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

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.

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 the 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.