Piperazine → 4-Piperazin-1-yl-quinoline

Participants

Reaction Steps

To a solution of 4-chloroquinoline (2.0 g, 12.2 mmol) in toluene (100 mL) was added piperazine (7.98 g, 92.7 mmol). The reaction mixture was heated to reflux and stirred for 96 hours, after which it was cooled to room temperature and then further cooled to 0° C. The resulting mixture was filtered to remove the hydrochloride salts that had precipitated. After washing the salts with toluene, the combined filtrate was washed with 10% aqueous acetic acid (2×25 mL). The combined aqueous extracts were washed with diethyl ether (25 mL) and then basified to pH 8-10 by adding 1M NaOH. The resulting aqueous mixture was extracted with dichloromethane (3×25 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated by rotary evaporation. The crude residue, 4-Piperazinylquinoline, was obtained as a yellow solid (2.54 g, 97%) and used without further purification. 1H NMR was consistent with that reported in the literature (Abel, M. D., et al., Journal of Heterocyclic Chemistry (1996), 33(2), 415-420).

Provenance & Evidence