Study on the Simultaneous Enantioseparation of Racemic Acid and Amine Combinations

我们最近报道，在结晶的外消旋酸和胺的组合，其中有效的对映体分离的非对映体盐的方法实现的聚集体形成的概率高达50%。为了证实这一现象的普遍性，我们试图将结晶扩展到各种外消旋酸和胺的组合。然而，只有少数外消旋和对映体纯形式的酸和胺，已解决了高效率，被发现，尽管沉重的书目搜索。因此，在检查之前开发了适用于本研究的新型拆分剂。本研究设计并合成了六种新型的含萘和/或硫代膦酰基骨架的酸性拆分剂和四种新型的含苯并茚满基和/或双羟基骨架的碱性拆分剂，利用文献报道的和本研究开发的各种拆分剂，进行外消旋酸和胺组合的结晶以分析聚集体形成的可能性。结果，我们发现，正如我们已经报道的那样，对于各种各样的组合，概率也约为50%。此外，澄清了不仅可以通过X射线晶体学分析，而且可以通过红外光谱和熔点分析的单晶和粉末状微晶，这是在结晶的外消旋酸和胺的组合中获得的测定砾岩。

We have recently reported that the probability for conglomerate formation is as high as 50% in the crystallizations of racemic acid and amine combinations, for which efficient enantioseparation is achieved by the diastereomeric salt method. In order to confirm the generality of the phenomenon, we tried to extend the crystallization to various kinds of racemic acid and amine combinations. However, only a few racemic and enantiopure forms of acids and amines, which have been resolved with high efficiency, were found, despite of heavy bibliographic search. Therefore, novel resolving agents suitable for the present study were developed prior to the examination. Six kinds of novel acidic resolving agents, which have a naphthalene and/or phosphonothioic skeleton, and four kinds of novel basic resolving agents, which have a benzindanylene and/or bishydroxy skeleton, were designed and synthesized for the present study.Using various kinds of resolving agents, which were reported in literatures and developed in the present study, crystallizations of racemic acid and amine combinations were carried out in order to analyze the probability of the formation of conglomerate. As a result, we found that the probability was also about 50% for a wide variety of the combination, as we have reported. Furthermore, it was clarified that the determination of conglomerate could be carried out not only by X-ray crystallographic analysis but also by IR spectral and melting point analyzes of a single crystal and powdery micro crystals, which were obtained in the crystallization of a racemic acid and amine combination.