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Abstract:
The separation of chiral compounds is of large interest since most of the (bio-)organic molecules are chiral. Usually only one of the enantiomers shows the wanted properties with regard to therapeutic activities or metabolism, whereas the other enantiomer may be inactive or may even cause some undesired effects. In recent years, besides the most commonly used classical resolution via formation of diastereomers, direct crystallization methods have become increasingly important. An attractive process is the enantioselective preferential crystallization [1, 2]. In a batch crystallizer conglomerate forming systems tend to reach an equilibrium state in solution in which the liquid phase will have racemic composition and the solid phase will consist of a mixture of crystals of both enantiomers. However, before approaching this equilibrium state, it is possible to preferentially produce just one of the enantiomers after seeding with homochiral crystals.
Ideally mixed batch crystallizers, typically used for preferential crystallization, can be described mathematically in a simplified manner using a dynamic, one dimensional model which includes experimentally determined kinetic parameters. As a model system the threonine-H2O system [3] has been studied. Based on a simplified approach a more attractive and effective operation mode using two batch crystallizers coupled via their liquid phases [4] has been investigated (see Fig. 1). In each vessel one of the two enantiomers is seeded and grows subsequently. An exchange of the crystal free liquid phases between the crystallizers leads to an increase of the concentrations of the preferred enantiomers and therefore the driving forces for the crystallization. This enhances also the productivity. The influence of the size distribution and the mass of the seeds on the process symmetry has been analyzed theoretically. It can be shown that by varying the initial CSD of the seeds the final product properties as well as important process parameters (e.g., productivity) can be controlled.
Theoretical studies have further shown that optimal process variables need to be adjusted according to the required product properties. Parallel to the theoretical analysis, an experimental validation of this process has been performed. The results will be given in this presentation.
[1] JACQUES, J.; COLLET, A.; WILEN, S.H. (1994): Enantiomers, racemates and resolutions, Krieger, Malabar
[2] ELSNER, M.P., FERNÁNDEZ MENÉNDEZ, D., ALONSO MUSLERA, E., SEIDEL-MORGENSTERN, A. (2005): Experimental study and simplified mathematical description of preferential crystallization, Chirality 17 (S1), S183-S195
[3] LORENZ, H., PERLBERG, A., SAPOUNDJIEV, D., ELSNER, M.P., SEIDEL-MORGENSTERN, A., (2006) Crystallization of enantiomers, Chem. Eng. and Proc. 45(10), 863-873
[4] ELSNER, M.P.; ZIOMEK, G.; SEIDEL-MORGENSTERN, A. (2006): Investigation of simultaneous preferential crystallization for enantioseparation. Lecture # 13d, Annual Meeting of the American Institute of Chemical Engineers (AIChE), 12th – 17th November 2005, San Francisco
