(70c) Scalable Pervaporation Membrane to Enable New Continuous Flow Chemical Synthesis Routes

Pervaporation membranes can be used to avoid azeotropic distillation, enable flow chemistry technology, degas organic solvents, dehydrate solvents, drive reactions towards product formation and more. Compact Membrane Systems (CMS) has demonstrated the effectiveness of their fluoropolymer pervaporation membranes to degas and dewater organic solvents for the pharmaceutical and specialty chemical industries in recent years. This has particular relevance in flow or continuous chemistry, which has gained momentum as the world moves to energy efficient, modular manufacturing.

A major challenge for the adoption of flow chemistry is transitioning from the laboratory bench to commercial scale. Teflon AF 2400 extruded tubing is the embodiment of this challenge. Researchers have successfully demonstrated the feasibility of flow chemistry reaction mechanisms at the benchtop scale, but many of these chemistries have not been implemented at large scale^1,2. This talk will present a side by side by side comparison of a CMS pervaporation membranes to Teflon AF tubing as a scalable, cost effective alternative solution. Oxygen removal rates were studied at ambient temperature at a variety of flow rates and concentration scenarios. The CMS membrane was able to match or exceed the Teflon AF 2400 tubing in recovery and degassing across all cases studied. Economic models also show that the CMS membrane is both an efficient and cost-effective solution. A case study will also be presented to show the effectiveness of the solution in the pharmaceutical and fragrance industries.

This case study was performed in collaboration with Snapdragon Chemistry and the Massachusetts Institute of Technology and published in OPRD in 2020³. A CMS membrane was used to selectively remove ethylene from a ring closing metathesis reaction to drive product formation and enable the use of flow chemistry.Using traditional batch techniques, implementing olefin metathesis reactions on the commercial scale has proven challenging, if not impossible. Ring closing reaction mechanisms are commonly used during the preparation of small molecules for the pharmaceutical and fragrance industries. Membranes are a modular, scalable solution that can continuously remove the ethylene byproduct and enable the use of commercial scale continuous ring closing metathesis. This case study details the advantage of using a sheet-in-frame membrane reactor as opposed to a stainless steel tubular reactor. The fluoropolymer membrane has excellent chemical and thermal stability which allows for an extended range of thermal conditions without sacrificing selectivity or flux. Pure ethylene flux of the membrane was also investigated to ensure that the mass transport across the membrane would always be greater than the reaction’s ethylene production rate. Scale up considerations including residence time, required ethylene removal rate and module design will be addressed. The feasibility of using a membrane reactor to remove byproducts shown in this case study is only one example of the reactions that could benefit from the implementation of membrane reactors.

References:

(1) Hughes, D.; Wheeler, P.; Ene, D. Olefin metathesis in drug discovery and development - examples from recent patent literature.

Org. Process Res. Dev. 2017, 21, 1938-1962.

(2) Higman, C. S.; Lummiss, J. A. M.; Fogg, D. E. Olefin metathesis

at the dawn of implementation in pharmaceutical and specialty chemicals

manufacturing. Angew. Chem., Int. Ed. 2016, 55, 3552-3565.

(3) Breen, C.; Parrish, C; Shangguan, N.; Majumdar, S.; Murnen, H.; Jaimson, T.; Bio, M. A Scalable Membrane Pervaporation Approach for Continuous Flow Olefin Metathesis. Org. Process Res. Dev. 2020, 24, 2298-2303