Investigating rate enhancements in alpha-keto esters using cinchona and non-cinchona alkaloids

Edwards, Miles Matthew 2022. Investigating rate enhancements in alpha-keto esters using cinchona and non-cinchona alkaloids. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

The products of the hydrogenation of alpha-ketoesters like ethyl pyruvate (EtPy), methyl benzoylformate (MBF) and ethyl benzoylformate (EBF) are used in many industries including pharmaceuticals, fragrances, solvent synthesis, and organic chemical intermediates. The rate of hydrogenation of EtPy increases substantially using cinchona alkaloid modifiers such as cinchonidine (CD) but the mechanism of rate enhancement is poorly understood, despite having been investigated extensively over the last few decades. The objective of this thesis is to investigate the mechanism of modifier-induced rate enhancement for the hydrogenation reactions of the alpha-keto esters EtPy, MBF and EBF. Rate enhancements were observed for the reactions of all three substrates (MBF, EBF and EtPy) using the different modifiers (CD, quinuclidine (QD) 3-quinuclidinol (QL), 1,4- diazabicyclo[2.2.2]octane (DABCO), and 4-aminoquinoline (AQ)). QD, QL, DABCO and AQ are modifiers that represent parts of the CD molecule, the aim of studying them being to deduce which parts of the CD molecule were involved in the rate enhancements. The concentrations of the modifiers were optimised, and the reaction data was kinetically fitted. Theoretical calculations were also completed to see if the rate enhancement mechanism could be understood computationally. The reaction mechanism when using CD may involve the 1:1 modifier: reactant model which stabilizes the half-hydrogenated state. This is suggested especially because of the rate enhancements observed for EBF and MBF which made the alternative theory for the mechanism of action via a ‘cleaning’ the catalyst model unlikely. The EtPy reaction mechanism may be a combination of the CD stabilizing the half-hydrogenated state and the cleaning effect. Concerning the achiral tertiary amines, the mechanism of action is unclear but the previous literature suggestion, supported by results from this project point to the modifier-surface complex being stabilized by the half-hydrogenated substrate. The cleaning effect and competitive adsorption may also be involved. Different substrates that were similar in structure to either EtPy, EBF and MBF were tested also to see if other rate enhancements could be found but none of these reactions gave significant rate enhancement. Theoretical computational results provided evidence for the existence of a solution-dimer intermediate.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Chemistry
Date of First Compliant Deposit:	16 June 2023
Last Modified:	06 Jan 2024 04:23
URI:	https://orca.cardiff.ac.uk/id/eprint/160409

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