The (R)-and (S)-baclofenium hydrogenomaleate system exhibits an extensive chiral discrimination in the solid state at room temperature. Nevertheless, above 145 °C, the critical temperature, a complete solid solution between the two enantiomers is stable. The 50−50 mixture does not form any racemic compound at any temperature, and at 20 °C, the two mirror phases show limited symmetrical solid solutions as the enantiomeric excess equals 98.5%. This is due to a large miscibility gap in the solid state. Close to room temperature, the racemic mixture can be resolved by preferential crystallization. The yield of the process can be enhanced in acidic aqueous solutions (e.g., in HCl aq 2 M), which increases the solubility.

trans-N,N 0 -Dibenzyldiaminocyclohexane (B) crystallizes with 2,3-dichlorophenylacetic acid (AH); the crystal structure, resolved by using crystal X-ray diffraction, revealed an odd stoichiometry composed of H 2 B 2+ , two A À and two AH forming an unexpected hybrid salt-cocrystal. As this compound is a stable conglomerate (i.e. every single crystal contains the enantiomerically pure cation H 2 B 2+ , RR or SS), several preferential crystallization attempts (AS3PC) were performed in methanol and in THF and gave unexpected final enantiomeric excesses greater than 20% for the entrainment in methanol. These results suggest that the crystal growth mechanism preferentially involves building units composed of [H 2 B 2+ ; 2A À and 2AH] or reconstruction of some crystal interfaces rather than a layer by layer construction.

Nowadays the detection of conglomerates has been improved; but with a view to implement an efficient preparative resolution by preferential crystallization, this is not enough. Indeed, when a conglomerate has been spotted, there is no other way to assess the feasibility of its preferential crystallization than to run various tests of entrainment. Three similar molecular structures in the series of 1,2-diaminocyclohexyl derivatives are presented in this work. The structures correspond to conglomerates with nonobvious stoichiometry. Two are successfully resolved by preferential crystallization; the third one cannot be resolved by entrainment.

The solid state landscape of (±)-modafinil presents several polymorphic forms and solvates. Some of these polymorphic forms ((±)-Forms V and VI) can only be obtained by means of desolvation of solvates ((±)-modafinil chloroform solvate and acetonitrile solvate). Moreover, a new hydrate ((±)-modafinil monohydrate) is obtained from an original protocol which uses a physical mixture of both enantiomers rather than the racemic compound. All these solvates present an efflorescent behavior, and this study highlights the formation of various polymorphic forms from the same solvate according to the temperature of desolvation. Indeed, when the desolvation process is performed below or above the glass transition temperature (T g) of the anhydrous modafinil, the resulting nonsolvated phases differ.

(±)-Bis-tetralone (BisT) crystallizes as a stable conglomerate that can be resolved by preferential crystallization. This preferential crystallization was performed by autoseeded polythermic programmed preferential crystallization (AS3PC) and autoseeded preferential crystallization induced by solvent evaporation (ASPreCISE) variants in dimethylformamide and dichloromethane. Prior to performance of these resolutions, an extensive purification was necessary because the presence of impurities had a strong negative impact on the stereoselective crystal growth. Moreover, the presence of multiepitaxy phenomena required a vigorous stirring during the preferential crystallization in order to avoid a poor optical purity of the crops. Several preferential crystallization attempts demonstrate that ASPreCISE is recommended when there is an unfavorable variation of solubility versus temperature or when chemical degradation occurs on heating.