Novel transient flow methods for the investigation of chemical reactions
File(s)
Author(s)
Schrecker, Linden
Type
Thesis
Abstract
Reaction data is important to collect not only for theoretically understanding chemistry better, but also for mass producing chemicals for medicine, agriculture, and society in general. The development of transient flow adds an efficient tool by which reactions can be studied.
In this thesis, the first comprehensive review of transient flow has been compiled, a foundational step in the establishment of any field. This review reveals the growth of the field over the past 12 years, although also shed light on areas in which further development is needed. Transient flow methods for collection of time series data are the most ubiquitous techniques, however justification of which method to use to collect such data is scarce. A comparison of different cumulative flow rate step and ramp methods on three reactions demonstrates the ‘reverse push-out’ step method as an accurate method, easy to implement by those inexperienced in flow chemistry.
Focus was then placed on developing novel transient flow methods in the investigation of the kinetics of the Knorr pyrazole synthesis. A novel reactant stoichiometry ramp and a related multivariate ramp were developed and utilised in this investigation. A microkinetic model was constructed for the reaction revealing unusual complex kinetic pathways, unlike previously simple proposed pathways.
Transient flow methods for the investigation of traditionally discrete reaction parameters were developed to further the efficiency of diverse data collection. The aromatic Claisen rearrangement was investigated to better understand the effect of substituent and solvent on the rate of reaction. Novel methods were developed: a ‘one-pot’ method by which six substituted reactions could be investigated simultaneously; and a solvent ramping method transforming solvents from a discrete reaction parameter into continuous parameters, which could be efficiently assessed. Access to such reaction data allows robust predictive models to be constructed and fundamental chemical insights to be obtained.
In this thesis, the first comprehensive review of transient flow has been compiled, a foundational step in the establishment of any field. This review reveals the growth of the field over the past 12 years, although also shed light on areas in which further development is needed. Transient flow methods for collection of time series data are the most ubiquitous techniques, however justification of which method to use to collect such data is scarce. A comparison of different cumulative flow rate step and ramp methods on three reactions demonstrates the ‘reverse push-out’ step method as an accurate method, easy to implement by those inexperienced in flow chemistry.
Focus was then placed on developing novel transient flow methods in the investigation of the kinetics of the Knorr pyrazole synthesis. A novel reactant stoichiometry ramp and a related multivariate ramp were developed and utilised in this investigation. A microkinetic model was constructed for the reaction revealing unusual complex kinetic pathways, unlike previously simple proposed pathways.
Transient flow methods for the investigation of traditionally discrete reaction parameters were developed to further the efficiency of diverse data collection. The aromatic Claisen rearrangement was investigated to better understand the effect of substituent and solvent on the rate of reaction. Novel methods were developed: a ‘one-pot’ method by which six substituted reactions could be investigated simultaneously; and a solvent ramping method transforming solvents from a discrete reaction parameter into continuous parameters, which could be efficiently assessed. Access to such reaction data allows robust predictive models to be constructed and fundamental chemical insights to be obtained.
Version
Open Access
Date Issued
2023-11
Date Awarded
2024-03
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Hii, King Kuok (Mimi)
Hellgardt, Klaus
Sponsor
BASF
Engineering and Physical Sciences Research Council
Grant Number
EP/S023232/1
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)