Multinuclear High-Resolution Flow NMR for In-Operando Investigation & Self-Optimisation of Chemical Reactions

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The importance of catalysis for the chemical industry is still increasing with the need to generate new materials in an increasingly sustainable matter. Catalysts are currently designed and optimised with multiple techniques used separately at the end of a reaction, which often leads to long development times. Nuclear Magnetic Resonance (NMR) is frequently used during the chemical development process due to its easy use, high information content and inherently quantitative nature. Recently, FlowNMR systems have been developed where, as opposed to a static solution being placed in a spectrometer, a solution can be flowed through the magnet. This has been shown to quickly provide data not achievable from traditional NMR methods with no perturbation of the reaction system. After success with FlowNMR for organic and homogenous transition metal catalysed reactions, continuation of reaction monitoring will take place for more complex organic molecules, transition metal complexes and other multinuclear complexes. With this, expansion of fundamental knowledge of the system, including the effect of flow conditions, will be investigated to ensure that meaningful results are achieved. Exploration of the usefulness of the technique will also take place, extending FlowNMR to other types of reactions which are particularly tedious to monitor by conventional techniques such as photochemistry and electrochemistry.FlowNMR has already shown to aid understanding of catalyst activation/de-activation mechanisms, identification of multiple states in the catalytic cycle alongside providing improved kinetic data. Currently there is not one readily available technique that can be used as universally during reaction development. With improved understanding of catalytic cycles in the early stages of development, there is potential to speed up chemical development across many sectors in both academia and industrial R&D. Without the need to use multiple laborious techniques for characterisation, and the consequential shorter time frames, there is potential to save both time and money with FlowNMR.Although a wide range of compounds are NMR active, it would be advantageous to devise complementary techniques that may be coupled with FlowNMR to achieve comprehensive reaction monitoring. For this purpose, we will look into the possibility of developing FlowEPR to detect, characterise and quantify paramagnetic species in real time that would otherwise go undetected by FlowNMR alone. This, and coupling with other techniques including real-time mass spectrometry, UV-vis spectroscopy and high-performance liquid chromatography will be pursued within Bath's new Reaction Monitoring Facility.Finally, together with our industrial partner AstraZeneca we will explore the possibility of using real-time reaction progress data derived from FlowNMR and/or FlowEPR to self-regulate and self-optimise continuous flow systems using appropriate algorithms.