Mechanism of a new type of solvent-assisted solid-to-solid polymorphic transition causing preferential enrichment: Prominent influence of C(sp(2))H center dot center dot center dot O interaction on the control of a crystal structure

A new mode of the solvent-assisted solid-to-solid transformation of the first-formed and least stable gamma-polymorphic form into the most stable epsilon-polymorphic one occurring during crystallization from the supersaturated EtOH solution of (+/-)-[2-[4-(3-ethoxy-2-hydroxypropoxy)phenylcarbamoyl]ethyl]trimethylammonium benzenesulfonate [(+/-)-2], which shows an unusual enantiomeric resolution phenomenon called Preferential Enrichment, has been revealed. The crystal structure of the new epsilon-form, which was obtained as the monophasic powder sample by exhaustive polymorphic transitions via three other metastable polymorphic forms in contact with the solvent, has been solved from the powder X-ray diffraction data by the direct-space approach employing the Monte Carlo method with the subsequent Rietveld refinement. By comparison of the crystal structure of the least stable gamma-form with that of the most stable epsilon-one, the mechanism of this polymorphic transition has been interpreted in terms of a new type of rearrangement of weak intermolecular interactions caused by a slight molecular movement inside the crystal lattice, in which intermolecular C(sp(2))H...O interactions prominently control the crystal structure. This new finding complements our recent report on the mechamisn of Preferential Enrichment.