The importance of solvent reorganisation in the effect of an ionic liquid on a unimolecular substitution processw Hon Man Yau, a Susan A. Barnes, b James M. Hook, c Tristan G. A. Youngs, d Anna K. Croft* b and Jason B. Harper* a Received (in Cambridge, UK) 28th March 2008, Accepted 30th April 2008 First published as an Advance Article on the web 9th June 2008 DOI: 10.1039/b805255g Temperature dependent rate studies demonstrate an enthalpic benefit and an entropic cost associated with the change in the rate of a unimolecular substitution process on addition of a high proportion of an ionic liquid, the latter effect being supported by molecular dynamics simulations. Ionic liquids have been touted as potential alternatives to environmentally damaging volatile organic solvents. 1 These salts, typically made up of a bulky organic cation and a charge diffuse anion, 2,3 are attractive as alternative solvents due to their negligible vapour pressures and the ability to ‘tune’ the properties of the solvent based on the modification of the component ions. 3,4 The major focus of research into the use of ionic liquids as solvents has been processes with industrial relevance. 5 Differ- ences in the rates and selectivities of the processes are often observed when compared with the corresponding reactions in molecular solvents, however, there are only limited reports detailing the origins of the changes. 6 z This contrasts with the extensive understanding of the effect on reaction outcome on changing from one molecular solvent to another. 7 We have developed a research programme that seeks to understand the origin of the effects of ionic liquids on organic processes. Our initial experimental studies in this area 8 have focused on the unimolecular substitution of the chloride 1 in systems containing different proportions of an ionic liquid, 1-butyl-3-methylimidazolium ([Bmim] + ) bis(trifluorometha- nesulfonyl)imide ([N(CF 3 SO 2 ) 2 ]  ) (Scheme 1). The effect de- monstrated for the substrate 1 was that there was an initial increase in the rate of reaction with ionic liquid concentration, followed by a subsequent decrease. A hypothesis that might account for the observed rate changes is that the addition of small amounts of ionic liquid acts to stabilise the transition state leading to the ion-pair intermediate. Upon further in- creasing the proportion of the ionic liquid, the magnitude of the interactions between components of the solution increases, meaning that the requirement of any solvent reorganisation would also increase. Described herein are studies to test this proposition. The methanolysis of the chloride 1 was observed as de- scribed previously 8 z in solutions containing either 0%, ca.12% or ca. 90% of the [Bmim][N(CF 3 SO 2 ) 2 ] by volume over a range of temperatures. These concentrations, which correspond to mole fractions of ionic liquid of w = 0, 0.02 and 0.50, respectively, were chosen as they represent neat molecu- lar solvent, the solvent mixture which previously showed the greatest rate for the reaction and the concentration of ionic liquid which gave a rate of reaction the same as for neat methanol. From the kinetic data obtained, Eyring plots 9 were generated and values for the activation parameters, DH z and DS z , were calculated (Table 1). The values for the activation parameters do not change, within the limits of experimental error, on addition of a small amount (0.02 mol fraction) of ionic liquid to the reaction mixture. On addition of large quantities of ionic liquid (0.50 mol fraction) there are dramatic changes in the activation parameters, even though at 313 K the rates of reactions at w = 0 and 0.50 ionic liquid are the same within error. 8 There is a significant decrease in the activation enthalpy, as is consistent with stabilisation of the incipient charges in the transition state. At the same time, there is a dramatic change in the activation entropy, indicating that there is a major increase in organisation on going to the transition state. Such a value suggests that there is significant reorganisation of the compo- nents of the solvent around the substrate as reaction occurs due to the interactions between the ions of the ionic liquid and the developing charges on the substrate.8 From the above discussion, there are opposing effects on the rate of reaction of the substrate 1 upon addition of ionic liquid Scheme 1 Nucleophilic substitution of the chloride 1 to give the ether 2, carried out in a mixture of alcohol and ionic liquid.y a School of Chemistry, University of New South Wales, Sydney, NSW, 2052, Australia. E-mail: j.harper@unsw.edu.au; Fax: +61 2 9385 6141; Tel: +61 2 9385 4692 b School of Chemistry, University of Wales Bangor, Bangor, Gwynedd, UK LL57 2UW. E-mail: a.k.croft@bangor.ac.uk; Fax: +44 1248 370528; Tel: +44 1248 382391 c Analytical Centre, University of New South Wales, Sydney, NSW, 2052, Australia d Atomistic Simulation Centre, School of Mathematics and Physics, Queen’s University, Belfast, UK BT7 1NN w Electronic supplementary information (ESI) available: Eyring plot for the data represented in Table 1, description of computational methodology for Fig. 1, probability distribution for the components of the ionic liquid around tert-butyl chloride, sample radial distribution functions to demonstrate ordering, analysis of literature data using bimolecular form of the Eyring equation. See DOI: 10.1039/b805255g 3576 | Chem. Commun., 2008, 3576–3578 This journal is  c The Royal Society of Chemistry 2008 COMMUNICATION www.rsc.org/chemcomm | ChemComm