Equilibrium Acidities of Nitroalkanes in an Ionic Liquid

Article abstract of DOI:10.1021/acs.joc.8b02183

The acidity ladder scale in [BMPY][NTf₂] was successfully expanded toward the weak acidity region for about five more pK units compared to the previously established one. This allows the acidities of a series of 13 aliphatic and aromatic nitroalkanes to be determined accurately by the UV-vis spectroscopic method. The acidity of nitroalkane in [BMPY][NTf₂] covers ～8 pK units and is significantly weaker than those in DMSO and water. The Hammett plot for 4-substituted phenylnitromethanes shows an excellent linearity with a slope of 2.06, which is rather close to that in DMSO but significantly larger than that in water (0.80). The regression analyses reveal that the solvation behavior of [BMPY][NTf₂] on the acidic dissociations of C-H acids is similar to that of DMSO.

Full text of DOI:10.1021/acs.joc.8b02183

Subscriber access provided by UNIV OF DURHAM
Article
Equilibrium Acidities of Nitroalkanes in an Ionic Liquid
Feixiang Gao, Pengju Ji, and Jin-Pei Cheng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02183 • Publication Date (Web): 16 Nov 2018
Downloaded from http://pubs.acs.org on November 16, 2018
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the
course of their duties.

Page 1 of 19
The Journal of Organic Chemistry
1
2
3
4
5
Equilibrium Acidities of Nitroalkanes in an Ionic Liquid
6
7
Feixiang Gao,† Pengju Ji*,† and Jin-Pei Cheng*,†,‡
8
9
†Center of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua University,
Beijing 100084, China.
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
‡State Key Laboratory of Elemento-organic Chemistry, Collaborative Innovation Center of
Chemical Science and Engineering, Nankai University, Tianjin 300071, China.
jipengju@mail.tsinghua.edu.cn; jinpei_cheng@mail.tsinghua.edu.cn
ABSTRACT
The acidity ladder scale in [BMPY][NTf2] was successfully expanded towards weak acidity region
for about five more pK units compared to the previously established one. This allows the acidities
of a series of 13 aliphatic and aromatic nitroalkanes to be determined accurately by UV-vis
spectroscopic method. The acidity of nitroalkane in [BMPY][NTf2] covers ~8 pK units and is
significantly weaker than those in DMSO and water. Hammett plot for 4-substituted
phenylnitromethanes shows an excellent linearity with a slope of 2.06, which is rather close to that
in DMSO but significantly larger than that in water (0.80). The regression analyses reveal that the
solvation behavior of [BMPY][NTf2] on the acidic dissociations of C-H acids is similar to that of
DMSO.
INTRODUCTION
Carbon acids (C-H acids) are ubiquitous in organic chemistry, since practically almost all organic
compounds contain C-H bonds.1 C-H acids are one of chemical curiosities to organic chemists for
many years. Our interest in thermodynamic properties and kinetic behaviors of C-H acids extends
into contemporary chemical research.1,2 In general, most C-H acids, such as hydrocarbons, are rather
weak Brönsted acids, but with the presence of nearby electron-withdrawing group(s) (EWGs), or
under sufficiently strong basic conditions, they are capable of undergoing deprotonation and
producing the corresponding carbanions. Carbanions are one of the most well-known and -studied
nucleophiles and have been widely used in many important biological and synthetic reactions for
building up various carbon-carbon and carbon-heteroatom bonds.3 Research on the C-H acidities
has a long and rich history and has laid the foundation for the establishment of general theories of
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 19
1
2
3
4
5
6
7
8
9
organic chemistry, in this respect, the determination of C-H acidity is of fundamental importance to
the progress in physical organic chemistry.1,3 Accordingly, previously tremendous effort has been
devoted to establish acidity scales for C-H acids in various solvent systems by different methods,1,4,5
and several reliable acidity scales have been achieved in commonly used organic solvents.4,5
Conceptually different from molecular solvents, ionic liquids (ILs) are entirely composed of
charged species, which endows them with a number of distinctive physicochemical properties such
as negligible vapor pressure, low flammability, high conductivity, a wide liquid range and good
thermal stability.6 Furthermore, their tuneable features which can be achieved through varying the
identities of composing ions, make ILs a versatile functional material that may potentially fulfill
various task-specific jobs.7 Owing to these favorable characteristics, ILs have received tremendous
amount of research attention, and have found their broad applications in catalysis, material and
biological science as well as energy storage, etc.8 However, compared with the knowledge that has
been accumulated in molecular solvents,9 currently our understanding on some fundamental aspects
of ILs, especially at the molecular level, such as explicit solvent structure and solvation behavior,
etc., still remains in a primitive stage. Unavoidably, the incipient theories for ILs were based on only
very limited work in this connection and are often subject to debates.10 It is well-known that the
study of acid-base equilibria in molecular solvents can provide some crucial information on the
solvation behaviors and solvent effects.9c,11 In recent years, we have precisely measured several
series of organic Brönsted acids in both aprotic and protic ILs by a classical UV-vis spectroscopic
method,12 a number of unique solvation patterns of ILs which are distinctive from those of molecular
solvents were revealed.12c,12e,12g
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
Nitroalkanes are important branch of C-H acids and have been widely used in organic synthesis
for C-C bond formations.13 Due to a strong electron-withdrawing power of the mesomeric nitro
group, nitroalkanes are normally more acidic than other types of C-H acids. To date, there has been
a considerable amount of research into the determination of acidities for nitroalkanes in both protic
and aprotic molecular solvents,4d however, surprisingly, there is no relevant study on the acidic
dissociation of nitroalkanes in ILs. Previously we measured a number of C-H acids in 4 imidazolium
and pyrrolidinium based aprotic ILs, but the C-H acids involved were mainly fluorene, malononitrile
and ylide derivatives.12a,12e Herein we wish to report the equilibrium acidities of several commonly
seen nitroalkanes in an aprotic IL, i.e. [BMPY][NTf2] ( [BMPY] = 1-butyl-1-methylpyrrolidinium,
2
ACS Paragon Plus Environment

Page 3 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
[NTf2] = bis(trifluoromethanesulfonimide), whereby linear free energy analyses were established
and utilized in order to understand the solvation behaviors of ILs.
7
8
9
RESULTS AND DISCUSSION
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
Expanding the acidity ladder. In the pKa determination by the UV-vis spectroscopic approach, one
first needs to establish an acidity ladder which can be used as a standard scale for the acidity
measurement of target acids (HA) in a specific solvent. The acidity ladder contains the acidities of
a series of standard indicator acids (HIn) whose pKaHIns are carefully measured with high precision.
The span of the acidity ladder dictates the number and identities of target acids that can be potentially
measured.
B
In
A
H-In +
+ H-B
+ H-In
Keq
K
In
H-A
+
HA
HIn
K
K
p
p
p
a
a
=
eq
+
Scheme 1. The Principle of pKa Determination by the UV-vis Spectroscopic Method in Solutions.
As shown in Scheme 1, the pKa determination by the UV-vis spectroscopic method in solutions
requires a base (B−) which is strong enough to firstly deprotonate the indicator acid (HIn) with a
known pKa value (in the same solvent which the measurement is conducted), then the resulting
indicator anion (In−) is titrated with a target acid (HA). The acidity of HA (pKaHA) then can be
derived from the equilibrium constant (Keq) and the acidity of indicator (pKaHIn).4a,4b Normally in
order to establish an equilibrium whereby Keq can be accurately measured by UV-vis approach, the
acidity gap (∆pKa) between pKaHIn and pKaHA should be less than 2 pK units.4a,14 In addition, the
ideal base (B−) should have no UV-vis absorbance and should be strong enough to fully deprotonate
the indicator acids but without destroying the solvent system. Furthermore, it must have a sufficient
solubility and should be free from various modes of ion associations, such as ion-pairs, in the solvent
of measurement.15 Therefore, the selection of appropriate indicator acids and bases (B−) requires a
series of stringent tests and is critical for the pKa determination by the UV-vis spectroscopic method.
Fortunately, the choice of indicators (HIn) and target acid (HA) for the pKa determination in ILs can
be facilitated by the acidity comparisons in DMSO,4a since we have shown that there exist good
linear correlations between the acidities of the C-H acids in both protic and aprotic ILs and those in
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 19
1
2
3
4
DMSO.12
5
iPr
S
6
7
8
9
pKa in [BMPY][NTf2]
25.2
9-iPrS-FH
25.3
1e
HIn-5
tBu
S
CN
24.0
9-tBuS-FH
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
HIn-4
NC
24.3
1d
Ph
CN
S
23.7
9-PhS-FH
23.35
1c
S
S
HIn-3
O
O O
O
Ph
NH
N
23.1
1b
S
S
22.3
9-PhNH-N=FH
O
O O
O O
O
O
HIn-2
SO2Me
S
S
21.55
1a
O
20.6
9-MeSO2-FH
20.2
2d
HIn-1
SO2Et
NO2
MeO
12a
20.25
9-EtSO2-FH
(FH = fluorene)
Figure 1. The Extended Acidity Ladder in [BMPY][NTf2]
Based on the acidities of aliphatic nitroalkanes in DMSO (pKas ≈ 174d), such as nitromethane (2a)
and nitroethane (2b), the indicators and base precursor (1b) which were used previously12 are no
longer suitable for the pKa determination of the nitroalkanes involved in this work (For details, see
SI). Accordingly, a stronger base, i.e., the potassium salt of diethyl isopropylmalonate (base-2,
Figure S4), and several fluorene-based indicator acids (HIn-1 to HIn-5, Figure 1) with a higher
pKaHIn were synthesized and rigorously tested for the acidity measurement in [BMPY][NTf2]. As
have noted, the pKa determination in solution should avoid ion-associations, typically ion-pair
formations between the indicator anions (In−) and the metal cation which is introduced into the
system by the adding of base in the first place. If this occurs, it would result in an “apparent pKa”
(or called ion-pair pKa)15 rather than the desired true pKa (or “free-ion pKa”).4a Since the base-2 is a
potassium salt, if the ion-pair formation occurs between the carbanion of diethyl isopropylmalonate
or indicator anion (In−) and potassium cation in the IL solution, the measured acidity value should
be affected by the addition of an equal molar (relative to the base) of chelating reagent, i.e., 2,2,2-
cryptand, a well-known potassium cation scavenger.14a Our test results showed that there is no
change in the pKas of 2 representative C-H acids with and without adding 2,2,2-cryptand (SI, Table
S2), which indicates that our pKa measurements in [BMPY][NTf2] are free from ion-pair
complications. This is in line with our previous findings that salts are totally free in ILs under our
4
ACS Paragon Plus Environment

Page 5 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
experimental conditions.12e Further tests on the base-2 showed that it can perfectly repeat the pKa
values of several C-H acids which were obtained previously by using the old base (base-1, SI)
without compromising the precision. (Table S1). Subsequently, an extended acidity ladder was
realized, which is about 5 more pK units wider than the previous established one (Figure 1). In
addition, the acidities of several weak C-H acids that are not available previously, i.e., disulfone
(1a-1c) and benzylnitrile (1d, 1e) derivatives, were also obtained. In principal, current acidity ladder
enables us to measure the weaker acids with a pKa up to ~27 in [BMPY][NTf2], combining with the
previously established ones in this IL,12a,12f the overall acidity ladder covers more than 20 pK units
now (Figure S5 provides our previously established acidity ladder).
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
R
NO2
NO2
NO2
NO2
NO2
NO2
R = CH3 (2a)
= Et (2b)
= n-Pr (2c)
MeO
Cl
2d
2h
2e
2f
2j
NO2
NO2
Br
CF3
F
2i
2g
NO2
NO2
NO2
NO2
CN
O
2m
2k
2l
Figure 2. Structures of Nitroalkanes Involved in This Work.
Table 1. pKa Values of Nitroalkanes in Various Solvents
anitroalkane
bpKa[BMPY][NTf ]
cpKaDMSO
17.2
cpKaH O
2
2
CH3NO2 (2a)
24.6
10.2
8.6
CH3CH2NO2 (2b)
CH3CH2CH2NO2 (2c)
24.05
24.35
20.2
16.7
17.0
9.0
4-MeOC6H4CH2NO2 (2d)
C6H5CH2NO2 (2e)
19.8
12.0
11.1
6.9
4-tBuC6H4CH2NO2 (2f)
4-FC6H4CH2NO2 (2g)
4-ClC6H4CH2NO2 (2h)
4-BrC6H4CH2NO2 (2i)
4-CF3C6H4CH2NO2 (2j)
d4-BzC6H4CH2NO2 (2k)
4-CNC6H4CH2NO2 (2l)
4-NO2C6H4CH2NO2 (2m)
19.8
19.5
19.2
19.05
18.35
17.9
17.65
9.3
8.6
6.2
5.9
16.9
aThe acidic hydrogens are indicated by boldface type. bIn pKa units, SD: ≤ ± 0.05 pK unit. cref.4d. dBz = benzoyl.
Acidities of nitroalkanes in [BMPY][NTf2]. With the expanded acidity ladder in our hands, next
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 19
1
2
3
4
5
6
7
8
9
the acidities of a series of nitroalkanes (Table 1 and Figure 2) were precisely measured (SD ≤ ± 0.05
pK unit), including aliphatic (2a-2c) and aromatic ones (2d-2m), the results are listed in Table 1,
together with the available data in molecular solvents. Table 1 shows that the acidity scale of
nitroalkanes covers a range of about 8 pK units in [BMPY][NTf2], and the acidities of aliphatic
nitroalkanes (2a-2c) are significantly lower (~4-7 pK units) than those of aromatic ones (2d-2m),
which is mainly due to the absence of a resonance stabilization of incipient anions from benzene
ring. In general, the acidity of nitroalkane is much weaker in [BMPY][NTf2] than those in DMSO
and water, which is consistent with the acidity order observed in our previous studies.12 Presumably,
this is because of large negative Gibbs transfer energy of proton from ILs to DMSO or water
[∆G*trans(H+, IL→S)]. In specific, the absolute single-ion solvation free energies of proton ∆G*(H+)
in DMSO, water and an aprotic IL [EMIM][NTf2] ([EMIM] = 1-ethyl-3-methylimidazolium) were
obtained both experimentally and theoretically16 as -273.3,16a -265.916a and -257.116c,d kcal mol-1,
respectively, which yields a Gibbs transfer energy of proton from the IL to water or DMSO
[∆G*trans(H+, IL→S)] of -8.8 or -16.2 kcal mol-1. In addition, the dielectric constant of
[BMPY][NTf2] (er = 14.717), is much lower than those for water (80.1) and DMSO (46.5).9c This
may also be part of a reason for a weaker acidity of nitroalkane in [BMPY][NTf2], though there
exist controversies on the suitability of the microwave dielectric spectroscopy or electrical
capacitance method for measuring the dielectric constants for ILs.6c
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
From Table 1, one can also find that the acidity for the aliphatic nitroalkane follows an order of
nitroethane (2b) > 1-nitropropane (2c) > nitromethane (2a) in [BMPY][NTf2] as well as in molecular
solvents. The gas-phase acidity difference between 2a and 2b is practically negligible (349.7 and
349.5 kcal mol-1, respectively),4d being only 0.2 kcal mol-1, in addition, there is no available gas-
phase acidity data for 2c (and other aromatic nitroalkanes). In solution, the acidity of 2b is about 4
times (DpKa = 0.6) stronger than 2a in [BMPY][NTf2], which is similar to that found in DMSO, but
the acidity difference between 2a and 2b is significantly smaller than in water (DpKa = 1.6).
Although the acidity order for the aliphatic nitroalkanes in protic solutions has been rationalized
through hyperconjugation effects in previous literature,18 since the magnitude for the acidity
differences observed here for 2a, 2b and 2c in [BMPY][NTf2] are relatively small, this could also
be understood, alternatively, on the basis of the subtle solvation differences in the IL.9c
6
ACS Paragon Plus Environment

Page 7 of 19
The Journal of Organic Chemistry
1
2
3
4
5
21
6
7
8
9
Slope = 2.06, R2 = 0.990
20
19
18
17
16
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
-0.6 -0.3
0
0.3
0.6
0.9
1.2
1.5
-
sp
Figure 3. Hammett Type Plot for 4-Substituted Phenylnitromethanes (2d-2m) in [BMPY][NTf2]
Hammett analyses and acidity correlations. In order to probe the solvation difference for these
nitro compounds, the substituent effect for the aromatic nitroalkanes was studied through
constructing Hammett type plots in [BMPY][NTf2] and compared with those in molecular solvents.
The Hammett correlation for 4-substituted phenylnitromethanes (2d-2m) shows a good linear
relationship (R2 = 0.990) with a slope of 2.06 (Figure 3), which is rather close to that found in
DMSO (2.60, R2 = 0.997, Figure S6), but significantly larger than those in water (0.80, R2 = 0.993)
and 50% (v/v) aqueous methanol (0.91, R2 = 0.978) (Figures S7 and S8). This indicates that the
substituent dependence for these phenylnitromethanes in the IL is similar to that in DMSO but not
like that in protic solvents. In the protic solvent water or aqueous binary solvent system, due to a
strong hydrogen-bonding solvation stabilization,19 the internal resonance stabilization through
benzene ring is less important. Consequently, the incipient negative charge can be readily
delocalized into the nitro group and hence the resonance structure C is favored (Scheme 2). On the
other hand, aprotic DMSO is well-known for its relatively weak solvability towards the charge less
delocalized anions, such as phenoxides and azides, etc.20 Therefore, the relative importance of
resonance structure B in DMSO, as well as in [BMPY][NTf2], is greater than that of C in protic
solvents, and thus, leading to a more pronounced substituent effect (a larger Hammett r value).
O
O
O
N
O
N
O
N
O
G
G
G
C
B
A
Scheme 2. The Resonance Structures of 4-Substituted Phenylnitromethane Anions
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 19
1
2
3
4
5
6
7
8
It is also worth noting that the Hammett r value for the 4-substitutited phenylmalononitriles in
DMSO and [BMPY][NTf2] is 4.77 and 3.66, respectively (Figures S9 and S10), using the data we
measured previously in this IL.12a
9
27
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
y = 0.89x + 9.18
R2 = 0.997
2a
25
23
21
19
17
15
2b
2c
2i
2e
2m
2l
7
9
11
13
15
17
19
pKa in DMSO
Figure 4. The Acidity Correlation of Nitroalkanes in [BMPY][NTf2] and DMSO
The acidity correlations between solvents of various properties can be a powerful tool to detect
the differential solvation on a series of substrates of interest. As shown in Figure 4, the acidities of
nitroalkanes correlate excellently (R2 = 0.997) with those available data in DMSO, which is
consistent with our previous findings for C-H acids in ILs.12a This is not unexpected since the pKas
measured in the IL and DMSO are free from ion-pairing perturbation and specific solvation which
are generally found in the solvents of low polarity and strong hydrogen-bonding.9c,21 Indeed, a
comprehensive correlation of acidities for nearly 30 structurally different C-H acids, i.e., fluorenes,
nitriles, disulfones and nitroalkanes in [BMPY][NTf2] and those in DMSO shows a very good linear
relationship (R2 = 0.991, Figure S11) over more than 19 pK units in DMSO, from which the pKa of
an unknown C-H acid in [BMPY][NTf2] and DMSO can be conveniently estimated through the
correlation equation described in Equation. 1.
pKa[BMPY][NTf ] = 0.922pKaDMSO + 8.84
Eqn. 1
2
CONCLUSIONS
To summarize, based on our previous work on the acidity determination of C-H acids in ILs, in
this work we have successfully expanded the acidity ladder scale in an aprotic IL [BMPY][NTf2],
which is about 5 more pK units wider than that previously established. The newly enlarged scale
enables us to precisely measure the acidities of a series of aliphatic and aromatic nitroalkanes. The
8
ACS Paragon Plus Environment

Page 9 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Hammett type plots and excellent linear correlations exhibit in the regression analyses for these
nitroalkanes suggest that the solvation behavior of [BMPY][NTf2] on the acidic dissociations of
these C-H acids is similar to that of dipolar aprotic DMSO. The equilibrium acidities of these
nitroalkanes and the solvation behavior revealed in this work may potentially serve either as a
benchmark or as reliable references for the development of appropriate computational methods in
[BMPY][NTf2].
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 SECTION
General considerations. [BMPY][NTf2] was synthesized and purified as described in our
previous work.12 In addition, [BMPY][NTf2] was dried in vacuum at 70 oC for 5 hours and stored
in desiccators with argon protection. The water content is less than 15 ppm, which was determined
by the Karl-Fischer titration and was routinely monitored before each individual pKa determination.
All the chemicals, solvents were purchased from commercially available sources and used directly
except otherwise noted. The indicator acids, bases and nitroalkanes involved in this work are not
new compounds, except otherwise noted, were synthesized and purified as reported before.
Synthesis of indicator acids. The indicator acids (HIn-1 to HIn-5) were prepared by previously
reported procedures.22
9-(methylsulfonyl)fluorene (HIn-1) was synthesized according to the reported procedures
(Figure S1).22a In specific, 20 mmol 9-bromofluorene and 20 mmol thiourea were dissolved in 100
ml THF, the mixture was refluxed for 3h and the solvent was removed. Then 100 ml aqueous NaOH
(~3 mol L-1) was added, the reaction mixture was further heated and stirred at 100 oC for 4h. After
cooling down to room temperature, 125 ml aqueous H2SO4 (10% wt) was added slowly to the
mixture which was cooled with an ice-bath. The liquid mixture was extracted with CHCl3 (50 ml*3).
The organic phase was dried with anhydrous Na2SO4, and evaporated in vacuo to afford crude 9-
mercaptofluorene. Next, the crude 9-mercaptofluorene, together with 9 mmol of NaOMe and 90 ml
MeI were dissolved in 70 ml dry MeOH, the reaction mixture was stirred at 30 oC for 4h. The solvent
was removed and 36 ml H2SO4 aqueous (5% wt) was added to the reaction residue. The aqueous
layer was extracted with DCM (90 ml*3) and dried with anhydrous Na2SO4, evaporated in vacuo to
give a crude product 9-methylthiofluorene. Then, the crude 9-methylthiofluorene was dissolved in
a mixture of 80 ml AcOH and 30 ml aqueous H2O2 (30% wt). The reaction mixture was stirred
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 19
1
2
3
4
5
6
7
8
9
vigorously at 50 °C for 30 min, then cooled and poured into 360 ml ice water. The precipitate was
collected by filtration and then dissolved in DCM. This DCM solution was filtered and the filtrate
was dried with anhydrous Na2SO4 and evaporated to afford a crude 9-(methylsulfonyl)fluorene
(HIn-1) product. 0.63 g HIn-1 was obtained as white needles after multiple crystallization from
MeOH.
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-(9H-fluoren-9-ylidene)-2-phenylhydrazine (HIn-2) was synthesized according to the reported
procedures (Figure S2).22b 8.3 mmol 9H-fluoren-9-one was dissolved in 30 ml dry EtOH, then 1 ml
AcOH was added to the mixture which was cooled with an ice-bath. After 10 mins, 9.3 mmol
phenylhydrazine was added to the mixture. The reaction mixture was stirred at 78 oC for 0.5h until
all the solid suspended in solution. 0.70 g 1-(9H-fluoren-9-ylidene)-2-phenylhydrazine (HIn-2) was
obtained as yellow solid after multiple crystallization from EtOH.
9-alkylthiofluorenes (HIn-3 to HIn-5) was synthesized according to the known procedures
(Figure S3).22c 10 mmol thiol (R-SH, R = Ph, iPr and tBu) was dissolved to 150 ml dry menthol, 0.21
ml sodium methylate solution (5.4 mol/L) was added to the mixture dropwise which was cooled
with an ice-bath. After 0.5h, 10 mmol 9-bromo-9H-fluorene was added to the mixture under inert
atmosphere. The mixture was stirred at 78 oC for about 1h to allow all the solid to suspend in the
solution. The mixture was filtered and the corresponding 9-alkylthiofluorenes were then obtained as
a white solid after repeated crystallization from MeOH.
9-(methylsulfonyl)fluorene (HIn-1), white needles (0.63 g, the overall yield: 13%). 1H NMR (400
MHz, DMSO-d6): δ 8.00 (d, J = 7.6 Hz, 2H), 7.83 (d, J = 7.6 Hz, 2H), 7.56 (t, J = 7.5 Hz, 2H), 7.45
(t, J = 7.5 Hz, 2H), 5.86 (s, 1H), 2.49 (d, J = 13.2 Hz, 3H). 13C{1H} NMR (100 MHz, DMSO-d6) δ
141.4, 136.0, 129.6, 127.9, 126.6, 120.8, 69.4, 36.0 ppm.22a
1-(9H-fluoren-9-ylidene)-2-phenylhydrazine (HIn-2), yellow solid (0.70 g, yield: 31%). 1H NMR
(400 MHz, DMSO-d6) δ 10.34 (s, 1H), 8.44 (d, J = 7.0 Hz, 1H), 8.03–7.93 (m, 1H), 7.91–7.78 (m,
2H), 7.59–7.43 (m, 4H), 7.42–7.30 (m, 4H), 6.95 (t, J = 7.3 Hz, 1H). 13C{1H} NMR (100 MHz,
DMSO-d6) δ 145.3, 139.9, 139.2, 137.7, 137.4, 129.3, 129.1, 129.0, 128.0, 127.7, 127.6, 125.8,
121.1, 120.5, 120.4, 120.0, 114.1 ppm.22b
9-(phenylthio)fluorene (HIn-3), white solid (1.84 g, yield: 67%). 1H NMR (400 MHz, DMSO-
d6) δ 7.81 (d, J = 7.5 Hz, 2H), 7.49 (d, J = 7.4 Hz, 2H), 7.38 (t, J = 7.3 Hz, 2H), 7.34–7.24 (m, 4H),
7.23–7.16 (m, 3H), 5.66 (s, 1H).13C{1H} NMR (100 MHz, DMSO-d6) δ 144.1, 139.9, 133.1, 132.0,
10
ACS Paragon Plus Environment

Page 11 of 19
The Journal of Organic Chemistry
1
2
3
4
128.8, 128.1, 127.6, 127.4, 125.0, 120.2, 50.3 ppm.22c
5
6
7
8
9-(tert-butylthio)fluorene (HIn-4), white solid (1.91 g, yield: 75%). 1H NMR (400 MHz, DMSO-
d6) δ 7.99–7.76 (m, 2H), 7.63 (d, J = 6.7 Hz, 2H), 7.49–7.30 (m, 4H), 5.12 (s, 1H), 1.47 (s, 9H).
13C{H} NMR (100 MHz, DMSO-d6) δ 146.7, 139.5, 127.6, 127.5, 125.6, 119.9, 47.1, 44.2, 31.8
ppm.22c
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
9-(isopropylthio)fluorene (HIn-5), white solid (1.44 g, yield: 60%). 1H NMR (400 MHz, DMSO-
d6) δ 7.87 (d, J = 6.8 Hz, 2H), 7.64 (d, J = 7.3 Hz, 2H), 7.50–7.30 (m, 4H), 5.18 (s, 1H), 2.69 (dt, J
= 13.5, 6.7 Hz, 1H), 1.00 (d, J = 6.7 Hz, 6H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 145.4, 139.8,
127.8, 127.5, 125.3, 120.2, 47.7, 33.6, 24.1 ppm.22c
Synthesis of base precursors. The bis(ethylsulfonyl)methanes (1a-1c) were synthesized
according to the reported procedures.23 These disulfone derivatives are the base precursors whose
potassium salts were used to deprotonate the indicator acids in our previous pKa determinations in
ILs.12 Although the basicities of their conjugated bases are not sufficient strong to undergo a
measurable deprotonation of indicator acids used in current work, they are crucial components for
the building up the expanded acid ladder in a stepwise fashion (Figure 1).
50 mmol aldehyde (RCHO, R = H, Et and iPr) and 100 mmol ethanethiol were dissolved in
300 ml chloroform. 91 ml chlorotrimethylsilane was added dropwise into the mixture with the
evolution of gas. The solution was cooled with an ice-bath and stirred for 2h until it became clear.
Then aqueous Na2CO3 (5% wt) was added to the solution until the reaction mixture became alkaline.
Subsequently, the solution was washed with deionized water and the organic layer was dried with
anhydrous Na2SO4. The crude product bis(ethylthio)methane was obtained after the organic layer
was evaporated. Next, cooled with an ice-bath, the crude bis(ethylthio)methane, together with 605
ml aqueous H2O2 (30% wt) were dissolved in 1140 ml CH3COOH. After 30 mins, the reaction
o
mixture was stirred at 50 C for 2h. Then the mixture was poured into 3000 ml ice water. The
aqueous layer was extracted with DCM (800 ml*3) and was washed with deionized water (500
ml*2). The organic phase was evaporated to afford crude bis(ethylsulfonyl)methanes. 1a-1c was
obtained as white solid after multiple crystallization from EtOH.
EtSO2CH2SO2Et (1a), white solid (4.01 g, yield: 40%). 1H NMR (400 MHz, DMSO-d6) δ 5.43
(s, 2H), 3.35 (dd, J = 14.7, 7.3 Hz, 4H), 1.27 (t, J = 7.4 Hz, 6H). 13C{1H} NMR (100 MHz, DMSO-
d6) δ 67.0, 48.6, 5.9 ppm.23
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 19
1
2
3
4
5
6
7
8
9
EtSO2CH(iPr)SO2Et (1b), white solid (5.09 g, yield: 42%). 1H NMR (400 MHz, CDCl3-d1) δ 4.01
(d, J = 1.5 Hz, 1H), 3.60 (dq, J = 14.9, 7.5 Hz, 2H), 3.27 (dq, J = 14.9, 7.4 Hz, 2H), 2.95 (heptd, J
= 7.1, 1.5 Hz, 1H), 1.55–1.33 (m, 12H). 13C{1H} NMR (100 MHz, CDCl3-d1) δ 83.9, 49.2, 28.2,
21.0, 5.8 ppm.23
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
EtSO2CH(Et)SO2Et (1c), white solid (5.25 g, yield: 46%). 1H NMR (400 MHz, DMSO-d6) δ 5.14
(t, J = 5.7 Hz, 1H), 3.40 (q, J = 7.4, 4H), 2.24-2.12 (m, 2H) 1.28 (t, J = 7.4 Hz, 6H). 1.19 (t, J = 7.4,
3H). 13C{1H} NMR (100 MHz, DMSO-d6) δ 78.5, 47.1, 17.9, 13.1, 5.4 ppm.23
Synthesis of nitroalkanes. The aliphatic nitroalkanes (2a-2c) were purchased from the available
commercial sources, and were purified from multiple reduced pressure distillations before used as
the substrates. The aromatic nitroalkanes (2d-2m) were synthesized and purified according to the
known procedures.24 The mass and yield for the following specific aromatic nitroalkane were based
on 20 mmol starting material respectively.
4-MeOC6H4CH2NO2 (2d), clear oil (2.88 g, yield: 86%). 1H NMR (400 MHz, CDCl3-d1) δ 7.51–
7.29 (m, 2H), 7.06–6.81 (m, 2H), 5.37 (s, 2H), 3.83 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3-d1) δ
161.0, 131.7, 122.1, 114.6, 79.7, 55.5 ppm.24b
C6H5CH2NO2 (2e), clear oil (1.73 g, yield: 63%). 1H NMR (400 MHz, CDCl3-d1) δ 7.45 (d, J =
2.3 Hz, 5H), 5.45 (s, 2H). 13C{1H} NMR (101 MHz, CDCl3-d1) δ 130.2, 130.1, 129.9, 129.2, 80.2
ppm.24c
4-tBuC6H4CH2NO2 (2f), clear solid (1.93 g, yield: 50%). 1H NMR (400 MHz, CDCl3-d1) δ 7.45
(d, J = 8.3 Hz,2H), 7.39 (d, J = 8.3 Hz, 2H), 5.42 (s, 2H), 1.33 (s, 9H). 13C{H} NMR (100 MHz,
CDCl3-d1) δ 153.3, 129.8, 126.9, 126.1, 79.8, 34.9, 31.3 ppm.24c
4-FC6H4CH2NO2 (2g): clear oil (1.99 g, yield: 65%). 1H NMR (400 MHz, CDCl3-d1) δ 7.45 (dd,
J = 8.5, 5.2 Hz, 2H), 7.11 (t, J = 8.6 Hz, 2H), 5.41 (s, 2H). 13C{1H} NMR (100 MHz, CDCl3-d1) δ
163.7(d, J = 250.0 Hz), 132.2 (d, J = 8.7 Hz), 125.8 (d, J = 3.3 Hz), 116.3 (d, J = 22.0 Hz), 79.2
ppm.24c
4-ClC6H4CH2NO2 (2h), white solid (2.40 g, yield: 70%). 1H NMR (400 MHz, CDCl3-d1) δ 7.41
(m, 4H), 5.41 (s, 2H). 13C{1H} NMR (100 MHz, CDCl3-d1) δ 136.5, 131.5, 129.5, 128.2, 79.3
ppm.24c
4-BrC6H4CH2NO2 (2i), white solid (1.64 g, yield: 38%). 1H NMR (400 MHz, CDCl3-d1) δ 7.58
(d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.3 Hz, 2H), 5.40 (s, 2H). 13C{1H} NMR (100 MHz, CDCl3-d1) δ
12
ACS Paragon Plus Environment

Page 13 of 19
The Journal of Organic Chemistry
1
2
3
4
132.5, 131.8, 128.6, 124.7, 79.4 ppm.24a
5
6
7
8
4-CF3C6H4CH2NO2 (2j), white solid (3.04 g, yield: 74%). 1H NMR (400 MHz, CDCl3-d1) δ 7.72
(d, J = 8.2 Hz, 2H), 7.60 (d, J = 8.1 Hz, 2H), 5.51 (s, 2H). 13C{1H} NMR (100 MHz, CDCl3-d1) δ
133.3, 132.3 (q, J = 32.8 Hz), 126.2 (q, J = 3.8 Hz), 123.8 (q, J = 272.5 Hz), 79.3 ppm.24c
4-BzC6H4CH2NO2 (2k), white solid (3.23 g, yield: 67%). 1H NMR (400 MHz, CDCl3-d1) δ 7.86
(d, J = 8.2 Hz, 2H), 7.83–7.77 (m, 2H), 7.61 (dd, J = 15.5, 7.8 Hz, 3H), 7.50 (t, J = 7.6 Hz, 2H),
5.54 (s, 2H).13C{1H} NMR (100 MHz, CDCl3-d1) δ 195.9, 139.2, 137.2, 133.5, 133.0, 130.8, 130.2,
130.1, 128.6, 79.7 ppm.24b
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
4-CNC6H4CH2NO2 (2l), white solid (2.59 g, yield: 80%). 1H NMR (400 MHz, CDCl3-d1) δ 7.75
(d, J = 8.3 Hz, 2H), 7.59 (d, J = 8.3 Hz, 2H), 5.51 (s, 2H). 13C{1H} NMR (100 MHz, CDCl3-d1) δ
134.1, 133.0, 130.9, 118.0, 114.4, 79.2 ppm.24c
4-NO2C6H4CH2NO2 (2m), white solid (1.86 g, yield: 51 %). 1H NMR (400 MHz, CDCl3-d1) δ
8.32 (d, J = 8.6 Hz, 2H), 7.67 (d, J = 8.6 Hz, 2H), 5.56 (s, 2H). 13C{1H} NMR (100 MHz, CDCl3-
d1) δ 149.0, 135.8, 131.3, 124.4, 78.9 ppm.24a
pKa Measurement of nitroalkanes in [BMPY][NTf2].
The procedures for pKa determination in [BMPY][NTf2] were similar to those described
previously.12 In specific, the pKa measurement was initiated by the adding of 1.5 ml [BMPY][NTf2]
solution of base-2 (~5 × 10-4 M) into an empty UV cell with a specially made 3-way valve,12f and
then the spectrum for baseline was recorded on a UV instrument. Next an IL solution of an
appropriate indicator acid (HIn) with the known pKa was added dropwisely until the UV absorbance
was not increasing with a further addition. Then a [BMPY][NTf2] solution of nitroalkane (~0.06 M)
was added in several portions (the final concentration of the nitroalkane in the IL solution was about
10-4 M). The weight of the UV cell and the corresponding spectrum were also recorded upon each
addition. The pKa of nitroalkane was then calculated from the change of absorbance and the amount
of nitroalkane added.
ASSOCIATED CONTENT
Supporting Information
Detailed experimental procedures; regression analyses; representative UV-vis and NMR spectra.
This material is available free of charge via the Internet at http://pubs.acs.org.
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 19
1
2
3
4
5
6
AUTHOR INFORMATION
Corresponding Author
7
8
9
jipengju@mail.tsinghua.edu.cn; jinpei_cheng@mail.tsinghua.edu.cn.
Notes
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
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful for the financial grants from National Natural Science Foundation of China (Nos.
21672124, 21390401). The partial of this work was also supported by Tsinghua University Initiative
Scientific Research Program (No. 20141081295).
REFERENCES
(1) Reutov, O. A.; Beletskaya, I. P.; Butin, K. P. C-H Acids; Pergamon Press: Oxford, 1978.
(2) (a) Hammett, L. P. Physical Organic Chemistry, 2nd ed.; McGraw-Hill: New York, 1970; (b)
Isaacs, N. Physical Organic Chemistry, 2nd ed.; Prentice Hall: London, 1996; (c) Anslyn, E.
V.; Dougherty, D. D. Modern Physical Organic Chemistry, University Science Books:
Sausalito, CA, 2006.
(3) (a) Cram, D. J. Fundamentals of Carbanion Chemistry, Academic Press: New York, 1965; (b)
Bates, R. B.; Ogle, C. A. In Carbanion Chemistry-Reactivity and Structure Concepts in
Organic Chemistry; Hafner, K.; Lehn, J. M.; Rees, C. W.; Schleyer, P. von R.; Trost, B. M.;
Zahradnik, R., Eds.; Springer-Verlag: Berlin, 1983; Vol. 17. (c) Buncel, E.; Dust, J. M.
Carbanion Chemistry-Structures and Mechanism; Oxford: New York, 2003.
(4) For comprehensive and critical reviews on the methods for acidity determination and the
established scales of carbon acids in molecular solvents, see: (a) Yang, J.-D.; P. Ji.; Xue, X.-S.;
Cheng, J.-P. Recent Advances and Advisable Applications of Bond Energetics in Organic
Chemistry. J. Am. Chem. Soc. 2018, 140, 8611–8623 and the references cited therein. (b) Xue,
X.-S.; Ji, P.; Zhou, B.; Cheng, J.-P. The Essential Role of Bond Energetics in C–H
Activation/Functionalization. Chem. Rev. 2017, 117, 8622–8648. (c) Kütt, A.; Selberg, S.;
Kaljurand, I.; Tshepelevitsh, S.; Heering, A.; Darnell, A.; Kaupmees, K.; Piirsalu, M.; Leito, I.
pKa Values in Organic Chemistry–Making Maximum Use of the Available Data. Tetrahedron
Lett., 2018, 59, 3738–3748 and the references cited therein. (d) Internet Bond-energy Databank
14
ACS Paragon Plus Environment

Page 15 of 19
The Journal of Organic Chemistry
1
2
3
4
(iBonD), ibond.chem.tsinghua.edu.cn or ibond.nankai.edu.cn.
5
6
7
8
(5) For a series of representative work, but certainly not limited to, on the acidity determination of
carbon acids in various molecular solvents, see: (a) Bordwell, F. G. Equilibrium Acidities in
Dimethyl Sulfoxide Solution. Acc. Chem. Res. 1988, 21, 456–463. (b) Streitwieser, A.
Carbanion Ion Pairs and Triplets. Acc. Chem. Res. 1984, 17, 353−357. (c) Ritchie, C. D.;
Uschold, R. E. Acidity in Nonaqueous Solvents. IV. Hydrocarbon Acids in Dimethyl Sulfoxide.
J. Am. Chem. Soc. 1967, 89, 1721−1725. (d) Koppel, I. A.; Koppel, J.; Pihl, V.; Leito, I.;
Mishima, M.; Vlasov, V. M.; Yagupolskii, L. M.; Taft, R. W. Comparison of Brønsted Acidities
of Neutral CH Acids in Gas Phase and Dimethyl Sulfoxide. J. Chem. Soc., Perkin Trans. 2
2000, 0, 1125−1133. (e) Amyes, T. L.; Richard, J. P. Substituent Effects on Carbon Acidity in
Aqueous Solution and at Enzyme Active Sites. Synlett 2017, 28, 1407−1421.
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
(6) (a) Welton, T. Room-Temperature Ionic Liquids. Solvents for Synthesis and Catalysis. Chem.
Rev. 1999, 99, 2071–2084. (b) Rogers, R. D.; Seddon, K. R. Ionic Liquids−Solvents of the
Future? Science 2003, 302, 792–793. (c) Hallett, J. P.; Welton, T. Room-Temperature Ionic
Liquids: Solvents for Synthesis and Catalysis. 2. Chem. Rev. 2011, 111, 3508–3576.
(7) (a) Ahrens, S.; Peritz, A.; Strassner, T. Tunable Aryl Alkyl Ionic Liquids (TAAILs): The Next
Generation of Ionic Liquids. Angew. Chem. Int. Ed. 2009, 48, 7908–7910. (b) Giernoth, R.
Task-Specific Ionic Liquids. Angew. Chem. Int. Ed. 2010, 49, 2834–2839. (c) Yang, Z.-Z.; Zhao,
Y.-N.; He, L.-N. CO2 Chemistry: Task-Specific Ionic Liquids for CO2 Capture/Activation and
Subsequent Conversion. RSC Adv. 2011, 1, 545–567.
(8) (a) Wasserscheid, P.; Keim, W. Ionic Liquids−New “Solutions” For Transition Metal Catalysis.
Angew. Chem. Int. Ed. 2000, 39, 3772–3789. (b) Rantwijk, F. V.; Sheldon, R. A. Biocatalysis
in Ionic Liquids. Chem. Rev. 2007, 107, 2757–2785. (c) Wasserscheid, P.; Welton, T., Eds. Ionic
Liquids in Synthesis; Wiley-VCH: Weinheim, 2008. (d) Pinkert, A.; Marsh, K. N.; Pang, S.;
Staiger, M. P. Ionic Liquids and Their Interaction with Cellulose. Chem. Rev. 2009, 109, 6712–
6728. (e) Bideau, J. L.; Viau, L.; Vioux, A. Ionogels, Ionic Liquid Based Hybrid Materials.
Chem. Soc. Rev. 2011, 40, 907–925. (f) Sun, X.-Q.; Luo, H.-M.; Dai, S. Ionic Liquids-Based
Extraction: A Promising Strategy for the Advanced Nuclear Fuel Cycle. Chem. Rev. 2012, 112,
2100–2128. (g) MacFarlane, D. R.; Tachikawa, N.; Forsyth, M.; Pringle, J. M.; Howlett, P. C.;
Elliott, G. D.; Davis, Jr., J. H.; Watanabe, M.; Simon, P.; Angell, C. A. Energy Applications of
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 19
1
2
3
4
5
6
7
8
Ionic Liquids. Energy Environ. Sci. 2014, 7, 232–250. (h) Watanabe, M.; Thomas, M. L.;
Zhang, S.; Ueno, K.; Yasuda, T.; Dokko, K. Application of Ionic Liquids to Energy Storage
and Conversion Materials and Devices. Chem. Rev. 2017, 117, 7190–7239.
9
(9) (a) Ben-Naim, A. Solvation Dynamics; Springer-Verlag: Boston, 1987. (b) Hirata, F. Molecular
Theory of Solvation; Kluwer Academic Publishers: Dordrecht, 2003. (c) Reichardt, C.; Welton,
T. Solvents and Solvent Effects in Organic Chemistry, 4th ed.; Wiley-VCH: Weinheim, 2011.
(d) Mennucci, B.; Cammi, R. Continuum Solvation Models in Chemical Physics: From Theory
to Applications; John Wiley & Sons: Chichester, 2007.
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
(10) (a) Gebbie, M. A.; Valtiner, M.; Banquy, X.; Fox, E. T.; Henderson, W. A.; Israelachvili, J. N.
Ionic Liquids Behave as Dilute Electrolyte Solutions. Proc. Natl. Acad. Sci. U. S. A. 2013, 110,
9674–9679. (b) Perkin, S.; Salanne, M.; Madden, P.; Lynden-Bell, R. Is a Stern and Diffuse
Layer Model Appropriate to Ionic Liquids at Surfaces? Proc. Natl. Acad. Sci. U. S. A. 2013,
110, E4121. (c) Lee, A. A.; Vella, D.; Perkin, S.; Goriely, A. Are Room-Temperature Ionic
Liquids Dilute Electrolytes? J. Phys. Chem. Lett. 2015, 6, 159–163. (d) Chen, H.; Chen, X.;
Deng, J.; Zheng, J. Isotropic Ordering of Ions in Ionic Liquids on the Sub-nanometer Scale.
Chem. Sci. 2018, 9,1464–1472.
(11) (a) Taft, R. W.; Bordwell, F. G. Structural and Solvent Effects Evaluated from Acidities
Measured in Dimethyl Sulfoxide and in the Gas Phase. Acc. Chem. Soc. 1988, 21, 463–469.
(b) Goumont, R.; Magnier, E.; Kizilian, E.; Terrier, F. Acidity Inversions of α-NO2 and α-
SO2CF3 Activated Carbon Acids as a Result of Contrasting Solvent Effects on Transfer from
Water to Dimethyl Sulfoxide Solutions. J. Org. Chem. 2003, 68, 6566–6570. (c) El Seoud, O.
A. Understanding Solvation. Pure Appl. Chem. 2009, 81, 697–707.
(12) (a) Deng, H.; Li, X.; Chu, Y.; He, J.-Q.; Cheng, J.-P. Standard pKa Scales of Carbon-Centered
Indicator Acids in Ionic Liquids: Effect of Media and Structural Implication. J. Org. Chem.
2012, 77, 7291–7298. (b) Wang, Z.; Deng, H.; Li, X.; Ji, P.; Cheng, J.-P. Standard and Absolute
pKa Scales of Substituted Benzoic Acids in Room Temperature Ionic Liquids. J. Org. Chem.
2013, 78, 12487–12493. (c) Wang, Z.; Ji, P.; Li, X.; Cheng, J.-P. Double-Line Hammett
Relationship Revealed through Precise Acidity Measurement of Benzenethiols in Neat Ionic
Media: A Typical “Ionic Liquid Effect”? Org. Lett. 2014, 16, 5744–5747. (d) Mao, C.; Wang,
Z.; Ji, P.; Cheng, J.-P. Is Amine a Stronger Base in Ionic Liquid Than in Common Molecular
16
ACS Paragon Plus Environment

Page 17 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Solvent? An Accurate Basicity Scale of Amines. J. Org. Chem. 2015, 80, 8384–8389. (e) Mao,
C.; Wang, Z.-D.; Wang, Z.; Ji, P.; Cheng, J.-P. Weakly Polar Aprotic Ionic Liquids Acting as
Strong Dissociating Solvent: A Typical “Ionic Liquid Effect” Revealed by Accurate
Measurement of Absolute pKa of Ylide Precursor Salts. J. Am. Chem. Soc. 2016, 138, 5523–
5526. (f) Wang, Z.-D.; Li, X.; Ji, P.; Cheng, J.-P. Absolute pKas of Sulfonamides in Ionic
Liquids: Comparisons to Molecular Solvents. J. Org. Chem. 2016, 81, 11195–11200. (g) Wang,
Z.; Gao, F. X.; Ji, P.; Cheng, J.-P. Unexpected Solvation-stabilisation of Ions in a Protic Ionic
Liquid: Insights Disclosed by a Bond Energetic Study. Chem. Sci. 2018, 9, 3538–3543.
(13) (a) Demicheli, G.; Maggi, R.; Mazzacani, A.; Righi, P.; Sartori, G.; Bigi, F. Supported Organic
Catalysts: Synthesis of (E)-Nitrostyrenes from Nitroalkanes and Aromatic Aldehydes Over
Propylamine Supported on MCM-41 Silica as a Reusable Catalyst. Tetrahedron Lett. 2001, 42,
2401–2403. (b) Ballini, R.; Bosica, G.; Livi, D.; Palmieri, A.; Maggi, R.; Sartori, G. Use of
Heterogeneous Catalyst KG-60-NEt2 in Michael and Henry Reactions Involving Nitroalkanes.
Tetrahedron Lett. 2003, 44, 2271–2273. (c) Ballini, R.; Bosica, G.; Fiorini, D.; Palmieri, A.;
Petrini, M. Conjugate Additions of Nitroalkanes to Electron-Poor Alkenes:ꢀ Recent Results.
Chem. Rev. 2005, 105, 933–972. (d) Peng, W.-M.; Shreeve, J. M. Convenient Fluorination of
Nitro and Nitrile Compounds with Selectfluor. Tetrahedron Lett. 2005, 46, 4905–4909. (e)
Handa, S.; Gnanadesikan, V.; Matsunaga, S.; Shibasaki, M. syn-Selective Catalytic
Asymmetric Nitro−Mannich Reactions Using a Heterobimetallic Cu−Sm−Schiff Base
Complex. J. Am. Chem. Soc. 2007, 129, 4900–4901.
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
(14) (a) Matthews, W. S.; Bares, J. E.; Bartmess, J. E.; Bordwell, F. G.; Cornforth, F. J.; Drucker, G.
E.; Margolin, Z.; McCallum, R. J.; McCollum, G. J.; Vanier, N. R. Equilibrium Acidities of
Carbon Acids. VI. Establishment of an Absolute Scale of Acidities in Dimethyl Sulfoxide
Solution. J. Am. Chem. Soc. 1975, 97, 7006–7014. (b) It should be noted that the acidity gap is
closely dependent on the molar extinction coefficient of indicator anion (In−).
(15) Otherwise, the measured acidity is the apparent or ion-pair pKa, especially in the solvents of
relatively low polarity, however, the ion-pair pKa may be corrected by Fouss equation to yield
the absolute one. For details, see: (a) Fouss, R. M. Ionic Association. III. The Equilibrium
Between Ion Pairs and Free Ions. J. Am. Chem. Soc. 1958, 80, 5059–5061. (b) Kim, Y.-J.;
Streitwieser, A. Basicity of a Stable Carbene, 1,3-Di-tert-butylimidazol-2-ylidene, in THF. J.
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 19
1
2
3
4
5
6
7
8
9
Am. Chem. Soc. 2002, 124, 5757–5761. (c) Kolomeitsev, A. A.; Koppel, I. A.; Rodima, T.;
Barten, J.; Lork, E.; Roschenthaler, G.-V.; Kaljurand, I.; Kutt, A.; Koppel, I.; Maemets, V.;
Leito, I. Guanidinophosphazenes: Design, Synthesis, and Basicity in THF and in the Gas Phase.
J. Am. Chem. Soc. 2005, 127, 17656–17666. (d) Saame, J.; Rodima, T.; Tshepelevitsh, S.; Kutt,
A.; Kaljurand, I.; Haljasorg, T.; Koppel, I. A.; Leito, I. Experimental Basicities of Superbasic
Phosphonium Ylides and Phosphazenes. J. Org. Chem. 2016, 81, 7349−7361.
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
(16) (a) Kelly, C. P.; Cramer, C. J.; Truhlar, D. G. Single-Ion Solvation Free Energies and the
Normal Hydrogen Electrode Potential in Methanol, Acetonitrile, and Dimethyl Sulfoxide. J.
Phys. Chem. B 2007, 111, 408–422. (b) Bernales, V. S.; Marenich, A. V.; Contreras, R.; Cramer,
C. J.; Truhlar, D. G. Quantum Mechanical Continuum Solvation Models for Ionic Liquids. J.
Phys. Chem. B 2012, 116, 9122–9129. (c) Xue, X.-S.; Wang, Y.; Yang, C.; Ji, P.; Cheng, J.-P.
Toward Prediction of the Chemistry in Ionic Liquids: An Accurate Computation of Absolute
pKa Values of Benzoic Acids and Benzenethiols. J. Org. Chem. 2015, 80, 8997–9006. (d)
Matsubara, Y.; Grills, D. C.; Koide, Y. Experimental Insight into the Thermodynamics of the
Dissolution of Electrolytes in Room-Temperature Ionic Liquids: From the Mass Action Law
to the Absolute Standard Chemical Potential of a Proton. ACS Omega 2016, 1, 1393–1411.
(17) Weingärtner, H. The Static Dielectric Permittivity of Ionic Liquids. J. Mol. Liq. 2014, 192,
185–190.
(18) (a) Kresge, A. J. Deviant Brönsted Relations. J. Am. Chem. Soc. 1970, 92, 3210–3211. (b)
Kresge, A. J. The Nitroalkane Anomaly. Can. J. Chem. 1974, 52, 1897–1903.
(19) Jeffrey, G. A. An Introduction to Hydrogen Bonding; Oxford University Press: New York, 1997.
(20) (a) Miller, J.; Parker, A. J. Dipolar Aprotic Solvents in Bimolecular Aromatic Nucleophilic
Substitution Reactions. J. Am. Chem. Soc. 1961, 83, 117–123. (b) Parker, A. J. The Effects of
Solvation on the Properties of Anions in Dipolar Aprotic Solvents. Quart. Rev. Chem. Soc.
1962, 16, 163–187. (c) Parker, A. J. Protic-Dipolar Aprotic Solvent Effects on Rates of
Bimolecular Reactions. Chem. Rev. 1969, 69, 1–32.
(21) Marcus, Y.; Hefter, G. Ion Pairing. Chem. Rev. 2006, 106, 4585–4621.
(22) (a) Bavin, P. M. G. Aliphatic Chemistry of Fluorene: Part IV. Preparation and Alkylation of
Some Sulphides and Sulphones. Can. J. Chem. 1960, 38, 917–922. (b) Hofmann, J.; Schulz,
K.; Zimmermann, G. Thermal Ring Enlargement of Aromatic Cyclopentadienylidene Iminyl
18
ACS Paragon Plus Environment

Page 19 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Radicals. Intramolecular Radical Addition to the N Atom of Nitriles Results in High Yields of
Aza-aromatics. Tetrahedron Lett. 1996, 37, 2399–2402. (c) Bordwell, F. G.; Drucker, G. E.;
McCollum, G. J. Stabilization of Carbanions by Polarization of Alkyl Groups on Nonadjacent
Atoms. J. Org. Chem. 1982, 47, 2504–2510.
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
(23) Ong, B. S.; Chan, T. H. A Simple Method of Dithioacetal– and Ketalization. Synth. Commun.
1977, 7, 283–286.
(24) (a) Asghar, B. H. Reactions of Substituted Phenylnitromethane Carbanions with Aromatic
Nitro Compounds in Methanol: Carbanion Reactivity, Kinetic, and Equilibrium Studies. Int. J.
Chem. Kinet. 2014, 46, 477–488. (b) Walvoord, R. R.; Berritt, S.; Kozlowski, M. C. Palladium-
Catalyzed Nitromethylation of Aryl Halides: An Orthogonal Formylation Equivalent. Org. Lett.
2012, 14, 4086–4089. (c) Marcé, P.; Lynch, J.; Blacker, A. J.; Williams, M. J. Conversion of
Nitroalkanes into Carboxylic Acids via Iodide Catalysis in Water. Chem. Comm. 2016, 52,
1013–1016.
TOC
Indicator Acids
Ph
NH
iPr
Ph
tBu
NO2
COOMe
SO2Ph
19.2
SO2Me
N
S
S
S
O2N
16.9
18.4
20.6
22.3
23.7
24.0
25.25
Nitroalkanes
NO2
24.6
NO2
NO2
24.35
G = 4-CN (17.65), 4-PhCO (17.9),
4-CF3 (18.35), 4-Br (19.05),
NO2
24.05
4-Cl (19.2), 4-F (19.5), 4-H (19.8),
4-tBu (19.8), 4-MeO (20.2).
G
pKa in [BMPY][NTf2]
19
ACS Paragon Plus Environment