Targeted and Systematic Approach to the Study of pKa Values of Imidazolium Salts in Dimethyl Sulfoxide

Article abstract of DOI:10.1021/acs.joc.7b00716

A range of more than 25 imidazolium salts, chosen for their differing steric and electronic features, were prepared, and their pK_a values were determined using the bracketing indicator method. Through the systematic change in the structure of the imidazolium cation, the effect of varying substituents at each position on the heterocyclic ring was determined; particularly, the transmission of electronic effects was quantified using Hammett parameters. These new data give an indication of the strength of base required for deprotonation and the potential to correlate these data with the nucleophilicity of the corresponding carbenes.

Full text of DOI:10.1021/acs.joc.7b00716

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Article
A targeted and systematic approach to the study
of pKa values of imidazolium salts in DMSO
Michelle H Dunn, Nicholas Konstandaras, Marcus Lawford Cole, and Jason Brian Harper
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b00716 • Publication Date (Web): 26 Jun 2017
Downloaded from http://pubs.acs.org on June 26, 2017
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The Journal of Organic Chemistry
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A targeted and systematic approach to the study of pKa
values of imidazolium salts in DMSO
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Michelle H. Dunn, Nicholas Konstandaras, Marcus L. Cole* and Jason B. Harper*
School of Chemistry, University of New South Wales, Sydney NSW 2052, Australia
KEYWORDS NꢀHeterocyclic carbenes, imidazolium salts, acidity, pKa values, organocatalysis
ABSTRACT: A range of more than 25 imidazolium salts, chosen for their differing steric and electronic features, were prepared
and their pKa values were determined using the bracketing indicator method. Through systematically changing the structure of the
imidazolium cation the effect of varying substituents at each position on the heterocyclic ring was determined; particularly, the
transmission of electronic effects was quantified using Hammett parameters. This new data gives an indication of the strength of
base required for deprotonation and the potential to correlate these data with the nucleophilicity of the corresponding carbenes.
al.21 used deuterium exchange to determine the
kinetic acidities of a number of imidazolium catiꢀ
ons in the aqueous phase.
INTRODUCTION
Over the last two decades there has been conꢀ
siderable development
Studies by
in
the
use
of
O’Donoghue22ꢀ25 extended this to involve a large
number of imidazolium and triazolium cations in
aqueous solutions. Work by Yates et al,26 inꢀ
volved the determination of gas phase acidities.
The most relevant study to this work is by Chu et
al.,27 who investigated the pKa values of a small
number of alkyl imidazolium salts in DMSO usꢀ
ing the bracketing indicator method, with the
values obtained ranging between 19.7 and 23.4.
NꢀHeterocyclic Carbenes (NHCs) in organocatalꢀ
ysis.1ꢀ7 They have been used to facilitate a wide
range of reactions including the reaction of two
aromatic aldehydes (benzoin condensations),8ꢀ10
1,4ꢀadditions (Stetter reactions),11ꢀ13 reactions of
α,βꢀunsaturated
aldehydes,14ꢀ16
and
1,2ꢀadditons.17 In the majority of these reactions,
the carbene catalyst is generated in situ through
deprotonation of the corresponding air stable azꢀ
olium salt. Given this, the pKa value of the correꢀ
sponding salt is of great interest. The pKa allows
the extent of deprotonation of the preꢀcatalyst in
the reaction mixture (and hence the amount of
catalyst present) to be determined and it gives
insight into the nucleophilic nature of the carbene
through the Brønsted relationship.18,£
Despite the aforementioned literature, there has
been no systematic study examining the acidity
of both alkyl and aromatic imidazolium salts in
DMSO. This study aims to extend the current
knowledge of pKa values of azolium cations, with
particular emphasis on Nꢀalkyl and Nꢀaryl imidꢀ
azolium cations. The study was conducted using
a range of imidazolium salts in order to observe
the effect of specific structural changes across the
molecule and to correlate the structure of a given
imidazolium salt with its pKa value.
There have been few studies of the pKa values
of azolium salts. An early study by Alder19 found
the
acidity
of
1,3ꢀdiisopropylꢀ4,5ꢀ
dimethylimidazolium cation to be 24.0 in DMSO
using an NMRꢀbased method. A study by Kim
and Streitwieser20 looked into the acidity of the
1,3ꢀdiꢀtertꢀbutylimidazolium cation in THF,
where it was found to be 20.0, while it was found
to be in the range 22.7ꢀ23.0 in DMSO. Amyes et
RESULTS AND DISCUSSION
The pKa data presented in this paper were deꢀ
termined using the bracketing/overlapping indiꢀ
cator method,28 in which the position of the equiꢀ
librium for the reaction of an indicator of known
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pKa value and the imidazolium salt of interest
Values obtained using the tertꢀbutyl fluorene 6
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2
3
4
5
6
7
8
was measured. The indicators 1-6 chosen (Chart
1) were based on fluorene 5 as their deprotonated
forms absorb significantly in the UVꢀVisible reꢀ
gion; the change in such absorption on addition
of azolium salt allowed determination of the posiꢀ
tion of equilibrium. All pKa values discussed are
determined in DMSO, with values anchored to
those of indicators with known pKa values.28ꢀ30
were routinely higher by ca. 1.4 which suggested
that the reported value for the indicator is incorꢀ
rect.
Consequently, the pKa value of the indicator 6
was determined through titration with benzamide,
which has a literature pKa value of 23.35.31 Using
this data it was determined that the tertꢀbutyl fluꢀ
orene indicator 6 is more acidic than reported in
the literature and has a pKa value of 22.96 ± 0.10.
There are no reports in the literature that use this
indicator in the determination of pKa values, posꢀ
sibly due to the error in the reported pKa value.31
The value of 22.96 was used throughout the calꢀ
culations described herein and gave consistent
data with that measured using other indicators. It
should be noted that the pKa is not unrealistic
given that 9ꢀisobutyl fluorene (pKa = 23.2) and
9ꢀmethylfluorene 4 (pKa = 22.3) exhibit similar
pKa values.28
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Chart 1. Indicators used in this study and their corresponding pKa
values in DMSO;28ꢀ30 the value for compound 6 was determined
herein.
The first series of compounds investigated was
that containing Nꢀalkyl chains; compounds 7-12
(Chart 2). While these aren’t as common in the
field of NHC organocatalysis as their Nꢀaryl sysꢀ
tems counterparts, they represent a useful starting
point and are the cation of many ionic liquids.16,32
The compounds chosen allow the effects of varyꢀ
ing the nature of the Nꢀalkyl substituents from
primary through tertiary, on the pKa value of the
imidazolium salt to be determined (Table 1).
Note that all the salts investigated had a common
anion (chloride) to allow direct comparison.
Whilst there is the potential for ion pairing even
in a dissociating solvent such as DMSO20 (and
ion pairing would be expected to affect the obꢀ
served pKa value for salts containing the same
cation but different anion) at the concentrations
used here ion pairing would be expected to be
negligible.33 There is literature precedent supꢀ
porting this argument, with demonstration that
the anion has no effect (with all values within
uncertainty) on the pKa values of Nꢀalkyl imidazꢀ
In determining the position of equilibrium, the
absorption due to both the NHC and the salt are
also considered, though that of the deprotonated
fluorene indicator dominates. The position of
equilibrium for each compound is based on all
data from the titration. The uncertainties are
based on replicate experiments, which are typiꢀ
cally greater than any uncertainties from regresꢀ
sion analysis, and hence are a truer representation
of the uncertainty. Each of the pKa values reportꢀ
ed herein is the result of at least three measureꢀ
ments with an appropriate indicator and bracketꢀ
ed with at least one other indicator. It is imꢀ
portant to use an appropriate fluorene indicator
for each titration; that is a fluorene possessing a
pKa value that is within two pKa of the imidazoliꢀ
um salt to be measured.27 Outside of this, changꢀ
es in the equilibrium for the reaction described
are too difficult to follow reliably.
Several inconsistencies were noted during the
application of tertꢀbutylfluorene 6 as an indicator.
These resulted from use of its reported pKa value
of 24.4.29 It was initially chosen for use as a
bracketing indicator for compounds with pKa
values >22.6 but in each experiment the indicator
6 gave a different pKa value to those determined
using fluorene 5 as the indicator (pKa = 22.6).
olium
salts,
in
particular
1ꢀbutylꢀ3ꢀ
methylimidazolium salts in dimethyl sulfoxide
under similar conditions to those used here,27
suggesting ion pairing does not affect the pKa
values determined. This will be commented upon
further below.
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The Journal of Organic Chemistry
The pKa data for the six imidazolium salts
bon in species 7 and 8) and solvation (larger side
chains maybe harder to solvate, hence affecting
the relative stability of the cationic and neutral
forms). Deconvoluting each of these is not realꢀ
istic with the data available.
1
2
3
4
5
6
7
8
measured herein is listed in Table 1. Data for
compounds 9 and 10 are consistent with those
reported.20,27 On changing the substituents at the
nitrogen centres of the imidazolium salts, from
primary (compound 10) to secondary (comꢀ
pounds 7 and 8) and tertiary (compound 9), an
increase was observed in the pKa values. This
increase, along with the magnitude of such, is
consistent with that observed previously for simiꢀ
lar systems by Chu et al.27
From a comparison of the pKa values of the
4,5ꢀdiprotioimidazolium salt 10 and the
4,5ꢀmethylated derivative 11, incorporating meꢀ
thyl groups at both the 4ꢀ and 5ꢀpositions inꢀ
creases the pKa value by 0.93 ± 0.15. This can be
attributed to the electron donating ability of the
methyl substituents, adding electron density into
the imidazolium ring and stabilising the cationic
form relative to the carbene. The magnitude of
this change is consistent with a similar compariꢀ
son between the diisopropylimidazolium salt 7
and its 4,5ꢀdimethylated counterpart which has a
reported pKa value of 24.0.19
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R'
R''
N
N
N
N
R
R
Cl
Cl
7 R = iPr
8 R = Cy
9 R = tBu
10 R'/R'' = H
11 R'/R'' = Me
12 R' = Cl, R'' = H
Chlorination of the 4ꢀposition on the imidazoliꢀ
um ring results in a substantial decrease in the
pKa value of the species; salt 12 has a pKa value
ca. 1.7 lower than its 4ꢀprotio counterpart, 10.
Whilst a decrease in the pKa value on chlorinaꢀ
tion was expected, based on the electron withꢀ
drawing nature of the substituent being added, it
is perhaps surprising that the magnitude of the
change is greater than for the addition of two meꢀ
thyl groups. It may therefore be inferred that the
relative effect of inductive and resonance contriꢀ
butions in these systems is different.
Chart 2. The alkyl imidazolium salts 7-12 investigated in this
study.
Table 1. pKa values of the N-alkyl imidazolium salts 7-12 in
DMSO at 25°C determined using the bracketing indicator
method. Uncertainties are reported as the standard devia-
tion multiplied by the t-student value for between four and
six measurements.
Compound
pKa value
22.84 ± 0.09
22.26 ± 0.09
22.70 ± 0.11
22.00 ± 0.07
22.93 ± 0.13
20.29 ± 0.14
7
8
9
10
11
12
Given these substituent effects, it is also of inꢀ
terest to consider the impact of extending the arꢀ
omatic system on the acidity of such salts by conꢀ
sidering the benzimidazolium 13. This salt has a
pKa value of 20.60 ± 0.13, which is markedly
lower than the corresponding protiated imidazoꢀ
lium compound 9, with a difference in the pKa
values of 2.1 ± 0.2. This increase in acidity is
reasonable given the greater ability of salt 13 to
delocalise the positive charge whilst the magniꢀ
tude of the difference is consistent with the work
of Amyes,21 who noted a decrease in pKa of 1.4 ±
0.71 for the corresponding N,N'ꢀdimethyl species.
These results suggest that increased substitution
at the αꢀcarbon results in stabilization of the imꢀ
idazolium salt relative to the conjugate carbene.
However there is a negligible difference in the
pKa value between the Nꢀisopropyl system 7 and
the Nꢀtertꢀbutyl system 9, while the pKa value of
the Nꢀcyclohexylimidazolium 8 is 0.44 ± 0.14
lower than the tertꢀbutyl substituted salt 9. This
suggests that pKa value of a system relies on
more than purely inductive effects (in such a
case, the order of pKa values might be expected
to be 10 < 7 ≈ 8 < 9).
Given the demonstrated importance of electronꢀ
ic effects on azolium salt pKa values and the
ubiquity of N,N'ꢀdiarylimidazolium precatalysts
in the literature, the next series considered were
the compounds 14-28 (Chart 3). These permit
Potential contributing factors to be considered
here are through space interactions, conformaꢀ
tional differences (for example at the alpha carꢀ
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14 X = OMe
15 X = Me
16 X = H
17 X = F
18 X = Cl
19 X = Br
N
N
N
N
Cl
X
X
X
X
Cl
13 R = tBu
the effects of varying the arene electronics and
the imidazolium to Nꢀarene conformation on the
pKa values of imidazolium salts to be discerned
(Table 2). Once again all the salts investigated
had a common anion (chloride) to allow direct
comparison though, as discussed above, the naꢀ
ture of the anion would not be expected to have a
significant effect in DMSO at the concentrations
used. Note that in this case, in addition to salt 20,
20 X = Me
21 X = H
22 X = F
23 X = Cl
24 X = Br
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N
N
Cl
R
N
R
N
25 R = H
26 R = Me
six
other
1,3ꢀbis(2',4',6'ꢀ
Cl
trimethylphenyl)imidazolium salts containing
different anions (bromide, tetrafluoroborate, triꢀ
flate,
perchlorate,
hexafluorophosphate,
bis(trifluomethanesulfonyl)imide) were considꢀ
ered. All were found to have the same pKa value
(within uncertainty) thereby demonstrating that
the pKa value of the salt is solely dependent on
the cation (see Supporting Information).
R'
R''
27 R' = H, R'' = Me
28 R'/R'' = Me
N
N
Cl
A comparison of the pKa values listed in Tables 1
and 2 indicates that the pKa values of the Nꢀaryl
imidazolium salts are significantly lower than
those determined for the Nꢀalkyl imidazolium
salts with equivalent 4,5ꢀdisubstitution (Table 1).
This is consistent with the previous observations
in deuterium oxide22 and suggests that in DMSO
the aryl groups behave as electron withdrawing
groups relative to the Nꢀalkyl substituents of
7ꢀ12. This destabilises the parent cation relative
to the carbene causing a decrease in the pKa valꢀ
ue.
Chart 3. The Nꢀaryl imidazolium salts 14-28 investigated in this
study.
Table 2. pKa values of the N-aryl imidazolium salts 14-28 in
DMSO at 25°C determined using the bracketing indicator
method. Uncertainties reported are reported as the stand-
ard deviation multiplied by the t-student value for between
four and six measurements.
Compound
pKa value
18.75 ± 0.10
18.50 ± 0.16
18.33 ± 0.09
18.21 ± 0.16
18.05 ± 0.22
18.07 ± 0.11
19.40 ± 0.12
19.28 ± 0.14
19.07 ± 0.16
18.91 ± 0.11
18.95 ± 0.18
19.29 ± 0.07
23.71 ± 0.16
22.75 ± 0.14
23.79 ± 0.15
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
The effect of the 4'ꢀaryl substituents on imidazꢀ
olium salt pKa values can be quantified through
considering a plot of the measured pKa value
against the Hammett sigma (σ) value of the inꢀ
cluded 4ꢀaryl substituent in each of the salts 14ꢀ
19 (Figure 1). A clear trend in pKa values can be
seen for compounds 14-19 with 4'ꢀsubstituted
aryl substituents on the nitrogen centres. As
changing the substituent at this position would
not be expected to have any steric effects, the difꢀ
ferences in pKa values in these systems derive
from
the
electronic
nature
of
the
4'ꢀsubstituent on the aryl rings.
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The Journal of Organic Chemistry
19
18.8
19.6
19.5
19.4
19.3
19.2
19.1
19
1
2
3
4
5
6
7
8
18.6
18.4
18.2
9
18.9
18.8
18.7
18
10
11
12
13
14
15
17.8
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
-0.2
-0.1
0
0.1
0.2
0.3
Hamme
σ
value
Hamme
σ
value
FIGURE 1. Correlation between the Hammett σ value of the
4'ꢀaryl substituents34 of the imidazolium salts 14-19 and their
measured pKa values in DMSO at 25°C.
FIGURE 2. Correlation between the Hammett σ value of the
4'ꢀaryl substituents34 of the imidazolium salts 20-25 and their
measured pKa values in DMSO at 25°C.
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17
18
19
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21
22
23
24
25
26
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The negative slope of the linear fit is consistent
with the more electron withdrawing groups deꢀ
stabilising the cation relative to the correspondꢀ
ing carbene thus lowering the pKa value. The
slope corresponds to the negative of the Hammett
susceptibility constant, ρ, thus allowing compariꢀ
son to systems in the literature. In this case the
slope is ꢀ1.25 ± 0.09 demonstrating that the subꢀ
stituents are having a larger effect on the acidity
of the imidazolium salts 14-19 than in the acid
dissociation of substituted benzoic acids. A furꢀ
ther useful comparison is with the effect of subꢀ
stitution on the acid dissociation of protonated
anilines, given that both reactions involve posiꢀ
tive charges on a nitrogen centre (or centres).
That process has a ρ value of ca. 2ꢀ4 across a
range of solvents and temperatures;35 the effect of
the substituent is less in the case of the imidazoꢀ
lium salts 14-19. The decrease in the magnitude
of ρ is consistent with delocalisation of the posiꢀ
tive charge on the imidazolium systems rather
than on a single nitrogen centre as in the aniline
case.
σ value of the 4'ꢀsubstituent for each of the imidꢀ
azolium salts 20-24 as before (Figure 2).
Immediately apparent is that the slope of the
linear fit is once again negative, consistent with
the increase of acidity of the salts with increasing
electron withdrawing ability of the 4'ꢀsubstituent.
The slope of the linear fit is ꢀ1.23 ± 0.10; this is
the same as the slope determined from the pKa
data for 2',6'ꢀdiprotioimidazolium salts 14-19
indicating that in both cases the substituents on
the phenyl group affect the acidity of the salt to
the same extent. That is, the methyl groups at the
2'ꢀ and 6'ꢀpositions do not change the transmisꢀ
sion of electronic effects, irrespective of any
changes to conformation that may result.
It is of interest to consider the magnitude of the
difference between the parallel lines presented in
Figures 1 and 2; based on the line of best fit, the
difference in pKa between the two systems is ca.
0.9 at the intercept. This difference can be atꢀ
tributed to the electronic effects of the methyl
groups at the 2'ꢀ and 6'ꢀpositions; being electron
donating they stabilise the cation relative to the
corresponding carbene resulting in a higher pKa
value.
Further to the N,N'ꢀdiarylimidazolium salts
above, the pKa values of salts 20-24 that contain
2',6'ꢀalkylsubsituents are also of interest. Comꢀ
parison with the previous cases not only allows
the effect of methylation on the pKa values to be
determined but also the investigation of the
transmission of electronic effects in a system
with different steric constraints, wherein the
N,N'ꢀdiarylimidazolium arene to imidazolium
interplanar angles could affect conjugation. The
measured the pKa values were plotted against the
The effect of changing the steric nature of the
substituents at the 2'ꢀ and 6'ꢀpositions on pKa can
be determined by comparing the acidities of salts
20 and 25. The pKa values of these two species
are the same (within uncertainty) which, in comꢀ
bination with the very similar electronic nature of
the two substituents, suggest that any steric efꢀ
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aAverage of the two angles; see Supporting Information for the
individual values.
fects of groups at these positions on pKa value are
negligible
1
2
3
4
5
6
7
8
9
On addition of methyl groups to the 4ꢀ and
5ꢀpositions of the N,N'ꢀdiarylimidazolium scafꢀ
fold, the pKa value of the salt increases by ca. 4.4
based comparison of salts 20 and 28, and 25 and
26. This is significantly larger than the effect
seen in the case of N,N'ꢀdialkylimidazolium salts
(a change in pKa of ca. 1). Including analysis of
Firstly, the addition of methyl groups at the
2'ꢀ and 6'ꢀpositions results in substantial torsion
within the resultant species (viz. compounds 15
and 20). These substituents promote twisting of
the Nꢀaryl substituent out of the imidazolium
plane (see Figure S2, Supporting Information),
thereby diminishing conjugation of the
πꢀsystems. This likely contributes to the inꢀ
creased acidities of imidazoliums 15-19 relative
to their 2',6'ꢀdimethyl counterparts 20-24 respecꢀ
tively.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
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data for the salt 27, where
a
single
4,5ꢀposition is methylated, these data show that
the addition of the first methyl group results in an
increase in the pKa value of 3.35 ± 0.18, while the
addition of the second methyl group leads to an
increase in the pKa value of 1.04 ± 0.21. The
latter is comparable to the effect of two methyl
groups at the 4ꢀ and 5ꢀpositions of
N,N'ꢀdialkylimidazolium systems (viz. salts 10
and 11).
Secondly, while one might expect the 4ꢀmethyl
and 4,5ꢀdimethyl imidazolium salts 27 and 28 to
adopt dihedral angles closer to 90° due to inꢀ
creased steric buttressing between the substituꢀ
ents, the observed dihedral angles are comparable
to those in salt 20 and likewise substantially
greater than those of 2',6'ꢀdiprotio analogue 15
(Table 3, Figure S3). Thus, the observed reducꢀ
tion in acidity from species 20 to compounds 27
and 28 results from the electronic influence of the
methyl substituents rather than conformational
changes.
Crystal structures of salts 27 and 28 were deꢀ
termined (see Supporting Information) and comꢀ
pared with that reported for the 4,5ꢀdiprotio salt
2036 and the related 4ꢀtolyl derivative 15.37 Table
3 summarises the salient information from these
data; the C2'ꢀC1'ꢀNꢀC2 dihedral angle is a measꢀ
ure of rotational conformation of the Nꢀaryl and
imidazolium rings in the compound whilst the
endocyclic NꢀCꢀN bond angle is a measure of
Further to the Nꢀaryl to imidazolium dihedral
angles, there is no difference in the NꢀCꢀN bond
angles in the species 15, 20, 27 and 28. This is
π
ꢀdelocalisation with a greater value indicating
greater delocalization.
consistent
with
a
similar degree of
πꢀdelocalisation across all four imidazolium sysꢀ
tems.
With the caveat that correlations between solidꢀ
state data and solution behaviour are inherently
fraught, the dihedral angles presented in Table 3
allow several predictions to be made regarding
the likely conformation of the Nꢀaryl groups relaꢀ
tive to the imidazolium rings of compounds 14ꢀ
28.
Whilst these data give some insight into the
structural nature of the salts 15, 20, 27 and 28,
they alone do not account for the differences in
observed pKa values. Factors (such as packing
effects) may dominate other aspects which are
important outside of the solid state.
Semiꢀempirical (PM338) gas phase calculations
were also carried out using the EMPIRE software
suite39,40 and the same information as discussed
above was determined for the structure of miniꢀ
mum energy for the cations of salts 20, 27 and 28
(Table 4). The data determined gave significantly
different information to that from the crystal
structures.
Table 3. Comparison of N-C-N bond angle and interplanar
dihedral angles of the salts 15, 20, 27 and 28 from crystal
structure data with their corresponding pKa values.
N-C-N bond
angle / °
C2'-C1'-N-C2
Salt
pKa value
bond angle a / °
1537
2036
27
109.8
12.8
77.9
74.5
82.4
18.50 ± 0.16
19.40 ± 0.12
22.75 ± 0.14
23.79 ± 0.15
108.25(9)
108.1(2)
107.9(2)
Of particular interest from the gas phase calcuꢀ
lations is the increase in the torsion angles upon
28
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The Journal of Organic Chemistry
Table 4. Comparison of N-C-N bond angle and torsion
angles of the cation of salts 20, 27 and 28 determined using
gas phase calculations with their corresponding pKa values.
greater than one. This indicates that the theoretiꢀ
1
2
3
4
5
6
7
8
cal calculations reported overestimate pKa values
at the upper end of the scale and underestimate
them for lower values.
Cation of
compound
N-C-N bond C2'-C1'-N-C2
pKa value
angle / °
bond angle / °
Comparison of the pKa data obtained in DMSO
with that in water allows an assessment of the
effect of solvation. Comparison of the data for
species 9, 10, 14, 18, 21 and 25 in water22 and
DMSO shows a reasonable correlation (Figure 3).
While the data set is limited, as the slope of the
correlation is ca. 1 the relative energy differences
(between the protonated and deprotonated forms
for two different species) are approximately the
same in both solvents.
106.5
77.4, 77.4
19.40 ± 0.12
22.75 ± 0.14
23.79 ± 0.15
20
27
28
106.6
85.9,a 75.8
90.0, 90.0
108.8
9
aFor the aromatic ring nearest the 4ꢀmethyl group.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
comparing the 4,5ꢀdiprotiated system to the
4ꢀmethylated system, with a further increase upꢀ
on addition of the second methyl group. The inꢀ
crease in torsion angles is consistent with the meꢀ
thyl groups forcing the aryl groups to be out of
the plane with the azolium ring. This change in
orientation may alter the extent to which electron
density is donated from the nitrogen substituents.
26
25
24
23
22
21
20
19
In order to investigate this potential electronic
effect, the energies of the highest occupied moꢀ
lecular orbitals (HOMOs) and the lowest unocꢀ
cupied molecular orbitals (LUMOs) along with
their corresponding electron density maps were
determined (see Figure S4 and Table S4, Supportꢀ
ing Information).
17
18
19
pK
20
21
22
23
From the calculations, the largest HOMO–
LUMO gap was observed in the 4,5ꢀdimethyl
system, with systematically smaller gaps noted
for the 4ꢀmethylated and protiated systems; the
predominant origin of the change is the energy of
the LUMO. Consideration of the electron density
in the LUMO shows that 4,5ꢀdimethylated 28 has
less electron density located on the aryl substituꢀ
ents than its single methylated and protiated
counterparts. This highlights that the positioning
of the Nꢀaryl substituent compared to the heteroꢀ
cyclic portion can affect the extent of conjugation
even at relatively high torsion angles. Therefore
the increase in electron donation at the carbenic
centre and subsequent increase in pKa is likely
due to a combination of the addition of methyl
groups and the change in orientation (and conjuꢀ
gation) of the Nꢀaryl substituents.
a
value in DMSO
FIGURE 3. Correlation between the pKa values of the salts 9, 10,
14, 18, 21 and 25 in DMSO at 25°C (this work) and in water at
25°C.22
It would be very useful to be able to make comꢀ
parisons of acidity of the imidazolium salts menꢀ
tioned above in other solvents such as tetrahydroꢀ
furan (particularly given its prevalence as a solꢀ
vent in organocatalytic systems), however only
one such pKa value has been reported; that of the
cation of salt 9. This cation has a pKa value of
20.0 in tetrahydrofuran,20 which is significantly
lower than the same compound in dimethyl sulꢀ
foxide (pKa = 22.70 ± 0.11, vida supra) and water
(pKa = 25.222). This could be due to there being a
greater amount of hydrogen bonding in both diꢀ
methyl sulfoxide and water compared to tetrahyꢀ
drofuran; this greater hydrogen bonding in the
DMSO and water stabilises the protonated form
relative to the carbene, resulting in a higher pKa
value in these solvents.
Given these data, it is important to compare
them to existing measurements of pKa values.
Initially, comparison of experimental data here
with values determined computationally for the
cations 7, 8, 16 and 21 in DMSO26 (Figure S5).
Though the data set is limited, the correlation is
good (R2 = 0.987) and, interestingly, the slope is
In conclusion, the pKa values of a wide range of
systematically chosen imidazolium salts have
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been determined. From this work, an understandꢀ
1,3-bis(4'-Chlorophenyl)imidazolium chlo-
1
2
3
4
5
6
7
8
ing of the effect on the acidity of an imidazolium
salt on varying the structure of the cation has
been gained. This has been quantified in terms of
ride 18. To a solution of pꢀchloroaniline (3.19 g,
25.0 mmol) in acetic acid/water (3:1 v/v, 20 cm3),
37% aqueous formaldehyde (1.0 cm3, 0.37 g, 12
mmol) was added dropwise over ten minutes. Afꢀ
ter a few seconds, a solid precipitated from soluꢀ
tion. To this mixture, glyoxal (40% in water, 1.50
cm3, 1.89 g, 13.1 mmol) was added and the mixꢀ
ture was stirred at 40oC for an hour. After being
allowed to cool to room temperature, hydrochloꢀ
ric acid (6.0 cm3, 3 M, 18 mmol) was added and
the mixture was heated at reflux for 30 minutes
during, which time all the solids dissolved. The
solution was allowed to cool to room temperature
and diluted with water (20 cm3), whereupon a
solid precipitated from solution. The solid was
collected through filtration, air dried and recrysꢀ
tallised from dichloromethane/diethylether to
give the title compound 18 as a white crystalline
solid (4.95 g, 15.2 mmol, 61%). m.p. 260ꢀ262°C
varying
the
electronic
properties
of
Nꢀsubstituents. Further the importance of conꢀ
formation was probed for 4,5ꢀsubstituted
N,N'ꢀdiaryl imidazolium salts. These data, along
with acting as a guide to the acidity of related
imidazolium salts, allow determination of approꢀ
priate bases for the use of these azolium salts as
precursors for organocatalysts, as well as offering
the potential for their correlation with the nucleoꢀ
philicity of their corresponding carbenes.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
EXPERIMENTAL
Fluorene 5 and carbazole 3 were acquired from
commercial sources and used without further puꢀ
rification. The substituted fluorenes 1, 2, 4 and 6
were prepared through reaction of fluorenone
with the corresponding Grignard reagent, folꢀ
lowed by reduction of the resultant alcohols (see
Supporting Information).41
1
(lit.22 not reported). H NMR (300 MHz, dimeꢀ
thyl sulfoxideꢀd6) δ 10.50 (br s, 1H, C2ꢀH), 8.61
(s, 2H, C4,5ꢀH), 7.99 (m, 4H, C3'ꢀH), 7.82 (m,
4H, C2'ꢀH). 13C NMR (300 MHz, dimethyl sulꢀ
foxideꢀd6) δ 135.1 (C2), 134.6 (C4'), 133.5 (C1'),
130.5 (C2'), 124.9 (C3'), 121.9 (C4,5). IR (Solꢀ
id): vmax 3339 (br, w), 3090 (w), 2999 (w), 1554
(sh,m), 1488 (sh, m), 1310 (w), 1257 (sh, m),
1096 (sh, s), 1008 (sh, m) 824 (sh, s) cmꢀ1.
Found HRMS (ESIꢀTOF) m/z: (M+). Calcd for
Imidazolium salts 8 and 13 were acquired from
commercial sources and used without further puꢀ
rification. The diaryl derivatives 16 and 26 were
purchased from Star Synthesis Inc. The alkyl
imidazolium salts 10 and 11 were prepared acꢀ
cording to literature methods from the correꢀ
sponding imidazoles,27 while the chloro derivaꢀ
tive 12 was the generous gift of Rebecca Hawkꢀ
er.42 The symmetrical salts 7, 9, 15 and 17-19
were prepared from the corresponding amines in
a one pot synthesis with glyoxal and paraformalꢀ
dehyde.36,43 The aryl imidazolium salts 14 and
20-25 were prepared from the corresponding aniꢀ
lines through the 1,4ꢀdiazabutadiene intermediꢀ
ates with subsequent reaction with paraformaldeꢀ
hyde.44,45 The methylated imidazolium salts 27
and 28 were prepared from the corresponding
anilines through the formamidine intermediates
in a manner analagous to previously reported.46,47
A range of 1,3ꢀbis(trimethylphenyl)imidazolium
salts with different anions were prepared through
metathesis of the chloride 20; ion chromatogꢀ
raphy was used to confirm successful transforꢀ
mation of the precursor (see Supporting Inforꢀ
mation). High resolution mass spectra were obꢀ
tained on a Waters QꢀTOF Ultima tandem mass
spectrometer.
+
C15H11Cl2N2 : 289.0294; Found 289.0295. .
Found:
C
52.32;
H
3.93;
N
7.93%.
C15H11Cl3N2.H2O requires C 52.43; H 3.81; N
8.15%.
1,3-bis(4'-Bromophenyl)imidazolium chlo-
ride 19. To a solution of pꢀbromoaniline (4.27 g,
24.8 mmol) in acetic acid/water (3:1 v/v, 20 cm3),
aqueous formaldehyde (1.0 cm3, 0.37 g, 12
mmol) was added dropwise over 10 minutes. Afꢀ
ter a few seconds, a solid precipitated from soluꢀ
tion. To this mixture, glyoxal (40% in water, 1.50
cm3, 1.89 g, 13.1 mmol) was added dropwise
over 10 minutes and the mixture was stirred at
40°C for an hour. After being allowed to cool to
room temperature, hydrochloric acid (6.0 cm3, 3
M, 18 mmol) was added and the mixture was
heated at reflux for 30 minutes, during which
time all the solids dissolved. The solution was
allowed to cool to room temperature and diluted
with water (20 cm3), whereupon a solid precipiꢀ
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The Journal of Organic Chemistry
tated from solution. The solid was collected
added portionwise over 5 minutes with stirring.
1
through filtration, air dried and recrystallised
from dichloromethane/diethylether to give the
title compound 19 as a white crystalline solid
(3.27 g, 7.89 mmol, 64%) m.p. >245°C (dec.). 1H
NMR (300 MHz, dimethyl sulfoxideꢀd6) δ 10.49
(br s, 1H, C2ꢀH), 8.60 (s, 2H, C4,5ꢀH), 7.95 (m,
4H, ArꢀH), 7.91 (m, 4H, ArꢀH). 13C NMR (75
MHz, dimethyl sulfoxideꢀd6) δ 135.0 (C2), 133.9
(C4'), 133.1 (C1'), 124.1 (C3'), 123.0 (C4'), 121.9
(C4,5). IR (Solid): vmax 3338 (br, w), 3087 (w),
3010 (w), 1665 (m), 1588 (sh, w), 1552 (m),
1484 (s), 1424 (m), 1341 (m), 1307 (m), 1255
(sh, m), 1072 (sh, s), 1005 (sh, s), 904 (w), 820
(sh, s), 768 (sh, m) cmꢀ1. Found HRMS (ESIꢀ
After the reaction mixture had been stirred for an
hour at room temperature, the resulting mixture
was filtered through celite, the filtrate was colꢀ
lected and the solvent was removed under reꢀ
duced pressure. The resulting white solid was
dried in vacuo over 30 minutes and recrystallised
from dichloromethane/hexane to yield the desired
salt as white crystals (3.59 g, 8.87 mmol, 90%).
m.p. 244ꢀ247°C (lit.49 not reported). 1H NMR
(300 MHz, chloroformꢀd1) δ 9.00 (m, 1H, C2ꢀH),
7.57 (m, 2H, C4,5ꢀH), 7.04 (s, 4H, ArꢀH), 2.35 (s,
6H, C4'ꢀCH3), 2.12 (s, 12H, C2'ꢀCH3). 13C NMR
(75.5 MHz, chloroformꢀd1) δ 141.7 (C2), 137.5
(ArꢀC), 134.0 (ArꢀC), 130.3 (ArꢀC), 130.0 (C3'),
125.0 (C4,5), 21.2 (C4'ꢀCH3), 17.3 (C2'ꢀCH3).
Found: C 62.33; H 6.28; N 6.98%. C21H25ClO4N2
requires C 62.30; H 6.22; N 6.92%.
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
+
TOF) m/z: (M+) Calcd for C15H1179/81Br2N2
376.9482 (50%), 378.9263 (100%), 380.9243
(50%); Found 376.9286 (50%), 378.9261
(100%). 380.9236 (50%). Found: C 41.97; H
3.09; N 6.29%. C15H11Cl1Br2N2.H2O requires C
41.65; H 3.03; N 6.48%.
1,3-bis(2',4',6'-Trimethylphenyl)imidazolium
trifluoromethanesulfonate. To a suspension of
the chloride salt 20 (0.760 g, 2.23 mmol) in chloꢀ
roform (25 cm3), silver(I) trifluoromethanesulꢀ
fonate (0.620 g, 2.41 mmol) was added portionꢀ
wise over 5 minutes with stirring. After the reacꢀ
tion mixture had been stirred for an hour at room
temperature, the resulting mixture was filtered
through celite, the filtrate collected and the solꢀ
vent was removed under reduced pressure. The
resulting white solid was dried in vacuo over 30
minutes and recrystallised from dichloromethane.
This gave the title compound as a white crystalꢀ
line solid (0.66 g, 1.21 mmol, 54%). m.p. 203ꢀ
1,3-bis(2',4',6'-Trimethylphenyl)imid-
azolium tetrafluoroborate. To a solution of the
chloride salt 20 (8.69 g, 25.5 mmol) in dichloroꢀ
methane (40 cm3), sodium tetrafluoroborate (2.80
g, 25.5 mmol) was added in portions over 15
minutes. The resulting mixture was stirred for 12
hours at room temperature. To the reaction mixꢀ
ture after this time, water (40 cm3) was added and
the resulting mixture was washed with dichloroꢀ
methane (4 x 10 cm3), the organic layers were
combined and cooled on an ice bath. The solid
that formed was recrystallised from dichloroꢀ
methane/hexane to give the title compound as a
white crystalline solid (9.83 g, 25.1 mmol, 98%).
m.p. 230ꢀ231°C (lit.48 240ꢀ243°C). 1H NMR
(300 MHz, chloroformꢀd1) δ 8.92 (t, J = 1.6 Hz,
1H, C2ꢀH), 7.55 (d, J = 1.6 Hz, 2H, C4,5ꢀH),
7.06 (s, 4H, ArꢀH), 2.36 (s, 6H, C4'ꢀCH3), 2.14 (s,
12H, C2'ꢀCH3). 13C NMR (75.5 MHz, chloroꢀ
formꢀd1) δ 141.7 (C2), 137.6 (ArꢀC), 134.0 (Arꢀ
C), 130.3 (ArꢀC), 130.0 (C3'), 124.9 (C4,5), 21.2
(C4'ꢀCH3), 17.2 (C2'ꢀCH3). 19F NMR (282 MHz,
chloroformꢀd1) δ ꢀ152.83 (s, 4F, BF4), ꢀ152.77 (s,
1F, BF4).$ Found: C 64.54; H 6.45; N 7.15%.
C21H25BF4N2 requires C 64.30; H 6.42; N 7.14%.
1
205°C (lit.49 not reported). H NMR (300 MHz,
chloroformꢀd1) δ 9.22 (m, 1H, C2ꢀH), 7.56 (m,
2H, C4,5ꢀH), 7.02 (s, 4H, ArꢀH), 2.35 (s, 6H, C4'ꢀ
CH3), 2.10 (s, 12H, C2'ꢀCH3). 13C NMR (75.5
MHz, chloroformꢀd1) δ 141.5 (C2), 138.0 (ArꢀC),
134.0 (ArꢀC), 130.4 (ArꢀC), 129.9 (C3'), 124.9
(C4,5), 21.2 (C4'ꢀCH3), 17.3 (C2'ꢀCH3). 19F
NMR (282 MHz, chloroformꢀd1) δ ꢀ78.73 (CF3).
Found:
C
58.16;
H
5.56;
N
6.20%.
C22H25F3N2O3S requires C 58.14; H 5.54; N
6.16%.
1,3-bis(2',4',6'-Trimethylphenyl)imidazolium
hexafluorophosphate. To a solution of the chloꢀ
ride salt 20 (5.34 g, 15.7 mmol) in water (50
cm3), ammonium hexafluorophosphate (2.56 g,
15.7 mmol) was added portionwise over five
minutes and the mixture was stirred at room temꢀ
perature for one hour. The resulting suspension
1,3-bis(2',4',6'-Trimethylphenyl)imidazolium
perchlorate. To a suspension of the chloride salt
20 (3.37 g, 9.89 mmol) in chloroform (100 cm3),
silver(I) perchlorate (2.25 g, 10.8 mmol) was
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was filtered and the residue was washed with
1,3-bis(2',4',6'-Trimethylphenyl)imidazolium
1
hexane. Ion chromatography demonstrated that
the material was ca. 6% by mole the chloride 20.
This material was suspended in water (50 cm3)
and ammonium hexafluorophosphate (1.27 g,
7.79 mmol) was added. The resultant mixture
was stirred at room temperature for one hour. The
resulting suspension was filtered and the residue
was washed with hexane, yielding the title comꢀ
pound as a white solid (6.35 g, 14.10 mmol,
bromide. To a suspension of the tetrafluoroboꢀ
rate salt 19 (4.96 g, 12.7 mmol) in ethyl acetate
(100 cm3), a solution of tetrapropylammonium
bromide (13.37 g, 50.21 mmol) in acetone (200
cm3) was added dropwise over ten minutes. The
resulting mixture was stirred overnight at room
temperature. The resulting suspension was filꢀ
tered and the residue was washed with ethyl aceꢀ
tate and dried under vacuum. Analysis (19F NMR
spectroscopy) indicated the presence of tetraꢀ
fluoroborate anions in this crude product. As
such, the procedure was repeated with the crude
product suspended in ethyl actetate (150 cm3),
with the addition of a solution of tetrabuꢀ
tylammonium bromide (20.03 g, 62.13 mmol) in
acetone (250 cm3). The mixture was stirred for 24
hours at room temperature. The resultant suspenꢀ
sion was filtered and the precipitate washed with
ethyl acetate and dried under reduced pressure.
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
90%). m.p. >300°C (lit.50 >300°C). H NMR
(300 MHz, chloroformꢀd1) δ 8.59 (t, J = 1.6 Hz,
1H, C2ꢀH), 7.54 (d, J = 1.6 Hz, 2H, C4,5ꢀH),
7.04 (s, 4H, ArꢀH), 2.35 (s, 6H, C4'ꢀCH3), 2.10 (s,
12H, C2'ꢀCH3). 13C NMR (75.5 MHz, chloroꢀ
formꢀd1) δ 141.8 (C2), 136.6 (ArꢀC), 134.0 (Arꢀ
C), 130.2 (ArꢀC), 130.0 (C3'), 125.2 (C4,5), 21.2
(C4'ꢀCH3), 17.1 (C2'ꢀCH3). 19F NMR (282 MHz,
2
chloroformꢀd1) δ ꢀ72.69 (d, JFP = 710 Hz, PF6).
Found: C 55.98; H 5.50; N 6.26%. C21H25F6N2P
requires C 56.00; H 5.59; N 6.22%.
19
Analysis using F NMR spectroscopy indicated
no residual tetrafluoroborate anions. The solid
was taken up into dichloromethane (100 cm3) and
washed with water (3 x 50 cm3), the organic
phase was collected, dried with magnesium sulꢀ
fate and volatiles were removed under reduced
pressure. This gave the title compound as a white
solid (2.10 g, 5.45 mmol, 43%). m.p. 229ꢀ231°C
1,3-bis(2',4',6'-Trimethylphenyl)imidazolium
bis(trifluoromethanesulfonyl)imide. To a soluꢀ
tion of the chloride salt 20 (7.51 g, 22.0 mmol) in
water
(80
cm3),
lithium
bis(trifluoromethanesulfonyl)imide (6.47 g, 22.5
mmol) in water (40 cm3) was added dropwise,
with stirring, over a 20 minute period. After an
additional 20 minutes of stirring the bright red
solution, a yellow precipitate formed. The solid
was lixiviated with dichloromethane (4 x 50
cm3), the organic layers were combined, washed
with water (2 x 40 cm3) and dried over anhydrous
magnesium sulfate. The volatile components
were removed under reduced pressure and the
product dried in vacuo over 30 minutes. The
compound was recrystallised from dichloroꢀ
methane/hexane to give the title compound as
white crystals (7.25 g, 12.4 mmol, 56%). m.p.
1
(lit.51 232ꢀ234°C). H NMR (300 MHz, chloroꢀ
formꢀd1) δ 8.89 (t, J = 1.6 Hz, 1H, C2ꢀH), 7.55
(d, J = 1.6 Hz, 2H, C4,5ꢀH), 7.04 (s, 4H, ArꢀH),
2.35 (s, 6H, C4'ꢀCH3), 2.12 (s, 12H, C2'ꢀCH3).
13C NMR (75.5 MHz, chloroformꢀd1) δ 141.6
(C2), 137.4 (ArꢀC), 134.1 (ArꢀC), 130.4 (ArꢀC),
130.0 (C3'), 125.0 (C4,5), 21.2 (C4'ꢀCH3), 17.2
(C2'ꢀCH3). Found: C 65.75; H 6.39; N 7.22%.
C21H25BrN2 requires C 65.46; H 6.54; N 7.27%.
General methodology for pKa titrations. Soꢀ
lutions were prepared containing either the apꢀ
propriate indicator (ca. 1 mM) or the salt being
analysed (ca. 0.2 M) in dry DMSO (distilled
from calcium hydride and stored over freshly acꢀ
tivated 3 Å molecular sieves, <50 ppm water by
Karl Fischer methodology). The spectrophotoꢀ
metric cell was sealed, evacuated and purged
with nitrogen before being charged with the deꢀ
sired indicator solution (3 mL) and the first UV
spectrum of the solution was recorded to deterꢀ
mine the baseline. Aliquots (2.5 ꢀL each) of soꢀ
dium methylsulfinylmethylide (DIMSYL, ca.
1
128ꢀ130°C. H NMR (300 MHz, chloroformꢀd1)
δ 8.96 (s, 1H, C2ꢀH), 7.50 (m, 2H, C4,5ꢀH), 7.06
(s, 4H, ArꢀH), 2.37 (s, 6H, C4'ꢀCH3), 2.11 (s,
12H, C4'ꢀCH3). 13C NMR (75.5 MHz, chloroꢀ
formꢀd1) δ 141.8 (C2), 138.0 (ArꢀC), 133.9 (Arꢀ
C), 130.2 (ArꢀC), 129.9 (C3'), 124.7 (C4,5),
1
119.4 (q, JCF = 321 Hz, CF3), 21.1 (C4'ꢀCH3),
17.1 (C2'ꢀCH3). 19F NMR (282 MHz, chloroꢀ
formꢀd1) δ ꢀ79.38 (s, CF3). Found: C 47.42; H
4.26; N 7.23%. C23H25F6N3O4S2 requires C
47.17; H 4.30; N 7.18%.
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MHD and NK acknowledge the support of the Australian govꢀ
0.25 M) in DMSO (prepared through addition of
1
2
3
4
5
6
7
8
ernment through the receipt of Australian Postgraduate Awards.
JBH acknowledges financial support from the Australian Reꢀ
search Council Discovery Project Funding Scheme (project supꢀ
ported in part by DP130102331) and the University of New South
Wales Faculty of Science Goldstar Scheme. MLC acknowledges
financial support from the Australian Research Council Discovery
Project Funding Scheme (project supported in part by
DP110104759). 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. Prof. Tim
Clark is gratefully acknowledged for support and comments reꢀ
garding the computational aspects presented. Ms R. R. Hawker is
thanked for the generous gift of a sample of compound 11 while
Dr T. R. Unky, Jr, is thanked for useful discussions.
sodium hydride to DMSO) were added and the
UV spectrum of the solution recorded after each
step, until no further increase of the absorbance
value at the appropriate wavelength (dependent
on indicator, see Supporting Information).
To the cell containing a solution of the deprotoꢀ
nated fluorene indicator, aliquots of the azolium
salt solution (ca. 5 ꢀL each) were added and the
UV spectrum of the solution recorded after each
step, until either no further decrease of the abꢀ
sorbance was observed or 300 ꢀL had been addꢀ
ed. Scans were taken in duplicate after each inꢀ
jection to ensure that the system had reached
equilibrium before further injections were added.
With an appropriate indicator (with a pKa value
within 2 of that of the salt), an equilibrium was
established resulting in a decrease in the absorbꢀ
ance value, indicating reprotonation of the chosen
indicator.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Footnotes
£ It is important to acknowledge that the nucleophilic addition
step is just the first in a series that form the catalytic cycle for
NHC catalysed processes. To fully understand such processes the
relative rates of each step must be known; the relative importance
to the overall rate of the nucleophilic addition step varies with the
nature of the process, the substrate and the catalyst (for example,
see reference 7 and references cited therein).
$ The two signals are due to an isotope chemical shift and the
ratio of 4:1 is consistent with the natural abundances of the two
isotopes of boron – 11B and 12B.
The equilibrium constants for the titration were
determined by fitting using Datafit 9 (Oakdale
Engineering). Details of the fitting equation and
its derivation are given in the Supporting Inforꢀ
mation.
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ASSOCIATED CONTENT
Supporting Information. Absorbance data for the deprotonated
form of each of the indicators 1-6; derivation of the fitting equaꢀ
tion; summary tables of pKa data for the species 6-28; pKa data for
a range of 1,3ꢀbis(trimethylphenyl)imidazolium salts with differꢀ
ent anions; crystal structure data for compounds 27 and 28; overꢀ
lay of the crystal structures of compounds 15 and 20; overlay of
the crystal structures of compounds 20 and 28; HOMO and
LUMO graphical representations and their relative energies for
the cations of salts 20, 27 and 28; correlation of pKa data with that
determined computationally; NMR spectra of new compounds;
EMPIRE outputs for calculations of the cations of the salts 20, 27
and 28. This material is available free of charge via the Internet at
http://pubs.acs.org
AUTHOR INFORMATION
Corresponding Author
* Eꢀmail: m.cole@unsw.edu.au, j.harper@unsw.edu.au
Author Contributions
The manuscript was written through contributions of all authors.
All authors have given approval to the final version of the manuꢀ
script.
Funding Sources
This work was supported in part through the Australian Research
Council Discovery Projects programme and the University of
New South Wales Faculty of Science Goldstar Scheme.
(23) Massey, R. S.; Collett, C. J.; Lindsay, A. G.; Smith, A. D.;
O’Donoghue, A. C. J. Am. Chem. Soc. 2012, 134, 20424.
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J.; Bramley, C. R.; Smith, A. D.; O’Donoghue, A. C. J. Phys. Org. Chem.
2015, 28, 108.
ACKNOWLEDGMENT
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Insert Table of Contents artwork here
19.8
1
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6
N
N
19.6
19.4
19.2
19
Cl
X
X
7
8
9
18.8
18.6
18.4
18.2
18
N
N
X
Cl
X
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17.8
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
Hamme0
σ
value
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