Water as A Green Reaction Medium: Realising Its Full Potential

Supervisor(s)

Contact Dr Bao Nguyen, to talk about this project further informally.

Project description

The use of water in place of traditional organic solvents in chemical processes is a key objective of modern green chemistry. While some successes have been achieved, e.g. enzymatic transformations, water-based processes often suffer from low concentration/ productivity. This can result in high volume of contaminated waterm, negating the green benefits of such processes. An elegant solution for this is micellar catalysis, aqueous processes wherein a surfactant is employed to generate micelles containing organic reactants. No organic solvent is required and the micelles absorb the organic reactants, giving rise to rate acceleration through concentration effect and potential charge stabilisation of transition states at the aqueous-organic interface. Its applications in organic reactions, e.g. SNAr, SN2, hydrolysis of esters, amides, carbamates, heterocyclic condensation, amide formation, cycloaddition, and oxidation,[1] have been previously studied by many research groups and recently extended to catalytic reactions, e.g. Suzuki, Heck, Sonogashira, Stille couplings, metathesis, Fe-catalyzed nitro reduction, by Lipshutz and co-workers with PEG-based surfactants, giving >5 times reduction of E-factors.[2] Improved green metrics, productivity and economics of synthetic routes using micellar catalysis was demonstrated by researchers at Norvatis.[3] In spite of these successes, application of micellar catalysis in industrial processes is non-trivial.

The reactions often happen at the organic-aqueous interface, which means size and population of micelles are critical. Each type of reaction also benefits from a specific type of surfactants, i.e. cationic, anionic and neutral. Given the wide range of commercially available surfactants, the lack of a rational approach, e.g. surfactant/co-solvent selection for solubilising capability and reaction performance, screening strategy, critical parameter operational space, is a major obstacle in more wide-spread adoption of micellar catalysis in synthetic processes.

In this project, the student will develop a discovery and development toolkit which can streamline much wider application of micellar catalysis.

This toolkit will consist of:

  • A surfactant knowledge base to support surfactant screening, in the same manner of the ligand maps developed by Opren and Fey,[4] for homogeneous metal catalysis.
  • Critical parameter operational space for micellar catalysis process design.
  • Workup/purification strategies to minimize the amount of organic solvent and aqueous waste.

The toolkit will be demonstrated in case studies, including an API-relevant synthetic steps, in collaboration with AstraZeneca.

The project will build on the uniquely established capability at the iPRD in multiphase reactors, analytical tools and process design. The project is best suited to a student with strong background and interest in synthetic and physical chemistry. No prior knowledge of process design or flow chemistry is required, as training will be provided for these important transferable skills. The student will also benefit from interdisciplinary training and seminar programmes in process chemistry as a member of the Institute of Process Research & Development, Leeds.

More detail on this and other projects will be made available by contacting Dr Bao N. Nguyen.

References

[1] for a recent review see Green Chem. 2015, 17, 644.

[2] Angew. Chem. Int. Ed. 2016, 52, 10952.

[3] Green Chem. 2016, 18, 14.

[4] Angew. Chem. Int. Ed. 2012, 51, 118; Organometallics 2010, 29, 6245; Dalton Trans. 2009, 8183.

Entry requirements

Applications are invited from candidates with or expecting a minimum of a UK upper second class honours degree (2:1), and/or a Master's degree in Chemistry.

Additional staff contact

This proposal is representative of the projects currently on offer in our group. For more details of active research projects, please visit the website. Institute of Process Research & Development, Leeds.

How to apply

Formal applications for research degree study should be made online through the university's website. Please state clearly in the research information section that the PhD you wish to be considered for is the 'Water as A Green Reaction Medium: Realising Its Full Potential’ as well as Dr Bao Nguyen as your proposed supervisor.

If English is not your first language, you must provide evidence that you meet the University’s minimum English Language requirements.

We welcome scholarship applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates. All scholarships will be awarded on the basis of merit.

If you require any further information please contact the Graduate School Office e: maps.pgr.admissions@leeds.ac.uk