Multi-nuclear operando FlowNMR investigations of catalytic amine formation reactions

In this project I will apply the operando spectroscopic capabilities of Bath's Dynamic Reaction Monitoring Facility to
gain new insights into the mechanisms of a range of homogeneously catalysed amine formation reactions (including
imine 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 RPKA
methods) with catalyst speciation profiles acquired under the same conditions. This will give new insights into
activation and inhibition/deactivation pathways as well as information on dormant off-cycle species. In line with the
CSCT ethos of sustainability, this will hopefully lead to the rational development of improved protocols (including
aspects of ease of operation, facilitated downstream separations, process-mass-intensity, energy demand, cost and
toxicity) and catalysts with increased efficiency in terms of activity, selectivity, productivity or stability. In line with the
ethos of the CSCT, these studies will hopefully lead to the development of more sustainable protocols for
homogeneously catalysed amine formation reactions. Lastly, we would like to develop novel transformations based
upon 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 that
enable 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 hardware
modifications (adaption of tubing materials, filters, reactors, pumps, flow-tube tips etc.) as well as optimisation of one
and two-dimensional pulse sequences as dictated by concentrations and lifetimes of reaction intermediates of
interest. Furthermore, diffusional (DOSY) and dynamic (EXSY, CEST) NMR methods will be used as well as
integration and cross-calib ration with complementary techniques such as UV-vis and IR/Raman spectroscopies and
sampling HPLC and MS as required.
In addition, we hope to develop methods for automated data analysis and quantification (across multiple techniques if
required) as well as reaction progress kinetic analysis using graphical methods (VTNA). Further, we envision, and will
pursue if appropriate, the use of use of real-time analysis and automated data interpretation with regulation of
process parameters using algorithms to establish a fully autonomous self-optimising system for homogeneous
catalysis
Most of the experimental work will be conducted at the