**Stereoselective Crystallization of Chiral 3,4-Dimethylphenyl Glycerol Ether Complicated by Plurality of Crystalline Modifications**

Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov St., 8, 420088 Kazan, Russia; dmzakhar@gmail.com (D.V.Z.); zemfira@iopc.ru (Z.A.B.); alexeykurenkov84@gmail.com (A.V.K.); a\_samigullina@iopc.ru (A.I.S.); aidar@iopc.ru (A.T.G.) **\*** Correspondence: baa@iopc.ru

Received: 28 February 2020; Accepted: 12 March 2020; Published: 14 March 2020

**Abstract:** Spontaneous resolution of Pasteur's salt was historically the first way to obtain pure enantiomers from the racemate. The current increase in interest in the direct racemates resolution during crystallization is largely due to the opened prospects for the industrial application of this approach. The chiral 3-(3,4-dimethylphenoxy) propane-1,2-diol 1 is a synthetic precursor of practically useful amino alcohols, the enantiomers of which exhibit different biological effects. In this work, it was first discovered that racemic diol 1 is prone to spontaneous resolution. However, the crystallization process is complicated by the existence, along with the conglomerate, of two other crystalline forms. Using the differential scanning calorimetry (DSC) approach, methods have been developed to obtain individual metastable phases, and all identified modifications ((*R*)-1, (*R*+*S*)-1, α-*rac*-1, β-*rac*-1) were ranked by energy. The IR spectroscopy and powder X-ray diffraction (PXRD) methods demonstrated the identity of the first two forms and their proximity to the third, while β-*rac*-1 is significantly different from the rest. The crystal structure of the forms (*R*)-1 and α-*rac*-1 was established by the single crystal X-ray diffraction (SC-XRD) method. Preliminary information on the structure of β-*rac*-1 phase was obtained by the PXRD approach. Based on the information received, the experimental conditions for a successful direct resolution of racemic 1 into individual enantiomers by a preferential crystallization procedure were selected.

**Keywords:** chirality; deracemization; preferential crystallization; racemic conglomerate; phase behavior; polymorphism; aryl glycerol ethers
