(641g) Continuous Membrane Reactors for Asymmetric Synthesis and Separation in Organic Media

Due to the numerous advantages over conventional transition-metal catalysis, organocatalytic methodologies have become an attractive synthetic tool in asymmetric catalysis. However, the cumbersome product purification by column chromatography, and the need for catalyst recovery and reuse, call for the design of more flexible and sustainable organocatalytic strategies. Membrane-based separations, and in particular nanofiltration, have been recognized as sustainable technologies allowing the purification and concentration of chemicals under mild conditions. Nevertheless, due to the insufficient rejection of catalysts, the slow leaching of the catalyst or its adsorption to the membrane lead to decreased reaction rate and product contamination in membrane-assisted catalysis.^[1] Polymer immobilised catalysts showed excellent activity in a continuous organocatalysis – membrane separation hybrid process,^[2] but the deterioration in enantioselectivity remained an issue. Here we present the new methodology of covalent grafting of organocatalysts on nanofiltration membranes for integrated synthesis−separation.^[3] Polybenzimidazolium (PBI) nanofiltration membranes were prepared with different rejection profiles and decorated with cinchona-squaramide type organocatalysts via azide-alkyne click reaction to obtain the membrane catalysts. The membrane catalysts were applied in Micheal addition and aza-Michael addition reactions in a catalytic membrane cascade reactor system configuration. A solution of dibenzyl malonate and β-nitrostyrene in toluene was loaded into the first stage of a membrane rig. The first stage was equipped with the membrane catalyst (0.01 eq. cinchona-squaramide unit). The catalysis was performed by recirculating the reaction mixture for 12 h at 30 bar using cross-flow configuration with tangential flow of 90 L h^-1. The asymmetric organocatalysis with integrated separation was successfully demonstrated in a two-stage membrane cascade reactor. The integrated separation allowed at least 98% product recovery and 99% unreacted substrate recovery. The demonstrated new synthetic methodology with in situ solvent recovery mitigated the need for solvent addition for purification. The concept of catalyst-grafted membrane cascade reactor enables new possibilities for fine chemical manufacturing, and further boosts growth in the exciting new era of organocatalysis.

References

[1] L. Cseri, T. Fodi, J. Kupai, A. Garforth, G. Szekely, Membrane-Assisted Catalysis in Organic Media, Adv. Mater. Lett., 2017, 8, 1094–1124.

[2] T. Fodi, G.T. Balogh, P. Huszthy, G. Szekely, Nanofiltration‐Enabled In Situ Solvent and Reagent Recycle for Sustainable Continuous‐Flow Synthesis, ChemSusChem, 2017, 10, 3435–3444.

[3] C. Didaskalou, J. Kupai, L. Cseri, J. Barabas, E. Vass, T. Holtzl, G. Szekely, Membrane-Grafted Asymmetric Organocatalyst for an Integrated Synthesis–Separation Platform, ACS Catal., 2018, 8, 7430–7438.