Phosphorus oxychloride → 2-chloro-5-phenylnicotinonitrile

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, 68.4 grams (0.45 mole) of phosphorus oxychloride is warmed to a gentle reflux, and 38.9 grams (0.18 mole) of 3-cyano-5-phenylpyridin-2-one is added. Upon completion of addition, 93.6 grams (0.45 mole) of phosphorous pentachloride is added in small portions to maintain the gentle reflux. Upon completion of addition, the reaction mixture is then warmed slowly to about 140° C. where it is stirred for one hour. The reaction mixture is cooled, and excess phosphorus oxychloride is removed under reduced pressure. The concentrate is then poured into 400 grams of ice, where it is stirred until the ice melts. The mixture is then extracted with three 200 mL portions of methylene chloride and 100 mL of diethyl ether. The combined extracts are washed with 150 mL of water and 150 mL of an aqueous solution saturated with sodium chloride. The organic layer is dried with sodium sulfate and filtered. The filtrate is concentrated under reduced pressure at 30° C. to a residue. The residue is distilled under vacuum, yielding 35.4 grams of 2-chloro-3-cyano-5-phenylpyridine, bp 175°-179° C./4 mm Hg., as a crystalline material. The crystalline 2-chloro-3-cyano-5-phenylpyridine is recrystallized from hexane/methylene chloride, mp 149°-150° C.

Provenance & Evidence