Reactors and Reproducibility: Advancing Electrochemistry for Organic Synthesis
Lead Research Organisation:
University of Bristol
Department Name: Chemistry
Abstract
Organic synthesis allows humans to develop molecules that treat disease, efficiently grow crops, power our homes with innovative fuels and lubricants, and develop materials and plastics that are essential for modern life. Redox reactions are an important class of organic transformation where electrons are added or removed from molecules to engender a chemical reaction. This reaction is typically driven by the addition of a reactive redox reagent, which creates large quantities of waste that are often toxic and expensive to dispose of. Electrochemistry is an enabling technology for organic synthesis, as it replaces these reagents by directly transferring electrons at the surface of electrodes submerged in the reaction solution. There are two main advantages to this technique. The first is that lower amounts of waste, or no waste at all, is produced and less energy is needed, providing a more efficient and environmentally sustainable way to conduct redox reactions. The second is that the applied potential, or driving force, can be readily tuned, which provides greater selectivity, new reactivity, higher functional group tolerance and less undesired side-products. While providing efficiency, selectivity and environmental benefits, there are practical challenges associated with electrochemical reactions when compared to standard synthetic organic reactions. The greatest challenge with using the technique is often associated with the set-ups, which can be complex, expensive, are not well suited for parallelisation/reaction development and often lead to poor reproducibility. Thus, there is an urgent need to tackle these problems in order to advance the field.
In this project, we will develop new reactor systems to aid each stage of reaction development, namely; discovery, optimisation, dissemination and replication. We will focus on additive manufacturing (3D printing) as an inexpensive, rapid and flexible prototyping tool to generate systems that are accessible, inexpensive and, importantly, highly reproducible for organic synthesis. We will develop new materials, innovative designs, print procedures and optimisation tools for reactors, which will be used in the development of a number of synthetic transformations, for which we have preliminary data, but require new reactor-systems to advance further. We will also conduct fundamental studies to further understand the reproducibility issues that currently plague the use of electrochemistry in synthesis. Specifically, the high-level objectives are to a) invent a screening system for organic electrochemistry, b) solve the reproducibility problem, c) create Super-Cells: the next generation of reactors of organic electrochemistry. This 3D printed approach to organic electrochemistry will increase the speed and ease with which novel organic transformations are developed and reproduced, ensuring electrochemistry can deliver on its potential of highly efficient and sustainable chemical reactions. This project will facilitate wide-spread adoption of the technique in organic synthesis, and deliver fundamental understanding, environmental and economic benefits to industry, academia and society as a whole.
In this project, we will develop new reactor systems to aid each stage of reaction development, namely; discovery, optimisation, dissemination and replication. We will focus on additive manufacturing (3D printing) as an inexpensive, rapid and flexible prototyping tool to generate systems that are accessible, inexpensive and, importantly, highly reproducible for organic synthesis. We will develop new materials, innovative designs, print procedures and optimisation tools for reactors, which will be used in the development of a number of synthetic transformations, for which we have preliminary data, but require new reactor-systems to advance further. We will also conduct fundamental studies to further understand the reproducibility issues that currently plague the use of electrochemistry in synthesis. Specifically, the high-level objectives are to a) invent a screening system for organic electrochemistry, b) solve the reproducibility problem, c) create Super-Cells: the next generation of reactors of organic electrochemistry. This 3D printed approach to organic electrochemistry will increase the speed and ease with which novel organic transformations are developed and reproduced, ensuring electrochemistry can deliver on its potential of highly efficient and sustainable chemical reactions. This project will facilitate wide-spread adoption of the technique in organic synthesis, and deliver fundamental understanding, environmental and economic benefits to industry, academia and society as a whole.
Planned Impact
This project will invent novel reactor systems and develop fundamental understanding to improve the discovery, optimisation and replication of synthetic organic electrochemical reactions. The new reactor systems will facilitate the sustainability and selectivity benefits of electrochemistry to impact the field of organic synthesis, while improving the reproducibility and robustness of the technique. This research will decrease the cost of conducting electrochemistry and make it easier for non-specialists to adopt the technique for research and manufacture.
Economic impact: With exports of nearly £50 billion each year, the chemical and pharmaceutical sector is the UK's largest manufacturing export sector. Expanding the strength and resilience of these industries with innovative technologies is essential to maintain the UK's competitive edge to support a sustainable export market. Electrochemistry is precisely one of these innovative technologies for organic synthesis, delivering increases in sustainability and selectivity for industry. The reactor systems developed in this project will impact the economy through:
1) The fine chemical, process and medicinal chemistry industries taking advantage of more efficient, sustainable and inexpensive processes to generate their products. In turn, this will lower the cost and cycle time of their processes, which will lead to higher profits.
2) The innovative electrochemical technologies providing access to new chemical reactivity, and consequently to new products. For example, in the pharmaceutical industry, the on-demand synthesis of novel compounds is a significant bottleneck. Thus, new high-throughput systems, like that developed in this project, will offer direct, measurable improvements to their compound discovery processes, leading to new drug targets and more revenue streams.
Societal impact: Improved electrochemical methods in organic synthesis will impact society by, for example:
1) reducing the cost of important pharmaceutical and agrochemical products. Electrochemistry provides more efficient syntheses and will therefore lead to greater availability of these beneficial products to society, as well as providing economic benefits to the UK and international societies.
2) enabling the development of new products that are beneficial to society. Electrochemistry can enable new reactivity, which will be discovered more readily with the more robust and high-throughput reactor systems.
3) reducing the environmental impact of the industrial scale synthesis of chemicals. Electrochemistry is a more sustainable way to conduct redox reactions (lower waste and lower energy). Therefore, a greater use of the technique will aid the UK's obligation to reduce its environmental impact and to meet the carbon budget laid down in the Climate Change Act 2008 and the international COP21 Paris agreements.
4) increasing general knowledge of the technique through our website.
Academic impact: Academia will benefit directly from having more inexpensive reactor systems available and a lower barrier entry to this technical field. Increasing the level of academic research in organic electrochemistry will lead to more synthetic transformations being developed and a greater understanding of the advantages/limitations of the technology. This creates a virtuous cycle of development, testing and application, which ultimately creates the industrial and societal impacts described above. Specifically, those researching in organic synthesis, fundamental electrochemistry, reactor design, process chemistry/engineering and materials chemistry will be impacted.
Economic impact: With exports of nearly £50 billion each year, the chemical and pharmaceutical sector is the UK's largest manufacturing export sector. Expanding the strength and resilience of these industries with innovative technologies is essential to maintain the UK's competitive edge to support a sustainable export market. Electrochemistry is precisely one of these innovative technologies for organic synthesis, delivering increases in sustainability and selectivity for industry. The reactor systems developed in this project will impact the economy through:
1) The fine chemical, process and medicinal chemistry industries taking advantage of more efficient, sustainable and inexpensive processes to generate their products. In turn, this will lower the cost and cycle time of their processes, which will lead to higher profits.
2) The innovative electrochemical technologies providing access to new chemical reactivity, and consequently to new products. For example, in the pharmaceutical industry, the on-demand synthesis of novel compounds is a significant bottleneck. Thus, new high-throughput systems, like that developed in this project, will offer direct, measurable improvements to their compound discovery processes, leading to new drug targets and more revenue streams.
Societal impact: Improved electrochemical methods in organic synthesis will impact society by, for example:
1) reducing the cost of important pharmaceutical and agrochemical products. Electrochemistry provides more efficient syntheses and will therefore lead to greater availability of these beneficial products to society, as well as providing economic benefits to the UK and international societies.
2) enabling the development of new products that are beneficial to society. Electrochemistry can enable new reactivity, which will be discovered more readily with the more robust and high-throughput reactor systems.
3) reducing the environmental impact of the industrial scale synthesis of chemicals. Electrochemistry is a more sustainable way to conduct redox reactions (lower waste and lower energy). Therefore, a greater use of the technique will aid the UK's obligation to reduce its environmental impact and to meet the carbon budget laid down in the Climate Change Act 2008 and the international COP21 Paris agreements.
4) increasing general knowledge of the technique through our website.
Academic impact: Academia will benefit directly from having more inexpensive reactor systems available and a lower barrier entry to this technical field. Increasing the level of academic research in organic electrochemistry will lead to more synthetic transformations being developed and a greater understanding of the advantages/limitations of the technology. This creates a virtuous cycle of development, testing and application, which ultimately creates the industrial and societal impacts described above. Specifically, those researching in organic synthesis, fundamental electrochemistry, reactor design, process chemistry/engineering and materials chemistry will be impacted.
People |
ORCID iD |
Alastair Lennox (Principal Investigator) |
Publications
Atkins AP
(2022)
Electrochemical Benzylic C(sp3)-H Acyloxylation.
in Organic letters
Heard DM
(2021)
Dichloromeldrum's Acid (DiCMA): A Practical and Green Amine Dichloroacetylation Reagent.
in Organic letters
Heard DM
(2020)
Minimal manual input.
in Nature chemistry
Heard D
(2021)
3D Printed Reactionware for Synthetic Electrochemistry with Hydrogen Fluoride Reagents
in ChemElectroChem
Rowett AC
(2024)
A Stoichiometric Haloform Coupling for Ester Synthesis with Secondary Alcohols.
in Angewandte Chemie (International ed. in English)
Heard DM
(2020)
Electrode Materials in Modern Organic Electrochemistry.
in Angewandte Chemie (International ed. in English)
Rowett A
(2024)
A Stoichiometric Haloform Coupling for Ester Synthesis with Secondary Alcohols
in Angewandte Chemie
Heard D
(2020)
Electrode Materials in Modern Organic Electrochemistry
in Angewandte Chemie
Description | We have developed new ways to produce reactors to be able to conduct electrochemical reactions that use hydrogen fluoride reagents. This type of reaction is useful for adding fluorine into organic molecules, which is a process that is important for the synthesis of bioactive molecules, such as drugs. |
Exploitation Route | Others can conduct electrochemical reactions using HF |
Sectors | Chemicals |
Description | The research that has evolved from this grant is slowly developing impact. We have filed a patent on a new suite of composite conductive materials that are capable of being 3D printed and are very robust and chemically resistant. We have won additional funding to help realise the impact, including an EPSRC Impact Acceleration Account award, as well as a place on iCURE Explore programme. These activities are on-going and the final route to market is still being explored. Due to the patent filing, our work on 3D printed electrodes and reactors is yet to be all published, but we expect will do so in the coming year and so more will be reported on it next year. |
Sector | Chemicals,Electronics,Energy,Healthcare |
Description | 3D printable electroactive materials for organic electrochemistry |
Amount | £80,000 (GBP) |
Funding ID | 2268766 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2019 |
End | 08/2023 |
Title | 3D print files for electrochemical reactors |
Description | .stl files for 3D printing electrochemical reactors designed by the LennoxLab |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | The scientific community are able to download these files to be able to print the reactors, which leads to more reproducible reactions |
URL | https://data.bris.ac.uk/data/dataset/2yj6li188q2911zo0rla600gbf/ |
Description | Dr Kevin Lam |
Organisation | University of Greenwich |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have developed a CAD tool that can be used to generate CAD drawings for electrochemical reactors, which is highly accessible and does not require pre-training in the use of CAD software. |
Collaborator Contribution | The Lam group have tried and tested the CAD tool and provided us with feedback on the tool. |
Impact | The publication is in preparation |
Start Year | 2023 |
Title | ElectroSynthesis Exchange |
Description | We have developed and published a website that is called the ElectroSynthesis Exchange. It is essentially a huge repository of information on how to use the technique and how to learn it. We felt there was a need to design such a resource because the barrier to get into electrosynthesis is high and there are many companies and other academics that want to use it as a tool in organic synthesis. Therefore, we extracted information from the literature and put it all in one place. We have also created a huge list of reviews and tutorials, as well as information about purchasing the equipment and where and what to buy. We have had great feedback about this resource from the community. |
Type Of Technology | Webtool/Application |
Year Produced | 2023 |
Impact | Several people from industry and academia have reported to me that they have benefited from the website. It has directly answered their questions and enabled them to use organic electrosynthesis. It has brought more people into this field of research. |
URL | https://www.lennoxlab.com/electrosynthesisexchange |
Description | Chair of conference: Electrochem |
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 | I co-chaired and organised a large annual international conference in Bristol, called Electrochem, in September 2023. We had over 225 delegates attend the conference, which consisted of 5 parallel sessions, a large poster session, 8 industrial sponsors, 5 plenary lectures and prize winners, a gala dinner and a welcome drinks reception. It was a fantastic success that was enjoyed by all. |
Year(s) Of Engagement Activity | 2023 |
Description | Course on flow chemistry |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | A course was written and delivered a course on flow chemistry to a group of 1st year PhD students. In addition ,a course was written and delivered on 3D printing and Computer aided design (CAD) to the group of 1st year PhD students. |
Year(s) Of Engagement Activity | 2021,2022,2023,2024 |
Description | Organisation of conference |
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 | A new national conference has been set up and is run annually. It is called "Bristol Electrosynthesis Meeting" and occurs in April of each year. The meeting is a free event that is funded by 3 sponsors. It brings together all groups and industry working in the field of organic electrosynthesis in the UK. Talks are given by international plenary speakers and supported by PhD students and a poster session. In total we have 70-80 participants at the event. |
Year(s) Of Engagement Activity | 2022,2023,2024 |
Description | Outreach article for Post-16 students |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Dr Heard wrote an article for departmental outreach website, which contains pieces of insight and information about the research that goes on in the department. It is made available to post-16 students at schools and is used as a teaching resource for them. Questions and answers are included alongside readily digested test and schemes on the subject. |
Year(s) Of Engagement Activity | 2020 |
URL | https://bristoloutreachproject.wordpress.com/research-projects/ |
Description | Visit to 6th form college |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Alongside a PhD student of mine, I gave a talk to a group of 6th form science students on our careers routes so far, chemistry research and some high impact stories of chemistry research from our department. Many questions were asked and a healthy discussion took place. The school reported high interest in the talk afterwards to me. |
Year(s) Of Engagement Activity | 2023 |
Description | Visit to primary school |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | I gave a talk at a local primary school on chemistry and the research we do at Bristol. |
Year(s) Of Engagement Activity | 2023 |