Bromine‐Mediated C‐S Bond Formation: Synthesis of Thiazoles from α‐Methylene Ketones by Using Oxone Oxidative System

Abstract

A novel method for the synthesis of various 2,4,5‐trisubstituted thiazoles from methylketones and thiourea/thioacetamide/amidinothiourea using NaBr/Oxone oxidative system has been developed. The three intimately connected advantages of this method, which form a whole, are that the reaction underwent a one‐pot α‐bromination/cyclization process, the use of more common methylene ketones as the raw material rather than α‐halomethylene ketones and a cheap and easily available catalytic amount sodium bromide as the bromine source instead of stoichiometric bromine or NBS.

Copper-mediated [3 + 2] oxidative cyclization of oxime acetate and its utility in the formal synthesis of fentiazac

“…4-Phenyl-2-aminothiazole (2a). 21 White solid; 32 mg; yield 64%; mp: 148-151 °C; R f : 0.5 (8 : 2, EA : Pet ether); IR (ν cm −1 ): 3382 (w), 1610 (s), 1532 (s), 1489 (s), 1040 (s), 837 (s), 730 (s); 1 H NMR (500 MHz, CDCl 3 ): δ 7.77 (d, J = 7.6 Hz, 2H), 7.38 (t, J = 7.5 Hz, 2H), 7.29 (t, J = 7.3 Hz, 1H), 6.72 (s, 1H) 5.10 (s, 2H); 13 C NMR (126 MHz, CDCl 3 ): δ 167. 2, 151.3, 134.6, 128.6, 128.6 127.7, 126.0, 126.0, 102.8; HRMS (ESI-qTOF) calcd for C 9 H 8 N 2 S [M + H] + , 177.0408, found 177.0818.…”

“…4-(4′-Methoxy-phenyl)-2-aminothiazole (2b). 21 White solid; 32 mg; yield 64%; mp: 198-201 °C; R f : 0.3 (9 : 1, EA : Pet ether); IR (ν cm −1 ): 3438 (w), 3272 (w), 3116 (w), 1625 (s), 1607 (s), 1535 (s), 1492 (s), 1034 (s), 834 (s), 736 (s); 1 H NMR (500 MHz, DMSO-d 6 ): δ 7.71 (d, J = 6.9 Hz, 2H), 7.28 (bs, 2H), 6.94 (d, J = 6.8 Hz, 2H), 6.86 (s, 1H), 3.77 (s, 3H), 5.10 (s, 2H); 13 C NMR (126 MHz, DMSO-d 6 ): δ 168.8, 159. 2, 129.9, 129.9, 127.3, 114.3, 114.3, 114.0, 99.9, 55.…”

“…4-(3′-Nitro-phenyl)-2-aminothiazole (2h). 21 Yellow solid; 27 mg; yield 54%; mp: 189-191 °C; R f : 0.4 (6 : 4, EA : Pet ether); IR (ν cm −1 ): 3388 (w), 3314 (w), 1580 (s), 1550 (s), 1600 (s), 1450 (s), 1043 (s), 837 (s), 739 (s); 1 H NMR (400 MHz, DMSOd 6 ): δ 8.63 (t, J = 2.0 Hz, 1H), (t, J = 1.0 Hz, 1H), 8.24 (t, J = 1.0 Hz, 1H), 8.11 (dd, J 1 = 8.2 Hz, J 2 = 2.4 Hz, 1H), 7.67 (t, J = 8.0 Hz, 1H), 7.34 (s, 1H), 7.24 (s, 2H); 13 C NMR (101 MHz, DMSO-d 6 ): δ 169. 0,148.6,147.8,136.8,131.8,130.5,122.1,120.5,104.7; 4-(4′-Flouro-phenyl)-2-aminothiazole (2i).…”

“…0,148.6,147.8,136.8,131.8,130.5,122.1,120.5,104.7; 4-(4′-Flouro-phenyl)-2-aminothiazole (2i). 21 Yellow solid; 35 mg; yield 70%; mp: 111-115 °C; R f : 0.1 (9 : 1, EA : Pet ether); IR (ν cm −1 ): 3470 (w), 3305 (w), 3125 (w), 1639 (s), 1532 (s), 1487 (s), 1037 (s), 832 (s), 728 (s); 1 H NMR (400 MHz, DMSOd 6 ): δ 7.86-7.80 (m, 2H), 7.19 (t, J = 8.9 Hz, 2H), 7.08 (s, 2H), 6.98 (s, 1H); 13 C NMR (101 MHz, DMSO-d 6 ): δ 168. 7, 163.0, 160.6, 149.3, 149.3 131.7, 127.9, 127.9, 115.8 153.8, 139.3, 136.5, 136.5, 132.7, 132.7, 125.3, 107.6 31 mg; yield 62%; mp: 190-194 °C; R f : 0.1 (9.5 : 0.5, EA : Pet ether); IR (ν cm −1 ): 3394 (w), 1655 (w), 1047 (s), 1023 (s), 994 (s), 824 (w), 761 (w); 1 H NMR (400 MHz, DMSO-d 6 ): δ 7.88 (d, J = 8.5 Hz, 1H), 7.64 (d, J = 2.0 Hz, 1H), 7.46 (dd, J = 8.5, 2.2 Hz, 1H), 7.11 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ): δ 167.…”

Visible-light-induced C–S bond formation in the synthesis of 2,4-disubstituted thiazoles through cascade difunctionalization of acetophenone: a greener approach

“…It may be more efficient to build heterocycles using chemicals that contain sulfur. Numerous natural substances contain organosulfur compounds, which have essential uses in batteries, 29 semiconductors, and medicine. Among these, sulfur ylide is a useful reagent since it contains both a carbanion and a sulfur cation.…”