FlowNMR Spectroscopy for Mechanistic Studies in Homogeneous Catalysis and Automated Equilibrium Measurements

: (Alternative Format Thesis)

Abstract

FlowNMR has been presented as an invaluable technique for the acquisition of mechanistic insight into dynamic molecular processes in the last decade. While NMR analysis of flowing liquids (flow NMR) has existed for decades, FlowNMR has been coined in recent years for the specific online study of chemical systems using a removable umbilical that doesn’t require changes in instrumental configuration. The development of this apparatus has sparked a new surge in impactful research using online NMR analyses as part of modern mechanistic and process analysis. This thesis explores utilization of high-field FlowNMR for specialist and routine applications across an array of subject areas.

The informed development and employment of flowing chemical systems requires a breadth of interdisciplinary knowledge. In this work, flow and heat transfer mechanic of the apparatus are explored and discussed critically with their effect on obtained analytical data. In addition, the use of flow facilitates the integration of multiple analytical techniques in series throughout a flow system. As such UV-Vis, high-performance liquid chromatography, mass spectrometry, and headspace mass spectrometry were successfully hyphenated with high field NMR.

The direct observation of low concentration reagents in real-time under realistic conditions is a significant challenge for modern mechanistic analysis. Operando reaction monitoring is essential in catalysis for the elucidation of mechanistic processes, leading to their rational improvement. In this work the combination of instruments above was used to delve into the asymmetric transfer hydrogenation of acetophenone using a bifunctional ruthenium catalyst. Comparison of reaction profiles with catalyst speciation, reductant consumption, gas evolution and enantioselectivity painted a more comprehensive picture of this catalysis which led to an expanded reaction mechanism. The understanding afforded by this data led to rational reaction optimization whereby the excess formation of hydrogen gas was minimized, which has important safety implications on large scales.

The triethylamine base, thought to be responsible for catalyst activation in this catalysis was observed to not activate catalyst precursor when added in the absence of formic acid. An investigation into the role of acid and base relative to their absolute loading was conducted. It was found that adding excess triethylamine to pre-activated catalyst precursor resulted in a change in co-ordination number indicated by a distinct colour change. This behaviour contradicts its proposed purpose in literature and was therefore investigated further.

The observation of reliable and reproducible shifts in peak position during catalysis led to the suggestion of FlowNMR as an effective method for automated online titrations. To explore this application examples were taken from the fields of acid/base, supramolecular, and coordination chemistry. High field FlowNMR proved to be an effective method, which when combined with modern analytical techniques can quickly and efficiently produce data dense titration profiles composed of information rich data points. This led to the characterization of thermodynamic parameters in these equilibria and observation of hydrogen bonding behaviour that would not have been explored by routine offline analysis.

Developments in analytical chemistry and computer science combined with the increasing need for process characterization in industry have triggered a rise in the publication of (and value placed on) the use of online analytical techniques as process analytical technologies. The final section of this work discusses real-time high field NMR data export and employment of a PID controller for automated process control. The combination of these components created a responsive online analysis system that was capable of accurately titrating reagents to a defined setpoint using chemical shift. This apparatus was also used to attempt regulation of a catalytic process based on chemical shift. Results showed that regulation was possible for the first half of the catalytic reaction profile, but after this point the chemical shift of the spectroscopic handle no longer correlated to catalytic activity. Computational elements (data export and PID controller) were developed for application with NMR integrals. While these were not used on real-time data analysis due to time constraints, they are expected to facilitate the responsive regulation of chemical concentration in real-time.

Date of Award	22 Jun 2022
Original language	English
Awarding Institution	University of Bath
Sponsors	Bruker UK Ltd
Supervisor	Uli Hintermair (Supervisor) & John Lowe (Supervisor)