Phosphorus oxychloride → 2-Methyl-5-(2-nitro-phenylamino)-thiazole-4-carbonitrile

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Reaction Conditions

Reaction Steps

Combine 2-methyl-5-(2-nitroanilino)thiazole-4-carboxylic acid amide (60 g, 215 mmol) and toluene and add POCl3 (40 mL, 430 mmol) and reflux the reaction mixture. After 2.5 h cool to 0° C. Add saturated NaHCO3 solution to quench the extra POCl3 (Caution!!) until the aqueous was around pH 8. Add ethyl acetate (2×2 L) to extract the product. Combined organic layer and wash with brine (2×1 L), dry over MgSO4. and evaporate to give a reddish solid which triturated with 25% ethyl acetate in hexane to give a reddish solid (36 g). Evaporate the filtrate to half volume to give second batch of compound (3.2 g). Total yield (39.2 g, 70%): mass spectrum (m/e): 261(M+1); 1HNMR(300 MHz, DMSO-d6, ppm): δ 2.70(s, 1H), 7.02(t, 1H), 7.22(d, 1H), 7.58(t, 1H), 8.25(d, 1H), 9.78(s, 1H): 13CNMR(75 MHz, DMSO-d6, ppm): δ20.4, 113.1, 116.2, 118.7, 121.2 127.0, 134.9, 136.6, 140.0, 148.6, 161.5. Formula: C11H8N4O2S

Provenance & Evidence