Investigating Variation of the Pnicogen Nucleophilic Heteroatom on Ionic Liquid Solvent Effects in Bimolecular Nucleophilic Substitution Processes

Article abstract of DOI:10.1002/cplu.201900188

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.

Full text of DOI:10.1002/cplu.201900188

Accepted Article
Title: Investigating Variation of the Pnicogen Nucleophilic Heteroatom
on Ionic Liquid Solvent Effects in Bimolecular Nucleophilic
Substitution Processes
Authors: Jason Brian Harper, Karin Schaffarczyk McHale, and Ronald
Haines
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Investigating Variation of the Pnicogen Nucleophilic Heteroatom
on Ionic Liquid Solvent Effects in Bimolecular Nucleophilic
Substitution Processes
Karin S. Schaffarczyk McHale,[a] Ronald S.[a] Haines and Jason B. Harper*[a]
Abstract: 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 liquid. 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.
proportion of ionic liquid in the reaction mixture affects the
observed reaction outcome.[4d, 6b, 10e, 10f, 11] Determining activation
parameters at key solvent compositions in these cases allowed
the microscopic interactions of the observed ionic liquid solvent
effects to be elucidated.[12] Such studies have examined using a
variety of substitution processes,[13] with those studies focusing
on bimolecular nucleophilic substitution reactions[14] being of
greatest relevance to this work.
Rate constant enhancement relative to a molecular solvent
has been observed for bimolecular substitution processes[14a-g]
and a related bimolecular process[15] with a nitrogen nucleophile.
The origin of the rate constant enhancement was an increase in
the entropy of activation with organisation of the ionic liquid,
15b]
particularly the cation,[14b,
about the lone pair of the
nucleophilic nitrogen centre being disrupted upon moving to the
15a]
transition state.[14a,
Subsequently, knowledge of this key
Introduction
interaction was exploited to rationally design ionic liquids to
maximise the rate constant.[14f]
Ionic liquids, being salts with low melting points (<100 ºC),[1]
have been considered for a range of purposes including but not
limited to; electrolytes for batteries,[2] bioprocessing[3] and as
solvents for synthesis.[4] An added advantage of ionic liquids is
that there is the potential to alter their physicochemical
properties (i.e. viscosity, density, etc.)[5] such that by simply
choosing the appropriate cation and anion combination these
‘designer solvents’ may be tailored to best benefit a given
scenario.[6] Another advantage of the use of ionic liquids,
particularly as solvents, is that they have negligible vapour
pressures,[1a, 4a] making them potentially safer[7] and greener[4b, 4c]
alternative solvents to conventional organic solvents. There are,
however, some drawbacks to using ionic liquids; currently they
are expensive relative to conventional organic solvents and
properties such as their comparatively high viscosity may be
disadvantageous in certain applications. As a counterpoint, a
potential significant benefit of using ionic liquids as solvents is
that, compared to conventional organic solvents, ionic liquids
have the potential to make reactions more rapid, as well as
potentially facilitating new reactivity not available in traditional
molecular solvents.[8]
The effect on ionic liquid solvent effects of changing the
nucleophilic heteroatom from nitrogen to phosphorus, 1a and 1b
respectively, in a bimolecular process has also been considered
in
solvent
mixtures
of
the
ionic
liquid
1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide
([Bmim][N(SO2CF3)2]) 2 and the co-solvent acetonitrile.[14g] It was
found that the systems with phosphorus nucleophiles were more
susceptible to ionic liquid-transition state interactions, with a
greater dependence on the leaving group and the electronics of
the electrophile[14g, 14h] than corresponding systems with nitrogen
nucleophiles.[14a-f] The leaving group, in particular, had the
greatest influence on the balance of ionic liquid solvent
interactions in these systems involving phosphorus nucleophiles;
the more charge diffuse the leaving group was, the greater the
effect and thus dominance of ionic liquid-transition state
interactions over those between the ionic liquid and the starting
material.[14h, 16]
The focus of the present work is to expand the current
understanding of ionic liquid solvent effects on bimolecular
nucleophilic substitution reactions to encompass a greater range
of nucleophilic heteroatoms and to allow the determination of
trends that might be generally applied as the nucleophile
changes. For this purpose the reaction between each of the
triphenylpnicogens 1c-e with benzyl bromide 3 was considered
in mixtures containing the ionic liquid ([Bmim][N(SO2CF3)2]) 2
and the co-solvent acetonitrile (Scheme 1), allowing direct
Ionic liquids have been considered across a myriad of
synthetic processes, with studies ranging from reporting the
differences between reaction outcomes in ionic liquids and
molecular solvents[4e, 8a, 9] through to quantifying, and beginning
to explain, the origins of these differences.[10] A particular subset
of these latter studies have investigated how varying the
comparison with previously studied systems containing nitrogen
14h]
1a and phosphorus 1b nucleophiles.[14g,
These studies
support those previously which link the reactivity of the reagents
to the position of the pnicogen in the periodic table,[17] though it
should be noted that such reports predominately have focused
on inorganic complexes and processes.[18]
[a]
K. S. Schaffarczyk McHale, Dr R. S. Haines, Assoc. Prof. J. B.
Harper
School of Chemistry, University of New South Wales,
UNSW Sydney, NSW 2052, Australia
E-mail: j.harper@unsw.edu.au
Supporting information for this article is given via a link at the end of
the document.
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Br
triphenylphosphine 1b resulted in a negligible decrease of 0.3
units.[23] It is reasonable to suggest that any effects of the
adjacent conjugated system will become even less marked on
increasing the atomic number of the pnicogen. Considering the
argument, above the triphenylamine 1a system will not be
discussed further in the following analysis.
In the kinetic studies of the dependence of the amount of the
ionic liquid 2 in the reaction mixture for the previously studied
triphenylphosphine 1b system there was an initial ca. two-fold
increase in the rate constant from c2 = 0 and c2 » 0.4 followed by
a decrease in the rate constant from c2 » 0.4 to c2 » 0.7 (with the
rate constant at c2 » 0.7 being equivalent to that observed at c2
= 0). Finally, the ca. two-fold rate constant enhancement
CH3CN
YPh3
YPh3
+
Br
N
O
N
4
2
1
3
O
N
a = N
b = P
c = As
d = Sb
e = Bi
a = N
b = P
c = As
d = Sb
e = Bi
S
S
CF3
F3C
O
O
Scheme 1. The bimolecular nucleophilic substitution reaction between one of
the triphenylpnicogens 1a-e and benzyl bromide 3 to give the salts 4a-e, which
have been examined in mixtures of [Bmim][N(SO2CF3)2] 2 in acetonitrile. The
triphenylamine 1a and triphenylphosphine 1b systems were studied previously
by Schaffarczyk McHale et al.[14g]
(relative to acetonitrile) was again observed on going from c2
»
0.7 to c2 » 0.9, the highest mole fraction of the salt 2 studied.
Overall, these changes result in the mole fraction dependence
Results and Discussion
plot having
a sinusoidal appearance as shown by the
reproduced data in Figure 1.[14g] At this stage, it should be noted
that these triphenylphosphine 1b system kinetic studies were
conducted at 24.4 ºC whereas the mole fraction dependence
kinetic studies conducted here for the triphenylpnicogen 1c-e
systems were done at 75.0 ºC. Whilst the difference in
temperature will affect comparisons of the magnitude of the any
rate changes observed it should not impact significantly on the
trend in the rate constants as the proportion of the ionic liquid 2
changes. The different temperatures chosen reflect the relative
reactivity of the phosphorus nucleophile 1b and the other
pnicogen nucleophiles 1c-e with benzyl bromide 3 and were
chosen to facilitate obtaining the rate constant data.
From Figure 1, for the reaction of triphenylarsine 1c with
benzyl bromide 3, there is a gradual increase in the rate
constant as the proportion of the salt 2 in the reaction mixture
increases. The greatest rate constant enhancement observed is
a two-fold increase in the rate constant, relative to acetonitrile, in
the mixture containing the greatest proportion of the ionic liquid
2 used (c2 » 0.8), with the majority of this rate constant
enhancement having occurred by c2 » 0.2. It is not unusual for
the majority of the rate enhancement seen for bimolecular
processes to occur after the addition of only a low proportion of
the ionic liquid 2 to the reaction mixture with little change on
The bimolecular rate constants for the reactions between the
triphenylpnicogens 1c-e and benzyl bromide 3 across a range of
solvent compositions of the ionic liquid [Bmim][N(SO2CF3)2] 2 in
acetonitrile were determined (Figure 1).[19] Both the ionic liquid 2
and the co-solvent, acetonitrile, have been used in the
aforementioned studies directly related to this work,[14g, 14h] as
well as in studies on a number of other bimolecular processes[14a,
14c, 14d, 15b]
and, as such, these solvents allow for direct
comparisons to be made. Importantly, acetonitrile has a similar
apparent polarity to, and is miscible with, the ionic liquid 2.[20]
Before continuing, it is useful to discuss the previously
studied nitrogen 1a and phosphorus 1b systems.[14g] The rate
constants determined for the reaction between triphenylamine
1a and benzyl bromide 3 in the range of solvent mixtures were
ca. four orders of magnitude slower than those observed for the
triphenylphosphine 1b system under the same conditions. This
marked difference in reactivity is likely due to the significant
orbital overlap of the nitrogen lone pair with the aromatic system
of the phenyl substituents of the nucleophile 1a relative to the
other pnicogen nucleophiles 1b-e. This effect is consistent with
the measured nucleophilicity parameters of related systems,
where changing from aniline[21] to benzylamine[21-22] (removal of
a single interaction) increases the nucleophilicity parameter by
1.6 units, whilst changing from tri(cyclohexyl)phosphine to
subsequent addition; examples of note are the substitution
15c]
processes[14] and condensation reactions[15b,
involving a
nitrogen nucleophile. This trend in the dependence of the rate
constant on the amount of ionic liquid in the reaction mixture is
different to the trends observed in the previous
triphenylpnicogen study;[14g] whilst there is a slight decrease in
the rate constant at c2 » 0.4, the trend is not as marked as was
the case for the phosphorus nucleophile 1b at c2 » 0.7 as
discussed above. The differences in the observed trends
between the triphenylphosphine 1b and triphenylarsine 1c
systems immediately suggest that the microscopic interactions
involving the ionic liquid are likely different in each system.
Further information is needed to better understand the
microscopic origin of these solvent effects and shall be
discussed in detail below.
When triphenylantimony 1d is used as the nucleophile for
the reaction depicted in Scheme 1, a different trend in the mole
fraction dependence of the rate constant is observed compared
to that when triphenylarsine 1c was used. There is an
approximately four-fold rate constant enhancement observed on
changing the composition of the solvent from c2 = 0 to c2 » 0.2; a
Figure 1. The bimolecular rate constants for the reaction of triphenylpnicogens
1b (blue), 1c (red), 1d (purple) or 1e (green) with benzyl bromide 3 across a
range of different solvent compositions of the ionic liquid [Bmim][N(SO2CF3)2]
2 in acetonitrile at 24.4 ºC for the phosphine 1b system (reproduced from
Schaffarczyk McHale et al.[14g]) and 75.0 ºC for the other pnicogen 1c-e
systems, with the exception of the case of species 1d in acetonitrile (c2 = 0);
see Experimental for more details. Uncertainties are reported as the standard
deviation of three replicates.
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decrease in the rate constant is observed as the amount of ionic
liquid 2 is increased above c2 » 0.2. Importantly, for all solvent
mixtures c2 ³ 0.2 the rate constant is at least two-fold greater
than that observed at c2 = 0. As discussed above, rate constant
enhancement on changing the solvent composition from c2 = 0
to c2 » 0.2 is not unusual for bimolecular processes, although
the subsequent decrease in the rate constant at c2 > 0.2 is
more significant, resulting in the rate constant enhancement
observed. These changes in the activation parameters could be
due to a decrease in stabilisation of, and organisation of the
solvent about, the starting materials when the ionic liquid 2 is
present in the reaction mixture relative to acetonitrile. The
alternative is an increase in stabilising interactions with, and
organisation of the salt 2 about, the transition state relative to
unusual and resembles trends observed for unimolecular
the molecular solvent. As there is a degree of charge
13a, 13e]
substitution processes.[12e,
These observations could
development in the transition state that the ionic liquid, also
being a charged species, would be expected to interact with the
latter argument is considered more likely. There are insignificant
differences in the activation parameters determined for c2 » 0.2,
0.4 and 0.8 suggesting that the majority of the change in solvent
interaction has occurred by c2 » 0.2 with little or no significant
change on further addition of ionic liquid. This argument is
consistent with the mole fraction dependent kinetic studies
above, where the majority of the rate constant enhancement
observed has occurred by c2 » 0.2; the slight increase in the rate
constant above this proportion of ionic liquid in the reaction
mixture is likely due to a subtle change in the balance of these
interactions which is unable to be determined from the technique
used.
It is of interest to note that these trends in the activation
parameters are not observed in any bimolecular nucleophilic
process involving a nitrogen nucleophile[14b-g, 15b, 15c] and are only
seen at a high mole fraction of the ionic liquid 2 (c2 » 0.7) for the
equivalent reaction involving a phosphorus nucleophile.[14g, 14h]
This suggests that proceeding down group 15 from phosphorus
intimate that there are similar interactions occurring in the
triphenylantimony 1d system that are responsible for the
observed effects on the rate constant as have been noted in the
unimolecular substitution processes[13a] (those between the ionic
liquid and the transition state), once again this shall be
discussed subsequently when further data is presented.
The trend in the mole fraction dependence of the rate
constant for the triphenylbismuth 1e system is most reminiscent
of the triphenylantimony 1d case, though the scale of the effects
is smaller. An approximately 2-fold increase in the rate constant
is observed on changing the solvent composition from c2 = 0 to
c2 » 0.3 with a subsequent slight decrease in the rate constant
as the proportion of the ionic liquid 2 in the reaction mixture
increases.
It Is worth briefly reflecting on these trends as the nature of
the group 15 element involved is changed. First of all, the data in
acetonitrile are as one would expect, with the triphenylphosphine
1b being the most nucleophilic species and the other systems
having comparable reactivity. A second point to note is the
gradual trend in the shape of the mole fraction dependence plots, to arsenic-based nucleophiles there is a ‘shift’ in the dominant
from sinusoidal in the case of the phosphorus nucleophile
through to a shallow concave plot in the case of the bismuth
nucleophile. Least systematic is the rate constant enhancement;
the triphenylantimony 1d case had the greatest rate constant
enhancement observed (ca. 4 times at c2 » 0.2, relative to
acetonitrile) compared to the triphenylarsine 1c and
triphenylbismuth 1e systems (ca. 2 times at c2 » 0.2 – 0.3 for
both, relative to acetonitrile) and the phosphorus system 1b (a
2-fold increase at both c2 » 0.4 and c2 » 1).[14g]
Both the changes in the shape of the plots observed and the
different rate constant enhancements suggest different
interactions at the microscopic level are affecting reaction
outcome. In order to understand these interactions (and to
investigate whether these solvent effects might be predictable)
temperature dependent kinetic studies were undertaken. The
rate constants of each process were measured across a range
of temperatures at particular solvent compositions of interest.
These data were analysed using the bimolecular form of the
Eyring equation[24] to determine the activation parameters for the
chosen solvent compositions (Table 1, with the data for the
corresponding phosphorus case 1b reproduced from
previously[14g] for comparison). The solvent compositions chosen
were; c2 = 0 (acetonitrile), c2 » 0.2 (for the nucleophiles 1c and
1d, where significant rate constant enhancement relative to
acetonitrile was observed), c2 » 0.4 (for nucleophiles 1c and 1e
where notable rate constant changes relative to c2 = 0 were
observed), c2 » 0.8 (ionic liquid 2 is diluted by reagents only).
For the reaction of triphenylarsine 1c with benzyl bromide 3
in all solvent compositions containing the salt 2, there was a
decrease in both the enthalpy and entropy of activation relative
to the molecular solvent case (c2 = 0); the enthalpic change is
ionic liquid solvent interaction for bimolecular nucleophilic
substitution processes. This change is likely due to the
decreased localisation of the lone pair on the arsine 1c (cf.
phosphorus 1b) and hence less ionic liquid-starting material
interaction. An alternative argument is that there is a relative
increase in ionic liquid-transition state interactions affecting the
overall balance of interactions between the two pnicogen 1b and
1c systems. This phenomenon has been observed for the
reaction of triphenylphosphine 1b with benzyl halides (an
equivalent reaction to that shown in Scheme 1) as the leaving
group of the electrophile became more charge diffuse (i.e. as the
halide series went down the periodic table), the ionic liquid-
transition state interaction became the dominate interaction in
the system.[14h] Distinguishing between these two cases is not
possible with the data available. Irrespective there is the
potential to apply this trend to other related systems (such as
going from sulphur to selenium reagents).
For the triphenylantimony 1d system, upon increasing the
amount of ionic liquid in the reaction mixture from c2 = 0 to c2 »
0.2 there is no measurable change in the enthalpy of activation,
but there is an increase in the entropy of activation, such that the
rate constant enhancement might be considered entropically
driven. The origin of this trend is likely increased interaction of
the ionic liquid 2 with, and organisation of the ionic liquid 2 about,
the starting material 1d. Upon increasing the proportion of the
salt 2 in the reaction mixture there is a decrease in both the
enthalpy and entropy of activation at c2 » 0.8 compared to the
parameters determined at both c2 = 0 and c2 » 0.2. This is the
opposite of the trend observed on going from c2 = 0 to c2 » 0.2
suggesting a change in the dominant solvent interaction in the
system as the amount of the ionic liquid 2 in the system
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Table 1. The activation parameters determined for the reaction between the one of the triphenylpnicogens 1b-e and benzyl bromide 3 in mixtures of
[Bmim][N(SO2CF3)2] 2 in acetonitrile. Uncertainties are propagated from the linear regression of the appropriate Eyring plot.
Triphenylphosphine 1b system[a, b]
Triphenylarsine 1c system[b[
Triphenylantimony 1d system[b]
Triphenylbismuth 1e system[b]
c2
»
∆H‡ / kJ mol-1
41.7 ± 3.4
N/A[c]
∆S‡ / J K-1 mol-1
-221 ± 12
N/A[c]
∆H‡ / kJ mol-1
69.3 ± 3.1
59.0 ± 2.6
52.9 ± 3.4
54.5 ± 3.4
∆S‡ / J K-1 mol-1
-175 ± 9
∆H‡ / kJ mol-1
77.3 ± 2.4
81.6 ± 2.7
N/A[c]
∆S‡ / J K-1 mol-1
-151 ± 8
∆H‡ / kJ mol-1
66.0 ± 3.2
N/A[c]
∆S‡ / J K-1 mol-1
-185 ± 10
N/A[c]
0
0.2
0.4
0.8
-199 ± 8
-127 ± 8
57.1 ± 1.5
57.2 ± 1.5[d]
-163 ± 5
-218 ± 10
-212 ± 10
N/A[c]
50.4 ± 3.2
44.3 ± 1.4
-225 ± 10
-244 ± 4
-163 ± 5[d]
63.2 ± 3.2
-187 ± 9
[a]Reproduced from Schaffarczyk McHale et al.[14g] Activation parameters were also determined at c2 » 0.7, these were the same within uncertainty as those
determined at c2 = 0. [b]Uncertainties reported are propagated from the fit of the linear regression. [c] Activation parameters not determined at this solvent
composition, [d]A c2 » 1, rather than c2 » 0.8, was studied for the triphenylphosphine 1b system.[14g]
increases. As was discussed earlier, the origin of a decrease in
both activation parameters in this instance is most likely due to
ionic liquid-transition state interactions; the overall balance of
interactions in solution has changed. Importantly, the balance of
enthalpic and entropic contributions has changed as a result
with the rate constant enhancement at c2 » 0.8 being due to a
net decrease in the enthalpy of activation.
The changes in interactions compared to the other group 15
nucleophiles do not match the trend above and suggest greater
starting material-ionic liquid interaction at low proportions of the
ionic liquid 2 than might be expected with the decreased
localisation of the lone pair on the antimony nucleophile 1d. It
might simply be that the increased size of the antimony atom
allows for better packing of the ionic liquid 2 around the
nucleophilic centre or that changing the pnicogen changes the
nature of the transition state. Notably, the result is a significant
rate constant enhancement. Irrespective, at high proportions of
the salt in the reaction mixture, ionic liquid-transition state
interactions dominate and an enthalpically driven rate constant
enhancement is noted.
In the triphenylbismuth 1e system there is a decrease in both
activation parameters upon increasing the amount of the salt 2
present in the reaction mixture, at both c2 » 0.4 and c2 » 0.8
relative to acetonitrile (c2 = 0). As discussed above, this is most
likely due to ionic liquid-transition state interactions, particularly
as this is the pnicogen furthest down group 15 and, as such, the
lone pair will be the most charge diffuse. The greatest decrease
in both activation parameters occurs on changing the solvent
composition from c2 = 0 to c2 » 0.4 with a less significant, but still
notable, further decrease in both parameters on increasing the
amount of salt in the reaction mixture from c2 » 0.4 to c2 » 0.8.
The initial rate constant enhancement at low proportions of the
salt 2 in the reaction mixture (c2 = 0 to c2 » 0.4) is caused by
favourable ionic liquid-transition state interaction; it is
enthalpically driven. As this interaction changes (due to a
Overall, in each of the systems considered here (and in the
14h]
phosphorus case considered earlier)[14g,
favourable ionic
liquid-transition state interactions dominate at the highest
proportion of the ionic liquid 2 in the reaction mixture (c2 » 0.8)
resulting in rate constant enhancement relative to the molecular
solvent (c2 = 0). Generally, the importance of these effects
increase with the atomic number of the pnicogen, likely due to
reduced interaction of the solvent 2 with the starting material
1.[25] Such trends have the potential to be applied to other
nucleophilic centres from other groups in the periodic table.
Conclusions
From this study, the current predictive rationale for using
ionic liquids for bimolecular nucleophilic substitution processes
has been expanded to incorporate an understanding of how
varying the nucleophilic heteroatom down a group affects the
observed ionic liquid solvent effect. The further down a group
the heteroatom, the more diffuse the electron density on the
nucleophilic centre and ionic liquid-transition state interactions
are more likely to be the dominant in the overall balance of
solvent interactions in the system; there is the potential to exploit
this trend not only in this series, but in other series of
nucleophiles. For all of the pnicogen nucleophiles studied here
and previously,[14g, 14h] rate constant enhancement is observed at
all solvent compositions containing the ionic liquid 2 regardless
of the dominate ionic liquid interaction with species along the
reaction coordinate. Generally, the greatest rate constant
enhancements are observed when ionic liquid-starting material
interactions are present but ionic liquid-transition state
interactions still result in at least a two-fold increase in the rate
constant relative to the molecular solvent.
Comparing this to the previous study where the nature of
the electrophile was varied, in instances where ionic liquid-
transition state interaction was the dominant interaction, rate
constant decreases were observed relative to the molecular
greater amount of the ionic liquid 2 in the reaction mixture, c2
»
0.8) the balance of enthalpic and entropic effects changes and
thus causes the minor decrease in the rate constant observed
(relative to c2 » 0.4).
It is of interest to return to the trend down the series
considered; in this case, interactions involving the transition
state dominate across the range of solvent compositions studied.
As described above, this is likely due to less localisation of
electron density on the triphenylbismuth 1e.
solvent. This difference in the outcome demonstrates
a
difference in the balance of enthalpic and entropic contributions
and allows insight into rational design of bimolecular nucleophilic
substitution processes when choosing an ionic liquid as the
solvent. The nature of the electrophile has a more significant
14h]
and potentially detrimental effect on reaction outcome[14g,
whereas variation of the nucleophilic heteroatom is less critical
and retains the previously noted rate constant enhancement
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that pseudo-first order conditions were maintained) in differing solvent
compositions of the ionic liquid 2 in d3-acetonitrile. The reaction mixtures
were stored at -20 ºC until use as ca. 0.5 mL aliquots in 5 mm NMR
tubes. The temperature of the NMR spectrometer was equilibrated to
75.0 ºC and reaction progress was monitored in situ until the integral of
the signal being monitored had plateaued (>95% completion). Rate
constant data was found to be independent of changes in the
concentration of the nucleophile (cf. reference 11b and references cited
therein). For the triphenylantimony 1d system in acetonitrile signal
overlap was observed at temperatures above 55.0 ºC and as such the
rate constant data for the mole fraction dependence study was
extrapolated from the temperature dependence kinetic studies (vide infra).
expected in bimolecular nucleophilic substitution reactions in the
presence of an ionic liquid.[14a-f]
With the above work in hand, it is possible to summarise
the current state of the art for understanding and predicting ionic
liquid solvent effects on bimolecular nucleophilic substitution
reactions. The electrophile plays a role in controlling transition
state-ionic liquid interactions. Electrophiles which have electron
withdrawing groups and leaving groups that are more charge
diffuse typically result in increased transition state-ionic liquid
interactions. The nucleophile influences whether the ionic liquid
more favourably interacts with either the starting materials or the
transition state. Nucleophiles with a readily accessible lone pair
typical exhibit starting material-ionic liquid interactions whereas
nucleophiles with less accessible lone pairs (such as when the
lone pair is delocalised or more diffuse, i.e. further down a group,
irrespective of that group) tend to result in transition state-ionic
liquid interactions. Unlike the electrophile cases, the balance of
the activation parameters resulting from either of the
aforementioned ionic liquid interactions result in rate
enhancement, relative to the molecular solvent.
For all of the reactions studied, the temperature dependent kinetic
studies were undertaken in an analogous manner to those used in the
mole fraction dependent kinetic studies above. For reactions of the
arsenic and bismuth derivatives 1c and 1e, the rate constants were
determined at 4 different temperatures across a range of 45.0 – 75.0 ºC
at solvent compositions of interest. Due to the aforementioned signal
overlap observed in the triphenylantimony 1d system in acetonitrile, the
temperature range was 34.0 – 55.0 ºC. Fitting these rate constant data to
the bimolecular Eyring equation[24] allowed determination of the activation
parameters of each system at the chosen solvent compositions.
Additional experimental details pertaining to the stock solution
compositions (masses and concentrations of reagents and mole fractions
of ionic liquid), rate constants and equations used to determine these
rate constants can be found in the Supplementary Information.
Experimental Section
The reagents
1
and
3
were purified using literature
was distilled and stored over
methodology.[26]
Benzyl bromide
3
activated 3 Å molecular sieves at -20 ºC prior to use. Triphenylarsine 1c,
triphenylantimony 1d and triphenylbismuth 1e were recrystalised from
acetonitrile and stored at room temperature. d3-Acetonitirile was stored
over activated 3 Å molecular sieves and stored at room temperature. The
ionic liquid [Bmim][N(SO2CF3)2] 2 was prepared through a literature
procedure.[27] 1-Methylimidazole and 1-bromobutane, both distilled before
use, were stirred together for 2 days to form the precursor bromide salt.
Acknowledgements
JBH acknowledges financial support from the Australian
Research Council Discovery Project Funding Scheme (Projects
DP130102331, DP180103682). KSSM acknowledges the
support of the Australian government through the receipt of a
Research Training Programme Stipend. 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.
A
salt
methathesis
reaction
involving
lithium
bis(trifluoromethanesulfonyl)imide was then undertaken to afford the
desired ionic liquid 2. The ionic liquid 2 was dried at room temperature
under reduced pressure until a constant pressure reading (< 0.1 mbar)
was obtained. Karl-Fischer titrimetry showed a water content < 200 ppm
and
a bromide content of < 1 mol% was determined from ion
chromatography proving an absence of the bromide precursor. Further
experimental details can be found in the Supporting Information.
Keywords: ionic liquids • kinetics • nucleophilic substitution •
pnicogens • solvent effects
Unless, otherwise specified reactions were monitored via 1H NMR
spectroscopy using either a Bruker Avance III 400, 500 or 600 NMR
spectrometer equipped with either a BBO, BBFO or TBI probe with
results proving to be reproducible regardless of the spectrometer or the
probe used. The exception to this analytical technique was the reaction
of triphenylantimony 1d with benzyl bromide 3 in acetonitrile. At this
solvent composition significant signal overlap of key resonances due to
the starting material 3 and the product 4d was observed and, as such,
determination of the rate constant using the standard method was not
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a C HSQC broadband selective NMR
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Entry for the Table of Contents
FULL PAPER
An ionic liquid affects the reactivity of
related nucleophiles in bimolecular
substitution reactions differently.
Changing the nucleophilic atom from
P to As to Sb to Bi results in
systematic variation of the ionic
liquid interactions with species along
the reaction coordinate. These
variations result in different effects
as the proportion of the ionic liquid in
the reaction mixture changes and the
periodic trends seen might be
Karin S. Schaffarczyk McHale, Ronald
S. Haines, Jason B. Harper*
Page No. – Page No.
Investigating Variation of the
Pnicogen Nucleophilic Heteroatom
on Ionic Liquid Solvent Effects in
Bimolecular Nucleophilic
Substitution Reactions
applied to other systems.
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