(257c) Novel Metal-Enzyme Catalyst for One-Pot Dynamic Resolution in a Spinning Cloth Disc Reactor

A large industrial problem with catalysts are that most are not compatible with each other and often several processing steps are necessary, including intermediate product purification and catalyst separation , both of which are expensive and energy intensive processes [1]. One novel approach (little researched but is starting to receive more academic attention) is to have a continuous flow across two or more catalysts spatially separated– i.e. single flow – multi catalysis, or continuous cascade chemistry [2]. Multi-catalyst, one-pot reactions find extensive application in pharmaceuticals where one enantiomer is more active and responsible for the necessary action of the drug and the other is less active and often causes adverse side effects [3]. The spinning mesh disc reactor (SMDR) is a novel technology and has the potential to augment this chemistry [4]. The SMDR uses centrifugal forces to allow an even spread of a thin film across a spinning horizontal disc covered by a replaceable cloth. The cloth can have a range of catalysts immobilized onto it, so as to have a series of reactions occurring in ‘One-Pot’. The aim of this study is thus to investigate and optimise the SMDR for cascade reactions.

Henry’s reaction coupled with the kinetic resolution using copper triflate and lipase as catalysts was chosen as a model reaction to allow easy comparison to literature [3]. Wool was pre-treated with a solution of hydrogen peroxide and sodium silicate and modified with PEI. The modified cloth was rinsed with distilled water and soaked in copper triflate solution (in methanol) for 24 hours. Enzyme immobilisation was carried out by soaking the PEI modified cloth in lipase solution followed by cross-linking with glutaraldehyde. The cascade reactions were carried out in the SMDR by stacking the two different catalytic cloths on top of each other. The liquid firstly flowed through the cloth with the metal catalyst and then penetrated through to the enzyme immobilised cloth [5]. Reaction conversion was monitored continuously using NMR and HPLC. The effect of spinning speed, flowrate on conversion was also investigated. Conversion in batch (using both free and immobilized catalysts) and in the SMDR showed similar conversion of ~90%, which were in agreement with literature [6]. However, the reaction time for the same conversion in SMDR was significantly shorter than the batch process, thus showing proof of concept and achieving process intensification.

To the best of the authors’ knowledge, this is the first study that successfully has achieved a cascade reaction in a spinning disc reactor or in any kind of a similar reaction system. This further implies the huge potential in this area and we are currently investigating ways to further improve and optimise the reaction conditions in the SMDR.

References

[1] Supramol. Chem. (2014), 32, 73-77

[2] Curr. Opin. Biotechnol. (2014), 28, 10-16.

[3] Adv. Synth. Catal. (2008), 350(3), 448-452.

[4] Chem. Eng. J. (2013), 221, 407-417.

[5] Chem. Eng. J. (2014), 255, 356-364.

[6] J. Mol. Catal. A: Chem. (2010), 325(1), 8-14.