邻氯扁桃酸的绿色手性拆分研究.pdf

364
化学世界
2012年
邻氯扇桃設的绿色手性拆分研究
胡呈
俞卓尔,庄晓晓,孙晓2,郭瑛,李利
(1.南昌大学a.化学系;b.基础化学实验中心,江西南昌330031;
2.江西科技师范学院有机功能分子研究所,江西南晶330013)
摘要:用酒石酸衍生物O,O-ニ苯甲酰基酒石酸(DBTA)代替有机胺类化合物,通过金属配合拆
分方法有效地拆分邻氯扁桃酸。研究了拆分溶剂体系、固体析出方式、主客体比对拆分效率的影
响,建立了在“绿色溶剂”水为主要溶剂条件下,添加适量的异两醇,搅拌析出的最佳工艺条件。实
验结果表明,主客体比n(DBTA与CaO):n(邻氟扁桃酸)为1:1,2.5mmol邻象扁桃酸在6mL
水和4mnL异丙醇剂体系下,拆分效率可达到58.5%。
关键词:邻氯扁桃酸;金属配合拆分;绿色手性拆分
中图分类号:O621.3
文献标志码:A
文章编号:0367-6358(2012)06-0364-04
Green Chiral Resolution of 2-chloromandelic Acid
HU. Yu]l, YU Zhuo-erla, ZHUANG Xiao-xiao, SUN Xiao-xia, GUO Ying, LI Li
(I. Nanchang University, a. Department of Chemistry
b. Education Center for Basic Chemistry Experiments, Jiangri Nanchang 339031, Chin
2. Jiangxi Key Laboratory of Functional Organic Molecwles, Jiangxi Normal University of
Science &Technology, Jiangzi Nanchang 330013, China)
Abstract: O, O,-dibenzoyltartaric acid(DBTA) prepared from tartaric acid could substitute chiral amines
for the coordination-mediated resolution of racemic 2-chloromandelic acid. The effects of solvent system
solid preciptation method and ratio of host and guest on the resolution of 2-chloromandelic acid were
studied. The best resolution efficiency was obtained when the ratio of host and guest was 1 i l in the
mixture of green solvent water and isopropyl alcohol. The results showed that 2. 5mmol racemic 2-
chloromandelic acid was efficiently resoluted in 6 ml water and 4 ml isopropyl alcohol through cooling by
stirring. Under the optimum conditions, the resolution efficiency could reach 58.5%
Key words: 2-chloromandelic acid; coordination-mediated resolution; green chiral resolution
邻氯扁桃酸是一种重要的有机合成中间体,广元,近几年单药傜收入排名全球第二,是目前最畅
泛应用于医药、化工等多个领域,其中(R)-邻氯扁销的药物之一,因此获取其重要中间体手性邻氯扁
桃酸是新型安全高效抗血小板聚集药物氯吡格雷的桃酸具有广阔市场。
重要手性中间体。氯吡格雷硫酸氢盐是由法国赛
虽然不对称合成手性邻氯扁桃酸技术取得很大
诺菲和美国施贵宝于1996年联合开发,1997.年获发展,但目前工业化制备(R)一邻氯扁桃酸还是以拆
得FDA批准上市,2008年全球销售额为94亿美分法为主。对邻氯扇桃酸的拆分通常是利用天然的
收稿日期:2011-09:-05
基金项目:江西省科技厅科技计划项目(2010BSA18700)江西省卫生厅科技计划项目(20092044)
作者简介:胡昱(1979-),男,江画安义人。副教授,主要从事生物有机化学和不对称合成的研究工作。E-mail:huyu@ncu.edu.cn。