There is currently much interest in developing biorenewable alternatives to the multitude of bulk and fine chemicals required by a modern society that are currently sourced from non-renewable petroleum sources. However many of the biomass sources that have been considered as replacement chemical feedstocks for oil such as cellulosic materials or fatty acids are highly oxygenated and are not well suited to constructing the aromatic rings present in many drug molecules. Terpenes, on the other hand, are an abundant class of biomass derived hydrocarbons that are deoxygenated and amenable to aromatisation. Monoterpenes in particular can be easily separated from aqueous environments and can potentially be upgraded into a range of commodity, fine chemicals and drug molecules; complimenting the other biomass chemical sources. Epoxidation is an especially useful transformation for the formation of important intermediates in the synthesis of fine and bulk chemicals such as pharmaceuticals and polymers. We have optimized a selective, solvent free epoxidation process based upon a tungsten polyoxometalate catalyst that works for a broad range of commonly available terpenes, including crude sulphate turpentine, having expanded its scope and developed an optimal protocol that enables epoxidation in shorter reaction times, with fewer additives, at milder temperatures and without the need for undesirable solvents compared to previous epoxidation protocols. We have also investigated various other catalytic methods to selectively epoxidize the other alkene substitution patterns present in a wide variety of terpene substrates that enables access to a number of key terpene bis-epoxides and this is discussed in chapter 2.We have also combined the optimal catalytic protocol with flow engineering, to develop a sustainable, catalytic flow epoxidation protocol that is suitable for both laboratory and industrial scale synthesis of biomass derived terpene epoxides. In particular, targeting the replacement of stoichiometric and expensive reagents and environmentally polluting solvents with green H2O2 and solvent free conditions and this is discussed in chapter 3.This catalytic epoxidation protocol was then adapted to enable the sustainable production of terpene and non-terpenoid anti-diols without the need for toxic co-solvents, corrosive acid or time consuming neutralisation steps. These anti-diol substrates are promising monomers for polymerisation and have other important applications such and this is discussed in chapter 4.Chapter 5 discusses the development of synthetic routes to sustainable paracetamol via the pharmaceutical intermediate 4-hydroxyacetophenone that is economically comparable with current petrochemical routes. Chapter 6 discusses the development of a number of selective synthetic routes to a number of isomers of the mosquito repellent, p-menthane-3,8-diol, with a novel all-cis isomer, made with excellent selectivity, that has the potential to have enhanced repellent properties.Ultimately, this PhD concerns the development of protocols for the conversion of terpene feedstocks into value-added chemicals that will be used as precursors for the synthesis of commodity drug targets such as paracetamol (pain relief); for the synthesis of renewable polymer epoxide and diol monomers and for the synthesis of biologically active molecules such as p-menthane-3,8-diol (insect repellent).
|Date of Award||20 Sep 2018|
|Supervisor||Steven Bull (Supervisor) & Pawel Plucinski (Supervisor)|