Double Trouble: A Peculiar Case of Solid Solution Cocrystals Involving Two Chiral Compounds

Cocrystals have been widely studied in the context of chiral resolution. Enantiospecific and diastereomeric cocrystal resolution processes, as well as preferential resolution based on cocrystallization, are becoming more and more common. The formation of solid solutions is a rare phenomenon (less than 1% of compounds), with solid solutions between cocrystallization of two racemic compounds rarely described. In this contribution, we study such a case between two chiral compounds, 2-(2-Oxopyrrolidin-1-yl)butanamide (1) and methylsuccinic acid (2). Both diastereomers S-1:S-2 and S-1:R-2 form double-sided solid solutions, which are solid solutions where the enantiomers of either 1, 2, or both 1 and 2 can be partially replaced by their counterparts. Solid solution formation was proven by the observed disorder in the crystal structures. The limits of each solid solution are determined through a solid-state stability diagram. A double-sided solid solution based on cocrystallization offers potential as enantiomeric excess of both components can be varied with a given degree of freedom, without changing the nature of the solid phase present.