Manufacturing in Flow: Controlled Multiphase Reactions on Demand (CoMRaDe)

Lead Research Organisation: Imperial College London
Department Name: Department of Chemical Engineering

Abstract

In the production of pharmaceutical and fine chemicals, most of the reactions are conducted 'homogeneously' in one phase, i.e. a suitable solvent is used to dissolved all of the starting material, reagent and catalyst. At the end of the reaction, extra operations (known as 'work up') are required to separate the product from byproducts and any remaining starting materials. Work up/separation procedures can be complicated and time-consuming, and can constitute 40-70% of the costs of chemical processes. It also consumes extra resources (energy, material, additional solvent), which is detrimental to the environment.

One way of overcoming the separation issue is to conduct multiphase reactions, where the starting material and the reagent are dissolved in immiscible solvents (such as oil and water). After the reaction, the products remain physically separated from the reagent and byproducts, which simplifies the workup procedure. However, there are several fundamental issues that need to be addresse; namely, how fast reactions can occur at the interface, and how to control it precisely to afford reproducible and predictable outcomes (which is very important for its eventual application in industry).

The proposed programme will develop a new type of continuous manufacturing process for multiphase oxidations. First, it will use electrochemistry to generate inorganic oxidants in water from non-hazardous inorganic salts and electricity. The solution of oxidant will be mixed with reactants in an immiscible solvent, using a specially designed reactor that generates an emulsion from the two immiscible fluids. After the reaction, the two different phases then separate out naturally, thus simplifying the workup procedure.

The research programme will focus on the generation of different oxidants and their intrinsic reactivity. We will also develop novel emulsion forming systems to handle liquid/liquid reactive flows. The rates of the various steps in the process will be deteremined, to produce a predictive model that we can be used to construct a mini-plant for demonstration purposes.

Planned Impact

End-user engagement strategy: A number of key stakeholders, including research partners and beneficiaries, were involved in the preparation of the proposal (see supporting letters). In particular, Sulzer, Jorin and Micropore Technologies Ltd will be providing resources (reactors and equipment) as research partners of the project; none of these partners will claim any rights on the IP arising (this will belong to either Imperial College and/or Loughborough University, subject to negotiations). Interactions and knowledge-transfer between the collaborators will be promoted through mobility of Researchers between the laboratories, including periods of secondment. Additional engagement with other potential beneficiaries in manufacturers of larger-volume chemicals, e.g. agro- and fine-chemicals, to test the applicability of the developed technology at larger scale. This can be achieved through existing industrial contacts at Pharmacat and Manufacturing Future lab. Joint bids with the appropriate industrial collaborators will be submitted to TSB to support technology transfer (KTP programme) or collaborative R&D projects.

Contribution to economic development (UK plc): The global economic crisis has heightened the need to develop the manufacturing sector as a more sustainable means to rebalance the UK economy. According to the data produced by the CIA, the chemical and pharmaceutical businesses were estimated to be worth £60 billion, of which the pharmaceutical industry (largest in the world when normalised per capita) is worth an annual turnover of ca. £50 billion. In recent years, the industry is facing increasing pressure and competition from the Far East (such as China and India). High-value manufacturing has been identified to have the best potential to bring sustainable growth and high economic value to the UK economy. In the immediate to medium term (5-10 years), the knowledge, skills and expertise developed within this project supports the chemical industry by t generation of novel IP, and the training to provide a highly-qualified workforce to maintain the UK's capability and global competitiveness in manufacturing.

Economic and societal impact: Over the forseeable future, the high-value chemical industry will continue to move from batch to continuous processing to reduce down time, increase quality and productivity, which, at the same time, making processes more atom economical, environmentally freindly, and intrinsically safe. In the longer term (>10 years), the research will provide sustainable manufacturing routes to reduce the demand for critical raw materials, delivering processes with minimal environmental footprint. This will have an important impact on the quality of life, particularly for the population of industrialised nations.

During the course of the project (2-5 years), there are opportunities to generate IPs in the following areas:
1) Design of novel multiphase reactors for oxidation reactions that can be implemented on scale;
2) Electrochemical and membrane technology integrated with a flow chemistry platform;
3) Patent(s) on the process of integration.

The IP developed within the project will be managed by the relevant Technology Transfer offices in London and Loughborough, including the implementation of NDAs between project partners and beneficiaries, patent protection and management, licensing activities, and support for spin-out companies.

Publications

10 25 50
 
Description The construction of a mini pilot plant (e.g. ~7kg/day diol production) has been completed.
An electrochemical flow cell system has been scaled up by 10 times for incorporation into the mini pilot plant system.
A lab-scale electrochemical flow system has been constructed for the generation and delivery of inorganic oxidants on demand without using additives. Inorganic oxidants have been generated for the green di-hydroxylation of alkenes.
Two patents have been filed - second patent may be taken up through license agreement (via Imperial Innovations plc).
Exploitation Route Electrogeneration (and regeneration) of environmentally safe inorganic oxidants from inorganic electrolytes, for organic reactions 'on demand'.
Generation and separation of unstable fluid emulsions via a continuous pulsed flow system, as a way of overcoming mass transport limitations by enhancing liquid/liquid interactions.
A continuous mini plant system which integrated the electrochemical oxidant production and the membrane (de)mulsification.
Sectors Agriculture, Food and Drink,Chemicals,Electronics,Environment,Pharmaceuticals and Medical Biotechnology

URL http://pubs.acs.org/doi/full/10.1021/acssuschemeng.5b01372
 
Description Evaluation of patent and license opportunity for electrochemical generation of oxidants - ongoing license evaluation through Ideal Standards. Now complete - not taken up due to change of focus. Funding of up to 6 studentships through international chemicals company (BASF) - materialised in 2018 - ongoing. Funding of studentships contributed to the award of a CDT in next generation synthesis and reaction technology. New license opportunity with Miele - a German white goods manufacturer.
First Year Of Impact 2018
Sector Chemicals,Healthcare,Manufacturing, including Industrial Biotechology
Impact Types Economic

 
Description EPSRC Centre for Doctoral Training in Next Generation Synthesis & Reaction Technology
Amount £6,134,110 (GBP)
Funding ID EP/S023232/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 03/2019 
End 09/2027
 
Description CoMRaDe 
Organisation Jorin Limited
Country United Kingdom 
Sector Private 
PI Contribution Imperial - Chemistry, Reaction Engineering
Collaborator Contribution Loughborough University - (D)emulsification, Population Balance Modelling
Impact Patent: Apparatus and method for production of oxidants (P62616GB, 2015) Publication: Loponov K. N. Deadman B. J., Zhu J., Reilly C., Holdich R. G., Hii K. K., Hellgardt K. Controlled multiphase oxidations for continuous manufacturing of fine chemicals. Chemical Engineering Journal, 2017 (in submission). Zhu, J., Hii, K. K., Hellgardt, K. Toward a green generation of oxidant on demand: Practical electrosynthesis of ammonium persulfate. ACS Sustainable Chem. Eng. 2016, accepted (DOI: 10.1021/acssuschemeng.5b01372). Conferences: Talk x1, 2016 AIChE Annual Meeting, San Francisco, USA (13-16 Nov 2016) Talk x1 and poster x1, 22nd International Conference on Chemical Reactors, London, UK (19-23 Sep 2016) Posters x2, SCI/RSC Continuous Flow Technology III, Cambridge, UK (14-16 Mar 2016) Exhibition showcase at ACHEMA 2015, Frankfurt, Germany (15-19 Jun 2015)
Start Year 2014
 
Description CoMRaDe 
Organisation Loughborough University
Country United Kingdom 
Sector Academic/University 
PI Contribution Imperial - Chemistry, Reaction Engineering
Collaborator Contribution Loughborough University - (D)emulsification, Population Balance Modelling
Impact Patent: Apparatus and method for production of oxidants (P62616GB, 2015) Publication: Loponov K. N. Deadman B. J., Zhu J., Reilly C., Holdich R. G., Hii K. K., Hellgardt K. Controlled multiphase oxidations for continuous manufacturing of fine chemicals. Chemical Engineering Journal, 2017 (in submission). Zhu, J., Hii, K. K., Hellgardt, K. Toward a green generation of oxidant on demand: Practical electrosynthesis of ammonium persulfate. ACS Sustainable Chem. Eng. 2016, accepted (DOI: 10.1021/acssuschemeng.5b01372). Conferences: Talk x1, 2016 AIChE Annual Meeting, San Francisco, USA (13-16 Nov 2016) Talk x1 and poster x1, 22nd International Conference on Chemical Reactors, London, UK (19-23 Sep 2016) Posters x2, SCI/RSC Continuous Flow Technology III, Cambridge, UK (14-16 Mar 2016) Exhibition showcase at ACHEMA 2015, Frankfurt, Germany (15-19 Jun 2015)
Start Year 2014
 
Description CoMRaDe 
Organisation Micropore Technologies Ltd
Country United Kingdom 
Sector Private 
PI Contribution Imperial - Chemistry, Reaction Engineering
Collaborator Contribution Loughborough University - (D)emulsification, Population Balance Modelling
Impact Patent: Apparatus and method for production of oxidants (P62616GB, 2015) Publication: Loponov K. N. Deadman B. J., Zhu J., Reilly C., Holdich R. G., Hii K. K., Hellgardt K. Controlled multiphase oxidations for continuous manufacturing of fine chemicals. Chemical Engineering Journal, 2017 (in submission). Zhu, J., Hii, K. K., Hellgardt, K. Toward a green generation of oxidant on demand: Practical electrosynthesis of ammonium persulfate. ACS Sustainable Chem. Eng. 2016, accepted (DOI: 10.1021/acssuschemeng.5b01372). Conferences: Talk x1, 2016 AIChE Annual Meeting, San Francisco, USA (13-16 Nov 2016) Talk x1 and poster x1, 22nd International Conference on Chemical Reactors, London, UK (19-23 Sep 2016) Posters x2, SCI/RSC Continuous Flow Technology III, Cambridge, UK (14-16 Mar 2016) Exhibition showcase at ACHEMA 2015, Frankfurt, Germany (15-19 Jun 2015)
Start Year 2014
 
Description CoMRaDe 
Organisation Sulzer
Country Switzerland 
Sector Private 
PI Contribution Imperial - Chemistry, Reaction Engineering
Collaborator Contribution Loughborough University - (D)emulsification, Population Balance Modelling
Impact Patent: Apparatus and method for production of oxidants (P62616GB, 2015) Publication: Loponov K. N. Deadman B. J., Zhu J., Reilly C., Holdich R. G., Hii K. K., Hellgardt K. Controlled multiphase oxidations for continuous manufacturing of fine chemicals. Chemical Engineering Journal, 2017 (in submission). Zhu, J., Hii, K. K., Hellgardt, K. Toward a green generation of oxidant on demand: Practical electrosynthesis of ammonium persulfate. ACS Sustainable Chem. Eng. 2016, accepted (DOI: 10.1021/acssuschemeng.5b01372). Conferences: Talk x1, 2016 AIChE Annual Meeting, San Francisco, USA (13-16 Nov 2016) Talk x1 and poster x1, 22nd International Conference on Chemical Reactors, London, UK (19-23 Sep 2016) Posters x2, SCI/RSC Continuous Flow Technology III, Cambridge, UK (14-16 Mar 2016) Exhibition showcase at ACHEMA 2015, Frankfurt, Germany (15-19 Jun 2015)
Start Year 2014
 
Title Apparatus and method for production of oxidants 
Description An apparatus and method which enables a user to manufacture a wide variety of different species of oxidants on-demand and in-situ. The apparatus and method of the present invention can be used in a laboratory or in a chemical plant, to deliver a desired oxidant type to a chemical process, at the time the oxidant is required and with user defined characteristics, for example, at a desired temperature, concentration and flow rate. The apparatus and method of the present invention thus avoids the need for oxidant storage in quantities which would be of safety and quality concern and gives the option of delivering freshly prepared oxidant which can be used immediately and in-situ.The present invention provides an apparatus for manufacturing an oxidant, the apparatus comprising an electrochemical reactor, a feed inlet for receiving feed materials and a product outlet for dispensing the oxidant; the electrochemical reactor being in fluid communication with the feed inlet and the product outlet and comprising one or more anode and one or more cathode; and wherein the apparatus further comprises: means for detecting an oxidant (an oxidant detector) within the apparatus; and flow controlling means configured to control the flow of fluid through the product outlet and to communicate with the means for detecting an oxidant. 
IP Reference GB1509769.4 
Protection Patent application published
Year Protection Granted 2015
Licensed No
Impact Follow-on patent
 
Title ELECTROCHEMICAL CELL 
Description An oxidant production apparatus comprises an electrochemical reactant reservoir, an electrolysis compartment, a porous first electrode and a second electrode. The porous first electrode defines a boundary between the reservoir and the electrolysis compartment and is configured to allow an electrochemical reactant to pass from the reservoir, through the first electrode and into the electrolysis compartment. The second electrode disposed at least substantially in the electrolysis compartment and spaced apart from the first electrode. The apparatus is configured to produce an oxidant in an electrochemical reaction when a voltage is applied across the first and second electrodes and a current is passed through the first and second electrodes and an electrolyte disposed in the electrolysis compartment. 
IP Reference WO2019008344 
Protection Patent application published
Year Protection Granted 2019
Licensed No
Impact Idea Standards have funded a licence evaluation programme to consider a specific application in their sector. After an approximately 6 month evaluation period, the head of research changed and activities have taken a different focus. Currently in discussions with Miele - a high end German white goods manufacturer for potential evaluation funding.
 
Title Electrochemical Cell 
Description The application of an electrochemical device to dispense disinfectant on-site and on-demand, thus minimising need for storage (safety) and transport.(reduce carbon footprint) of hazardous material. 
IP Reference GB1710655.0 
Protection Patent application published
Year Protection Granted 2018
Licensed Commercial In Confidence
Impact none
 
Description 8th International Conference on Green and Sustainable Chemistry (GSC8) - Mimi Hii 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Keynote address at flow conference
Year(s) Of Engagement Activity 2017
 
Description Flow Chemistry Meeting at BASF 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Industry/Business
Results and Impact Seminar on Flow Chemistry
Year(s) Of Engagement Activity 2018
 
Description Impact Acceleration: Flow Chemistry Youtube video 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Youtube video on flow chemistry
Year(s) Of Engagement Activity 2015
URL https://www.youtube.com/watch?v=8N-98QTRzU0
 
Description Invited Lecture RSC-ACG "Successful Scale-Up of Catalytic Processes", Stockton-on-Tees, UK, 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited lecture to also disseminate work carried out during the EPSRC project.
Year(s) Of Engagement Activity 2017
 
Description Invited Lecture at Flow Chemistry Europe, Cambridge 2018 (Prof. K. Hellgardt) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Annual European conference on Flow Chemistry - highlighting the research work that has been carried out during the EPSRC programme. Further discussions with CPI representatives regarding future applications of technology.
Year(s) Of Engagement Activity 2018
 
Description Invited Speaker (Prof. Mimi Hii) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 6th Conference on Frontiers in Organic Synthesis Technology (FROST6), Budapest, Hungary
Year(s) Of Engagement Activity 2017
 
Description Invited speaker (Prof. Mimi Hii) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Invited speaker, Flow Chemistry Europe 2016
Year(s) Of Engagement Activity 2016
 
Description Meeting to discuss potential collaboration 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact Meeting to discuss potential collaboration to develop technology with CPI, Teeside
Year(s) Of Engagement Activity 2017
 
Description Plenary Lecture (Prof. Mimi Hii) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Asia-Oceania Conference on Sustainable and Green Chemistry (AOC-SGC6), City University of Hong Kong, November 27-30, 2016.
Year(s) Of Engagement Activity 2016
 
Description Research Seminar (Prof. Mimi Hii) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Institute of Chemical and Engineering Sciences (ICES, A*Star Institute), Singapore
Year(s) Of Engagement Activity 2016
 
Description Research Seminar (Prof. Mimi Hii) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact McGill University, Montreal, Canada
Year(s) Of Engagement Activity 2017