Polymorphism and hydration of zopiclone : Determination of crystal structures, and thermodynamic studies as a function of temperature and water vapor pressure

Crystal Structures, Dehydration Mechanism, and Chiral Discrimination in the Solid State of a Hydantoin Derivative

“…Although attempts to get structural information about AR-18H were unsuccessful, it can be supposed that the crystal packing of the latter is probably closely related to that of HR-18H, composed of alternate R and S layers made of H-bonded 1D molecular ribbons. A similar behavior has been reported by Giovannini and co-workers, showing that the reversible dehydration at room temperature of the racemic dihydrate of zopiclone leads to a metastable anhydrous racemic compound . In this latter study, the structures of both phases were determined and were shown to be isomorphous.…”

“…More recently, various solid state transitions between racemic compounds and conglomerates have been investigated and different situations have been envisaged: (i) thermodynamic equilibrium between a low-temperature conglomerate and a high-temperature racemic compound through a eutectoid invariant; (ii) reverse situation through a peritectoid invariant; , (iii) irreversible transition from a metastable conglomerate toward a stable racemic compound; , (iv) reverse situation, of particular interest since it corresponds actually to a spontaneous resolution, either from a racemic compound toward a conglomerate − or by transition from an anomalous conglomerate toward a usual one . When possible, another interesting approach consists of considering the evolution of the relative stability of homo- and heterochiral solid phases within a series of chemical derivatives as a function of the molecular structure. ,,, For instance, Nemak et al have shown that increasing the length of the alkyl chain in the series of ( N -alkyl)-2′,6′-pipecoloxylidides decreases the relative stability of the racemic compound, thus inducing the formation of a conglomerate for the longest butyl chain …”

Solid–Solid Transition between Hydrated Racemic Compound and Anhydrous Conglomerate in Na-Ibuprofen: A Combined X-ray Diffraction, Solid-State NMR, Calorimetric, and Computational Study

“…As a matter of fact, this kind of solid state transformation of a racemic compound into a conglomerate, or vice versa, is quite an uncommon case. − …”

Polymorphism and Migratory Chiral Resolution of the Free Base of Venlafaxine. A Remarkable Topotactical Solid State Transition from a Racemate to a Racemic Conglomerate

“…The major difference with enantiomeric epitaxial crystallization, however, is the fact that the polymorphic epitaxial layers of the metastable polymorph were able to transform via a solution mediated mechanism to the stable polymorph structure. Giovannini et al 16 described a transition of a true racemate to a racemic conglomerate. A racemic dihydrate of Zopiclone is dehydrated forming a metastable anhydrate which, upon further heating, melts, and the racemic conglomerate phase crystallizes out.…”