(523e) Continuous Enzymatic Reactive Distillation with Immobilized Enzyme Beads

Chemical industry is facing economic and ecologic challenges and therefore looks for intensified processes and new green synthesis routes like biocatalytic reactions. Enzymes are biocatalysts, able to convert a wide range of substrates with high regio- and enantioselectivity and thus to replace classical chemical catalysts. They are obtained from renewable resources and can be formulated with protein or genetic engineering to a desired specification.

Most current enzymatic reactions are carried out in batch reactors and exhibit small space-time yields due to equilibrium-limitations or product inhibitions [1, 2, 3]. In order to increase space-time yields we investigate the combination of enzymes and reactive distillation, which integrates reaction and separation in one unit operation to overcome reaction as well as thermodynamic equilibrium limitations. Therefore, combining enzymatic reactions and reactive distillation to Enzymatic Reactive Distillation (ERD) can create synergies enabling efficient production of totally new products and savings in operational and capital costs.

While batch ERD has been investigated experimentally and the feasibility has successfully been shown [4], continuous operation of ERD has not been reported in literature so far and will be demonstrated in this study. Compared to batch operation, the continuous operation offers additional benefits through steady-state operation and constant product composition. Similar to batch ERD, it is essential to integrate the enzyme inside the distillation column and to guarantee that no temperature-induced denaturation occurs in the column. In our work the enzyme is immobilized on an acrylic polymer resin, filled in structured packing Sulzer Katapak-SP ® above the stripping section of the column.

Experiments of the ERD are carried out at a continuously operated reactive distillation column in pilot-scale with a diameter of 50 mm. The lipase-catalyzed and equilibrium-limited transesterification of ethyl-butyrate with n-butanol is investigated as case study and a high conversion of the substrates is reached. Investigations of varying process conditions allow for the identification of important process parameters that have a high influence on substrate conversion and product purity.

Based on kinetic and thermodynamic data, a detailed rate-based model of the ERD is developed. Simulation results and experimental data of the ERD setup are in good agreement. Consequently, the validated model can be used for equipment design, scale-up, process analysis and optimization of the investigated ERD systems.

References

[1] Woodley, J. M.; Pollard, D. J.; Biocatalysis for pharmaceutical intermediates: the future is now, Trends Biotechnol 2007, 25 (2), p. 66–73

[2] Liese, A.; Kragl, U.; Einfluss der Reaktorkonfiguration auf die Enantioselektivität einer kinetischen Racematspaltung, Chem. Ing. Tech. 2013, 85 (6), p. 826–832

[3] Rao, N. N.; Lütz, S.; Würges, K.; Minör, D.; Continuous Biocatalytic Processes, Org. Process Res. Dev. 2009, 13 (3), p. 607–616

[4] Heils, R.; Sont, A.; Bubenheim, P.; Liese, A.; Smirnova, I.; Integration of Enzymatic Catalysts in a Reactive Distillation Column with Structured Packings ,Ind. Eng. Chem. Res. 2012, 51 (35), p. 11482–11489