A Novel Method for the Direct Synthesis of Symmetrical and Unsymmetrical Sulfides and Disulfides from Aryl Halides and Ethyl Potassium Xanthogenate

Abstract

An efficient and new method for the synthesis of disulfides and sulfides via the reaction of aryl halides with ethyl potassium xanthogenate in the presence of MOF-199 is described. O-Ethyl-S-aryl ­carbonodithioate has a key role as an intermediate in this procedure; it was converted into symmetrical diaryl disulfides in DMF. Additionally, this could be applied to the synthesis of unsymmetrical aryl alkyl(aryl′) disulfides by the reaction with S-alkyl(aryl) sulfurothioates (Bunte salts) as well as unsymmetrical aryl alkyl(aryl′) sulfides in DMSO.

Key words

MOF-199 - unsymmetrical disulfides - ethyl potassium ­xanthogenate - sulfides

• References and Notes

• 1a Cremlyn RJ. W. An Introduction to Organosulfur Chemistry . John Wiley and Sons; Chichester: 1996
• 1b Oae S. Organic Chemistry of Sulfur . Springer; Berlin: 2012
• 1c Schaumann E. Sulfur-Mediated Rearrangements I . Springer; Berlin: Heidelberg: 2007
• 1d Dubbaka SR. Vogel P. Angew. Chem. Int. Ed. 2005; 44: 7674
• 1e Sahu SC. J. Environ. Sci. Health, Part C: Environ. ­Carcinog. Ecotoxicol. Rev. 2002; 20: 61
• 2a Zhang L. Chou CP. Moo-Young M. Biotechnol. Adv. 2011; 29: 923
• 2b Saito G. Swanson JA. Lee K.-D. Adv. Drug Delivery Rev. 2003; 55: 199
• 2c Dar AA. Enjamuri N. Shadab M. Ali N. Khan AT. ACS Comb. Sci. 2015; 17: 671
• 2d Bodanszky M. Principles of Peptide Synthesis . Springer; Berlin: 1984
• 3a Jones RC. Katritzky AR. Comprehensive Organic Functional Group Transformations II: Carbon with Two Attached Hetero­atoms with at Least One Carbon-to-heteroatom Multiple Link. Elsevier; Amsterdam: 2005
• 3b Mandal B. Basu B. RSC Adv. 2014; 4: 13854
• 3c Witt D. Synthesis 2008; 2491
• 3d Rayner CM. Contemp. Org. Synth. 1995; 2: 409
• 4a Fernández-Rodríguez MA. Shen Q. Hartwig JF. J. Am. Chem. Soc. 2006; 128: 2180
• 4b Bastug G. Nolan SP. J. Org. Chem. 2013; 78: 9303
• 4c Murata M. Buchwald SL. Tetrahedron 2004; 60: 7397
• 4d Oderinde MS. Frenette M. Robbins DW. Aquila B. Johannes JW. J. Am. Chem. Soc. 2016; 138: 1760
• 4e Xu H.-J. Zhao Y.-Q. Feng T. Feng Y.-S. J. Org. Chem. 2012; 77: 2649
• 4f Uyeda C. Tan Y. Fu GC. Peters JC. J. Am. Chem. Soc. 2013; 135: 9548
• 4g Hunter R. Caira M. Stellenboom N. J. Org. Chem. 2006; 71: 8268
• 4h Antoniow S. Witt D. Synthesis 2007; 363
• 4i Bao M. Shimizu M. Tetrahedron 2003; 59: 9655
• 4j Wu X.-m. Yan G.-b. Synlett 2015; 26: 537
• 4k Mukherjee N. Chatterjee T. Ranu BC. J. Org. Chem. 2013; 78: 11110
• 5a Kondo T. Mitsudo T. Chem. Rev. 2000; 100: 3205
• 5b Beletskaya IP. Ananikov VP. Chem. Rev. 2011; 111: 1596
• 5c Li Y. Pu J. Jiang X. Org. Lett. 2014; 16: 2692
• 5d Singh N. Singh R. Raghuvanshi DS. Singh KN. Org. Lett. 2013; 15: 5874
• 5e Qiao Z. Wei J. Jiang X. Org. Lett. 2014; 16: 1212
• 5f Akkilagunta VK. Kakulapati RR. J. Org. Chem. 2011; 76: 6819
• 5g Prasad DJ. C. Sekar G. Org. Lett. 2011; 13: 1008
• 5h Wang L. Zhou W.-Y. Chen S.-C. He M.-Y. Chen Q. Synlett 2011; 3041
• 5i Lee J.-Y. Lee PH. J. Org. Chem. 2008; 73: 7413
• 6 Bunte H. Ber. Dtsch. Chem. Ges. 1874; 7: 646
• 7a Milligan B. Swan JM. J. Chem. Soc. 1963; 6008
• 7b Milligan B. Saville B. Swan JM. J. Chem. Soc. 1961; 4850
• 7c Xiao X. Feng M. Jiang X. Chem. Commun. 2015; 51: 4208
• 8a Chughtai AH. Ahmad N. Younus HA. Laypkov A. Verpoort F. Chem. Soc. Rev. 2015; 44: 6804
• 8b Gascon J. Corma A. Kapteijn F. Llabrés FX. ACS Catal. 2014; 4: 361
• 8c Dhakshinamoorthy A. Alvaro M. Corma A. Garcia H. Dalton Trans. 2011; 40: 6344
• 8d Deria P. Mondloch JE. Karagiaridi O. Bury W. Hupp JT. Farha OK. Chem. Soc. Rev. 2014; 43: 5896
• 9 Furukawa H. Cordova KE. O’Keeffe M. Yaghi OM. Science 2013; 341: 974
• 10 Dhakshinamoorthy A. Asiric AM. Garcia H. Chem. Soc. Rev. 2015; 44: 1922
• 11a Soleiman-Beigi M. Arzehgar Z. Heteroat. Chem. 2015; 26: 355
• 11b Soleiman-Beigi M. Yavari I. Sadeghizadeh F. RSC Adv. 2015; 5: 87564
• 11c Soleiman-Beigi M. Sadeghizadeh F. Basereh A. J. Sulfur Chem. 2017; 38: 572
• 11d Soleiman-Beigi M. Yavari I. Sadeghizadeh F. Phosphorus, Sulfur Silicon Relat. Elem. 2018; 193, 41
• 11e Soleiman-Beigi M. Mohammadi F. J. Sulfur Chem. 2016; 38: 134
• 12 Savegnago L. Environ. Toxicol. Pharmacol. 2006; 21: 86
• 13 Britt D. Tranchemontagne D. Yaghi OM. Proc. Natl. Acad. Sci. U.S.A. 2008; 105: 11623
• 14 General Procedure for the Synthesis of S-Alkyl Sulfurothioates The requisite alkyl halide (10.0 mmol) and sodium thiosulfate pentahydrate (2.98 g, 12.0 mmol) dissolved in methanol–water (3:1, 20 mL). The reaction mixture was stirred and heated to 65 °C. Upon completion of the reaction, the mixture was cooled to room temperature, and then concentrated at 40–45 °C. The resultant solid was treated with methanol (50 mL), heated to 50 °C (most solid dissolved), and filtered. This removed the excess sodium thiosulfate and sodium chloride. The filtrate was concentrated to a white solid. The mixture was washed with n-hexane, filtered, and dried under vacuum at 50 °C.
• 15 General Procedure for the Synthesis of S-Aryl Sulfurothioates To a stirred mixture of iodobenzene (1.02 g, 5.0 mmol), sodium thiosulfate pentahydrate (1.88 g, 7.5 mmol) and CuI (0.09 g, 0.5 mmol, 10 mol%) in DMSO (5 mL) was added 1,10-phenanthroline (0.18 g, 1.0 mmol, 20 mol%), and the mixture was stirred for 5 min at room temperature and then heated to 80 °C for 4 h under a nitrogen atmosphere until completion of reaction. The reaction mixture was cooled to room temperature, brine (15 mL) was added, and the mixture was stirred vigorously at room temperature for 1 h. The mixture was filtered, and the solid was washed successively with brine and n-hexanes. The solid was dried under vacuum at 50 °C for 3 h.
• 16 General Procedure for the Synthesis of Unsymmetrical Disulfides The requisite alkyl (aryl) halide (1.0 mmol), potassium O-ethylcarbonodithioate (0.24 g, 1.5 mmol) and MOF-199 (4.0 mg) were added to DMSO (2.0 mL) and the mixture heated to 80 °C for 12 h. After complete conversion of the alkyl (aryl) halide into O-ethyl-S-phenyl carbonodithioate, RS₂O₃Na (1.0 mmol) and K₂CO₃ (0.14 g, 1.0 mmol) were added and the mixture heated to 80 °C for a further 12 h. The progress of reaction was monitored by TLC. Upon completion of the reaction, the mixture was cooled to room temperature and then filtered. The filtrate was evaporated under vacuum, CH₂Cl₂ (20 mL) was added, and the mixture was washed with H₂O (2 × 15 mL). The combined organic layers were dried over Na₂SO₄, filtered, and evaporated to afford the crude unsymmettrical alkyl (aryl) disulfide, which was purified by thick-layer chromatography (silica gel, eluting wth n-hexane–ethyl acetate, 20:1; in the case of 5d,f,i,j,n,p, 4:1). O-Ethyl-S-phenyl Carbonodithioate (3) Oil.¹H NMR (300 MHz, CDCl₃): δ = 7.76 (d, 2 HAr), 7.37–7.12 (m, 3 HAr), 3.26 (q, 2 HOEt), 1.14 (t, 3 HOEt) ppm.¹³C NMR (100 MHz, CDCl₃): δ = 210.2 (C=S), 138.7, 136.4, 131.4, 126.4 (CAr), 66.0 (CH₂), 13.7 (CH₃) ppm. GC–MS (EI): m/z = 198.3 [M⁺]. 1-Benzyl -2-(naphthalen-2-yl)disulfide (5b) Oil. ¹H NMR (300 MHz, CDCl₃): δ = 5.82–7.55 (m, 12 HAr), 2.32 (s, 2 HCH₂) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 162.3, 158.4, 147.1, 136.1, 130.4, 129.5, 129.0, 128.8, 127.9, 127.3, 125.2, 124.9, 122. 6, 115.8, 31.4 ppm. 1-(4-Methoxyphenyl)-2-phenyldisulfide (5p) White solid. ¹H NMR (300 MHz, CDCl₃): δ = 7.73–7.09 (m, 9 HAr), 3.80 (s, 3 HOMe) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 136.1, 132.5, 129.8, 127.9, 125.2, 123.2, 115.9, 127.2, 31.9 ppm. For other compounds, see the Supporting Information.
• 17 General Procedure for the Synthesis of Symmetrical Disulfides A mixture of the requisite alkyl (aryl) halide (2.0 mmol), potassium O-ethylcarbonodithioate (0.48 g, 3.0 mmol) and MOF-199 (8 mg) in DMF (15.0 mL) in a 25 mL round-bottom flask was stirred at 120 °C for 8 h. The reaction was monitored by TLC analysis. Upon completion of the reaction, the mixture was cooled to room temperature and then filtered. The filtrate was evaporated under vacuum, CH₂Cl₂ (20 mL) was added, and the mixture was washed with H₂O (2 × 15 mL). The combined organic layers were dried over Na₂SO₄, filtered, and solvent was removed in vacuo. The residue was purified by thick-layer chromatography on silica gel (eluting with n-hexane–ethyl acetate, 20:1; in the case of 4e and 4f, 4:1 and 2:1, respectively) to give the corresponding products. Diphenyl Disulfide (4a) White solid.¹H NMR (400 MHz, CDCl₃): δ = 7.24–7.36 (m, 6 H), 7.54 (m, 4 H) ppm.¹³C NMR (100 MHz, CDCl₃): δ = 137.0, 129.1, 127.5, 127.2 ppm. GC–MS (EI): m/z = 218.0 [M⁺].
• 18 General Procedure for the Synthesis of Unsymmetrical Sulfides The aryl halide (1.0 mmol), potassium O-ethylcarbonodithioate (0.24 g, 1.5 mmol) and MOF-199 (4.0 mg) were added to DMSO (2 mL) and the mixture heated to 80 °C for 12 h. After complete conversion of the alkyl (aryl) halide into O-ethyl-S-phenyl carbonodithioate, the requisite alkyl (aryl) halide (1.0 mmol) and K₂CO₃(0.058 g, 1.0 mmol) were added and the mixture heated at 80 °C for a further 12 h. The progress of reaction was monitored by TLC. Upon completion of the reaction, the mixture was cooled to room temperature and filtered. The filtrate was evaporated under vacuum, CH₂Cl₂ (20 mL) was added, and the mixture was washed with H₂O (2 × 15 mL). The combined organic layers were dried over Na₂SO₄, filtered, and evaporated to afford the crude unsymmetrical alkyl (aryl) sulfide, which was purified by thick-layer chromatography (silica gel, n-hexane–ethyl acetate, 20:1; in the case of 6g,k,l, 4:1). Phenyl(o-tolyl)sulfide (6i) The product was obtained as a oil.¹H NMR (300 MHz, CDCl3): δ = 7.85–7.00 (m, 9 HAr), 2.34 (s, 3 HMe) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 138.4, 137.8, 136.4, 131.4, 131.3, 130.8, 129.1, 128.4, 127.2, 127.1, 29.1 ppm. GC–MS (EI): m/z = 200.0 [M⁺]. Benzyl(o-tolyl)sulfide (6c) The product was obtained as a oil.¹H NMR (400 MHz, CDCl₃): δ = 7.39–7.28 (m, 9 H), 4.23 (s, 2 H), 2.31 (s, 3 HMe) ppm.¹³C NMR (100 MHz, CDCl₃): δ = 130.0, 129.5, 129.2, 128.8, 128.0, 127.9, 127.6, 127.5, 126.1, 39.6, 21.6 ppm. GC–MS (EI): m/z = 214.0 [M⁺].