Technical Support Center and §Graduate School of Science and Engineering, Saitama University , Shimo-Ohkubo, Sakura-ku, Saitama City, Saitama 338-8570, Japan.
J Org Chem. 2013 Sep 20;78(18):9309-16. doi: 10.1021/jo401517q. Epub 2013 Sep 4.
Solvent-induced chirality switching in reciprocal optical resolution between mandelic acid (1) and erythro-2-amino-1,2-diphenylethanol (2) has been demonstrated. The stereochemistry of the deposited salts was controlled by changing the crystallization solvent from 1-PrOH or 1-BuOH to 1,4-dioxane. It was revealed from (1)H NMR spectra, thermogravimetric analysis, and X-ray crystallography of the salts that an equimolar amount of the crystallization solvent was incorporated in each diastereomeric salt. On the basis of the crystal structures, it was found that both the hydrogen-bonding ability and the size of the solvent molecule played an important role. Differences in the formed hydrogen-bonding networks (columnar or sheetlike structure) and their packing manner were found to be crucial for the reversed stereoselectivity. Furthermore, pseudopolymorphic salt crystals that incorporated 1,4-dioxane were obtained during the enantioseparation of racemic 2, and their solid-state properties were examined by measurement of their IR spectra. This solvent-induced dual stereocontrol technique was successfully applied to the successive resolution process, eliminating the need to change the resolving agent for access to both enantiomers of 1 and 2.
溶剂诱导的扁桃酸（1）和（R）-2-氨基-1,2-二苯基乙醇（2）对映体之间的相互光学拆分中的手性转换已得到证实。通过将结晶溶剂从 1-丙醇或 1-丁醇改变为 1,4-二氧六环，控制了所沉积盐的立体化学。从盐的（1）H NMR 光谱、热重分析和 X 射线晶体学中揭示，每个非对映异构体盐中都掺入了等摩尔量的结晶溶剂。基于晶体结构，发现溶剂分子的氢键能力和大小都起着重要作用。所形成的氢键网络（柱状或片状结构）的差异及其堆积方式对于反转立体选择性至关重要。此外，在对映体拆分外消旋 2 时获得了包含 1,4-二氧六环的假多晶型盐晶体，并通过测量其红外光谱研究了它们的固态性质。该溶剂诱导的双重立体控制技术成功应用于连续拆分过程，无需改变拆分剂即可获得 1 和 2 的两种对映体。
