Synthesis of new dihydropyrrol-2-one derivatives bearing sulfonamide groups and studies their antibacterial activity

Article abstract of DOI:10.1007/s00706-016-1847-y

Abstract: A novel series of dihydropyrrol-2-one compounds bearing sulfonamide groups were synthesized and assayed for in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Streptococcus epidermidis bacteria. Antibacterial results showed that most of the compounds exhibited the antibacterial activity against P. aeruginosa and S. epidermidis and displayed no inhibition against S. aureus and E. coli. Interestingly, most of the screened compounds were more active than the reference drug trimethoprim-sulfamethoxazole against P. aeruginosa. Among them, one compound exhibited good antibacterial activity in comparison with the reference drugs against P. aeruginosa and may make it as potential an antibacterial agent. Graphical abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s00706-016-1847-y

Monatsh Chem
DOI 10.1007/s00706-016-1847-y
ORIGINAL PAPER
Synthesis of new dihydropyrrol-2-one derivatives bearing
sulfonamide groups and studies their antibacterial activity
1
1
2
Masoume Bavadi
•
Khodabakhsh Niknam
•
Marzieh Gharibi
Received: 3 June 2016 / Accepted: 1 September 2016
Ó Springer-Verlag Wien 2016
Abstract A novel series of dihydropyrrol-2-one compounds
bearing sulfonamide groups were synthesized and assayed
for in vitro antibacterial activity against Staphylococcus
aureus, Escherichia coli, Pseudomonas aeruginosa, and
Streptococcus epidermidis bacteria. Antibacterial results
showed that most of the compounds exhibited the antibac-
terial activity against P. aeruginosa and S. epidermidis and
displayed no inhibition against S. aureus and E. coli. Inter-
estingly, most of the screened compounds were more active
than the reference drug trimethoprim-sulfamethoxazole
against P. aeruginosa. Among them, one compound exhib-
ited good antibacterial activity in comparison with the
reference drugs against P. aeruginosa and may make it as
potential an antibacterial agent.
Keywords Synthesis Á Dihydropyrrol-2-one Á
Antibacterial activity Á Sulfonamide Á Reference drug
Introduction
Dihydropyrrol-2-one (c-lactam) derivatives have attracted a
significant attention because of their existence in many
natural biologically active compounds, pharmaceutical
molecules [1–3]. For example, pyrrocidine A (1; Fig. 1) is a
potential antibiotic isolated from the fermentation broth of a
fungus (LL-Cyan426) [4]. Quinolactacins A (2) and B (3)
were obtained from the cultured broth of Penicillium sp.
EPF-6 and have been found to inhibit tumor necrosis factor
production [5]. Microcolins A (4) and B (5) were isolated
from blue–green alga Lyngbya majuscule in 1992 by Kohen
and co-workers [6], and have been shown to possess
immunosuppressive and antiproliferative properties [7–9].
Violacein (6), a natural product, possesses antibiotic and
antitumor activities which were extracted from the gram-
negative bacterium Chromobacterium violaceum [10].
Graphical abstract
5
-(4-Chlorophenyl)-4-(furan-2-carbonyl)-3-hydroxy-1-(6-
methoxybenzothiazol-2-yl)-1,5-dihydropyrrol-2-one (7)
inhibited ASK1 with an IC50 of 4.2 lM [2b]. Moreover,
several other natural products containing pyrrol-2-one
moiety include jatropham [11], talaroconvolutin A [12],
oteromycin [13], and (Z)-pulchellalactam [14]. In addition,
pyrrol-2-one and its derivatives have been used as anti-
influenza [15], DNA polymerase inhibitors [16], HIV
integrase [17, 18], herbicidals [19], and anti-cancer [20].
Sulfonamides are extremely important class of com-
pounds in medicinal chemistry, with a broad spectrum of
biological activities, including anti-cancer [21], antibacte-
rial [22, 23], antimalarial [24], anti-inflammatory [25, 26],
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-016-1847-y) contains supplementary
material, which is available to authorized users.
&
Khodabakhsh Niknam
niknam@pgu.ac.ir
1
2
Department of Chemistry, Faculty of Sciences, Persian Gulf
University, Bushehr 75169, Iran
Department of Microbiology, Food and Drug Deputy,
Bushehr University of Medical Sciences, Bushehr, Iran
123

M. Bavadi et al.
Fig. 1 The biologically active
compounds containing the
pyrrol-2-one moiety
antihypertensive [27], anticonvulsant, herbicidal properties
for their antibacterial activities against gram-positive and
gram-negative bacteria.
[
28, 29], and also as protecting groups [30]. Furthermore,
compounds bearing a sulfonamide moiety have been ther-
apeutically utilized as antibacterial agents for many
decades. Sulfonamides are also known as inhibitors the
activity of the enzymes, such as dihydropteroate synthase
Results and discussion
(
DHPS) [31], matrix metalloproteinase [32], and carbonic
The preparation of the sulfonamide derivatives 12a–12e
has been carried out according to the steps shown in
Scheme 1. In the first step, the reaction of p-anisidine (8)
with acetic anhydride afforded N-(4-methoxyphenyl)ac-
etamide (9), which was further subjected to
chlorosulfonylation reaction to give compound 10. The
reaction of synthesized arylsulfonyl chloride with various
anhydrase (CA) [33].
Recently, a series of drugs with a sulfonamide structure
have been reported, such as sulfonamide KCN1 (used as an
antitumor agent), the HIV protease inhibitor amprenavir
(
[
used for the treatment of AIDS and HIV infections)
34–36], sulfonamide drugs as acetazolamide AZA, and
methazolamide MZA (mainly used as anti-glaucoma
agents) [37–39] (Fig. 2). However, due to the rapid
appearance microbial resistance in humans and some ani-
mals, the researchers are necessary to discover and develop
novel effective sulfonamide drugs.
amines in the presence of anhydrous NaHCO under sol-
3
vent-free condition at room temperature and then
hydrolysis afforded the compounds 12a–12e in high yields
and purity. The structures of the synthesized compounds
1
13
were characterized by IR, H NMR, and C NMR. The IR
According to the above facts, and in continuation of our
studies on synthesis of dihyropyrrol-2-one compounds
spectra of the sulfonamide derivatives 12a–12e revealed
clearly the presence of the absorption bands for the NH ,
2
1
SO NH, and SO functions (Fig. 3). The H NMR spectra
[
40], we designed a new series of dihyropyrrol-2-one
2
2
compounds bearing sulfonamide groups and elevated them
of these compounds also exhibited sharp signals in and
1
23

Synthesis of new dihydropyrrol-2-one derivatives bearing sulfonamide groups and studies…
Fig. 2 Structure of some sulfonamides
Scheme 1
Fig. 3 IR spectrum of
compound 12a
around 5 ppm and 9.45–10.00 ppm (except 12e) which
were related to the NH and SO NH groups, respectively
The synthesis of dihydropyrrol-2-one compounds bear-
1
ing sulfonamide groups confirmed fully by IR, H NMR,
2
2
1
3
1
C NMR, and mass spectral data. For example, the H
(
Fig. 4).
Reaction between synthesized aniline bearing sulfon-
NMR spectrum of compound 15d displayed three signals,
one at 8.31 ppm assigned to the NH group and another two
broad singlets in the regions 9.77–9.84 ppm due to NH
protons of sulfonamide moiety which disappeared on
deuteration. The vinylic, aliphatic, and aromatic protons
amide derivatives 12a–12e, aldehydes, and ethyl pyruvate
under catalyst-free and solvent-free conditions led to the
synthesis of novel dihydropyrrol-2-one compounds bearing
sulfonamide groups 15a–15k (Scheme 2; Table 1).
123

M. Bavadi et al.
1
Fig. 4 H NMR spectrum of
compound 12a
Scheme 2
Table 1 Preparation of various dihyropyrrol-2-one derivatives 15a–15k
a
Entry
Aniline derivative
R–CHO (13)
Product
Time/min
Yield/%
1
2
3
4
5
6
7
8
9
12a (G = C
12b (G = 4-Cl-C
12c (G = 4-Me-C
12d (G = 3,4-Me
12e (G = morpholino)
6
H
5
)
C
C
C
C
C
6
6
6
6
6
H
H
H
H
H
5
5
5
5
5
–
–
–
–
–
15a
15b
15c
15d
15e
15f
15g
15h
15i
30
35
30
30
55
45
60
20
40
20
30
80
84
83
79
81
80
67
75
59
78
84
6 4
H )
6 4
H )
2 6 3
-C H )
12b (G = 4-Cl-C
12b (G = 4-Cl-C
6
H
4
)
)
3-Cl-C
6
H
4
6
4
4
–
H
6 4
4-MeO-C
H
4
–
12c (G = 4-Me-C
12c (G = 4-Me-C
12c (G = 4-Me-C
12c (G = 4-Me-C
6 4
H
6 4
H
6 4
H
6 4
H
)
3-Cl-C
4-Cl-C
6
H
H
–
)
)
)
6
–
1
1
a
0
4-Me-C
6
H
4
–
15j
15k
1
CH CH CH –
2 2
3
Isolated yield
1
23

Synthesis of new dihydropyrrol-2-one derivatives bearing sulfonamide groups and studies…
1
Fig. 5 H NMR spectrum of
compound 15d
Table 2 Antimicrobial data of the dihyropyrrol-2-one compounds bearing sulfonamide derivatives 15a–15k
Compound
Name of bacteria
Gram-positive bacteria
S. aureus
Gram-negative bacteria
S.e
P. aeruginosa
E. coli
a
Diameter of zone of inhibition /mm
1
1
1
1
1
1
1
1
1
1
1
5a
5b
5c
5d
5e
5f
–
–
–
–
–
–
–
–
–
–
–
–
–
35
–
–
12, 14, 15
9, 10, 14
15, 16, 17
7, 8, 12
8, 10, 13
9, 9, 11
11, 12, 12
9, 11, 13
9, 12, 13
12, 13, 14
12, 12, 14
14
–
12, 13, 13
–
10, 11, 12
–
–
–
–
–
12, 13, 15
–
5g
5h
5i
9, 10, 11
–
–
–
10, 15, 16
–
5j
–
–
5k
7, 15, 16
–
Chloramphenicol
Ampicillin
33
20
27
–
20
12
30
–
13
Trimethoprim-sulfamethoxazole
DMSO
–
–
–
, resistant
a
3
Zone of inhibition was measured in mm at concentrations 1000, 2000, and 3000 lg/cm
1
were observed at expected chemical shifts (Fig. 5). The H
were appeared at 5.99 and 6.03 ppm as doublet
(J = 2.4 Hz), and aromatic protons were observed at
expected chemical shifts. In addition, the NH proton of
dihydropyrrol-2-one ring and the NH of sulfonamide
NMR spectrum of compound 15g showed three singlets at
3
.73, 3.81, and 3.82 ppm for methoxy protons. The ali-
phatic and vinylic protons of dihydropyrrol-2-one ring
123

M. Bavadi et al.
protons were observed as one sharp signal and two broad
singlets at 8.32 and 10.20–10.29 ppm, respectively.
All the synthesized compounds were evaluated for their
antibacterial activity against gram-positive bacteria,
gram-negative bacteria. Chloramphenicol, ampicillin, and
sulfonamide, such as trimethoprim-sulfamethoxazole
were used as reference drugs, the solvent DMSO as the
control, and the results were summarized in Table 2. The
results indicated that most of the tested compounds were
active against both P. aeruginosa and S. epidermidis
bacteria and displayed no activity against S. aureus and
E. coli bacteria.
spectroscopy (Shimadzu FT-IR 8300 spectrophotometer)
was employed for the characterization of the products.
Melting points determined in open capillary tubes in a
Barnstead Electrothermal 9100 BZ circulating oil melt-
ing point apparatus. The reaction monitoring was
accomplished by TLC on silica gel PolyGram SILG/
UV254 plates. The American-Type Culture Collection
(ATCC) strains of Staphylococcus aureus (ATCC
25923), Staphylococcus epidermidis (ATCC 14990),
Pseudomonas aeruginosa (ATCC 27853), and Escher-
ichia coli (ATCC 25922) were examined as test
microorganisms. These microorganisms were purchased
from the Iranian Research Organization for Science and
Technology, Tehran, Iran. The Mueller–Hinton agar was
purchased from Merck, Darmstadt, Germany. Commer-
cially available drugs, such as Chloramphenicol (30 lg),
Ampicillin (10 lg), and trimethoprim-sulfamethoxazole
(1.25/23.75 lg), were purchased from Padtanteb com-
pany, Iran.
It can be observed from Table 2 that the standard
drug trimethoprim-sulfamethoxazole was totally inac-
tive particularly toward P. aeruginosa, while most of
these compounds showed a promising antibacterial
activity. Among the screened compounds against P.
aeruginosa, compound 15c demonstrated antibacterial
activity with greater zone of inhibition compare to the
standard drugs. Compound 15e bearing morpholine
substitution on the sulfonamide moiety showed
antibacterial activity almost equivalent to the standard
drug ampicillin toward P. aeruginosa and displayed no
inhibition against S. epidermidis. The compounds 15a,
General procedure for the synthesis
of N-(4-methoxyphenyl)acetamide (9)
3
p-Aanisidine (0.123 g, 1 mmol) and 0.2 cm acetic anhy-
1
5d, 15h, and 15j were totally inactive, and the
remaining compounds exhibited lower antibacterial
dride (2 mmol) were grinded in a mortar at room
temperature. The grinding was continued for 30 more s,
and the progress of the reaction was monitored by TLC.
activity toward S. epidermidis.
3
After the completion of the reaction, 10 cm water was
added to the mixture and the product collected by filtration
and washed with additional water.
Conclusion
In this study, a series of new dihydropyrrol-2-one com-
pounds bearing sulfonamide groups were successfully
prepared in high yields. These compounds screened for
in vitro antibacterial activity against gram-positive and
gram-negative bacteria. According to obtained results,
most of the compounds demonstrated antibacterial activity
against both P. aeruginosa and S. epidermidis bacteria and
showed no activity against S. aureus and E. coli bacteria.
General procedure for the synthesis of 5-acetamido-
2-methoxybenzene-1-sulfonyl chloride (10)
3
Chlorosulfonic acid (1 cm ) was added dropwise to
0.165 g N-(4-methoxyphenyl)acetamide (1 mmol) at
0 °C during 30 min. After addition was complete, the
reaction mixture was stirred for 2 h at room temperature.
Then, the solution was poured in crushed ice and the
obtained solid was filtered and washed with excess water
and dried.
Experiment
General procedure for the synthesis
of N-arylsulfamoylacetamides 11
Chemicals were purchased from Merck and Aldrich
Chemical Companies and use as is. The products were
characterized by the comparison of their spectral and
physical data with those reported in the literature. For
A mixture of amine (1 mmol), anhydrous NaHCO3
(1 mmol), and 0.263 g arylsulfonyl chloride (1 mmol) was
1
grinded in a mortar. The reaction was ground for 5–10 min,
and the progress of the reaction was monitored by TLC.
3
After the completion of the reaction, 10 cm water was
recorded H NMR spectra, we were used Bruker
(
400 MHz) Avance Ultrashield in pure DMSO-d and
6
CDCl solvents with tetramethylsilane (TMS) as internal
3
added and the product collected by filtration and washed
with additional water [41].
standards. Mass spectra were recorded on a FINNIGAN-
MAT 8430 mass spectrometer operating at 70 eV. FT-IR
1
23

Synthesis of new dihydropyrrol-2-one derivatives bearing sulfonamide groups and studies…
1
3
General procedure for the synthesis
of N-arylbenzenesulfonamides 12
C NMR (100 MHz, DMSO-d ): d = 56.8, 63.1, 109.1,
6
113.8, 114.4, 119.1, 119.2, 120.7, 121.3, 123.8, 123.9,
1
24.4, 126.2, 126.8, 127.8, 128.0, 128.4, 128.7, 129.3,
3
A mixture of compound 11a–11e, 1 cm HCl, and 0.5 cm
3
129.4, 129.9, 132.7, 132.8 135.4, 135.5, 137.1, 137.3,
distilled water was refluxed for 6 h. The progress of the
reaction was monitored by TLC. After the completion of
the reaction, the reaction mixture was cooled to room
temperature, and then, pH was adjusted to 7 with sodium
bicarbonate at 0–5 °C. The residue was extracted with
ethyl acetate and the solvent concentrated under reduced
pressure, to give compounds 12a–12e in good yields.
137.4, 137.8, 150.7, 153.5, 166.6 ppm; MS (70 eV): m/z
?
(%) = 767.6 (M , 0.01), 765.1 (M , 0.04), 603.7 (1.1),
2
?
293.1 (6.2), 63.0 (100).
2-Methoxy-5-[[1-[4-methoxy-3-[N-(p-tolyl)sulfamoyl]-
phenyl]-2-oxo-5-phenyl-2,5-dihydro-1H-pyrrol-3-yl]a-
mino]-N-(p-tolyl)benzenesulfonamide
(
15c, C H N O S )
38 36 4 7 2
White cream solid; m.p.: [250 °C; IR (KBr): mꢀ = 3425,
General procedure for the synthesis
of N-(4-methoxyphenyl)-acetamides 15
-1 1
266 (N–H), 1687 (N–C=O), 1331, 1161 (SO ) cm ; H
3
2
NMR (400 MHz, DMSO-d ): d = 2.12 (s, 3H, CH ), 2.16
6
3
(
s, 3H, CH ), 3.82 (s, 3H, OCH ), 3.83 (s, 3H, OCH ), 6.01
3 3 3
A mixture of aldehyde (1 mmol), sulfonamide derivatives
(s, 2H, CH, =CH), 6.86–6.98 (m, 8H, Ar), 7.07–7.11 (m,
1
2 (2 mmol), and ethyl pyruvate (1 mmol) was heated with
2
7
H, Ar), 7.18–7.20 (m, 2H, Ar), 7.25–7.32 (m, 3H, Ar),
stirring in an oil bath at 110 °C under catalyst-free and
solvent-free conditions. The progress of the reaction was
monitored by TLC. After the completion of the reaction,
the crude product was washed with warm ethanol.
.44 (dd, 1H, J = 8.8, J = 2.8 Hz, Ar), 7.64 (d, 1H,
1
2
J = 2.8 Hz, Ar), 7.69 (dd, 1H, J = 8.8, J = 2.8 Hz, Ar),
1
2
8
.04 (d, 1H, J = 2.8 Hz, Ar), 8.28 (s, 1H, NH), 9.82–9.87
1
brs, 2H, 2 9 SO NH) ppm; C NMR (100 MHz, DMSO-
3
(
2
2
-Methoxy-5-[[1-[4-methoxy-3-(N-phenylsulfa-
d6): d = 20.7, 20.7, 56.7, 56.8, 63.0, 108.9, 113.6, 114.3
119.3, 119.6, 120.3, 123.8, 124.4, 126.7, 127.1, 127.3,
128.4, 129.3, 129.8, 129.9, 132.8, 132.9, 133.3, 135.4,
135.5, 135.6, 137.8, 150.8, 153.5, 166.6 ppm; MS (70 eV):
moyl)phenyl]-2-oxo-5-phenyl-2,5-dihydro-1H-pyrrol-3-
yl]amino]-N-phenylbenzenesulfonamide
(
15a, C H N O S )
36 32 4 7 2
?
White solid; m.p.: 187–189 °C; IR (KBr): mꢀ = 3334, 3265
m/z (%) = 724.1 (M , 0.06), 384.2 (11.4), 293.1 (100),
-1 1
N–H), 1687 (N–C=O), 1336, 1161 (SO ) cm ; H NMR
(
236.1 (19.8), 57.1 (28.3).
2
(
400 MHz, DMSO-d ): d = 3.81 (s, 3H, OCH ), 3.82 (s,
H, OCH ), 6.02 (s, 2H, CH, =CH), 6.90–6.97 (m, 4H, Ar),
3
6
3
N-(3,4-Dimethylphenyl)-5-[[1-[3-[N-(3,4-dimethylphenyl)-
sulfamoyl]-4-methoxyphenyl]-2-oxo-5-phenyl-2,5-dihydro-
3
7
.07–7.16 (m, 8H, Ar), 7.19–7.22 (m, 2H, Ar), 7.25–7.32
1H-pyrrol-3-yl]amino]-2-methoxybenzenesulfonamide
(
m, 3H, Ar), 7.45 (dd, 1H, J = 8.8, J = 2.8 Hz, Ar),
1 2
(
15d, C H N O S )
4
0 40 4 7 2
7
.67–7.73 (m, 2H, Ar), 8.08 (d, 1H, J = 2.8 Hz, Ar), 8.32
White cream solid; m.p.: [250 °C; IR (KBr): mꢀ = 3389,
(
s, 1H, NH), 10.00 (s, 1H, SO NH), 10.08 (s, 1H, SO NH)
2 2
-1 1
279 (N–H), 1707 (N–C=O), 1322, 1158 (SO ) cm ; H
3
1
3
2
ppm; C NMR (100 MHz, DMSO-d ): d = 56.7, 56.8,
6
NMR (400 MHz, DMSO-d ): d = 2.01 (s, 3H, CH ), 2.02
6
3
6
1
1
1
0
5
3.0, 108.9, 113.7, 114.3, 119.1, 119.2, 119.9, 123.7,
23.8, 124.1, 124.3, 127.2, 127.3, 128.4, 129.3, 129.4,
29.9, 132.9, 135.5, 137.8, 138.2, 138.3, 138.4, 150.8,
(s, 3H, CH ), 2.07 (s, 6H, 2 9 CH ), 3.82 (s, 3H, OCH ),
3 3 3
3
1
7
1
8
.84 (s, 3H, OCH ), 6.01 (s, 2H, CH, =CH), 6.69–6.72 (m,
3
H, Ar), 6.77–6.87 (m, 6H, Ar), 7.07–7.11 (m, 2H, Ar),
.18–7.19 (m, 2H, Ar), 7.23–7.29 (m, 3H, Ar), 7.44 (dd,
H, J = 8.8, J = 2.4 Hz, Ar), 7.64–7.67 (m, 2H, Ar),
?
53.5, 166.6 ppm; MS (70 eV): m/z (%) = 695.8 (M ,
.2), 603.7 (5.8), 368.4 (8.5), 293.1 (16.8), 236.3 (11.2),
7.1 (100).
1
2
.09 (d, 1H, J = 2.8 Hz, Ar), 8.31 (s, 1H, NH), 9.77–9.84
1
3
N-(4-Chlorophenyl)-5-[[1-[3-[N-(4-chlorophenyl)sulfa-
moyl]-4-methoxyphenyl]-2-oxo-5-phenyl-2,5-dihydro-
(brs, 2H, 2 9 SO NH) ppm; C NMR (100 MHz, DMSO-
2
d6): d = 19.0, 19.1, 19.9, 20.0, 56.7, 56.8, 63.0, 108.8,
113.6, 114.3, 116.9, 117.7, 119.2, 119.3, 120.9, 121.5,
123.7, 123.8, 124.4, 126.8, 127.1, 127.3, 128.4, 129.3,
129.9, 130.2, 131.7, 132.1, 132.8, 132.9, 135.3, 135.4,
135.7, 135.8, 137.1, 137.9, 150.8, 153.5, 166.6 ppm; MS
1
H-pyrrol-3-yl]amino]-2-methoxybenzenesulfonamide
(
15b, C H Cl N O S )
3
6
30
2 4 7 2
White solid; m.p.: 220–222 °C; IR (KBr): mꢀ = 3444, 3275
-
1 1
N–H), 1698 (N–C=O), 1330, 1159 (SO ) cm ; H NMR
(
2
?
(
400 MHz, DMSO-d ): d = 3.80 (s, 3H, OCH ), 3.81 (s,
(70 eV): m/z (%) = 751.0 (M , 0.1), 603.7 (3.2), 368.4
6
3
3
H, OCH ), 6.03 (d, 1H, J = 2.4 Hz, CH), 6.08 (d, 1H,
3
(8.8), 236.2 (15.3), 57.1 (100).
1
J = 2.4 Hz, = CH), 6.98–6.99 (m, 2H, Ar), 7.06–7.32 (m,
H NMR (400 MHz, DMSO-d and two drops of D O):
6
2
1
7
8
3H, Ar), 7.48 (dd, 1H, J = 8.8, J = 2.8 Hz, Ar),
1
d = 1.96 (s, 3H, CH ), 1.97 (s, 3H, CH ), 2.03 (s, 3H,
CH ), 2.08 (s, 3H, CH ), 3.75 (s, 3H, OCH ), 3.82 (s, 3H,
3 3 3
2
3
3
.70–7.75 (m, 2H, Ar), 8.07 (d, 1H, J = 2.8 Hz, Ar),
.35 (s, 1H, NH), 10.20–10.25 (2H, brs, 2 9 SO NH) ppm;
2
OCH ), 5.90 (s, 1H, CH), 5.93 (s, 1H, =CH), 6.66–6.68 (m,
3
123

M. Bavadi et al.
1
7
H, Ar), 6.73–6.85 (m, 6H, Ar), 7.04–7.08 (m, 2H, Ar),
.11–7.12 (m, 2H, Ar), 7.23–7.25 (m, 3H, Ar), 7.36 (d, 1H,
Ar), 6.97–6.99 (m, 2H, Ar), 7.09–7.18 (m, 8H, Ar),
7.20–7.24 (m, 2H, Ar), 7.48 (dd, 1H, J1 = 8.8,
J2 = 2.4 Hz, Ar), 7.70 (d, 1H, J = 2.8 Hz, Ar), 7.77 (dd,
1H, J = 8.8, J = 2.8 Hz, Ar), 8.04 (d, 1H, J = 2.4 Hz,
J = 8.4 Hz, Ar), 7.56–7.60 (m, 2H, Ar), 8.01 (s, 1H, Ar),
.31 (s, 1H, NH, D O-exchange), 9.77–9.84 (brs, 2H, 2 9
8
2
1
2
SO NH, D O-exchange) ppm.
2
Ar), 8.32 (s, 1H, NH), 10.20–10.29 (brs, 2H, 2 9 SO NH)
2
2
1
3
ppm; C NMR (100 MHz, DMSO-d ): d = 55.5, 56.8,
6
1
-[4-Methoxy-3-(morpholinosulfonyl)phenyl-3-[[4-meth-
6
1
1
1
2.6, 109.3, 113.8, 114.4, 114.7, 119.1, 120.4, 121.3,
23.9, 124.4, 126.2, 126.8, 127.6, 128.1, 128.6, 128.7,
29.2, 129.3, 129.4, 129.9, 132.7, 135.6, 137.3, 137.4,
50.7, 153.4, 159.3, 166.5 ppm; MS (70 eV): m/z
oxy-3-(morpholinosulfonyl)phenyl]amino]-5-phenyl-1H-
pyrrol-2(5H)-one (15e, C H N O S )
3
2 36 4 9 2
White solid; m.p.: 176–178 °C; IR (KBr): mꢀ = 3377 (N–
-
H), 1695 (N–C=O), 1342, 1160 (SO ) cm ; H NMR
1
1
?2
?
2
(%) = 797.4 (M , 0.05), 795.6 (M , 0.03), 603.7 (16.3),
(
400 MHz, DMSO-d ): d = 2.81–2.90 (m, 8H, 4 9 CH ),
6
2
339.4 (16.6), 254.3 (0.9), 111.1 (26.3), 57.1 (100).
3
.04–3.11 (m, 8H, 4 9 CH ), 3.82 (s, 3H, OCH ), 3.83 (s,
2 3
5-[[5-(3-Chlorophenyl)-1-[4-methoxy-3-[N-(p-tolyl)sulfa-
3
H, OCH ), 6.03 (d, 1H, J = 2.4 Hz, CH), 6.17 (d, 1H,
3
moyl]phenyl]-2-oxo-2,5-dihyro-1H-pyrrol-3-yl]amino]-2-
methoxy-N-(p-tolyl)benzenesulfonamide
J = 2.4 Hz, = CH), 7.21–7.30 (m, 7H, Ar), 7.55 (dd, 1H,
J = 8.8, J = 2.8 Hz, Ar), 7.68 (d, 1H, J = 2.8 Hz, Ar),
1
2
(
15h, C H ClN O S )
38 35 4 7 2
7
.83 (d, 1H, J = 2.8 Hz, Ar), 7.93 (dd, 1H, J = 8.8,
1
1
J2 = 2.8 Hz, Ar), 8.37 (s, 1H, NH) ppm; C NMR
3
White solid; m.p.: 206–208 °C; IR (KBr): mꢀ = 3422 (N–
-
H), 1692 (N–C=O), 1332, 1161 (SO ) cm ; H NMR
1
1
(
100 MHz, DMSO-d ): d = 46.2, 46.3, 56.7, 56.8, 63.3,
2
6
(
400 MHz, DMSO-d ): d = 2.12 (s, 3H, CH ), 2.16 (s, 3H,
6
1
1
6.1, 66.4, 109.2, 114.2, 114.8, 115.5, 119.7, 123.6, 124.6,
25.8, 127.4, 128.5, 129.4, 130.1, 132.9, 135.7, 137.8,
6
3
CH ), 3.84 (s, 6H, 2 9 OCH ), 6.01 (d, 1H, J = 2.4 Hz,
3
3
CH), 6.05 (d, 1H, J = 2.4 Hz, = CH), 6.86–6.99 (m, 8H,
51.1, 153.9, 166.7 ppm; MS (70 eV): m/z (%) = 684.5
?
Ar), 7.07–7.09 (m, 1H, Ar), 7.12–7.14 (m, 2H, Ar),
(
M , 1.1), 483.4 (21.7), 385.3 (11.9), 272.2 (100), 131.1
3.0), 86.0 (33.0), 56.1 (22.0).
7
.29–7.34 (m, 3H, Ar), 7.44 (dd, 1H, J1 = 8.8,
J2 = 2.4 Hz, Ar), 7.65 (d, 1H, J = 2.8 Hz, Ar), 7.73 (dd,
H, J = 8.8, J = 2.8 Hz, Ar), 8.03 (d, 1H, J = 2.4 Hz,
(
N-(4-Chlorophenyl)-5-[[5-(3-chlorophenyl)-1-[3-[N-(4-
chlorophenyl)sulfamoyl]-4-methoxyphenyl]-2-oxo-2,5-di-
hyro-1H-pyrrol-3-yl]amino]-2-methoxybenzenesulfon-
1
1
2
Ar), 8.31 (s, 1H, NH), 9.83–9.90 (s, 2H, 2 9 SO NH) ppm;
2
1
3
C NMR (100 MHz, DMSO-d ): d = 20.6, 20.7, 56.7,
6
amide (15f, C H Cl N O S )
2
3
6
29
3
4
7
56.8, 62.3, 108.2, 113.7, 114.3, 119.5, 120.3, 123.9, 124.3,
White solid; m.p.: 142–144 °C; IR (KBr): mꢀ = 3424 (N–
1
25.8, 127.1, 127.3, 128.3, 128.5, 129.6, 129.7, 129.8,
-
H), 1686 (N–C=O), 1329, 1161 (SO ) cm ; H NMR
1
1
2
131.3, 132.8, 133.2, 133.3, 133.8, 135.2, 135.3, 135.4,
(
400 MHz, DMSO-d ): d = 3.80 (s, 3H, OCH ), 3.81 (s,
H, OCH ), 6.02 (d, 1H, J = 2.4 Hz, CH), 6.07 (d, 1H,
3
6
3
135.5, 135.6, 135.7, 140.7, 150.9, 153.5, 166.5 ppm; MS
?
2
?
3
(70 eV): m/z (%) = 760.9 (M , 0.15), 758.9 (M , 0.2),
05.7 (7.4), 368.4 (35.6), 293.1 (37.3), 236.2 (36.3), 111.1
35.6), 57.1 (100).
J = 2.4 Hz, = CH), 6.99 (d, 2H, J = 8.8 Hz, Ar),
6
7
1
8
1
.08–7.13 (m, 3H, Ar), 7.16–7.30 (m, 9H, Ar), 7.47 (dd,
(
H, J = 8.8, J = 2.8 Hz, Ar), 7.69–7.75 (m, 2H, Ar),
1
2
5-[[5-(4-Chlorophenyl)-1-[4-methoxy-3-[N-(p-tolyl)sulfa-
.06 (d, 1H, J = 2.8 Hz, Ar), 8.33 (s, 1H, NH),
1
3
0.19–10.25 (brs, 2H, 2 9 SO NH) ppm; C NMR
moyl]phenyl]-2-oxo-2,5-dihyro-1H-pyrrol-3-yl]amino]-2-
methoxy-N-(p-tolyl)benzenesulfonamide
2
(
100 MHz, DMSO-d ): d = 56.8, 63.1, 109.1, 113.7,
6
(
15i, C H ClN O S )
38 35 4 7 2
1
1
1
1
0
14.4, 119.1, 120.7, 121.3, 123.8, 124.4, 126.1, 126.8,
27.3, 127.8, 128.1, 128.4, 128.7, 129.3, 129.4, 129.9,
32.7, 132.8, 135.4, 135.5, 137.1, 137.3, 137.8, 150.7,
White solid; m.p.: 185–187 °C; IR (KBr): mꢀ = 3330 (N–
-
1
H), 1690 (N–C=O), 1331, 1162 (SO ) cm ; H NMR
1
2
?
(400 MHz, DMSO-d ): d = 2.11 (s, 3H, CH ), 2.16 (s, 3H,
6
3
53.5, 166.6 ppm; MS (70 eV): m/z (%) = 798.4 (M ,
CH ), 3.82 (s, 3H, OCH ), 3.83 (s, 3H, OCH ), 5.97 (d, 1H,
3
3
3
.2), 603.7 (21.4), 434.2 (15.3), 312.1 (51.4), 91.1 (100).
J = 2.4 Hz, CH), 6.04 (d, 1H, J = 2.4 Hz, = CH),
6.83–7.00 (m, 8H, Ar), 7.07–7.12 (m, 2H, Ar), 7.22 (d,
2H, J = 8.4 Hz, Ar), 7.35 (d, 2H, J = 8.4 Hz, Ar), 7.43
(dd, 1H, J = 8.8, J = 2.8 Hz, Ar), 7.62 (d, 1H,
N-(4-Chlorophenyl)-5-[[1-[3-[N-(4-chlorophenyl)sulfa-
moyl]-4-methoxyphenyl]-5-(4-methoxyphenyl)-2-oxo-2,5-
dihyro-1H-pyrrol-3-yl]amino]-2-methoxybenzenesulfon-
amide (15g, C H Cl N O S )
1
2
3
7
32
2
4
8
2
J = 2.8 Hz, Ar), 7.73 (dd, 1H, J = 8.8, J = 2.8 Hz,
2
1
White solid; m.p.: 243–245 °C; IR (KBr): mꢀ = 3424 (N–
Ar), 7.97 (d, 1H, J = 2.8 Hz, Ar), 8.29 (s, 1H, NH),
13
-
H), 1686 (N–C=O), 1329, 1161 (SO ) cm ; H NMR
1
1
2
9.82–9.91 (s, 2H, 2 9 SO NH) ppm; C NMR (100 MHz,
2
(
400 MHz, DMSO-d ): d = 3.73 (s, 3H, OCH ), 3.81 (s,
DMSO-d ): d = 20.6, 20.7, 62.3, 108.4, 113.7, 114.3,
6
3
6
3
H, OCH ), 3.82 (s, 3H, OCH ), 5.99 (d, 1H, J = 2.4 Hz,
3
116.8, 119.4, 120.4, 120.6, 123.9, 124.5, 126.6, 127.0,
3
CH), 6.03 (d, 1H, J = 2.4 Hz, = CH), 6.85–6.88 (m, 2H,
127.9, 128.5, 129.2, 129.3, 129.6, 129.7, 129.8, 132.8,
1
23

Synthesis of new dihydropyrrol-2-one derivatives bearing sulfonamide groups and studies…
1
1
32.8, 132.9, 133.1, 133.4, 135.3, 135.5, 135.6, 136.9,
14990) bacteria by the agar well diffusion method [42].
The standard drugs, such as chloramphenicol, ampicillin,
and trimethoprim-sulfamethoxazole, were tested against
bacteria. DMSO was used as a solvent and negative control
for antibacterial activity and the diameter of zone of inhi-
bition of each well was measured in mm. Results were
interpreted according to Clinical and Laboratory Standards
Institute (CLSI) guidelines [43].
50.9, 153.6, 166.5 ppm; MS (70 eV): m/z (%) = 760.6
?
2
?
, 0.6), 758.4 (M , 1), 603.7 (0.6), 400.3 (5.5), 292.1
(
M
(
35.3), 197.1 (24.9), 91.1 (100).
2
-Methoxy-5-[[1-[4-methoxy-3-[N-(p-tolyl)sulfamoyl]-
phenyl-2-oxo-5-(p-tolyl)-2,5-dihyro-1H-pyrrol-3-yl]a-
mino]-N-(p-tolyl)benzenesulfonamide
(
15j, C H N O S )
39 38 4 7 2
White solid; m.p.: 183–185 °C; IR (KBr): mꢀ = 3351, 3273
Acknowledgments We are thankful to the Persian Gulf University
Research Council for the partial support of this work.
-1 1
N–H), 1682 (N–C=O), 1332, 1159 (SO ) cm ; H NMR
(
2
(
400 MHz, DMSO-d ): d = 2.11 (s, 3H, CH ), 2.16 (s, 3H,
6
3
CH ), 3.82 (s, 3H, OCH ), 3.83 (s, 3H, OCH ), 5.98 (s, 2H,
3
3
3
CH, = CH), 6.87–6.98 (m, 8H, Ar), 7.06–7.11 (m, 6H, Ar),
.44 (dd, 1H, J = 8.8, J = 2.8 Hz, Ar), 7.63 (d, 1H,
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35 38 4 7 2
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-
1
1
687 (N–C=O), 1300, 1160 (SO ) cm
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(
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(
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2
1
3
(
s, 1H, NH), 9.86–9.96 (s, 2H, 2 9 SO NH) ppm;
2
C
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6
5
1
1
1
6.9, 62.5, 66.8, 68.5, 107.9, 114.1, 114.3, 119.7, 120.0,
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(
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