Synthesis of α-Ketothioamides via Willgerodt–Kindler Reaction of Arylglyoxals with Amines and Sulfur under Solvent-Free Conditions

Abstract

Willgerodt–Kindler reaction of arylglyoxal hydrates with secondary amines and elemental sulfur under solvent-free conditions at 80 °C is developed, in which α-ketothioamides are obtained in 70–90% yield in 0.6–1 hour. The X-ray crystal-structure analysis for one compound was obtained.

Key words

α-ketothioamides - Willgerodt–Kindler reaction - aryl­glyoxals - green chemistry - solvent-free

• References and Notes

• 1a Lincke T, Behnken S, Ishida K, Roth M, Hertweck C. Angew. Chem. Int. Ed. 2010; 49: 2011
• 1b Kloss F, Lincke T, Hertweck C. Eur. J. Org. Chem. 2011; 1429
• 2a Hanzlie RP, Vyas KP, Traiger GJ. Toxicol. Appl. Pharmacol. 1980; 46: 685
• 2b Walter H, Zambach W. Chem. Abstr. 1996; 125: 55871
• 3a Wingert H, Sauter H, Bayer H, Oberdorf K, Lorenz G, Ammermann E. EP 35, 1994 ; Chem. Abstr. 1994, 121, 533719
• 3b Wei Q.-L, Zhang S.-S, Gao J, Li W.-H, Xu L.-Z, Yu Z.-G. Bioorg. Med. Chem. 2006; 14: 7146
• 4a Searle RJ. G, Boyce CB. C, Bay H. US 4,096,275, 1978
• 4b Fauss R, Findeisen K, Becker B, Hamman I, Homeyer B. US 4,581,375, 1986
• 5a Bandgar BP, Gawande SS, Warangkar SC, Totre JV. Bioorg. Med. Chem. 2010; 18: 3618
• 5b Harrowven DC, Lucas MC, Howes PD. Tetrahedron Lett. 1999; 40: 4443
• 6 Reynard P, Moreau RC, Samama JP. Bull. Soc. Chim. Fr. 1965; 12: 3623
• 7 Jeschke P, Harder A, Etzel W, Gau W, Thielking G, Bonse G, Iinuma K. Pest Manage. Sci. 2001; 57: 1000 ; Chem. Abstr. 2001, 136, 839295
• 8a Suzuki Y, Yazaki R, Kumagai N, Shibasaki M. Chem. Eur. J. 2011; 17: 11998
• 8b Suzuki Y, Yazaki R, Kumagai N, Shibasaki M. Angew. Chem. Int. Ed. 2009; 48: 5026
• 8c Sureshkumar D, Kawato Y, Iwata M, Kumagai N, Shibasaki M. Org. Lett. 2012; 14: 3108
• 8d Koduri ND, Scott H, Hileman B, Cox JD, Coffin M, Glicksberg L, Hussaini SR. Org. Lett. 2012; 14: 440
• 8e Ogawa T, Mouri S, Yazaki R, Kumagai N, Shibasaki M. Org. Lett. 2012; 14: 110
• 8f Yazaki R, Kumagai N, Shibasaki M. Org. Lett. 2011; 13: 952
• 8g Murai T, Ui K Narengerile J. Org. Chem. 2009; 74: 5703
• 8h Arshad N, Hashim J, Kappe CO. J. Org. Chem. 2009; 74: 5118
• 9a Jagodziński TS. Chem. Rev. 2003; 103: 197
• 9b Kadzimirsz D, Kramer D, Sripanom L, Oppel IM, Rodziewicz P, Doltsinis NL, Dyker G. J. Org. Chem. 2008; 73: 4644
• 9c Matloubi Moghaddam F, Zali Boinee H. Tetrahedron Lett. 2003; 44: 6253
• 9d Matloubi Moghaddam F, Zali Boinee H. Tetrahedron 2004; 60: 6085
• 9e Du W, Curran DP. Org. Lett. 2003; 5: 1765
• 9f Klingele MH, Brooker S. Eur. J. Org. Chem. 2004; 3422
• 9g Ransborg LK, Albrecht Ł, Weise CF, Bak JR, Jørgensen KA. Org. Lett. 2012; 14: 724
• 9h Androsov DA. J. Org. Chem. 2008; 73: 8612
• 9i Yanagida Y, Yazaki R, Kumagai N, Shibasaki M. Angew. Chem. 2011; 123: 8056
• 9j Kim BS, Kim K. J. Org. Chem. 2000; 65: 3690
• 9k Cheng Y, Yang J, Qu Y, Li P. Org. Lett. 2012; 14: 98
• 9l Murai T, Hori F, Maruyama T. Org. Lett. 2011; 13: 1718
• 9m Zhang X, Teo WT, Chan S, Chan PW. H. J. Org. Chem. 2010; 75: 6290
• 9n Padwa A, Beall LS, Heidelbaugh TM, Liu B, Sheehan SM. J. Org. Chem. 2000; 65: 2684
• 10a Batjargal S, Wang YJ, Goldberg JM, Wissner RF, Petersson EJ. J. Am. Chem. Soc. 2012; 134: 9172
• 10b Xie J, Okano A, Pierce JG, James RC, Stamm S, Crane CM, Boger DL. J. Am. Chem. Soc. 2012; 134: 1284
• 10c Sharma I, Crich D. J. Org. Chem. 2011; 76: 6518
• 10d Wang L, Xu Z, Ye T. Org. Lett. 2011; 13: 2506
• 11a Mason CR, Maynard-Atem L, Al-Harbi NM, Budd PM, Bernardo P, Bazzarelli F, Clarizia G, Jansen JC. Macromolecules 2011; 44: 6471
• 11b Deletre M, Levesque G. Macromolecules 1990; 23: 4876
• 11c Kanbara T, Kawai Y, Hasegawa K, Morita H, Yamamoto T. J. Polym. Sci., Part A: Polym. Chem. 2001; 39: 3739
• 12a Cao J.-L, Qu J. J. Org. Chem. 2010; 75: 3663
• 12b Geng X.-L, Wang J, Li G.-X, Chen P, Tian S.-F, Qu J. J. Org. Chem. 2008; 73: 8558
• 12c Chen P, Qu J. J. Org. Chem. 2011; 76: 2994
• 12d Hernández JG, García-López V, Juaristi E. Tetrahedron 2012; 68: 92
• 12e Ganesh M, Seidel D. J. Am. Chem. Soc. 2008; 130: 16464
• 13a Raucher S, Klein P. J. Org. Chem. 1981; 46: 3558
• 13b Curphey TJ. J. Org. Chem. 2002; 67: 6461
• 13c Cho D, Ahn J, De Castro KA, Ahn H, Rhee H. Tetrahedron 2010; 66: 5583
• 13d Bergman J, Pettersson B, Hasimbegovic V, Svensson PH. J. Org. Chem. 2011; 76: 1546
• 14 Smith DC, Lee SW, Fuchs PL. J. Org. Chem. 1994; 59: 348
• 15 Pathak U, Pandey LK, Tank R. J. Org. Chem. 2008; 73: 2890
• 16 Shibahara F, Sugiura R, Murai T. Org. Lett. 2009; 11: 3064
• 17 Kaboudin B, Malekzadeh L. Synlett 2011; 2807
• 18a Coats SJ, Link JS, Hlasta DJ. Org. Lett. 2003; 5: 721
• 18b Kaleta Z, Makowski BT, Soós T, Dembinski R. Org. Lett. 2006; 8: 1625
• 18c Kaleta Z, Tárkányi G, Gömöry A, Kálmán F, Nagy T, Soós T. Org. Lett. 2006; 8: 1093
• 18d Soukara S, Wünsch B. Tetrahedron 2001; 57: 4359
• 18e Koketsu M, Ishihara H. Curr. Org. Synth. 2007; 4: 15
• 19 Aki S, Fujioka T, Ishigami M, Minamikawa J.-i. Bioorg. Med. Chem. Lett. 2002; 12: 2317
• 20a Brown EV. Synthesis 1975; 358 ; and references cited therein
• 20b Zbruyev OI, Stiasni N, Kappe CO. J. Comb. Chem. 2003; 5: 145
• 20c Darabi HR, Aghapoor K, Tajbakhsh M. Tetrahedron Lett. 2004; 45: 4167 ; and references cited therein
• 20d Salim SD, Pathare SP, Akamanchi KG. Catal. Commun. 2011; 13: 78
• 21 Eftekhari-Sis B, Zirak M, Akbari A. Chem. Rev. 2013; in press; DOI: 10.1021/cr300176g
• 22a Dauben WG, Rogan JB. J. Am. Chem. Soc. 1956; 78: 4135
• 22b Harris TW, Smith HE, Mobley PL, Manier DH, Sulser F. J. Med. Chem. 1982; 25: 855
• 22c Harrowven DC, Lucas MC, Howes PD. Tetrahedron 1999; 55: 1187
• 22d Liu W.-W, Zhao Y.-Q, Xu R.-B, Tang L.-J, Hu H.-W. Chin. J. Chem. 2006; 24: 1472
• 23 Valdez-Rojas JE, Ríos-Guerra H, Ramírez-Sánchez AL, García-González G, Álvarez-Toledano C, López-Cortés JG, Toscano RA, Penieres-Carrillo JG. Can. J. Chem. 2012; 90: 567
• 24a Matloubi MoghaddamF, Mirjafary Z, Saeidian H, Javan MJ. Synlett 2008; 892
• 24b Murata S, Suzuki K, Miura M, Nomura M. J. Chem. Soc., Perkin Trans. 1 1990; 361
• 24c Darabi HR, Aghapoor K, Tabar-Heydar K, Nooshabadi M. Phosphorus, Sulfur Silicon Relat. Elem. 2002; 177: 1189
• 24d Asinger F, Gentz F. Angew. Chem., Int. Ed. Engl. 1963; 2: 397
• 24e Creary X, Zhu C. J. Am. Chem. Soc. 1995; 117: 5859
• 25 Zhang C, Zong X, Zhang L, Jiao N. Org. Lett. 2012; 14: 3280
• 26 Riley HA, Gray AR. Org. Synth., Coll. Vol. II 1943; 509
• 27 Crystallographic data for the structure in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication nos. CCDC 901556. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, [fax: [phone] or e-mail: [e-mail]].
• 28 Okamoto K, Yamamoto T, Kanbara T. Synlett 2007; 2687
• 29 Spectroscopic and Analytical Data for Selected Novel Compounds 1-(3,4-Dimethoxyphenyl)-2-(pyrrolidin-1-yl)-2-thioxo-ethanone (3g) Dark yellow solid; mp 113–115 °C. FTIR (KBr): 2967 (CH), 1648 (C=O), 1589 (C=C), 1508 (C=S), 1451 (CH₂ bending), 1270 (CO), 1229 (CN), 1019 (C=S) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.59–7.63 (dd, J = 2.0, 8.4 Hz, 1 H, CH_Ar), 7.57 (d, J = 2.0 Hz, 1 H, CH_Ar), 6.90 (d, J = 8.4 Hz, 1 H, CH_Ar), 3.96–3.99 (m, 2 H, CH₂N), 3.98 (s, 3 H, OCH₃), 3.96 (s, 3 H, OCH₃), 3.56–3.59 (m, 2 H, CH₂N), 2.06–2.17 (m, 4 H, CH₂). ¹³C NMR (100 MHz, CDCl₃): δ = 193.1 (C=S), 188.3 (C=O), 154.3, 149.4, 126.0, 125.8, 111.1, 110.2, 56.2, 51.3, 26.1, 23.9. Calcd for C₁₄H₁₇NO₃S: C, 60.19; H, 6.13; N, 5.28. Found: C, 60.20; H, 6.13; N, 4.99. 1-(3-Methoxyphenyl)-2-morpholino-2-thioxoethanone (3r) Dark yellow oil. FTIR (KBr): 2920 (CH), 1642 (C=O), 1600 (C=C), 1489 (C=S), 1435 (CH₂ bending), 1268 (CO), 1246 (CN), 1110 (C=S) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.51–7.56 (m, 2 H, CH_Ar), 7.40 (t, J = 8.0 Hz, 1 H, CH_Ar), 7.16–7.19 (m, 1 H, CH_Ar), 4.32–4.35 (m, 2 H, CH₂O), 3.90–3.93 (m, 2 H, CH₂O), 3.87 (s, 3 H, OCH₃), 3.70–3.72 (m, 2 H, CH₂N), 3.60–3.62 (m, 2 H, CH₂N). ¹³C NMR (400 MHz, CDCl₃): δ = 195.6 (C=S), 187.7 (C=O), 160.1, 134.5, 130.2, 122.8, 121.8, 113.4, 66.7, 55.6, 51.9, 47.1. Anal. Calcd for C₁₃H₁₅NO₃S: C, 58.85; H, 5.70; N, 5.28. Found: C, 58.44; H, 5.39; N, 5.00. 1-(4-Methoxyphenyl)-2-morpholino-2-thioxoethanone (3s) Yellow solid; mp 117–118.5 °C. FTIR (KBr): 3110, 2969 (CH), 1654 (C=O), 1595 (C=C), 1500 (C=S), 1437 (CH₂ bending), 1263 (CO), 1234 (CN), 1110 (C=S) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.97–8.01 (m, 2 H, CH_Ar), 6.97–7.01 (m, 2 H, CH_Ar), 4.34–4.37 (m, 2 H, CH₂O), 3.92–3.94 (m, 2 H, CH₂O), 3.91 (s, 3 H, OCH₃), 3.70–3.73 (m, 2 H, CH₂N), 3.62–3.63 (m, 2 H, CH₂N). ¹³C NMR (400 MHz, CDCl₃): δ = 196.2 (C=S), 187.3 (C=O), 164.6, 132.3, 126.1, 114.3, 66.5, 55.7, 51.9, 47.1. Anal. Calcd for C₁₄H₁₇NO₄S: C, 56.93; H, 5.80; N, 4.74. Found: C, 56.61; H, 5.80; N, 4.42.