Products > TCI Topics Archives > TCI Topics 2023 >

TCI Practical Example: Thiazole Ring Construction Reaction Using 1-Bromo-3,3,3-trifluoroacetone

We are proud to present the thiazole ring construction reaction using 1-bromo-3,3,3-trifluoroacetone and thiobenzamide.

Used Chemicals

• Thiobenzamide [T0194]
• 1-Bromo-3,3,3-trifluoroacetone [B1240]
• p-Toluenesulfonic Acid Monohydrate (= TsOH·H₂O) [T0267]
• Ethanol
• Toluene

Procedure

1-Bromo-3,3,3-trifluoroacetone (0.252 mL, 2.4 mmol, 1.2 eq.) was added to a ethanol (20 mL) solution of thiobenzamide (274 mg, 2.0 mmol) at room temperature and the mixture was refluxed for 4 hours. Then the solvent was removed under reduced pressure. Toluene (20 mL) and p-toluenesulfonic acid monohydrate (190 mg, 1.0 mmol, 0.5 eq.) were added to the residue and refluxed for overnight. After that the solvent was remove under reduced pressure and the residue was purified by column chromatography (on silica gel, ethyl acetate:hexane = 0:1 - 1:10) to give 2-phenyl-4-(trifluoromethyl)thiazole as a pale yellow solid (387 mg, 84% yield).

Experimenter’s Comments

The reaction mixture was monitored by UPLC.

Analytical Data

2-Phenyl-4-(trifluoromethyl)thiazole

¹H NMR (400 MHz, CDCl₃); δ 7.99-7.97 (m, 2H), 7.74 (s, 1H), 7.49-7.46 (m, 3H).

Lead Reference

• Optimization of Novel 1-Methyl-1H-Pyrazole-5-carboxamides Leads to High Potency Larval Development Inhibitors of the Barber's Pole Worm
• • T. G. Le, A. Kundu, A. Ghoshal, N. H. Nguyen, S. Preston, Y. Jiao, B. Ruan, L. Xue, F. Huang, J. Keiser, A. Hofmann, B. C. H. Chang, J. Garcia-Bustos, A. Jabbar, T. N. C. Wells, M. J. Palmer, R. B. Gasser, J. B. Baell, J. Med. Chem. 2018, 61, 10875.