Multifunctional Electrochemical Flow Platform for High-Throughput Synthesis & Optimisation of Catalysts
Lead Research Organisation:
University of Leeds
Department Name: Sch of Chemistry
Abstract
We will develop new technology that greatly accelerates the process of discovering, developing and implementing sustainable organometallic catalysts for industrially-relevant reactions.
Many reactions in pharmaceutical, agrochemical and fine chemicals processes require metal catalysts which rely on platinum group metals (PGMs) such as palladium, platinum and rhodium. PGMs are expensive and are on the European Commission's 2014 list of 20 critical raw materials (http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:52014DC0297), which possess serious risk of dwindling supply. Furthermore, PGMs are toxic, hence must be removed from final products to levels that are often difficult/costly to achieve (<5ppm for active pharmaceutical ingredients). The currently increasing use of PGMs in the chemicals industry is therefore untenable in the medium to long-term.
Base-metals such as copper and iron are much more attractive to use as catalysts due to being significantly more abundant and typically having lower toxicity (depending upon speciation). Despite this, the use of base-metals in catalysis is rare in industry; a lack of understanding of the active species and mechanistic profiles of base-metal catalysts, which are more challenging to study than PGMs, means that reactions are unpredictable and often irreproducible. In addition, high catalyst loadings and harsh reaction conditions (when compared to, for example, palladium-catalysed reactions) are usually required.
Catalysts are generally discovered and developed using a linear process, whereby a catalyst is designed and synthesised, tested and optimised in a specific reaction, examined for substrate scope under optimised conditions, and redesigned to try and produce more active and selective (2nd generation) catalysts. In addition to being slow and labour intensive, this process risks overlooking potentially valuable catalysts. For example, due to time constraints, a 2nd generation catalyst may only be tested under conditions that are optimum for the 1st generation catalyst, when alternative and improved conditions could be more suitable.
This proposal seeks to bring together a range of complementary expertise across chemistry and engineering to develop new technology that is capable of rapidly synthesising, screening and self-optimising base-metal catalysts. Both the catalyst synthesis and catalytic reaction stages will be performed in flow cells, which enables online analysis of the output at each stage, and allows modification of the conditions as the reactions are running. Algorithms will be used so that the reactions become self-optimising i.e. conditions are automatically varied in response to the analytical data, enabling several sets of conditions to be screened for a number of catalysts within a relatively short period of time.
Our aim is for the technology to be adopted by both academic and industrial laboratories for the development of catalysts more broadly. We will make all information relating to reactor designs, variables, algorithms etc. open access, so that other researchers can replicate and apply the technology. Data relating to base-metal catalysed reactions will be added to a searchable database; this will provide a valuable resource to others studying these types of reactions, enabling a more knowledge-based and frontier-leading approach to catalyst development.
Many reactions in pharmaceutical, agrochemical and fine chemicals processes require metal catalysts which rely on platinum group metals (PGMs) such as palladium, platinum and rhodium. PGMs are expensive and are on the European Commission's 2014 list of 20 critical raw materials (http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:52014DC0297), which possess serious risk of dwindling supply. Furthermore, PGMs are toxic, hence must be removed from final products to levels that are often difficult/costly to achieve (<5ppm for active pharmaceutical ingredients). The currently increasing use of PGMs in the chemicals industry is therefore untenable in the medium to long-term.
Base-metals such as copper and iron are much more attractive to use as catalysts due to being significantly more abundant and typically having lower toxicity (depending upon speciation). Despite this, the use of base-metals in catalysis is rare in industry; a lack of understanding of the active species and mechanistic profiles of base-metal catalysts, which are more challenging to study than PGMs, means that reactions are unpredictable and often irreproducible. In addition, high catalyst loadings and harsh reaction conditions (when compared to, for example, palladium-catalysed reactions) are usually required.
Catalysts are generally discovered and developed using a linear process, whereby a catalyst is designed and synthesised, tested and optimised in a specific reaction, examined for substrate scope under optimised conditions, and redesigned to try and produce more active and selective (2nd generation) catalysts. In addition to being slow and labour intensive, this process risks overlooking potentially valuable catalysts. For example, due to time constraints, a 2nd generation catalyst may only be tested under conditions that are optimum for the 1st generation catalyst, when alternative and improved conditions could be more suitable.
This proposal seeks to bring together a range of complementary expertise across chemistry and engineering to develop new technology that is capable of rapidly synthesising, screening and self-optimising base-metal catalysts. Both the catalyst synthesis and catalytic reaction stages will be performed in flow cells, which enables online analysis of the output at each stage, and allows modification of the conditions as the reactions are running. Algorithms will be used so that the reactions become self-optimising i.e. conditions are automatically varied in response to the analytical data, enabling several sets of conditions to be screened for a number of catalysts within a relatively short period of time.
Our aim is for the technology to be adopted by both academic and industrial laboratories for the development of catalysts more broadly. We will make all information relating to reactor designs, variables, algorithms etc. open access, so that other researchers can replicate and apply the technology. Data relating to base-metal catalysed reactions will be added to a searchable database; this will provide a valuable resource to others studying these types of reactions, enabling a more knowledge-based and frontier-leading approach to catalyst development.
Planned Impact
Organometallic catalysis is an essential area of scientific research, directly impacting on chemical industries worldwide, such as pharmaceuticals, agrochemicals and materials. For these industries to survive and grow, they must work towards a sustainable future, which includes reducing demand on diminishing resources such as platinum group metals (PGMs), or using them in a more efficient manner (e.g. recovering from waste streams and recycling). The proposed research will result in a new flow technology for rapid synthesis, screening and optimisation of catalysts, with a focus on base-metal catalysis. The data generated in this research will benefit chemical industries, as greater understanding of base-metal catalysed processes will be achieved with new and optimised catalysts being discovered. This project will move base-metal catalysed processes towards being 'fit for purpose' for industry. Through working with the industrial advisory board, industrially-relevant processes will be identified and studied. Furthermore, the technology will be developed so that it can be translated into industry for reaction screening (i.e. catalyst discovery and optimisation), or be scaled up for synthesis (i.e. catalyst generation and catalytic reactions on a large scale). It is envisaged that the technology will be adopted for broader use, including making reactions that can only be catalysed by PGMs more efficient, and using the electrochemical technology for metal recovery/recycling.
In providing a technology and generating data and valuable knowledge that will benefit chemical industries, this research will ultimately have a positive impact on society. New and improved pharmaceuticals, agrochemicals and materials will be developed, giving society better healthcare, food security and technology. More efficient and sustainable routes to known compounds will also lead to reduced costs.
This research will have an impact on academics across several areas of the physical sciences. Those working in organometallic chemistry and catalysis will benefit from the technology, as more efficient routes to catalyst synthesis, reaction screening and optimisation will be available. The data generated and searchable databases developed will also be valuable to researchers in these areas, in addition to those working in mechanistic and physical organic chemistry. Information relating to the technology will be valuable to process chemists and chemical engineers, as it can be translated to flow-reactors for similar or different purposes.
All researchers involved will benefit significantly from having the opportunity to carry out this programme of research. The PDRAs will expand their research and technical skills in areas that are of direct relevance to industry, such as organic/organometallic synthesis and analysis, catalysis and chemical engineering. They will benefit from working with a multi-disciplinary team, in addition to liaising with members of the industrial advisory board. They will have ample opportunity to present results to a range of audiences (conference, industrial and departmental meetings) and will be involved in manuscript preparation, thus strengthening skills of importance to future employers. Further training in generic skills such as research management and public engagement will be offered through courses. The PI and CoIs will benefit hugely from having the opportunity to work together and become an internationally-leading team in electrochemical flow technology for metal catalyst screening and optimisation. In addition to the anticipated outputs from this specific research, it is likely to lead to future collaboration with other internationally-leading researchers.
In providing a technology and generating data and valuable knowledge that will benefit chemical industries, this research will ultimately have a positive impact on society. New and improved pharmaceuticals, agrochemicals and materials will be developed, giving society better healthcare, food security and technology. More efficient and sustainable routes to known compounds will also lead to reduced costs.
This research will have an impact on academics across several areas of the physical sciences. Those working in organometallic chemistry and catalysis will benefit from the technology, as more efficient routes to catalyst synthesis, reaction screening and optimisation will be available. The data generated and searchable databases developed will also be valuable to researchers in these areas, in addition to those working in mechanistic and physical organic chemistry. Information relating to the technology will be valuable to process chemists and chemical engineers, as it can be translated to flow-reactors for similar or different purposes.
All researchers involved will benefit significantly from having the opportunity to carry out this programme of research. The PDRAs will expand their research and technical skills in areas that are of direct relevance to industry, such as organic/organometallic synthesis and analysis, catalysis and chemical engineering. They will benefit from working with a multi-disciplinary team, in addition to liaising with members of the industrial advisory board. They will have ample opportunity to present results to a range of audiences (conference, industrial and departmental meetings) and will be involved in manuscript preparation, thus strengthening skills of importance to future employers. Further training in generic skills such as research management and public engagement will be offered through courses. The PI and CoIs will benefit hugely from having the opportunity to work together and become an internationally-leading team in electrochemical flow technology for metal catalyst screening and optimisation. In addition to the anticipated outputs from this specific research, it is likely to lead to future collaboration with other internationally-leading researchers.
Publications
Nicholls T
(2020)
Electrochemistry in continuous systems
in Current Opinion in Green and Sustainable Chemistry
Nicholls TP
(2021)
On-Demand Electrochemical Synthesis of Tetrakisacetonitrile Copper(I) Triflate and Its Application in the Aerobic Oxidation of Alcohols.
in Inorganic chemistry
Schotten C
(2021)
Alternating polarity for enhanced electrochemical synthesis
in Reaction Chemistry & Engineering
Schotten C
(2020)
Making electrochemistry easily accessible to the synthetic chemist
in Green Chemistry
Schotten C
(2022)
Development of a multistep, electrochemical flow platform for automated catalyst screening
in Catalysis Science & Technology
Schotten C
(2021)
Electrochemical Generation of N -Heterocyclic Carbenes for Use in Synthesis and Catalysis
in Advanced Synthesis & Catalysis
Scott NWJ
(2021)
A Dichotomy in Cross-Coupling Site Selectivity in a Dihalogenated Heteroarene: Influence of Mononuclear Pd, Pd Clusters, and Pd Nanoparticles-the Case for Exploiting Pd Catalyst Speciation.
in Journal of the American Chemical Society
Stephen H
(2022)
Steps, hops and turns: examining the effects of channel shapes on mass transfer in continuous electrochemical reactors
in Reaction Chemistry & Engineering
Stephen H
(2020)
A Versatile Electrochemical Batch Reactor for Synthetic Organic and Inorganic Transformations and Analytical Electrochemistry
in Organic Process Research & Development
Description | The key findings were documented last year. |
Exploitation Route | Academic - technology to develop new catalysts, understand catalytic mechanisms and new reactions. Industry - similar to above with the added opportunity for scale-up. |
Sectors | Chemicals Digital/Communication/Information Technologies (including Software) Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
Description | An electrochemical batch reactor developed during this work has led to commercialisation of the reactor (https://www.asynt.com/product/electroreact-flexible-electrochemistry-platform/). The work has also gained significant industrial interest and follow-on projects with industrial partners (PhD funding) to further develop and implement the work, particularly the automation, is ongoing. |
First Year Of Impact | 2020 |
Sector | Other |
Impact Types | Economic |
Description | European Research Council travel grant to attend CHAOS summer school |
Amount | € 500 (EUR) |
Organisation | European Research Council (ERC) |
Sector | Public |
Country | Belgium |
Start | 08/2019 |
Description | Internally-Distributed Funding. Development of Sustainable Palladium Catalysis through Circular Flow Technology: Towards Electrochemical R3 (Reduce, Recover, Reuse). |
Amount | £29,459 (GBP) |
Organisation | University of York |
Sector | Academic/University |
Country | United Kingdom |
Start | 11/2023 |
End | 03/2024 |
Description | RSC Travel Bursary |
Amount | £120 (GBP) |
Organisation | Royal Society of Chemistry |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 11/2019 |
Title | Electrochemical batch reactor for synthesis and analytical chemistry |
Description | A standardised and versatile electrochemical batch reactor that has wide applicability in both organic and inorganic synthesis and analytical electrochemistry was developed, with the full design being published. The reactor is also in the process of being commercialised in collaboration with a company. |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | Several groups within our own department are using the technology for electrochemical synthetic and analytical applications. We have also provided groups in other departments with reactors to use. |
URL | https://pubs.acs.org/doi/10.1021/acs.oprd.0c00091 |
Title | Electrochemical flow reactor technology and automation |
Description | The development of an integrated multistep flow platform that incorporates high-throughput electrochemical synthesis of metal catalysts and catalysis screening was developed. Ligand libraries can be screened through the implementation of an autosampler, and online HPLC analysis facilitates continuous monitoring of the reaction. The equipment is controlled via a computer which enables the process to be automated, with the platform running ligand/catalysis screens autonomously. |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | The method is being used broadly within our own group and the publication is starting to pick up citations. |
URL | https://pubs.rsc.org/en/content/articlelanding/2022/cy/d2cy00587e |
Title | Data set for the use of alternating polarity in synthetic chemistry |
Description | This is the affiliated data set for the publication "Alternating polarity for enhanced electrochemical synthesis" including all raw and processed data used in this study. |
Type Of Material | Database/Collection of data |
Year Produced | 2020 |
Provided To Others? | Yes |
URL | http://archive.researchdata.leeds.ac.uk/788/ |
Description | ElectroReact - a commercial electrochemical batch reactor |
Organisation | Asynt Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | Following work during the grant which resulted in a flexible and robust batch reactor for electrochemical synthesis (https://pubs.acs.org/doi/10.1021/acs.oprd.0c00091), the reactor has been further devloped in collaboration with Asynt and is now commercialised (https://www.asynt.com/product/electroreact-flexible-electrochemistry-platform). |
Collaborator Contribution | Asynt have commercialised the reactor that we developed. It was launched in February 2024. |
Impact | https://www.asynt.com/product/electroreact-flexible-electrochemistry-platform/ |
Start Year | 2020 |
Description | High Throughput Synthesis, screening and optimisation of Fe Catalysis in industrially Relevant Transformations |
Organisation | AstraZeneca |
Country | United Kingdom |
Sector | Private |
PI Contribution | A PhD student sponsored by the 3 companies is working on a project that uses the electrochemical flow platform developed as part of the EPSRC project. I am principal supervisor for the student, with project co-investigators Richard Bourne and Nik Kapur being co-supervisors. |
Collaborator Contribution | Industrial advisory board meetings are held every 6 months to discuss the overall EPSRC project, as outlined in the original Pathways to Impact document. The PhD student also attends these meetings, presents findings and industrial partners provide feedback. In addition, shorter meetings are held every month with the CASE student and the 3 industrial partners to discuss progress. Ideally the student would have done a placement in one or more of the companies - as this has not been possible we are focussing on a project they would have carried out, with the regular industrial meetings being in lieu of the student remaining in Leeds. |
Impact | H. R. Stephen, C. Schotten, T. P. Nicholls, M. Woodward, R. A. Bourne, N. Kapur, C. E. Willans. A Versatile Electrochemical Batch Reactor for Synthetic Organic and Inorganic Transformations and Analytical Electrochemistry. Organic Process Research & Development, 2020, 24, 1084-1089. |
Start Year | 2018 |
Description | High Throughput Synthesis, screening and optimisation of Fe Catalysis in industrially Relevant Transformations |
Organisation | Johnson Matthey |
Country | United Kingdom |
Sector | Private |
PI Contribution | A PhD student sponsored by the 3 companies is working on a project that uses the electrochemical flow platform developed as part of the EPSRC project. I am principal supervisor for the student, with project co-investigators Richard Bourne and Nik Kapur being co-supervisors. |
Collaborator Contribution | Industrial advisory board meetings are held every 6 months to discuss the overall EPSRC project, as outlined in the original Pathways to Impact document. The PhD student also attends these meetings, presents findings and industrial partners provide feedback. In addition, shorter meetings are held every month with the CASE student and the 3 industrial partners to discuss progress. Ideally the student would have done a placement in one or more of the companies - as this has not been possible we are focussing on a project they would have carried out, with the regular industrial meetings being in lieu of the student remaining in Leeds. |
Impact | H. R. Stephen, C. Schotten, T. P. Nicholls, M. Woodward, R. A. Bourne, N. Kapur, C. E. Willans. A Versatile Electrochemical Batch Reactor for Synthetic Organic and Inorganic Transformations and Analytical Electrochemistry. Organic Process Research & Development, 2020, 24, 1084-1089. |
Start Year | 2018 |
Description | High Throughput Synthesis, screening and optimisation of Fe Catalysis in industrially Relevant Transformations |
Organisation | Syngenta International AG |
Department | Syngenta Ltd (Bracknell) |
Country | United Kingdom |
Sector | Private |
PI Contribution | A PhD student sponsored by the 3 companies is working on a project that uses the electrochemical flow platform developed as part of the EPSRC project. I am principal supervisor for the student, with project co-investigators Richard Bourne and Nik Kapur being co-supervisors. |
Collaborator Contribution | Industrial advisory board meetings are held every 6 months to discuss the overall EPSRC project, as outlined in the original Pathways to Impact document. The PhD student also attends these meetings, presents findings and industrial partners provide feedback. In addition, shorter meetings are held every month with the CASE student and the 3 industrial partners to discuss progress. Ideally the student would have done a placement in one or more of the companies - as this has not been possible we are focussing on a project they would have carried out, with the regular industrial meetings being in lieu of the student remaining in Leeds. |
Impact | H. R. Stephen, C. Schotten, T. P. Nicholls, M. Woodward, R. A. Bourne, N. Kapur, C. E. Willans. A Versatile Electrochemical Batch Reactor for Synthetic Organic and Inorganic Transformations and Analytical Electrochemistry. Organic Process Research & Development, 2020, 24, 1084-1089. |
Start Year | 2018 |
Description | High-Throughput SYnthesis, Screening and Optimisation of Nickel Catalysts |
Organisation | AstraZeneca |
Country | United Kingdom |
Sector | Private |
PI Contribution | This project uses the flow platform developed in the EPSRC grant for the generation, screening and optimisation of nickel catalysts in reactions of interest to industry. This is a PhD project sponsored by AstraZeneca and Johnson Matthey. |
Collaborator Contribution | Industrial advisory board meetings are held every 6 months to discuss the overall EPSRC project, as outlined in the original Pathways to Impact document. The PhD student also attends these meetings, presents findings and industrial partners provide feedback. In addition, shorter meetings are held every month with the CASE student and the 3 industrial partners to discuss progress. The student will carry out an industrial placement in one of the companies. |
Impact | None as yet. |
Start Year | 2021 |
Description | CHAIR winterschool |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | The aim was to train 15 young (PhD) chemists to the audience in the use of flow chemistry and digital technologies |
Year(s) Of Engagement Activity | 2022 |
URL | https://chair-itn.eu/2022/10/oktober-flow-fest-22/ |
Description | Industrial Club Meetings |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Industry/Business |
Results and Impact | The Industrial Club Meetings are part of the Institute of Process Research and Development in Leeds, and brings together industrialists with chemistry and engineering academics to share research findings and discuss current industrial challenges. This has led to further collaboration with industry e.g. 3 industry-funded students since 2018. |
Year(s) Of Engagement Activity | 2018,2019,2020 |
Description | STEM for Britain |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | Presenting and discussing "ground-breaking" and frontier UK research and R&D to Members of both Houses of Parliament at Westminster. Fostering greater dialogue and engagement between early-stage researchers and Members both in Westminster and in their Constituencies. Encouraging personal interaction between all researchers. Raising the profile of Britain's early-stage researchers at Parliament and elsewhere. |
Year(s) Of Engagement Activity | 2020 |
Description | Summer School 2018: Dial-A-Molecule, An EPSRC Grand Challenge Network |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | The residential Summer School focussed on the Enabling Technologies theme which included some electrochemical flow technology. Parts of this were run by Prof Nik Kapur and Dr Richard Bourne, and gave Postgraduate students training and hands on experiences with various enabling technologies, which they were able to take back to their own institutions and use in their own research. |
Year(s) Of Engagement Activity | 2018 |