Reactors and Reproducibility: Advancing Electrochemistry for Organic Synthesis

Lead Research Organisation: University of Bristol
Department Name: Chemistry


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.

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.


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Heard D (2020) Electrode Materials in Modern Organic Electrochemistry in Angewandte Chemie

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Heard DM (2020) Electrode Materials in Modern Organic Electrochemistry. in Angewandte Chemie (International ed. in English)

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Heard DM (2020) Minimal manual input. in Nature chemistry