Applications of photo-oxidation with 1O2 in multistep reactions

There is an increasing drive to perform chemical synthesis in a greener and more environmentally friendly way, particularly on an industrial scale. Usually, this can be achieved by designing new routes to higher value chemicals, by using low hazardous solvents and avoiding the emission of high quantities of waste in an existing process. This Thesis mainly describes the progress towards the applications of dense carbon dioxide as a solvent for conducting the continuous flow reaction with photochemically generated singlet oxygen in a multistep synthesis process. This method helps to achieve a green and efficient way to produce versatile chemicals on a relatively large scale to meet the demand for the production of personalised pharmaceuticals. Chapter 1 provides the new challenges in the chemical and pharmaceutical industry and the applications of continuous flow photochemistry in dense carbon dioxide to meet the demand for the new challenges in Pharma, as well as singlet oxygen, including a review of its known reactions. A brief introduction to green chemistry is also included. Chapter 2 describes the batch and flow reactors that are used to carry out the high-pressure experiments discussed in this Thesis. The experimental results are discussed in three chapters: Chapter 3, Chapter 4, and Chapter 5. Chapter 3 describes the four versatile compounds, (1R, 3S)-cyclopent-4-ene-1,3-diol, 4-hydroxy-2-cyclopentenone, 4,5-epoxy-cis-2-pentenal, and furfuryl alcohol, were successfully synthesised from a single feedstock, cyclopentadiene, in the high-pressure continuous flow reactor on a relatively larger scale, which successfully combines the photochemistry with thermal chemistry. These experiments include the reaction conducted in dense carbon dioxide, in traditional solvents at atmospheric pressure and in a vortex reactor, with in-line analysis by FT-IR and NMR for the kinetics study of photo-oxidation of cyclopentadiene in supercritical carbon dioxide also being discussed in this chapter. Chapter 4 presents the photo-oxidation of fulvenes to synthesise the unsaturated caprolactone in a daisy-chained high-pressure flow reactor. This method provides a new route to introducing oxygen functional group into a hydrocarbon compound. The valorisation of these lactones by hydrogenation or photochemistry processes is also discussed. Chapter 5 describes the continuous flow synthesis of 1,2,4-trioxane chemicals in supercritical carbon dioxide. Dearomatisation of para-alkyl phenols with singlet oxygen is a key step in this synthesis followed by the cyclisation of peroxides with aldehydes with the help of solid acid catalysts. This Chapter also presents the multistep processes were adapted and optimised for the scale-up of a series of synthetic 1,2,4-trioxanes in the high-pressure continuous flow reactor. Finally, Chapter 6 summarises the work described in this Thesis and demonstrates the progress has been successfully achieved in a continuous high-pressure flow carbon dioxide reactor. A summary of potential research directions for further study is also discussed