Thionyl Chloride → 2-Chloronicotinoyl chloride

Participants

Reaction Steps

A mixture of 2.226 g (14.36 mmol) of 2-chloronicotinic acid, 15 ml of thionyl chloride and two droplets of DMF was heated under reflux for 2 hours. The resulting reaction solution was allowed to cool, and then concentrated under reduced pressure to obtain 2-chloronicotinoyl chloride. The compound thus obtained was dissolved in 10 ml of acetone. The solution thus obtained was then added dropwise to a solution of 1.21 of ammonium thiocyanate in 15 ml of acetone with stirring in 5 minutes. After the termination of dropwise addition, the reaction mixture was heated to a temperature of 40° C. with stirring for 6 minutes. The resulting insoluble matters were then removed by filtration to obtain a solution of 2-chloronicotinoyl isothiocyanate. To the solution thus obtained was then added dropwise a solution of 1.80 g of 4-fluoro-N-methylaniline in 10 ml of acetone with stirring in 5 minutes. The reaction mixture was stirred at room temperature for 15 hours, and then poured into about 1,000 ml of ice-water. The resulting crystal was collected by filtration, washed with water, dried under reduced pressure, and then recrystallized from ethanol to obtain 2.99 g of 2-[N-(4-fluorophenyl)-N-methylamino]-4H-pyrido[3,2-e]-1,3-thiazin-4-one.

Provenance & Evidence