Single-crystal – oriented-crystal – and epitaxy growth processes; – Processes of growth from liquid or supercritical state – Having growth from a solution comprising a solvent which is...
Patent
1996-10-02
2000-02-08
Kunemund, Robert
Single-crystal, oriented-crystal, and epitaxy growth processes;
Processes of growth from liquid or supercritical state
Having growth from a solution comprising a solvent which is...
117 70, 117925, 117926, 117927, 23300, 23311, C30B 714, C30B 2954
Patent
active
060224096
DESCRIPTION:
BRIEF SUMMARY
The present invention concerns the area of separation of two antipodes optical of a species chemical by crystallization preferential. This method rests on crystallization alternate of two compounds chiral designated R and S, by producing a conglomerate in a solvent A and for a range given of temperature .DELTA.T. This means that in this range of temperature any mixture in equilibrium thermodynamic of two antipodes with the solution consists of two types of crystals containing each only molecules of the same configuration, incorporating or not the molecules of solvent (solvates). The existence of such conglomerate without miscibility in the state-solid will be implicitly assumed in that which follows, at least in the range of temperature .DELTA.T and for the solvent A.
The technique of crystallization preferential is widely employed in laboratories and in the industry owing to the major advantages that it offers: later implies losses rarely less than 10% (De Min. M., Levy. G., and Michaeu, J. C. (1988) J. Chim. Phys. 85, 603-19). resolution classic by formation of salts diastereoisomeric; successive;
Two classes of factors influence crystallization of antipodes optical, on the one hand, parameters related to equilibrium heterogeneous ternary and on the other hand, factors that intervene in the kinetics of crystallization.
The parameters related to equilibrium heterogeneous ternary comprise: deposited at each temperature, and more particularly, the values of the solubilities of the phases stable and metastable, of the mixture racemic s(.+-.) and the antipodes s(+)=s(-), as a function of the temperature, and the ratio of solubilities .alpha.=s(.+-.)/s(+); racemate, of solvate racemic, of solvate active and varieties polymorphic of the solids crystallized.
The factors intervening in the kinetics of crystallization comprise: molecules, which are nonmodifiable by the experimenter; the nature of the solvent, the nature and the concentration of the impurities, the supersaturation acquired as a function of the time, the range of the temperature .DELTA.T, the rate and the method of agitation, the weight and the particle size of the nuclei, the effect of the wall, etc.
These two classes of factors influence directly the yield, the purity of the phases obtained and the sequence of operations of separation. The feasibility of filtration will be thus dependent on the spectrum particle size and the habit of the crystals, the viscosity of the suspension, the pressure of vapor of the solvent, supersaturations acquired by each of the antipodes and the presence possible of a racemate true with characteristics metastable. These choices can also intervene in the kinetics of racemization of antipodes or degradation of the molecule.
For each aggregate comprising the pair of antipodes (R and S) and solvent (A), the factors intervening on kinetics are a case special.
The present invention seeks to improve the methods for crystallization preferential of the art prior from a better understanding of the equilibria heterogeneous ternary achieved from solvent A and antipodes optical R and S. In effect, knowledge of the equilibrium heterogeneous furnished data exploited in the process of the invention to accomplish resolution more effective and rational of the two antipodes optical by crystallization preferential (or balancing).
More particularly, the process of the invention permits optimization and generalization of a process of the type described in Patent French No. 1 456 627 concerning resolution of acid glutamic and its salts.
SUMMARY OF INVENTION
The process of the invention rests on a modification of the scope general of the processes classic designated below SIPC for "Seeded isothermal prefrential crystallization" and the variants polythermal, owing to the exploitation of the information contained in the representation of the equilibria ternary: antipode R--antipode S--solvent A.
SUMMARY OF INVENTION
The process of the invention consists: the form of conglomerate, a first enantiomer and solvent, whose point figurative E,
REFERENCES:
G. Coquerel, et al., "optical Resolution of (.+-.) -N-Acylnorfenfluramine Derivatives by Preferential Crystallization", Tetrahedron Letters, vol. 31, No. 15, pp. 2143-21244 (1990).
A. Collet, et al, "Optical Resolution by Direct Crystallization of Enantiomer Mixtures", Chemical Reviews, vol. 80, No. 3, pp. 215-230 (1980).
G. Amiard, "Sur le dedoublement direct de la threonine, par entrainement", Bulletin De La Societe Chimique De France, No. 81, p. 447, (1956).
Bouaziz Roger
Coquerel Gerard
Petit Marie-Noelle
Kunemund Robert
The University of Rouen
Weiser Gerard J.
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