Absolute pKas of Sulfonamides in Ionic Liquids: Comparisons to Molecular Solvents

Article abstract of DOI:10.1021/acs.joc.6b02182

Absolute pK_as of 25 sulfonamides in four ionic liquids (ILs) were measured spectroscopically with high precision and subsequently compared with those in conventional molecular solvents. It is found that the acidity order of these sulfonamides i

Full text of DOI:10.1021/acs.joc.6b02182

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Article
Absolute pKas of Sulfonamides in Ionic
Liquids: Comparisons to Molecular Solvents
Zedong Wang, Xin Li, Pengju Ji, and Jin-Pei Cheng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02182 • Publication Date (Web): 07 Oct 2016
Downloaded from http://pubs.acs.org on October 12, 2016
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Absolute pKas of Sulfonamides in Ionic Liquids:
Comparisons to Molecular Solvents
Zedong Wang,† Xin Li,† Pengju Ji,*,‡ and Jin-Pei Cheng*,†,‡
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†State Key Laboratory of Elemento-organic Chemistry, Collaborative Innovation Centre of Chemical
Science and Engineering, Nankai University, Tianjin, 300071, China.
‡Center of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua University, Beijing,
100084, China.
jipengju@mail.tsinghua.edu.cn (P. Ji); jinpei_cheng@mail.tsinghua.edu.cn (J.-P. Cheng)
TOC
O
O
R2 S NR1
O
Ka
R2 S NHR1
+
H
ILs
O
1a-4c
O
S
O
S
O
NH2
O2N
NHTos
TfNH2
Tos2NH
1c
NHTf
2b
O
1a
1b
4c
20.9
14.9
6.7
12.2
5.7
pKa Scale in [BMPY][NTf2]
ABSTRACT
Absolute pKas of 25 sulfonamides in four ionic liquids (ILs) were measured spectroscopically with high
precision and subsequently compared with these in conventional molecular solvents. It is found that the acidity
order of these sulfonamides follows: in water > in DMSO > in ILs > in acetonitrile (ACN). The well-known
solvent polarity index ε fails to explain the observed stronger bond-weakening effect of ILs than that of ACN
whose ε is much greater. In addition, the regression analyses show that the pKas of sulfonamides determined in
ILs linearly correlate with these in molecular solvents of distinct properties, but with various slopes. A rationale
and related discussion on the effect of solvation in ILs are presented.
INTRODUCTION
Solvents are ubiquitous, and in most circumstances, are indispensable in chemistry. In a sense, the
selection of solvent based on the knowledge of solvation reflects a rational development of chemistry,
which, in return, can significantly improve the image of organic reactions regarding the environment
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issue.1 In recent years, as it became more and more crucial, many volatile organic solvents are listed as
“unclean”, and various room temperature ionic liquids (RTILs) come into play as their alternatives, in
spite of a severe shortage of the knowledge on their solvation behavior.
9
Ionic liquids are composed entirely of ions and exhibit unique properties that are significantly
different from these of conventional molecular solvents.2 As a rising mainstream medium category, ILs
are labelled as green solvent3 which have aroused enormous research interests in recent decade and
have also been extensively used in industry.4 Compared to the tremendous attentions paid on the
development of their synthetic applications, fundamental aspects on the solvation phenomena of ILs
are very scarce, however. As it is well known that solvents have strong impacts on the acidity of
substrate by virtue of their differential strengths of solvation towards various species in solution, we
believe that to study the pKas in different media would provide quantitative understandings in this
regard.
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Some acidity scales in various molecular solvents have been established in past,5 which allowed a
good understanding of solvation behavior for conventional media. By contrast, acidity studies in neat
ILs are far less, and the early works reported relative pKas in most cases6 that are not suitable for the
solvation study. Although more recent works showed that the absolute acidity in ILs could be obtained
electrochemically,7 the narrow substrate scope and large uncertainty associated with irreversible
electrode data make its use in solvation study problematic. However, we have recently found that the
overlapping indicator method, which has been dominantly used in molecular media for most of the
authentic pKas data known today8, can be well adopted to measure the acidities in ILs with high
precision9 and hence should be able to fulfil the current research need.
Sulfonamides are important compounds in pharmaceutical and agricultural chemicals industry. A
large number of drugs, such as antimicrobials and diuretics, and several novel herbicides, bear this
sulfonamide moiety. This is mainly due to their unique structure that resembles the tetrahedral
intermediate involved in many acyl substitutions and stabilized by proteases and esterases.10
Sulfonamide is known to be more acidic than carboxamides. The knowledge on sulfonamide acidities is
important to pharmaceutical industry because it delivers valuable information on the mechanisms of
drug actions and metabolisms. The acidities of sulfonamides have been investigated extensively in the
conventional molecular solvents.11 However, till present almost no attention has been paid on the
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acidities of N−H bonds in IL. On the other hand, recent seminal study shows that developing IL drugs
and use of ILs as a drug delivery medium may bring a revolution to pharmaceutical industry.12 This,
from another angle, points out the need of the information on sulfonamides acidities in ILs, especially
on their relations to the solvation strength of different types of media in a more quantitative manner.
Towards this end, here we have measured 68 absolute acidity values of 25 sulfonamides in 4 ILs
(Scheme 1) with high precision with the standard deviation (SD) of ≤±0.05 pK units. A variety of
structurally different sulfonamides (Scheme 2), such as benzenesulfonamides (1a-8a),
trifluoromethylsulfonamides (1b-6b) and several more acidic sulfonamides (9a-10a, 7b-11b and 1c-4c),
were included in this work. The measured pKa data (Tables 1) are compared with the known acidities in
molecular solvents by regression analysis, which revealed insightful and interesting information
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regarding the change on the solvation strength by ILs and molecular media.
Cation
N
N
N
N
R
R
N
R
[BM2IM]+
[BMPY]+
[BMIM]+
Anion
R = n-butyl
O O
O
O
O
O
S
S
S
N
O
F3C
CF3
F3C
[OTf]
[NTf2]
Scheme 1. Cations and anions of the ILs used in this study, the ILs are: [BMIM][OTf], [BMIM][NTf2],
[BMPY][NTf2] and [BM2IM][NTf2]
O
O
G1 NH
S
G2 NH S CF3
G2 NHTf
O
O
benzenesulfonamide derivatives
trifluoromethanesulfonamide derivatives
1a: G1= H 2a: G1=
OCH3 4a: G1=
1b: G2= H 2b: G2=
3a: G1=
6a: G1=
CH3
OCH3
4b: G2=
3b: G2=
Cl
O
C
CH3
NO2
Cl
5b: G2=
8b: G2=
10b: G2=
CF3
6b: G2=
NO2
7b: G2=
5a: G1=
8a: G1=
7a: G1=
Cl
O
C
O
C
OCH3
9b: G2=
11b: G2=
CH3
F
O
S
O
S
O
C
9a: G1=
O
10a: G1=
Cl
O
C
Cl
O
O
S
G3 NH
G3 NHTos
O
toluenesulfonamide derivatives
O
O
S
1c: G3=
3c: G3=
S
O
O
CH3
CH3
2c: G3=
O
O
S
S
4c: G3=
NO2
O
O
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Scheme 2. The structures of sulfonamide derivatives (1a-4c) involved in this work
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RESULTS AND DISCUSSION
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Table 1 shows that the acidity scale of these N−H acids spreads over 15 pK units, which covers by far the
largest energetic span and substrates collection for one R−H acid family in ILs, and provides with rich
information of the effect of structural change on the N−H acidity in ILs. For examples, an additional sulfonyl
group causes a dramatic increase of the acidity of 1a (20.9) by as large as 14 orders of magnitude compared to
that of 9a (6.3), while a carbonyl group makes the acidity of 7b (6.7) 1.6×108 times stronger than 1b, due to
their strong inductive as well as resonance stabilization effect on the sulfonamide nitrogen anion. This is
supported by the fact that the carbon acid, PhSO2CH2SO2Ph (pKa = 19.2 in [BMPY][NTf2]9a) is much less acidic
than its analogue 9a in ILs, apart from the fact that the electronegativity of N is greater than C atom, the large
acidity difference (ΔpKa ≈ 13) may also be as a consequence of a significant p-d π-resonance between the anion
center and sulfonyl group of sulfonamides.14
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Table 1. pKa Values of sulfonamides (Scheme 2) in ILs and molecular solvents
b
b
b
b
Sulfonamidesa
pKa
pKa
pKa
pKa
pKa
pKa
pKa
[Bmpy][NTf2]
[Bmim][NTf2]
20.25
18.2
[Bm2im][NTf2]
[Bmim][OTf]
water
DMSO
ACN
PhSO2NH2 (1a)
20.9
18.7
18.4
18.2
18.0
17.15
16.7
15.7
14.9
12.2
12.9
11.4
10.6
9.45
7.2
21.9
19.3
19.1
18.9
18.7
17.75
17.4
16.2
15.5
12.7
13.35
11.8
11.0
9.8
18.1
16.1
15.7
15.5
15.4
14.6
14.3
13.3
9.4c
8.9e
8.6e
8.5e
8.2e
7.9e
7.7f
15.2d
14.2e
13.9e
13.7e
13.5e
12.7e
11.7e
11.2e
9.7h
24.6d
22.9e
22.6e
22.7e
22.6e
21.6e
p-MeO-PhNHSO2Ph (3a)
p-Me-PhNHSO2Ph (4a)
m-Me-PhNHSO2Ph (5a)
PhNHSO2Ph (2a)
p-Cl-PhNHSO2Ph (6a)
m-Cl-PhNHSO2Ph (7a)
m-NO2-PhNHSO2Ph (8a)
TfNH2 (1b)
17.75
17.6
17.4
16.7
16.3
15.3
14.45
20.4e
12.8
6.3g
PhNHTf (2b)
p-MeO-PhNHTf (3b)
p-Cl-PhNHTf (4b)
11.8
12.4
11.0
10.25
9.05
6.7
9.95
10.6
9.2
8.5
7.6
4.5g
4.9g
3.9g
p-CF3-PhNHTf (5b)
p-NO2-PhNHTf (6b)
p-MeO-PhCONHTf (8b)
TosNHSO2Me (2c)
p-Me-PhCONHTf (9b)
Tos2NH (1c)
11.6i
7.2
7.0
6.7
6.7
6.5
6.3
6.3
6.3
6.6
6.6
6.2
11.5i
12.0j,k
11.1i
1.7k
PhCONHTf (7b)
PhSO2NHTos (3c)
6.25
6.0
f
PhSO2NHSO2Ph (9a)
p-F-PhCONHTf (11b)
p-Cl-PhCONHTf (10b)
p-Cl-PhSO2NHSO2Ph (10a)
p-NO2-PhSO2NHTos (4c)
5.8 (9.7l)
5.9
1.45
11.3j
10.7i
10.4i
5.8
5.3
5.0
5.9
5.7
10.1j
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b
c
d
e
aThe acidic hydrogens are indicated by boldface type. In pKa units, SD: ≤ ±0.05 pK unit. Reference 11e. Reference 11f. Reference 11g.
fReference 11b. Reference 11a. Reference 13. Reference 11m. Reference 11j. Reference 11i. Reference 7c, in [EMIM][NTf2], where
g
h
i
j
k
l
[EMIM]+=1-ethyl-3-methylimidazolium, the value is a simulated one based on electrochemical measurement.
The structure and composition of the ILs in this study have pronounced effect on the N−H acidic dissociation
equilibrium. Normally, the anion of IL plays a dominant role on the acidity, due to the relatively large proton
solvation energy [∆GSolv*(H+)] by anion (-258 kcal mol-1 for [NTf2]−), compared with that by cation on the
deprotonated species of various substrates.15 From Table 1, the acidity of individual sulfonamide decreases in a
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sequence of [BMIM][OTf] > [BMIM][NTf2] > [BMPY][NTf2] > [BM2IM][NTf2], which is consistent with our
previous observations for other series of acids.9 It is not difficult to understand that the acidity of these
sulfonamides are more acidic in [BMIM][OTf] than in [BMIM][NTf2]. This should be ascribed to a more
localized negative charge and smaller size of [OTf]− compared to [NTf2]−, both leading to a stronger solvation of
proton. The trend of pKa change in the ILs with [NTf2]− as the common counter anion could be rationalized on
the basis of the extent of charge delocalization and the accessibility of the cation moiety towards the
sulfonamide anion. For example, the observed stronger acidity of sulfonamide in [BMIM][NTf2] than in the
other two ILs with [NTf2]− as a common anion should be due to the less hindered [BMIM]+ moiety than the
other two and its C2-H that is capable of providing an H-bonding with the sulfonamide nitranion.
Table 1 also shows that the acidities of sulfonamides in various solvents follow the order, in water > in
DMSO > in [BMIM][OTf] > [BMIM][NTf2] > [BMPY][NTf2] > [BM2IM][NTf2] > in ACN, which actually
reflects the order of solvability for these solvents.7b This sequence is beyond one’s expectation, however,
because AILs are known for their relatively low polarity (ε = 10-1516), which would otherwise suggest a weaker
acidity in ILs than in ACN, whose dielectric constant is much greater (ε = 36.117). Nonetheless, as we recently
found, the cations and anions in AILs should exist essentially as “free ions” rather than as ion-pairs9e (showing
an “ionic liquid effect”9c,9e,18,19), it may not be too big a surprise to see that some classical parameters suitable
for describing properties in molecular media (such as ε) may not always be so for certain properties in ILs. Thus,
the presently observed but yet unanticipated unusually strong N−H bond weakening ability of the low-polarity
ILs could be understood by considering that the IL’s anion and cation should be able to act separately in
stabilizing the proton and the incipient sulfonamide nitranion upon deprotonation by virtue of their respective
solvability (via Coulombic, resonance, π-π interactions, etc.) towards ions of opposite charges. This in situ
situation occurred in a solvation process in IL is not exactly the same as the status of an IL in a dielectric
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constant measurement,16 and thus, it should be the reason behind the unusually strong N−H bond-weakening
ability of these superficially weakly-polar ILs.
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Next, we carried out a regression study on the sulfonamides acidities measured in the 4 ILs. All the
correlations between the pKas in any two ILs show excellent linearity with R2 = 0.999 (see SI, Figure S3, one of
them is shown in Figure 1). Furthermore, regression analyses between the pKas in one representative IL
([BMPY][NTf2]) and these in molecular solvents were performed. Remarkably, in spite of the tremendous
differences in solvent properties of water, DMSO and ACN from ILs, good to excellent linearity is observed in
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slope (DMSO) = 1.00
23
R² = 0.990
slope (water) = 1.68
R² = 0.990
18
13
slope (ACN) = 1.02
R² = 0.997
8
slope ([BMIM][NTf2])
= 1.02
R² = 0.999
3
-2
3
8
13
18
23
28
pKa in an AIL and molecular solvent
Figure 1. pKas of sulfonamides in [BMPY][NTf2] against these in [BMIM][NTf2] and molecular solvent; filled
square, circle, triangle and diamond represents the pKas in water, DMSO, [BMIM][NTf2] and ACN, respectively.
all the correlations (Figure 1). It is noteworthy that the slope of the correlation between the pKas in
[BMPY][NTf2] and in water is significantly greater than unity (slope = 1.68), indicating a much lower
sensitivity of sulfonamide acidity towards structure variation in water than in AILs. This is understandable,
because the negative charge of the sulfonamide anion can be better dispersed in water than in IL due to the
greater solvability of water caused mainly by its strong hydrogen-bondings. This reduces the charge density on
nitrogen and weakens the influence of a structural change more significantly than the situation in ILs. On the
other hand, the slopes of the correlations between the acidities in ILs (taking [BMPY][NTf2] as example) vs.
DMSO and vs. ACN are all observed to be around unity (Figure 1, slope = 1.00 and 1.02, respectively). Though
this seeming coincidence in the slope values cannot be fully understood based on our present knowledge on
solvation, these correlation Equations 1-3 (Scheme 3) together with those in ILs mentioned above can provide a
practically very useful way for estimating unknown pKas in these molecular and ionic solvents for relevant
compounds.
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pKa ([BMPY][NTf2]) = 1.68 pKa (water) + 4.24
pKa ([BMPY][NTf2]) = pKa (DMSO) + 4.76
Eqn.1
Eqn. 2
7
8
pKa (ACN) ≈ pKa ([BMPY][NTf2]) + 4.81
Eqn. 3
9
Scheme 3. The acidity correlation equations between pKas in IL and molecular media
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In summary, the absolute acidities of 25 N−H acids (altogether 68 pKa values) were accurately measured in four
ILs. The wide energetic range (>15 pK units) of the obtained data enabled regression analyses among the pKas
scales in both ILs and molecular media, which exhibit excellent linear correlations of the acidity scales both in
ILs and in between the ILs and molecular solvents (water, DMSO and ACN). Such relationships allow
reasonable estimates for the unknown acidities of sulfonamides in these solvents. A detailed comparison among
the acidity scales in these ionic and molecular media finds an interesting trend that the ILs of low ε value can
show an unusually strong ability (vs. ACN, ε = 36.1) in facilitating deprotonation. The absolute acidities and the
solvation insights disclosed in this work may serve either as benchmark values or reliable references for the
development of appropriate theoretical solvation models and for mechanistic analyses in ILs.
EXPERIMENTAL
General
ILs (Scheme 1)20, carbon indicator acids (fluorene derivatives, Table S1) and the base used in this work were
o
synthesized and purified as described in previous work.9 In addition, ILs were dried in vacuum at 70 C for 5
hours before use and were stored in desiccators under argon. The water contents of ILs are less than 10 ppm,
which was determined by the Karl-Fischer titration. Sulfonamides, except otherwise noted, were commercially
available and were carefully recrystallized and dried before used as substrates. The sulfonamides and indicator
acids were kept in a glove box. The principle of acidity measurement by indicator overlapping method11c, 13is
introduced as Equation 4:
Keq
In_
_
A_
[HIn] A
+
+
HIn
HA
_
]
]
[
_
lgKeq pK
=
pKa = pKHIn
lg
_
Eqn. 4
HIn
[HA][
In
Where HIn and HA denotes the indicator and substrate acids respectively. It is worth noting that all the
acidities of indicator acids were referenced to an anchor compound whose acidity was measured by self-
dissociation (SI), so the pKas of these indicator acids are absolute values in essence. All manipulations were
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carried out under dry argon using standard Schlenk techniques. The pKa measurement started by adding 1.5
ml IL solution of base (~5 × 10-4 M) into an empty UV cell with a 3-way valve (Figure S1), and then the
spectrum for baseline was recorded on a UV instrument. Next an IL solution of an appropriate indicator acid
(HIn) with known pKa was added dropwisely until the UV absorbance was not increasing with the addition.
Then the IL solution (10-5 to 10-4 M) of substrate acid of interest (HA) was added in several portions. The
weight of the UV cell and the corresponding spectrum were also recorded upon each addition. The pKa of HA
was then calculated from the change of absorbance and the amount of acid added.
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Synthesis of picric derivatives as indicators21
a. 3-chloropicric acid (Scheme S1, C):
To a 100 ml 3-neck round bottom flask charged with 2.5 g (19.5 mmol) 3-chlorophenol, under an acetone/dry
ice bath, 10 ml concentrated sulfuric acids (98% w/w, 0.183 mol) was added slowly, then the temperature of
reaction mixture was raised cautiously to 90 oC and kept at this temperature for 40 mins before the
o
temperature was cooled down to 0 C by a water and ice bath (NaCl/icewater). Again under the acetone/dry
ice bath, with cautions 10 ml fuming nitric acid (90% w/w, 0.214 mol) was added dropwisely, then the reaction
o
temperature was allowed to rise to 80 C and was held at this temperature for 50 mins. After system was
cooled down to ambient temperature, the reaction mixture was then poured into ice water, the brown
yellowish precipitates were collected and recrystallized from water once and CCl4 twice to give a yellowish
solid 2.3g. Yield: 45%. 1H NMR (400 MHz, DMSO-d6) δ 8.77 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ 127.9.
b. 3, 5-dichloropicric acid (Scheme S1, D):
The starting material was 3,5-dichlorophenol, synthetic procedures were similar to these for 3-chloropicric
1
acid (C) describe above, which gave a yellow solid with a yield of 38%. H NMR (400 MHz, DMSO-d6) δ 14.58
(s, 1H); 13C NMR (100 MHz, DMSO-d6) δ 155.6, 143.1, 127.7, 121.0.
Synthesis of sulfonamides
The commercial available (1a and 1b) and prepared sulfonamides (2a-8a, 2b-4c) were carefully recrystallized
at least 3 times and stored in glove box before used in pKa measurement. The synthetic procedures for the
sulfonamides used in this work can be found elsewhere.22
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PhNHSO2Ph (2a), yield: 72%. 1H NMR (400 MHz, DMSO-d6) δ 10.37 (s, 1H), 7.80 (d, J = 7.2 Hz, 2H), 7.60−7.48
(m, 3H), 7.22 (t, J = 7.8 Hz, 2H), 7.14 (d, J = 7.7 Hz, 2H), 7.00 (t, J = 7.2 Hz, 1H); 13C NMR (100 MHz, DMSO-d6)
δ 140.0, 138.2, 133.3, 129.7, 129.6, 127.1, 124.5, 120.5.22b
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p-MeO-PhNHSO2Ph (3a), yield: 58%. H NMR (400 MHz, DMSO-d6) δ 9.94 (s, 1H), 7.69 (d, J = 7.1 Hz, 2H),
7.60−7.45 (m, 3H), 6.98 (d, J = 7.2 Hz, 2H), 6.80 (d, J = 8.6 Hz, 2H), 3.66 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
δ 157.0, 139.9, 133.2, 130.5, 129.6, 127.1, 123.9, 114.7, 55.5.22b
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p-Me-PhNHSO2Ph (4a), yield: 68%. H NMR (400 MHz, DMSO-d6) δ 10.53 (s, 1H), 7.80 (d, J = 7.1 Hz, 2H),
7.60- 7.48 (m, 3H), 7.28 (d, J = 8.7 Hz, 2H), 7.15 (d, J = 8.7 Hz, 2H). 10.14 (s, 1H), 7.73 (d, J = 7.1 Hz, 2H), 7.58-
7.49 (m, 3H), 7.04−6.95 (m, 4H), 2.17 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 139.9, 135.4, 133.9, 133.3, 130.0,
129.7, 127.1, 121.1, 20.8.22b
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m-Me-PhNHSO2Ph (5a), yield: 69%. H NMR (400 MHz, DMSO-d6) δ 10.29 (s, 1H), 7.80 (d, J = 7.2 Hz, 2H),
7.60−7.50 (m, 3H), 7.09 (t, J = 8.1 Hz, 1H), 7.16 (s, 1H), 6.98−6.88 (m, 2H), 6.82 (d, J = 7.9 Hz, 1H), 2.16 (s, 3H);
13C NMR (100 MHz, DMSO-d6) δ 140.0, 138.9, 138.1, 133.3, 129.7, 129.4, 127.1, 125.3, 121.0, 117.5, 21.5.22b
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p-Cl-PhNHSO2Ph (6a), yield: 63%. H NMR (400 MHz, DMSO-d6) δ 10.53 (s, 1H), 7.80 (d, J = 7.1 Hz, 2H),
7.60−7.48 (m, 3H), 7.28 (d, J = 8.7 Hz, 2H), 7.15 (d, J = 8.7 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ 139.6, 137.1,
133.5, 129.7, 129.6, 128.7, 127.1, 122.0.22b
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m-Cl-PhNHSO2Ph (7a), yield: 65%. H NMR (400 MHz, DMSO-d6) δ 10.66 (s, 1H), 7.82 (d, J = 7.2 Hz, 2H),
7.63−7.50 (m, 3H), 7.24 (t, J = 8.1 Hz, 1H), 7.16 (s, 1H), 7.11 (d, J = 8.2 Hz, 1H), 7.05 (d, J = 7.9 Hz, 1H); 13C NMR
(100 MHz, DMSO-d6) δ 139.8, 139.6, 133.9, 133.6, 131.3, 129.8, 127.1, 124.2, 119.5, 118.4.22b
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m-NO2-PhNHSO2Ph (8a), yield: 48%. H NMR (400 MHz, DMSO-d6) δ 10.98 (s, 1H), 7.99 (s, 1H), 7.85 (d, J =
7.2 Hz, 2H), 7.81 (d, J = 7.9 Hz, 1H), 7.60−7.51 (m, 4H), 7.48 (t, J = 8.1 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ
148.6, 139.6, 139.4, 133.7, 131.1, 129.9, 127.1, 125.7, 118.8, 113.9.22b
PhSO2NHSO2Ph (9a), yield: 33%. 1H NMR (400 MHz, DMSO-d6) δ 13.87 (s, 1H), 7.71 (d, J = 7.4 Hz, 4H), 7.51 (t, J
= 7.2 Hz, 2H), 7.44 (t, J = 7.4 Hz, 4H); 13C NMR (100 MHz, DMSO-d6) δ 144.3, 131.9, 128.9, 126.8.22c
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p-Cl-PhSO2NHSO2Ph (10a), yield: 31%. H NMR (400 MHz, DMSO-d6) δ 13.65 (s, 1H), 7.74−7.68 (m, 4H),
7.50−7.45 (m, 3H), 7.41 (t, J = 7.2 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ 144.4, 143.5, 136.5, 131.8, 128.9, 128.8,
126.8.22c
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PhNHTf (2b), yield: 67%. 1H NMR (400 MHz, DMSO-d6) δ 11.91 (s, 1H), 7.42 (t, J = 7.7 Hz, 2H), 7.29 (d, J = 6.8
Hz, 3H); 13C NMR (100 MHz, DMSO-d6) δ 135.3, 130.0, 127.1, 123.3, 120.2 (1J CF = 322 Hz).22b
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p-MeO-PhNHTf (3b), yield: 59%. 1H NMR (400 MHz, DMSO-d6) δ 11.60 (s, 1H), 7.21 (t, J = 8.3 Hz, 2H), 6.97 (d,
J = 8.8 Hz, 2H), 3.75 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 158.6, 127.3, 126.5, 120.3 (1J CF = 323 Hz), 55.7.22b
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p-Cl-PhNHTf (4b), yield: 72%. 1H NMR (400 MHz, DMSO-d6) δ 12.02 (s, 1H), 7.49 (d, J = 8.8 Hz, 2H), 7.29 (d, J
= 8.3 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ 134.4, 131.3, 130.0, 124.8, 120.1 (1J CF = 321 Hz).22b
p-CF3-PhNHTf (5b), yield: 64%. 1H NMR (400 MHz, DMSO-d6) δ 12.33 (s, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.46 (d,
J = 8.3 Hz, 2H).22b
p-NO2-PhNHTf (6b), yield: 68%. 1H NMR (400 MHz, DMSO-d6) δ 12.12 (s, 1H), 8.26 (d, J = 9.0 Hz, 2H), 7.46 (d,
J = 9.0 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ 144.5, 143.1, 125.6, 121.4, 120.1 (1J CF = 322 Hz).22b
PhCONHTf (7b), yield: 59%. 1H NMR (400 MHz, DMSO-d6) δ 14.16 (s, 1H), 7.93 (d, J = 7.3 Hz, 2H), 7.47 (d, J =
7.3 Hz, 1H), 7.40 (t, J = 7.2 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ 169.9, 131.6, 129.0, 128.3. 22d
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p-MeO-PhCONHTf (8b), yield: 62%. H NMR (400 MHz, DMSO-d6) δ 14.10 (s, 1H), 7.91 (d, J = 8.6 Hz, 2H),
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6.98 (d, J = 8.7 Hz, 2H), 3.79 (s, 3H); C NMR (100 MHz, DMSO-d6) δ 167.8, 163.1, 131.4, 127.0, 120.3 (1J = 322
CF
Hz), 113.9, 55.8.22d
p-Me-PhCONHTf (9b), yield: 66%. 1H NMR (400 MHz, DMSO-d6) δ 14.23 (s, 1H), 7.83 (d, J = 7.9 Hz, 2H), 7.23
(d, J = 7.9 Hz, 2H), 2.32 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 168.9, 142.5, 133.0, 129.3, 129.1, 120.5 (1J CF = 322
Hz), 21.5.22d
p-Cl-PhCONHTf (10b), yield: 61%. 1H NMR (400 MHz, DMSO-d6) δ 14.30 (s, 1H), 7.92 (d, J = 8.3 Hz, 2H), 7.43
(d, J = 8.3 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ 168.9, 136.7, 135.8, 130.9, 128.5, 120.6 (1J CF = 322 Hz).22d
p-F-PhCONHTf (11b), yield: 49%. 1H NMR (400 MHz, DMSO-d6) δ 14.43 (s, 1H), 7.98 (dd, J = 8.5 Hz, 4J HF = 5.9
Hz, 2H), 7.19 (t, J = 8.8 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ 168.8, 164.6 (1J CF = 248 Hz), 133.5, 131.7 (3J CF
9 Hz), 120.6 (1J CF = 323 Hz), 115.3 (2J CF = 21 Hz).22d
=
MeSO2NHTos (2c), yield: 48%. 1H NMR (400 MHz, DMSO-d6) δ 13.09 (s, 1H), 7.75 (d, J = 8.2 Hz, 2H), 7.39 (d, J
= 8.1 Hz, 2H), 3.15 (s, 3H), 2.38 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 143.6, 138.5, 129.8, 127.3, 43.8, 21.5.22c
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PhSO2NHTos (3c), yield: 28%. 1H NMR (400 MHz, DMSO-d6) δ 13.80 (s, 1H), 7.75 (d, J = 7.4 Hz, 2H), 7.63 (d, J
= 8.2 Hz, 2H), 7.56 (t, J = 7.3 Hz, 1H), 7.48 (t, J = 7.5 Hz, 2H), 7.27 (d, J = 8.1 Hz, 2H), 2.33 (s, 3H); 13C NMR (100
MHz, DMSO-d6) δ 143.1, 142.8, 139.9, 132.7, 129.6, 129.2, 127.1, 127.0, 21.4.22c
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p-NO2-PhSO2NHTos (4c), yield: 25%. H NMR (400 MHz, DMSO-d6) δ 13.76 (s, 1H), 8.21 (d, J = 8.7 Hz, 2H),
7.88 (d, J = 8.6 Hz, 2H), 7.54 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 7.9 Hz, 2H), 2.28 (s, 3H); 13C NMR (100 MHz,
DMSO-d6) δ 151.6, 148.7, 142.6, 141.1, 129.0, 128.3, 126.8, 124.0, 21.3.22c
ASSOCIATED CONTENT
Supporting Information.
The Supporting Information is available free of charge on the ACS Publications website. Picture of the
UV-cell; expansion of the indicator acidity scale; indicators used in this work and their corresponding
pKas in ILs; UV-vis spectra for representative measurements; regression analysis; NMR spectra.
NOTES
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was supported by National Natural Science Foundation of China (NSFC, Grant Nos. 21172118,
21390401) and Tsinghua University Initiative Scientific Research Program (Grant Nos. 20131080083,
20141081295). We thank Miss J.-J. Zhang for her assistance with the NMR experiments.
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