Production Of Pure Enantiomers By Integrating (Continuous) Chromatography And Racemisation Reactions

Chemical processes most generally consist of a reaction step and a subsequent separation of the target product from unconverted educts and side products. This holds also for the production of enantiomers (i.e., optical isomers with a special importance for pharmaceuticals, flavours, etc.). However, since usually only one enantiomer has the intended physiological effect, it is highly desirable to combine enantioseparations with an interconversion (racemisation) of the undesired enantiomer. Ultimately, this would increase the maximum overall yield of the desired species from 50% to 100%. Racemisation reactions can be triggered, for example, by increased temperature, adjusting pH value, or by enzymes, homogeneous and heterogeneous catalysts, respectively. Furthermore, several chromatographic techniques are available where the classical four-zone SMB process might represent a sub-optimal choice. Interesting alternatives are here SMB schemes with a different number of zones and single column processes like one-column SMB analogs, closed loop and steady state recycling, etc. Obviously, the manifold options for reaction and separation lead to a multitude of possible process schemes that combine enantioseparation and racemisation of the undesired enantiomer. In this work, different integrated processes will be studied systematically, ranging from fully integrated chromatographic reactors (SMB and single column) to flowsheet-integrated schemes with racemisation in a recycle stream. Investigations are performed both model-based as well as experimentally for a model substance. The presentation will conclude with a comparison of the different processes and the derivation of design guidelines