双光气法合成中枢松弛剂氯唑沙宗-高校化学工程学报.PDF

第20 卷第2 期 高 校 化 学 工 程 学 报 No.2 Vol.20 2006 年 4 月 Journal of Chemical Engineering of Chinese Universities Apr . 2006 文章编号：1003-9015(2006)02-0254-04 双光气法合成中枢松弛剂氯唑沙宗 , , 李永曙 吴春雷 苏为科 (浙江工业大学 药学院, 浙江 杭州 310014) 摘 要：研究了新的具有工业生产价值的中枢松弛剂——氯唑沙宗的合成新工艺。该法以氯甲酸三氯甲酯(俗称双光气) 和2-氨基-6-氯苯酚为原料，通过对影响反应的多种因素进行研究以及反应条件的优化得到比较合理的工艺条件：双光 气和2-氨基-6-氯苯酚的投料摩尔比为0.525:1 ，无须加催化剂，以甲苯为溶剂，在回流的条件下滴加双光气反应1 h， 即能以92% 的高收率得到氯唑沙宗，产品纯度达到99.5%(HPLC) 。该过程条件温和，操作方便，后处理简单，具有工 业化应用前景。 关键词：中枢松弛剂；氯唑沙宗；双光气；2-氨基-6-氯苯酚；合成 中图分类号：TQ460.31 ；R971.8 文献标识码： A Synthesis of Chlorzoxaone by the Method of Diphosgene LI Yong-shu, WU Chun-lei, SU Wei-ke (College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China) Abstract: A new synthetic technological route of chlorzoxaone production was studied, in which the chlorzoxaone can be synthesized in one-step by using trichloromethy1 chlorzoxaone (diphosgene) and 2-amino-6-chlorophenol as the starting materials. The effects of various factors including feed molar ratio, solvent, catalysts and reaction temperature were investigated and the optimum reaction conditions were obtained. It is found that the reaction can be carried out without any catalyst, and the reaction will be out of control if any catalyst, such as active carbon, pyridine, triethylamine or N, N-dimethylformamide (DMF) is used. When the feed molar ratio (diphosgene:2-amino-6-chloropenol) is 0.525:1, the toluene is used as solvent, the reaction time is 1h under reflux and the product is recrystallized in the mixture o