反应详情

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.

1. customat room temperature
2. custom(˜20° C.)
3. customThe resulting reaction mixture
4. temperaturewas refluxed for a period of 16 hours
5. customThe cooled reaction mixture
6. concentrationwas concentrated in vacuo
7. customthe thus obtained residue partitioned between 100 ml of diethyl ether and 100 ml of 3N aqueous sodium hydroxide
8. washThe separated aqueous layer was then washed three times with 100 ml of diethyl ether
9. temperaturecooled in an ice-water bath
10. filtrationThe resulting solids were filtered
11. customair-dried
12. filtrationAfter filtering while hot and
13. customdrying the product there