Understanding and predicting the outcomes of organic processes in ionic liquids.

Presented herein are a series of studies designed to increase the fundamental understanding of the effects that ionic liquid solvents have on the outcome of organic reactions. There is particular focus on understanding the microscopic interactions that exist between an ionic liquid and species along the reaction coordinate, and how the magnitude of these different interactions affect reaction outcome. The reaction between 3-chloropyridine and bromodiphenylmethane, which proceeds through both unimolecular and bimolecular substitution mechanisms concurrently, was examined. The rate constant for each pathway was determined in a number of mixtures of an ionic liquid and acetonitrile, demonstrating that the rate constant of each mechanism is affected differently as the mole fraction of ionic liquid in the reaction mixture is varied. Temperature-dependent kinetic studies indicated that the marked increase in the rate constant for the unimolecular substitution pathway was due to favourable interactions between the ionic liquid and the incipient charges in the transition state. Further, the importance of considering the magnitude of this ionic liquid – transition state interaction was demonstrated, and was shown to be essential in determining the effect of an ionic liquid solvent on the rate constant of a carbocation forming process. The effect of changing the component ions of the ionic liquid was investigated using the related bimolecular substitution reaction between benzyl bromide and pyridine, focusing on the effect of varying the anion of the ionic liquid solvent. Through a series of temperature-dependent kinetic analyses it was demonstrated that for most of the ionic liquids considered the increased rate constant of this process, relative to acetonitrile, was due to favourable interactions between the ionic liquid cation and the nucleophile pyridine. While a general anion effect was demonstrated, there were limited trends in the activation parameters. The effects of changing the constituent ions of the ionic liquid solvent were extensively investigated on the condensation reaction between either benzaldehyde or 4-methoxybenzaldehyde and hexan-1-amine; a number of ionic liquids featuring different cationic and anionic components were considered. Through a series of temperature-dependent kinetic analyses it was revealed that by changing the component ions of the ionic liquid solvent the extent of cation – nucleophile interaction could be controlled, resulting in systematic changes in the activation parameters. The less predictable changes in the rate constant on varying the constituent ions highlighted the difficulty in predicting the delicate balance between the competing enthalpic and entropic effects. By examining how the rate constant of this process was affected when the proportion of each ionic liquid in the reaction mixture was varied it was shown that the main changes in the rate constant occur at lower mole fractions of ionic liquid. The condensation reaction between a number of substituted benzaldehydes and hexan-1-amine was then investigated in mixtures of an ionic liquid and acetonitrile. This allowed the kinetics of each part of this two-step addition-elimination mechanism to be analysed across a number of mole fractions of ionic liquid in the reaction mixture. Further, using the Hammett relationship, it was demonstrated that the solvent effects observed in an ionic liquid are more affected by changes in the extent of charge development in the transition state than acetonitrile. Generally, the changes in the extent of transition state solvation when the substituent was varied, accounted for the different substituent effects observed when the solvent composition was changed. In order to gain a better understanding of how the properties of the solvent change when different mixtures of an ionic liquid and acetonitrile are used, the bulk structure of the different mixtures were investigated using small and wide angle X-ray scattering experiments. These studies indicated that the main changes in the structuring of the mixtures considered occurred at low mole fractions of ionic liquid in the mixture. A series of NMR diffusion experiments on similar systems revealed that the main changes in the self-diffusion coefficients of the components of ionic liquid / acetonitrile mixtures also occurred on addition of small amounts of ionic liquid to the mixture. Additionally, it was shown that specific interactions between components of these mixtures affected the self-diffusion coefficient of acetonitrile across the different solvent compositions. Analysis of the self-diffusion coefficients of a series of solutes dissolved in these ionic liquid / acetonitrile mixtures demonstrated that specific interactions between the ionic liquid and a nitrogen containing solute are greater than that with analogous oxygen containing solutes. Lastly, the effect of a number of molecular solvents and an ionic liquid on the rate constant of some simple pericyclic rearrangements was examined. For the Cope rearrangement of 3-phenyl-1,5-hexadiene it was found that the rearrangement proceeded much faster in the ionic liquid than in the molecular solvents. After considering many possible sources of these effects, it was proposed that solvophobic effects are responsible for the changes in the rate constant observed in the different solvents. Kinetic analyses on the Claisen rearrangement of allyl vinyl ether suggested that a similar solvophobic effect contributed to the changes in the rate constant observed in the different solvents. However, for this reaction, stabilisation of the incipient charges in the transition state was shown to be important, with the rate enhancement observed in the ionic liquid also due to enhanced transition state solvation, relative to the molecular solvents. Temperature-dependent kinetic analyses demonstrated that the ionic liquid behaves like a polar aprotic solvent, rather than a polar protic solvent, indicating that the microscopic interactions between the ionic liquid and species along the reaction coordinate are coulombic in nature, rather than directional, hydrogen bonding interactions