Evaluating the application and limitations of bio-based solvents within organic synthesis

  • Kirsty Wilson

Student thesis: Doctoral Thesis

Abstract

The growing sustainability movement within the chemical industries endeavours to forge cleaner manufacturing processes which integrate the key principles of Green Chemistry.At the forefront of these initiatives are solvent replacement strategies, driven, in part, by increasingly stringent regulations surrounding the use of solvents of concern. A group of solvents which have fallen under particular scrutiny are polar aprotic solvents, such as DMF, NMP and DMAc. This solvent class is characterised by high polarity and superior solvating abilities, which has firmly established their use within synthetic organic and medicinal chemistry. However, they are also associated with reproductive toxicity and are regarded as teratogens. As such, their continued use within industry is becoming increasingly discouraged.Direct replacement of polar aprotics using existing solvents often fails and, as such, novel alternatives are required. In this regard, the use of biomass feedstocks in the development of new solvents is an expanding area within Green Chemistry which aims to minimise the dependence on petroleum-based chemicalsCyrene and dimethyl isosorbide (DMI) are two emerging solvents derived from cellulose. However, their application within organic chemistry is under explored and, as such, their use within industry is currently limited.This research programme aims to investigate the use of these alternative solvents in synthetic transformations commonly utilised within the context of drug discovery in the pharmaceutical industries. Robust and general condition sets have been developed and thoroughly evaluated in the application of Cyrene as a medium for the Sonogashira and Suzuki–Miyaura cross-couplings, and amide bond formation. In addition, the methodology developed for the Sonogashira cross-coupling was extended to enable the efficient synthesis of pharmaceutically relevant heterocycles. Cyrene exhibited a pronounced base sensitivity, the effect and limitations of which were studied within organic reactions.Additionally, the utilisation of DMI as an alternative solvent within prominent Pdcatalysed transformations was also evaluated. Accessible conditions for the Suzuki–Miyaura, Mizoroki–Heck and Sonogashira cross-coupling reactions were developed and the scope of the reactions investigated. Ultimately, it is hoped that exemplifying the use of these solvents within organic synthesis and highlighting their limitations will influence their uptake by industrial practitioners.
Date of Award1 Oct 2018
LanguageEnglish
Awarding Institution
  • University Of Strathclyde
SupervisorCraig Jamieson (Supervisor) & (Supervisor)

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