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要旨:
The separation of enantiomer mixtures into the pure enantiomers is of growing importance for the pharmaceutical, food and agrochemical industries.
One possibility to separate these mixtures is preferential crystallization [1]. Depending on the system under investigation it is possible to crystallize a single enantiomer of a conglomerate or racemic compound forming system via seeding with crystals of the desired species [2]. The seeds trigger the crystallization of the target species which crystallizes inside the three-phase region of the phase diagram until nucleation of the unwanted species occurs. The applicability and productivity of this process is mainly governed by the crystallization kinetics. This process is already known for some time but still lacks examples of industrial application. One reason for this might be the complexity and sensitivity of the process on the process conditions. The difficulties in process design and control can hopefully be overcome if suitable online- and inline-measurement techniques are used.
The objective of the present study is to show the synergy that can be achieved, if an online monitoring of the liquid phase with a polarimeter and densitymeter is coupled with an inline monitoring of the solid phase using a Lasentec® FBRM- and PVM-probe in the vessel. As case studies enantioseparation of two systems is investigated in a 1L-scale:
1) DL-threonine in water (conglomerate) and
2) (RS)-mandelic acid in water (racemic compound).
The experiments show the trajectories of the liquid-phase concentration and enantio-meric composition as well as the particle appearance and the dynamics of crystal dissolution, nucleation and crystal growth of the solid phase for two different seeding strategies.
The results presented for these combined process analytics are new and demonstrate the potential for the application of coupled analytics for process monitoring, model development, process design, optimization and scale-up in the field of complex crystallization processes. The preferential crystallization separations of the two species mentioned above act as challenging case studies.
References
[1] Jacques, J., Collet, A., Wilen, S. H. (1994): Enantiomers racemates and resolutions, Krieger Publishing Company Malabar, Florida
[2] Lorenz, H., Polenske, D., Seidel-Morgenstern, A. (2006): Application of preferential crystallization to resolve racemic compounds in a hybrid process, Chirality 18, 828-840
