Investigation of Solvent Interactions Affecting Reactions Rates Through Electrostatic Interactions

This thesis describes the application of an electrostatic competition model used to predict and rationalise binding equilibria to predicting the solvent dependence of organic reactions. Initial studies explored the applicability of the model to charged species, which are central to many organic reactions, and were followed by specific representative examples of transesterification and addition reactions. Chapter one describes how solvent effects have been approached previously, leading up to descriptions of contemporary free energy relationships and the supramolecular electrostatic competition model utilised in this thesis. Chapter two presents the analysis of phenolates as exemplars of charged species relevant to organic reactions as nucleophiles and leaving groups. The independently measured values of α (a hydrogen bond donor parameter) and β (A hydrogen bond acceptor parameter) showed a weak correlation, and previous reports of compensating effects in homodimer formation do not seem well founded. The β values of phenolates are found to be in the range 11.5 to 14.3, but without a simple relation to pKa or substituent and strongly affected by the formation of an initial hydrogen bond. Chapter three examines the solvent dependence of a range of transesterification reactions between phenolates and aryl acetates using the α and β values obtained in chapter two. The solvent dependencies of the reactions are dominated by interactions with the ground state phenolates, and the equilibirum constant for the reaction also shows a related dependence on the hydrogen bond donor properties of the solvent. Model systems which introduced intramolecular hydrogen bond donors were partly successful in demonstrating the impact of different interactions between the solvent and the nucleophile or electrophile. Chapter four expands the approach to explore an addition reaction, and it is shown that both nucleophile and electrophile are affected by specific solvent properties which can be quantified. This leads to the observation that solvent mixtures show the lowest reactivity for the addition reaction, and contrasts with previous assumptions in quantifying electrophilicity in particular. The different impacts of the solvent components are used to control the reactivity of a common nucleophile with two electrophiles in a rationale manner, holding out the prospect that binary solvent mixtures can be used to direct sites of reaction. Chapter five presents the general conclusions of the work, noting the success of predicting changes in reactivity based on independently measured solvent parameters that only quantify hydrogen bond donating and accepting properties, and chapter 6 provides the experimental details of the work carried out.