Rare Case of Polymorphism in the Binary System of Enantiomers of a Praziquantel Derivative

A rare case of a polymorphic racemic compound has been discovered in the binary system of enantiomers of the praziquantel derivative 2-(cyclopropanecarbonyl)dodecahydro-4H-pyrazino[2,1-a]isoquinolin-4-one. Solid-state characterization of the three polymorphs has been performed, including the resolution of their crystal structures and the construction of a binary phase diagram between the enantiomers. Although the three polymorphs demonstrate high kinetic stability at room temperature, a thorough examination of the binary phase diagram through thermodynamic consideration reveals a complex situation in which the three racemic forms are found to be enantiotropically related. As a result of major structural differences between the polymorphs, no solid–solid polymorphic transition was observed, and the conversion from one form to the other systematically required melting and recrystallization. Such enantiotropic behavior is rarely observed and highlights the diversity of crystallization behaviors that can result from slight chemical modification.