*3.2. Thermochemical Investigations*

Figure 2 shows differential scanning calorimetry (DSC) thermograms of enantiopure (curve 1) and racemic (curves 2-4) samples of diol **1**. The thermogram of an enantiopure sample (*R*)-**1** is represented by a single narrow peak, which indicates its phase uniformity. The thermochemical parameters for this sample are presented in Table 3. The same parameters for the sample (*R*)-**1** obtained by crystallization from the melt practically do not differ from those for the sample crystallized from solution.

On the contrary, a thermogram of a freshly-prepared chemically-pure racemate obtained by crystallization from a hexane/ethyl acetate mixture demonstrates the complex contour of the melting process curve 2. The main peak, located in the temperature range of ~ 75 ◦C, has a leading edge with a pronounced kink, which is preceded by a minor endothermic peak, observed at a significantly lower temperature (~ 68 ◦C). This behavior is characteristic of phase-inhomogeneous systems represented by a mixture of several crystalline modifications. Intensive mixing of a suspension of such a sample in hexane for several hours at room temperature results in a thermodynamically equilibrium phase-homogeneous racemic sample, the thermogram of which is a narrow peak with a regular shape (curve 3). The demonstration of spontaneous resolution of *rac*-**1** (Section 3.1) suggests that the main crystalline form of the racemate is a conglomerate, which we denote by the symbol (*R*+*S*). The melting point of the brought to equilibrium *rac*-**1** sample, calculated as the intersection of the free energy curves of the crystalline enantiopure phase and melted (*R*+*S*)-**1** (Figure 4) was 76.2 ◦C, which practically coincides with the actually observed for conglomerate (76.3 ◦C) (Table 3).

**Figure 2.** Differential scanning calorimetry (DSC)traces of an enantiopure sample (*R*)-**1** (blue curve 1), a freshly recrystallized racemic sample *rac*-**1** (wine curve 2), the same sample after prolonged stirring of a suspension in hexane (red curve 3), and after crystallization of the racemate from the melt (olive curve 4). Sample weight ~ 1 mg.

**Table 3.** Thermochemical characteristics of the identified crystalline forms of 3-(3,4-dimethylphenoxy) propane-1,2-diol **1**.


<sup>1</sup> In parentheses are the values calculated on the basis of the DSC data for the dependence of the thermodynamic potentials of the phases on temperature (Section 3.3, Figure 3).

If a racemic sample of diol **1** of any prehistory is melted and quickly cooled to room temperature, then the supercooled melt in the range of ~10 min undergoes spontaneous crystallization. The melting of the phase thus obtained (β-*rac*-**1**) is described by a peak at ~ 66 ◦C (curve 4), which on the temperature scale is practically in the same region as the minor endothermic peak in curve 2, Figure 2. This suggests that the β-*rac*-**1** phase is present in the samples, which initially precipitate from solutions, and the minor endothermic peak arises due to this.

The general appearance of melting curve 2 indicates that the phase behavior of the primary *rac*-**1** crystals is even more complex and, in addition to the identified (*R*+*S*)-**1** and β-*rac*-**1**, other crystalline modifications can be present in the system. Indeed, after the β-*rac*-**1** phase is heated to 72 ◦C and held at this temperature, it melts almost completely, but then crystallizes again. The melting parameters of the resulting α-*rac*-**1** phase (Figure 3, violet) are close, but not identical to those for the equilibrium racemic sample (Figure 3, red; Table 3).

Taken together, the thermochemical data show that for the enantiopure forms of diol **1** the only one crystalline phase is realized, and the racemate can be represented by a thermodynamically equilibrium conglomerate (*R*+*S*)-**1**, two polymorphs α-*rac*-**1** and β-*rac*-**1**, as well as a mixture of these modifications. Table 3 shows the thermochemical parameters of the corresponding systems.

**Figure 3.** DSC traces of an equilibrium racemic sample identified as a conglomerate (red curve), a racemic sample obtained by crystallization from melt at 72 ◦C (violet curve), and crystallization from melt upon rapid cooling to 20 ◦C (olive curve). Sample weight ~ 8 mg.
