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Enantioseparation; Process intensification; Crystallization; Optimization
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 (Jacques et al., 1994). 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 enantioselective preferential crystallization (Elsner et al., 2005) In a batch crystallizer racemic mixture of conglomerate forming systems tend to reach an equilibrium state in solution in which the liquid phase has racemic composition and the solid phase is 1:1 mixture of crystals of both enantiomers. However, before approaching this state, it is possible to preferentially produce just one of the enantiomers after seeding with homochiral crystals.
Among all available crystallizer configurations the batch mode is obviously the easiest one. The principle of batch process is quite simple: the vessel is filled with a supersaturated solution of the racemate (enantiomers Ep and Ec). After addition of homochiral seeds e.g., merely Ep is crystallizing within a limited time period. In order to gain the target enantiomer as a product of high purity, the process must be stopped before the nucleation of the undesired counter-enantiomer occurs (Lorenz et al., 2006). During this batch crystallization, the concentration of the desired enantiomer in the solution is decreasing, whereas the concentration of the counter-enantiomer remains constant. Based on analysis of these concentration profiles a more attractive and effective operation mode using two batch crystallizers coupled via liquid phase (see Fig. 1) has been studied (Ziomek et al., 2007). In each vessel one of both enantiomers is seeded and grows subsequently. An exchange of the crystal free liquid phases between the crystallizers leads to an increase of driving forces and consequently process productivity.
The influence of important process variables like initial seed size distribution, exchange flow rates between crystallizers, and temperature has been analyzed experimentally using threonine-H2O as a model system. The influence of initial seed size distribution on the productivity and product quality will be shown. By varying size of particles used as a seeds, nucleation as well as growth kinetics are influenced. It will be demonstrated that by appropriate changing of free operating parameters the process performance can be controlled and improved. Parallel to the experimental analysis, a modeling approach will be also presented.
References
Jacques, J., Collet, A., Wilen, S.H., (1994): Enantiomers, racemates and resolutions, Krieger, Malabar
Elsner, M.P., Fernández Menéndez, D., Alonso Muslera, E., Seidel-Morgenstern, A. (2005): 17 (S1), S183-S195
Lorenz, H., Perlberg, A., Sapoundjiev, D., Elsner, M.P., Seidel-Morgenstern, A., (2006) Chem. Eng. and Proc., doi, 10.1016/ j. cep. 2005.11.013
Ziomek, G., Elsner, M.P. Seidel-Morgenstern, A., (2007) Submitted to Chemical Engineering Science
