5-Chloroquinoline

611-34-7

635-27-8

General procedure for the synthesis of 5-chloroquinoline from 5-aminoquinoline: 5-aminoquinoline (756 mg, 5.24 mmol) was suspended in an aqueous 2N HCl solution (31 mL) and cooled to 0°C. A solution of NaNO2 (470 mg, 6.80 mmol) in water (14 mL) was added slowly with stirring. The reaction mixture was kept stirred at 0 °C for 30 min. Subsequently, a concentrated hydrochloric acid solution of CuCl (644 mg, 6.51 mmol) was added and additional concentrated hydrochloric acid (16 mL) was added. The reaction mixture was gradually warmed to room temperature and stirring was continued for 24 hours. After the reaction was completed, saturated NaHCO3 solution was added slowly until no more gas was produced. The organic phase was extracted with dichloromethane (3 x 50 mL) and the combined organic layers were washed with brine and dried over anhydrous MgSO4. The solvent was removed by concentration under reduced pressure and the resulting crude product was purified by silica gel column chromatography (eluent: EtOAc/hexane=1:1) to afford the target product 5-chloroquinoline (579 mg, 68% yield).