The general procedure for the synthesis of 4,5,6-trichloropyrimidine from 4,6-dihydroxypyrimidine was as follows: 89.7 g of 4,6-dihydroxypyrimidine and 179.3 g of chlorobenzene were added to a 1000 mL four-neck flask. The mixture was heated to 40 °C, and then 129.6 g of sulfonyl chloride was slowly added dropwise over a period of 1 hour. After the dropwise addition was completed, the reaction mixture was kept stirred at 40 °C for 6 hours. Subsequently, 269.9 g of phosphoryl chloride was added to the reaction mixture at the same temperature. Next, 178.1 g of triethylamine was slowly added dropwise over a period of 2 hours at temperatures ranging from 40 to 80 °C. After completion of the dropwise addition, the reaction mixture was warmed up to 83 °C and kept for 10 hours. Upon completion of the reaction, the mixture was cooled to room temperature. To another 100 mL four-necked flask was added 269.0 g of water and heated to 40 °C. The above reaction mixture was slowly added dropwise to the water over a period of 30 minutes, keeping the internal temperature between 30 and 50 °C during the dropwise addition. Upon completion of the reaction, the mixture was filtered using Radiolite (registered trademark) to separate the organic and aqueous layers. The aqueous layer was extracted with 44.8 g of chlorobenzene and the organic layers were combined. The combined organic layers were washed with 44.8 g of water and subsequently concentrated under reduced pressure to give 169.2 g of black oil. The oily substance was analyzed by high performance liquid chromatography (HPLC) with internal standard method and it was determined that the oily substance contained 126.9 g of 4,5,6-trichloropyrimidine in 86% yield.
