Continuous Manufacturing with Carbon Supported Nanoparticle Catalysts for the Self Optimisation of Heterogeneous Reduction Reactions

Heterogeneous catalysis is used widely in industry, both in batch systems and in continuous flow, via the use of packed bed reactors. The advantages of converting traditional batch processes to continuous flow are well defined in the literature. These include improved heat and mass transfer, easier scale up and better process control, leading to less waste and improved safety of the systems. Optimisation of these flow processes leads to further efficiency in exploring new reactions, as with higher yield often comes higher purity, reduced waste, and a greener synthesis. Despite the vast number of processes that make use of heterogeneous catalysis in the pharmaceutical industry, the adoption of continuous flow for these systems is limited.
The combination of automation and optimisation algorithms with continuous flow through closed-loop feedback control has been shown to be highly beneficial for chemical reaction optimisation in recent decades. However, this has mainly been limited to homogeneous systems. With a drive towards converting traditionally homogeneously catalysed reactions to heterogeneous ones, to improve the sustainability of the process, more work is required to develop and integrate solid catalysts into self-optimising platforms.
The work reported in this thesis aims to highlight the current challenges in the implementation of heterogenous continuous systems and improve existing technologies. This includes the development of an online continuous flow packed bed reactor platform, the improvement of processes via self-optimising algorithms in the formulation of APIs, the application of self-optimisation in the development of a telescoped system, the demonstration of a novel catalyst deactivation optimisation protocol, and the formulation of new spherical carbon supported catalysts for heterogeneously catalysed three-phase reactions.