A mathematical model describing the separation of enantiomers by simultaneous preferential crystallization in a coupled crystallizer configuration is developed. The model was validated against experimental data for a chemical model compound, the conglomerate forming system of asparagine monohydrate in water. The kinetic parameters required were taken from available literature sources and simulations compared to experimental data. Simulations were found to be in good agreement with experimental data. Additional model simulations suggest that the separation process can be improved by increasing the mean residence time of the liquid phase in the crystallizers, and the mass of seeds supplied. Reducing the size of seed crystals will also lead to an improved separation. The model can also be used to simulate the performance of the crystallization process for a racemic compound forming system. The racemic compound and the pure enantiomer can be separated simultaneously in each crystallizer, having sufficient enrichment of the pure enantiomer in the feed solution. The model can also be extended to represent a fully continuous separation process taking into account the continuous supply of enantiopure seed crystals and liquid feed solution and the continuous removal of solid product and mother liquor.
Organic Process Research and Development, 2014, Vol 18, Issue 5, p. 601-612