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Schlagwörter:
Nucleation and Growth; Optimization and Control; On-line Monitoring
Zusammenfassung:
With the movement by pharmaceutical companies to develop single enantiomers instead of racemic mixtures as drug candidates, the focus of their research interest has turned to problems associated with an efficient preparation or separation of pure enantiomers. Despite the rapid development of enantioselective catalysts for asymmetric synthesis over the past 30 years, very few are really applied in technical scale due to limitations in cost, time for process development and catalyst stability. The resolution of racemates still holds a key position for the production of pure enantiomers. Among other enantioseparation methods, like diastereomeric salt formation and preferential crystallization, enantioseparation can always be performed by crystallization from asymmetric chiral mixtures, where the desired enantiomer is enriched to a certain extent. If this is not resulting from the previous chemical synthesis or production step, the symmetry of racemic mixtures can be broken by a previous resolution step, e. g. by chromatography. Understanding of crystallization kinetics plays an important role for the design and optimization of successful enantioselective crystallization processes. As the final purity of the desired enantiomer is affected by crystal growth, the impact of growth kinetics on the economic potential of this separation process is evident. Furthermore, the influence of the counter enantiomer present in the solution both on crystallization kinetics and product purity is of interest. On this background the work to be presented is concerned with a detailed study on crystal growth kinetics on the example of mandelic acid in water. Based on preceding measurements of thermodynamic data and the metastable zone width in the chiral system [1] experimental data collected during isothermal crystal growth experiments will be shown and analyzed. The studies were performed at different crystallization temperatures and with varying enantiomeric ratio in the initial solution. Growth kinetic data and the applied model are presented and discussed in detail. The influence of the studied parameters on the potential of an efficient enantioselective crystallization process is evaluated.
[1] Perlberg, A., H. Lorenz and A. Seidel-Morgenstern Determination of crystallization relevant data for enantioseparation purposes Chemical Engineering Transactions (Volume I) Proceedings of the 15th Int. Symp. on Industrial Crystallization, (Ed.) A. Chianese, pp. 173-178, AIDIC, Sorrento, Italy 2002
