While bulk chemicals are generally manufactured in efficient continuous processes, generating relatively little waste (E-factor <1-5), high value chemical products (fine chemicals, agrochemicals, pharmaceuticals) are usually manufactured in batch units, generating enormous waste (E-factor ca. 25-100). There is therefore a clear business advantage, if continuous manufacturing techniques could be adapted for use in these industries. Continuous processing can facilitate safe manipulation of potentially hazardous reagents that can nevertheless effect low-waste transformations, e.g. by efficient heat-transfer in very exothermic processes & minimising local inventory of hazardous material. Whilst most oxidations of bulk chemicals can be performed continuously using molecular oxygen in the gas phase, safety considerations (exotherm, formation of explosive mixtures) preclude its use in batch processes, particularly for thermally sensitive, involatile substrates found in fine chemical manufacture. This leads to two undesirable behaviours: a) adoption of costly, atom inefficient, waste-generating stoichiometric oxidants, with consequent negative environmental impact, and b) a tendency to avoid oxidative transformations by using inevitably less efficient 'workarounds'. It is therefore clear that oxidation is a potentially key enabling technology. The demonstration of cost-effective, safe, and efficient use of aerobic oxidation in an organic solvent would be transformative since a wide and increasing range of catalytic organic transformations would be considered seriously by industry, and not avoided due to safety concerns. The potential to drive further efficiency by 'telescoping' subsequent transformations would also be facilitated by continuous, work-up free oxidation. Thus, this project aims to instigate a step change in efficiency in the manufacture of many products by developing safe continuous oxidative transformations.

Potential Impact:
Financial as well environmental factors drive the development of safer, cleaner, cheaper chemical processes. The chemicals industry is vital to the fiscal health of UK plc. It contributes about £5bn to the UK balance of payments (£50bn gross) and represents ca. 2% of GDP. It is the UK's number one manufacturing exporter, and contributes ca. 11% of manufacturing GVA. Further, about half of the products go to service downstream UK industries. The industry is under pressure from low cost manufacturing economies in Asia and South America, and hence innovation to retain IP and the associated revenue streams in the UK is both vital and timely. The chemical industry, in particular pharmaceuticals, fine chemicals, catalyst producers, will be main beneficiaries from this work, by accessing novel technology and catalysts for clean oxidation processes. The proposed approach will ultimately help reduce time and cost associated with scaling up from laboratory to production, due to information-rich experimentation that is proposed. These will give a significant competitive advantage to the chemicals industry, assisting it to remain at the forefront of innovation worldwide. The research will also benefit equipment manufacturers, by allowing them to introduce in the market innovative products. This can help place the UK as a leading supplier of flow chemistry equipment, where the UK currently has a strong position. Finally, more efficient, cleaner and cheaper process solutions, will benefit the society through the use of these technological advances for green and sustainable chemical manufacture.