The synthesis and acid-catalyzed hydrolysis of N-(4-substitutedphenyl)-O- benzenedisulfonimides

Article abstract of DOI:10.1080/10426507.2011.642431

The acid catalyzed hydrolyses of some cyclic disulfonimides, N-(4-substitutedphenyl)-o-benzenedisulfonimides (1a-d) have been studied in concentrated aqueous acidic solutions. Analysis of the data by the Excess Acidity Method, activation parameters, substituent, and solvent deuterium isotope effect are all indicate hydrolysis by an A-1 mechanism in the studied range. Copyright

Full text of DOI:10.1080/10426507.2011.642431

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Phosphorus, Sulfur, and Silicon and the
Related Elements
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The Synthesis and Acid-Catalyzed
Hydrolysis of N-(4-Substitutedphenyl)-O-
Benzenedisulfonimides
Yunus Bekdemir a , Bilge Eren b & Halil Kütük a
a Department of Chemistry, Faculty of Science and Arts , Ondokuz
Mayıs University , Kurupelit , Samsun , Turkey
b Department of Chemistry, Faculty of Science and Arts , Bilecik
University , Bilecik , Turkey
Accepted author version posted online: 04 Jan 2012.Published
online: 05 Apr 2012.
To cite this article: Yunus Bekdemir , Bilge Eren & Halil Kütük (2012) The Synthesis and Acid-
Catalyzed Hydrolysis of N-(4-Substitutedphenyl)-O-Benzenedisulfonimides, Phosphorus, Sulfur, and
Silicon and the Related Elements, 187:6, 689-696, DOI: 10.1080/10426507.2011.642431
To link to this article: http://dx.doi.org/10.1080/10426507.2011.642431
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Phosphorus, Sulfur, and Silicon, 187:689–696, 2012
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.642431
THE SYNTHESIS AND ACID-CATALYZED HYDROLYSIS
OF N-(4-SUBSTITUTEDPHENYL)-O-
BENZENEDISULFONIMIDES
Yunus Bekdemir,1 Bilge Eren,2 and Halil Ku¨tu¨k1
1Department of Chemistry, Faculty of Science and Arts, Ondokuz Mayıs University,
Kurupelit, Samsun, Turkey
2Department of Chemistry, Faculty of Science and Arts, Bilecik University,
Bilecik, Turkey
GRAPHICAL ABSTRACT
Abstract The acid catalyzed hydrolyses of some cyclic disulfonimides, N-(4-
substitutedphenyl)-o-benzenedisulfonimides (1a–d) have been studied in concentrated
aqueous acidic solutions. Analysis of the data by the Excess Acidity Method, activation
parameters, substituent, and solvent deuterium isotope effect are all indicate hydrolysis by an
A-1 mechanism in the studied range.
Keywords Disulfonimides; acid-catalysis; excess acidity; hydrolysis; mechanism
INTRODUCTION
Compounds containing sulfonamide groups ( SO2NH ) have long been known as
a result of their biological importance and chemical applications. They occupy a unique
position in the drug industry with their antibacterial,1 antitumor,2 hypoglycemic,3 and
carbonic anhydrases enzyme (CA) inhibitory properties.4 Disulfonimides are sulfonamide
Received 20 August 2011; accepted 12 November 2011.
Address correspondence to Bilge Eren, Department of Chemistry, Faculty of Science and Arts, Bilecik
University, Bilecik, Turkey. E-mail: bilge.eren@bilecik.edu.tr
689

690
Y. BEKDEMIR ET AL.
derivatives that contain two sulfone group connected to the nitrogen atom. They are also
used in medicine for their antitumor effects and CA inhibitory properties.5 Their complexes
with transition metals are very common.6 The complexes obtained from chiral derivatives
of them used in asymmetric synthesis as catalysts.7
The derivatives of o-benzenedisulfonimide 2 are especially attractive as synthetic
tools, since the two sulfonyl groups flanking nitrogen provide anionic charge stabilization
so that the imide anion should be a good leaving group. Several N-substituted derivatives
of it was used as an active source of electrophile in many substitution8–10 and oxidation11
reactions efficiently.
O2
S
O2
S
NH
N
R
S
S
O2
O2
2
1 a; R= OCH3
b; R= CH3
c; R= H
d; R= Cl
Scheme 1
The acid catalyzed hydrolyses of sulfonamides12 and sultams13 (the corresponding
cyclic sulfonamides) has been studied in some detail. Despite their obvious importance,
there has been no systematic study of the acid-catalyzed hydrolysis of disulfonimides.
We now report a detailed study of the acid-catalyzed hydrolysis of a series of N-(4-
substitutedphenyl)-o-benzenedisulfonimides 1a–d (Scheme 1) in concentrated aqueous
acidic solutions.
RESULTS AND DISCUSSION
Profiles for the acid catalyzed hydrolysis of 1a–d in sulfuric acid solutions at 60.0
0.1 ◦C are shown in Fig. 1. In all cases, the rates of hydrolysis increased continuously with
increasing acid concentration in the studied range (13.00–16.00 M). There is no indication
of a rate maximum even at quite high acidity. The hydrolysis reaction was very slow and
cannot be followed by an ultraviolet (UV) spectrometer in lower acidic solutions. So, it was
impossible to obtain reproducible results. Because of this, no kinetic data were obtained
for HCl and HClO4.
The kinetic data in Table 1 were also analyzed by the Excess Acidity treatment of
Cox and Yates.14–16 The appropriate kinetic equation for mainly unprotonated substrates
Eq. (1) was used;
=
∗
+
+
+
log k1 − log CH − log CS/(CS + CSH ) = m m X + log aNu¨ + log(k0/kSH
)
(1)
Owing the extremely low basicity of the cyclic disulfonimides studied, the protonation
correction term, [logCS/(CS + CSH+)] can be neglected. In the equation, k1 is the pseudo
first order rate constant in aqueous acid concentration CH+ and of excess acidity X.

THE SYNTHESIS AND ACID-CATALYZED HYDROLYSIS
691
8.00
6.00
4.00
2.00
0.00
MeO
Me
H
Cl
13.0
14.0
15.0
16.0
[H2SO4]/M
Figure 1 Plots of k1 for acid-catalyzed hydrolysis of N-(4-substitutedphenyl)-o-benzenedisulfonimides 1a–d in
sulfuric acid solutions at 60.0 0.1◦C.
Plots of logk1 – logCH+ versus X are shown in Fig. 2 for the hydrolyses of 1a–d in
sulfuric acid solutions. The resulting straight lines with high correlations (r2: 0.989–0.997)
for all compounds are typical of an A-1 mechanism in the studied range of acid, which
means there is no involvement of nucleophile in the transition state. Similar behavior has
been observed for the hydrolyses of some sulfamates17 and a number of sulfonimidic esters
at higher acidity region.18
The values of the rate constants for the hydrolysis of all compounds (1a–d) at different
temperatures were also obtained as shown in Table 2. The temperature dependence of the
Table 1 Values of 103 k1 (s−1) for the hydrolysis of 1a–d in sulfuric acid solutions at 60.0 0.1 ◦C
103 k1 (s−1
)
H2SO4 (M)
1a
1b
1c
1d
13.00
13.50
14.00
14.50
15.00
15.50
16.00
1.24
1.52
2.22
3.22
4.23
5.68
7.25
0.97
1.38
2.12
3.11
3.96
5.37
6.65
0.88
1.20
1.98
2.82
3.65
4.55
5.75
0.72
1.10
1.85
2.41
3.25
4.23
5.32

692
Y. BEKDEMIR ET AL.
3.20
3.40
3.60
3.80
4.00
4.20
4.40
MeO
Me
H
Cl
5.30
5.80
6.30
6.80
7.30
7.80
X
Figure 2 Plot of logk1 – logCH+ vs. excess acidity for the acid catalyzed hydrolysis of 1a–d in sulfuric acid
solutions at 60.0 0.1◦C.
rate constants of the hydrolysis reaction was analyzed by a least-square procedure and
calculated activation enthalpy and entropy values are shown in Table 3. The hydrolysis
of all compounds have ꢀS= of small negative or positive values. It is consistent with an
A-1 mechanism that substrat molecule has more rotational and translational freedom in the
transition state, where a water molecule does not involved. The acid-catalyzed hydrolysis−o1f
esters and amides19 proceeding by an A-1 mechanism have ꢀS= ≈ 0 to −41.8 JK−1mol
while those proceeding by an A-2 mechanism have ꢀS= ≈ −62.8 to −125.5 JK−1mol−1
,
.
Over the range 14.00–16.00 molar sulfuric acid, the values of ꢀS= for the hydrolysis
Table 2 Values of 103 k1 (s−1) for the hydrolysis of the 1a–d at different temperatures
H2SO4 (M)
14.00
Compound
55.0◦C
60.0◦C
65.0◦C
70.0◦C
1a
1b
1c
1d
1a
1b
1c
1d
1.35
1.33
1.19
1.26
3.68
3.65
3.42
3.21
2.22
2.12
1.98
1.85
7.25
6.65
5.75
5.32
3.56
3.40
2.85
5.61
5.51
5.21
3.48
5.32
16.00
11.20
10.40
9.58
18.50
16.50
15.20
13.90
8.87

THE SYNTHESIS AND ACID-CATALYZED HYDROLYSIS
693
Table 3 Arrhenius parameters for the hydrolysis of 1a–d
Compound
H2SO4 (M)
ꢀS= (JK−1mol−1
)
ꢀH= (kJmol−1
)
r2
1a
1b
1c
1d
14.00
16.00
14.00
16.00
14.00
16.00
14.00
16.00
−12.86
+9.58
94.59
98.89
88.55
93.18
93.16
93.36
90.56
91.83
0.997
0.999
0.999
0.996
0.994
0.999
0.998
0.999
−30.89
−8.03
−17.77
−8.25
−25.55
−13.48
of 1a–d become increasingly less negative with increase of acidity suggests that the A-1
mechanism becomes more dominant at higher acidities (Table 3).
The kinetic solvent isotope effect (k1D2O/k1H2O) observed for the hydrolysis of 1c
is shown in Table 4. The values obtained in 13.50 and 16.00 molar sulfuric acid solutions
are 1.80 and 2.08 respectively that is also consistent with an A-1 mechanism. Generally,
for an A-2 mechanism, values of k1D2O/k1H2O lie closer to unity, on the other hand it is
expected to be around 2–4 for an A-1 mechanism.20,21
In the studied acidity range, electron-donating substituents produce the highest rate
of hydrolysis (i.e., 1a > 1d), and the substituent effects are well correlated by a satisfactory
Hammett ρσ plot [at 14.00 M H2SO4, ρ = −0.157 (corr. 0.991) and at 16.00 M H2SO4, ρ =
−0.281 (corr. 0.961)], i.e., as shown in Fig. 3 for 14.00 M H2SO4. Clearly, at these acidities,
electron-donating substituents facilitate both protonation of the substrate and stabilize the
sulfur cation in the A-1 mechanism.
There is no direct evidence concerning the site of the protonation of o-
benzenedisulfonimides, however, the protonation of sultams13 and sulfinamides22
occur preferentially at the nitrogen atom.
As a result of all these observations, we propose that the acid catalyzed hydrolysis
of N-(4-substitutedphenyl)-o-benzenedisulfonimides occur by an A-1 mechanism in the
studied range, as shown in Scheme 2. A rapid protonation on nitrogen atom is followed by
S–N bond cleavage in the rate determining step.
O2
S
O2
S
N+
R
+
H3O+
H2O
N
R +
H
S
S
O2
O2
Slow
SO3H
SO2
H
H2O
Fast
H+
+
S
NH
R
S
N
R
O2
O2
Scheme 2

694
Y. BEKDEMIR ET AL.
Table 4 Deuterium solvent isotope effect for the hydrolysis of N-fenil-o-benzendisulfonimit 1c in sulfuric acid
solutions at 60 0.1◦C
Acid (M)
103 k1 (s−1
)
kD O/kH O
2 2
H2SO4 (13.50)
D2SO4 (13.50)
H2SO4 (16.00)
D2SO4 (16.00)
1.20
2.16
5.75
1.80
2.08
12.00
EXPERIMENTAL
Material
N-(4-Substitutedphenyl)-o-benzenedisulfonimides 1a–d were prepared as described
by Sorbye et al.8 by making minor changes. The modified process: o-Benzenedisulfonyl
chloride was dissolved in benzene and stirred under reflux. The solution of corresponding
p-substituted aniline (1 eq.) and triethylamine (1 eq.) in benzene was added stepwise into
the stirring solution. The reaction was allowed to reflux for 5 h. The heterogenous mixture
obtained was cooled and filtered to remove triethylamine hydrochloride. The liquid phase
was placed in a flask again. While stirring the system, potassium tert-butoxide (1.5 eq.) and
catalytic amounts of 18-crown-6 were added in portions, respectively. Then, the reaction
was allowed to reflux for additional 20 h. The reaction mixture was cooled, filtered, and the
0.06
MeO
0.04
Me
0.02
0.00
0.02
0.04
0
−0.3
−0.2
−0.1
0
0.1
0.2
0.3
-
-
Cl
σ
Figure 3 The plot of log k1 vs. Hammett σ values for the acid-catalyzed hydrolyses (14.00 M H2SO4) of
N-(4-substitutedphenyl)-o-benzenedisulfonimides (1a–d) at 60.0 0.1◦C.

THE SYNTHESIS AND ACID-CATALYZED HYDROLYSIS
695
solvent was stripped of under vacuum up to half volume and was left to crystallization in the
same solvent. By repeating the benzene recyrstallization, pure cyristalline products 1a–d
was obtained with 34–40% yield. Elemental analyses were performed by Test Analyses
˙
Laboratory (ATAL) of TUBITAK in Ankara, Turkey. Disulfonimide 1a had m.p. 185–186
◦C; 1H NMR (CDCl3), δ 8.15–7.90 (m, 4H), 7.57 (d, 2H), 7.07 (d, 2H), 3.80 (s, 3H); found
C, 48.65; H, 3.80; N, 4.27; S, 19.63; calc. for C13H11NS2O5 C, 47.98; H, 3.41; N, 4.31;
◦
S, 19.71%; 1b had m.p. 216–218 C; 1H NMR (CDCl3), δ 8.20–7.83 (m, 4H), 7.67–7.36
(m, 4H), 2.45 (s, 3H); found C, 51.65; H, 3.85; N, 4.55; S, 20.28; calc. For C13H11NS2O4
C, 50.46; H, 3.59; N, 4.53; S, 20.73%; 1c had m.p. 193–195 ◦C (lit.23 195 ◦C); 1H NMR
◦
1
(CDCl3), δ 7.61–7.80 (m, 5H), 7.96–8.20 (m, 4H); 1d had m.p. 242–245 C; H NMR
(CDCl3), δ 8.21–7.90 (m, 4H), 7.67–7.48 (m, 4H); found C, 44.32; H, 2.39; N,4.20; S,
19.83; calc. for C12H8NS2O4Cl C, 43.70; H, 2.45; N, 4.25; S, 19.45%.
Kinetic Procedure
The rates of hydrolysis of the disulfonimides were followed at 215 nm with using a
GBC Cintra 20 model UV–VIS spectrophotometer fitted with a thermostated cell holder
( 0.05 ◦C). Good first-order behavior was observed with clean isobestic points. Values of
the first order rate coefficients k1 were calculated from the standard equation using a least-
squares procedure. All kinetic measurements were duplicated and the average deviation
from the mean was <5%.
Product Analysis
The product of the hydrolysis was determined by comparing the UV spectrum ob-
tained at the completion of the kinetic experiment with the spectrum of the expected product
that was run at the same concentration and under the same conditions. The UV spectra of
the hydrolysis of N-phenyl-o-benzenedisulfonimide (1c) were shown to be identical to
that of corresponding 2-(phenylsulfamoyl)benzenesulfonic acid, m.p. 91–95 ◦C (dec). This
compound was prepared by treating water with the product, which was obtained from the
reaction of o-benzenedisulfonyl chloride and aniline in benzene. Its structure was confirmed
by IR and 1H-NMR techniques.
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