Single Enantiomer’s Urge to Crystallize in Centrosymmetric Space Groups: Solid Solutions of Phenylpiracetam

Abstract

A detailed thermochemical and structural study of the phenylpiracetam enantiomer system was performed by characterizing the solid solutions, rationalizing the structural driving force for their formation, as well as identifying a common structural origin responsible for the formation of solid solutions of enantiomers. Enantiomerically pure phenylpiracetam forms two enantiotropically related polymorphs (enant–A and enant–B). The transition point (70(7) °C) was determined based on isobaric heat capacity measurements. Structural studies revealed that enant–A and enant–B crystallize in space groups P1 (Z′ = 4) and P212121 (Z′ = 2), respectively. However, pseudoinversion centers were present resulting in apparent centrosymmetric structures. The quasi centrosymmetry was achieved by a large variety of phenylpiracetam conformations in the solid state (six in total). As a result, miscibility of the phenylpiracetam enantiomers in the solid state is present for scalemic and racemic samples, which was confirmed by th...