Thionyl Chloride → 3-Fluoroisonicotinoyl chloride

Participants

Reaction Steps

A mixture of 1.658 g (11.75 mmol) of 3-fluoroisonicotinic acid, 15 ml of thionyl chloride and three droplets of DMF was heated under reflux for 2 hours. The reaction mixture was allowed to cool, and then concentrated under reduced pressure to obtain 3-fluoroisonicotinoyl chloride. The compound thus obtained was then dissolved in 10 ml of acetone. The solution thus obtained was then added dropwise to a solution of 984 mg 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 5 minutes. The resulting insoluble matters were then removed by filtration to obtain an acetone solution of 3-fluoroisonicotinoyl isothiocyanate. To the solution thus obtained was then added dropwise a solution of 1.55 g of 4-chloro-N-methylaniline in 10 ml of acetone with stirring for 5 minutes. The reaction mixture was stirred at room temperature for 17 hours, and then poured into about 1,000 ml of ice-water. The resulting crystal was collected by filtration, washed with water, and then dried under reduced pressure. The resulting crude product was then purified through silica gel column chromatography (eluant: CHCl3 +2% methanol) to obtain 1.452 g of 1-(4-chlorophenyl)-3-(3-fluoroisonicotinoyl)-1-methylthiourea.

Provenance & Evidence