The application of Green Chemistry to Organic Syntheses and Mass-Based Reaction Metrics

This thesis explores the use of mass-based reaction metrics to analyses a chemical process and identify areas for improvement. The use of mass-based metrics to guide organic synthesis can lead to improvements in the green credentials and potential of a reaction. Mass-based reaction metrics have become an increasingly popular method of evaluating the performance and green credentials of a reaction or process. However, the use of metrics is not perfect, and several pitfalls have been identified. Through the analysis of published procedures for amide formation reactions, it was shown that Atom Economy (AE) and Reaction Mass Efficiency (RME) have the potential to be applied incorrectly due to operator error, and the data obtained from Process Mass Intensity (PMI) can be misinterpreted if no context to reaction conditions are applied. These issues can be amplified when the metric results are used in direct comparisons of processes. The use of reaction metrics has enabled improvements in various organic reactions to be identified and realised. The use of ethanol and HCl lead to improvements in the synthesis of cytosine, while 3,3-diethoxypropanitrile was synthesised from acrylonitrile in an improved catalytic process. 2,2,5,5-Tetramethyloxolane (TMO) was used as a substitute for traditional solvents in several chemical transformations; enzymatic catalysed synthesis of 1,3-oxathiolanes, the Mitsunobu reaction and various OH activated nucleophilic substitution reactions. The reactivity of cytosine and its protected derivatives towards 1,3-oxathiolanes under Mitsunobu conditions was also successfully investigated. Finally, the use of a potentially bio-based Brønsted acid p-cymene sulphonic acid (p-CSA) was used for OH activation reactions with numerous nucleophiles reacting with allylic and propargylic alcohols as well as alcohols derived from carvone.