The manufacture of chemicals makes a major contribution to the UK's economy; £10 bn p.a. in the chemicals and £9bn in the pharmaceuticals sectors alone. The recent report of the Chemistry Growth Strategy Group states that 'By 2030, the UK chemical industry will have further reinforced its position as the country's leading manufacturing exporter and enabled the chemistry-using industries to increase their Gross Value Added contribution to the UK economy by 50%' with "smart manufacturing" as one of three priorities in realising their vision. Our proposal aims to contribute to this smart manufacturing by transforming the way in which continuous photochemistry can be applied to commercial chemical manufacture. There is considerable current academic interest in new photochemical reactions for organic synthesis but how they might be used industrially is usually ignored. Nevertheless the potential of photochemistry in manufacturing is widely recognized if only it could be made scalable and efficient. Traditionally the pharmaceutical and fine chemicals industries have used batch reactors for manufacture, which are difficult to adapt effectively for photochemistry. Therefore, this proposal focuses on continuous reactors which not only permit innovation in design to overcome technical limitations of current photoreactors but also provide a direct route to increased throughput via scale up or scale out. We will tackle some of the technical and engineering issues inherent in conventional photoreactors. These engineering problems include getting light efficiently into the reactors, build-up of opaque material on transparent surfaces key safety issues, particularly in reactions involving oxidation, as well as cost issues related to low efficiency of many light sources and difficulties of scale up. Our project proposes to create new engineering approaches to continuous photochemical manufacture of chemicals, which could transform chemical processes and cost. Our proposal addresses key technical/scientific barriers frustrating current commercial use of photochemistry and promises cheaper products in the pharmaceutical, agrochemical and fine chemicals sectors. Our team consists of three investigators with a proven track record of taking chemical processes from laboratory to commercial plant. Between us, we have the expertise needed for success; namely, in photochemistry, continuous organic reactions, manufacturing, mechanical and chemical engineering and process monitoring.

Our vision is to use continuous photochemistry and electrochemistry to transform how fine chemicals, agrochemicals and pharmaceuticals are manufactured in the UK. We aim to minimize the amount of chemicals, solvents and processing steps needed to construct complex molecules. We will achieve this by exploiting light and/or electricity to promote more specific chemical transformations and cleaner processes. By linking continuous photochemistry and electro-chemistry with thermal flow chemistry and environmentally acceptable solvents, we will create a toolkit with the power to transform all aspects of chemical synthesis from initial discovery through to chemical manufacturing of high-value molecules. The objective is to increase efficiency in terms of both atoms and energy, resulting in lower cost, low waste, low solvent footprints and shorter manufacturing routes. Historically photo- and electro-chemistry have been under-utilised in academia and industry because they are perceived to be complicated to use, difficult to scale up and engineer into viable processes despite their obvious environmental, energy and cost benefits. We will combine the strategies and the skills needed to overcome these barriers and will open up new areas of science, and deliver a step-change (i) providing routes to novel molecular architectures, hard to reach or even inaccessible by conventional methodologies, (ii) eliminating many toxic reagents by rendering them unnecessary, (iii) minimizing solvent usage, (iv) promoting new methodologies for synthetic route planning. Our proposal is supported by 21 industrial partners covering a broad range of sectors of the chemistry-using industries who are offering £1.23M in-kind support. Therefore, we will study a broad range of reactions to provide a clear understanding of the most effective areas for applying our techniques; we will evaluate strategies for altering the underlying photophysics and kinetics so as to accelerate the efficiency of promising reactions; we will transform our current designs of photochemical and electrochemical reactors, with a combination of engineering, modelling and new fabrication techniques to maximize their efficiency and to provide clear opportunities for scale-up; we will exploit on-line analytics to accelerate the optimisation of continuous photochemical and electrochemical reactions; we will design and build a new generation of reactors for new applications; we will identify the most effective strategies for linking our reactors into integrated multi-step continuous processes with minimized waste; we will demonstrate this integration on at least one synthesis of a representative pharmaceutical target molecule on a larger scale; we will apply a robust series of sustainability metrics to benchmark our approaches against current manufacturing.