Search Results
You are looking at 1 - 9 of 9 items for
- Author or Editor: G. Coquerel x
- Refine by Access: All Content x
Abstract
5-methyl-5-(4’-methylphenyl) hydantoin is a chiral compound whose racemic mixture crystallizes as a conglomerate. This molecule has two polymorphs: an orthorhombic form (stable form) and a monoclinic form of monotropic character. These forms share extensive structural analogies (identical 2D periodic fragment) and consistently their lattice energies are quite close. The analyses of the crystal structures lead to propose an irreversible polymorphic transition based on a destructive/reconstructive mechanism. Under comparable conditions (mass of solid, temperature, etc.) the conversion is completed within 14 days by means of slurring in ethanol (10 days if seeded) whereas 5 h only are necessary by means of mechanical activation under wet conditions and 9 h under dry milling. In the latter conditions the resulting materials appears significantly more defective in comparisons to the other modes of conversion.
Abstract
Heterogeneous equilibria are reviewed in binary and ternary systems of enantiomers without and with in situ racemization. The twofold symmetry between the two chiral components is also found in the phase diagrams except for stable conglomerate forming systems associated with a fast in situ racemization in the liquid phase. In this particular case, a gentle attrition speeds up the irreversible evolution of the system towards a spontaneous symmetry breaking, i.e., a single crystallized enantiomer in equilibrium with its racemic solution. This final evolution is predicted to reach the limit of miscibility in the solid state for conglomerate forming system with partial solid solution and in situ racemization.
Abstract
A combined analysis of structural data and experimental results (DSC, temperature-resolved XRPD and hot stage optical microscopy) revealed that the dehydration mechanism of cortisone acetate monohydrate (CTA·H2O) involves a collective and anisotropic departure of water molecules followed by a cooperative structural reorganization toward the anhydrous polymorph CTA (form 2). In spite of the lack of crystal structure data, it can be postulated from experimental data that thermal decomposition of the dihydrated form (CTA·2H2O) and of the tetrahydrofuran solvate (CTA·THF) toward another polymorph (CTA (form 3)) also proceeds according to a cooperative mechanism, thus giving rise to probable structural filiations between these crystalline forms of CTA. The crystal structure determination of two original solvates (CTA·DMF and CTA·DMSO) indicates that these phases are isomorphous to the previously reported acetone solvate. However, their desolvation behaviour does not involve a cooperative mechanism, as could be expected from structural data only. Instead, the decomposition mechanism of CTA·DMF and CTA·DMSO starts with the formation of a solvent-proof superficial layer, followed by the partial dissolution of the enclosed inner part of crystals. Hot stage optical microscopy observations and DSC measurements showed that dissolved materials (resulting from a peritectic decomposition) is suddenly evacuated through macroscopic cracks about 30°C above the ebullition point of each solvent. From this unusual behaviour, the necessity to investigate rigorously the various aspects (thermodynamics, kinetics, crystal structures and physical factors) of solvate decompositions is highlighted, including factors related to the particular preparation route of each sample.
Abstract
Dehydration of trehalose dihydrate implemented by slow heating (1 K min−1), has been monitored by Raman microspectroscopy from 25 to 110�C directly on single crystals. Between 90 and 120�C, gas initially trapped in irregular macroscopic defects, reorganizes to form spherical vacuoles. The Raman analysis of these vacuoles highlights that the areas in vicinity of the defects are the first affected by the dehydration mechanisms. Indeed, the progressive amorphization of the crystal starts around these defects.
Abstract
The resolution of (�)-5-phenyl-5-trifluoromethyl-imidazolidine-2,4-dione ((�)-CF361H hereafter) using 1-phenyl-ethylamine (αMBA hereafter) in ethanol was investigated. At 20�C, the evolution of the resolution
efficiency vs. the excess of αMBA was studied by establishing a part of the quaternary system: (+) and (−)-CF361H/(−)-αMBA/ethanol.
Competition between two equilibria has been highlighted:
•
Metastable equilibria between distereomeric salts ((�)-CF361H and enantiopure (−)-αMBA).
•
Stable equilibria involving a double salt Q which exhibits a non-congruent solubility.
Abstract
Discontinuous isoperibolic thermal analysis (ΔITA) is a phase diagram investigation technique applicable to organic components systems (with at least one liquid phase). The elementary signal is composed by the evolution of the temperature of the system vs. time after a composition shift. A theoretical analysis and a mathematical modeling of this signal show that the overall enthalpy exchanged multiplied by a proportional factor can be obtained. From different experiments, evidence is given that this semi-quantitative calorimetric measurement is reliable. Thus, ΔITA allows consistent and accurate descriptions of phase diagrams and is a real relative calorimetric measurement technique.
Abstract
The crystallization behaviour and the physical characterization of supramolecular complexes formed between permethylated-α-cyclodextrin (TMα-CD) and the enantiomers of phenylethanol (PE) are investigated. According to crystal structure analyses, complexes containing the pure guest enantiomers are almost isomorphous, indicating that the host presents a poor ability to distinguish PE enantiomers at a molecular level. Nevertheless, crystallizations from racemic PE in water induce an efficient chiral discrimination and allow the enantio-separation of the guests despite the existence of a solid solution revealed by XRPD and coupled TG-DSC analyses. The enantiodifferentiation is explained by solubility differences between the two diastereomeric complexes in the studied temperature range. Moreover, it is shown that the diastereomeric complex TMα-CD/(S)-PE crystallizes in two distinct phases: a monohydrate and an anhydrous form, with a transition temperature close to 37C. The insertion of a water molecule in the crystals grown below 37C does not involve any other change of the crystal packing nor of the molecular conformation, but leads to different crystal growth mechanisms inducing different morphologies and distinct thermal behaviours.
Abstract
Solid-solid transformations between solvates of pharmaceutical compounds are investigated under various conditions. In the case of Roxithromycin, it is shown that starting from single crystals of the acetonitrile solvate, a transformation towards the monohydrate occurs according to a cooperative mechanism. This smooth exchange of solvent probably involves a transport of matter within channels, and the comparison of crystal structures is consistent with the persistence of the main features of the 3D lattice. By contrast, starting from the DMSO solvate of Dexamethasone acetate, the transformation towards the sesquihydrated form, induced by the immersion of the DMSO solvate in water, is fully destructive and reconstructive. This occurs far-from-equilibrium and is therefore controlled by kinetic factors. The existence of an intermediate liquid phase within the particle is postulated to account for the appearance of whisker-like crystals growing first on high-energy sites of the former particle. An extended analysis of these transformations between solvates shows that they could be classified according to rules previously proposed in the case of desolvation mechanisms.
