The University of Pretoria Flow Chemistry Group

The University of Pretoria currently plays host to one of the most sophisticated flow chemistry facilities globally. Within the group we focus on the development of new methodologies for chemical syntheses employing flow chemistry and another advanced manufacturing techniques. We routinely investigate the use of flow technology to facilitate the development of improved process routes to pharmaceuticals with a focus on making said processes more economical, greener and safer. In addition, we are also involved in method development under flow conditions, the development on novel flow reactors and the utilisation of flow chemistry to expedite drug discovery.

What is flow chemistry

Flow chemistry involves performing chemical transformations in continual flowing streams wherein reagents are introduced at appropriate time periods and allowed to react in a variety of reactor types including mixing chips, tubular reactors and packed-bed reactors. Thereafter, down-stream processing and purification can also also performed in-line, and ideally one can also link multiple reactions together to afford truly continuous processes.

Flow chemistry – Method Development

As a research group, we are always striving to develop innovative methods for chemical synthesis, particularly involving novel flow methods. This involves improvement of existing batch-based processes through shorter reaction times, high temperature or pressure, inline purification techniques, minimal handling of hazardous chemicals etc. As a result, we have developed several flow process routes whereby we have demonstrated improvements over traditional batch-based synthesis including:

• The preparation of diazonium salts and their utilisation as coupling reagents
• Green reductions of aryl nitro and carbonyl functional groups
• Selective reductions of aldehydes in the presence of ketones
• Selective ozonolysis reactions
• Cleaner Claisen rearrangements

Flow chemistry – Equipment and Reactor Design

As flow chemists, we make use of a variety of flow tools to carry out the specific transformations required for our reactions to occur. Some of the equipment available in our labs include:

• Uniqsis FlowSyn
• Uniqsis FlowSyn Maxi
• Uniqsis FlowStart
• Uniqsis Binary Pumps
• VapourTec R2R4 reactors
• VapourTec E-MedChem Reactor
• VapourTec E-Photochemistry Reactor
• Syrris Asia 130 reactors
• Agilent LCMS

In addition, we are also actively involved in the development of bespoke reactor to allow access to a wider range of chemistries, down-stream processing techniques and purifications, these include:

• Gas-Liquid Reactors
• Photochemical Reactors
• In-line triturators
• Evaporation modules

Continuous manufacturing and API synthesis

Our research groups primary driver is in developing new continuous flow or batch-flow hybrid processes to pharmaceuticals that are economical, safe, green and scalable. Current and former API flow manufacturing projects include:

• Continuous batch-flow hybrid synthesis of the antipsychotic clozapine.
• A scalable process to manufacture celecoxib utilizing flow techniques.
• The development of a flow route to manufacture fluoxetine.
• The development of a green flow-based route for the preparation of bupropion.

Flow chemistry Advantages and Disadvantages

Current Students

Wessel Bonnet (MSc) – Flow process development and drug discovery - Tubercolosis

Zen Johnson (MSc) – Flow process development – Neglected Tropical Diseases

Lerato Dibokwane (PhD) – Flow process development and methodology – Anesthetics and Alzheimer’s Disease

Michelle Reinhardt (PhD) – Automation of flow processes and process development - Anesthetics

Lorinda van Wyk (PhD) – Flow process development and reactor design – Neurological drugs

G Valerie Maswanganyi (Post-Doc) – Process development

Nicole Neyt (Post-Doc) – Process development and reactor design

C Johan van der Westhuizen (Post-Doc) – Flow automation and machine learning

Contact Details

Prof Darren L Riley

Tel : +27(0) 124203097

Email : [email protected]

Office : NS1, Room 4-50