Process Strategies for Batch Preferential Crystallization
An abundance of molecules belongs to the class of chiral compounds that exist in two possible three dimensional mirrored conformations (enantiomers) Apart from the spatial arrangement they are virtually identical sharing the same physical and chemical properties. Over the course of evolution, nature eventually favored one of two enantiomers of a molecule to build living organisms. This is commonly referred to as homochirality of life. As a consequence, every biological entity is capable to distinguish between enantiomers. This can have fatal consequences especially when chiral molecules are used in pharmaceutical drugs. The most prominent example for such a failure was the thalidomide tragedy, which led to the insight that chiral active pharmaceutical ingredients have to be provided as single enantiomers and not as a 50:50 mixture (racemate) Access is, however, complicated by their identity. It is possible to selectively synthesize one enantiomer by chemical means with significant effort. In many cases the final product has to be in the solid state though requiring additional steps such as crystallization or precipitation. An alternative strategy is the separation of the racemate. Apart from chromatography, which results in a highly pure but very dilute product stream, crystallization is an attractive process combining separation and solid formation in one step. The enantiomers of a certain class of chiral molecules can be separated by so called preferential crystallization. This technique allows direct crystallization of single enantiomers from a racemic solution. The focus of this work is a systematic experimental and theoretical investigation of preferential crystallization. The aim is to increase robustness and yield as well as the optimization of process conditions, which involves the study of novel operating modes.