The last 15 years have seen tremendous advances in using different metal catalysts to functionalize traditionally unreactive C–H bonds. Given the high potential of these seemingly ideal strategic bond forming reactions, the uptake of C–H activation in fine chemical manufacture is slow. Part of the reason for this deficiency is limited mechanistic understanding of these complex reactions. This can preclude industrial applications of either batch or continuous C–H activation processes. Owing to the synthetic utility of C–H activation reactions, it is highly desirable to design intensified processes for this family of transformations, what can possibly facilitate industrialisation of C–H activation reactions. Firstly, an ab initio process design of a novel C(sp3)–H activation reaction giving access to aziridines yielded a predictive mechanistic model that has been used in an in silico optimisation. The identified set of conditions was suitable for a scalable continuous process. A separation technique was developed, and the utility of the process was extended by a subsequent reaction, a nucleophilic ring opening. Secondly, a black-box optimisation of the investigated reaction was performed. The applied algorithm was able to identify a set of conditions fulfilling the set targets within few experimental trails. The second project has set out to design a process for a C–H oxidative carbonylation. A kinetic study has shown that the reaction is CO-starved even at elevated pressures and that there is an optimal CO concentration. The turn-over number was increased from 8 to nearly 500. Two scalable processes were then developed. The first was a batch process, characterised by a very low catalyst loading. The second was, to the best of author’s knowledge, the first continuous process for an oxidative carbonylation reaction. The continuous process was tested on several oxidative carbonylations yielding excellent results with virtually no optimisation performed. Finally, an environmental sustainability assessment was performed using both, simplified metrics and an LCI analysis. The developed mechanistic understanding allowed identification of sources of inherent inefficiencies of C–H activation reactions. Appropriate solutions to these obstacles were suggested. Thus, it is believed that a step towards generic principles of design of intensified, scalable processes for C–H activation-type reactions has been made.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:744946 |
| Date | January 2018 |
| Creators | Zakrzewski, Jacek |
| Contributors | Lapkin, Alexei |
| Publisher | University of Cambridge |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://www.repository.cam.ac.uk/handle/1810/277176 |
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