Increase in productivity for enantioseparation by simultaneous preferential crystallization

An increasing demand for pure enantiomers in last years is motivated by the high interest of the pharmaceutical and agricultural industry in chiral components. The well known fact is that usually, only one of the enantiomers shows the desired properties. In general two strategies for achieving pure enantiomers has been developed, i.e. enantioselective synthesis and separation of enantiomers from racemic mixtures. In opposite to the commonly used separation methods like chromatography an attractive and relatively simple process is the so-called enantioselective preferential crystallization [1]. Up to now this concept has been applied only for conglomerates. In solution such systems tend to reach an equilibrium state 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. Perfectly mixed batch crystallizers can be described mathematically in a simplified manner using a dynamic, one dimensional model which includes experimentally determined kinetic parameters. Such a model was applied in order to describe the process for the threonine-H₂O system [2]. Based on the simplified approach, attractive and more effective operation modes using two crystallizers coupled via liquid phase has been studied. In each vessel one of both enantiomers is crystallizing simultaneously. An exchange of the liquid phase between the crystallizers leads to an increase of the process productivity. The influence of important process variables like enantiomeric excess, initial seed size distribution, exchange flow rate between crystallizers, and temperature has been analyzed theoretically. The results of the influence of enantiomeric excess (e.e.) in mother liquor on the productivity of the process are shown in Fig. 1 where an increase of e.e. leads to higher productivity. Furthermore for a given e.e. an optimal time exists for starting the exchange of the crystal-free mother liquids. [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-S19