. RSC Adv. 2014; 4: 13854
  Crossref
• 7 Sengupta D, Basu B. Tetrahedron Lett. 2013; 54: 2277
  Crossref
• 8 Prabhu KR, Ramesha AR, Chandrasekaran S. J. Org. Chem. 1995; 60: 7142
  Crossref
• 9 Jia X, Zhang Y, Zhou X. Tetrahedron Lett. 1994; 35: 8833
  Crossref
• 10 Guo H, Zhan Z, Zhang Y. Synth. Commun. 1997; 27: 2721
  Crossref
• 11 Burns CJ, Field LD, Morgan J, Ridley DD, Vignevich V. Tetrahedron Lett. 1999; 40: 6489
  Crossref
• 12 Fuska J, Šturdíkova M, Proksa B. Lett. Appl. Microbiol. 1994; 19: 124
  Crossref
• 13 Dye JL, Cram KD, Urbin SA, Redko MY, Jackson JE, Lefenfeld M. J. Am. Chem. Soc. 2005; 127: 9338
  CrossrefPubMed
• 14a Costanzo MJ, Patel MN, Petersen KA, Vogt PF. Tetrahedron Lett. 2009; 50: 5463
  Crossref
• 14b Nandi P, Redko MY, Petersen K, Dye JL, Lefenfeld M, Vogt PF, Jackson JE. Org. Lett. 2008; 10: 5441
  CrossrefPubMed
• 14c Maurya CK, Gupta PK. Tetrahedron Lett. 2015; 56: 2228
  Crossref
• 15 Kiasat AR, Mehrjardi MF. Bull. Korean Chem. Soc. 2008; 29: 2346
  Crossref
• 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
  Crossref

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