Acetic Acid → 4-Chloro-2-(methylsulfonyl)pyrimidine

Participants

Reaction Steps

To a stirred solution of 4-chloro-2-methylthiopyrimidine (10.00 g, 62.3 mmol) in glacial acetic acid (50 ml) at 10°-15° C. was added a solution of potassium permanganate (12.50 g, 79.15 mmol) in water (100 ml). The reaction mixture was stirred overnight at room temperature, cooled to 5° C. and then treated with gaseous sulphur dioxide until the dark solution was decolourised. Water was added and the mixture extracted with chloroform. The combined organic layers were washed with saturated aqueous sodium bicarbonate solution and then water, and dried. Evaporation gave 4-chloro-2-methanesulphonylpyrimidine as a white solid (10.84 g),mp 91°-3° C. 4-Chloro-2-methanesulphonylpyrimidine (7.00 g,36.33 mmol) was treated with sodium phenoxide [from phenol (3.41 g,36.33 mmol) and sodium hydride (1.74 g, 39.97 mmol, 50% dispersion in oil)] in dry DMF (100 ml) at 0°-5° C. After 30 minutes, the starting material had been consumed (GC analysis). The reaction mixture was diluted with water and then extracted with ether (×2). The combined extracts were washed with 5% aqueous sodium hydroxide solution (×2) and brine, and then dried. Evaporation of the solvent gave a very pale yellow, mobile oil (5.35 g). Chromatography (eluent ether:n-hexane, 2:3) followed by crystallisation afforded 4-chloro-2-phenoxypyrimidine as a white solid (3.50 g, 84% pure by GC). Further chromatography yielded pure product (2.50 g,33%), mp 59°-60° C.

Provenance & Evidence