Intricate Phase Behavior and Crystal Structure Features of Chiral para-Methoxyphenyl Glycerol Ether Forming Continuous and Partial Solid Solutions

Abstract

Heterogeneous equilibria, crystallization, and polymorphism of chiral para-methoxyphenyl glycerol ether 1 have been inspected, and, as a result, the binary phase diagram and the Gibbs free energy vs temperature plot were constructed and analyzed. This enantiomeric system forms a stable racemic compound, which turns into an almost ideal continuous solution of the enantiomers in the crystalline phase at elevated temperatures. At room temperature the system represents a stoichiometric racemic compound and two symmetrical eutectoid invariants with partial solid solutions based on the enantiomers. Crystal structures of the true racemate, the pseudoracemate, and the pure enantiomer were investigated by single crystal X-ray diffraction. The true racemate crystallizes in the Pc space group with Z′ = 2. The pseudoracemate was solved in the Pbcn group with the only independent molecule equally disordered into two mirror-related positions. The enantiomeric crystals belong to the P21212 group and are characterized by six symmetry independent molecules (Z′ = 6), two of which undergo disordering. We also discussed possible connection between the phase behavior features and the details of the crystal structure, in particular, bilayer supramolecular organization, pseudosymmetry, high Z′, and disordered packing. General considerations about the crystalline nature of solid solutions of enantiomers were also made.

Structural aspects of partial solid solution formation: two crystalline modifications of a chiral derivative of 1,5-dihydro-2H-pyrrol-2-one under consideration

“…Although the number of symmetry-independent molecules does not relate to the enthalpy or entropy of a solid phase directly, in all probability, Z′ > 1 provides more flexibility to accommodate the packing, which could contribute to or contradict the best crystal formative motif. 23,[28][29][30] Moreover, the presence of a second and more "extra" symmetrically independent molecule in crystals is often accompanied by the pseudosymmetry phenomenon, 31 which we exemplified earlier in glycerol derivatives 20,21 and a pair of mucochloric acid polymorphs.…”

“…It is worth noting that the choice of the space group P2 1 rather than P2 1 /n was clear for the experiment at 150 K but was more ambiguous for the room temperature data. The E-statistics suggest a centrosymmetric space group but this behavior can be explained, especially at 293 K, by the pseudosymmetry of the crystal structure, 21,23,45 which increases with heating. The data measured at 150 K include 137 unique h0l (<I/σ(I)> = 3.9), h + l odd reflections, 41 of which have I > 3σ(I) and 15 have I > 10σ(I).…”

“…6 Nevertheless, a complete theory of solid solution formation has not been elaborated yet. 7 One of the obvious reasons for this is the difficulty in identifying and studying the scarce partial [8][9][10][11][12][13][14] and continuous [15][16][17][18][19][20][21][22][23] solid solutions of enantiomers.…”

“…7,23 At the same time, the problem of observing multiple molecules in an asymmetric unit is currently at the forefront of modern chemical crystallography. 24,25 According to recent reviews on Z′ problems, 26,27 the amount of structures with Z′ > 1 is estimated at ca.…”

Spontaneous Resolution of Chiral 3-(2,3-Dimethylphenoxy)propane-1,2-diol under the Circumstances of an Unusual Diversity of Racemic Crystalline Modifications

“…Polymorphism is an evergreen theme for researchers of molecular crystals. , Current interest in this problem is largely supported by the needs of pharmaceutical science and industry. , In recent years, chiral compounds are increasingly becoming objects of the research. − An additional feature of chiral systems that is absent in the case of achiral substances is the possible interconversion of homochiral (scalemic, enantiopure) and heterochiral (mainly racemic) crystalline forms. − In the strict sense of the word, conglomerate homochiral crystals are not polymorphic with respect to any racemic solid. However, like ordinary polymorphs, those and others can be formed from a common feed medium (solution or melt) and can transform into each other both as a result of solid-phase transitions and as a result of contact with the common liquid phase .…”