On the reaction products of 4-substituted 3-pyridinesulfonamides with some benzenesulfonyl chloride derivatives

Article abstract of DOI:10.1002/jhet.1013

The reactions of 4-substituted 3-pyridinesulfonamides 1a, 1b, 1c, 1d, 1e with benzenesulfonyl chlorides 2a, 2b, 2c, 2d, 2e, 2f in acetonitrile were investigated. Depending on the structure of arylsulfonyl chlorides and the reaction conditions the followin

Full text of DOI:10.1002/jhet.1013

January 2014 On the Reaction Products of 4‐Substituted 3‐Pyridinesulfonamides with
11
Some Benzenesulfonyl Chloride Derivatives
a
a
a
*
Zdzisław Brzozowski, Jarosław Sławiński, and Krzysztof Szafrański
Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80‐416 Gdańsk, Poland
*
E-mail: jaroslaw@gumed.edu.pl
Received March 12, 2011
DOI 10.1002/jhet.1013
Published online 7 October 2013 in Wiley Online Library (wileyonlinelibrary.com).
The reactions of 4‐substituted 3‐pyridinesulfonamides 1a–e with benzenesulfonyl chlorides 2a–f in
acetonitrile were investigated. Depending on the structure of arylsulfonyl chlorides and the reaction condi-
tions the following four types of products were obtained in good yields: 3‐sulfamoyl‐4‐R‐1‐arylpyridinium
chlorides 3–8; 1,10‐bis(3‐nitrobenzenesulfonylimino)deca‐2,4,6,8‐tetraene‐2,9‐disulfonamides 9–12; 1‐substituted
1,4‐dihydro‐4‐oxo‐3‐pyridinesulfonamides 13–14; and 4‐methoxy‐3‐[N‐(2,5‐dichlorophenyl)sulfonyl] sulfonamidates
15 and 16. The mechanisms of these reactions were discussed.
J. Heterocyclic Chem., 51, 11 (2014).
INTRODUCTION
MZA, EZA, DCP, and IND (KIs = 24–50 nM). In this
work, a possibility of using reactions of 4‐substituted
3‐pyridinesulfonamides with arylsulfonyl chlorides for
the synthesis of novel sulfonamides with expected activity
as potential carbonic anhydrase inhibitors has been
surveyed. It was expected that these reactions may provide
either 1‐(arylsulfonyl)pyridinium chlorides of type III and/
or typical N‐(arylsulfonyl)pyridine‐3‐sulfonamide deriva-
tives of type IV (Fig. 1).
The aryl/heteroaryl sulfonamide constitutes an important
class of compounds with several types of biological activ-
ities and well‐established safety profiles [1]. Currently,
there is significant interest in the discovery and develop-
ment of novel sulfonamides for the treatment of cancer
and HIV infection [2–5]. As part of extensive research
program on the synthesis of compound containing
2‐thiobenzenesulfonamide scaffold, several series of novel
sulfonamides with remarkable anticancer activity [6–20],
anti‐HIV activity [14], [20–29], or carbonic anhydrase
inhibitors [30–32] were discovered in our laboratories. In
the course of study on the synthesis of heterocyclic
compounds bearing sulfonamide moiety, we developed
new methods for preparation of novel series of
3‐pyridinesulfonamides [33–36] and found that numerous
sulfonamides of type I [35] and II [36] (Fig. 1) showed
excellent inhibitory efficacy against carbonic anhydrase
isozyme hCA IX (cancer‐associated) with inhibition
constants of 4.6–12.0 nM, being much more effective in
comparison to the clinically used sulfonamides AAZ,
RESULTS AND DISCUSSION
First, we found that the reaction of 3‐pyridinesulfonamide
1a with one molar equivalent of 2,5‐dichlorobenzenesylfonyl
chloride 2a carried out in boiling acetonitrile (6–12 h) led to
the formation of a mixture of brown pithy products. However,
treatment of 1a with 2a in acetonitrile initially at room
temperature for 32 h, and further heating at reflux for 40 h,
led to 4‐chloro‐3‐sulfamoyl‐1‐(2,5‐dichlorophenyl)pyridinium
chloride 3 in 85% yield (Scheme 1). An analogous reaction
of 3‐pyridinesulfonamides 1a or 1b with benzenesulfonyl
© 2013 HeteroCorporation

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Z. Brzozowski, J. Sławiński, and K. Szafrański
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substituents effect) leading to the pyridones 13 and 14 is
outlined in Scheme 3. Similar to the reaction sequence
presented in Scheme 1 (for 1b with benzenesulfonyl
chloride 2a–d), the initial formation of intermediate F
was stabilized in the two main routes. In the route A,
via two‐step addition–elimination process led to the
intermediate G and unstable 6‐chloro‐4‐methoxy‐1‐
(2,4‐dinitrophenyl)‐3‐pyridinesulfonamide H, which by
elimination of 1‐chloro‐2,4‐dinitrobenzene I gave starting sul-
fonamide J. Then, the reaction of intermediates I with J gave
the 1‐(2,4‐dinitrophenyl)‐4‐methoxy‐3‐sulfamoylpyridinium
chloride intermediate K, which undergoes a SN2 substitution
on the methyl by chloride to form 1,4‐dihydro‐1‐(2,4‐
dinitrophenyl)‐4‐oxo‐3‐pyridinesulfonamide 13 as final
product.
In the route B however, the intermediate F by migration pro-
cess of CH3 group to nitrogen atom of pyridine ring led to the
1,4‐dihydro‐1‐methyl‐4‐oxo‐1‐(2,4‐dinitrophenylsulfonyl)‐3‐
pyridinium chloride, intermediate L, which by elimination of
starting 2,4‐dinitrobenzenesulfonyl chloride 2f gave 1,4‐
dihydro‐1‐methyl‐4‐oxo‐3‐pyridinesulfonamide 14 as a sec-
ond final product.
Figure 1. General structures of effective hCA IX inhibitors I, II, and
structures of novel pyridine‐3‐sulfonamide derivatives III and IV.
chlorides 2a–d (bearing substituents in the benzene ring with a
relatively weak electron‐withdrawing effect) afforded the
corresponding 3‐sulfamoyl‐4‐R‐1‐arylpyridinium chlorides
4–8 in 50–90% yields (Scheme 1).
The reaction sequence involved the initial formation of
1‐arylsulfonylpyridinium chloride A (Scheme 1), followed
by elimination of SO2 process which gave rise to the
formation of final products 3–8. On the other hand, an
analogous reaction of 3‐pyridinesulfonamides 1b–e with
benzenesulfonyl chloride 2e (having an strong elec-
tron‐withdrawing NO2 group in the benzene ring)
furnished 1,10‐bis‐(3‐nitrobenzenesulfonylimino)‐deca‐
2,4,6,8‐tetraene‐2,9‐disulfonamides 9–12, which have
been isolated in 69–83% yields. We propose a reaction
sequence for these transformations as shown in Scheme
2. The initial step is believed to be the formation of
1‐(3‐nitrobenzenesulfonyl) pyridinium chloride interme-
diate B, and then 6‐chloro‐1‐(3‐nitrobenzenesulfonyl)‐3‐
pyridinesulfonamide intermediate C which undergoes
ring opening with the formation of intermediate D. In the
final stage of the reaction, the non‐isolable intermediate
D was, under these reaction conditions, converted into a
free radical E, which was stabilized by dimerization to
give the corresponding disulfonamide derivatives 9–12.
The proposed mechanism of the reaction of 4‐methoxy‐3‐
pyridinesulfonamide (1b) with 2,4‐dinitrobenzenesulfonyl
chloride (2f) (with a relatively stronger electron‐withdrawing
However, an analogous reaction of 4‐methoxy‐3‐
pyridinesulfonamide 1b with 2,5‐dichlorobenzenesulfonyl chlo-
ride 2a carried out in the presence of 4‐dimethylaminopyridine
(DMAP) led to the formation of expected 1H+‐pyridinium‐4‐
methoxy‐3‐[N‐(2,5‐dichlorophenyl)sulfonyl]sulfonamidate 16
and its dimethylaminopyridinium salt 15 in 94 and 91% yields,
respectively. According to the mechanism proposed (Scheme
4), the initial step is believed to be the formation of a mixture
of intermediates M and N, followed by nucleophilic attack
of sulfonamidate anion of M at the sulfonyl group of N led
to the pyridinesulfonamide salt 15. Then, upon acidification
of the salt 15 with hydrochloric acid, the corresponding free
sulfonamide intermediate O was produced, and finally
tautomerized to a stable betaine of type 16.
1
The H‐NMR spectra of the 1‐arylpyridinium chlorides
3–8 and betaine 16 revealed the characteristic three signals
of pyridine protons, two doublet signals with coupling
Scheme 1. Synthesis of 3-sulfamoyl-4-R-1-arylpyridinium chlorides 3-8 in the reaction of 3-pyridinesulfonamide 1a and 1b with some arylsulfonyl
chlorides 2a-d.
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On the Reaction Products of 4‐Substituted 3‐Pyridinesulfonamides with Some
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Scheme 2. Synthesis and plausible mechanism of the formation of 1,10-bis(3-nitrobenzenesulfonylimino)deca-2,4,6,8-tetraene-2,9-disulfonamides 9-12
in the reaction of 3-pyridinesulfonamides 1b-d with 3-nitrobenzenesulfonyl chloride 2e.
constants J = 5.2–7.8 Hz of H‐5 and H‐6 protons in the re-
gions δ 7.76–7.84 and 8.74–8.93 ppm, respectively, and
sharp singlet of H‐2 at downfield region of δ 8.29–9.04
ppm. Moreover, the sulfonamide NH2 protons (3–8) are
found as a singlet signal at δ 7.41–7.93 ppm that integrated
for two protons. As could be expected, the resonance signals
of H‐5 and H‐6 protons of pyridone ring in 13 and 14 are
shifted upfield to the region δ 6.35–6.52 and 7.76–8.04
ppm, respectively. The same upfield shift concerns the signal
of H‐2 proton (δ 8.29–8.52 ppm). Is worth emphasizing that
signals of pyridine protons in dimethylaminopyridinium salt
15 are found in the different region as compared in 1‐
arylpyridinium chlorides 3–8 or betaine 16, for instance,
doublet signal of H‐5 proton (J = 5.8 Hz) at δ = 6.90 ppm,
and doublet of H‐6 (J = 5.8 Hz) at δ = 8.40 ppm, in the ab-
sence of the sulfonamide NH proton signal.
chloride 2a–e in acetonitrile, depending on the nature of
electron‐withdrawing substituent X at benzene ring led to
the formation of three types of novel sulfonamides:
3–8 (X = 4‐Cl; 4‐Br; 2,5‐diCl or 2,4diCl‐5‐Me); 9–12 (X =
3‐NO2) and 13–14 (X = 2,4‐diNO2). An analogous reaction
of 4‐methoxy‐3‐pyridinesulfonamide (1b) with 2,5‐
dichlorobenzenesulfonyl chloride (2c) carried out in the
presence of DMAP afforded the expected 1H+‐pyridinium‐
4‐methoxy‐3‐[N‐(2,5‐dichlorophenyl)sulfonyl]sulfonamidate
(16) and its dimethylaminopyridinium salt 15.
Further structural modifications and biological evolution
of these compounds are in progress and will be described
elsewhere.
EXPERIMENTAL
The following instruments and parameters were used: melting
1
The H‐NMR spectra of compounds 9–12 showed two
points Buchi 535 apparatus; IR spectra: KBr pellets, 400–4000
1
cm−1 Perkin Elmer 1600 FTIR spectrometer; H and 13C‐NMR:
doublet signals corresponding to magnetically equivalent
pairs H‐5 and H‐6 (J = 6.2–6.6 Hz) δ 7.09–7.71 ppm, as
well as H‐4 and H‐7 protons (J = 6.2–6.6 Hz) δ 8.76–
8.99 ppm, and singlet signal of magnetically equivalent
pairs H‐1 and H‐10 in the region δ = 8.95–9.06 ppm, that
integrated for two protons, whereas singlet signal of sul-
fonamide NH2 protons was observed at δ = 7.30–7.80.
Furthermore, the 13C‐NMR and IR spectroscopic data
are in accordance with the proposed structures which were
confirmed also by elemental analyses (C, H, N) (see Exper-
imental section).
Varian Gemini 200 apparatus at 200 and 50 MHz, respectively;
chemical shifts are expressed at δ values relative to Me4Si as stan-
dard. Thin‐layer chromatography was performed on Merck TLC
Silica gel 60 F254 plates using benzene/ethanol (4:1) or chloro-
form/hexane/acetone (1:1:1) as mobile phases, and visualized
with UV light or with iodine vapour. The starting 4‐substituted
3‐pyridinesulfonamide 1a–e were prepared according to the
method described previously [[35]].
Procedure for the preparation of 3‐sulfamoyl‐4‐R‐1‐
arylpyridinium chlorides (3–8).
A
mixture of the
corresponding 3‐pyridinesulfonamides 1a or 1b (0.01 mol) and
the appropriate arylsulfonyl chloride 2a–d (0.0106 mol) in dry
acetonitrile (35 mL) was stirred at room temperature for 32 h,
followed at reflux for 40 h. After cooling to room temperature
and standing overnight, the precipitate of the adequate 1‐aryl‐
6‐chloro‐1,6‐dihydro‐3‐pyridinesulfonamide was filtered off,
washed with acetonitrile, and dried.
CONCLUSION
We have demonstrated that the reactions of 4‐substituted
3‐pyridinesulfonamides 1a–e with X‐benzenesulfonyl
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Scheme 3. Synthesis and plausible mechanism of the formation of 1,4-dihydro-4-oxo-3-pyridinesulfonamides 13 and 14 in the reaction of 4-methoxy-3-
pyridinesulfonamide 1b with 2,4-dinitrobenzenesulfonyl chloride.
4‐Chloro‐3‐sulfamoyl‐1‐(2,5‐dichlorophenyl)pyridinium chloride
(3). Starting from 4‐chloro‐3‐pyridinesulfonamide 1a (1.93 g) and
2,5‐dichlorobenzenesulfonyl chloride 2a (2.6 g), the title compound
3 was obtained (3.2 g, 85%): m.p. 197–198°C; IR (KBr) 3320,
3200, 3105 (SO2NH2), 1365, 1175 (SO2) cm−1; 1H‐NMR (dimethyl
sulfoxide‐d6) δ 7.40 (d, J = 2.2 Hz, 1H, H‐6, 2,5‐diClPh), 7.80 (d, J
= 5.3 Hz, 1H, H‐5, pyrid.), 7.90–8.10 (m, 2H, H‐3 and H‐4, 2,5‐
diClPh), 8.74 (d, J = 5.3 Hz, 1H, H‐6, pyrid.), 9.04 (s, 1H, H‐2,
pyrid.), 9.96 (br.s, 2H, SO2NH2) ppm; 13C‐NMR (dimethyl
sulfoxide‐d6) δ 126.68, 128.76, 130.05, 131,00, 132.47, 137.50,
141.47, 142.96, 146.90, 148.72, 153.65 ppm. Analysis calculated for
C11H8Cl4N2O2S (374.06): C, 35.32; H, 2.15; N, 7.49. Found: C,
35.30; H, 2.19; N, 7.55.
4‐Chloro‐3‐sulfamoyl‐1‐(2,5‐dichloro‐5‐methylphenyl)pyridinium
chloride (4). Starting from 4‐chloro‐3‐pyridinesulfonamide 1a (1.93
g) and 2,4‐dichloro‐5‐methylbenzenesulfonyl chloride 2b (2.75 g), the
title compound 4 was obtained (3.5 g, 90%): m.p. 204–206°C; IR
(KBr) 3330, 3190 (SO2NH2), 1365, 1175 (SO2) cm−1; 1H‐NMR
(dimethyl sulfoxide‐d6) δ 2.29 (s, 3H, CH3), 7.46 (s, 1H, H‐6, Ph),
7.80 (d, J = 5.2 Hz, 1H, H‐5, pyrid.), 7.93 (br.s, 3H, SO2NH2 and H‐
3, Ph), 8.74 (d, J = 5.2 Hz, 1H, H‐6, pyrid.), 9.03 (s, 1H, H‐2, pyrid.)
ppm; 13C‐NMR (dimethyl sulfoxide‐d6) δ 19.23, 126.68, 129.07,
130.09, 131.36, 133.85, 133.91, 137.49, 141.44, 144.13, 148.75,
153.69 ppm. Analysis calculated for C12H10Cl4N2O2S (388.09):
C, 37.38; H, 2.59; N, 7.22. Found: C, 37.33; H, 2.64; N, 7.33.
4‐Methoxy‐3‐sulfamoyl‐1‐(4‐chlorophenyl)pyridinium chloride
(5).
Starting from 4‐methoxy‐3‐pyridinesulfonamide 1b (1.88 g)
and 4‐chlorobenzenesulfonyl chloride 2c (2.24 g), the title compound
5 was obtained (2.3 g, 68%): m.p. 190–191°C; IR (KBr) 3330, 3165
(SO2NH2), 1350, 1170 (SO2) cm−1; 1H‐NMR (dimethyl sulfoxide‐d6)
δ 4.19 (s, 3H, CH3O), 7.38 (d, J = 8.3 Hz, 2H, 4‐ClPh), 7.59 (d, J =
8.3 Hz, 2H, 4‐ClPh), 7.84 (d, J = 6.6 Hz, 1H, H‐5, pyrid.), 7.88 (s,
2H, SO2NH2), 8.92 (d, J = 6.6 Hz, 1H, H‐6, pyrid.), 8.97 (s, 1H, H‐
2, pyrid.) ppm; 13C‐NMR (dimethyl sulfoxide‐d6) δ 58.99, 111.34,
127.73, 128.01, 129.87, 133.31, 142.45, 147.34, 148.54, 167.32 ppm.
Analysis calculated for C12H12Cl2N2O3S (335.21): C, 42.99; H, 3.61;
N, 8.35. Found: C, 42.97; H, 3.73; N, 8.43.
4‐Methoxy‐3‐sulfamoyl‐1‐(4‐bromophenyl)pyridinium chloride
(6).
Starting from sulfonamide 1b (1.88 g) and 4‐
bromobenzenesulfonyl chloride 2d (2.7 g), the title compound 6 was
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Benzenesulfonyl Chloride Derivatives
Scheme 4. Proposed mechanisms of the formation 4‐dimethylaminopyridinium‐3‐pyrimidinesulfonamidate 15 and 1H+‐pyridinium‐3‐sulfonamidate 16
in the reaction of 4‐methoxy‐3‐pyridinesulfonamide 1b with DMAP and 2,5‐dichlorobenzenesulfonyl chloride 2a.
obtained (1.9 g, 50%): m.p. 186–188°C; IR (KBr) 3345, 3170
(SO2NH2), 1350, 1170 (SO2) cm−1; 1H‐NMR (dimethyl sulfoxide‐d6)
δ 4.20 (s, 3H, CH3O), 7.52 (s, 4H, 4‐BrPh), 7.77 (d, J = 6.7 Hz, 1H,
H‐5, pyrid.), 7.87 (s, 2H, SO2NH2), 8.93 (d, J = 6.7 Hz, 1H, H‐6,
pyrid.), 8.98 (s, 1H, H‐2, pyrid.) ppm; 13C‐NMR (dimethyl sulfoxide‐
d6) δ 59.03, 111.39, 121.99, 128.02, 129.90, 130.94, 142.34, 147.73,
148.42, 167.41 ppm. Analysis calculated for C12H12BrClN2O3S
(379.65): C, 37.96; H, 3.18; N, 7.37. Found: C, 38.03; H, 3.20; N, 7.41.
4‐Methoxy‐3‐sulfamoyl‐1‐(2,5‐dichlorophenyl)pyridinium
chloride (7). Starting from sulfonamide 1b (1.88 g) and 2,5‐
dichlorobenzenesulfonyl chloride 2a (2.6 g), the title compound
7 was obtained (3.3 g, 89%): m.p. 207–208°C; IR (KBr) 3320,
1H, H‐2, pyrid.), ppm. Analysis calculated for C13H13Cl3N2O3S
(383.67): C, 40.69; H, 3.41; N, 7.30. Found: C, 40.72; H, 3.40;
N, 7.29.
Procedure for the preparation of 1,10‐bis(3‐nitrobenzene-
sulfonylimino)deca‐2,4,6,8‐tetraene‐2,9‐disulfonamide derivatives
(9–12). A mixture of 3‐nitrobenzenesulfonyl chloride 2e (1.2
g, 0.0054 mol) and the appropriate 3‐pyridinesulfonamide 1b,
1c, 1d, or 1e (0.005 mol) in dry acetonitrile (25 mL) was
stirred at room temperature for 48 h, followed at reflux until the
evolution of HCl had ceased (80–110 h). After cooling to room
temperature and standing overnight the precipitate was filtered
off, washed with acetonitrile (4× 1.5 mL) and dried. In this
manner, the following products were obtained.
3220 (SO2NH2), 1355, 1175 (SO2) cm−1 1H‐NMR (dimethyl
;
sulfoxide‐d6) δ 4.20 (s, 3H, CH3O), 7.41 (s, 2H, SO2NH2), 7.76
(d, J = 6.8 Hz, 1H, H‐5, pyrid.), 7.83–7.92 (m, 3H, 2,5‐diClPh),
8.92 (d, J = 6.8 Hz, 1H, H‐6, pyrid.), 8.98 (s, 1H, H‐2, pyrid.)
3,8‐Dimethoxy‐1,10‐bis(3‐nitrobenzenesulfonylimino)deca‐
2,4,6,8‐tetraene‐2,9‐disulfonamide (9).
Starting from 4‐
methoxy‐3‐pyridinesulfonamide 1b (0.94 g), the title compound
9 was obtained (1.4 g, 75%): m.p. 180–181°C; IR (KBr) 3310,
3215 (SO2NH2), 2920, 2850 (CH3O), 1635, 1175, (NO2), 1350,
ppm; 13C‐NMR (dimethyl sulfoxide‐d6)
δ 50.06, 111.42,
128.76, 129.94, 130.05, 131.01, 132.47, 142.26, 148.32, 148.94,
153.93, 167.48 ppm. Analysis calculated for C12H11Cl3N2O3S
(369.65): C, 38.99; H, 3.00; N, 7.57. Found: C, 38.97; H, 3.07;
N, 7.58.
1155 (SO2) cm−1 1H‐NMR (dimethyl sulfoxide‐d6) δ 4.18
;
(s, 6H, 3,8‐diCH3O), 7.65 (t, J = 7.8 Hz, 2H, H‐5 and H‐5′,
benzene rings), 7.71 (d, J = 6.3 Hz, 2H, H‐5 and H‐6), 7.80 (s,
4H, 2,9‐di‐SO2NH2), 8.02 (d, J = 7.8 Hz, 2H, H‐6 and H‐6′,
benzene rings), 8.19 (d, J = 7.8 Hz, 2H, H‐4 and H‐4′, benzene
rings), 8.34 (s, 2H, H‐2 and H‐2′, benzene rings), 8.89 (d, J =
6.3 Hz, 2H, H‐4 and H‐7), 8.95 (s, 2H, H‐1 and H‐10) ppm;
13C‐NMR (dimethyl sulfoxide‐d6) δ 58.66, 110.95, 119.08,
120.33, 123.64, 130.05, 132.24, 138.88, 140.05, 143.25,
149.48, 166.61 ppm. Analysis calculated for C24H24N6O14S4
(748.76): C, 34.49; H, 3.23; N, 11.22. Found: C, 34.55; H,
3.30; N, 11.11.
4‐Methoxy‐3‐sulfamoyl‐1‐(2,4‐dichloro‐5‐methylphenyl)
pyridinium chloride (8). Starting from sulfonamide 1b (1.88 g)
and 2,4‐dichloro‐5‐methylbenzenesulfonyl chloride 2b (2.75 g),
the title compound 8 was obtained (3.3 g, 86%): m.p. 189–190°
C; IR (KBr) 3205, 3180 (SO2NH2), 1350, 1170 (SO2) cm−1
;
1H‐NMR (dimethyl sulfoxide‐d6) δ 2.29 (s, 3H, CH3), 4.20 (s,
3H, CH3O), 7.46 (s, 1H, H‐6, 2,4‐diCl‐5‐MePh) 7.76 (d, J = 6.8
Hz, 1H, H‐5, pyrid.), 7.81(s, 1H, H‐3, 2,4‐diCl‐5‐MePh), 7.86
(s, 2H, SO2NH2), 8.93 (d, J = 6.8 Hz, 1H, H‐6, pyrid.), 8.98 (s,
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3,8‐Diethoxy‐1,10‐bis(3‐nitrobenzenesulfonylimino)deca‐
2,4,6,8‐tetraene‐2,9‐disulfonamide (10). Starting from
250–251°C; IR (KBr) 3370, 3270 (SO2NH2), 1645 (C O), 1610,
1600 (NO2), 1345, 1160 (SO2) cm−1 1H‐NMR (dimethyl
;
4‐ethoxy‐3‐pyridinesulfonamide 1c (1.01 g), the title compound
10 was obtained (1.6 g, 82%): m.p. 175–176°C; IR (KBr) 3300,
3200 (SO2NH2), 2925, 2850 (EtO), 1635, 1190 (NO2), 1355,
sulfoxide‐d6) δ 6.52 (d, J = 7.8 Hz, 1H, H‐5, pyrid.), 7.02
(s, 2H, SO2NH2), 8.02 (dd, Jortho = 7.8 Hz, Jmeta = 2.3 Hz, 1H,
H‐6 pyrid.), 8.18 (d, J = 8.7 Hz, 1H, H‐6, 2,4‐diO2NPh), 8.52
(d, Jmeta = 2.3 Hz, 1H, H‐2, pyrid.), 8.74 (dd, Jortho = 8.7 Hz,
Jmeta = 2.6 Hz, 1H, H‐5 di‐O2NPh ), 8.98 (d, Jmeta = 2.6 Hz,
1H, H‐3, 2,4‐di O2NPh) ppm; 13C‐NMR (dimethyl sulfoxide‐d6)
δ 119.98, 121.70, 129.82, 130.99, 132.24, 139.88, 141.30,
142.13, 144.35, 147.87, 172.86 ppm. Analysis calculated for
C11H8N4O7S (340.27): C, 38.82; H, 2.37; N, 16.45. Found: C,
38.83; H, 2.41; N, 16.47.
1
1145 (SO2) cm−1; H‐NMR (dimethyl sulfoxide‐d6) δ 1.44 (t, J =
7.0 Hz, 6H, 3,8‐di CH3CH2O), 4.55 (q, J = 7.0 Hz, 4H, 3,8‐di
CH3CH2O), 7.61 (t, J = 7.7 Hz, 2H, H‐5, and H‐5′, benzene
rings), 7.71 (d, J = 6.6 Hz, 2H, H‐5 and H‐6), 7.79 (s, 4H, 2,9‐
di‐SO2NH2), 8.04 (d, J = 7.7 Hz, 2H, H‐6 and H‐6′, benzene
rings), 8.19 (d, J = 7.8 Hz, 2H, H‐4 and H‐4′, benzene rings),
8.33 (s, 2H, H‐2, and H‐2′, benzene rings), 8.87 (d, J = 6.6 Hz,
2H, H‐4 and H‐7), 8.96 (s, 2H, H‐1 and H‐10) ppm. Analysis
calculated for C26H28N6O14S4 (776.81): C, 40.20; H, 3.63; N,
10.81. Found: C, 40.22; H, 3.65; N, 10.92.
The acetonitrile filtrate was evaporated to 1/3 volume at nor-
mal pressure and left to stand at room temperature for three days.
The precipitate of title compound 14 was filtrated off, washed
with acetonitrile (1.5 mL) and recrystallized from acetonitrile.
Yield: 1.0 g (53%): m.p. 246–247°C; IR (KBr) 3350, 3150
3,8‐Di(2,4‐dichlorophenoxy)‐1,10‐bis(3‐nitrobenzenesulfony-
limino)deca‐2,4,6,8‐tetraene‐2,9‐disulfonamide (11).
Starting
1
(SO2NH2), 1650 (C O), 1330, 1160 (SO2) cm−1; H‐NMR (di-
from 4‐(2,4‐dichlorophenoxy)‐3‐pyridinesulfonamide 3d (1.6 g),
the title compound 11 was obtained (2.1 g, 83%): m.p. 175–176°
C; IR (KBr) 3230, 3165 (SO2NH2), 1630, 1180 (NO2), 1355,
methyl sulfoxide‐d6) δ 3.73 (s, 3H, CH3), 6.35 (d, J = 7.5 Hz,
1H, H‐5), 6.79 (s, 2H, SO2NH2), 7.76 (dd, Jortho = 7.5 Hz, Jmeta
= 2.2 Hz, 1H, H‐6), 8.29 (d, Jmeta = 2.2 Hz, 1H, H‐2) ppm;
13C‐NMR (dimethyl sulfoxide‐d6) δ 43.65, 120.04, 129.93,
142.19, 143.45, 172.34 ppm. Analysis calculated for C6H8N2O3S
(188.20): C, 38.29; H, 4.28; N, 14.88. Found: C, 38.34; H, 4.30;
N, 14.90.
1
1145 (SO2) cm−1; H‐NMR (dimethyl sulfoxide‐d6) δ 7.09 (d, J
= 6.3 Hz, 2H, H‐5 and H‐6), 7.30 (s, 4H, 2,9‐di‐SO2NH2), 7.49
(d, J = 8.7 Hz, 2H, H‐6 and H‐6′, 2,4‐diClPh), 7.62 (d, Jmeta
=
2.0 Hz, 2H, H‐3 and H‐3′, 2,4‐diClPh), 7.68 (d, J = 7.6 Hz, 2H,
H‐5 and H‐5′, 3‐O2NPh), 7.93 (dd, Jortho = 8.7 Hz, 2H, H‐5 and
H‐5′, 2,4‐diClPh), 8.03 (d, J = 7.6 Hz, 2H, H‐6 and H‐6′,
3‐O2NPh), 8.19 (dd, Jortho = 7.6 Hz, Jmeta = 1.1 Hz, 2H, H‐4 and
H‐4′, 3‐O2NPh), 8,32 (s, 2H, H‐2 and H‐2′, 3‐O2NPh), 8.74 (d, J
= 6.3 Hz, 2H, H‐4 and H‐7), 9.06 (s, 2H, H‐1 and H‐10) ppm;
13C‐NMR (dimethyl sulfoxide‐d6) δ 112.06, 120.33, 123.69,
125.45, 127.30, 129.56, 129.86, 130.07, 130.97, 132.22, 132.29,
146.30, 147.31, 147.49, 150.14, 151.84, 152.87 ppm. Analysis
calculated for C34H24Cl4N6O14S4 (1010.68): C, 40.40; H, 2.39;
N, 8.31. Found: C, 40.40; H, 2.41; N, 8.32.
Synthesis of 4‐dimethylaminopyridinium 4‐methoxy‐N‐
(2,5‐dichlorophenylsulfonyl)‐3‐pyridinesulfonamidate
and 1H+‐pyridinium‐4‐methoxy‐3‐[N‐(2,5‐dichlorophenyl)
sulfonyl]sulfonamidate (16). To a stirred suspension of
(15)
4‐methoxy‐3‐pyridinesulfonamide 1b (1.5 g, 8 mmol) and
4‐dimethyaminopyridine (2.1 g, 17 mmol) in acetonitrile (25
mL), the 2,5‐dichlorobenzenesulfonyl chloride 2a (2.0 g, 8.1
mmol) was added portion wise. The reaction mixture was stirred
at room temp. for 12 h, followed at reflux for 6 h. The solution
obtained was cooled to room temperature and the resulting
suspension was left overnight. The precipitate of title compound
15 was filtered off, washed successively with water (4× 2 mL)
and tetrahydrofuran (3× 2 mL) and dried. Yield: 3.8 g (91%);
m.p. 185–186°C; IR (KBr) 3225 (NH), 2925 (CH3), 2850,
2805, 2690 (NH+), 1645 (C N), 1580, 1555 (C C), 1315, 1160
3,8‐Di(4‐cyanophenoxy)‐1,10‐bis(3‐nitrobenzenesulfonyli-
mino)deca‐2,4,6,8‐tetraene‐2,9‐disulfonamide (12).
Starting
from 4‐(4‐cyanophenoxy)‐3‐pyridinesulfonamide 1e (1.4 g), the
title compound 12 was obtained (1.6 g, 69%): m.p. 274–275°C;
IR (KBr) 3350, 3250 (SO2NH2), 2235 (C N), 1690, 1175 (NO2),
1
1350, 1150 (SO2) cm−1; H‐NMR (dimethyl sulfoxide‐d6) δ 7.22
(SO2) cm−1 1H‐NMR (dimethyl sulfoxide‐d6) δ 3.17 (s, 6H,
;
(d, J = 8.0 Hz, 4H, H‐3,3′ and H‐5,5′, PhC N), 7.45 (d, J = 8.0
Hz, 4H, H‐2,2′ and H‐6,6′, PhC N), 7.56 (s, 4H, 2,9‐di‐SO2NH2),
7.15 (d, J = 6.2 Hz, 2H, H‐5 and H‐6), 7.96 (d, J = 7.6 Hz, 2H,
H‐5,5′, 3‐O2NPh), 8.02 (d, J = 7.6 Hz, 2H, H‐6,6′, 3‐O2NPh),
8.17 (d, J = 7.6 Hz, 2H, H‐4,4′, 3‐O2NPh), 8.30 (s, 2H, H‐2,2′,
3‐O2NPh), 8.76 (d, J = 6.2 Hz, 2H, H‐4 and H‐7), 9.06 (s, 2H,
H‐1 and H‐10) ppm; 13C‐NMR (dimethyl sulfoxide‐d6) δ 109.00,
113.58, 118.24, 120.06, 121.89, 123.42, 129.81, 130.47, 131.96,
135.09, 146.58, 146.75, 149.90, 152.12, 156.54, 162.14 ppm.
Analysis calculated for C36H26N8O14S4 (922.93): C, 46.85; H,
2.84; N, 12.14. Found: C, 46.81; H, 2.30; N, 12.12.
Synthesis of 1,4‐dihydro‐1‐(2,4‐dinitrophenyl)‐4‐oxo‐3‐
pyridinesulfonamide (13) and 1,4‐dihydro‐1‐methyl‐4‐oxo‐
3‐pyridinesulfonamide (14) in the reaction of 4‐metoxy‐3‐
pyridinesulfonamide (1b) with 2,4‐dinitrobenzenesulfonyl
chloride. A mixture of pyridinesulfonamide 1b (1.89 g, 0.01
mol) and 2,4‐dinitrobenzenesulfonyl chloride 2f (2.72 g, 0.0102
mol) in dry acetonitrile (35 mL) was stirred at room temperature
for 48 h, followed at reflux for 40 h, and then left to stand
overnight. The title compound 13 thus obtained was collected
by filtration, washed with acetonitrile (3× 1.5 mL), (filtrates was
left for further work‐up), and dried. Yield: 0.85 g (25%): m.p.
CH3‐ N‐CH3), 3.35 (s, 1H, NH), 3.71 (s, 3H, CH3O), 6.90 (d, J
= 5.8 Hz, 1H, H‐5, Py‐SO2N), 6.98 (d, J = 7.1 Hz, 2H,
DMAP), 7.41 (s, 2H, H‐3 and H‐4, 2,5‐diClPh), 7.49 (s, 1H, H‐
6, 2,5‐diClPh), 8.21 (d, J = 7.1 Hz, 2H, DMAP), 8.40 (d, J =
5.8 Hz, 1H, H‐6, Py‐SO2N), 8.49 (s, 1H, H‐2, Py‐SO2N) ppm.
Analysis calculated for C19H20Cl2 N4O5S2 (519.44): C, 43.93;
H, 3.88; N, 10.78. Found: C, 43.90; H, 3.92; N, 10.80.
To a stirred suspension of dimethylamino pyridinium‐3‐
pyridinesulfonamidate 15 (2.08 g, 4 mmol) in water (25 mL)
was slowly acidified to pH 1 with 1% hydrochloric acid. After 2
h of stirring, the title compound 16 was filtered off, washed with
water (4× 5 mL) and methanol (3× 1.5 mL), and dried. Yield: 1.5
g (94%); m.p. 269–270°C; IR (KBr) 3090 (CH‐arom) 2920
(CH3O), 2785, 2610 (NH+), 1635 (C N), 1555, 1495 (C C),
1330, 1145 (SO2) cm−1 1H‐NMR (dimethyl sulfoxide‐d6) δ
;
4.00 (s, 3H, CH3O), 7.42 (d, J = 7.4 Hz, 1H, H‐5, Py‐SO2N),
7.50 (s, 2H, H‐3 and H‐4, 2,5‐diClPh), 7.61 (s, 1H, H‐6, 2,5‐
diClPh), 8.21 (br.s, 1H, NH+), 8.70 (d, J = 7.4 Hz, 1H, H‐6,
Py‐SO2N), 8.76 (s, 1H, H‐2, Py‐SO2N) ppm. Analysis calculated
for C12H10Cl2 N2O5S2 (397.26): C, 36.28; H, 2.53; N, 7.05.
Found: C, 36.30; H, 2.64; N, 7.10.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2014
On the Reaction Products of 4‐Substituted 3‐Pyridinesulfonamides with Some
17
Benzenesulfonyl Chloride Derivatives
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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