1-Methylpiperazine → 4-[(4-methylpiperazin-1-yl)methyl]benzoic Acid Dihydrochloride

Participants

Reaction Steps

To a well-stirred suspension consisting of 17.1 g. (0.10 mole) of α-chloro-p-toluylic acid in 150 ml of absolute ethanol under a nitrogen atmosphere at room temperature (˜20° C.), a solution consisting of 44.1 g. (0.44 mole) of N-methylpiperazine dissolved in 50 ml. of ethanol was added dropwise. The resulting reaction mixture was refluxed for a period of 16 hours and then cooled to room temperature. The cooled reaction mixture was concentrated in vacuo and the thus obtained residue partitioned between 100 ml of diethyl ether and 100 ml of 3N aqueous sodium hydroxide. The separated aqueous layer was then washed three times with 100 ml of diethyl ether, cooled in an ice-water bath and subsequently acidified with concentrated hydrochloric acid. The resulting solids were filtered and air-dried, followed by trituration with 150 ml of boiling isopropyl alcohol and stirring for a period of two minutes. After filtering while hot and drying the product there were obtained 9.4 g (35%) of pure 4-(4-methylpiperazinomethyl)benzoic acid dihydrochloride (9) as the hemihydrate, m.p. 310°-312° C. MS: 235.1 (M+H); 1H NMR (D2O) δ 8.04 (d, J=8.21 Hz, 2H), 7.59 (d, J=8.21 Hz, 2H), 3.50 (s, 2H), 3.63 (br, 8H), 2.97 (s, 3H); 13C NMR δ 170.18, 133.13, 131.91, 130.90, 60.22, 50.61, 48.77, 43.25.

Provenance & Evidence