[Synthesis]
General procedure for the synthesis of 8-chloro-1,2,3,4-tetrahydroisoquinoline hydrochloride from 2-(2-chloro-benzylamino)-ethanol: To a mixture of 2-(2-chloro-benzylamino)-ethanol (10.00 g, 45.05 mmol) and ammonium chloride (1.76 g, 32.9 mmol) was added, at 185°C, aluminum chloride (11.60 g, 87.02 mmol). After 40 and 70 minutes of reaction, additional portions of aluminum chloride (5.80 g, 43.5 mmol and 11.60 g, 87.02 mmol) were added and the mixture continued to be stirred at the same temperature. The reaction mixture was poured into a slurry of ice and 3M HCl solution under strong stirring. The resulting solution was alkalized to pH 14 with 40% NaOH solution and subsequently extracted with ether (300 mL and 2 x 150 mL). The organic layers were combined, dried with anhydrous magnesium sulfate, and the solvent was evaporated to give an oily residue (7.07 g, 94%) containing both isomers (9:1 ratio, as determined by GC-MS). The oily substance was dissolved in isopropanol (50 mL) and the isopropanol solution of hydrochloric acid gas was added dropwise. The precipitate was collected by filtration and the residue was recrystallized twice with isopropanol to give 8-chloro-1,2,3,4-tetrahydroisoquinoline hydrochloride (2.32 g, 25%) as a light brown solid. Melting point 244-246 °C (isopropanol, off-white solid).IR (KBr): ν= 3423, 1587, 1468 cm-1.1H NMR (400 MHz, CD3OD): δ= 7.37 (br d, J = 7.7Hz, 1H), 7.31 (t, J = 7.7Hz, 1H), 7.24 (br d, J = 7.7Hz. 1H), 4.37 (s, 2H), 3.49 (t, J = 6.3 Hz, 2H), 3.14 (br t, J = 6.3 Hz, 2H).13C NMR (100 MHz, CD3OD): δ= 135.6, 133.3, 130.2, 129.0, 128.8, 127.3, 43.9, 42.2, 26.2. HRMS calculated value C9H11ClN + ([M + H] +): 168.0575, measured value: 168.0580. |