|
|
|
| Synthesis of 1-[(4-Chlorophenyl)phenyl methyl] Piperazine |
| DONG Chuan-ming, CHU Ji-cheng, LI Mao-xia |
| Chemtech (Tianjin) Chemical Corporation Ltd., Tianjin 300380, China |
|
|
|
|
Abstract 1-[(4-chlorophenyl)phenyl methyl] piperazine, the key intermediate of cetirizine hydrochloride, was synthesized from 4-chlorobenzophenone via reduction with zinc dust, bromination with hydrogen bromide and final reaction with anhydrous piperazine. The optimum reaction conditions were obtained as follow: molar ratio of reagent (zinc/4-chlorobenzophenone) was 2.5; bromination temperature was between 75~80 ℃, and temperature of piperazine reaction was between 80~85 ℃. The final product (HPLC 98.7%) was prepared with an overall yield of 71.2%. The materials of this route were cheap and common and it was suitable for industrial production.
|
|
|
|
|
|
| [ 1 ] 李荣东，朱志宏，段立新.盐酸西替利嗪的合成[ J ]. 中国药物化学杂志，2000，10（1）：66 - 67.
[ 2 ] Guy D, Vincent Z, Guy B. Process for the preparation of 2-[2-[4-[(4-chlorophenyl) phenyl methyl] -1-piperazinyl] ethoxy] acetic acid and its salts[ P ] . EP：801064, 1996-04-10.
[ 3 ] 金永生，姚 斌，吴秋业，等.1-[(4-氯苯基)苯甲基]哌嗪合成方法的改进[ J ] . 实用医药杂志，2005,22（12）：1 108 - 1 109.
[ 4 ] Robert HB, Loren EL. Catalysis with aluminum 2-methylbutoxide[ J ]. J Am Chem Soc, 1949, 71(2): 1 399-1 401.
[ 5 ] Yung DK, Gilroy ML, Mahony DE. Synthesis and quantitative structure-activity relationships of antibacterial 1-(substituted benzhydryl)-4-(5-nitro-2 -furfurylideneamino) piperazines[ J ]. J Pharm Sci, 1978, 67(7): 900-905. |
|
|
|
