2-Bromophenyl isothiocyanate 1.0mL (1.593g, 7.44 mmol) was added dropwise into a stirred 7M anh NH3 solution in methanol (40mL), the mixture was stirred for 1 hour and then evaporated. The residue was dissolved in ethanol 25mL, heated to reflux, cooled, filtered from a small amount of cloudy precipitate and the filtrates were evaporated. The residue was induced to crystallization by addition of few drops of water, the solidified mass was dried on highvac. The obtained crude thiourea (1.737 g of a light tan crystalline solid) was dissolved in ethanol 50 mL with a gentle heating.The solution was cooled to RT and solid bromopyruvic acid 1.242g (7.44 mmol) was added, the mixture was stirred for 30 min and then evaporated. The residue was suspended in water 50mL with sonication (for 10 min), anhydrous sodium acetate solid 840mg was added to raise the pH of the mixture and the slurry was sonicated for additional 5 min. The precipitated product was collected by filtration, washed with water, dried by suction and then on highvac.
Y=1.749g (78.5%) of a white crystalline solid.
1H-NMR(d6-DMSO, 400MHz): 12.681 (very br s, 1H), 9.629(very br s, 1H), 8.144(dd, 8.2Hz, 1.6Hz, 1H), 7.718(s, 1H), 7.652(dd, 8.0Hz, 1.5Hz, 1H), 7.394(m, 1H), 7.039(m, 1H); LC-MS(+ESI): 299, 301
Using the same procedure, 1.0mL of 2-chlorophenyl isothiocyanate (1.310g, 7.72mmol) and 40mL of 7M methanolic NH3 provided 1.452g of a crude thiourea that was cyclized with bromopyruvic acid 1.289g (7.72 mmol) and neutralized with AcONa 900mg to provide 1.401g (71%) of 2-(2′-chlorophenylamino)-thiazole-4-carboxylic acid as a white crystalline solid. 1H-NMR(d6-DMSO, 400MHz): 12.705 (very br s, 1H), 9.779(very br s, 1H), 8.358(dd, 8.3Hz, 1.5Hz, 1H), 7.748(s, 1H), 7.477(dd, 8.0Hz, 1.4Hz, 1H), 7.350(m, 1H), 7.070(m, 1H); LC-MS(+ESI): 255, (257)