Elemental Fluorine for the Greener Synthesis of Life-Science Building Blocks

Abstract

Fluorinated organic compounds are increasingly important in many areas of our modern lives, especially in pharmaceutical and agrochemical applications where the incorporation of this element can have a major influence on biochemical properties. The introduction of the carbon-fluorine bond into such systems is typically carried out using well established multistep, nucleophilic fluorination processes that usually lead to large waste streams. Despite the availability of alternative electrophilic fluorination methods which have found several
applications on discovery scale, the direct transformation of C-H to C-F bonds on large scale is scarce. Elemental fluorine is the only electrophilic fluorinating reagent that is viable for manufacturing scale applications, but, in spite of the advances in this field in the past 25 years, there are only a handful of processes where it is used, most notably in the manufacturing of 5-fluorouracil.

In this thesis the direct fluorination of several industrially relevant organic systems was investigated with an aim to provide optimised, high yielding and scalable processes that could be compared with existing manufacturing methods using a green chemistry metrics package developed by the EU IMI Chem21 consortium.