Superacidifiers: Assessing the activation and the mode of charge transmission of the extraordinary electron-withdrawing SO2CF 3 and S(O)C=NSO2CF3CF3 substituents in carbanion stabilization

Article abstract of DOI:10.1021/ja0436291

We report on a structural (multinuclear NMR), thermodynamic (pK _a), and kinetic (Marcus intrinsic reactivity) study of the ionization of benzylic carbon acids activated by an exocyclic (α) SO ₂CF₃ group and SO₂C

Full text of DOI:10.1021/ja0436291

Published on Web 03/22/2005
Superacidifiers: Assessing the Activation and the Mode of
Charge Transmission of the Extraordinary
Electron-Withdrawing SO2CF3 and S(O)(dNSO2CF3)CF3
Substituents in Carbanion Stabilization
Franc¸ois Terrier,*,† Emmanuel Magnier,† Elyane Kizilian,† Claude Wakselman,† and
Erwin Buncel*,‡
Contribution from the Laboratoire SIRCOB, UMR 8086, Institut LaVoisier-Franklin,
UniVersite´ de Versailles, 45, AVenue des Etats-Unis, 78035 Versailles Cedex, France, and
Department of Chemistry, Queen’s UniVersity, Kingston, Ontario, K7L 3N6, Canada
Received October 20, 2004; E-mail: terrier@chimie.uvsq.fr; buncele@chem.queensu.ca
Abstract: We report on a structural (multinuclear NMR), thermodynamic (pKa), and kinetic (Marcus intrinsic
reactivity) study of the ionization of benzylic carbon acids activated by an exocyclic (R) SO2CF3 group and
SO2CF3 or S(O)(dNSO2CF3)CF3 in the para position of the phenyl ring. The latter exerts an enormous
acidifying effect of ca. 8 pK units as compared with 4-H benzyltriflone in Me2SO solution, (corresponding
to remarkably high Hammett σ values σp ≈ 1.35, σp- ≈ 2.30). In considering the origin of this effect, important
information was derived in comparing medium effects on pKa’s for NO2, SO2CF3, and S(O)(dNSO2CF3)-
CF3 activated carbon acids. Highly contrasting behavior was thus induced by H2O f Me2SO transfer, with
a large decrease in acidity of R-nitro activated carbon acids but a large increase in acidity of R-SO2CF3
analogues, leading to remarkable inversions in C-H acidity. These results support the view that in the
case of the triflones the carbanion negative charge resides for the most part at the exocyclic CR carbon,
implying a major role of a polarizability effect. 1H, 13C, and 19F NMR data fully support this proposal. Most
importantly, the intrinsic reactivity (log k0) positioning 9 and 10 on the Marcus scale for carbon acids could
be kinetically measured in 50%H2O-50%Me2SO; for 9, log k0 ) 3.80 and for 10, log k0 ) 4.20. Such high
log k0 values correspond to low intrinsic barriers which can only be reconciled on the basis of minimum
electronic and structural reorganization in formation of the conjugate carbanions. This further emphasizes
polarization as the predominant mechanistic mode of charge stabilization in these species.
Introduction
Recently, we have reported on the ionization equilibria of a
number of R-SO2CF3 activated carbon acids, including aliphatic
Electron-withdrawing groups in molecules are prerequisite
for enabling a variety of transformations in organic chemistry,
including processes proceeding via carbanionic intermediates,
nucleophilic substitutions, elimination reactions, and so forth.1
The nitro group has traditionally been considered as an electron-
withdrawing group per excellence, with a mode of action both
inductive and through resonance.2,3 Yet, in recent years, other
structural moieties have been explored with the possibility of
rivalling, or even exceeding, the electron-withdrawing capability
of NO2.4-6 One avenue of approach, developed since the 1960s
by Yagupol’skii and by Sheppard, was through modification
of the sulfonyl (SO2)R group via electron-withdrawing substit-
uents as in SO2CF3.7-11 In turn, these novel substituents have
found utility in different realms of chemistry.12-16
and benzylic triflones.17,18 Mainly through a combination of
(2) For reviews on the chemistry of nitro compounds, see for example: (a)
Kornblum, N. In The Chemistry of the Amino, Nitroso and Nitro
Compounds, Suppl. F; Patai, S., Ed., Wiley: New York, 1982; pp 361-
393. (b) Nitro Compounds, Recent AdVances in Synthesis and Chemistry;
Feuer, H., Nielsen, A. T., Eds.; Organic Nitro Chemistry Series; VCH:
New York, 1990 and other books in this series. (c) Nielsen, A. T. In
Nitrones, Nitronates and Nitroxides; Breuer, E., Aurich, H. G., Nielsen,
A. T., Eds.; Wiley: New York, 1989. (d) Buncel, E. In The Chemistry of
Amino, Nitro and Nitroso Compounds, Suppl. F; Patai, S., Ed.; Wiley: New
York, 1982; pp 1225-1260. (e) Terrier, F. In Nucleophilic Aromatic
Displacement; Feuer, H., Ed.; VCH: New York, 1991. (f) Buncel, E.; Dust,
J. M.; Terrier, F. Chem. ReV. 1995, 95, 2261.
(3) Bernasconi, C. F. AdV. Phys. Org. Chem. 1992, 27, 119.
(4) Leito, I.; Kaljurand, I.; Koppel, I. A.; Yagupol’skii, L. M.; Vlasov, V. M.
J. Org. Chem. 1998, 63, 7868.
(5) Koppel, A. I.; Taft, R. W.; Anvia, F.; Zhu, S.-Z.; Hu, L.-Q.; Sung, K.-S.;
DesMarteau, D. D.; Yagupol’skii, L. M.; Yagupol’skii, Y. L.; Ignatev, N.
V.; Kondratenko, N. V.; Volkonskii, A. Y.; Vlasov, V. M.; Notario, R.;
Maria, P.-C. J. Am. Chem. Soc. 1994, 116, 3047.
(6) (a) Koppel, A. I.; Koppel, J.; Leito, I. V.; Koppel, I. V.; Mishima, M.;
Yagupol’skii, Lev M. J. Chem. Soc., Perkin Trans. 2 2001, 229. (b)
Yagupol’skii, L. M.; Petrik, V. N.; Kondratenko, N. V.; Soova¨li, L.;
Kaljurand, I.; Leito, I. V.; Koppel, A. I. J. Chem. Soc., Perkin Trans. 2
2002, 1950.
(7) (a) Sheppard, W. A. J. Am. Chem. Soc. 1963, 85, 1314. (b) Sheppard, W.
A.; Taft, R. W. J. Am. Chem. Soc. 1972, 94, 1919.
(8) (a) Yagupol’skii, L. M.; Yagupol’skaya, L. N. Proc. Acad. Sci. USSR (Engl.
Transl.) 1960, 134, 1207. (b) Yagupol’skii, L. M.; Bystrov, V. F.;
Utyanskaya, E. Z. Dokl. Acad. Nauk. USSR 1960, 135, 377.
† Universite´ de Versailles.
‡ Queen’s University.
(1) (a) Carey, F. A.; Sundberg, R. J. In AdVanced Organic Chemistry, 3rd ed.;
Plenum Press: New York, 1990. (b) Smith, M. B.; March, J. In AdVanced
Organic Chemistry, 5th ed.; Wiley: New York, 2001. (c) Richard, J. P. In
The Chemistry of Enols; Rappoport, Z., Ed.; Wiley: New York, 1990. (d)
Streitwieser, A., Jr.; Juaristi, E.; Nebenzahl, L. L. In ComprehensiVe
Carbanion Chemistry; Buncel, E., Durst, T., Eds.; Elsevier: Amsterdam,
1980; p 323. (e) Baxter, N. J.; Rigoreau, L. J. M.; Laws, A. P.; Page, M.
I. J. Am. Chem. Soc. 2000, 122, 3375.
9
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J. AM. CHEM. SOC. 2005, 127, 5563-5571
5563

A R T I C L E S
Terrier et al.
results of thermodynamic investigations with the structural
information provided by NMR studies, the exceptional electron-
withdrawing capability of the SO2CF3 group in carbanion
stabilization was convincingly demonstrated. However, of equal
importance perhaps was the discovery of a dominant solvent
dependence of the carbon acidity, which was in marked contrast
for the SO2CF3 group as compared with the well-recognized
situation for the NO2 group.18a Thus, going from water to Me2-
SO strongly decreases the acidity of R-nitro activated carbon
acids, in accord with the well-established nitronate structure of
the conjugate carbanions.3,14,19,20 In such species, negative charge
is predominantly delocalized onto the oxygens of the NO2 group,
resulting in loss of H-bonding as the H2O content of the medium
is decreased. On the other hand, the same solvent transfer
increases the acidity of R-SO2CF3 activated carbon acids.18a In
the series of benzyltriflones 1-6, it could be shown through
substituent effects in the phenyl ring that the negative charge
in the generated benzylic anions remains largely localized on
the exocyclic carbon center, even in the case of a trinitro
activation of the phenyl ring.18b Because of a predominance of
polarization effects, a situation first recognized in a study of
the ionization of dimethyl sulfone,21 Me2SO is thus rendered
especially favorable in stabilizing charge through dispersion,
thereby increasing the carbon acidity. A striking illustration of
the contrasting response of R-nitro and R-SO2CF3 activated
carbon acids to H2O-Me2SO transfer is the observation of
inversions in relative acidities of these two classes of com-
pounds, for example, nitromethane 7 is 1 order of magnitude
more acidic than trifluoromethanesulfonylmethane 8 in water
but it becomes 500-fold less acidic than 8 in pure Me2SO.18a
Such a clear reversal in the relative acidifying effects of the
NO2 and SO2CF3 groups within a family of structurally similar
carbon acids was unprecedented and revealed further that Me2-
SO is a solvent of choice in taking advantage of the mode of
stabilization of negative charge by the SO2CF3 group and
therefore of its acidifying potential.
Recent efforts have been directed toward development of
novel substituents that would be even more effective than the
SO2CF3 group in charge withdrawal, and these substituents have
been referred to as superacidifiers.4-6 In the present work, we
report on not only a structural (NMR) and thermodynamic study
but also a kinetic study (Marcus intrinsic barrier) of the
ionization of the two benzyltriflones 9 and 10 to give the
conjugate carbanions C-9 and C-10 in pure Me2SO solution
and H2O-Me2SO mixtures of different compositions (eq 1). In
these triflones, the effect of the exocyclic SO2CF3 group is
opposed to the effect of para substitution of the phenyl ring by
a -S(O)(dNSO2CF3)CF3 group or a SO2CF3 group, respec-
tively. As will be seen, our results will first emphasize the much
stronger electron-withdrawing capability of the former fragment,
not only with respect to a SO2CF3 group but also to a NO2
group. Estimates of the Hammett σp and σp- constants for S(O)-
(dNSO2CF3)CF3 could be obtained. Comparison of the data
obtained for 9 and 10 with those previously reported for the
ionization of the para-nitrobenzyltriflone 4 and two related
carbon acids, namely the phenylnitromethanes 11 and 12, will
allow us to delineate the charge-transfer mechanism contributing
to the stabilization of negative charge by the aforementioned
CF3 modified sulfonyl and sulfoximinyl groups. Of major
importance for this discussion has been the successful position-
ing of 9 and 10 on the Marcus intrinsic reactivity scale for
carbon acids.3,20,22 Such a ranking is in itself a significant result
since it has thus far proved to be very difficult to determine
accurately the intrinsic reactivity of R-sulfur substituted carbon
acids.17,23
(9) (a) Kondratenko, N. V.; Popov, V. I.; Radchenko, O. A.; Ignatev, N. V.;
Yagupol’skii L. M. Zh. Org. Khim. 1986, 22, 1716. (b) Yagupol’skii L.
M.; Popov, V. I.; Pavlenko, N. V.; Gavrilov, R. Y.; Orda, V. V. Zh. Org.
Khim. 1986, 22, 2169. (c) Yagupol’skii, L. M.; Ilchenko, A. Y.; Kon-
dratenko, N. B. Usp. Khim. 1974, 43, 64.
(10) Yagupol’skii, L. M. In Aromatic and Heterocyclic Compounds with
Fluorine-Containing Substituents; Naukova Dumka: Kiev, Ukraine, 1988.
(11) (a) Boiko, V. N.; Kirii, N. V.; Yagupol’skii L. M. J. Fluorine Chem. 1994,
67, 119. (b) Yagupol’skii, L. M.; Garlyanskajte, R. Yu; Kondratenko, N.
V. Synthesis 1992, 749. (c) Yagupol’skii, L. M. J. Fluorine Chem. 1987,
36, 1.
(12) (a) Millot, F.; Chatrousse, A. P.; Yagupol’skii, L. M.; Boiko, V. N.;
Shchupak, G. M.; Ignatev, N. V. J. Chem. Res., Synop. 1979, 272. (b)
Yagupol’skii, L. M.; Gogoman, I. V.; Shchupak, G. M.; Boiko, V. N. Zh.
Org. Chem. 1986, 22, 664.
(13) (a) Terrier, F.; Millot, F.; Morel, J. J. Org. Chem. 1976, 41, 3892. (b)
Terrier, F.; Millot, F. NouV. J. Chem. 1980, 4, 255. (c) Terrier, F.;
Chatrousse, A. P.; Kizilian, E.; Ignatev, N. V.; Yagupol’skii, L. M. Bull.
Soc. Chim. Fr. 1989, 627.
(14) (a) Bordwell, F. G.; Vanier, N. R.; Matthews, W. S.; Hendrickson, J. B.;
Skipper, P. L. J. Am. Chem. Soc. 1975, 97, 7160. (b) Hendrickson, J. B.;
Sternbach, D. D.; Bair K. W. Acc. Chem. Res. 1997, 10, 306.
(15) Koppel, I. A.; Burk, P.; Koppel, I. V.; Leito, I. V.; Sonoda, T.; Hishima,
M. J. Am. Chem. Soc. 2000, 122, 5114.
(16) Raabe, G.; Gais, H. J.; Fleischhauer, J. J. Am. Chem. Soc. 1996, 118, 4622.
(17) Terrier, F.; Kizilian, E.; Goumont, R.; Faucher, N.; Wakselman, C. J. Am.
Chem. Soc. 1998, 120, 9496.
(18) (a) Goumont, R.; Magnier, E.; Kizilian, E.; Terrier, F. J. Org. Chem. 2003,
68, 6566. (b) Goumont, R.; Kizilian, E.; Buncel, E.; Terrier, F. Org. Biomol.
Chem. 2003, 1741.
(19) Bordwell, F. G. Acc. Chem. Res. 1988, 21, 456.
(20) (a) Bernasconi, C. F.; Kliner, D. A. V.; Mullin, A. S.; Ni, J. X. J. Org.
Chem. 1988, 53, 3342. (b) Bernasconi, C. F.; Wenzel, P. J. J. Am. Chem.
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9257.
(22) (a) Marcus, R. A. J. Phys. Chem. 1968, 72, 891. (b) Cohen, A. O.; Marcus,
R. A. J. Phys. Chem. 1968, 72, 4249. (c) Guthrie, J. P. J. Am. Chem. Soc.
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9
5564 J. AM. CHEM. SOC. VOL. 127, NO. 15, 2005

SO2CF3 and S(O)(dNSO2CF3)CF3 Substituents
A R T I C L E S
Table 1. Changes in Representative Chemical Shifts (∆δHR, ∆δCR, ∆δC4, ∆δF) and Coupling Constants (∆1JCRHR) upon Ionization of
Substituted Benzyltriflones (1, 4, 9, 10) and Related Phenylnitromethanes (11, 12)a
carbon acid
δ
HR
∆δHR
δ
CR
∆δCR
1JC
∆
1JC
RHR
δC4
∆δC4
δF
(R-SO2CF3)
∆δF
RHR
1b
5.25
3.38
5.53
4.07
5.45
4.37
5.56
4.06
5.71
6.70
5.95
6.84
54.8
55.0
53.7
65.7
53.7
70.4
53.8
65.2
79.3
109.2
77.6
109.8
142.8
163.9
143.2
168.0
129.6
116.9
148.1
131.5
127.5
102.2
130.5
110.1
132.5
123.0
148.0
140.1
-79.1
-80.8
-79.8
-81.3
-72.1
-74.8
-72.0
-75.0
C-1b
4b
-1.87
-1.46
-1.08
-1.50
0.99
0.2
12.0
16.7
11.4
29.9
32.2
21.1
24.8
-12.8
-16.6
-25.3
-20.4
-9.5
-1.7
-1.5
-2.7
-3.0
-
C-4b
9
C-9
10c
143.0
169.0
146.0
175.2
149.1
180.1
C-10c
11d
26.0
29.2
31.0
C-11d
12d
-
-
C-12d
0.89
-7.9
-
a In Me2SO-d6. b Reference 17. c Reference 24. d Reference 27.
Table 2. pKa Values for 9 and 10 and Related Benzyltriflones
(1-4) and Phenylnitromethanes (11, 12) in H2O, Me2SO, and
Various H2O-Me2SO Mixturesa
Results
Structural Studies. Addition of dilute tetramethylammonium
hydroxide to ∼5 × 10-5 M solutions of 9 and 10 in H2O-
Me2SO mixtures containing 30, 50, and 70% Me2SO by volume
resulted in the reversible and complete formation of species
exhibiting intense absorption maxima at the following wave-
lengths: 384 nm, ꢀ ) 30 000 M-1 cm-1 (C-9), and 359 nm, ꢀ
) 42 000 M-1 cm-1 (C-10) in 50% Me2SO. Use of sodium
hydride as the base reagent induced a similar interconversion
in pure Me2SO solutions.
carbon acid
H2O
30% Me2SO
50% Me2SO
70% Me2SO
Me2SO
9
9.70b
11.60
-
8.55
10.65
11.75
12.82
13.82
-
7.60
9.77
7.15
8.67
9.55
11.02
-
6.45
8.85
9.46
10.70
11.95
14.62
8.62
10c
4c
10.57
12.00
13.30
15.10
6.02
3c
-
2c
-
-
5.89
6.77
1c
14.80
-
12d
11e
-
-
7.93
8.53
12.32
(12.20)
That the addition of base to 9 and 10 afforded the carbanions
C-9 and C-10 was unambiguously demonstrated by carrying
out a 1H, 13C, and 19F NMR study of the ionization reactions in
Me2SO. Because of an observable exchange between the two
conformers A and B at probe temperature, the chemical shifts
given in Table 1 refer to spectra recorded at temperatures where
the process of eq 2 was found to be fast on the NMR time scale,
that is, T ) 366 K for 9 and T ) 362 K for 10. Note that a
detailed investigation of the rotational isomerism of eq 2 for X
) SO2CF3 has been made at different temperatures in Me2SO
as well as in acetone and acetonitrile. The results of this dynamic
NMR study have been recently reported.24
a T ) 25 °C; % Me2SO by volume. b 90%H2O-10%Me2SO. c Reference
18b. d Reference 27. e Reference 20.
value of the ratio of the concentration of the ionized to un-
CH
ionized triflone as a function of pH (eq 3). The pKa values
thus obtained together with those previously measured for 10
as well as other carbon acids of eq 1 are given in Table 2.
[C-9]
log
) pH - pKaCH
(3)
[9]
Kinetic Measurements. Rates of equilibration of 9 and 10
with the respective conjugate bases C-9 and C-10 according to
eq 4 were found to be rather high but nevertheless accessible
by stopped-flow spectrophotometry provided that the kinetic
experiments be carried out in buffers made up from primary
amines (B) with pKaBH values close to the pKaCH value. Kinetic
data were obtained at constant ionic strength of 0.5 M (Me4-
NCl) and 25 °C in 50%H2O-50%Me2SO (v/v). Buffers used
were aminoacetonitrile, glycine ethyl ester, glycinamide, and
2-methoxyethylamine for 9, and glycinamide, 2-methoxyethyl-
amine, and butylamine for 10. All experiments were performed
under pseudo-first-order conditions with a large excess of the
buffer reagents over the concentration of 9 or 10 (∼5 × 10-5
M). Depending on the pH studied, equilibrium (4) was ap-
proached from either the reactant side (pH > pKaCH) or the
product side (pH e pKaCH), but in all instances, a sole relaxation
process was associated with the interconversion of the carbon
acid and the carbanion.
pKa Measurements. Using mostly aliphatic and alicyclic
amine buffers (i.e., aminoacetonitrile, glycine ethyl ester,
glycinamide, morpholine, 2-methoxyethylamine, butylamine,
CH
and piperidine), we determined the pKa values of 9 in H2O
and in H2O-Me2SO mixtures containing 10, 30, 50, and 70%
Me2SO as well as in pure Me2SO from observed absorbance
variations at λmax of C-9 obtained at equilibrium as a function
of pH. These variations described regular acid-base equilibra-
tions, as illustrated in Figure S1, which shows that excellent
straight lines with unit slopes were obtained on plotting the log
H
O
-
kp
+ kpB[B] + kpOH[OH ]
2
9 (or 10) y
z C-9 (or C-10) (4)
H
O
k-pH[H+] + k-pBH[BH] + k-p
2
(23) (a) Stefanidis, D.; Bunting, J. W. J. Am. Chem. Soc. 1991, 113, 991. (b)
Stefanidis, D.; Bunting, J. W. J. Am. Chem. Soc. 1990, 112, 3163. (c)
Wodzinki, S.; Bunting, J. W. J. Am. Chem. Soc. 1994, 116, 6910.
(24) Gromova, M.; Be´guin, C. G.; Goumont, R.; Faucher, N.; Tordeux, M.;
Terrier, F. Magn. Reson. Chem. 2000, 38, 655.
BH
k-p
r
B
B
kobsd ) kp [B] + k-pBH[BH] ) k
+
[B] (5)
(
)
p
9
J. AM. CHEM. SOC. VOL. 127, NO. 15, 2005 5565

A R T I C L E S
Terrier et al.
Table 3. Rate Constants for the Ionization of the Benzyltriflones 9 (pKa ) 7.60) and 10 (pKa ) 9.77) in 50%H2O-50%Me2SO (v/v)a
carbon acid
9
10
kpB, M-1 s-
k- BH, M-1 s-
kpB, M-1 s-
k- BH, M-1 s-
BH
1
1
1
1
buffer basic species B
N°
pKa
p
p
aminoacetonitrile
glycine ethyl ester
glycinamide
2-methoxyethylamine
butylamine
1
5.26
7.24
8.01
9.11
9.99
550b
9500
1.2 × 105
2.1 × 104
6830
-
-
2
3
4
5
-
-
1.6 × 104
7.7 × 104
-
4000b
2.3 × 105
5.9 × 104
1.5 × 104
2400b
-
1.6 × 104
3.5 × 104
a I ) 0.5 M NMe4Cl; experimental error in the rate constants in the range 5-10% for 9 and 10, pKaBH values taken from refs 17 and 26. b Calculated from
B
BH
kp or k-p via eq 6.
Figure 2. Effect of buffer concentration and pH on the observed rate
constant, kobsd, for the ionization of 10 in butylamine buffers in 50%H2O-
50%Me2SO (v/v): T ) 25 °C, I ) 0.5 M (NMe4Cl).
Figure 1. Effect of buffer concentration and pH on the observed rate
constant, kobsd, for the ionization of 9 in glycine ethyl ester buffers in
50%H2O-50%Me2SO (v/v): T ) 25 °C, I ) 0.5 M (NMe4Cl).
Analysis of the data pertaining to the interconversion of 9
and C-9 indicated that only the buffer pathways of eq 4 were
important in determining kobsd in the pH range of 5.26-9.11
covered in our measurements. In agreement with the reduced
eq 5, all plots of kobsd versus free amine concentration ([B])
were linear with negligible intercepts. However, a pH depen-
dence of the slopes was observed in buffers with pKaCH - 1 <
pH < pKaCH + 1, namely the glycine ethyl ester and glycinamide
buffers. In these instances, the individual rate constants kpB and
k-pBH (r ) [B]/[BH]) were determined from a standard treatment
of the data obtained at three or more different buffer ratios
(Figure 1).
studied. While the data pertaining to the glycinamide and
2-methoxyethylamine buffers (pH e 9.59) fit eq 5 satisfactorily
(Figures S4, S5), the kobsd versus [B] plots pertaining to the
four butylamine buffers at hand are characterized by non-
negligible and pH-dependent intercepts (Figure 2), suggesting
OH
B
that the kp pathway of eq 4 begins to compete with the kp
BH
and k-p pathways at pH g 9.7 in 50%H2O-50%Me2SO.
From these intercepts, which are subject to large errors, only a
OH
rough estimate of the rate constant kpOH could be obtained: kp
≈ 107 M-1 s-1 25
.
Discussion
B
In other buffers, eq 5 simplified to either kobsd ) kp [B] at
Superacidifiers. S(O)(dNSO2CF3)CF3 versus SO2CF3. In
our quest to investigate novel substituents with extremely strong
electron-withdrawing properties, which we have termed super-
acidifiers,4-6,17 we report on a combined NMR, kinetic, and
equilibrium study of the ionization of carbon acids 9 and 10
which include substitution by dNSO2CF3. The results have
allowed us to evaluate the electron-withdrawing capability of
this latter fragment in aqueous and Me2SO solutions as well as
to gain insights into the mode of electronic action of the overall
S(O)(dNSO2CF3)CF3 moiety.
high pH (2-methoxyethylamine buffers, Figure S2) or kobsd
)
B
k-p [BH] at low pH (aminoacetonitrile buffers, Figure S3),
B
BH
allowing a facile determination of the kp and k-p
rate
constants from the slopes of the kobsd versus [B] or [BH] plots.
BH
B
Then, the corresponding k-p or kp values were calculated
CH
BH
by means of eq 6, where Ka and Ka represent the acidity
constants of the carbon acid (CH) and the amine (BH),
B
BH
respectively. All kp and k-p rate constants for equilibrium
attainment between 9 and C-9 are given in Table 3.
The outstanding electron-withdrawing capability of the para-
S(O)(dNSO2CF3)CF3 substituent becomes strikingly apparent
on examination of the pKa values collected in Table 2. As can
be seen, an enormous pKa change of 8 pK units accompanies
the substitution of 4-H in the unsubstituted benzyltriflone 1 by
the S(O)(dNSO2CF3)CF3 group in pure Me2SO. Also apparent
B
kp
KaCH
KaBH
)
(6)
BH
k-p
In accord with a higher pKa value, the interconversion of 10
and C-10 has been kinetically studied in a more basic pH range
(i.e., 8.01-10.47) than the one employed for 9. Although this
process proceeds with somewhat higher rates than that found
for the equilibrium 9 a C-9, the related kp and k-p rate
constants could be derived with sufficient accuracy from the
kobsd values measured in the three primary amine systems
H2O
OH
(25) From the value of kpOH, the rate constant k-p
can be calculated as kp
Ks/KaCH with Ks being the autoprotolysis constant of the 50:50 (v/v) H2O-
B
BH
H2O
Me2SO mixture (pKs ) 15.83 at 25 °C).26 One thus obtains: k-p
≈ 7
s-1, a value which is actually too low to give rise to meaningful intercepts
in the kobsd versus [B] plots pertaining to the glycinamide and 2-methoxy-
ethylamine buffers.
9
5566 J. AM. CHEM. SOC. VOL. 127, NO. 15, 2005

SO2CF3 and S(O)(dNSO2CF3)CF3 Substituents
A R T I C L E S
nitromethanes 11 and 12, the pKa values of which increase
regularly on going from water to Me2SO.20,27 Striking evidence
of this opposite behavior is that the phenylnitromethane
molecule 11 is more acidic than the triflones 9 and 10 in aqueous
solution but much less acidic in Me2SO.
Figure 3. Effect of H2O-Me2SO transfer on the acidity of benzyltriflones
(1-4, 9, and 10) and related phenylnitromethanes (11, 12). See text for
structural identification.
is that the activation brought about by this substituent surpasses
the effect exerted by a para-SO2CF3 group by 2.4 pK units as
well as that of a para-NO2 group (compound 4) by 3 pK units
in Me2SO solution. Interestingly, the 2.4-pK-unit difference
between 9 and 10 can be regarded as a measure of the gain in
activation incurred by substitution of one of the two oxygens
of a SO2CF3 group by the dN-SO2CF3 fragment. In a recent
study, Koppel et al. measured the effect of substituting an
oxygen of a SO2NH2 group by the dN-SO2CF3 fragment on
the acidity of a series of 4-X substituted arenesulfonamides.6a
In that instance, the acidity enhancement brought about by this
substitution which occurs immediately adjacent to the ionization
site was very large, amounting to 8.3 pKa units in Me2SO
solution. More related to our system is the finding of a 5-pKa-
unit increase in the acidity of the anilino NH2 group on going
from 4-trifluoromethanesulfonylaniline to the 4-S(O)(dNSO2-
CF3)CF3 substituted aniline in the same solvent.6a In this case,
the two activating substituents act through a phenyl ring in a
conjugative manner. Even though the conjugate situation extends
to the carbanions C-9 and C-10 (but not in the parent acids), it
is reasonable to anticipate that the acidifying effect of the 4-X-
substituent will become attenuated because the exocyclic R-SO2-
CF3 group acts in juxtaposition with the para substituent in
determining the acidity.
Interestingly, pertinent information on the mode of electronic
transmission in carbanions C-9 and C-10 can be derived from
further analysis of the trends in pKa values that are revealed in
Table 2.
Medium Effects on Acidity as Evidence of Charge-
Transfer Mechanism. Figure 3 illustrates the effect of medium
composition on pKa values of the R-SO2CF3 (1-4, 9, 10) and
the R-NO2 (11,12) substituted carbon acids.
It is apparent that, for the triflones, the medium change from
highly aqueous to Me2SO-rich is accompanied by a continuous
increase in acidity. This increase amounts to ca. 3.25 pK units
for the sulfoximine 9. A similar trend, noted earlier, is observed
for the para-SO2CF3 and para-NO2 analogues 10 and 4 as well
as for the parent unsubstituted triflone 1.17,18b This is in marked
contrast with the situation that prevails for the two phenyl-
In the case of R-nitro substituted carbon acids such as 11
and 12, it has been recognized that the resonance structure R2
with the charge essentially delocalized on the nitronate oxygen
is by far the main contributor to stabilization of the conjugate
carbanions, including when X ) NO2 (C-11 and C-12).20,27 It
follows that, on changing from water to Me2SO, there ensues a
loss of H-bonding on this nitronate moiety and, hence, a decrease
in the stability of the carbanion structure.28 This explains the
observed decrease in acidity of R-nitro activated carbon acids
in general and of compounds 11 and 12 in the context of Figure
3 in particular.
Interestingly, the increase in acidity that is observed with the
sulfoximine 9 as well as with the other triflones (1-4, 10)
suggests that the primary factor in stabilization of the derived
carbanions is through polarizability effects. In this regard, a
major feature of these compounds is that the ease of ionization
is governed by combination of the electron-withdrawing effects
of the R-SO2CF3 substituent and the para-X substituent (X )
H, CF3, CN, NO2, SO2CF3, S(O)(dNSO2CF3)CF3). In the case
of 10, it is noteworthy that the ∆Hq value measured for the
rotational conversion of eq 2 is much less than the average of
(26) Terrier, F.; Lelie`vre, J.; Chatrousse A. P.; Farrell, P. G. J. Chem. Soc.,
Perkin Trans. 2 1985, 1479.
(27) Moutiers, G.; Thuet, V.; Terrier, F. J. Chem. Soc., Perkin Trans. 2 1997,
1479.
(28) Bernasconi, C. F. Tetrahedron 1985, 41, 3219.
9
J. AM. CHEM. SOC. VOL. 127, NO. 15, 2005 5567

A R T I C L E S
Terrier et al.
those reported for internal rotation in many benzylic carbanions.
This indicates that the π-order of the CAr-CR bond in C-10 is
not very high and that the presence of the para-SO2CF3 group
has a relatively minor effect in inducing transfer of negative
charge from the exocyclic R-SO2CF3 substituted carbanion
center to the phenyl ring.24 Indeed, the experimental evidence
is in accord with predominance of the resonance structure R5
to stabilization of the carbanion C-10, as well as the carbanions
C-1-C-4.18,24 While resonance structures (R8, R9) implying
charge delocalization through the ring contribute to a minor
extent when X is strongly electron-withdrawing, in all cases
those involving charge delocalization through the exocyclic SO2-
CF3 group (R6, R7) play a negligible role.
Figure 4. Brønsted plot for the ionization of 9 by primary amine buffers
in 50%H2O-50%Me2SO (v/v): T ) 25 °C, I ) 0.5 M (NMe4Cl). The
numbering of the various catalysts is given in Table 3.
As further elaborated below, in the case of the sulfoximine
9, the pKa value data are also explicable in terms of the
polarizability phenomena of carbanion stabilization invoked to
account for the behavior of 1-4 and 10. The NMR and kinetic
data discussed below will provide complementary information
on this matter.
above conclusion that both the cyclohexadienyl structures R8
and R9 as well as the structures implying d-p π-bonding (R6)
and negative hyperconjugation (R7) do not play a primary role
in the stabilization of C-9.
At this stage, however, an important point can be addressed,
namely the possibility of getting an estimate of the Hammett
σp and σp- values of the S(O)(dNSO2CF3)CF3 substituent.29
Even though charge delocalization through the 4-X substituted
phenyl ring is a minor factor contributing to the stabilization
of the carbanions C-1,4, C-9, and C-10, the evidence from the
pKa data in Table 2 is that the acidity of the related carbon
acids increases regularly with increasing the electron-withdraw-
ing effect of the X substituent. Plotting the pKa values measured
in a given solvent (e.g., 50%H2O-50%Me2SO), versus the
known σp (or σp-) parameters for H, CF3, CN, NO2, and
Table 1 reveals, however, that there is a clear trend in the
∆δHR values becoming less negative along the R-SO2CF3 series
1 f 4 f 10 f 9 as well as in the corresponding ∆δCR values
which increase progressively in magnitude in this series. These
trends are in agreement with the idea that charge transfer to the
phenyl ring, even though it is not a dominant factor, is increasing
to some extent on increasing the activating effect of the 4-X
substituent. In other words, the contribution of the two cyclo-
hexadienyl structures R8 and/or R9 is not totally negligible when
the 4-X substituent is strongly electron-withdrawing, in agree-
ment with the observation of rotational isomerism in C-9 and
C-10 (vide supra).24
30
SO2CF3 gives rise to reasonable and meaningful linear
correlations, with a better fit to the data when using σp- instead
of σp. This is shown in Figure S6, which refers to the data
obtained in 50%H2O-50%Me2SO. On the basis of these
relationships, the following estimates of the σp and σp- values
for the S(O)(dNSO2CF3)CF3 substituent can be obtained: σp
) 1.35 ( 0.1, σp- ) 2.30 ( 0.1. Interestingly, the σp value is
in accord with a previous estimate derived by Yagupolskii from
a
19F NMR study of 4-X substituted chlorobenzenes.11c As to
the previously unknown σp- value, it highlights nicely the super
electron-withdrawing character of the S(O)(dNSO2CF3)CF3
substituent.
In this regard, it can be noted in Table 1 that there is a greater
shielding of the C4 carbon of the phenyl ring upon ionization
of the 4-S(O)(dNSO2CF3)CF3 and 4-SO2CF3 triflones 9 and
10 than of the 4-NO2 triflone 4; ∆δC4 ) -25.3 ppm for 9;
∆δC4 ) -20.4 ppm for 10; ∆δC4 ) -16.69 ppm for 4. These
data can be understood in terms of a preferred contribution of
the resonance structure R8 in the accommodation of negative
charge by the 4-SO2CF3 and the 4-S(O)(dNSO2CF3)CF3 groups
at the para position of the phenyl ring. This is in accord with
our above conclusions that the preferred mode of electronic
action of these groups is in terms of polarizability effects.
Kinetic Evidence. Marcus Intrinsic Reactivity of 9 and
10. Figure 4 shows that a satisfactory Brønsted plot may be
NMR Evidence for Polarizability Effects. As can be seen
in Table 1, the ionization of 9 is accompanied by a significant
upfield shift of the HR resonance (∆δHR ) -1.08 ppm), and
concomitantly the CR resonance moves moderately to low field
(∆δCR ) 16.75 ppm). This has to be compared with the strong
downfield shifts of the HR and CR resonances which are
commonly found in ionization reactions giving rise to pure sp2
hybridized cyclohexadienyl carbanions (e.g., ∆δHR ≈ 2-2.2
ppm; ∆δCR ≈ 50-60 ppm for carbanions C-13a,b).31 Also,
the ionization of 9 induces only a weak upfield shift of the
fluorine resonance (∆δF ) -2.70 ppm). Altogether, these
results clearly indicate that a high charge density must be
retained on the CR carbon of the carbanion C-9, supporting the
BH
drawn on the basis of the measured rate constants kpB and k-p
pertaining to deprotonation of the 4-S(O)(dNSO2CF3)CF3
substituted benzyltriflone 9 by primary amines in 50%H2O-
50%Me2SO eq 4. Although it is based on the results obtained
with three primary amines, a similar Brønsted plot can be drawn
for the 4-SO2CF3 substituted benzyltriflone 10 (Figure 5). The
corresponding âB values are equal to 0.55 and 0.48 for 9 and
(29) We thank a reviewer for raising the question of the σp (σp-) determinations.
(30) Exner, O. In Correlation in Chemistry; Chapman, N. B., Shorter, J., Eds.;
Plenum Press: New York, 1978.
(31) (a) Moutiers, G.; El Fahid, B.; Goumont, R.; Chatrousse A. P.; Terrier, F.
J. Org. Chem. 1996, 61, 1978. (b) Edlund, U.; Buncel, E. Prog. Phys. Org.
Chem. 1993, 19, 225.
9
5568 J. AM. CHEM. SOC. VOL. 127, NO. 15, 2005

SO2CF3 and S(O)(dNSO2CF3)CF3 Substituents
A R T I C L E S
Table 4. Intrinsic Rate Constants for Deprotonation of Some
Representative Carbon Acid Structures in 50%H2O-50%Me2SOa
carbon acid
log k0
b
RCH(CN)2
∼7
1, 3, 4c
6c
g5
∼4.5
10d
9d
4.2
3.84
9-cyanofluorenee
3.76
3.46
3
2.44
2.05
2.06
0.85
0
5c
18f
1,3-indandioneg
19f
acetylacetoneh
13ai
j
CH3NO2
phenylnitromethane (11)j
-1
-2.15
Figure 5. Brønsted plot for the ionization of 10 by primary amine buffers
in 50%H2O-50%Me2SO (v/v): T ) 25 °C, I ) 0.5 M (NMe4Cl). The
numbering of the various catalysts is given in Table 3. Due to the high
rates of ionization, the log k0 and R and â values are subject to some
uncertainty accounting in particular for R + â > 1.
4,6-dinitro-7-methylbenzofuroxank
a At 25 °C unless indicated otherwise; log k0 refers to ionization by
primary amines. b Reference 3. c Reference 17. d This work. e Reference 31b
at 20 °C. f References 20b,c at 20 °C. g Reference 35a at 20 °C. h Reference
35b at 20 °C. i Reference 30. j Reference 20a at 20 °C. k Reference 36; log
k0 refers to ionization by carboxylate bases.
10, respectively, being in the range of 0.50 ( 0.10 commonly
found for ionization of carbon acids of similar pKaCH values in
that solvent.3,17,20,26,27,31 Using the classical definition of the
formation of C-13a from the picryl ketone 13a (vide supra)
and log k0 ) -2.15 for the formation of C-16 from 4,6-dinitro-
7-methylbenzofuroxan (16).31,36
B
BH
intrinsic rate constant (i.e., k0 ) kp /q when pKaCH - pKa
-
log(p/q) ) 0),3 we readily determined the log k0RNH2 value for
the ionization of 9 and 10 from the intersection of the two lines
in Figures 4 and 5: log k0 ) 3.80 for 9; log k0 ) 4.20 for 10.
Importantly, these values are comparable with the estimates
previously reported for the benzyltriflones 1, 3, 4 (log k0 g 5),
RNH
RNH
5 (log k0
≈ 3.4), and 6 (log k0
≈ 4.5).17
2
2
In the past few years, it has been recognized that there is
commonly an inverse relationship between the intrinsic reactivity
of a carbon acid and the extent of the structural and solvational
reorganization that is required to form the conjugate carb-
anion.3,17,20,32-34 The greater the resonance stabilization and
therefore the sp2-hybridized character of the resulting carbanion,
the greater in general are the structural and solvation changes
involved in the ionization process and the lower the intrinsic
reactivity.
The situation for 9, 10, and related triflones can be ap-
propriately discussed in terms of Table 4, which summarizes
the intrinsic reactivities (log k0 2) measured for a number of
Contrasted with nitro and carbonyl groups, a CN group
derives most of its electron-withdrawing character from a polar
effect.3,18a,27,37-39 Accordingly, the ionization of R-cyano acti-
vated carbon acids proceeds with very little structural reorga-
nization, accounting for the finding of high intrinsic reactivities
for compounds of general structure RCH2CN or RCH(CN)2 (log
k0 ≈ 7).3 Interestingly, the introduction of an additional
R-activating group with even moderate π-acceptor character
provides an appreciable potentiality of resonance stabilization
of the carbanion, as reflected by a marked decrease in log k0
from about 7 to 3.76 for 9-cyanofluorene (17).40 More important
decreases in log k0 occur upon introduction of nitro substituted
phenyl rings with log k0 values of 3 and 2.05 for the ionization
of 4-nitrophenylacetonitrile (18) and 2,4-dinitrophenylaceto-
nitrile (19), respectively.3,20b,c In these instances, the nitro
substituted rings contribute markedly to the resonance stabiliza-
tion of the conjugate carbanion (structures C-18a and C-19a,b),
RNH
carbon acids in 50%H2O-50%Me2SO. As can be seen, R-nitro
and R-carbonyl carbon acids exhibit low intrinsic reactivities,
reflecting the formation of conjugate carbanions which can be
structurally identified to the respective sp2-hybridized nitronate
and enolate structures.1c,3,19,20 This is exemplified by the
formation of the carbanions C-7 (log k0 ) 0) and C-11 (log k0
) -2) of nitromethane (7) and phenylnitromethane (11),
respectively, as well as the formation of the carbanions C-14
(log k0 ) 2.06) and C-15 (log k0 ) 2.44) of acetylacetone (14)
and 1,3-indandione (15), respectively.20a,35 Similarly, low to very
low intrinsic reactivities characterize the ionization of polyni-
trotoluene and related derivatives where an enormous structural
reorganization is required to form the resulting sp2-hybridized
cyclohexadienyl carbanions, for example, log k0 ) 0.85 for the
(32) (a) Bernasconi, C. F.; Bunnell, R. D. J. Am. Chem. Soc. 1988, 110, 2900.
(b) Bernasconi, C. F.; Terrier, F. J. Am. Chem. Soc. 1987, 109, 7115.
(33) Buncel, E.; Dust, J. M. In Carbanion Chemistry; Oxford University Press:
Oxford, 2003; Chapter 2.
(36) Terrier, F.; Croisat, D.; Chatrousse, A. P.; Pouet, M. J.; Halle´ J.-C.; Jacob,
G. J. Org. Chem. 1992, 57, 3684.
(37) Richard, J. P.; Williams, G.; Gao, J. J. Am. Chem. Soc. 1999, 121, 715.
(38) (a) Bradamante, S.; Pagani, G. A. J. Chem. Soc., Perkin Trans. 2 1986,
1035. (b) Abbotto, A.; Bradamante, S.; Pagani, G. A. J. Org. Chem. 1993,
58, 449.
(34) Richard, J. P.; Williams, G.; O’Donoghue, A.-M. C.; Amyes, T. L. J. Am.
Chem. Soc. 2002, 124, 2957
(35) (a) Bernasconi, C. F.; Paschalis, P. J. J. Am. Chem. Soc. 1986, 108, 2969.
(b) Bernasconi, C. F.; Bunnell, R. D. Isr. J. Chem. 1985, 26, 420.
(39) Wiberg, K. B.; Castejon, H. J. Org. Chem. 1995, 60, 6327.
(40) Bernasconi, C. F.; Terrier, F. J. Am. Chem. Soc. 1987, 109, 7115.
9
J. AM. CHEM. SOC. VOL. 127, NO. 15, 2005 5569

A R T I C L E S
Terrier et al.
Scheme 1. Synthesis of N-Trifluoromethylsulfonyl-S-trifluoromethyl-S-4-(trifluomethylsulfonylbenzyl)-sulfoximine 9
Experimental Section
accounting for the finding of intrinsic reactivities that approach
those of R-carbonyl carbon acids.3
Materials. All solvents were distilled prior to use. In particular,
dimethyl sulfoxide was refluxed over calcium hydride and distilled,
collecting the fractions of 32-35 °C (under 2 mmHg), which were
stored under nitrogen. Only freshly prepared solutions were used in
the spectrophotometric studies carried out in pure Me2SO. H2O-Me2-
SO solutions were prepared as described previously.17,18,26 Buffers
were purified commercial products. Chemicals were purchased from
Fluka or Aldrich Company. NMR spectra were recorded in CDCl3 or
Me2SO-d6 solutions on a Bruker AC-300 spectrometer. Reported
coupling constants and chemicals shifts were based on a first-order
1
analysis. Internal reference was tetramethylsilane for H (300 MHz),
central peak of CDCl3 (77 ppm referred to TMS) for 13C (75 MHz)
NMR spectra, internal CFCl3 (0 ppm) for 19F (282 MHz) NMR spectra.
The synthesis of the 4-SO2CF3 substituted benzyltriflone 10 was recently
reported.41
Scheme 1 depicts the strategy used to synthesize the N-trifluoro-
methylsulfonyl-S-trifluoromethyl-S-4-(trifluomethylsulfonylbenzyl)-sulfoximine
9. Following a previous report from our laboratory of a new and very
efficient synthetic route to 4-fluorophenyltrifluoromethyl sulfoxide 20,42
the sulfoximines 21 and 22 were prepared in good yields using the
reagents and experimental conditions described by Yagupol’skii et
al.9a,11c Then, the sulfoximine 9 was obtained in 51% yield through a
two-step process consisting of a nucleophilic aromatic substitution of
the fluorine atom with the carbanion of ethyl trifluoromethanesulfonyl
acetate 2341 with subsequent decarboxylation of the resulting substituted
product 24 in acidic medium. Because of the low stability of the
fluorinated sulfoximine group in basic medium, the substitution step
has to be carried out with a very careful control of the experimental
conditions, as detailed below.
S-Trifluoromethyl-S-p-fluorophenyl-sulfoximine 21. Sodium azide
(3.83 g, 59.0 mmol) was slowly added under argon at 0 °C to a solution
of 4-fluorophenyltrifluoromethyl sulfoxide (5 g, 23.6 mmol) in oleum
27-33% (23.5 mL). Then, the reaction was heated for 1.5 h at 70 °C
under a slight pressure of argon. The crude mixture was added to ice.
After filtration, a white solid of S-trifluoromethyl-S-p-fluorophenyl-
sulfoximine9a (4.56 g, 80%) was obtained without further purification.
mp 48.2 °C, δH(300 MHz, CDCl3) 8.17 (2H, m, HAro), 7.30 (2H, m,
A result of first significance is revealed in Table 4, namely
that the benzyl triflone with the lowest log k0 value, namely
the 2,4-dinitro compound 5 (log k0 ) 3.46), exhibits an intrinsic
reactivity that is not only 30-fold higher than that mesured for
the 2,4-dinitrobenzylcyanide analogue 19 but also 3-fold greater
than that for the mononitro substituted benzylcyanide 18. More
importantly, all other triflones, especially the 4-SO2CF3 and
4-S(O)(dNSO2CF3)CF3 derivatives 9 and 10 and the 2,4,6-
trinitrobenzyltriflone 6, have log k0 values that are located at a
higher level than 9-cyanofluorene 17 in the intrinsic reactivity
scale. Such high log k0 values provide evidence that no major
structural changes occur upon ionization of 9 and 10 and related
substrates. This implies first that d-p π-bonding and negative
hyperconjugation (resonance structure R6 and R7) do not
contribute appreciably to stabilization of the conjugate carban-
ions. Here, this also implies that charge transfer from the
exocyclic R-SO2CF3 substituted carbon to the phenyl ring occurs
at a lower extent in the triflone carbanions than in the
benzylcyanide carbanions, despite the presence of much stronger
activating groups in the ring of the former compounds. Overall,
the situation fully confirms the evidence reached above from
NMR and pKa data that polarizability effects are predominant
in governing the accommodation of negative charge by SO2R
groups, with the best structural picture of the carbanions C-9
and C-10 being in terms of canonical structures of type R5.
HAro), 3.80 (1H, bs, NH); δF(282 MHz, CDCl3) -79.4 (3F, s, SCF3),
-110.9 (1F, s, FAro); δC(77 MHz, CDCl3) 167.1 (CAroF, d, J 258.9),
133.6 (2CAroH, d, J 10.3), 127.3 (CAroS), 125.1 (CF3, q, J 331.3), 116.9
(2CAroH, d, J 22.9); m/z: (CI NH3) 245.
N-Trifluoromethylsulfonyl-S-trifluoromethyl-S-p-fluorophenyl-
sulfoximine 22. A solution of S-trifluoromethyl-S-p-fluorophenyl-
(41) Goumont, R.; Faucher, N.; Moutiers, G.; Tordeux M.; Wakselman, C.
Synthesis 1997, 691.
(42) Wakselman, C.; Tordeux M.; Freslon, C.; Saint-Jalmes, L. Synlett 2001,
550.
9
5570 J. AM. CHEM. SOC. VOL. 127, NO. 15, 2005

SO2CF3 and S(O)(dNSO2CF3)CF3 Substituents
A R T I C L E S
sulfoximine (5 g, 22 mmol) in CH2Cl2 (100 mL) was cooled to 0 °C,
and NaH (1.14 g, 28.6 mmol) was added portionwise under argon. The
reaction was stirred for 2 h at room temperature and cooled again to 0
°C. Triflic anhydride (7.78 mL, 46.2 mmol) was added dropwise, and
the mixture was refluxed for 8 h and added to ice. The aqueous phase
was extracted three times with diethyl ether, and the organic layers
were mixed, washed three times with 5% NaOH and water, dried, and
concentrated. N-Trifluoromethylsulfonyl-S-trifluoromethyl-S-p-fluo-
rophenyl-sulfoximine9a (7.14 g, 90%) was obtained without further
purification. δH(300 MHz, CDCl3) 8.17 (2H, m, HAro), 7.49 (2H, m,
Kinetic and Spectrophotometric Measurements. All aliphatic and
alicyclic amine buffers (see Results) used to study the thermodynamics
and the kinetics of the ionization of 9 and 10 in H2O and H2O-Me2-
SO mixtures as well as pure Me2SO were previously calibrated by
potentiometry or spectrophotometry.23,25,44 In these solvents, the spec-
trophotometric determination of the pKaCH values of 9 and 10 was
facilitated by the fact that the anions C-9 and C-10 exhibit a strong
absorption in the visible region where neither the parent molecules nor
the required buffers absorb UV-visible spectra. Spectra were taken
on a HP 8453 spectrophotometer; λmax values of C-9 and C-10 were
quoted in the Results.
HAro); δF(282 MHz, CDCl3) -75.8 (3F, s, NSO2CF3), -78.9 (3F, s,
SCF3), -94.5 (1F, s, FAro); δC(77 MHz, CDCl3) 168.8 (CAroF, d, J
265.1), 133.9 (2CAroH, d, J 11.9), 124.4(CAroS, d, J 4), 119.9 (CF3, q,
J 327.2), 118.9 (CF3, q, J 320.4), 118.6 (2CAroH, d, J 23.2); m/z: (EI)
290 (100%, M - CF3), 143(39), 95(90), 69(66).
Kinetic measurements of the ionization of 9 and 10 in 50%H2O-
50%Me2SO were carried out at 25 ( 0.2 °C with an Applied
Photophysics SX.18MV stopped-flow spectrophotometer.
Acknowledgment. We are grateful for the financial support
of this research by CNRS (F.T., E.M., C.W.) and the Natural
Sciences and Engineering Reasearch Council of Canada (NSERC)
(E.B.).
N-Trifluoromethylsulfonyl-S-trifluoromethyl-S-4-(trifluomethyl-
sulfonylbenzyl)-sulfoximine 9. Sodium hydride (0.9 g, 22.2 mmol)
was added slowly to a solution of ethyl (trifluoromethanesulfonyl)
acetate41,43 (4.19 g, 22.2 mmol) in DMSO (13 mL). The mixture was
heated for 1 h at 60 °C and cooled to ambient temperature. A solution
of N-trifluoromethylsulfonyl-S-trifluoromethyl-S-p-fluorophenyl-sul-
foximine (4 g, 11.1 mmol) in DMSO (10 mL) was added under argon
to the preformed anion, and the reaction was heated for 15 h at 80 °C.
A saturated solution of NH4Cl (20 mL) was added, and the mixture
was extracted three times with diethyl ether. The organic layers were
washed three times with a solution of NaHCO3 5%, dried, and
evaporated. The resulting compound 24 was heated for 12 h at 100 °C
in a solution of sulfuric acid (12.5 mL), acetic acid (25 mL), and water
(25 mL). Water was added, and the aqueous phase was extracted three
times with diethyl ether. The organic layers were washed three times
with a solution of 5% NaHCO3, dried, evaporated, and purified by
column chromatography on silica using ethyl acetate/pentane 1/9, and
then ethyl acetate/pentane 5/5 as eluent to give the desired compound
9 (2.76 g, 51%) as a white solid. mp 41 °C (Found: C, 24.39; H, 1.37;
N, 2.95. C10H6F9NS3O5 requires C, 24.64; H, 1.24; N, 2.87%). δH(300
MHz, CDCl3) 8.24 (2H, d, HAro, J 8.5), 7.87 (2H, d, HAro), 4.65 (2H,
s, CH2); δF(282 MHz, CDCl3) -75.0 (3F, s, NSO2CF3), -76.7 (3F, s,
SO2CF3), -78.8 (3F, s, SCF3); δC(77 MHz, CDCl3) 134.4 (CAro), 133.4
(CAroH), 131.2 (CAroH), 130.8 (CAro), 119.8 (CF3, q, J 328.9), 119.4
(CF3, q, J 327.8), 118.8 (CF3, q, J 320.4), 55.2 (CH2); m/z: (CI NH3)
505 (M + 18).
Supporting Information Available: Variation of the ratio of
ionized to un-ionized benzyl triflone 9 as a function of pH in
90%H2O-10%Me2SO, 70%H2O-30%Me2SO, and 100%Me2-
SO (v/v) (Figure S1); Effect of pH and buffer concentration on
the observed rate constant, kobsd, for the ionization of 9 in
2-methoxyethylamine buffers in 50%H2O-50%Me2SO (v/v)
(Figure S2); Effect of pH and buffer concentration on the
observed rate constant, kobsd, for the ionization of 9 in ami-
noacetonitrile buffers in 50%H2O-50%Me2SO (v/v) (Figure
S3); Effect of pH and buffer concentration on the observed rate
constant, kobsd, for the ionization of 10 in glycinamide buffers
in 50%H2O-50%Me2SO (v/v) (Figure S4); Effect of pH and
buffer concentration on the observed rate constant, kobsd, for
the ionization of 10 in 2-methoxyethylamine buffers in 50%H2O-
50%Me2SO (v/v) (Figure S5); Plots of the pKa values for the
triflones versus the Hammett σp (top) and σp- (bottom) constants
in 50%H2O-50%Me2SO (Figure S6). This material is available
free of charge via the Internet at http://pubs.acs.org.
JA0436291
(43) (a) Hendrickson, J. B.; Giga, A.; Warcing, J. J. Am. Chem. Soc. 1974, 96,
2275. (b) Euge`ne, F.; Langlois, B.; Laurent, E. J. Fluorine Chem. 1994,
66, 301.
(44) Terrier, F.; Boubaker, T.; Xiao, L.; Farell, J. G. J. Org. Chem. 1992, 57,
3924.
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