Research Area (Doctoral):
Continuous flow-chemistry as a disruptive technology is arguably seen as the next evolutionary step in pharmaceutical manufacturing affording many striking advantages over traditional batch manufacturing. Advantages include improved heat and mass transfer, reduced reaction residence times, improved safety, improved greeness and direct scalability. The technology, however, does not on its own solve all of the inherent short comings associated with batch processing and comes with its own challenges. Moving forward there is a clear need for the development of hybrid manufacturing platforms on which both flow and batch chemistry can be performed taking advantage of the best that both technologies have to offer. Nicole’s research involves the development of innovative batch-flow hybrid approaches for the synthesis of pharmaceuticals and pharmaceutical intermediates, research highlights include the development of a batch-flow hybrid synthesis of the antipsychotic clozapine incorporating green reductions and on-the-fly purification by trituration and the development of a bespoke ozonolysis reactor affording improved control not possible under batch conditions.
5. Mild and selective reductions of aldehydes utilising sodium dithionite under flow conditions.N.C. Neyt, D.L. Riley Beilstein Journal of Organic Chemistry 2018, 14, 1529-1536
We recently reported a novel hybrid batch–flow synthesis of the antipsychotic drug clozapine in which the reduction of a nitroaryl group is described under flow conditions using sodium dithionite. We now report the expansion of this method to include the reduction of aldehydes. The method developed affords yields which are comparable to those under batch conditions, has a reduced reaction time and improved space-time productivity. Furthermore, the approach allows the selective reduction of aldehydes in the presence of ketones and has been demonstrated as a continuous process.
4. Approaches for performing reductions under continous flow conditions. D.L. Riley, N.C. Neyt. Synthesis, 2018, eFirst
- Batch-flow hybrid synthesis of the anti-psychotic clozapine, N.C. Neyt, D. L. Riley. Reaction Chemistry and Engineering, 2018, Advance Article.
The development of batch–flow hybrid processes is becoming an attractive prospect through which chemists can make use of the best aspects of both technologies. We have reported the implementation of an on-the-fly purification by trituration which can also be utilised to perform solvent swaps. We have demonstrated this concept through the synthesis of the antipsychotic clozapine. In addition, we report a novel means of performing a reduction of an aryl nitro group under flow conditions and an overall improved process route for the total synthesis of clozapine.
- Utilising flow technology to synthesise neurological active pharmaceutical ingredients. N.C.Neyt, D.L. Riley Suid-Afrikaanse Tydskrif vir Natuurwetenskap en Tegnologie2017, 35(1), a1413.
- Thermochemical processing of a South African ultrafine coal fly ash using ammonium sulphate as extracting agent for aluminium extraction. Hydrometallurgy, 2016, 166, 174-184. Frédéric J. Doucet, Sameera Mohamed, Nicole Neyt, Barbara A. Castleman, Elizabet M. van der Merwe (2016)
2015 – SWAAK Conference (Bloemfontein) “Gebruik van vloei tegnologie vir die sintese van neurologiese aktiewe farmaseutiese bestanddele” Poster Prize
2016 – Frank Warren (Rhodes University) “Utilizing flow technology to synthesize Clozapine”
2017 – Young Chemists Symposium (Tshwane University of Technology) “Integrating batch and flow techniques to synthesize the antipsychotic clozapine” 2nd Prize Presentation
2018 – Flow Chemistry Europe (Cambridgeshire, UK) “Trituration under batch-flow hybrid conditions: A total synthesis of the anti-psychotic clozapine”. 2nd Prize Poster Presentation
2018 – RSC Twitter Poster Conference “Trituration under batch-flow hybrid conditions: A total synthesis of the anti-psychotic clozapine”. 1st Prize Engineering Catagory