Water as synthetic reaction medium: realising its green chemistry credential

Lead Research Organisation: University of Leeds
Department Name: Sch of Chemistry


This project aims to deliver the underpinning tools and design principles to support the use of water as a reaction media in High Value Chemical Manufacture. Water has long been promoted as an environmentally friendly and safe 'green' reaction media for synthetic processes which can lead to much more sustainable and cost effective manufacturing process. Nevertheless, the green credential of water has been limited due to issues related to organic contamination of the water waste stream, cost of subsequent treatment and the often required organic solvents at purification stage.

Water-accelerated reactions, i.e. reactions which proceed faster in water than in organic solvents and wherein organic reactants and products form hydrophobic droplets, are potential game-changers High Value Chemical Manufacture. They benefit from accelerated rates, improved productivity and much improved green metrics through reduction in the use of organic solvents. Their current limitations are: (i) a limited pool of known reactions; (ii) lack of suitable equipment and process understanding; and (iii) insufficient understanding of acceleration effects which can guide discovery and process design.

This project will address these knowledge gaps and deliver the following critical outputs, identified through discussion with our industrial partners in chemical industry sector: (i) a wider range of synthetically useful water-accelerated reactions, (ii) multi-scale batch and flow reactors to support the scale-up pathway for water-accelerated processes, (iii) standardised protocols for characterising such processes and basic process understanding for scaling up, and (iv) streamlined workup/product purification and recycling of water to truly deliver green processes. These outputs will have transformative impacts in the chemical manufacture industry, delivering lower cost and better quality controlled processes through shorter routes, reduced organic waste and facile interfacing between chemo- and biocatalytic processes.

Planned Impact

The proposed water-accelerated chemical processes are a highly important field of research, which can potentially transform High Value Chemical Manufacturing (HVCM) industry by increasing their productivity while reducing their waste and sustainability related expenses. This project will deliver water-accelerated reactions, dedicated open-access reactors, continuous workup/purification technology and analytical protocols which will provide underpinning process understanding for control and optimisation of a wide range of green processes in HVCM sector. The impact can be summarised as:

Economic impact: Industrial partners and collaborators in HVCM sector will benefit through access to reactions and supporting technologies leading to greener manufacturing processes and lower cost. The typical production cost of a pharmaceutical API is £100M p.a. If 2 out of 8 steps are replaced by this technology with productivity/waste saving of 50%, the economic benefit is £12.5M p.a. per API. This will be a significant competitive edge for the UK HVCM sector against competitors in Europe and in the US. The reactors and screening platforms in WP1 and WP2 will establish a sector-wide framework for the discovery and exploitation of water-accelerated processes. Finally, the continuous workup developed in WP3 will be immediately applicable to improve the throughput of chemical syntheses across the whole HVCM sector. Some of the outputs of the project, i.e. reactors and screening platform, can be commercialised, with suport from Asynt, to provide standardised equipment for researchers and development teams in this field. We will reinforce this with two technical workshops in Leeds and 1 workshop organised with the EPSRC Dial-a-Molecule network, and hands-on support for end-users through the Dial-a-Molecule Centre of Rapid On-line Analysis of Reactions. Case studies carried out with the project industrial partners will provide proven measure of the technology in real commercial processes. These will form the foundation for wider adaptation of the project output and further translational activities.

The UK chemical R&D community will gain a team of highly skilled researchers with experience at the interface of synthetic science and reaction engineering (1 PhDs, 2 PDRAs). In addition, the project will promote dialogue and interaction between researchers between different disciplines, e.g. Synthetic Chemistry, Process Chemistry, Chemical Engineering, Fluid Dynamics, in both academia and industry, ultimately leading to a research community and workforce more adapted to applying sustainable chemical manufacture.

Academic impact: This project will push the frontier in multiphase and water-accelerated processes and will provide the academic community (UK and world-wide) with variety of enabling technologies and techniques to discover and explore water-accelerated processes. Wherever possible, we will provide detailed information on the reactors and screening platforms via open-access publications and ROAR (supported with know-how). Thus, academics will be able to assemble similar systems in their laboratories for reaction discovery and development and adaptation to other multiphase processes beyond the current scope of the project, e.g. biotransformations, phase transfer catalysis, and 'micellar catalysis'. Furthermore, the dissemination of discovered processes and their data and understanding, through publications and conferences, will guide further academic research into mutiphase processes and lead to wider adaptation of this relatively underdeveloped technology. New collaborations will be established through our industrial club and the EPSRC Dial-a-Molecule network to address further major research challenges that are beyond the scope of this project.


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Description Process parameters, including an optimisation using Design of Experiment statistical approach, have been identified for water accelerated reactions. This have led to several reactor designs on lab and pilot scale for water-accelerated reactions.

Reactors and know-hows/designs for high-throughput reactors to carry out water-accelerated reaction discovery have been developed in the first 6 months of the project. These will be critical for WP2 (i.e. discovery of synthetically useful water-accelerated reactions), which has started in 01/2020.

Discussion with industrial partners in 2 Industrial Advisory Board meeting (07/2019 and 01/2020), in combination with literature research, had led to a shortlist of reactions which will be the focus of WP2.
Exploitation Route Reactions, which will be identified in WP2, can be directly adapted by industrial partners in our advisory board. Open-access publications of our reactions and reactors design will make them available for exploitation by other academic researchers and the wider chemical sector.
Sectors Chemicals,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL https://www.freactor.com/
Description Industrial Advisory Board meeting in Leeds 
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 Biannual Industrial Advisory Board meeting with representatives from AstraZeneca, Concept Life Science, Asynt and Sterling Chemicals. Research directions were discussed and input from the advisory board were obtained to inform the research and maintain its relevance to the UK chemical sector.
Year(s) Of Engagement Activity 2019
Description Industrial Advisory Board meeting in Leeds 
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 Second Industrial Advisory Board meeting. Research results were communicated and discussed along with future research directions. Detailed discussion was carried out on our research results, with important comments from industrial partners.
Year(s) Of Engagement Activity 2020