The effects of an ionic liquid on unimolecular substitution processes: The importance of the extent of transition state solvation

Article abstract of DOI:10.1039/c5ob02598b

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 k₁and k₂could be altered, highlighting the potential to use ionic liquids to control which pathway a reaction proceeds through.

Full text of DOI:10.1039/c5ob02598b

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The effects of an ionic liquid on unimolecular
substitution processes: the importance of the
Cite this: DOI: 10.1039/c5ob02598b
extent of transition state solvation†
Sinead T. Keaveney, Benjamin P. White, Ronald S. Haines and Jason B. Harper*
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–tran-
sition state interaction, as the incipient charges in the transition state were delocalized across the neigh-
bouring 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.
Received 18th December 2015,
Accepted 21st January 2016
DOI: 10.1039/c5ob02598b
www.rsc.org/obc
interactions determine the observed ionic liquid solvent
effects. While a number of interactions have now been identi-
Introduction
In recent years ionic liquids (salts that are molten below fied, it has become apparent that these interactions contribute
100 °C) have received much attention in areas including in opposing ways to the change in activation energy on intro-
electrochemistry,1–4 biomass processing1,5–7 and, in particular, ducing an ionic liquid solvent. Further, the magnitude of
as alternative solvents for organic reactions.8,9 Utilising ionic these interactions have a significant impact on the overall
liquids as solvents for organic processes is attractive due to ionic liquid effect observed.
their low flammability and vapour pressure,10–13 the ability to
This limitation is best exemplified by a number of studies
fine tune their physical and chemical properties and the on the effect of an ionic liquid solvent on bimolecular nucleo-
potential to achieve reaction outcomes different to those in philic substitution (SN2) processes, where it has been found
typical molecular solvents.8,9
There has been
that there is an interaction between the ionic liquid cation and
and the nucleophile. Generally, for a reaction featuring a charged
much
experimental8,9
computational14–18 work aimed at understanding the inter- nucleophile19–22 (or electrophile23) the strong electrostatic
actions that exist between the component ions of ionic liquids interactions between the ionic liquid components and the
and the species along the reaction coordinate, and how these charged reagent resulted in a significantly increased activation
enthalpy, relative to non-polar and polar aprotic molecular
solvents, reducing the rate constant of the reaction. For SN2
School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia.
processes involving neutral reagents, interaction between the
E-mail: j.harper@unsw.edu.au; Fax: +61 2 9385 6141; Tel: +61 2 9385 4692
ionic liquid cation and the reactive centre on the nucleophile
†Electronic supplementary information (ESI) available: Details of the prep-
also results in a significant enthalpic cost, relative to polar
arations of the ionic liquid 1 and bromodiphenylmethane 5; discussion on iden-
aprotic solvents.24–29 Yet, importantly, for these cases there
tifying a suitable reaction to analyse for this study; experimental details of the
kinetics analyses and the processing of the obtained 1H NMR data; the exact
was an increased rate constant in the ionic liquid solvent.
compositions of all the stock solutions prepared; nucleophile dependent rate
This change is likely due to differences in the strength of
constant data, including the data on which Fig. 1 and 3 are based; mole fraction
the ionic liquid–reagent interaction, and hence the magnitude
dependent rate constant data on which Fig. 2 and 5 are based; temperature
of the associated enthalpic cost, as well as differences
dependent kinetic data (shown in Fig. 4 and 6) from which the activation para-
in the extent of transition state solvation by the ionic liquid
meters shown in Tables 1 and 2 are derived. See DOI: 10.1039/c5ob02598b
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components resulting in differences in the entropy of
activation.
This idea is further reinforced by studies of the effect of
changing the nature of the cation30 and anion31 of the ionic
liquid solvent for a condensation reaction, which allowed the
strength of the cation – nucleophile interaction to be varied.
Changing the magnitude of this interaction resulted in
systematic changes in the activation enthalpy and entropy, but
changes in the overall activation energy (and hence rate con-
stant) were less predictable.30,31 Clearly, identifying the main
interactions between the ionic liquid components and species
along the reaction coordinate is possible, but predicting how
the differing strengths of these interactions affect the rate
constant still remains elusive.
The importance of such an understanding has also become
apparent for unimolecular nucleophilic substitution (SN1)
reactions, as these reactions involve carbocation formation
and hence feature considerable charge separation in the tran-
sition state.32,33 For an aliphatic substrate, use of mixtures
containing high proportions of the ionic liquid 1-butyl-
Scheme 2 The reaction between bromodiphenylmethane 5 and either
3-chloropyridine 6a, 2-chloropyridine 6b or pyridine 6c to produce the
salts 7a–c, respectively.
significant entropic cost associated with the use of an ionic
liquid. That is, the difference in reaction outcome for these
two cases arises from differing strengths of an interaction that
is of the same nature. Currently this proposal remains conjec-
ture as activation parameters for such an SN1 reaction, involv-
ing a more charge delocalized transition state, are yet to be
determined in an ionic liquid solvent.
3-methylimidazolium
bis(trifluoromethanesulfonyl)imide
The main conclusion from the previous work described
above is that to allow for predictions of the overall ionic liquid
solvent effect to be made, it is essential to have a thorough
understanding of both the interactions that exist between the
ionic liquid and species along the reaction coordinate, and the
relative strengths of these different interactions. To contribute
to this developing understanding, this manuscript describes
the effect of the ionic liquid [Bmim][N(SO2CF3)2] 1 on both the
rate constant and activation parameters of the reaction
between bromodiphenylmethane 5 and 3-chloropyridne 6a
(Scheme 2), relative to acetonitrile. This reaction proceeds
through both a unimolecular pathway involving formation of a
benzylic carbocation, with the transition state leading to this
carbocation involving an extent of charge delocalisation across
the π systems,33,39 and a bimolecular pathway. Menschutkin
reactions similar to the latter pathway between pyridine 6c
and benzyl halides have been extensively studied in ionic
liquids24–27,38,40 providing a further basis for comparison with
previous work. It was predicted that the effect of the ionic
liquid on the bimolecular reaction would be of comparable
magnitude and have the same microscopic origins as has been
described previously.24–27,35,39
([Bmim][N(SO2CF3)2], 1) resulted in a decreased rate constant
relative to methanol (Scheme 1).34,35 Detailed kinetic studies
showed that this was due to the significant increase in solvent
ordering about the relatively charge-separated transition state
(which is enthalpically favourable, but has a more significant
entropic cost).35 A decrease in k1 for adamantyl carbocation
formation was also seen in ionic liquid solvents, relative to
polar protic solvents.36
Conversely, for SN1 processes that involve carbocation for-
mation at the benzylic position (resulting in delocalisation of
the net positive charge across the neighbouring π systems),
both experimental37 and kinetic38 studies have found that
there is an increase in the rate of reaction in ionic liquids
relative to polar aprotic solvents. It could be speculated that
this is due to a lessened extent of solvation by the ionic liquid
about the more charge delocalized transition state, relative to
the aliphatic case described above; this would result is a less
By investigating the unimolecular reaction we hope to gain
a better understanding of how the magnitude of the ionic
liquid–transition state interaction affects the ionic liquid
solvent effect. The overarching aim of this work is to continue
developing our understanding of ionic liquid solvent effects so
that it is possible to predict the effect an ionic liquid will have
on the rate constant of a process, based on an understanding
of the magnitude of the solvent–reagent interactions along the
reaction coordinate.
Experimental
Scheme 1 The unimolecular substitution reaction between the linalool
derivative 2 and methanol, which proceeds through the intermediate
carbocation 3; this has been investigated in the ionic liquid 1 and
methanol.34,35
3-Chloropyridine 6a, 2-chloropyridine 6b and pyridine 6c were
all commercially available, and were distilled under reduced
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pressure and stored over 4 Å molecular sieves at 253 K prior to [Bmim][N(SO2CF3)2] 1 (χIL) and acetonitrile at 47.5 °C (as this
use. Analytical grade deuterated acetonitrile was dried over 3 Å temperature resulted in the reaction progressing at a con-
molecular sieves for at least 48 h before use. Bromodiphenyl- venient rate across the different solvent compositions). For
methane 5 was synthesised by reacting benzhydrol with phos- each mole fraction the reaction was conducted in triplicate at
phorus(III) bromide to give the compound of interest 5. The four different nucleophile concentrations allowing k1 and k2 to
ionic liquid [Bmim][N(CF3SO2)2] 1 was prepared according to be determined across
a range of solvent compositions
literature methods,41,42 where 1-methylimidazole was treated (eqn (S1),† an exemplar plot for this type of study is shown in
with butyl bromide to afford the intermediate bromide salt, Fig. 1).
followed by salt metathesis with lithium bis(trifluoromethane-
Discussion is first going to focus on the bimolecular mech-
sulfonyl)imide to give [Bmim][N(CF3SO2)2] 1. The ionic liquid anism, as this data can be readily compared with previous
1 was dried at 70 °C under reduced pressure immediately work on SN2 processes.24–27,35,39 As the amount of the ionic
before use, and was found to have <200 ppm water using Karl liquid 1 in the reaction mixture was increased it was found
Fischer titration methodology and contained <0.1 mol% that there was a gradual increase in k2 (Fig. 2), with the main
residual halide by ion chromatography. The details of all prep- changes in k2 occurring between χIL = 0 and 0.3. The rate con-
arations can be found in the ESI.†
stant then reached a plateau at higher mole fractions, with a
Kinetic analyses were carried out in solutions containing
the electrophile 5 (ca. 0.01 mol L−1) and the nucleophile of
interest (at either ca. 0.1, 0.2, 0.3 or 0.4 mol L−1, see ESI† for
further details) at a given temperature and specific mole frac-
tion of the ionic liquid, with the remaining solvent being
made up by deuterated acetonitrile. Reaction progress was
monitored using 1H NMR spectroscopy, and the pseudo-first
order rate constant (kobs) for the reaction in each solvent
mixture was calculated using integrations of the signal corres-
ponding to the benzylic proton in the electrophile 5 at
δ ca. 6.5. This subsequently allowed determination of the
unimolecular and bimolecular rate constants (k1 and k2,
respectively). All experimental details for the kinetic analyses
can be found in the ESI.†
Where appropriate, the activation enthalpy and entropy
were then determined through fitting the obtained rate con-
stants to either the unimolecular or bimolecular Eyring
equations.24,43 A complete description of this method, along
with tables containing the exact mole fractions of ionic liquid
1 used in the reaction mixture, the nucleophile concentrations,
temperature and rate constants for all the systems described
below can be found in the ESI.†
Fig. 1 The dependence of the observed pseudo first order rate con-
stant (kobs) on the concentration of the nucleophile 3-chloropyridine 6a,
for the reaction between the bromide 5 and the pyridine 6a at 47.5 °C in
either acetonitrile (black) or mixtures containing [Bmim][N(SO2CF3)2] 1;
χIL = 0.1 (green) and χIL = 0.88 (red). Values for k1 and k2 were deter-
mined from the intercept and slope, respectively, for each case.
Results and discussion
As discussed in the Introduction, the reaction outlined in
Scheme 2 proceeds concurrently through unimolecular and
bimolecular pathways. It should be noted that it was necessary
to choose a suitable combination of reagents to ensure that
there was a significant contribution from the unimolecular
process to the overall reaction profile, the details of which are
included in the ESI.†
Initially the effect of changing the amount of the ionic
liquid [Bmim][N(SO2CF3)2] 1 in the reaction mixture with
acetonitrile was investigated; ionic liquids are often used in
mixtures with other solvents, so it is important to know
how the rate constant is affected by changing the mole fraction
of ionic liquid in the reaction mixture. The reaction of bromo-
diphenylmethane 5 and 3-chloropyridine 6a was conducted
Fig. 2 The dependence of the bimolecular rate constant (k2) of the
reaction between 3-chloropyridine 6a and bromodiphenylmethane 5 as
the mole fraction of [Bmim][N(SO2CF3)2] 1 in acetonitrile was increased,
at 47.5 °C. Error bars represent the uncertainties from the linear
at eight different mole fractions of the ionic liquid regression from which k2 was determined.
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maximum increase in k2, relative to acetonitrile, of ca. 7-fold
occurring between χIL = 0.5 and 0.88. This trend, as well as the
magnitude of the rate enhancement when using the ionic
liquid 1 relative to acetonitrile, was expected based on previous
work examining SN224–27,38,40 and addition-elimination pro-
cesses,30,31,44 in which the rate-determining step of the pro-
cesses also involved nucleophilic attack by
a nitrogen-
containing nucleophile. In this previous work the mole frac-
tion dependence plot followed a similar trend, and the overall
rate enhancement ranged from ca. 4 to ca. 8, depending on the
reaction and the temperature used. In this current work, the
comparable change in the bimolecular rate constant as the
composition of the reaction mixture was varied further
reinforces the validity of the predictive rationale being develo-
ped for ionic liquid solvent effects, as a predictable ionic
liquid solvent effect is seen with this system.
Fig. 4 The Eyring plot of the bimolecular rate constant (k2) for the
reaction between bromodiphenylmethane 5 and 3-chloropyridine 6a in
acetonitrile (black), a mixture of acetonitrile and [Bmim][N(SO2CF3)2] 1
(χIL = 0.20, blue) or [Bmim][N(SO2CF3)2] 1 (χIL = 0.88, red) from which
the activation parameters were determined.
To further understand the microscopic origin of these
changes in the rate constant of the process, temperature
dependent kinetic studies were performed in acetonitrile, a
mixture of acetonitrile and [Bmim][N(SO2CF3)2] 1 (χIL = 0.20)
and [Bmim][N(SO2CF3)2] 1 (χIL = 0.88, in which the ionic liquid
1 was diluted only by reagents) to allow the activation para-
meters to be determined. For each temperature the reaction of
species 5 and 6a was conducted in triplicate at four different
nucleophile concentrations (an exemplar plot is shown in
Fig. 3), allowing k1 and k2 to be determined across a range of
temperatures (eqn (S1)†) for the different solvent compo-
sitions. This data was then used in combination with the
bimolecular Eyring equation (eqn (S3)†) to determine both the
enthalpy and entropy of activation for the process (Fig. 4 and
Table 1).
Table 1 The activation parameters for the bimolecular reaction
between bromodiphenylmethane 5 and 3-chloropyridine 6a, in either
acetonitrile, a mixture of acetonitrile and [Bmim][N(SO2CF3)2] 1 (χIL
0.20) or [Bmim][N(SO2CF3)2] 1 (χIL = 0.88)
=
χIL
ΔH‡/kJ mol−1 a
ΔS‡/J K−1 mol−1 a
0
0.20
0.88
60.8 1.5
78.9 6.1
72.8 3.3
−194.6 4.6
−124 19
−140 10
a Uncertainties quoted are from the fit of the linear regression.
given the experimental uncertainties. Clearly, the main effects
of the ionic liquid 1 are introduced by χIL ca. 0.2, with further
increases in the amount of [Bmim][N(SO2CF3)2] 1 in the reac-
tion mixture having little to no effect on the second order rate
constant and the activation parameters. Once again, this effect
was predicted by the framework that has been developed
based on previous work, where interaction between the ionic
liquid cation and the nitrogen lone pair on the nucleophile
has been shown to be important.24–26,30 For this case, it is
likely that there is again an interaction between the ionic
liquid cation and the lone pair on the nucleophile 6a,
which would stabilise (and hence deactivate) this nucleophile,
resulting in an increased enthalpy of activation relative to
acetonitrile. On moving to the transition state, where this lone
pair is no longer available to interact with the cation, there is
an increase in solvent disorder, resulting in an increased
entropy of activation relative to acetonitrile. The entropic
effects of this phenomenon dominate reaction outcome,
resulting in an increase in the rate constant when using the
ionic liquid 1.
It can clearly be seen that on moving from acetonitrile to
[Bmim][N(SO2CF3)2] 1 (χIL = 0.20) there was an increase in both
the enthalpy and entropy of activation, with insignificant
changes occurring when moving from χIL = 0.20 to χIL = 0.88,
Fig. 3 The dependence of the observed pseudo first order rate con-
stant (kobs) on the concentration of the nucleophile 3-chloropyridine 6a,
for the reaction between the bromide 5 and the pyridine 6a in aceto-
nitrile at either 39.4 °C (black), 47.5 °C (red) or 52.0 °C (green). Values
for k1 and k2 were determined from the intercept and slope, respectively,
for each case.
Overall, the ionic liquid solvent effects were as expected for
the SN2 component of the reaction between bromodiphenyl-
methane 5 and 3-chloropyridine 6a, based on the framework
for predicting ionic liquid solvent effects that is being develo-
ped by our group. This is important as it further reinforces the
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Fig. 6 The Eyring plot of the unimolecular rate constant (k1) for the
reaction between bromodiphenylmethane 5 and 3-chloropyridine 6a in
acetonitrile (black), a mixture of acetonitrile and [Bmim][N(SO2CF3)2] 1
(χIL = 0.20, blue) or [Bmim][N(SO2CF3)2] 1 (χIL = 0.88, red) from which
the activation parameters were determined.
Fig. 5 The dependence of the unimolecular rate constant (k1) of the
reaction between 3-chloropyridine 6a and bromodiphenylmethane 5 as
the mole fraction of [Bmim][N(SO2CF3)2] 1 in acetonitrile was increased,
at 47.5 °C. Error bars represent the uncertainties from the linear
regression from which k1 was determined.
Table 2 The activation parameters for the unimolecular reaction
between bromodiphenylmethane 5 and 3-chloropyridine 6a, in either
validity of this rationale, and demonstrates that this model can
be effectively applied to a variety of reactions.
acetonitrile, a mixture of acetonitrile and [Bmim][N(SO2CF3)2] 1 (χIL
0.20) or [Bmim][N(SO2CF3)2] 1 (χIL = 0.88)
=
Attention now turns to the unimolecular mechanism of the
reaction between compounds 5 and 6a; firstly the effect of
changing the mole fraction of ionic liquid 1 in the reaction
mixture on the unimolecular rate constant of the process will
be considered (Fig. 5).
χIL
ΔH‡/kJ mol−1 a
ΔS‡/J K−1 mol−1 a
0
0.20
0.88
69.4 3.5
62.3 5.6
47.1 6.0
−119 11
−120 17
−174 19
Interestingly, the rate constant of the unimolecular process
is affected very differently to that of the bimolecular mechan-
ism when the solvent composition is varied. Initially there is
a rapid increase in k1 when moving from acetonitrile to χIL
ca. 0.20, where there is a peak rate enhancement of ca. 13-fold,
relative to acetonitrile. This significant increase is then fol-
lowed by a gradual decrease in the rate constant with increas-
ing amounts of [Bmim][N(SO2CF3)2] 1 in the reaction mixture,
with k1 remaining constant above χIL ca. 0.7. Importantly, even
at χIL = 0.7, where the lowest k1 value for a mixture containing
the ionic liquid 1 was obtained, there is still a rate enhance-
ment of ca. 5-fold relative to acetonitrile. This result is very sig-
nificant as it demonstrates that use of the ionic liquid 1,
across all mixtures with acetonitrile, results in a substantial
increase in the rate constant when compared to acetonitrile.
a Uncertainties quoted are from the fit of the linear regression.
the rate constant was less than that in methanol. Overall, for
the reaction of the chloride 2 use of the ionic liquid 1 had
comparatively little effect, and use of a high mole fraction of
[Bmim][N(SO2CF3)2] 1 in the reaction mixture was not bene-
ficial to the rate constant. For the reaction of the benzylic
species 5 examined in this work, the maximum rate enhance-
ment was much more significant (ca. 13-fold at χIL = 0.20), and
the rate constant remained significantly larger than that in
acetonitrile for all solvent mixtures containing the ionic liquid
1. That is, across all solvent compositions use of [Bmim]
[N(SO2CF3)2] 1 might be considered advantageous, as there
was at least a 5-fold increase in the rate constant relative to
acetonitrile.
The difference in the mole fraction dependency plots
for these cases clearly suggest that the ionic liquid 1 affects
the formation of an aliphatic carbocation differently to a
benzylic carbocation. To allow the origin of these differences
to be probed it is essential to now consider the activation
parameters of the process (Fig. 6 and Table 2), which were
determined in acetonitrile, a mixture of acetonitrile and
[Bmim][N(SO2CF3)2] 1 (χIL = 0.20) and [Bmim][N(SO2CF3)2] 1
(χIL = 0.88, which was diluted only by reagents) through the
temperature dependent kinetics studies that were described
earlier.
This highlights that using the ionic liquid
1 in the
solvent mixture is advantageous for this unimolecular reaction
featuring an extent of charge delocalisation in the transition
state.
This trend in the rate constant resembles the mole fraction
dependency plot for the unimolecular reaction of the aliphatic
species 2 (Scheme 1).34,35 For both cases there is an initial
increase in the rate constant on addition of a small amount of
the ionic liquid 1, followed by a decrease in k1 at higher mole
fractions of [Bmim][N(SO2CF3)2] 1 in the reaction mixture. The
key difference between these two reactions is that for the ali-
phatic case the maximum rate constant increase occurs at χIL
ca. 0.02, and that increase is only 2-fold relative to methanol.
At higher concentrations of the salt 1 in the reaction mixture
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ca. 170 J K−1 mol−1 decrease in the entropy of activation,35
whereas for the SN1 reaction of the benzylic substrate 5 there
was only ca. 25 kJ mol−1 decrease in the enthalpy of activation
and ca. 55 J K−1 mol−1 decrease in the entropy of activation,
when moving from the polar organic solvent to [Bmim]
[N(SO2CF3)2] 1. While it is difficult to compare the absolute
changes in the activation parameters on moving from the
molecular solvent to the ionic liquid 1 as these are different
reactions, and the polar organic solvent used is different for
each case, it is still reasonable to conclude that the enthalpic
and entropic changes seen when moving from a polar organic
solvent to the ionic liquid 1 are significantly larger for the ali-
Scheme 3 The unimolecular mechanism being considered, which
involves dissociation of the bromide 5 to give the carbocation inter-
mediate 8 (which is the rate determining step); this intermediate sub-
sequently reacts with 3-chloropyridine 6a to give the product 7a.
It is first important to highlight that as this is a unimolecu- phatic substrate 2 than for the benzylic substrate 5.
lar process, any interactions between the ionic liquid 1 and the This conclusion is further reinforced by the magnitude of
nucleophile 6a are irrelevant when considering the kinetics of the changes in the rate constant for each process when using
the process, as this reagent is not involved in the rate deter- an ionic liquid solvent. For the aliphatic case 2 use of high
mining step of the reaction. Hence, only interactions between concentrations of ionic liquid 1 results in a decrease in the
the ionic liquid 1 and either the bromide 5 or the transition rate constant relative to methanol,34,35 while for the reaction
state leading to the carbocation intermediate 8 can be used to considered here there is an increase in the rate constant of the
rationalise the activation parameters determined for the uni- reaction (Fig. 5). Clearly, for the aliphatic case the entropic
molecular mechanism (Scheme 3).
cost dominates reaction outcome in the ionic liquid 1, result-
On addition of a small amount of ionic liquid 1 to the reac- ing in the decreased rate constant; while for the benzylic case
tion mixture (χIL = 0.20) there was a significant increase in the the entropic cost is less significant, resulting in the enthalpic
rate constant, indicating a change in the activation parameters benefit dominating reaction outcome and driving the increase
of the process. Unfortunately the determined activation para- in the rate constant in [Bmim][N(SO2CF3)2] 1, relative to the
meters in acetonitrile and χIL = 0.20 were the same within polar organic solvent. This can be readily rationalised by con-
experimental uncertainty, so the microscopic origin of the rate sidering the extent to which the incipient charges in the tran-
increase could not be determined. The same was observed in sition state will be delocalized for each of these cases, and how
the reaction of the chloride
2 through a unimolecular this would affect the magnitude of the interactions along the
process.34,35 In the case where the ionic liquid 1 was diluted reaction coordinate. The transition state associated with the
only by reagents (χIL = 0.88) a decrease in both activation para- SN1 reaction of bromodiphenylmethane 5 to give the inter-
meters, relative to acetonitrile, was observed. A decreased mediate carbocation 8 will feature a significant degree of
enthalpy of activation could either arise from: (1) the ionic charge delocalisation across the neighbouring π systems,
liquid components ordering about and stabilising the incipi- resulting in a decreased extent of charge localisation and
ent charges in the transition state to a greater extent than hence a decrease in the magnitude of the electrostatic inter-
acetonitrile; or (2) from destabilisation of the bromide 5 by the actions between the ionic liquid 1 and the transition state.
ionic liquid 1, relative to acetonitrile. Considering the extent of Conversely, the reaction of the aliphatic substrate 2 to produce
charge development in the transition state, leading to the the intermediate carbocation 3 will feature very little, if any,
intermediate carbocation 8, the former is more likely. This is charge delocalisation in the transition state, resulting in a
also consistent with the decreased entropy of activation; much more charge localised transition state, and stronger
greater stabilisation of the incipient charges in the transition ionic liquid–transition state interactions.‡ The activation para-
state by the ionic liquid 1 would result in a greater increase in meters determined in this current work clearly demonstrate
ordering of the ionic liquid about the transition state, relative that differences in the magnitude of the electrostatic inter-
to the starting material 5, causing a decrease in the activation actions between the ionic liquid and the transition state can
entropy in comparison to acetonitrile.
have a substantial effect on the overall ionic liquid solvent
The observed change in the activation parameters when effect: for the reactions considered above, when the ionic
using an ionic liquid solvent (χIL = 0.88) is in the same direc- liquid–transition state interactions are large, the entropic cost
tion as that seen for the unimolecular reaction of the linalool
derivative 2 with methanol (Scheme 1); for that case there was
also a decrease in both the enthalpy of activation (an enthalpic
‡It should be noted that the introduction of π systems may also introduce inter-
benefit) and the entropy of activation (an entropic cost) on actions between components of the ionic liquid and the starting material; this
has been shown previously.45,46 This would be expected to result in stabilisation
moving from the molecular solvent methanol to the ionic
liquid 1.35 Importantly, the magnitude of these changes in the
of, and ordering about, the bromide 5 and hence might be expected to result in
an increase in both the activation enthalpy and activation entropy. Whilst this
activation parameters is different for these two reactions;
may account in some part for the differences observed between the benzylic 5
for the SN1 reaction of the aliphatic substrate 2 there was
and aliphatic 2 cases, the effect of charge localisation is considered more
ca. 50 kJ mol−1 decrease in the enthalpy of activation and significant.
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dominates reaction outcome and there is a decrease in the
reaction rate; yet when there are weaker ionic liquid–transition
state interactions the enthalpic benefit dominates resulting in
a rate enhancement, relative to a polar organic solvent.
It is worth revisiting the data for the mixture of acetonitrile
and [Bmim][N(SO2CF3)2] 1 (χIL = 0.20); although the change of
solvent from acetonitrile to χIL = 0.20 caused a significant rate
enhancement, the resulting changes in the activation para-
meters were within the uncertainties of those values. As was
the case for the linalool derivative 2, it is likely that this rate
enhancement is a result of stabilisation of the transition state
(enthalpic benefit) overcoming any increase in order as a
result (entropic cost). Considering the trend in the rate con-
stant (Fig. 5), it is likely that the extent of solvent reorganis-
ation on moving to the transition state is less significant at
lower mole fractions of 1 in the reaction mixture, and at higher
mole fractions of 1 solvent reorganisation becomes more sub-
stantial, increasing the entropic cost and causing the
decreased rate constant at higher mole fractions.
Fig. 7 The ratio between k1 and k2[Nu] for the reaction between
bromodiphenylmethane 5 and 3-chloropyridine 6a across various mole
fractions of [Bmim][N(SO2CF3)2] 1 in acetonitrile at 47.5 °C. The nucleo-
phile 6a concentration was arbitrarily set to 0.1268 mol L−1 so that the
data can be readily interpreted (as the ratio = 1 in acetonitrile). Errors
bars represent the uncertainties from the linear regression, com-
pounded from the division.
The significantly larger rate constant at lower mole fractions
reinforces the importance of the balance of the opposing
enthalpic and entropic effects, rather than simply the magni-
tude of the change in each parameter. For this case a decrease
in the enthalpy of activation is associated with a decrease in
the entropy of activation (enthalpy–entropy compensation),
hence the changes in the enthalpic and entropic contributions
have opposite effects on the overall activation energy. As such,
if there are large changes in both parameters but the magni-
tude of the change in each parameter is the same, these oppos-
ing effects will cancel each other out and result in negligible
differences in the observed rate constant. Relating this now to
what was observed in this work, the change in the activation
parameters when moving from acetonitrile to χIL = 0.20 was
much smaller than that seen when going from acetonitrile to
χIL = 0.88, however the balance must be different to explain the
observed rate constants. At χIL = 0.88, the balance of the
changes in the activation parameters results in a smaller rate
enhancement than that observed at χIL = 0.20. That is, large
changes in the activation parameters don’t necessarily result
in a large change in the rate constant, it is the relative change
in each parameter that is important. Clearly, understanding
the balance between the opposing enthalpic and entropic
effects is essential when trying to predict the overall change in
the rate constant. The fact that the change in the activation
parameters on moving from acetonitrile to χIL = 0.20 are
within the uncertainties of the experiments demonstrates the
difficulties in understanding solvent effects, except in cases
where the changes in the activation parameters are large, as is
the case at higher proportions of the salt 1 in the reaction
mixture.
clearly seen in Fig. 7, where the ratio between k1 and k2[Nu]§ is
plotted against the mole fraction of the ionic liquid 1 in the
reaction mixture. Such a phenomenon has been observed in
previous work examining competing mechanisms,38 and
further highlights the possibility of using ionic liquids to
control reaction outcomes.
Conclusions
In summary, this work demonstrated a predictable ionic liquid
solvent effect on the bimolecular mechanism of the reaction
between the diphenyl species 5 and 3-chloropyridine 6a,
further validating the framework for predicting ionic liquid
solvent effects that is being developed. For the unimolecular
mechanism of this reaction, it was demonstrated for the first
time that use of an ionic liquid solvent can be beneficial for
benzylic carbocation formation; this effect was confirmed to
be enthalpically driven, due to the favourable ionic liquid–
transition state interactions.
Much previous work has identified the importance of
understanding the different interactions between the ionic
liquid and species along the reaction coordinate. In this
current work, the importance of understanding the strength of
these interactions has been revealed: the charge delocalisation
in the transition state for the benzylic system 5 resulted in a
reduced extent of ionic liquid–transition interaction, relative to
aliphatic carbocation formation, resulting in a significant
change in the balance between the opposing enthalpic and
Finally, it is worth considering another interesting outcome
from this work; that by changing the solvent composition one
mechanism can be favoured over the other. At lower mole frac-
tions of [Bmim][N(SO2CF3)2] 1 in the reaction mixture the
unimolecular mechanism is favoured, yet at higher mole frac-
§The concentration of the nucleophile 6a could be set to any value and the
trend in the plot would be qualitatively the same. In this case, a value of the con-
centration of the pyridine of 0.1268 mol L−1 was chosen so that in acetonitrile
the ratio of the species reacting through unimolecular and bimolecular pathways
tions the bimolecular mechanism is preferred. This is most was 1, allowing the trend to be clearly seen.
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Acknowledgements
STK acknowledges the support of the Australian government
through the receipt of an Australian Postgraduate Award. JBH
acknowledges financial support from the Australian Research
Council Discovery Project Funding Scheme (Project
DP130102331). The authors would like to acknowledge the
NMR Facility within the Mark Wainwright Analytical Centre at
the University of New South Wales for NMR support.
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