Max-Planck-Institut für Dynamik komplexer technischer Systeme

Motivation

The two enantiomers of a substance are stereoisomers with very similar physico-chemical properties (see Fig. 1). Usually only one of the two forms has the desired physiological effect – the other might be ineffective or harmful. Therefore, pure single enantiomers are of high importance in pharmaceutical and fine chemical industries.
A major problem related to obtaining a pure enantiomer is that conventional chemical synthesis delivers the 1:1 mixture of the two enantiomers, which necessitates a subsequent (expensive) separation and limits the overall yield to 50 % only. Thus, it is desirable to combine enantioseparations with a reactive interconversion of the undesired form.

Figure 1: Example for the two enantiomers of a substance (here: chlorthalidone).

Goal of the project is to is to improve the production of pure enantiomers by clever combinations of reaction and separation steps.

Approach

Improved and novel process concepts are developed that integrate enantioseparations (e.g. by crystallization or chromatography) and isomerization (racemization) reaction (see Fig. 2). Both flowsheet-integrated schemes (i.e. process combinations) and fully integrated systems (i.e. reactive separations) are considered. Furthermore, methods and tools are developed for optimal design and performance prediction at the process development stage.

Integrated process for production
of a pure enantiomer.

Figure 2: Schematic representation of an integrated process
that delivers a pure enantiomer from a mixture at a yield of 100%.

First promising results were obtained for flowsheet-integrated processes that combine chromatographic separations by Simulated Moving Bed (SMB) and Steady-state Recycling (SSR) chromatography [1]. It was shown that such schemes can operate at significantly improved process performance. In this context, design methods developed in other projects for SMB and SSR schemes [2, 3] proved to be very helpful.

A further systematic study was performed of integrated processes that combine SMB chromatography and enantiomerization. Systems of different degree of integration were developed and investigated by optimization of corresponding models. Interesting results were obtained in particular for processes with an internal spatial distribution of the functionalities [1]. The results can be fully explained based on the recent methodology developed from equilibrium theory for reactive separations [4, 5].

Future work

Further theoretical studies of fully integrated processes,
Experimental work on distribiuted functionalities,
Further development of methods and tools.

References

M. Kaspereit, J. García Palacios, T. Meixús Fernández and A. Kienle (2008). Systematic design of production processes for enantiomers with integration of chromatography and racemisation reactions. In: B. Braunschweig and X. Joulia (Eds.), ESCAPE 18, Elsevier, Amsterdam, pp. 97–102.
M. Kaspereit, A. Seidel-Morgenstern and A. Kienle (2007). Design of simulated moving bed processes under reduced purity requirements. J. Chromatogr. A, 1162, 2–13.
T. Sainio and M. Kaspereit (in press). Analysis of steady state recycling chromatography using equilibrium theory. Sep. & Purif. Technol.
S. Grüner and A. Kienle (2004). Equilibrium theory and nonlinear waves for reactive distillation columns and chromatographic reactors. Chem. Engng. Sci., 59, 901–918.
S. Grüner, M. Mangold and A. Kienle (2006). Dynamics of reaction separation processes in the limit of chemical equilibirium. AIChE J., 52, 1010–1026.