Understanding how variation of the reagents affects ionic liquid solvent effects for substitution processes

Abstract

The work presented in this thesis has focused on deepening the understanding of ionic liquid solvent effects, particularly the importance of the nature of the reagents in substitution processes to allow rational exploitation of these solvent effects. The ionic liquid solvent effect on the reaction of triphenylphosphine with a range of electronically different electrophiles was investigated. The dependence of the rate constant on the proportion of ionic liquid in the reaction mixture was determined alongside temperature dependent kinetic studies to understand the microscopic interactions. The charge diffusivity of the leaving group affected the balance of ionic liquid interactions and variation of the electronics of the electrophile changed the nature of the transition state, observed both experimentally and computationally. Similar kinetic studies on the related substitution reaction between benzyl bromide and a series of triphenylpnicogens were conducted. The nucleophilic heteroatom was varied down group 15 to understand how the ionic liquid solvent effects changed as the nature of the nucleophile varied, the microscopic origins of these effects, and whether there was any trend in the solvent effects observed. Again, it was found that the more charge diffuse the heteroatom of the nucleophile, the more prevalent ionic liquid-transition state interactions were. The effect on ionic liquid solvent effects upon variation of the nucleophilic heteroatom in nucleophilic aromatic substitution processes was also considered. Kinetic studies were undertaken for reaction of 1-fluoro-4-nitrobenzene with 1-butylamine or 1-propanethiol. The trend in the rate constant as the solvent composition was varied changed with different heteroatoms; reaction of the nitrogen nucleophile was greatest at low proportions of the ionic liquid whereas reaction of the sulphur nucleophile was greater as the amount of ionic liquid increased. These data suggested the possibility for selection of the solvent mixture to control reaction outcome, which has been demonstrated in a practical synthetic setting. Overall, the work presented in this thesis broadens the body of knowledge of ionic liquid solvent effects for substitution processes. Such an understanding allows rational prediction of reaction outcome that may be exploited to improve the efficacy of this class of reactions in synthetic settings.