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An attractive process for gaining pure enantiomers from racemic mixtures is the so-called enantioselective preferential crystallisation [1, 2]. In a batch crystalliser conglomerate 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 state, it is possible to preferentially produce just one of the enantiomers after seeding with homochiral crystals.
For all available crystalliser configurations, of course a batch mode is the easiest one to realise. The principle of this batch process is quite simple: the vessel is filled with a supersaturated solution of the racemate (Ep+Ec as 50%:50% mixture). After addition of homochiral seeds e.g., merely Ep is crystallising within a limited time period. In order to gain this enantiomer as a product of high purity, the process must be stopped before the undesired counter-enantiomer occurs [3]. During this batch crystallisation, the concentration of the desired enantiomer in the solution is decreasing, whereas the concentration of the counter-enantiomer remains constant (see Fig. 1, below). This phenomenon leads to an arrangement which might provide a better performance where two crystallisers are coupled via the liquid phase, i.e., the crystal free mother-liquor is exchanged between these two vessels. Because of this exchange, the liquid phase shows a higher overall concentration of the preferred enantiomer in that vessel in which the preferred enantiomer was seeded. As it is shown in Fig. 1 (below) the supersaturation level which corresponds to the crystallisation driving force is higher during the whole process in comparison to the case without an exchange (simple batch mode). Additionally, the concentration of the counter-enantiomer in the liquid phase for each of the vessels decreases. For the borderline case of infinite exchange flow rate racemic composition is reached in the fluid phase of both vessels. The described effect of decreasing the counter-enantiomer concentration in that crystalliser in which the preferred enantiomer shall be gained (i.e., vessel A in Fig. 1) makes the probability for primary nucleation lower. This corresponds to higher product purity at the end of the process and enhances also the productivity. The effect of racemisation by exchanging the fluid phase allows the specific manipulation of concentration profiles and seems to be a suitable lever for process intensification on the apparatus level. Similar manipulation of the concentration profiles during the crystallisation process can be also realized on molecular level if the racemisation is achieved by an enzymatic reaction in which a surplus of the counter-enantiomer in the liquid phase is transformed to the preferred one [4]. These different configurations for productivity enhancement will be presented in this contribution.
In particular, as a model system the threonine-H2O system [3] has been studied. Based on a simplified approach the more attractive and effective operation mode using two batch crystallisers coupled via their liquid phases [5] has been investigated theoretically. The influence of specific process parameters, like e. g. the size distribution and the mass of the seeds, on the process symmetry has been analysed 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 also 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] LÜTZ, S.; WANDREY, C.; SEIDEL-MORGENSTERN, A.; ELSNER, M.P. (2006): Verfahren zur Herstellung chiraler Substanzen durch selektive Kristallisation unterstützt durch eine enzymatische Racemisierungsreaktion. DE 10 2006 013 725.6 (24.03.2006)
[5] 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
