RESUMEN
The nucleofugality of bromide was measured in solvent mixtures containing ionic liquids. The solvolysis rate constants of the bromides of well-defined electrofuges were determined in mixtures containing different proportions of 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide in ethanol. Temperature-dependent kinetic studies allowed an explanation of the observed solvent effects in different mixtures in terms of interactions in solution. Using the solvolysis data, the nucleofugality of bromide in these systems was determined. Likewise, nucleofugality data for bromide were determined in mixtures containing high proportions of seven further ionic liquids. These data allowed quantification of the effects of both varying the amount of ionic liquid and the nature of ionic liquid components on the nucleofugality of bromide. Importantly, ionic liquid mixtures were shown to affect the nucleofugality in a manner similar to chloride, providing a method for predicting the effects of ionic liquids on other electrofuges. Further, the ionic liquids were shown to move the transition state earlier along the reaction coordinate, meaning that there is less charge development in the transition state.
RESUMEN
The nucleofugality of chloride has been measured in solvent mixtures containing ionic liquids for the first time, allowing reactivity in these solvents to be put in context with molecular solvents. Using well-described electrofuges, solvolysis rate constants were determined in mixtures containing different proportions of ethanol and the ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide; the different solvent effects observed as the mixture changed could be explained using interactions of the ionic liquid with species along the reaction coordinate, determined using temperature dependent kinetic studies. The solvolysis data allowed determination of the nucleofugality of chloride in these mixtures, which varied with the proportion of salt in the reaction mixture, demonstrating quantitatively the importance of the amount of ionic liquid in the reaction mixture in determining reaction outcome. Nucleofugality data for chloride were determined in seven further ionic liquids, with the reactivity shown to vary over more than an order of magnitude. This outcome illustrates that the components of the ionic liquid are critical in determining reaction outcome. Overall, this work quantitatively extends the understanding of solvent effects in ionic liquids and demonstrates the potential for such information to be used to rationally select an ionic liquid to control reaction outcome.
RESUMEN
A homologous series of biscationic ionic liquids based on two imidazolium centres, separated by alkyl chains of varying length, were examined as solvents for a bimolecular substitution reaction across a range of proportions of ionic liquid in the reaction mixture. Their effects on the rate constant of the process were compared to monocationic ionic liquids, with generally a greater rate constant increase observed. Importantly, it was observed that the magnitude of the effect was shown to vary with the length of the linking chain. To investigate the origins of these solvent effects, temperature dependent kinetic studies were performed to obtain activation parameters at high and low mole fractions of ionic liquid. The observed activation parameters showed the rate constant enhancement was due to interaction of the ionic liquid with the starting materials, consistent with previous results. Significantly, however, these data also showed that the balance of enthalpic and entropic effects varied dramatically with the length of the alkyl chain between the cationic centres.
RESUMEN
The reactions of an acetobromogalactose in mixtures of methanol and one of seven different ionic liquids with varying constituent ions were studied. In general, small amounts of ionic liquid in the reaction mixture led to increases in the rate constant compared to methanol, whilst large amounts of ionic liquid led to decreases in the rate constant; this outcome differs significantly from previous reactions proceeding through this mechansim. Temperature dependent kinetic studies indicated that the dominant interaction driving these changes was between the ionic liquid and the transition state of the process. Through considering solvent parameters of ionic liquids, a relationship was found between the changes in the rate constant and both the hydrogen bond accepting ability and polarisability of the solvent, indicating that the interactions affecting reaction outcome are both specific and non-specific in nature; once more, these interactions were different to those observed in previous similar reactions. By changing the amount of ionic liquid in the reaction mixture, additional products not seen in the molecular solvent case were observed, the ratios of which are dependent on the anion of the ionic liquid and the proportion of ionic liquid in the reaction mixture. This demonstrates the importance of considering solvent effects on both the rate and product determining steps and the potential application of such changes is discussed.
RESUMEN
Rate constants for a bimolecular nucleophilic substitution (SN2) process in a range of ionic liquids are correlated with calculated parameters associated with the charge localisation on the cation of the ionic liquid (including the molecular electrostatic potential). Simple linear regression models proved effective, though the interdependency of the descriptors needs to be taken into account when considering generality. A series of ionic liquids were then prepared and evaluated as solvents for the same process; this data set was rationally chosen to incorporate homologous series (to evaluate systematic variation) and functionalities not available in the original data set. These new data were used to evaluate and refine the original models, which were expanded to include simple artificial neural networks. Along with showing the importance of an appropriate data set and the perils of overfitting, the work demonstrates that such models can be used to reliably predict ionic liquid solvent effects on an organic process, within the limits of the data set.
RESUMEN
A unimolecular nucleophilic substitution reaction that proceeds through a xanthylium carbocation was studied in seven ionic liquid solvents. It was found that the general trend in the rate constant with changing proportion of ionic liquid in the reaction mixture was different to that seen for other unimolecular processes, with the rate constant increasing as more ionic liquid was added to the reaction mixture. A significant correlation was found between the natural logarithm of the rate constant and a combination of the Kamlet-Taft solvent parameters. This relationship indicated that the principal interaction involved hydrogen bonding between the ionic liquid and some species along the reaction coordinate. Further, this correlation enables prediction of the effects that other ionic liquids will have on this, and other, reactions that proceed through a similar intermediate.
RESUMEN
A unimolecular substitution process was studied in five different ionic liquids, with systematic variation of either the cation or anion, in order to determine the factors leading to the increase in the rate constant for the process relative to acetonitrile. It was found that both components of the ionic liquid, and the proportion of the salt in the reaction mixture, affect the rate constant. Activation parameters determined for the process suggest that there is a balance between interactions of the components of the ionic liquid with both starting material and transition state. A correlation was found between the rate constant and a combination of Kamlet-Taft solvent parameters; with the polarisability of the solvent being the most significant factor. As this reaction proceeds through both unimolecular and bimolecular pathways, competition experiments determined that the unimolecular pathway for the reaction can be favoured using small amounts of ionic liquid in the reaction mixture, demonstrating the potential to control reaction mechanisms using ionic liquids.
RESUMEN
The effects of solvate ionic liquids as solvents have been considered for two substitution processes where the solvent effects of typical ionic liquids have been extensively investigated previously; the bimolecular nucleophilic substitution (SN2) reaction between pyridine and benzyl bromide and the nucleophilic aromatic substitution (SNAr) reaction between ethanol and 1-fluoro-2,4-dinitrobenzene. It was found that use of solvate ionic liquids gave rise to similar trends in the activation parameters for both substitution processes as typical ionic liquids, implying the microscopic interactions responsible for the effects were the same. However, different effects on the rate constants compared to typical ionic liquids were observed due to the changes in the balance of enthalpic and entropic contributions to the observed rate constants. From these data it is clear that the reaction outcome for both of these substitution reactions fall within the 'predictive framework' established in previous studies with a cautionary tale or two of their own to add to the general knowledge of ionic liquid solvent effects for these processes, particularly with respect to potential reactivity of the solvate ionic liquids themselves.
RESUMEN
A variety of ionic liquids, each containing the same cation but a different anion, were examined as solvents for a nucleophilic aromatic substitution reaction. Varying the proportion of ionic liquid was found to increase the rate constant as the mole fraction of ionic liquid increased demonstrating that the reaction outcome could be controlled through varying the ionic liquid. The solvent effects were correlated with the hydrogen bond accepting ability (ß) of the ionic liquid anion allowing for qualitative prediction of the effect of changing this component of the solute. To determine the microscopic origins of the solvent effects, activation parameters were determined through temperature-dependent kinetic analyses and shown to be consistent with previous studies. With the knowledge of the microscopic interactions in solution, an ionic liquid was rationally chosen to maximise rate enhancement demonstrating that an ionic solvent can be selected to control reaction outcome for this reaction type.
RESUMEN
Correction for 'Rationalising the effects of ionic liquids on a nucleophilic aromatic substitution reaction' by Rebecca R. Hawker et al., Org. Biomol. Chem., 2017, 15, 6433-6440.
RESUMEN
The nucleophilic aromatic substitution reaction between 1-fluoro-2,4-dinitrobenzene and ethanol was examined in a series of ionic liquids across a range of mole fractions. Temperature-dependent kinetic analyses were undertaken to determine the activation parameters for this reaction at the highest mole fraction. As the mole fraction of ionic liquid was increased, the rate constant of the reaction also increased, however the microscopic origin of the rate enhancement was shown to be different between different ionic liquids and also between different solvent compositions. These results indicate a balance between microscopic interactions that result in the observed solvent effects and a qualitative method for analysing such interactions is introduced.
RESUMEN
The reaction of bromodiphenylmethane and 3-chloropyridine, which proceeds concurrently through both unimolecular and bimolecular mechanisms, was examined in mixtures of acetonitrile and an ionic liquid. As predicted, the bimolecular rate constant (k2) gradually increased as the amount of ionic liquid in the reaction mixture increased, as a result of a minor enthalpic cost offset by a more significant entropic benefit. Addition of an ionic liquid had a substantial effect on the unimolecular rate constant (k1) of the reaction, with at least a 5-fold rate enhancement relative to acetonitrile, which was found to be due to a significant decrease in the enthalpy of activation, partially offset by the associated decrease in the entropy of activation. This is in contrast to the effects seen previously for aliphatic carbocation formation, where the entropic cost dominated reaction outcome. This change is attributed to a lessened ionic liquid-transition state interaction, as the incipient charges in the transition state were delocalized across the neighbouring π systems. By varying the mole fraction of ionic liquid in the reaction mixture the ratio between k1 and k2 could be altered, highlighting the potential to use ionic liquids to control which pathway a reaction proceeds through.
RESUMEN
The reaction of a series of substituted benzaldehydes with hexylamine was examined in acetonitrile and an ionic liquid. In acetonitrile, as the electron withdrawing nature of the substituent increases, the overall addition-elimination process becomes faster as does the build-up of the aminol intermediate. Under equivalent conditions in an ionic liquid, less intermediate build up is observed, and the effect on the rate on varying the substituent is different to that in acetonitrile. Extensive kinetic analysis shows that the ionic liquid solvent increases the rate constant of all steps of the reaction, resulting in faster product formation relative to acetonitrile; these effects increase with the proportion of ionic liquid in the reaction mixture. Differences in the equilibrium position of the addition step in the ionic liquid were found to account for both the decrease in intermediate build up relative to acetonitrile, as well as the differing trend in the overall rate of product formation as the substituent was changed. The microscopic origins of these ionic liquid effects were probed through temperature dependent analyses, highlighting the subtle balance of interactions between the ionic liquid and species along the reaction coordinate, particularly the importance of charge development in the transition state.
RESUMEN
A series of ionic liquids containing anions of differing coordination strength were investigated as solvents for the condensation reaction of an alkyl amine and an aromatic aldehyde. As predicted, the rate constant of the process was found to increase with the proportion of the ionic liquid in the reaction mixture. Temperature-dependent kinetic analyses demonstrated that by varying the ability of the anion to interact with the cation the magnitude of both the enthalpy and entropy of activation could be controlled in a predictable manner, with the activation parameters being linearly dependent on the ionic liquid basicity. Interestingly, the unexpected trend in the rate constants observed when altering the anion of the ionic liquid highlighted the presence of more subtle secondary microscopic interactions involving the anion, further emphasizing the fragility of the enthalpy - entropy balance.
RESUMEN
The effects of a series of ionic liquids, with systematic variations in the cation, on the condensation of an alkyl amine with an aromatic aldehyde were investigated, and the outcomes compared with those predicted based on related reactions. The addition of ionic liquids increased the observed rate constant; the mole fraction dependence of this increase was qualitatively consistent with predictions. Temperature-dependent kinetic analyses were used to demonstrate that the microscopic origins of the effects were as forecast, though the relative weighting of enthalpic and entropic contributions was dependent on the salt used.
RESUMEN
The reaction of a chlorobenzene in mixtures containing ethanol and eight different ionic liquids was investigated in order to understand the effects of varying proportions and constituent ions of an ionic liquid on the rate constant of the process. The results were found to be generally consistent with previously studied reactions of the same type, with small proportions of an ionic liquid resulting in a rate constant increase compared to ethanol and large proportions causing a rate constant decrease. Temperature dependent kinetic studies were used to interpret the changes in reaction outcome, particularly noting an entropic cost on moving to high proportions of ionic liquid, consistent with organisation of solvent around the transition state. While attempts to use empirical solvent parameters to correlate outcome with the ionic liquid used were unsuccessful, use of recently acquired nucleofugality data for chloride and estimations for the electrofuge allowed for excellent prediction of the effects of ionic liquids, with rate constants quantitatively predicted in systems containing both different proportions of ionic liquid (mean absolute error (MAE) log(k1) = 0.11) and different ionic liquids (MAE log(k1) = 0.33). Importantly, this demonstrates the ready application of these quantitative reactivity parameters.
RESUMEN
Nucleophilic aromatic substitution (SN Ar) reactions of 1-fluoro-4-nitrobenzene using similar nitrogen and sulfur nucleophiles were studied through extensive kinetic analysis in mixtures containing ionic liquids. The interactions of the ionic liquid components with the starting materials and transition state for each process were investigated in an attempt to construct a broad predictive framework for how ionic liquids affect reaction outcome. It was found that, based on the activation parameters, the microscopic interactions and thus the ionic liquid solvent effect were different for each of the nucleophiles considered. The results from this study suggest that it may be possible to rationally select a given ionic liquid mixture to selectively control reaction outcome of an SN Ar reaction where multiple nucleophiles are present.
RESUMEN
A series of nucleophiles containing Group 15 nucleophilic heteroatoms has been used to expand and develop the current understanding of ionic liquid solvent effects on bimolecular nucleophilic substitution processes. It was found that when using arsenic-, antimony- and bismuth-based nucleophiles, rate constant enhancement was observed for all solvent compositions containing ionic liquids. This rate constant enhancement was driven by ionic liquid/transition state interactions, which contrasts with previous studies on earlier Group 15 nucleophiles. This study provides a holistic understanding and augments the predictive framework for the effects of ionic liquids on bimolecular nucleophilic substitution processes, with the potential for these periodic trends to be broadly applied.
RESUMEN
A range of ionic liquids was examined as solvents for a substitution reaction. They were chosen through rationally varying the ionic liquid cation in order to enhance the rate constant. Access to charge and electron-withdrawing substituents benefitted rate enhancement, allowing ionic liquids to be rationally selected to control reaction outcome.
RESUMEN
Bimolecular nucleophilic substitution reactions between triphenylphosphine and benzylic electrophiles have been examined in an ionic liquid to probe interactions with species along the reaction coordinate. Trends in the rate constant were found on both varying the leaving group and the electronic nature of the aromatic ring. In all the cases considered, interactions between the components of the ionic liquid and the transition state were shown to be more significant in determining reaction outcome than previously observed for this class of reaction. This demonstrates the importance of considering interactions of the ionic liquid components with all species along the reaction coordinate when investigating the origin of ionic liquid solvent effects, along with how such effects might be exploited.