Synthesis of Functionalized 1,3-Thiazoles from Acid Chlorides, Primary Amines, Ethyl Bromopyruvate, and Ammonium Thiocyanate

Abstract

An efficient synthesis of 1,3-thiazole-4(3H)-carboxylates is described via a four-component reaction between acid chlorides, primary amines, ethyl bromopyruvate, and ammonium thiocyanate.

Key word

1,3-thiazole - benzylamine - ethyl bromopyruvate - benzoyl isothiocyanate

References and Notes

• 1 Breslow R. J. Am. Chem. Soc.  1958,  80:  3719 
• 2 Miwatashi S. Arikawa Y. Kotani E. Miyamoto M. Naruo K.-I. Kimura H. Tanaka T. Asahi S. Ohkawa S. J. Med. Chem.  2005,  48:  5966 
• 3 Papadopoulou C. Geronikaki A. Hadjipavlou-Litina D. Farmaco  2005,  60:  969 
• 4 Kumar Y. Green R. Borysko KZ. Wise DS. Wotring LL. Townsend LB. J. Med. Chem.  1993,  36:  3843 
• 5 Pereira R. Gaudon C. Iglesias B. Germain P. Gronemeyer H. de Lera AR. Bioorg. Med. Chem. Lett.  2006,  16:  49 
• 6 Tsuruni Y. Ueda H. Hayashi K. Takase S. Nishikawa M. Kiyoto S. Okuhara M. J. Antibiot.  1995,  48:  1066 
• 7 Aguilar E. Meyers AI. Tetrahedron Lett.  1994,  35:  2473 
• 8 Varma RS. Pure Appl. Chem.  2001,  73:  193 
• 9 Ochiai M. Nishi Y. Hashimoto S. Tsuchimoto Y. Chen D.-W. J. Org. Chem.  2003,  68:  7887 
• 10 Yavari I. Djahaniani H. Tetrahedron Lett.  2006,  47:  2953 
• 11 Yavari I. Moradi L. Helv. Chim. Acta  2006,  89:  1942 
• 12 Yavari I. Sabbaghan M. Hossaini Z. Synlett  2006,  2501 
• 13 Yavari I. Souri S. Synlett  2007,  2969 

14

Ethyl 2-(Benzoylimino)-3-benzyl-1,3-thiazole-4(3 H )-carboxylate (5a); Typical ProcedureTo a stirred solution of NH₄SCN (0.15 g, 2 mmol) in acetone (15 mL) was added benzoyl chloride (0.28 g, 2 mmol), the mixture was refluxed for 5 min and a solution of ethyl bromopyruvate (0.39 g, 2 mmol) in acetone (10 mL) acetone was added dropwise. After addition of the primary amine (2 mmol) at r.t., the reaction mixture was then stirred for 24 h, the solvent was removed under reduced pressure, and the residue was purified by column chromatography (SiO₂; hexane-EtOAc, 9:1) to give 5a as colorless crystals; mp 119-121 °C, yield 0.62 g (85%). IR (KBr): ν_max = 1716, 1658, 1587, 1477, 1429, 1369, 1369, 1304, 1231, 1105, 1054 cm^-1. ¹H NMR (500.1 MHz, CDCl₃): δ = 1.33 (3 H, t, ³ J = 7.2 Hz, Me), 4.31 (2 H, q, ³ J = 7.2 Hz, OCH₂), 6.07 (2 H, s, NCH₂), 7.24-7.32 (3 H, m, 3 CH), 7.38 (2 H, d, ³ J = 7.4 Hz, 2 CH), 7.45 (2 H, t, ³ J = 7.2 Hz, CH), 7.51 (1 H, d, ³ J = 7.2 Hz, CH), 7.63 (1 H, s, CH), 8.34 (2 H, d, ³ J = 7.2 Hz, 2 CH) ppm. ¹³C NMR (500.1 MHz, CDCl₃): δ = 14.0 (Me), 50.4 (CH₂), 61.9 (OCH₂), 120.8 (CH), 127.7 (2 CH), 128.1 (3 CH), 128.6 (2 CH), 129.5 (3 CH), 131.8 (C), 136.5 (C), 136.8 (C), 158.3 (C=O), 169.3 (C=N), 174.8 (C=O). MS:
m/z (%) = 366 (10) [M⁺], 293 (75), 261 (62), 105 (100), 91 (82), 45 (84). Anal. Calcd (%) for C₂₀H₁₈N₂O₃S (366.43): C, 65.56; H, 4.95; N, 7.64. Found: C, 65.63; H, 4.99; N, 7.68. All other compounds 5b-j gave satisfactory analytical and spectroscopic data.