文献类型：期刊文献

英文题名：Resolution of Halogenated Mandelic Acids through Enantiospecific Co-Crystallization with Levetiracetam

作者：Wang, Jie[1];Peng, Yangfeng[1]

机构：[1]East China Univ Sci & Technol, Sch Chem Engn, Shanghai 200237, Peoples R China

年份：2021

卷号：26

期号：18

外文期刊名：MOLECULES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000701831300001)】；

语种：英文

外文关键词：co-crystal; resolution; halogenated mandelic acid; 3-chloromandelic acid; levetiracetam

摘要：The resolution of halogenated mandelic acids using levetiracetam (LEV) as a resolving agent via forming enantiospecific co-crystal was presented. Five halogenated mandelic acids, 2-chloromandelic acid (2-ClMA), 3-chloromandelic acid (3-ClMA), 4-chloromandelic acid (4-ClMA), 4-bromomandelic acid (4-BrMA), and 4-fluoromandelic acid (4-FMA), were selected as racemic compounds. The effects of the equilibrium time, molar ratio of the resolving agent to racemate, amount of solvent, and crystallization temperature on resolution performance were investigated. Under the optimal conditions, the resolution efficiency reached up to 94% and the enantiomeric excess (%e.e.) of (R)-3-chloromandelic acid was 63%e.e. All five halogenated mandelic acids of interest in this study can be successfully separated by LEV via forming enantiospecific co-crystal, but the resolution performance is significantly different. The results showed that LEV selectively co-crystallized with S enantiomers of 2-ClMA, 3-ClMA, 4-ClMA, and 4-BrMA, while it co-crystallized with R enantiomers of 4-FMA. This indicates that the position and type of substituents of racemic compounds not only affect the co-crystal configuration, but also greatly affect the efficiency of co-crystal resolution.