Multi-nuclear operando FlowNMR investigations of catalytic amine formation reactions

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In this project I will apply the operando spectroscopic capabilities of Bath's Dynamic Reaction Monitoring Facility togain new insights into the mechanisms of a range of homogeneously catalysed amine formation reactions (includingimine reduction, reductive amination, hydrogen-borrowing amination, and C-N cross coupling reactions).The approach will be to correlate product formation kinetics (analysed over the course of the reaction via RPKAmethods) with catalyst speciation profiles acquired under the same conditions. This will give new insights intoactivation and inhibition/deactivation pathways as well as information on dormant off-cycle species. In line with theCSCT ethos of sustainability, this will hopefully lead to the rational development of improved protocols (includingaspects of ease of operation, facilitated downstream separations, process-mass-intensity, energy demand, cost andtoxicity) and catalysts with increased efficiency in terms of activity, selectivity, productivity or stability. In line with theethos of the CSCT, these studies will hopefully lead to the development of more sustainable protocols forhomogeneously catalysed amine formation reactions. Lastly, we would like to develop novel transformations basedupon the mechanistic insights where appropriate.Our aim, with the help of NMR specialist's Dr John Lowe and Catherine Lyall, is to develop efficient protocols thatenable the quantitative real-time monitoring of catalytic reactions by multi-nuclear FlowNMR spectroscopy.Depending on conditions like temperature, pressure, viscosity and phase behaviour this may include hardwaremodifications (adaption of tubing materials, filters, reactors, pumps, flow-tube tips etc.) as well as optimisation of oneand two-dimensional pulse sequences as dictated by concentrations and lifetimes of reaction intermediates ofinterest. Furthermore, diffusional (DOSY) and dynamic (EXSY, CEST) NMR methods will be used as well asintegration and cross-calib ration with complementary techniques such as UV-vis and IR/Raman spectroscopies andsampling HPLC and MS as required.In addition, we hope to develop methods for automated data analysis and quantification (across multiple techniques ifrequired) as well as reaction progress kinetic analysis using graphical methods (VTNA). Further, we envision, and willpursue if appropriate, the use of use of real-time analysis and automated data interpretation with regulation ofprocess parameters using algorithms to establish a fully autonomous self-optimising system for homogeneouscatalysisMost of the experimental work will be conducted at the