Studies in synthesis using CO2 and H2 gases

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Lowry, Amy
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University College Cork
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Research Projects
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This thesis is split into two parts based on two different areas of research. Part 1 Part 1 is sub-divided into four chapters. Chapter 1 involves a review of the existing research conducted in this area. Chapter 2 provides details on the research carried out in this project on the development of a Wittig CO2 utilisation methodology for the synthesis of α,β unsaturated carboxylic acids. Chapter 3 involves discussion on the development of protocols for purification of the α,β-unsaturated carboxylic acids synthesised. The Conclusions and Future Work section relating to this area of research is found at the end of Chapter 3. Chapter 4 outlines the experimental work for Part 1. CO2 utilisation continues to capture the attention of chemists due to the ever-increasing levels of CO2 and the negative effects of global warming. CO2 is an inexpensive and environmentally friendly C1 building block, which can be used in the synthesis of value-added chemicals. Many medicinally important compounds and natural products contain the elements of CO2 within their structure, including carboxylic acids, enoates, and carbamates. In particular, α,β unsaturated carboxyl compounds are typically accessed by metal-catalysed transformations or condensation reactions, which often require hydrolysis of the ester product to furnish the corresponding acid. In this project, a telescoped process was developed, that not only achieves CO2 activation, but exploits a novel application of the Wittig reaction, enabling direct installation of the carboxyl group by two successive carbon-carbon bond forming events. Reaction optimisation and purification studies were carried out and 34 α,β-unsaturated carboxylic acids were synthesised using the method, containing a wide range of functional groups, as well as a number of pharmaceutical precursors, in moderate to excellent yields. As part of this work, a novel method for purification of α,β-unsaturated carboxylic acids was developed. Part 2 Part 2 is sub-divided into three chapters. Chapter 5 involves a discussion on the background of the project and a review of the existing research conducted in the area. Chapter 6 involves a discussion of the research carried out in this project on the dearomatisation of benzofuroquinolines by a Pd-catalysed hydrogenation reaction. The Conclusions and Future Work section relating to this part of the thesis is found at the end of Chapter 6. Chapter 7 outlines the experimental work for Part 2. Within the McGlacken group, development of C-H activation methodologies has been a large area of research, and, in particular, benzofuroquinolines have been synthesised via direct intramolecular arylation of 4-phenoxyquinolines. The quinoline nucleus is one of the most frequently occurring ring systems in approved drugs, and hydrogenation of the quinoline nucleus and the selectivity thereof, has been reported in the literature. In addition, increasing interest in the concept of ‘escaping flatland’, whereby the saturation of compounds is increased, allowing for the exploration of more architecturally complex molecules that will potentially give rise to enhanced biological activities. In this part of the thesis, a range of differently substituted benzofuroquinolines were hydrogenated to generate 18 selectively dearomatised benzofuroquinolines. Investigations were carried out into different reaction conditions tolerated by the reaction, and the fate of halogen substituents in the reaction. In addition, a double reduction product side-product was identified and characterised, opening up the methodology to the formation of a new class of novel compounds.
Carbon dioxide utilisation , Wittig reaction , Phosphonium ylide , Carboxylic acid , Hydrogenation , Dearomatisation , Quinolines , Heterogeneous catalysis
Lowry, A. 2023. Studies in synthesis using CO2 and H2 gases. PhD Thesis, University College Cork.
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