N-Methylimidazole-Promoted Efficient Synthesis of Functionalized 1,3-Oxazoline-2-thiones under Solvent-Free Conditions

Abstract

An efficient synthesis of ethyl 2-thioxo-2,3-dihydro-1,3-oxazole-5-carboxylates or ethyl 5-methyl-2-thioxo-2,3-dihydro-1,3-oxazole-4-carboxylates, under solvent-free conditions, is described via reaction between ammonium thiocyanate, acid chlorides, and ethyl bromopyruvate or ethyl 2-chloroacetoacetate in the presence of N-methylimidazole.

oxazole - ethyl bromopyruvate - N-methylimidazole - ammonium thiocyanate - benzoyl chloride - ethyl 2-chloroacetoacetate

References and Notes

<A NAME="RD05208ST-1">1</A> Willems JF. Vandenberghe A. Bull. Soc. Chim. Belg.  1961,  70:  745 

<A NAME="RD05208ST-2">2</A> Lacasse G. Muchowki JM. Can. J. Chem.  1972,  50:  3082 

<A NAME="RD05208ST-3">3</A> Bradscher CK. Jones WJ. J. Org. Chem.  1967,  32:  2079 

<A NAME="RD05208ST-4">4</A> Guimon C. Pfister-Guillouzo G. Arbelot M. Chanon M. Tetrahedron  1974,  30:  3831 

<A NAME="RD05208ST-5">5</A> Kapsomenos GS. Akrivos PDD. Can. J. Chem.  1988,  66:  2835 

<A NAME="RD05208ST-6">6</A> Shafer CM. Molinski TF. J. Org. Chem.  1998,  63:  551 

<A NAME="RD05208ST-7">7</A> Gonzalez-Romero C. Martinez-Palou R. Jimenez-Vazquez HA. Fuentes A. Jimenez F. Tamariz J. Heterocycles  2007,  71:  305 

<A NAME="RD05208ST-8">8</A> Bobosik V. Piklerova A. Maretvon A. Collect. Czech. Chem. Commun.  1983,  48:  3421 

<A NAME="RD05208ST-9">9</A> Tatibouët A. Lawrence S. Rollin P. Holman GD. Synlett  2004,  1945 

<A NAME="RD05208ST-10">10</A> Leconte N. Silva S. Tatibouët A. Rauter AP. Rollin P. Synlett  2006,  301 

<A NAME="RD05208ST-11">11</A> Yavari I. Mirzaei A. Moradi L. Helv. Chim. Acta  2006,  89:  2825 

<A NAME="RD05208ST-12">12</A> Yavari I. Sabbaghan M. Hossaini Z. Synlett  2006,  2501 

<A NAME="RD05208ST-13">13</A> Yavari I. Souri S. Synlett  2007,  2969 

<A NAME="RD05208ST-14">14</A>

General Procedure for the Preparation of Compounds 4 and 11: A stirred mixture of ammonium isothiocyanate (0.15 g, 2 mmol) and acid chloride 2 (2 mmol) was warmed at about 90 °C in a water bath for 5 min and ethyl bromopyruvate (0.39 g, 2 mmol) or ethyl 2-chloroaceto
acetate (0.33 g, 2 mmol) was added slowly. The mixture was allowed to cool to r.t. and N-methylimidazole (0.032 g, 20 mol%) was added. The reaction mixture was stirred for 12 h and extracted with Et₂O (2 mL) to afford the pure title compounds.
Compound 4a: pale yellow crystals; yield: 0.38 g (85%); mp 129-131 °C. IR (KBr): 1724, 1631, 1585, 1518, 1470 cm^-1. ¹H NMR: δ = 1.45 (t, ³ J = 7.2 Hz, 3 H, Me), 4.46 (q, ³ J = 7.2 Hz, 2 H, OCH₂), 7.52 (t, ³ J = 7.8 Hz, 2 H, 2 × CH), 7.61 (t, ³ J = 6.1 Hz, 1 H, CH), 7.65 (s, 1 H, CH), 7.52 (d, ³ J = 6.1 Hz, 2 H, 2 × CH). ¹³C NMR: δ = 14.6 (Me), 63.0 (OCH₂), 118.4 (CH), 128.9 (2 × CH), 130.5 (2 × CH), 133.8 (CH), 134.9 (C), 139.8 (C), 156.6 (C=O), 176.7 (C=O), 178.1 (C=S). EI-MS: m/z = 227 (10) [M⁺], 121 (20), 105 (100), 77 (90), 57 (30), 51 (64), 45 (36). Anal. Calcd for C₁₃H₁₁NO₄S (277.29): C, 56.31; H, 4.00; N, 5.05. Found: C, 56.30; H, 4.03; N, 5.00.
Compound 11a: white powder; yield: 0.49 g (85%); mp 140-142 °C. IR (KBr): 1720, 1635, 1582, 1510, 1475 cm^-1. ¹H NMR: δ = 1.38 (t, ³ J = 7.2 Hz, 3 H, Me), 2.68 (s, 3 H, Me), 4.34 (q, ³ J = 7.2 Hz, 2 H, OCH₂), 7.48 (t, ³ J = 7.5 Hz, 2 H, 2 × CH), 7.58 (t, ³ J = 7.5 Hz, 1 H, CH), 8.31 (d, ³ J = 7.5 Hz, 2 H, 2 × CH). ¹³C NMR: δ = 13.8 (Me), 14.1 (Me), 62.0 (OCH₂), 110.4 (C), 128.4 (2 × CH), 129.9 (2 × CH), 133.1 (CH), 134.8 (C), 155.5 (C), 160.6 (C=O), 176.1 (C=O), 177.5 (C=S). EI-MS: m/z = 291 (15) [M⁺], 186 (78), 105 (100), 77 (48), 45 (48). Anal. Calcd for C₁₄H₁₃NO₄S (291.32): C, 57.72; H, 4.50; N, 4.81. Found: C, 57.76; H, 4.54; N, 4.80.