XII PhD-Chem Day Bari, March 27- 28, 2015

A catalytic synthesis of paracetamol from limonene

Bill Cunningham, M. Hutchby, P.Plucinski, S. D. Bull

Doctoral Training Centre in Sustainable Chemical Technologies,
University of Bath, Bath BA2 7AY, UK

Typically pharmaceuticals are produced using inefficient batch reactors and wasteful stoichiometric
processes from unsustainable petrochemical feedstocks. Flow reactor technology, catalysis and
renewable feedstocks have been suggested as alternative means of pharmaceutical manufacture due
to numerous economic and sustainable advantages.

Terpene feedstocks are an untapped source of unsaturated carbon based frameworks that are
commonly found in essential oils of plants. They have diverse structures containing a wide range of
functional groups (i.e. hydroxyl, carboxyl or double bonds) that can provide broad reactivity, while
the presence of alkene motifs affords them similar properties to common petrochemical feedstocks.
This affords an opportunity to investigate terpenes as a source of drop-in renewable chemicals that
can complement bulk chemical precursors derived other biomass derived chemical platforms.

To demonstrate to the wider chemical community that useful chemical products can be synthesized
safely on a large scale using flow reactor technology and modern catalytic techniques we are
developing a synthesis of paracetamol from the renewable monoterpene feedstock limonene.

Excellent progress has been made with the development of successful methodology for the first
three steps. We have optimized a catalytic, solvent free epoxidation protocol using a tungsten based
POM catalyst. We have successfully shown that ring opening can occur catalytically and we have
also investigated the use of other hindered base species such as LDA and potassium tert-butoxide.
Investigations into ozonolysis have been conducted upon limonene oxide and limonene allylic
alcohol. These results, plus efforts to apply the catalytic epoxidation methodology to other terpene
substrates will be presented.

Figure 1: Proposed synthesis of green paracetamol

*Corresponding author: Bill Cunningham . e-mail address: w.cunningham@bath.ac.uk