联苯乙酸合成工艺的优化研究
x

请在关注微信后,向客服人员索取文件

篇名: 联苯乙酸合成工艺的优化研究
TITLE:
摘要: 目的:优化联苯乙酸合成工艺,为满足联苯乙酸原料药的市场需求提供技术支持。方法:对传统的联苯经傅克反应、缩酮反应、重排反应、水解等步骤制备联苯乙酸的合成路线进行优化改进,考察不同傅克反应溶剂(石油醚、二氯甲烷、1,2-二氯乙烷)、缩酮反应醇(乙二醇、1,3-丙二醇、新戊二醇、季戊四醇)、重排反应催化剂(联苯乙酸锌、氧化锌、辛酸锌、醋酸锌)和精制溶剂(95%异丙醇、异丙醇、乙醇、丙酮、乙酸乙酯)等条件对合成工艺的影响,以制得的中间体或联苯乙酸的纯度和收率筛选最优工艺。结果:以石油醚为傅克反应溶剂、以乙二醇为缩酮反应醇、以联苯乙酸锌为重排反应催化剂、以95%异丙醇为精制溶剂时,制备效果较好。关键中间体 2′ -氯代联苯乙酮收率达到95%以上;精制后的联苯乙酸纯度可达到99.9%,单一杂质含量小于0.1%,总收率在70%以上。结论:优化后的联苯乙酸合成工艺操作简单,反应条件温和易控,成本低,所用试剂更环保、安全性高,适于工业化大生产;产品纯度和收率均较高,符合欧洲药典、日本药典标准。
ABSTRACT: OBJECTIVE: To optimize the synthesis technology of 4-biphenylacetic acid, and to provide technology support to meet the market demand of 4-biphenylacetic acid raw material. METHODS: The synthesis route of 4-biphenylacetic acid from biphenyl by Friedel-Crafts reaction, ketal reaction, rearrangement reaction and hydrolysis was optimized and improved. The effects of different Friedel-Crafts reaction solvents (petroleum ether, dichloromethane, 1, 2-dichloroethane), ketal reaction ethanol (ethanediol, 1,3-propanediol, dimethyltrimethylene glycol, pentaerythritol), rearrangement reaction catalyzer (zinc biphenyl acetate, zinc oxide, zinc caprylate, zinc acetate) and refined solvent (isopropanol, 95% isopropanol, ethanol, acetone, ethyl acetate) on synthesis technology were investigated. The optimal synthesis technology was screened with the purity and yield of intermediate or 4-biphenylacetic acid. RESULTS: The petroleum ether as Friedel-Crafts reaction solvent, ethylene glycol as ketal reaction ethanol, zinc diphenylacetate as rearrangement catalyst and 95% isopropanol as refining solvent were used for the preparation to obtain better effects. The yield of key intermediate 2′ -chloroacetophenone reached above 95%. The purity of refined 4-biphenylacetic acid reached 99.9%; the content of single impurity was less than 0.1%; the total yield reached over 70%. CONCLUSIONS: The optimal synthesis technology of 4-biphenylacetic acid has the advantages of simple operation, mild and controllable reaction conditions, low cost, greener reagents and higher safety, and is suitable for industrial production. The purity and yield of the products are in high level and in line with the standards of European Pharmacopoeia and the Japanese Pharmacopoeia.
期刊: 2018年第29卷第20期
作者: 邓玉晓,孙晋瑞,段崇刚,林治秘,李丹,任业明,冯光玲
AUTHORS: DENG Yuxiao,SUN Jinrui,DUAN Chonggang,LIN Zhimi,LI Dan,REN Yeming,FENG Guangling
关键字: 联苯乙酸;合成工艺;优化;联苯乙酸锌
KEYWORDS: 4-biphenylacetic acid; Synthesis technology; Optimization; Zinc biphenylacetate
总下载数: 1 次
本日下载数: 0次
本月下载数: 1次
文件大小: 619.60Kb

* 注:未经本站明确许可,任何网站不得非法盗链资源下载连接及抄袭本站原创内容资源!在此感谢您的支持与合作!