The second example of doubly enantiophobic behavior during crystallization: a detailed crystallographic, thermochemical and spectroscopic study

Herein we have found a second example of doubly enantiophobic behavior during the crystallization of rac-1-benzyl-3-chloro-4-[(4-chlorophenyl)sulfanyl]-5-hydroxy-1,5-dihydro-2H-pyrrol-2-one, i.e., the formation of two conglomerates with different crystal structures in the absence of any racemic compounds. In both polymorphic modifications, the main supramolecular motif is appeared to be a hydrogen-bonded chain or helix of different symmetry, which is related to an alpha-hydroxyamide chain synthon. Additional crosslinking of the homochiral chains in the crystals of both crystalline forms, which is realized through weak, noncovalent interactions, can be a probable reason for the reproducibility and stability of the alpha-hydroxyamide chain synthon and polymorphic diversity registered. It was shown that each of the conglomerates is thermodynamically stable in certain temperature ranges. For the first time, a binary phase diagram for the chiral system complicated by an enantiotropic phase transition is reconstructed based on experimental data, which is characterized by the presence of a thermodynamic stability permutation line between the two racemic conglomerates.

Automated summary

This study identified a second example of doubly enantiophobic behavior during crystallization, with two conglomerates formed with different crystal structures in the absence of any racemic compounds. The main supramolecular motif in both polymorphic modifications appears to be a hydrogen-bonded chain or helix related to an alpha-hydroxyamide chain synthon. The additional crosslinking of homochiral chains through weak, noncovalent interactions may contribute to the reproducibility and stability of the alpha-hydroxyamide chain synthon and registered polymorphic diversity.