Abstract
Discovered in 1822, the haloform reaction is one of the oldest known synthetic reactions. The history of this methyl ketone-to-carboxylic acid transformation, as well as methodology advances and examples of its application in modern synthetic chemistry are discussed in Chapter 1. The extension of the reaction to ester synthesis is also introduced.There are two significant issues with the classical haloform reaction as a method of ester synthesis: the requirement for solvent-level alcohol, which severely limits the scope of the reaction; and the use of superstoichiometric quantities of hazardous hypohalite oxidants. An electrochemical method proceeding via halide oxidation and requiring only stoichiometric alcohol was proposed to address these issues; efforts toward the realisation of this electrochemical haloform coupling are discussed in Chapter 2. Although appreciable ester yields were achieved with just 2 equivalents of alcohol, fundamental issues with the electrochemistry hindered further development of this method. However, building on this work, a promising method for electrochemical synthesis of tetraethylammonium trichloride, a useful reagent for chlorination and alcohol oxidation reactions, was discovered.
The use of readily available and relatively non-hazardous elemental iodine was proposed as an alternative to electrochemical halide oxidation in the development of a haloform method with stoichiometric alcohol. The optimisation and scope of this ‘chemical’ haloform coupling with both primary and, significantly (since they have not been reported in the haloform reaction before), secondary alcohols are discussed in Chapter 3. Intriguing reactivity differences between primary and secondary alcohols were observed, and the mechanistic insights obtained through their investigation are also discussed.
A summary of the work is presented in Chapter 4 and the accompanying experimental details can be found in Chapter 5.
| Date of Award | 3 Oct 2023 |
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| Original language | English |
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| Supervisor | Alastair J J Lennox (Supervisor) |