Ascorbic Acid Promoted Metal-Free Synthesis of Aryl Sulfides with Anilines Nitrosated in Situ by tert-Butyl Nitrite

Abstract

A mild, metal-free synthesis of aryl sulfides has been disclosed. Aryl diazonium ion was generated by the in situ nitrosation of aniline, and it was reduced by ascorbic acid (vitamin C) to form aryl radical, which underwent a thiolation with disulfide to yield aryl sulfide. The reaction proceeded smoothly without heating or irradiation. This strategy was also expanded to the synthesis of aryl selenides.

Key words

aryl sulfide - metal-free - ascorbic acid - carbon–sulfur bond formation - radical reaction

• References and Notes

• 1a Parry RJ. Tetrahedron 1983; 39: 1215
• 1b Jacob C. Nat. Prod. Rep. 2006; 23: 851
• 1c Fontecave M, Ollagnier-de-Choudens S, Mulliez E. Chem. Rev. 2003; 103: 2149
• 1d Procter DJ. J. Chem. Soc., Perkin Trans. 1 2001; 335
• 1e Rayner CM. Contemp. Org. Synth. 1996; 3: 499
• 1f Hoyle CE, Lee TY, Roper T. J. Polym. Sci., Part A: Polym. Chem. 2004; 42: 5301
• 1g Clemenson PI. Coord. Chem. Rev. 1990; 106: 171
• 2a McGarrigle EM, Myers EL, Illa O, Shaw MA, Riches SL, Aggarwal VK. Chem. Rev. 2007; 107: 5841
• 2b Arrayas RG, Carretero JC. Chem. Commun. 2011; 47: 2207

For selected reviews, see:
• 3a Beletskaya IP, Ananikov VP. Chem. Rev. 2011; 111: 1596
• 3b Kondo T, Mitsudo T.-a. Chem. Rev. 2000; 100: 3205
• 3c Hoyle CE, Lowe AB, Bowman CN. Chem. Soc. Rev. 2010; 39: 1355
• 3d Chauhan P, Mahajan S, Enders D. Chem. Rev. 2014; 114: 8807
• 3e Ley SV, Thomas AW. Angew. Chem. Int. Ed. 2003; 42: 5400
• 4a Eichman CC, Stambuli JP. Molecules 2011; 16: 590
• 4b Baig RB. N, Varma RS. Chem. Commun. 2012; 48: 2582
• 4c Wu Q, Zhao D, Qin X, Lan J, You J. Chem. Commun. 2011; 47: 9188
• 4d Kundu D, Ahammed S, Ranu BC. Green Chem. 2012; 14: 2024
• 4e Cheng J.-H, Ramesh C, Kao H.-L, Wang Y.-J, Chan C.-C, Lee C.-F. J. Org. Chem. 2012; 77: 10369
• 5a Stadler O. Ber. Dtsch. Chem. Ges. 1884; 17: 2075
• 5b Ziegler JH. Ber. Dtsch. Chem. Ges. 1890; 23: 2469
• 6a Hilbert GE, Johnson TB. J. Am. Chem. Soc. 1929; 51: 1526
• 6b Szmant HH, Levitt G. J. Am. Chem. Soc. 1954; 76: 5459
• 6c Baleja JD. Synth. Commun. 1984; 14: 215
• 6d Petrillo G, Novi M, Garbarino G, Dell’Erba C. Tetrahedron Lett. 1985; 26: 6365
• 6e Petrillo G, Novi M, Garbarino G, Filiberti M. Tetrahedron Lett. 1988; 29: 4185
• 7 Wang X, Cuny GD, Noël T. Angew. Chem. Int. Ed. 2013; 52: 7860
• 8a Hartwig JF. Acc. Chem. Res. 2008; 41: 1534
• 8b Carril M, SanMartin R, Dominguez E. Chem. Soc. Rev. 2008; 37: 639
• 8c Beletskaya IP, Cheprakov AV. Coord. Chem. Rev. 2004; 248: 2337
• 8d Prim D, Campagne J.-M, Joseph D, Andrioletti B. Tetrahedron 2002; 58: 2041
• 8e Kunz K, Scholz U, Ganzer D. Synlett 2003; 2428
• 8f Alvaro E, Hartwig JF. J. Am. Chem. Soc. 2009; 131: 7858
• 8g Fernández-Rodríguez MA, Shen Q, Hartwig JF. Chem. Eur. J. 2006; 12: 7782
• 8h Fukuzawa S.-i, Tanihara D, Kikuchi S. Synlett 2006; 2145
• 8i Bhadra S, Sreedhar B, Ranu BC. Adv. Synth. Catal. 2009; 351: 2369
• 8j Zhang Y, Ngeow KC, Ying JY. Org. Lett. 2007; 9: 3495
• 9a Majek M, von Wangelin AJ. Chem. Commun. 2013; 49: 5507
• 9b Du B, Jin B, Sun P. Org. Lett. 2014; 16: 3032
• 9c Guo S.-r, Yuan Y.-q, Xiang J.-n. Org. Lett. 2013; 15: 4654
• 9d Wang PF, Wang XQ, Dai JJ, Feng YS, Xu HJ. Org. Lett. 2014; 16: 4586
• 10a Sandmeyer T. Ber. Dtsch. Chem. Ges. 1884; 17: 1633
• 10b Meerwein H, Büchner E, van Emster K. J. Prakt. Chem. 1939; 152: 237
• 10c Kosynkin D, Bockman TM, Kochi JK. J. Am. Chem. Soc. 1997; 119: 4846
• 10d Wetzel A, Pratsch G, Kolb R, Heinrich MR. Chem. Eur. J. 2010; 16: 2547
• 10e Hartmann M, Studer A. Angew. Chem. Int. Ed. 2014; 53: 8180
• 10f Matheis C, Jouvin K, Goossen LJ. Org. Lett. 2014; 16: 5984
• 11 Crisostomo FP, Martin T, Carrillo R. Angew. Chem. Int. Ed. 2014; 53: 2181
• 12a Lu G.-p, Cai C. Adv. Synth. Catal. 2013; 355: 1271
• 12b Feng J, Lv M, Lu G, Cai C. Eur. J. Org. Chem. 2014; 5312
• 12c Lu G.-p, Cai C. RSC Adv. 2014; 4: 59990
• 13a Galli C. Chem. Rev. 1988; 88: 765
• 13b Wetzel A, Ehrhardt V, Heinrich MR. Angew. Chem. Int. Ed. 2008; 47: 9130
• 14 Hofmann J, Jasch H, Heinrich MR. J. Org. Chem. 2014; 79: 2314
• 15a General Procedure for the Synthesis of Aryl Sulfides 3 With Solid Disulfides A 10 mL Schlenk tube with a magnetic stirring bar was charged with aniline 1 (0.2 mmol) and disulfide 2 (0.2 mmol). The tube was evacuated and backfilled with dry nitrogen (this operation was repeated three times). MeCN (1 mL) was added by syringe, followed by l-ascorbic acid (0.5 equiv, 20 mg) dissolved in DMSO (0.1 mL). With Liquid Disulfides A 10 mL Schlenk tube with a magnetic stirring bar was charged with aniline 1 (0.2 mmol). The tube was evacuated and backfilled with dry nitrogen (this operation was repeated three times). MeCN (1 mL) was added by syringe, followed by disulfide 2 (0.2 mmol or 0.4 mmol) and l-ascorbic acid (0.5 equiv, 20 mg) dissolved in DMSO (0.1 mL). The mixture was stirred vigorously for 1 min before t-BuONO (0.3 mmol, 36 μL) was added via syringe. After the resulting mixture was stirred at 20 °C for 4 h, the solvent was removed under reduced pressure. Purification of the crude product was achieved by column chromatography. (4-Chlorophenyl)(phenyl)sulfane (3a) ¹H NMR (500 MHz, CDCl₃): δ = 7.40–7.30 (m, 4 H), 7.30–7.20 (m, 5 H). ¹³C NMR (125 MHz, CDCl₃): δ = 135.2, 134.8, 133.1, 132.1, 131.4, 129.4, 127.6. GC–MS: m/z = 220 [M⁺]. Phenyl [4-(Trifluoromethyl)phenyl]sulfane (3h) ¹H NMR (500 MHz, CDCl₃): δ = 7.51–7.46 (m, 4 H), 7.43–7.36 (m, 3 H), 7.27 (d, J = 8.4 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 142.9, 133.6, 132.6, 129.8, 128.8, 128.4, 128.0, 125.9, 125.3, 123.1. ¹⁹F NMR (470 MHz, CDCl₃): δ = –62.5. GC–MS: m/z = 254 [M⁺]. Methyl 3-(Phenylthio)thiophene-2-carboxylate (3j) ¹H NMR (500 MHz, CDCl₃): δ = 7.63–7.57 (m, 2 H), 7.46–7.40 (m, 3 H), 7.30 (d, J = 5.3 Hz, 1 H), 6.35 (d, J = 5.3 Hz, 1 H), 3.92 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 162.7, 145.4, 135.1, 132.6, 130.6, 129.7, 129.4, 128.2, 121.4, 52.2. GC–MS: m/z = 250 [M⁺]. (2,5-Dimethoxyphenyl)(phenyl)sulfane (3m) ¹H NMR (500 MHz, CDCl₃): δ = 7.39 (dt, J = 3.3, 1.9 Hz, 2 H), 7.36–7.30 (m, 2 H), 7.30–7.26 (m, 1 H), 6.85–6.81 (m, 1 H), 6.73 (dd, J = 8.9, 3.0 Hz, 1 H), 6.60 (d, J = 3.0 Hz, 1 H), 3.83 (s, 3 H), 3.66 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 154.1, 151.5, 133.9, 132.3, 129.4, 127.6, 125.9, 116.9, 112.6, 111.9, 56.7, 55.8. GC–MS: m/z = 246 [M⁺]. 2-Methyl-3-[(4-nitrophenyl)thio]furan (3s) ¹H NMR (500 MHz, CDCl₃): δ = 8.11–8.04 (m, 2 H), 7.46 (d, J = 1.9 Hz, 1 H), 7.17–7.12 (m, 2 H), 6.40 (d, J = 1.9 Hz, 1 H), 2.35 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 158.1, 148.4, 145.2, 142.1, 125.2, 124.2, 115.2, 105.6, 12.0. GC–MS: m/z = 235 [M⁺].
• 15b General Procedure for the Synthesis of Aryl Selenides 5 A 10 mL Schlenk tube with a magnetic stirring bar was charged with aniline 1 (0.2 mmol) and 1,2-diphenyldiselane (4, 0.2 mmol, 63 mg). The tube was evacuated and backfilled with dry nitrogen (this operation was repeated three times). MeCN (1 mL) was added by syringe, followed by l-ascorbic acid (0.5 equiv, 20 mg) dissolved in DMSO (0.1 mL). The mixture was stirred vigorously for 1 min before t-BuONO (0.3 mmol, 36 μL) was added via syringe. After the resulting mixture was stirred at 20 °C for 6 h, the solvent was removed under reduced pressure. Purification of the crude product was achieved by column chromatography. (4-Nitrophenyl)(phenyl)selane (5a) ¹H NMR (500 MHz, CDCl₃): δ = 8.09–7.97 (m, 2 H), 7.63 (dd, J = 8.1, 1.2 Hz, 2 H), 7.47–7.38 (m, 3 H), 7.38–7.31 (m, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 146.3, 144.1, 136.0, 130.2, 129.8, 129.5, 127.3, 124.1. GC–MS: m/z = 279 [M⁺].
• 15c Radical-Capturing Experiment A 25 mL Schlenk tube with a magnetic stirring bar was charged with 4-nitroaniline 1b (0.5 mmol, 70 mg) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO, 0.55 mmol, 87 mg). The tube was evacuated and backfilled with dry nitrogen (this operation was repeated three times). MeCN (2.5 mL) was added by syringe, followed by l-ascorbic acid (0.5 equiv, 50 mg) dissolved in DMSO (0.25 mL). The mixture was stirred vigorously for 1 min before t-BuONO (0.75 mmol, 90 μL) was added via syringe. After the resulting mixture was stirred at 20 °C for 6 h, the solvent was removed under reduced pressure. Purification of the crude was achieved by column chromatography. 2,2,6,6-Tetramethyl-1-(4-nitrophenoxy)piperidine (6) ¹H NMR (500 MHz, CDCl₃): δ = 8.14 (d, J = 9.5 Hz, 2 H), 7.27 (br, 2 H), 1.73–1.57 (m, 5 H), 1.48–1.40 (m, 1 H), 1.23 (s, 6 H), 0.98 (s, 6 H). ¹³C NMR (125 MHz, CDCl₃): δ = 168.8, 141.2, 125.6, 114.3, 61.0, 39.7, 32.3, 20.5, 17.0. GC–MS: m/z = 278 [M⁺].
• 16a Mugesh G, du Mont W.-W, Sies H. Chem. Rev. 2001; 101: 2125
• 16b Nogueira CW, Zeni G, Rocha JB. T. Chem. Rev. 2004; 104: 6255
• 16c Weekley CM, Harris HH. Chem. Soc. Rev. 2013; 42: 8870
• 16d Balaguez RA, Ricordi VG, Freitas CS, Perin G, Schumacher RF, Alves D. Tetrahedron Lett. 2014; 55: 1057
• 16e Kundu D, Ahammed S, Ranu BC. Org. Lett. 2014; 16: 1814
• 17 Costas-Costas U, Gonzalez-Romero E, Bravo-Diaz C. Helv. Chim. Acta 2001; 84: 632