Mechanism of preferential enrichment, an unusual enantiomeric resolution phenomenon caused by polymorphic transition during crystallization of mixed crystals composed of two enantiomers.
Mechanism of preferential enrichment, an unusual enantiomeric resolution phenomenon caused by polymorphic transition during crystallization of mixed crystals composed of two enantiomers.
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优先富集机制，由两种对映体组成的混合晶体结晶过程中多晶型转变引起的一种不寻常的对映体拆分现象。
DOI：
10.1021/ja020454r
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发表时间：
2002
影响因子：
15
通讯作者：
K. Hirotsu
中科院分区：
文献类型：
--
作者：
R. Tamura;D. Fujimoto;Z. Lepp;K. Misaki;H. Miura;Hiroki Takahashi;T. Ushio;T. Nakai;K. Hirotsu
研究了一系列外消旋晶体在重结晶过程中出现的一种罕见的对映体拆分现象--优先富集现象的机理。根据溶液结晶过程中多晶型物的存在和由此产生的多晶型转变的发生，其机理被解释为：（1）在低ee值的外消旋或非外消旋样品的过饱和溶液中，优先的纯手性分子缔合形成一维链结构，（2）在成核过程中保持纯手性链结构的亚稳晶相的动力学形成，（3）从亚稳相到稳定相的多晶型转变，随后过量R（或S）的对映选择性释放在晶体生长开始时，从转化的晶体向溶液中释放对映异构体，导致轻微富集（高达10%ee）的相反S（或R）对映体，以及母液中R（或S）对映体的对映体富集，和（4）在随后的晶体生长过程中，通过一旦形成的富含S（或R）的稳定晶相的手性区分，导致母液中R（或S）对映体的相当大的对映体富集，高达100%ee。认为方法（3）和（4）直接导致母液中一种对映异构体的富集。通过（i）溶解度测量和（ii）数均分子量测量以及（iii）低聚物模型的分子动力学模拟研究了两种对映体在溶液中的缔合模式。通过红外光谱和差示扫描量热法对结晶过程中的多晶型转变进行了观察。亚稳和稳定的晶体已经获得，它们的晶体结构已阐明其单晶的X射线晶体学分析。
The mechanism of Preferential Enrichment, an unusual enantiomeric resolution phenomenon observed upon recrystallization of a series of racemic crystals which are classified as a racemic mixed crystal with fairly ordered arrangement of the two enantiomers, has been studied. On the basis of the existence of polymorphs and the occurrence of the resulting polymorphic transition during crystallization from solution, the mechanism has been accounted for in terms of (1) a preferential homochiral molecular association to form one-dimensional chain structures in the supersaturated solution of the racemate or nonracemic sample with a low ee value, (2) a kinetic formation of a metastable crystalline phase retaining the homochiral chain structures in a process of nucleation, (3) a polymorphic transition from the metastable phase to a stable one followed by enantioselective liberation of the excess R (or S) enantiomers from the transformed crystal into solution at the beginning of crystal growth to result in a slight enrichment (up to 10% ee) of the opposite S (or R) enantiomer in the deposited crystals, together with an enantiomeric enrichment of the R (or S) enantiomer in the mother liquor, and (4) a chiral discrimination by the once formed S (or R)-rich stable crystalline phase in a process of the subsequent crystal growth, leading to a considerable enantiomeric enrichment of the R (or S) enantiomer up to 100% ee in the mother liquor. The processes (3) and (4) are considered to be directly responsible for an enrichment of one enantiomer in the mother liquor. The association mode of the two enantiomers in solution has been investigated by means of (i) the solubility measurement and (ii) the number-averaged molecular weight measurement in solution by vapor pressure osmometry, together with (iii) the molecular dynamics simulation of oligomer models. The polymorphic transition during crystallization has been observed visually and by means of the in situ FTIR technique and DSC measurement. Both metastable and stable crystals have been obtained, and their crystal structures have been elucidated by X-ray crystallographic analysis of their single crystals.