General procedure for the synthesis of 2-chloro-3-cyano-4-methylpyridine from 3-cyano-4-methyl-2-pyridone: (c) Preparation of 2-chloro-3-cyano-4-methylpyridine (chlorination)
4-Methyl-3-cyano-2-pyridone (40.7 g, 0.304 mol) was added to a stirred mixed solution of phosphorus trichloride (POCL3, 140 g, 0.912 mol) and phosphorus pentachloride (PCl5, 19.0 g, 0.091 mol). The reaction mixture was heated to reflux (about 115 °C) and maintained at this temperature for 2 hours of reaction. Upon completion of the reaction, the excess phosphorous trichloride was removed by distillation. After the reaction mixture was cooled to room temperature, it was quenched by slowly adding water (30 mL). The aqueous phase was extracted with dichloromethane (30 mL), and the organic phases were combined and concentrated to give 43.2 g of a tan solid, which was identified as 2-chloro-3-cyano-4-methylpyridine (4). The melting point was 102-104 °C. The yield was 98.2%.
1H NMR (CDCl3): δ 8.03 (d, J = 2 Hz, 1H), 7.6 (d, J = 2 Hz, 1H), 2.5 (s, 3H).
13C NMR (CDCl3): δ 156.1, 152.6, 151.8, 124.9, 114.4, 111.8, 20.6; δ 156.1, 152.6, 151.8, 124.9, 114.4, 111.8, 20.6.
FTIR (KBr, cm-1): 3144, 2979, 2834, 2228, 1653, 1616, 1540, 1484, 1242, 1218, 1173, 819, 607.
