Microfluidic Electrolytic Cells for Routine Synthesis in the Pharmaceutical Industry
Lead Research Organisation:
University of Southampton
Department Name: Sch of Chemistry
Abstract
Electrolysis is a synthetic procedure that avoids the use of stoichiometric and toxic/hazardous reagents and is usually carried close to ambient conditions. In addition, there is an extensive literature showing that reactions of interest to the pharmaceutical industry can be carried out with good selectivity. Despite this, and the consequential opportunity to develop more environmentally acceptable synthetic methods, the use of electrolysis is rare because of the need for specialist equipment and know-how. This project brings together a manufacturer of microflow equipment, industrial and academic synthetic organic chemists and electrochemists with experience of both organic electrosynthesis and equipment design/development in order (a) to develop user friendly microflow electrolysis equipment suitable for integration with traditional microflow systems (b) to show that the equipment is well matched to the challenges found in the pharmaceutical industry by optimising several conversions including the selective oxidation of alcohols to carbonyl compounds, the amination of alcohols, and partial fluorination.
Publications
Ciriminna R
(2017)
Electrochemical Alcohol Oxidation Mediated by TEMPO-like Nitroxyl Radicals.
in ChemistryOpen
Hill-Cousins J
(2012)
TEMPO-Mediated Electrooxidation of Primary and Secondary Alcohols in a Microfluidic Electrolytic Cell
in ChemSusChem
Kuleshova J
(2012)
The methoxylation of N-formylpyrrolidine in a microfluidic electrolysis cell for routine synthesis
in Electrochimica Acta
Green R
(2013)
A voltammetric study of the 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) mediated oxidation of benzyl alcohol in tert-butanol/water
in Electrochimica Acta
Kuleshova J
(2011)
A simple and inexpensive microfluidic electrolysis cell
in Electrochimica Acta
Description | Electrosynthesis can enable the selective production of organic compounds under relatively mild experimental conditions and without the use of toxic/hazardous reagents. It is our belief that the discovery and evolution of cleaner synthetic procedures driven by the passage of electrical current have been hindered by the lack of user friendly electrolytic equipment, restricting more widespread uptake. The overall objective of this research was therefore to develop a microflow electrolysis cell that fits conveniently into commercial microflow systems for use by non-specialists for routine synthesis. During the project, two electrolysis microflow cells have been designed, fabricated and characterised and their performance defined using the methoxylation reactions of N-formylpyrrolidine and 4-t-butyltoluene as test reactions (Electrochimica Acta, 2011 and 2012). Both use the design concepts familiar to microflow scientists rather than modifying standard electrolysis flow cells, the approach used by other papers in the literature. The first was a simple and cheap cell that could be built in the laboratory. The second was a more sophisticated flow cell designed in collaboration with Syrris and the Dolomite Centre, and incorporating their fabrication technology. The overall dimensions were reduced while retaining similar the flow channel path length and dimensions, and materials. Also, a user friendly cell holder with electrical and flow tubing connectors, and a clamping system giving increased ease of assembly and largely eliminating leakage. The cell holder could also be run with two cells as a sandwich with the solution flows in series doubling the channel length and allowed higher flow rates, with increased rates of product formation. Significantly, and exceeding our original objectives methoxylation of N-formylpyrrolidine was shown to proceed with very high conversions (>> 90 %) in a single pass, and several grams of product per hour could be obtained with a good selectivity under optimised conditions (Electrochimica Acta, 2012). With this effective electrolysis cell in hand, we investigated some important synthetic transformations that would provide electrochemical methods in academic or industrial laboratories. Initially, an electrocatalytic flow oxidation of alcohols to carbonyl compounds was developed using TEMPO as a mediator in tert-butanol-water without added electrolyte (ChemSusChem 2012). Again, high conversions and selectivities could be achieved in a single pass through the cell to produce synthetically useful quantities of material. This reaction was also the subject of a mechanistic study, which is to be published (in preparation). In preliminary studies, were also able to develop some electrochemical fluorinations under flow conditions and these offer significant promise for the future considering the growing interest of fluorinated molecules. Flow electrosynthesis is an attractive technology and the award of this EPSRC grant has (a) stimulated flow electrochemistry research in Southampton leading to further industrially sponsored projects. (b) led to an electrolysis flow cell module that will soon be introduced by Syrris into their Asia Range of microflow equipment. |
Exploitation Route | A modified version of the electrochemical flow cell developed during the project is now commercially available through Syrris Ltd. (http://syrris.com/flow-products/asia-modules/asia-flux-for-electrochemistry). This device should find multiple applications in synthesis of chemicals, which may be used in many areas of research and development. Indeed, systems have been purchased by academic and industrial researchers in the UK and in other countries. |
Sectors | Chemicals,Pharmaceuticals and Medical Biotechnology |
Description | The research was carried out in collaboration with Syrris, and Pfizer Ltd (Sandwich, Kent), with an objective to develop an electrochemical flow cell suitable for laboratory scale synthesis. The electrochemical flow cell could be used for the synthesis of chemical intermediates or final products for applications in areas including drug discovery, or agrochemical research. Prototype devices were developed as part of the grant, and Syrris now market an electrochemical flow cell that is based upon the one developed during this award (Asia Flux system for Electrochemistry: http://syrris.com/flow-products/asia-modules/asia-flux-for-electrochemistry). The international commercial availability of the flow cell opens the door to wider uptake of electrochemical synthesis within academic and industrial labs, and we are aware of systems having been purchased by academic and industrial research groups around the world. Evidence for this can be seen from research papers being published on flow electrochemistry using this flow cell. |
First Year Of Impact | 2013 |
Sector | Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Description | Factory in a Fumehood: Reagentless Flow Reactors as Enabling Techniques for Manufacture |
Amount | £940,746 (GBP) |
Funding ID | EP/L003325/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 10/2013 |
End | 02/2017 |
Description | Industrial Studentship Funding from GSK: Amide Bond Formation from Alcohols by Electrochemical Oxidation |
Amount | £30,000 (GBP) |
Organisation | GlaxoSmithKline (GSK) |
Sector | Private |
Country | Global |
Start | 10/2010 |
End | 09/2013 |
Description | Lilly Research Awards Programme |
Amount | $265,000 (USD) |
Organisation | Eli Lilly & Company Ltd |
Sector | Private |
Country | United Kingdom |
Start | 12/2015 |
End | 11/2017 |
Title | Electrochemical Flow Cell for Laboratory Synthesis |
Description | A microfluidic electrochemical flow cell was developed during the project, which has subsequently been commercialised by Syrris as part of their Asia Flux system for Electrochemistry (http://syrris.com/flow-products/asia-modules/asia-flux-for-electrochemistry). The system enables laboratory scale electrosynthesis. |
Type Of Technology | Systems, Materials & Instrumental Engineering |
Year Produced | 2014 |
Impact | • Economic Impact: Syrris market a system for electrochemical synthesis that is based upon the electrolysis flow cell developed in collaboration with the Southampton team. The Asia Flux system for Electrochemistry has been sold around the world to industry and academic research groups. • The availability of a commercial product for laboratory scale flow electrosynthesis enables the uptake of the technology in non-expert labs, and this is currently an area of significant interest. |
URL | http://syrris.com/flow-products/asia-modules/asia-flux-for-electrochemistry |