An efficient method for the synthesis of N-acylsulfonamides: One-pot sulfonylation and acylation of primary arylamines under solvent-free conditions

Article abstract of DOI:10.1007/s00706-007-0783-2

The preparation of N-acylsulfonamides is described using primary amines, arylsulfonyl chlorides and acyl chlorides. Reaction of primary aryl amines with arylsulfonyl chlorides in the presence of NaHCO₃ produced N-arylsulfonamides, which reacted in situ with benzoyl chloride furnishing the corresponding N-benzoyl-N-arylsulfonamides in 72-96% yields. Accordingly, 4-nitrobenzoyl chloride and 3,5-dinitrobenzoyl chloride were used as acylating agents. All the reactions were carried out under solvent-free conditions at room temperature and the products were isolated after simple work-up in high yields and purity.

Full text of DOI:10.1007/s00706-007-0783-2

Monatsh Chem 139, 233–240 (2008)
DOI 10.1007/s00706-007-0783-2
Printed in The Netherlands
An Efficient Method for the Synthesis of N-Acylsulfonamides: One-pot
Sulfonylation and Acylation of Primary Arylamines under Solvent-Free
Conditions
Ahmad R. Massah1;ꢀ, Davood Azadi1, Hamid Aliyan1, Ahmad R. Momeni1,
Hamid Javaherian Naghash1, and Foad Kazemi2
1
Department of Chemistry, Islamic Azad University, Shahreza Branch, Isfahan, Iran
2
Department of Chemistry, Institute for Advanced Studies in Basic Science (IASBS), Zanjan, Iran
Received February 23, 2007; accepted August 14, 2007; published online February 12, 2008
# Springer-Verlag 2008
Summary. The preparation of N-acylsulfonamides is de-
scribed using primary amines, arylsulfonyl chlorides and acyl
chlorides. Reaction of primary aryl amines with arylsulfonyl
chlorides in the presence of NaHCO3 produced N-arylsulfon-
amides, which reacted in situ with benzoyl chloride fur-
nishing the corresponding N-benzoyl-N-arylsulfonamides in
72–96% yields. Accordingly, 4-nitrobenzoyl chloride and
3,5-dinitrobenzoyl chloride were used as acylating agents. All
the reactions were carried out under solvent-free conditions at
room temperature and the products were isolated after simple
work-up in high yields and purity.
In the majority of reports for the preparation of N-
acylsulfonamides the parent sulfonamide is used as
a starting material. Acylation with acyl chlorides,
anhydrides and N-acyl benzotriazoles [7–11], direct
condensation of carboxylic acid and sulfonamides in
the presence of condensing agents (e.g. EDC, DCC,
and carbonyl diimidazole) [2, 3, 12–14], have been
employed for this purpose. The reaction of amides
with sulfonyl chlorides is also used occasionally for
the synthesis of N-acylsulfonamides [15–17]. Most
of these reports are examples of reactions that were
typically carried out in a solvent.
Keywords. N-Acylsulfonamide; Solvent-free; Acylation;
Sulfonylation; N-Arylsulfonamide; N-Acyl-N-arylsulfonamide.
Among the N–H acids in which the acidity is
enhanced by neighboring electron withdrawing sub-
stituents, N-arylsulfonamides (pKa ¼ 5–10) [18] were
considered as capable of easily undergoing alkyl-
ation and acylation. On this basis, Kondo and co-
workers used N-arylsulfonamides as a precursor for
the synthesis of N-acyl-N-arylsulfonamides [6]. They
synthesized the starting sulfonamides from the aryl-
amines and appropriate sulfonylchloride in pyridine
as solvent in 48–79% yields. These reactions afford
the crude product as a mixture of N-mono and di-
sulfonylated arylamines. The second step involves
the reaction of N-arylsulfonamide with 4 equiv of
benzoyl chloride in pyridine. Recently, Padmavathi
reported the synthesis of a variety of N-acyl-N-aryl-
sulfonamides from araldoximes and chloramine-T
Introduction
The N-acylsulfonamide moiety is a common struc-
tural motif in organic synthesis. Several recent de-
velopmental drugs including therapeutic agents for
Alzheimer’s disease [1], inhibitors of tRNA synthe-
tases as antibacterial agents [2], prostaglandin F1a
sulfonamides for the potential treatments for osteo-
porosis [3], antagonists for angiotensin II [4], and
leukotriene D4-receptors [5], incorporate this func-
tionality. In addition, several N-acyl-N-arylmethansul-
fonamides have been employed as chemoselective
N-acylating reagents [6].
ꢀ
Massahar@yahoo.com
Corresponding author. E-mails: Massah@iaush.ac.ir;

234
A. R. Massah et al.
[19]. In this method reaction of araldoxime with 2
equiv of chloramine-T in refluxing methanol for 48 h
followed by purification on silica gel furnished N-
acyl-N-arylsulfonamides in 12–29% yield. These
methodologies suffer from some disadvantages such
as low yield, prolonged reaction time, use of toxic
organic solvent and the requirement of excess re-
agents. Therefore, an alternative route for the con-
struction of N-acylsulfonamides would be highly
desirable. Solvent-free reactions have attracted the
attention of chemists due to their simplicity in pro-
cessing and handling [20]. Along this line, we now
report an efficient, convenient and facile method for
the sulfonylation=acylation of primary aryl amines
under solvent-free conditions.
focus on the use of N-arylsulfonamides as a pre-
cursor of various N-acyl-N-arylsulfonamides since
these starting materials are expected to have lower
pKa values than N-benzoyl anilines. At first, sulfo-
nylation of anilines was examined in the presence
of anhydrous NaHCO3 as solid base under solvent-
free conditions at room temperature. N-arylsulfo-
namides were obtained in high yields and purity.
Then, N-arylsulfonamides were reacted with ben-
zoyl chloride in the presence of anhydrous K2CO3
under solvent-free conditions. The reactions were
completed very fast and the corresponding N-aryl-N-
benzoylsulfonamides were obtained in high yields
and purity.
In a second series of experiments we prepared
N-aryl-N-benzoylsulfonamides directly from aryla-
mines without any need to isolate the intermediate
N-arylsulfonamides. In order to reach this goal, we
had to optimize the reaction conditions. We found
that the N-arylsulfonamides were rapidly converted
into N-aryl-N-benzoylsulfonamides in situ in the
presence of 2 equiv benzoyl chloride in anhydrous
K2CO3 (Scheme 1). The reaction was carried out at
Results and Discussion
Our original plan was to react N-benzoyl anilines
bearing with different arylsulfonyl groups under sol-
vent-free conditions. However, even after considerable
experimentation our attempts remained unsuccessful.
In an effort to overcome this problem, we chose to
Scheme 1
Table 1. One-pot reaction of arylamines with some arylsulfonyl chloride and benzoyl chloride at room temperature
Entry
Arylamine
Arylsulfonyl chloride
Product
Time=min
Yield=%
1
2
3
4
5
6
7
8
9
aniline
benzensulfonyl chloride
benzensulfonyl chloride
tosylchloride
1a
1b
1c
1d
1e
1f
1g
1h
1i
9
20
5
7
20
8
10
17
35
92
72
86
86
72
95
96
90
89
2,4-dimethylaniline
2-methylaniline
2-methoxyaniline
4-methoxyaniline
3-chloroaniline
4-chloroaniline
4-methylaniline
4-chloroaniline
tosylchloride
tosylchloride
tosylchloride
tosylchloride
4-acetamidobenzensulfonyl chloride
4-acetamidobenzensulfonyl chloride

One-pot Sulfonylation and Acylation of Primary Arylamines under Solvent-Free Conditions
235
room temperature and the experimental procedure is
remarkably simple and requires no toxic solvents or
inert atmosphere.
zenesulfonyl chloride (2 mmol) in NaHCO3 provided
N-4-methoxyphenylbenzenesulfonamide; subsequent
in situ addition of 3,5-dinitrobenzoyl chloride
(4 mmol) and K2CO3 provided product 4a in 40%
yield after 15 h.
Therefore, we next turned our attention to a step-
wise method. It was found that if the product of the
sulfonylation reaction of arylamine was isolated and
then reacted with nitro substituted benzoyl chloride,
the reaction was clean and the product was produced
very fast. For this purpose, we synthesized a variety
of N-arylsulfonamides under solvent-free conditions
[20a].
Sulfonylation was achieved with benzenesulfonyl
chloride, p-methylbenzenesulfonyl chloride and 4-
acetamidobenzenesulfonyl chloride in NaHCO3 un-
der vigorous stirring. It was found that in this step
the use of K2CO3 instead of NaHCO3 as base, gives
rise to di-sulfonylated byproduct in some cases.
Upon completion of the reaction, K2CO3 was added
and the mixture was stirred vigorously for a minute.
Then, it was treated with benzoyl chloride to afford
the N-aryl-N-benzoylsulfonamides after a very sim-
ple work-up (Table 1).
Interestingly, the products of the second step,
acylation of N-aryl sulfonamides, were obtained
by simply grinding of N-arylsulfonamides 2a–2m
(2 mmol) with 3,5-dinitrobenzoyl chloride or 4-
nitrobenzoyl chloride (4 mmol) for 1–5 min at room
temperature in the presence of K2CO3 under sol-
vent-free conditions (Schemes 3, 4). The results
are summarized in Tables 2 and 3. It is worth men-
tioning that the electronic nature of the substituents
on the benzene rings does not have a noticeable
effect on the reaction times and the yields of the
products. Also, the reaction rates and the yields of
products were not greatly affected by the steric
bulk of substituents in the vicinity of the nitrogen
atom in the starting N-arylsulfonamides, which
was mentioned as a problem in preceeding reports
[6, 7].
Several functionalities present in the arylamines
and arylsulfonyl chloride such as halogen, methyl,
and methoxy groups in various positions (o, m, p)
were tolerated. In all cases the corresponding N-aryl-
N-benzoylsulfonamides were obtained in good to
excellent overall yields. Noteworthy here is that
the yield of the reaction was not greatly influenced
by the presence of electron-donating or electron-
withdrawing groups on the arylamine or arylsulfonyl
chloride. Under the same reaction conditions, 4-
nitrobenzoyl and 3,5-dinitrobenzoyl chlorides are
less reactive than benzoyl chloride and the corre-
sponding N-aryl-N-4-nitrobenzoylsulfonamides 3a–
3g and N-aryl-N-3,5-dinitrobenzoylsulfonamides
4a–4f were obtained in low yields. For example,
treatment of p-methoxyaniline (2 mmol) with ben-
Scheme 2

236
A. R. Massah et al.
Scheme 3
Table 2. Reaction of some N-arylsulfonamides with 4-nitro-
benzoyl chloride at room temperature in K2CO3 under sol-
vent-free condition
of amide groups was further supported by the pres-
ence of carbonyl carbon resonance at ꢁ ¼ 167–
170 ppm in the 13C NMR spectrum. Finally, the ele-
mental analysis is in accordance with the proposed
products.
Entry N-Arylsulfonamides Product Time=min Yield=%
1
2
3
4
5
6
7
2a
2b
2j
2g
2i
3a
3b
3c
3d
3e
3f
1
1
1
1
1
1
5
70
80
75
75
81
91
90
In conclusion, we have described a convenient syn-
thetic method for the preparation of N-acyl-N-arylsul-
fonamides from sterically and electronically diverse
arylamines or N-arylsulfonamides. The key feature is
the one-pot condensation of arylamines with arylsul-
fonyl chlorides and acyl chlorides, especially benzoyl
chloride, under solvent-free conditions in the pres-
ence of NaHCO3=K2CO3 as base at room tempera-
ture. All of the reactions are easy to operate, proceed
very fast, use inexpensive reagents and furnish the
products after simple work-up. Thus, this method
obeying several principles of green chemistry should
be widely applicable to the synthesis of various N-
acyl-N-arylsulfonamides.
2k
2l
3g
Spectral analysis of N-acyl-N-arylsulfonamides
supports the structure of the products. The IR spectra
indicated the absence of N–H bond and exhibited
the presence of sulfonyl (ꢀꢀ¼ 1150–1180 and 1350–
1380 cmꢁ1) and amide (1660–1700 cmꢁ1) groups.
1
The H NMR spectrum clearly showed the presence
of 1,4-disubstituted benzene moieties. The presence
Scheme 4

One-pot Sulfonylation and Acylation of Primary Arylamines under Solvent-Free Conditions
237
CDCl3): ꢁ ¼ 121.6, 124.4, 127.3, 127.5, 127.7, 128.9, 129,
129.1, 132.0, 132.2, 134.2, 139.7, 165.0ppm; IR: ꢀꢀ¼ 1691,
Table 3. Reaction of some N-arylsulfonamides with 3,5-dini-
trobenzoyl chloride at room temperature in K2CO3 under
solvent-free condition
1365, 1266, 1186, 1093, 582 cmꢁ1
.
Entry N-Arylsulfonamides Product Time=min Yield=%
N-(2,4-Dimethylphenyl)-N-(phenylsulfonyl)benzamide
(1b, C21H19NO3S)
1
2
3
4
5
6
2c
2d
2e
2f
2h
2m
4a
4b
4c
4d
4e
4f
1
1
1
1
1
3
73
84
70
80
95
86
Purification by silica gel column chromatography (ethyl
acetate–petroleum ether) afforded pure 1b as a colorless
powder, mp 168–170ꢂC; yield 72%; 1H NMR (500 MHz,
CDCl3): ꢁ ¼ 2.18 (3H, s), 2.31 (3H, s), 6.99 (2H, m), 7.06
(1H, d, J ¼ 8.0 Hz), 7.19 (2H, m), 7.32 (1H, m), 7.38 (2H,
d, J ¼ 7.0 Hz), 7.59 (2H, m), 7.72 (1H, m), 8.11 (2H, d, J ¼
7.5 Hz) ppm; 13C NMR (125MHz, CDCl3): ꢁ ¼ 18.22, 20.98,
127.03, 127.39, 127.72, 128.51, 128.56, 128.81, 129.55,
130.90, 131.35, 132.13, 133.42, 133.71, 133.83, 137.63,
138.81, 139.66, 169.63 ppm; IR: ꢀꢀ¼ 1686, 1453, 1366,
Experimental
1280, 1173 cmꢁ1
.
All chemicals were purchased from Merck and Fluka.
The products were characterized by comparing the physi-
cal data with those of known samples or by their spectral
data. Infrared spectra were recorded on a Nicolet (Impact
N-o-Tolyl-N-tosylbenzamide (1c, C21H19NO3S)
Purification by recrystallization (ethyl acetate–n-hexane) af-
forded pure 1c as a colorless powder, mp 156–158ꢂC; yield
86%; 1H NMR (500MHz, CDCl3): ꢁ ¼ 2.25 (3H, s), 2.51 (3H,
s), 7.18 (5H, m), 7.25 (1H, m), 7.30 (1H, m), 7.38 (4H, dd,
J ¼ 13.5, 8.0 Hz), 8.00 (2H, d, J ¼ 8.0 Hz) ppm; 13C NMR
(125 MHz, CDCl3): ꢁ ¼ 15.2, 24.3, 121.5, 124.3, 126.0,
127.2, 127.5, 128.9, 129.3, 129.4, 134.2, 134.3, 136.7, 138.5,
141.6, 165.0 ppm; IR: ꢀꢀ¼ 1676, 1596, 1348, 1281, 1167,
1
400D model) FTIR spectrophotometer. H and 13C NMR
spectra were recorded on Bruker DRX 500 Avance spectro-
photometer in CDCl3, acetone-d6, or DMSO-d6 as the
solvent and TMS as internal standard. Column chromato-
graphy was performed using silica gel 60 (230–400 mesh,
Merck). All yields refer to isolated yields. Results of
elemental analysis were found to agree with calculated
values.
580 cmꢁ1
.
General Procedure for the Prepration of N-Aryl-N-benzoyl-
sulfonamides
N-(2-Methoxyphenyl)-N-tosylbenzamide (1d, C21H19NO4S)
Purification by recrystallization (ethyl acetate–n-hexane) af-
forded pure 1d as a colorless powder, mp 213–215ꢂC; yield
86%; 1H NMR (500MHz, CDCl3): ꢁ ¼ 2.48 (3H, s), 3.49 (3H,
s), 6.71 (1H, d, J ¼ 8.0), 6.99 (2H, m), 7.16 (2H, m), 7.28 (1H,
m), 7.35 (2H, d, J ¼ 8.0 Hz), 7.41 (2H, d, J ¼ 7.0 Hz), 7.50
(1H, dd, J ¼ 8.0, 1.5 Hz), 7.94 (2H, d, J ¼ 8.0 Hz) ppm; 13C
NMR (125MHz, CDCl3): ꢁ ¼ 24.3, 55.9, 114.5, 121.3, 122.6,
123.8, 125.4, 127.2, 128.9, 129.4, 132.2, 134.2, 136.7, 141.6,
152.8, 165.1 ppm; IR: ꢀꢀ¼ 1703, 1596, 1449, 1361, 1261,
An amine (2 mmol) and anhydrous NaHCO3 (1 g) were
ground together into fine powder in a mortar and aryl-
sulfonyl chloride (2 mmol) was added under vigorous
stirring with a magnetic stirrer at room temperature.
The progress of the reaction was monitored by TLC until
the conversion of amine was completed. In all cases the
crude products showed one spot on TLC and were used
in the second step without prior purification. Benzoyl
chloride (4 mmol) and anhydrous K2CO3 were added to
the mixture and stirred vigorously at room temperature.
The reaction was monitored by TLC. Upon completion of
the reaction, water was added and the mixture was stirred
for a few minutes. The product was collected by filtration
of the suspension through a sintered glass funnel and
washed with additional water. The crude product was
purified by column chromatography on silica gel (60–
120 mesh, EtOAc-petroleum ether) or recrystallized (ethyl
acetate–n-hexane mixed solvent) to afford the corre-
sponding N-aryl N-benzoylsulfonamides in good to high
yield.
1167, 713 cmꢁ1
.
N-(4-Methoxyphenyl)-N-tosylbenzamide (1e, C21H19NO4S)
Purification by recrystallization (ethyl acetate–n-hexane) af-
forded pure 1e as a colorless powder, mp 178–180ꢂC; yield
72%; 1H NMR (500MHz, CDCl3): ꢁ ¼ 2.49 (3H, s), 3.80 (3H,
s), 6.81 (2H, d, J ¼ 8.5 Hz), 7.09 (2H, d, J ¼ 8.5 Hz), 7.22 (2H,
m), 7.31 (1H, m), 7.36 (2H, d, J ¼ 8.0 Hz), 7.49 (2H, d, J ¼
8.0 Hz), 7.87 (2H, d, J ¼ 8.0 Hz) ppm; 13C NMR (125 MHz,
CDCl3): ꢁ ¼ 24.4, 55.9, 114.7, 120.0, 122.6, 127.2, 127.5,
128.9, 129.4, 132.2, 134.2, 136.7, 141.6, 156.3, 165.2 ppm;
IR: ꢀꢀ¼ 1690, 1509, 1368, 1261, 1174cmꢁ1
.
N-Phenyl-N-(phenylsulfonyl)benzamide (1a, C19H15NO3S)
Purification by recrystallization (ethyl acetate–n-hexane) af-
forded pure 1a as a colorless powder, mp 123–125ꢂC; yield
N-(3-Chlorophenyl)-N-tosylbenzamide (1f, C20H16ClNO3S)
Purification by recrystallization (ethyl acetate–n-hexane) af-
forded pure 1f as a colorless powder, mp 136–138ꢂC; yield
1
92%; H NMR (500MHz, CDCl3): ꢁ ¼ 7.20 (4H, m), 7.32
1
(4H, m), 7.49 (2H, d, J ¼ 7.5 Hz), 7.57 (2H, m), 7.70 (1H,
m), 7.99 (2H, d, J ¼ 7.5 Hz) ppm; 13C NMR (125 MHz,
95%; H NMR (500MHz, CDCl3): ꢁ ¼ 2.50 (3H, s), 7.05 (1
H, d, J ¼ 8.0 Hz), 7.25 (4H, m), 7.31 (1H, m), 7.37 (3H, m),

238
A. R. Massah et al.
7.48 (2H, d, J ¼ 8.0 Hz), 7.86 (2H, d, J ¼ 8.0 Hz) ppm; 13C
NMR (125 MHz, CDCl3): ꢁ ¼ 21.64, 128.13, 128.52, 129.26,
129.30, 129.34, 129.40, 129.83, 130.40, 132.00, 133.26,
134.53, 134.91, 138.40, 145.07, 160.50; IR: ꢀꢀ¼ 1690, 1583,
filter cake was washed with additional solvent. The combined
filtrates were evaporated and the product was obtained as a
solid or liquid. The work-up method B was used preferentially
for liquid products. The products were obtained very pure and
can be used for the next reaction step without any further
purification.
1375, 1267, 1180, 1086 cmꢁ1
.
N-(4-Chlorophenyl)-N-tosylbenzamide (1g, C20H16ClNO3S)
Purification by recrystallization (ethyl acetate–n-hexane)
afforded pure 1g as a colorless powder, mp 163–165ꢂC;
Step 2. Acylation of N-arylsulfonamides: A mortar was
charged with anhydrous K2CO3 (1 g) and N-arylsulfonamide
(2mmol); the mixture was ground with a pestle and 3,5-dini-
trobenzoyl chloride or 4-nitrobenzoyl chloride (4mmol) was
added to the mixture. The reaction was ground for 1–5 min
and the progress of the reaction was monitored by TLC. After
completion of the reaction, water was added and the product
was collected by filtration through a sintered glass funnel and
washed with additional water. The crude product was purified
by column chromatography on silica gel (60–120 mesh,
EtOAc-petroleum ether) or recrystallized (ethyl acetate-n-
hexane mixed solvent) to afford the products in good to
high yield.
1
yield 96%; H NMR (500 MHz, CDCl3): ꢁ ¼ 2.50 (3H, s),
7.12 (2H, d, J ¼ 8.5 Hz), 7.24 (2H, m), 7.30 (2H, dd, J ¼
8.5, 1.7 Hz), 7.37 (3H, m), 7.47 (2H, d, J ¼ 8.5 Hz), 7.85
(2H, d, J ¼ 8.5 Hz) ppm; 13C NMR (125 MHz, CDCl3):
ꢁ ¼ 24.3, 123.0, 125.8, 127.1, 127.8, 128.9, 129.1, 129.3,
132.5, 134.2, 136.7, 141.6, 165.7 ppm; IR: ꢀꢀ¼ 1688, 1367,
1274, 1167 cmꢁ1
.
N-(4-Acetamidophenylsulfonyl)-N-p-tolylbenzamide
(1h, C22H20N2O4S)
Purification by silica gel column chromatography (ethyl ace-
tate–petroleum ether) afforded pure 1h as a colorless powder,
mp 192–194ꢂC; yield 90%; 1H NMR (500 MHz, CDCl3):
ꢁ ¼ 2.20 (3H, s), 2.34 (3H, s), 7.06 (2H, d, J ¼ 8.0 Hz), 7.11
(2H, d, J ¼ 8.0 Hz), 7.22 (2H, m), 7.35 (1H, m), 7.47 (2H,
d, J ¼ 8.0 Hz), 7.73 (2H, d, J ¼ 8.0 Hz), 7.91 (2H, d, J ¼
8.0 Hz), 9.85 (1, s) ppm; 13C NMR (125MHz, CDCl3):
ꢁ ¼ 21.09, 24.50, 118.70, 128.05, 129.17, 129.88, 130.02,
130.67, 131.77, 132.14, 133.62, 134.43, 139.51, 143.40,
169.31, 170.50ppm; IR: ꢀꢀ¼ 3339, 1710, 1656, 1368, 1254,
4-Nitro-N-phenyl-N-(phenylsulfonyl)benzamide
(3a, C19H14N2O5S)
Purification by silica gel column chromatography (ethyl ace-
tate–petroleum ether) afforded pure 3a as a colorless powder,
mp 192–194ꢂC; yield 70%; 1H NMR (500MHz, CDCl3):
ꢁ ¼ 7.15 (2H, d, J ¼ 7.0), 7.31 (3H, d, J ¼ 7.0), 7.56 (4H,
m), 7.68 (1H, t, J ¼ 7.0), 7.97 (2H, d, J ¼ 8.0), 8.01(2H, d,
J ¼ 8.0 Hz) ppm; 13C NMR (125 MHz, CDCl3): ꢁ ¼ 123.27,
128.87, 129.48, 129.61, 129.85, 130.14, 130.40, 134.27,
136.42, 137.71, 139.54, 149.09, 167.83 ppm; IR: ꢀꢀ¼
1174 cmꢁ1
.
3107, 1696, 1602, 1528, 1374, 1280, 1179, 1092, 581cmꢁ1
.
N-(4-Acetamidophenylsulfonyl)-N-(4-chlorophenyl)-
benzamide (1i, C21H17ClN2O4S)
4-Nitro-N-(phenylsulfonyl)-N-p-tolylbenzamide
Purification by silica gel column chromatography (ethyl
acetate–petroleum ether) afforded pure 1i as brownish white
powder, mp 240–242ꢂC; yield 89%; 1H NMR (500MHz,
acetone-d6): ꢁ ¼ 2.17 (3H, s), 7.29 (4H, m), 7.39 (3H, m),
7.52 (2H, d, J ¼ 7.5 Hz), 7.89 (4H, d, J ¼ 5.0 Hz), 9.79 (1H,
s); 13C NMR (125MHz, acetone-d6): ꢁ ¼ 22.9, 121.9, 123.1,
125.8, 127.5, 128.9, 129.1, 130.0, 132.2, 134.5, 135.3, 141.7,
165.1, 168.9ppm; IR: ꢀꢀ¼ 3347, 1709, 1662, 1367, 1254,
(3b, C20H16N2O5S)
Purification by recrystallization (ethyl acetate–n-hexane) af-
forded pure 3b as a colorless powder, mp 234–236ꢂC; yield
80%; 1H NMR (500MHz, CDCl3): ꢁ ¼ 2.31 (3H, s), 7.02 (2H,
d, J ¼ 7.5 Hz), 7.10 (2H, d, J ¼ 7.5 Hz), 7.56 (4H, m), 7.69
(1H, m), 7.98 (2H, d, J ¼ 8.0 Hz), 8.02 (2H, d, J ¼ 8.0 Hz)
ppm; 13C NMR (125 MHz, CDCl3): ꢁ ¼ 21.14, 123.18,
128.74, 129.45, 130.02, 130.04, 130.21, 133.65, 134.09,
137.74, 139.62, 140.18, 149.01, 167.80 ppm; IR: ꢀꢀ¼
1173 cmꢁ1
.
3108, 1688, 1602, 1529, 1377, 1277, 1117, 1091, 581cmꢁ1
.
General Procedure for the Preparation of N-Aryl-N-3,5-
dinitrobenzoylsulfonamides and N-Aryl-N-4-nitrobenzoyl-
sulfonamides
N-(4-Methoxyphenyl)-4-nitro-N-tosylbenzamide
(3c, C21H18N2O6S)
Purification by recrystallization (ethyl acetate–n-hexane)
afforded pure 3c as a brownish white powder, mp 171–
Step 1. Synthesis of N-arylsulfonamides: An amine (2mmol)
and anhydrous NaHCO3 (1g) were ground together into fine
powder in a mortar, and arylsulfonyl chloride (2mmol) was
added under vigorous stirring with a magnetic stirrer at room
temperature. The progress of the reaction was monitored by
TLC until the conversion of the amine was complete. The
product was obtained by one of the following two work-up
methods: Method A: water was added to the mixture and the
solid sulfonamide was collected by filtration and washed with
additional water. Method B: a suitable solvent such as diethyl
ether was added, the solid base was removed by filtration. The
1
173ꢂC; yield 75%; H NMR (500 MHz, CDCl3): ꢁ ¼ 2.44
(3H, s), 3.73 (3H, s), 6.77 (2H, d, J ¼ 8.0 Hz), 7.03 (2H, d,
J ¼ 8.0 Hz), 7.33 (2H, d, J ¼ 8.0 Hz), 7.56 (2H, d, J ¼
8.0 Hz), 7.84 (2H, d, J ¼ 8.0 Hz), 8.01 (2H, d, J ¼ 8.0 Hz)
ppm; 13C NMR (125 MHz, CDCl3): ꢁ ¼ 21.74, 55.46,
114.72, 123.24, 128.77, 129.47, 129.51, 130.03, 131.57,
134.71, 139.92, 145.38, 148.95, 160.35, 167.89 ppm; IR:
ꢀꢀ¼ 3111, 1689, 1603, 1517, 1365, 1286, 1252, 1173,
1034, 578 cmꢁ1
.

One-pot Sulfonylation and Acylation of Primary Arylamines under Solvent-Free Conditions
239
d, J ¼ 7.5 Hz), 8.57 (2H, s), 8.94 (1H, s) ppm; 13C NMR
(125 MHz, CDCl3): ꢁ ¼ 55.58, 115.25, 121.02, 128.10, 128.98,
129.04, 129.56, 131.50, 134.53, 137.21, 137.38, 148.06,
160.83, 165.12 ppm; IR: ꢀꢀ¼ 3092, 1693, 1627, 1547, 1348,
N-(2,4-Dimethylphenyl)-4-nitro-N-tosylbenzamide
(3d, C22H20N2O5S)
Purification by recrystallization (ethyl acetate–n-hexane) af-
forded pure 3d as a colorless powder, mp 172–174ꢂC; yield
75%; 1H NMR (500MHz, CDCl3): ꢁ ¼ 2.19 (3H, s), 2.27 (3H,
s), 2.47 (3H, s), 6.97 (3H, m), 7.37 (2H, d, J ¼ 6.0 Hz), 7.47
(2H, d, J ¼ 6.0Hz), 7.96 (2H, d, J ¼ 6.0Hz), 8.00 (2H, d,
J ¼ 6.0 Hz) ppm; 13C NMR (125 MHz, CDCl3): ꢁ ¼ 18.37,
21.14, 21.77, 123.10, 127.86, 129.33, 129.48, 129.78, 130.79,
132.54, 132.82, 135.35, 137.75, 140.08, 140.52, 145.51,
148.86, 167.76 ppm; IR: ꢀꢀ¼ 3100, 1690, 1602, 1522, 1367,
1255, 1176, 1096, 572 cmꢁ1
.
N-(4-Chlorophenyl)-3,5-dinitro-N-(phenylsulfonyl)-
benzamide (4b, C19H12ClN3O7S)
Purification by recrystallization (ethyl acetate–n-hexane) af-
forded pure 4b as brownish white powder, mp 215–217ꢂC;
yield 84%; 1H NMR (500MHz, CDCl3): ꢁ ¼ 7.15 (2H, d,
J ¼ 8.5 Hz), 7.35 (2H, d, J ¼ 8.5 Hz), 7.60 (2H, m), 7.75
(1H, m), 7. 95 (2H, d, J ¼ 7.5 Hz), 8.59 (2H, d, J ¼ 2.0 Hz),
9.00 (1H, s) ppm; 13C NMR (125MHz, CDCl3): ꢁ ¼ 121.40,
128.96, 129.13, 129.55, 130.37, 131.42, 134.34, 134.81,
136.89, 136.97, 148.21, 164.97 ppm; IR: ꢀꢀ¼ 3098, 1699,
1287, 1172, 1092, 581 cmꢁ1
.
N-(3-Chlorophenyl)-4-nitro-N-tosylbenzamide
(3e, C20H15ClN2O5S)
Purification by recrystallization (ethyl acetate–n-hexane) af-
forded pure 3e as a colorless powder, mp 152–154ꢂC; yield
81%; 1H NMR (500 MHz, CDCl3): ꢁ ¼ 2.47 (3H, s), 7.01
(1H, d, J ¼ 7.0 Hz), 7.23 (2H, m), 7.31 (1H, d, J ¼ 7.5 Hz),
7.36 (2H, d, J ¼ 7.5 Hz), 7.58 (2H, d, J ¼ 8.0 Hz), 7.83
(2H, d, J ¼ 7.5 Hz), 8.05 (2H, d, J ¼ 8.0 Hz) ppm; 13C NMR
(125 MHz, CDCl3): ꢁ ¼ 21.78, 123.44, 128.63, 129.53,
129.61, 130.07, 130.34, 130.48, 134.42, 135.10, 137.54,
139.27, 145.79, 149.25, 167.54 ppm; IR: ꢀꢀ¼ 3125, 1692,
1627, 1547, 1373, 1249, 1156, 1090, 586cmꢁ1
.
N-Benzyl-3,5-dinitro-N-(phenylsulfonyl)benzamide
(4c, C20H15N3O7S)
Purification by silica gel column chromatography (ethyl
acetate–petroleum ether) afforded pure 4c as a colorless pow-
der, mp 188–190ꢂC; yield 70%; 1H NMR (500MHz, DMSO-
d6): ꢁ ¼ 5.05 (2H, s), 7.28 (5H, m), 7.58 (2H, s), 7.78 (3H, m),
8.46 (2H, s), 8.88 (1H, s) ppm; 13C NMR (125MHz, DMSO-
d6): ꢁ ¼ 51.04, 118.53, 120.79, 127.27, 127.41, 127.76,
128.19, 128.70, 129.62, 134.81, 136.35, 137.22, 137.91,
147.74, 166.90ppm; IR: ꢀꢀ¼ 3086, 1686, 1626, 1547, 1349,
1587, 1527, 1369, 1283, 1171, 1091, 590 cmꢁ1
.
N-(Naphthalen-1-yl)-4-nitro-N-tosylbenzamide
(3f, C24H18N2O5S)
1171, 722, 596 cmꢁ1
.
Purification by recrystallization (ethyl acetate–n-hexane) af-
forded pure 3f as a colorless powder, mp 172–174ꢂC; yield
91%; 1H NMR (500MHz, CDCl3): ꢁ ¼ 2.46 (3H, s), 7.28 (1H,
d, J ¼ 7.0 Hz), 7.34 (3H, m), 7.40 (2H, d, J ¼ 8.5 Hz), 7.50
(1H, m), 7.58 (1H, m), 7.80 (3H, m), 7.98 (3H, m), 8.02 (1H,
d, J ¼ 8.5 Hz); 13C NMR (125 MHz, CDCl3): ꢁ ¼ 21.80,
122.91, 123.17, 125.18, 127.04, 128.09, 128.64, 128.70,
129.45, 129.53, 130.06, 131.00, 132.20, 133.03, 134.41,
134.82, 139.99, 145.75, 148.77, 168.45 ppm; IR: ꢀꢀ¼
3,5-Dinitro-N-p-tolyl-N-tosylbenzamide (4d, C21H17N3O7S)
Purification by recrystallization (ethyl acetate–n-hexane) af-
forded pure 4d as a colorless powder, mp 173–175ꢂC; yield
80%; 1H NMR (500MHz, CDCl3): ꢁ ¼ 2.31 (3H, s), 2.48
(3H, s), 7.07(2H, d, J ¼ 7.5 Hz), 7.15 (2H, d, J ¼ 7.5 Hz),
7.37 (2H, d, J ¼ 7.5 Hz), 7.83 (2H, d, J ¼ 7.5 Hz), 8.55 (2H,
s), 8.92 (1H, s) ppm; 13C NMR (125MHz, CDCl3): ꢁ ¼ 21.12,
21.69, 120.86, 128.93, 129.50, 129.98, 130.60, 133.22,
134.22, 137.37, 140.79, 145.75, 147.93, 165.01 ppm; IR:
3066, 1690, 1596, 1528, 1360, 1293, 1172, 1078, 581 cmꢁ1
.
ꢀꢀ¼ 3087, 1676, 1629, 1549, 1347, 1159, 1085, 568 cmꢁ1
.
N-(4-Acetamidophenylsulfonyl)-4-nitro-N-phenylbenzamide
(3g, C21H17N3O6S)
N-(2-Methoxyphenyl)-3,5-dinitro-N-tosylbenzamide
Purification by silica gel column chromatography (ethyl ace-
tate–petroleum ether) afforded pure 3g as a brownish white
powder, mp 202–204ꢂC; yield 90%; 1H NMR (500MHz,
CDCl3): ꢁ ¼ 2.11 (3H, s), 7.33 (5H, m), 7.67 (2H, d, J ¼
8.0 Hz), 7.86 (4H, m), 8.03 (2H, d, J ¼ 8.0 Hz), 10.52 (1H, s)
ppm; 13C NMR (125MHz, CDCl3): ꢁ ¼ 24.16, 118.37, 123.19,
129.35, 129.66, 129.75, 130.26, 130.49, 130.74, 135.79,
139.76, 144.64, 148.47, 167.60, 169.29 ppm; IR: ꢀꢀ¼ 3368,
(4e, C21H17N3O8S)
Purification by recrystallization (ethyl acetate–n-hexane) af-
forded pure 4e as a colorless powder, mp 186–188ꢂC; yield
95%; 1H NMR (500MHz, CDCl3): ꢁ ¼ 2.48 (3H, s), 3.64 (3H,
s), 6.79 (1H, s), 6.97 (1H, s), 7.36 (4H, s), 7.91 (2H, s), 8.56
(2H, s), 8.89 (1H, s) ppm; 13C NMR (125MHz, CDCl3):
ꢁ ¼ 21.73, 55.55, 112.21, 120.62, 121.64, 124.83, 128.10,
129.27, 129.67, 131.89, 132.33, 135.06, 137.81, 145.53,
147.80, 155.25, 165.52 ppm; IR: ꢀꢀ¼ 3100, 1701, 1596,
3110, 1705, 1683, 1588, 1526, 1369, 1167, 1087, 576 cmꢁ1
.
1549, 1501, 1360, 1260, 1179, 575 cmꢁ1
.
N-(4-Methoxyphenyl)-3,5-dinitro-N-(phenylsulfonyl)-
benzamide (4a, C20H15N3O8S)
N-(4-Acetamidophenylsulfonyl)-N-(2,4-dimethylphenyl)-3,5-
dinitrobenzamide (4f, C23H20N4O8S)
Purification by silica gel column chromatography (ethyl ace-
tate–petroleum ether) afforded pure 4a as brownish white
powder, mp 202–204ꢂC; yield 73%; 1H NMR (500MHz,
CDCl3): ꢁ ¼ 3.78 (3H, s), 6.84 (2H, d, J ¼ 8.5 Hz), 7.10
(2H, d, J ¼ 8.5 Hz), 7.58 (2H, m), 7.72 (1H, m), 7.96 (2H,
Purification by silica gel column chromatography (ethyl ace-
tate–petroleum ether) afforded pure 4f as brownish white
powder, mp 255–257ꢂC; yield 86%; 1H NMR (500 MHz,

240
A. R. Massah et al.: One-pot Sulfonylation and Acylation of Primary Arylamines under Solvent-Free Conditions
DMSO-d6): ꢁ ¼ 2.05 (3H, s), 2.11 (3H, s), 2.21 (3H, s), 7.06
(2H, m), 7.28 (1H, d, J ¼ 6.0 Hz), 7.89 (4H, m), 8.46 (2H, s),
8.73 (1H, s), 10.57 (1H, s) ppm; 13C NMR (125 MHz, DMSO-
d6): ꢁ ¼ 17.79, 20.53, 24.14, 118.31, 120.91, 127.85, 128.21,
128.33, 130.42, 130.66, 131.03, 132.04, 132.20, 136.30,
137.52, 140.14, 144.87, 147.44, 164.87, 169.31 ppm; IR:
ꢀꢀ¼ 3398, 3089, 1712, 1680, 1589, 1544, 1345, 1165, 1087,
[8] Ishizuka N, Matsumura KI, Hayashi K, Sakai K,
Yamamori T (2000) Synthesis 6: 784
[9] Martin MT, Roschangar F, Eaddy JF (2003) Tetrahedron
Lett 44: 5461
[10] Singh DU, Singh PR, Samant SD (2004) Tetrahedron
Lett 45: 4805
[11] Katritzky AR, Hoffmann S, Suzuki K (2004) Arkivoc
12: 14
572 cmꢁ1
.
[12] Liu DG, Gao Y, Voigt JH, Lee K, Nicklaus MC, Wu L,
Zhang ZY, Bruke TR (2003) Bioorg Med Chem Lett 13:
3005
Acknowledgements
[13] Sturino CF, Labelle M (1998) Tetrahedron Lett 39:
5891
[14] Johnson DC, Widlanski TS (2002) Synthesis 8:
809
We thank Dr. Taki for his kind help and also partial financial
support of Islamic Azad University of Shahreza Research
Council.
[15] Ohno M, Yoshioka M, Nakai H (1984) J Am Chem Soc
106: 1133
[16] Weinreb SM, Sisko J (1991) J Org Chem 56: 3210
[17] Ellis D (2001) Tetrahedron Asymm 12: 1589
[18] Thakur M, Thakur A, Khadikar PV, Supuran CT (2005)
Bioorg Med Chem Lett 15: 203
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