Pseudo-encapsulation-nanodomains for enhanced reactivity in ionic liquids

Article abstract of DOI:10.1002/anie.201206113

Domain constrained: Polar and nonpolar domains within 1-alkyl-3- methylimidazolium ionic liquids can affect reaction outcomes by pseudo-encapsulation of reactants and this has been explored for a nucleophilic substitution reaction using a cationic substrate and a range of nucleophiles. The significant rate enhancements observed correlate with the concentration of the polar reactants within the ionic liquid's polar domain. ([C _nMIM]=1-alkyl-3-methylimidazolium). Copyright

Full text of DOI:10.1002/anie.201206113

Angewandte
Chemie
DOI: 10.1002/anie.201206113
Ionic Liquids
Pseudo-Encapsulation—Nanodomains for Enhanced Reactivity in
Ionic Liquids**
Cameron C. Weber, Anthony F. Masters, and Thomas Maschmeyer*
Ionic liquids (ILs) have attracted intense scientific interest in
recent years owing to their unique chemical and physical
properties as well as their potential to replace volatile organic
compounds (VOCs).[1] One of the major questions inves-
tigated has been whether ILs, when used as solvents, display
any unique characteristics that may lead to unusual reaction
outcomes unattainable with neutral solvents of comparable
polarity.[1a,2] Results thus far suggest that, due to the strong
Scheme 1. General representation of the nucleophilic substitution of
Coulombic interactions present within ILs which are absent
[Ar3Pic][Cl]. Reactions were conducted at 294.3 K and monitored using
19F{1H} NMR spectroscopy.
within neutral solvents, ILs have the greatest effect on
reactions featuring either charged reactants or at least
considerable charge development over the course of the
reaction. However, investigations into such phenomena have
not focussed on the direct consequences of unique structural
features of ILs on reaction outcomes.
ILs, particularly those based on the imidazolium cation,
show significant structural heterogeneity resulting from the
hydrophobic nature of the alkyl side chains when the side
chain is propyl or longer, leading to the formation of separate
polar and nonpolar domains.[3] These domains have been
implicated in the use of ILs for separations and the size
control of nanoparticles and polymers;[4] however, their
potential role in providing unique reaction spaces that could
lead to unprecedented precision in the control of organic
reactions has not been examined to date. Whether in chemical
or biological systems, highly charged structured nanodomains
could play a significant and profound role across a vast range
of reactions, akin to transitory liquid zeolites.
states, it would be anticipated that the constituents of this salt
would reside preferentially within the polar domains of the
IL. Through variation of the alkyl side chains of the IL and the
R group on the nucleophile, any effects arising from
interactions of the alcohol, ROH, with the polar and nonpolar
domains can be delineated. To this end, the primary aliphatic
alcohols methanol, ethanol, 1-propanol, and 1-butanol as well
as water and benzyl alcohol have been examined as nucleo-
philes in the present work. The ILs investigated as solvents for
this reaction were 1-alkyl-3-methylimidazolium bis(trifluor-
omethanesulfonyl)imide salts ([CnMIM][NTf2] where n = 2, 4,
6 ,8, and 10). The mole fraction of IL employed in these
experiments varied from 0.68–0.77, depending primarily on
the length of the alkyl side chain, demonstrating that the IL
solvent represents the bulk of the reaction medium (see the
Supporting Information for precise mole fractions for each
system).
Thus, to examine the effect of these domains on reactivity
from a fundamental point of view, the bimolecular nucleo-
philic substitution of N-(p-fluorophenyldiphenylmethyl)-4-
picolinium chloride ([Ar3Pic][Cl]) has been chosen as a model
reaction (Scheme 1). Previously, this system has been shown
to be sensitive to the solvation environment of the nucleo-
phile, ROH, primarily on account of the similar charge of the
electrophile in its initial and transition states, an effect that
has also been found for other N-tert-alkyl pyridinium
systems.[5] As [Ar3Pic][Cl] is ionic in both initial and transition
As stated previously,[5c] we chose 4-picoline as a leaving
group for experimental convenience, to enable data collection
over a reasonable time scale at a moderate temperature. The
second-order rate constants obtained from these investiga-
tions are summarized in Table 1. While previous investiga-
tions of these systems have reported pseudo-first-order rate
constants,[5b,c] second-order rate constants are required to fit
the kinetic model discussed below and consequently are used
for all discussions herein. As is evident from the results in
Table 1, for every nucleophile examined significant rate
enhancements were observed when the length of the alkyl
side chain of the IL was increased. However, even though
a rate enhancement is seen in every case, it is evident that the
extent of the increase is not uniform across all substrates. For
example, the rate constant observed for water increased by
167% in [C10MIM][NTf2] relative to that in [C2MIM][NTf2],
while the corresponding rate increase for 1-butanol between
these two solvents was only 84%.
[*] C. C. Weber, Assoc. Prof. Dr. A. F. Masters, Prof. Dr. T. Maschmeyer
Laboratory of Advanced Catalysis for Sustainability
School of Chemistry, The University of Sydney
Sydney 2006 (Australia)
E-mail: th.maschmeyer@chem.usyd.edu.au
[**] We thank Dr. Jason Harper and Prof. Greg Warr for helpful
discussions, Dr. Ian Luck for his assistance with NMR experiments,
and the University of Sydney for funding. C.C.W. thanks the
University of Sydney for a Vice Chancellor’s Research Scholarship.
As the variation of the alkyl side chain of the IL is unlikely
to directly affect any solvent–transition-state interactions, this
rate enhancement must arise from a structural effect within
the IL itself. By way of comparison, a significant reduction in
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201206113.
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Table 1: Second-order rate constants for the nucleophilic substitution of [Ar3Pic][Cl] at 294.3 K in a range
of 1-alkyl-3-methylimidazolium ILs.
This can then be combined to
give Equation (3), where Vp is the
volume of the polar domain and Vtot
is the total volume of the system.
The full derivation of this expres-
sion and the underlying assump-
tions made can be found in the
Supporting Information.
Rate constants [ꢀ10ꢁ4 mꢁ1 sꢁ1 [a]
]
IL
Water
Methanol
Ethanol
1-Propanol
1-Butanol
Benzyl alcohol
[C2MIM][NTf2]
[C4MIM][NTf2]
[C6MIM][NTf2]
[C8MIM][NTf2]
[C10MIM][NTf2]
17.0ꢀ0.5
20.6ꢀ0.3
31.9ꢀ1.1
43.3ꢀ0.5
45.5ꢀ0.9
33.8ꢀ0.4
46.5ꢀ1.9
57.5ꢀ1.3
68.6ꢀ7.6
70.5ꢀ3.6
12.5ꢀ0.4
16.6ꢀ0.1
20.5ꢀ0.9
24.7ꢀ0.5
24.3ꢀ1.4
12.7ꢀ0.3
16.7ꢀ1.4
20.2ꢀ0.8
23.2ꢀ0.8
25.4ꢀ0.3
14.1ꢀ0.8
17.3ꢀ1.2
22.4ꢀ0.5
24.2ꢀ1.9
26.0ꢀ1.3
5.8ꢀ0.2
8.0ꢀ0.6
8.7ꢀ0.2
11.2ꢀ0.3
12.1ꢀ1.1
kpðVtotÞ ½ROHꢂtot½Ar3Picꢂtþot
2
[a] Rate constants were obtained by dividing the pseudo-first-order rate constants by the initial
concentration of nucleophile (0.515m for all reactions). Reported errors are standard deviations of at
least three replicate experiments.
À
Á
r ¼
ð3Þ
Vp KVtot þ Vpð1 ꢁ KÞ
As the total volume of the
the hydrogen bond strength caused by utilizing 1-butyl-2,3-
dimethylimidazolium bis(trifluoromethanesulfonyl)imide
system was maintained at 1.05 mL for all reactions, only the
volume of the polar domains is required in order to fit this
model to the observed bimolecular rate constants. The
volume of the nonpolar domains was estimated by a group
contribution method where the volume of a CH2 group was
treated as 17.2 mLmolꢁ1, a value that has previously been
found for imidazolium ILs,[9] and the CH3 group was assigned
a volume of 25.49 mLmolꢁ1 based on the findings of
Plyasunov et al. regarding aliphatic esters.[10]
Fitting these data to the Vp values estimated by this
method led to the plots in Figure 1. As can be observed, R2
values greater than 0.92 were obtained for all nucleophiles in
Figure 1 with excellent fits obtained in most cases, particularly
given the relative simplicity of the model. In addition, the
fitted K parameters obtained were consistent with values that
could be anticipated in light of literature precedence. The
fitted K value for water was zero (within error), indicating it
does not partition into the nonpolar domains, as has been
predicted through molecular dynamics (MD) simulations and
determined spectroscopically.[11]
The value of K increased with the length of the side chain
for the aliphatic alcohols, consistent with the increased
hydrophobicity leading to more favorable partitioning into
the nonpolar domains. The K values for the alcohols also
suggest significant interactions with both domains, as have
been predicted by MD.[11a] The K value obtained for benzyl
alcohol was similar to that for methanol rather than for
a longer chain alcohol and might arise from the quadrupolar
interactions between the polar domain of the IL and the
aromatic ring, as has been found for other aromatic systems in
ILs, thereby favoring benzyl alcoholꢁs solvation in the polar
domain.[12]
It is worth discussing that the rate constant obtained in
[C4MIM][NTf2] with water as a nucleophile (Vp = 0.85 mL)
lies significantly below that predicted by the fitted model.
[C4MIM][NTf2] has been found to possess a nonpolar domain;
however, owing to the bulk of the [NTf2] anion, this domain is
not a continuous microphase like that found for imidazolium
ILs with longer alkyl side chains.[3c] In addition, water has
been found to reduce the cohesion of [C4MIM][NTf2] even at
very low mole fractions[13] which suggests that the anomalous
result for [C4MIM][NTf2] with water employed as the
nucleophile may arise from the reduced cohesion of the IL
which already possesses weakly aggregated nonpolar
domains. The reduced dissociating power of the aliphatic
([C4MMIM][NTf2]) as a solvent rather than [C4MIM][NTf2]
has been found to yield a reaction rate constant for hydrolysis
of (36.5 ꢀ 0.8) ꢀ 10ꢁ4 mꢁ1 sꢁ1.[6,5c] This means that the rate
increase observed when the alkyl side chain is changed from
butyl to octyl is larger than that obtained when the hydrogen-
bond acidity of the medium is significantly reduced.[5c]
Furthermore, the larger rate enhancement for water
relative to the aliphatic alcohols or benzyl alcohol suggests
that the effect is more pronounced for more polar molecules.
The most logical explanation for such behavior arises from
the nanostructural heterogeneity of the solvent, that is, the
reactants concentrate in the polar domains which are
relatively smaller in volume as the alkyl side chain of the IL
increases. This phenomenon, that is, the pseudo-encapsula-
tion of reactants in the polar domains of the IL, changes the
effective concentrations of the reagents. Such effects have
been observed in micellar kinetics,[7] where the concentration
of reagents within the micelle can significantly affect reaction
rates. The aforementioned rate effects in micellar systems led
to the development of a pseudophase model for the inter-
pretation of kinetic data, where the two phases were defined
as the aqueous phase and the interior of the micelle.[8]
Applying such a pseudophase treatment to this non-
micellar, but domain-based reaction system involves separat-
ing the rate law into the rates within both the polar and
nonpolar domains, as shown in Equation (1), where [ROH]p
r ¼ kp½ROHꢂp½Ar3Picꢂþp þ knp½ROHꢂnp½Ar3Picꢂþ
ð1Þ
np
and [Ar3Pic]+p refer to the concentrations of alcohol or water
and substrate in the polar domains, respectively, and [ROH]np
and [Ar3Pic]+ refer to the corresponding concentrations in
np
the nonpolar domains.
Given the proposition above that [Ar3Pic]+ partitions
exclusively into the polar domains, then [Ar3Pic]+np ꢃ 0 and
the contribution of the nonpolar domain to the rate can
therefore be ignored. However, this assumption is not
necessarily true for the nucleophile, so it is necessary to
define a partition coefficient, K, to describe the proportion of
nucleophile, ROH, in the nonpolar relative to polar domains
and this is formalized in Equation (2).
½ROHꢂnp
K ¼
ð2Þ
½ROHꢂp
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Figure 1. Rate data were fitted to the pseudophase kinetic model using values of Vp estimated from a group-contribution method.
alcohols could account for the significantly better fits
obtained for these systems.
It is interesting to note a recent report that has mentioned
the inhibition of a dehydration reaction when long alkyl side
chains were used on the IL solvent.[14] The “pseudo-encapsu-
lation” effect outlined herein could be used to account for
these results as the effective water concentration in the polar
domains of [C10MIM][Cl] would be much higher than is the
case in [C2MIM][Cl]. The difference in the effective water
concentration would lead to a significant increase in the rate
of the reverse reaction and hence a lower overall yield, as was
observed in that system.
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167%, has been observed for a nucleophilic substitution
reaction simply through variation of the length of the alkyl
side chain of imidazolium ILs. This rate increase has been
attributed to the pseudo-encapsulation of reactants in the
polar domain of the IL, which changes the effective concen-
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interpretation has been found to accurately represent the
observed data.
This pseudo-encapsulation effect suggests that ILs may
have the potential to facilitate cascade reactions where, for
example, the rate of reaction of a set of polar reagents is
accelerated leading to the formation of a nonpolar product
that may then react more quickly with an added nonpolar
reagent, resulting in significant acceleration of the overall
reaction/process. It may also be possible to conduct reactions
in the presence of traditionally incompatible compounds, so
long as there is a preference for these components to be
solvated in separate domains. This would be comparable to
the use of nanoencapsulated systems, without the need for the
extensive synthetic procedures often associated with such
systems.[15] Furthermore, the use of mixtures of ILs and
nonpolar solvents may enhance the rate of reaction of polar
reagents through the relative decrease in volume of the polar
domains of these ILs for a given reaction volume. Consider-
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selection of ILs as solvents to facilitate favorable chemical
outcomes. The consequences of structural heterogeneity may
also account for some previously unexplained IL-mediated
phenomena, such as the inhibition of dehydration reactions
discussed above.
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) by the final
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Experimental Section
For the general kinetics protocol, an NMR tube equipped with
a Youngꢁs valve was charged with p-fluorophenyldiphenylmethyl
chloride (15–25 mg, 0.05–0.08 mmol) under a flow of nitrogen. 4-
Picoline (50 mL) was added to dissolve the substrate. Approximately
5 min before the reaction was to be monitored, the solution was
diluted with the IL containing ROH (0.98 mL of 0.55m ROH) and
cooled in an ice bath. The sample was then mixed using a Vortex
mixer and the reference capillary (1-bromo-4-fluorobenzene in
[D6]acetone (0.50m)) inserted co-axially. The tube was immediately
inserted into the NMR probe which had been precooled to 294.3 K,
the temperature of the NMR tube was allowed to equilibrate, and
19F{1H} NMR spectra were subsequently obtained at that temperature
every 65 seconds. For additional details on synthesis, characterization,
and calculation, see the Supporting Information.
Received: July 31, 2012
Published online: October 12, 2012
Keywords: ionic liquids · kinetics · nucleophilic substitution ·
.
solvent effects · structural heterogeneity
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