3-Chloro-4-cyanopyridine

100-48-1

68325-15-5

The general procedure for the synthesis of 3-chloro-4-cyanopyridine from 4-cyanopyridine was as follows: to a stirred solution of 2,2,6,6-tetramethylpiperidine (17.16 mL, 100.854 mmol) in tetrahydrofuran (THF, 100 mL) at -30 °C was slowly added n-butyllithium (n-BuLi, 2.17 M, 44.26 mL, 96.052 mmol). The reaction mixture was stirred at 25 °C for 15 min before being cooled to -78 °C and a solution of 4-cyanopyridine (5 g, 48.026 mmol) in THF (40 mL) was added slowly and dropwise. After continued stirring at -78 °C for 30 min, a THF (50 mL) solution of hexaethyl ethane (23.87 g, 100.854 mmol) was added. The resulting mixture was stirred at -78 °C for 30 min, followed by quenching the reaction with saturated ammonium chloride (NH4Cl) solution. Water (100 mL) was added to the reaction mixture and extracted with ethyl acetate (4 x 300 mL). The organic layers were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. The crude product was purified by column chromatography using silica gel (100-200 mesh) and 5% ethyl acetate-hexane as eluent to yield 3-chloropyridine-4-carbonitrile (3.5 g, 25.26±1 mmol, 53% yield) as a light-white solid.The GC-MS analysis showed the molecular ion peak to be 138 m/z. The molecular ions were analyzed by GC-MS.