Synthesis of potential biologically active 4,5-dimethoxy-2- [3-oxo-3-phenylprop-1-en-1-yl]benzene sulfonic acid derivatives

Article abstract of DOI:10.14233/ajchem.2013.14534

A series of potential biologically active 4,5-dimethoxy-2-[3-oxo-3- phenylprop-1-en-1-yl]benzenesulfonamides was synthesized. 3,4- Dimethoxybenzaldehyde was condensed with acetophenone followed by its chlorosulfonation to get 4,5-dimethoxy-2-[3-oxo-3-phen

Full text of DOI:10.14233/ajchem.2013.14534

Asian Journal of Chemistry; Vol. 25, No. 11 (2013), 6334-6338
http://dx.doi.org/10.14233/ajchem.2013.14534
Synthesis of Potential Biologically Active 4,5-Dimethoxy-2-
3-oxo-3-phenylprop-1-en-1-yl]benzene Sulfonic Acid Derivatives
[
1
,*
2
3
1
2
BILAL SHAHID , MUHAMMAD ZIA-UR-REHMAN , NAVEED AHMED , MUHAMMAD ATHAR ABBASI and MUHAMMAD ZAHEER
1
2
3
Department of Chemistry, Government College University Lahore-54000, Pakistan
Applied Chemistry Research Centre, PCSIR Laboratories Complex Lahore-54600, Pakistan
Forman Christian College (A Chartered University), Lahore-54600, Pakistan
*
Corresponding author: E-mail: bilalshahid_1@hotmail.com; rehman_pcsir@hotmail.com
Received: 6 September 2012; Accepted: 8 May 2013)
(
AJC-13466
A series of potential biologically active 4,5-dimethoxy-2-[3-oxo-3-phenylprop-1-en-1-yl]benzenesulfonamides was synthesized. 3,4-
Dimethoxybenzaldehyde was condensed with acetophenone followed by its chlorosulfonation to get 4,5-dimethoxy-2-[3-oxo-3-phenylprop-1-
en-1-yl]benzenesulfonyl chloride, which was further reacted with a number of amines and hydrazides to get the 4,5-dimethoxy-2-[3-oxo-3-
phenylprop-1-en-1-yl]benzenesulfonic acid derivatives. All the synthesized compounds were subjected to preliminary evaluation for their anti-
bacterial activity against selected strains of gram positive and gram negative bacteria. Some of the assayed compounds showed marked activity.
Key Words: Chalcones, Sulfonamides, Antibacterial activity.
12
the ability to inhibit the cancer cell proliferation in vivo and
INTRODUCTION
1
3,14
show a significant activity against cancer . Induction of
The term "chalcone" is a general term used to describe
apoptosis in many cell types specially the breast cancers is
15
one of the major properties of chalcones (Fig. 2).
compounds with the 1,3-diphenylprop-2-en-1-one (I) structure.
A large number of 1,3-di-substituted prop-2-ene-1-one deriva-
tives have been synthesized up till now. These compounds are
precursors of flavonoids and iso-flavonoids, which are abun-
Similarly, sulfonamides are much familiar for their
versatile nature of biological activities. These are found to
16
possess anti HIV , antiinflammatory and antimicrobial
17
1
dant in plant kingdom . Basic structure of 1,3-di- substituted
18
activities (Fig. 3). Chalcones with sulfonylamino side chain
prop-2-ene-1-one nucleus is configured in Fig. 1 having two
aromatic rings joined by a three carbon α-β unsaturated
carbonyl systems.
derivatives are very important category of α-glycosidase
19
inhibitors . In the past, most of the antimalarial drugs were
based on sulfonamide derivatives and were effective against
20
Plasmodium falciparum .
O
2
α
2'
H3C
O
O
O
CH3
CH3
CH3
CH3
β
4'
4
6
6'
O
O
HO
Fig. 1. An example of substituted prop-2-en-1-one
Sofalcone - An antiulcerative drug
H3C
Chalcones naturally occur in different plant species like
Angelica, Glycyrrhiza, Humulus and Scutellaria and constitute
an important class of flavonoid family. These possess a wide
spectrum of biological activities, including antibacterial,
OH
H3C
OH
HO
OH
3
4
5
6
antifungal , antiinflammatory , antitumor and antimutagenic .
O
O
O
Such compounds have also been found active for the inhibition
H C
3
7
of chemical mediator's release , leukotriene B4 , nitric oxide ,
8
9
Xanthohumol - An anticancer prenylflavonoid
MCHP - An insulin mimetic chalcone
10
11
tyrosinases and aldose reductase activities . These have also
Fig. 2. Structures of few medicinally important 1,3-di-substituted prop-2-
ene-1-ones

Vol. 25, No. 11 (2013)
Synthesis of 4,5-Dimethoxy-2-[3-oxo-3-phenylprop-1-en-1-yl]benzene Sulfonic Acid Derivatives 6335
purification. However, solvents were purified through distil-
Cl
SO NH2
2
OCH3
lation.
3
N
O
O
-(3,4-Dimethoxy-phenyl)-1-propenone (3): The
S
21
NH
N
product was synthesized according to the literature procedure .
A mixture of acetophenone (2) (12 g, 100 mmol), 3,4-dimethoxy
benzaldehyde (1) (16.6 g, 100 mmol), sodium hydroxide
(11.84 g), water (106 mL) and ethyl alcohol (95 %; 66.8 mL)
was heated and stirred magnetically at room temperature for
3 h.After completion of the reaction, the product was extracted
in cold ethanol (3 × 25 mL). The contents were dried to give
crude product which was crystallized from methanol. Bright
NH
COOH
O
H N
2
Sulfamethoxydiazine - An anti-bacterial
Furosemide - A loop diuretic
H
N
N
OCH3
H C
3
Cl
N
O
O
S
N
NH
SO NH2
2
-1
yellow crystalline solid; m.p. 75-78 ºC. IR (KBr, νmax, cm ):
O
H N
2
CH3
Metolazone - A diuretic
1
7
662, 1630, 1105. δ: 3.82 (s, 3H, OCH
.36-7.89 (m, 10H); MS m/z: 268 [M + 1].
,5-Dimethoxy-2-[3-oxo-3-phenylprop-1-en-1-yl]benzene-
3 3
), 3.89 (s, 3H, OCH ),
Sulfamethoxypyridazine - An anti-bacterial
Fig. 3. Structures of some known sulfonamide drugs
4
sulfonyl chloride (4): To a stirred solution of chlorosulfonic
acid (34.5 g, 0.3 mol) at 0 ºC, 3-(3,4-dimethoxyphenyl)-1-
propenone (3) (10 g, 0.038 mol) was added. The dark red so-
lution obtained by mixing was allowed to stir at room tem-
perature for 3 h. After completion of reaction, the contents
were poured over crushed ice and the resulting precipitate was
filtered, washed with water and dried. Recrystallization of the
product from acetonitrile yielded compound 4 (11.1 g, 80.5
Keeping in view the potential biological activities posse-
ssed by different compounds having the basic structure of 1,3-
disubstituted prop-2-en-1-one (Fig. 1) and sulfonamides. It was
perceived that synergism of both the moieties into a single
nucleus, may give rise to more potent compounds. In this quest,
novel 4,5-dimethoxy-2-[3-oxo-3-phenylprop-1-en-1-yl]-
benzenesulfonamides (6a-n) were synthesized from 3,4-
dimethoxychalcone and subjected to antibacterial activity
-1
%
): m.p. 173-174 ºC. IR (KBr, νmax, cm ): 1326, 1655, 1126.
(
Scheme-I).
1
H NMR (DMSO-d
.36-7.89 (m. 9H); MS m/z: 366 [M ], 368 [M + 2].
General procedure for the synthesis of 4,5-dimethoxy-
2-(3-oxo-3-phenylprop-1-en-1-yl)benzenesulfonamides
6a-n): A mixture of 4,5-dimethoxy-2-[3-oxo-3-phenylprop-
6
) δ: 3.82 (s, 3H, OCH
3 3
), 3.89 (s, 3H, OCH ),
+
+
7
O
H CO
3
CHO
COOCH3
H3CO
H3CO
NaOH
RNH2
+
(
H3CO
1
2
3
o
1-en-1-yl]benzenesulfonyl chloride (4) (3.67 g, 100 mmol)
and appropriate amine/hydrazine/ hydrazide (5a-n) (100
mmol) in tetrahydrofuran (100 mL) was heated on water bath
at 80 ºC (for reaction time; Table-1). After completion of the
reaction, contents were poured over ice cooled water and the
products were extracted with dichloromethane. Solvent was
evaporated under reduced pressure to get the crude product
which was recrystallized from methanol and dried to give crys-
talline products.
ClSO3H 0 C
(
5 a - n)
O
O
H3CO
H3CO
H3CO
H3CO
O
O
THF
S
SO Cl
2
6
a - n
4
NH
R
Scheme-I: Schematic diagram of the reactions involved
EXPERIMENTAL
4
,5-Dimethoxy-N-(4-nitrophenyl)-2-(3-oxo-3-phenyl-
prop-1-en-1-yl)benzenesulfonamide (6a): Blood red crystals,
Melting points were taken on Gallenkemp melting point
1
-1
1
apparatus and are uncorrected. H NMR spectra were taken
on the Bruker DPX-400 NMR spectrometer and chemical shifts
are given in ppm downfield from TMS as the internal standard.
IR spectra were recorded in the spectral range of 4000-400
m.p. 204-206 ºC. IR (KBr, νmax, cm ): 1384, 1635, 3543. H
NMR (DMSO-d ) δ: 3.78 (s, 3H, OCH ), 3.87 (s, 3H, OCH ),
6
3
3
5.23 (s, 1H, NH), 7.31 (s, 1H, ArH), 7.43 (s, 1H, ArH), 7.46
(d, 1H, J = 15.6, C=CH), 7.56-7.62 (m, 4H, ArH), 7.82-7.93
(m, 5H, ArH), 8.78 (d, 1H, J = 15.6, HC=C). MS m/z: 468
-1
cm on Perkin Elmer 1600-FT spectrometer. Mass spectra were
taken on Jeol SX-102 spectrometer. All the chemicals were
purchased from E. Merck, BDH or Fluka and used without
+
[M ]. Anal. calcd. (%) for C H N O S: C, 58.97; H, 4.30; N,
2
2
3
20
7
5.98; Found (%): C, 58.94; H, 4.32; N, 5.99.
TABLE-1
REACTION OF 4,5-DIMETHOXY-2-[3-OXO-3-PHENYLPROP-1-EN-1-YL]
BENZENESULFONYL CHLORIDE (4) WITH AMINO COMPOUNDS (5a-n)
Reaction time
Reaction time
(h)
Entry
Product
Yield (%)
Entry
Product
Yield (%)
(
h)
4
3
4
6
6
4
7
1
2
3
4
5
6
7
6a
6b
6c
6d
6e
6f
84
72
89
82
81
80
80
8
6h
6i
7
5
4
5
4
5
6
78
85
88
80
92
90
84
9
10
11
12
13
14
6j
6k
6l
6m
6n
6g

6
336 Shahid et al.
Asian J. Chem.
N-(2-Aminoethyl)-4,5-dimethoxy-2-(3-oxo-3-phenyl-
prop-1-en-1-yl)benzenesulfonamide (6b): Off-white crystal-
N'-(3,5-Dinitrophenyl)-4,5-dimethoxy-2-(3-oxo-3-
phenylprop-1-en-1-yl)benzenesulfonohydrazide (6h): Light
-1
-1
red solid, m.p. 275 ºC. IR (KBr, νmax, cm ): 1449.54, 1653.71,
line solid, m.p. 209-211 ºC. IR (KBr, νmax, cm ): 1408.56,
1
1
1105.28, 3544.98. H NMR (DMSO-d
1
3
5
7
624.20, 3551.13. H NMR (DMSO-d
.86 (s, 3H, OCH ), 4.01 (s, 2H, NH ), 4.73-4.79 (m, 2H, CH
.30 (s, 1H, NH), 6.69-6.72 (m, 2H, CH
.45 (s, 1H, ArH), 7.49 (d, 1H, J = 15.6, C=CH), 7.66-7.69
m, 5H, ArH), 8.80 (d, 1H, J = 15.6, HC=C) MS
6
) δ: 3.75 (s, 3H, OCH
3
),
6 3
) δ: 3.77 (s, 3H, OCH ),
3
2
2
),
3
3.89 (s, 3H, OCH ), 5.34 (s, 1H, NH),7.41 (s, 1H, ArH), 7.48
2
), 7.37 (s, 1H, ArH),
(s, 1H, ArH), 7.51(d, 1H, J = 15.6, C=CH), 7.56 (s, 1H, ArH),
8.80 (d, 1H, J = 15.6, HC=C), 7.59-7.64 (m, 2H, ArH), 8.11-
+
8.17 (m, 5H, ArH), 9.32(s, 1H, NH). MS m/z: 528 [M ].Anal.
(
+
m/z: 390 [M ].Anal. calcd. (%) for C19
.68; N, 7.17; Found (%): C, 58.48; H, 5.66; N, 7.20.
-[4,5-Dimethoxy-2-(3-oxo-3-phenylprop-1-en-1-yl)-
phenylsulfonamido]benzoic acid (6c): Light Green crystals;
22 2 5
H N O S: C, 58.45; H,
20 4 9
calcd. (%) for C23H N O S: C, 52.27; H, 3.81; N, 10.60; found
5
(%): C, 52.24; H, 3.82; N, 10.66.
2-[(4,5-Dimethoxy-2-(3-oxo-3-phenylprop-1-en-1-
yl)phenyl)sulfonyl]hydrazinecarboxamide (6i): Orange
2
-1
1
-1
crystalline solid, m.p. 197 ºC. IR (KBr, νmax, cm ): 1408.83,
m.p. 190 ºC. IR (KBr, νmax, cm ): 1420, 1637, 3547, 3595. H
NMR (DMSO) δ: 3.77 (s, 3H, OCH ),3.89 (s, 3H, OCH ),
.30 (s, 1H, NH), 7.44 (s, 1H,ArH), 7.50 (s, 1H, ArH), 7.55 (t,
H, J = 7.6, ArH), 7.58 (d, J = 15.6, 1H, C=CH), 7.69-7.73
1
1661.24, 3540. H NMR (DMSO-d
3
3
6
) δ: 3.78 (s, 3H, OCH
3
),
5
1
3.85 (s, 3H, OCH
(s, 1H, ArH), 7.47 (s, 1H, ArH), 7.48(d, 1H, J = 15.6, C=CH),
7.65-7.67 (m, 5H, ArH), 8.83 (d, 1H, J = 15.6, HC=C), 9.34
3
), 4.01 (s, 2H, NH ), 5.31 (s, 1H, NH), 7.39
2
(
m, 4H, ArH), 8.10-8.17 (m, 4H, ArH), 8.77 (d, 1H, J = 15.6,
+
+
(s, 1H, NH). MS m/z: 405 [M ]. Anal. calcd. (%) for
HC=C) 12.43 (s, 1H, OH). MS m/z: 467 [M ]. Anal. calcd.
S: C, 61.66; H, 4.53; N, 3.0; found (%): C,
1.63; H, 4.59; N, 3.09.
-[4,5-Dimethoxy-2-(3-oxo-3-phenylprop-1-en-1-yl)-
phenylsulfonamido]benzoic acid (6d): Dark grey crystals,
(
%) for C24
H21NO
7
18 19 3 6
C H N O S: C, 53.32; H, 4.72; N, 10.36; found (%): C, 53.35;
6
H, 4.71; N, 10.34.
4,5-Dimethoxy-N'-benzoyl-2-(3-oxo-3-phenylprop-1-
en-1-yl)benzenesulfonohydrazide (6j): Light brown crystal-
3
-1
-1
line solid, m.p. 220 ºC. IR (KBr, νmax, cm ): 1419.42, 1651.52,
m.p. 201-203 ºC. IR (KBr, νmax, cm ): 1442, 1622, 3509, 3572.
1
1
3531.89. H NMR (DMSO-d
H NMR (DMSO-d
OCH ), 5.34 (s, 1H, NH), 7.43 (s, 1H,ArH), 7.49 (s, 1H,ArH),
.54 (s, 1H, ArH), 7.57 (d, J = 15.6, 1H, C=CH), 7.67-7.74
m, 5H, ArH), 8.12-8.18 (m, 3H, ArH), 8.78 (d, 1H, J = 15.6,
6
) δ: 3.78 (s, 3H, OCH
3
), 3.87 (s, 3H,
6
3
) δ: 3.79 (s, 3H, OCH ), 3.88 (s,
3
3H, OCH
3
), 5.33 (s, 1H, NH),7.43 (s, 1H, ArH), 7.49 (s, 1H,
7
ArH), 8.80 (d, 1H, J = 15.6, HC=C), 7.55 (m, 1H, C=CH),
8.10 (d, 2H, J = 7.2, ArH), 7.94 (d, 2H, J = 7.2, ArH), 7.26-
+
7.62 (m, 6H,ArH), 9.30 (s, 1H, NH). MS m/z: 466 [M ].Anal.
(
+
HC=C) 12.47(s, 1H, OH). MS m/z: 467 [M ]. Anal. calcd.
S: C, 61.66; H, 4.53; N, 3.0; found (%): C,
1.60; H, 4.56; N, 3.09.
-Chloro-5-(4,5-dimethoxy-2-(3-oxo-3-phenylprop-1-
en-1-yl)phenylsulfonamido)benzoic acid (6e): Light brown
(
%) for C24
H21NO
7
22 2 6
calcd. (%) for C24H N O S: C, 61.79; H, 4.75; N, 6.0; found
6
(%): C, 61.80; H, 4.72; N, 5.95.
4,5-Dimethoxy-N'-(4-nitrobenzoyl)-2-(3-oxo-3-phenyl-
prop-1-en-1-yl)benzenesulfonohydrazide (6k): Red crystal-
2
-1
-1
line solid, m.p. 193 ºC. IR (KBr, νmax, cm ): 1419.42, 1651.52,
solid, m.p. 210 ºC. IR (KBr, νmax, cm ): 1420.56, 1672.38,
3
1
570.29, 3568.10, 683.56. H NMR (DMSO-d
1
3531.89. H NMR (DMSO-d
6
) δ: 3.78 (s,
6
3
) δ: 3.78 (s, 3H, OCH ), 3.88 (s,
3
H, OCH ),3.87 (s, 3H, OCH ), 5.34 (s, 1H, NH), 7.43 (s, 1H,
3
3
3H, OCH ), 5.33 (s, 1H, NH),7.45 (s, 1H, ArH), 7.48 (d, 1H,
3
ArH), 7.49 (s, 1H, ArH), 7.55 (s, 1H, ArH), 7.59 (d, J = 15.6,
J = 15.6, C=CH), 7.50 (s, 1H, ArH), 8.80 (d, 1H, J = 15.6,
HC=C), 7.58-7.63 (m, 4H,ArH), 8.10-8.16 (m, 5H,ArH), 9.32
1
8
5
5
H, C=CH), 7.67-7.74 (m, 5H,ArH), 8.07-8.11 (m, 2H,ArH),
.72 (d, 1H, J = 15.6, HC=C), 12.49 (s, 1H, OH). MS m/z:
+
(s, 1H, NH). MS m/z: 511 [M ]. Anal. calcd. (%) for
+
+
01 [M ], 503 [M + 2]. Anal. calcd. (%) for C24
7
H20NO SCl: C,
C
24
H
21
N
3
O
8
S: C, 56.35; H, 4.14; N, 8.22; found (%): C, 56.33;
H, 4.10; N, 8.23.
N'-(2-Hydroxybenzoyl)-4,5-dimethoxy-2-(3-oxo-3-
7.43; H, 4.02; N, 2.79; found (%): C, 57.42; H,3.97; N, 2.81.
N-Hydroxy-4,5-dimethoxy-2-(3-oxo-3-phenylprop-1-
en-1-yl)benzenesulfonamide (6f): Pale yellow solid, m.p. 162
phenylprop-1-en-1-yl)benzenesulfonohydrazide (6l): White
-1
solid, m.p. 238 ºC. IR (KBr, νmax, cm ): 1441.40, 1652.08,
-1
1
ºC. IR (KBr, νmax, cm ): 1384.08, 1635.99, 3550.29. H NMR
1
3567.88, 3505.32. H NMR (DMSO-d
(
DMSO-d
6
) δ: 3.78 (s, 3H, OCH
3
), 3.83 (s, 3H, OCH
3
), 5.31
s, 1H, NH), 7.39 (s, 1H, ArH), 7.47 (s, 1H,ArH), 7.48 (d, 1H,
6
) δ: 3.83 (s, 3H, OCH
3.87 (s, 3H, OCH ), 5.36 (s, 1H, NH), 6.90 (d, 2H, J = 7.6,
3
3
),
(
J = 15.6, C=CH), 7.65-7.67 (m, 5H, ArH), 8.83 (d, 1H, J =
ArH), 6.93 (d, 2H, J = 8.4, ArH), 7.32 (s, 1H, ArH), 7.46 (s,
1H, ArH), 7.48 (d, 1H, J = 15.6, C=CH), 7.51 (s, 1H, ArH),
7.57-7.64 (m, 4H, ArH), 8.81 (d, 1H, J = 15.6, HC=C), 9.32
+
1
5.6, HC=C), 13.01 (s, 1H, OH ). MS m/z: 363 [M ]. Anal.
calcd. (%) for C17 S: C, 56.19; H, 4.72; N, 3.85; found
%): C, 56.22; H, 4.69; N, 3.86.
,5-Dimethoxy-2-(3-oxo-3-phenylprop-1-en-1-yl)-N'-
phenylbenzenesulfonohydrazide (6g): Black crystalline
H17NO
6
+
(
(s, 1H, NH), 13.03 (s, 1H, OH ). MS m/z: 482 [M ]. Anal.
4
22 2 7
calcd. (%) for C24H N O S: C, 59.74; H, 4.60; N, 5.81; found
(%): C, 59.71; H, 4.61; N, 5.83.
N'-(4-Hydroxybenzoyl)-4,5-dimethoxy-2-(3-oxo-3-
-1
solid, m.p. 190-193 ºC. IR (KBr, νmax, cm ): 1383.89, 1635.53,
3
1
544.98. H NMR (DMSO-d
6 3
) δ: 3.78 (s, 3H, OCH ), 3.88 (s,
phenylprop-1-en-yl)benzenesulfonohydrazide (6m): Grey
-1
3H, OCH ), 5.33 (s, 1H, NH),7.45 (s, 1H, ArH), 7.48 (d, 1H,
J = 15.6, C=CH), 7.51 (s, 1H, ArH), 8.80 (d, 1H, J = 15.6,
3
crystalline solid, m.p. 215 ºC. IR (KBr, νmax, cm ): 1436.64,
1
1623.26, 3534.05, 3503.81. H NMR (DMSO-d
6
) δ: 3.79 (s,
HC=C), 7.59-7.64 (m, 5H, ArH), 8.11-8.17(m, 5H,ArH), 9.32
+
s, 1H, NH). MS m/z: 438 [M ]. Anal. calcd. (%) for
3H, OCH ), 3.86 (s, 3H, OCH ), 5.35 (s, 1H, NH), 6.90 (d,
3
3
(
2H, J = 7.6, ArH), 6.93 (d, 2H, J = 8.4, ArH), 7.32 (s, 1H,
ArH), 7.46 (s, 1H, ArH), 7.48 (d, 1H, J = 15.6, C=CH), 7.51
(s, 1H, ArH), 7.53-7.64 (m, 4H, ArH), 8.81 (d, 1H, J = 15.6,
C
23
22 2 5
H N O S: C, 63.0; H, 5.06; N, 6.39; found (%): C, 63.03;
H, 5.04; N, 6.36.

Vol. 25, No. 11 (2013)
Synthesis of 4,5-Dimethoxy-2-[3-oxo-3-phenylprop-1-en-1-yl]benzene Sulfonic Acid Derivatives 6337
HC=C), 9.31 (s, 1H, NH), 13.03 (s, 1H, OH ). MS m/z: 482
NMR and mass spectrometry) along with their elemental analyses
and were found in accordance with the calculated values.
All the newly synthesized compounds (dissolved in
dimethylformamide) were subjected to antibacterial screening
against four gram positive bacteria (Bacillus cereus, Bacillus
subtilis, Bacillus thuringiensis and Staphylococcus aureus) and
three gram negative bacteria (Escherichia coli, Pseudomonas
aeruginosa, Salmonella typhi) by determining their minimum
inhibitory concentrations (MICs) using agar dilution tech-
+
[
M ]. Anal. calcd. (%) for C24
.81; found (%): C, 59.76; H, 4.59; N, 5.78.
N'-(4-Chlorobenzoyl)-4,5-dimethoxy-2-(3-oxo-3-phenyl-
prop-1-en-1-yl)benzenesulfonohydrazide (6n): Pale yellow
22 2 7
H N O S: C, 59.74; H, 4.60; N,
5
-1
crystalline solid, m.p. 207 ºC. IR (KBr, νmax, cm ): 1383.65,
1
1
660.56, 3503.66, 620.03. H NMR (DMSO-d
6
) δ: 3.76 (s,
3
H, OCH ), 3.87 (s, 3H, OCH ), 5.36 (s, 1H, NH), 7.45 (s, 1H,
3
3
ArH), 7.48 (d, 1H, J = 15.6, C=CH), 7.52 (s, 1H, ArH), 7.59-
23
7.64 (m, 3H, ArH), 8.07-8.13 (m, 6H, ArH), 8.81 (d, 1H, J =
+
15.6, HC=C), 9.31 (s, 1H, NH). MS m/z: 500 [M ].Anal. calcd.
nique and streptomycin as reference drug. The choice of
streptomycin as a clinical standard was based on the fact that
at low concentrations, it only inhibits growth of the bacteria
through induction of prokaryotic ribosomes to misread mRNA.
Streptomycin also prevents initiation of protein synthesis and
leads to death of microbial cells. Also, in humans, they have
structurally different ribosomes from bacteria, thereby allowing
21 2 6
(%) for C24H N O SCl: C, 57.54; H, 4.23; N, 5.59; found (%):
C, 57.57; H, 4.21; N, 5.68.
Antibacterial activity: All the newly synthesized com-
pounds (dissolved in dimethylformamide) were subjected to
antimicrobial screening by determining the minimum inhibi-
22
24
tory concentration (MIC) using the agar dilution technique .
The in vitro antimicrobial activity of the prepared compounds
the selectivity of this antibiotic for bacteria .
The MICs of the active compounds against the susceptible
pathogenic organisms are presented in Table-3. The results
showed that in general, compounds (6a-f) synthesized by the
reaction of sulfonyl chloride (4) with amines were found active
against gram positive bacteria while sulfonohydrazides (6g-
n) were found more active against gram negative bacteria. An
insight to the activities of different compounds obtained reveals
that the compounds (6a-n) are more active against Bacillus
species (B. subtilis, B. cereus, B. thuringiensis) than that of S.
aureus. It is also evident that the compounds (6a, 6b and 6f)
are more active than the others perhaps due to the presence of
nitrogen atoms with lone pairs. In contrast to the behaviour
shown by the compounds (6a-f), sulfonohydrazides (6g-n)
showed their activity against gram negative bacteria. Compounds
bearing nitro, hydroxyl and chloro groups were found active
(
6a-n) against three gram negative bacteria i.e., Escherichia
coli, Pseudomonas aeruginosa, Salmonella typhi and four
gram positive bacteria i.e., Bacillus cereus, Bacillus subtilis,
Bacillus thuringiensis and Staphylococcus aureus was deter-
mined by preparing suspensions of each micro-organism to
5
6
contain approximately 10 -10 CFU (colony forming units)/
well. The test compounds were applied to the wells at concen-
-1
trations ranging from 200 to 3.0 mg mL in DMF solution,
in addition to the 0 (control) and the standard, streptomycin.
The plates were incubated for 24 h at 37 ºC and growth assessed
by visual inspection. The minimum inhibitory concentration
(MIC) was defined as the lowest concentration of inhibitor at
which microbial growth was not apparent disregarding a single
colony or a faint haze caused by the inoculums.
2
and their activity is in the following order: NO > p-OH >
RESULTS AND DISCUSSION
p-Cl > o-OH. Rest of the compounds were either found inactive
or with MIC greater than 15.
3
-(3,4-Dimethoxyphenyl)-1-propenone (3) synthesized by
usual Claisen Schmidt condensation was chlorosulfonylated
using chlorosulphonic acid at 0 ºC to yield 4,5-dimethoxy-2-
Conclusion
The present study revealed that synergism of sulfonamide
and sulfonohydrazide moieties to 3-(3,4-dimethoxyphenyl)-
[
3-oxo-3-phenylprop-1-en-1-yl]benzenesulfonyl chloride (4).
It was found that reaction temperature plays crucial role for
the reaction. Slow addition of the chalcone to chlorosulfonic
acid at 0 ºC yields a single desired product, while addition at
slight higher temperatures ended up with unextractable multi-
spotted product containing dichlorosulfonylated products. This
sulfonyl chloride (4) was then reacted with a number of amino
compounds (amines, hydrazines and hydrazides) to get the
corresponding sulphonamides (6a-f) and sulfonohydrazides
1
-propenone could be useful as a template for future develop-
ment through modification or derivatization to design a more
potent biologically active compounds. The new skeleton may
also possess other biological activities of the parent ring systems.
ACKNOWLEDGEMENTS
The authors are grateful to Pakistan Council of Scientific
& Industrial Research Laboratories Complex, Lahore for the
provision of bench facilities and chemicals.
(6g-n) (Table-2).All of the newly synthesized compounds were
characterized through spectroscopic techniques (FT-IR, H
1
TABLE-2
REACTANT AMINES USED FOR THE SYNTHESIS OF TITLE COMPOUNDS (5a-n)
Reactant amines
Name
4-Nitroaniline
Reactant amines
Name
5a
5h
5i
Dinitrophenyl hydrazine
Semicarbazide hydrochloride
Benzohydrazide
5b
Ethane-1,2-dimaine
5c
2-Aminobenzoic acid
5j
5
d
3-Aminobenzoic acid
5k
5l
4-Nitrobenzohydrazide
2-Hydroxybenzohydrazide
4-Hydroxybenzohydrazide
4-Chlorobenzohydrazide
5
e
5-Amino-2-chlorobenzoic acid
Hydroxylamine hydrochloride
Phenylammoniumchloride
5
f
5m
5n
5
g

6
338 Shahid et al.
Asian J. Chem.
TABLE-3
ANTIBACTERIAL ACTIVITY (MIC, µg mL ) OF COMPOUNDS
-1
Susceptible microorganism
Entry
Compound
Gram Positive Bacteria
Gram Negative Bacteria
B. cereus
6.1
5.9
14.9
14.2
8.6
6.1
–
B. subtilis
B. thuringiensis
S. aureus
E. coli
14.9
–
P. aeruginosa
S. typhi
3
4
5
6
7
8
9
6a
7.2
6.3
14.1
–
6.3
5.6
13.7
–
14.5
13.4
14.7
–
–
14.3
–
–
–
–
–
–
6b
6c
–
6d
14.8
–
–
6e
7.9
5.9
–
7.7
7.3
–
–
–
6f
9.1
–
6g
–
–
–
–
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
6h
8.9
9.3
–
8.2
9.6
–
–
–
6.5
7.1
6i
–
–
–
7.3
7.9
6j
–
–
–
11.7
10.2
11.2
7.3
11.9
11.7
12.7
6.4
6k
13.2
14.2
–
–
–
–
12.8
13.8
6.8
7.7
4.3
6l
6m
–
–
–
–
–
–
6n
–
–
–
–
7.3
8.7
Streptomycin
4.3
4.3
4.3
4.3
4.3
4.3
1
1
1
1
4. S. Yamamoto, E. Aizu, H. Jiang, T. Nakadate, I. Kiyoto, J.C.Wang and
R. Kato, Carcinogenesis, 12, 317 (1991).
REFERENCES
5. C.A. Calliste, J.C. Le Bail, P. Trouillas, C. Pouget, G. Habrioux, A.J.
Chulia and J.L. Duroux, Anti-cancer Res., 21, 3949 (2001).
6. M. Liu, P. Wilairat, S.L. Croft, A. Lay-Choo Tan and M.-L. Go, Bioorg.
Med. Chem., 11, 2729 (2003).
1
2
.
N. Shimada, T. Aoki, S. Sato, Y. Nakamura, S. Tabata and S. Ayabe,
Plant Physiol., 131, 941 (2003).
.
T. Hussain, H.L. Siddiqui, M. Zia-ur-Rehman, M.M. Yasinzai and M.
Parvez, Eur. J. Med. Chem., 44, 4654 (2009).
S. Ducki, IDrugs, 10, 42 (2007).
7. J.N. Dominguez, J.E. Charis, G. Lobo, N.G. de Domínguez, M.M.
Moreno, F. Riggione, E. Sanchez, J. Olson and P.J. Rosenthal, Eur. J.
Med. Chem., 36, 555 (2001).
3
4
5
6
.
.
.
.
N.J. Lawrence andA. T. McGown, Curr. Pharm. Des., 11, 1679 (2005).
Z. Nowakowska, Eur. J. Med. Chem., 42, 125 (2007).
J.R. Dimmock, D.W. Elias, M.A. Beazely and N.M. Kandepu, Curr.
Med. Chem., 6, 1125 (1999).
1
1
2
2
2
8. N. Ahmed, M. Zia-ur-Rehman, H.L. Siddiqui, M.F. Ullah and M. Parvez,
Eur. J. Med. Chem., 46, 2368 (2009).
9. W.D. Seo, J.H. Kim, J.E. Kang, H.W. Ryu, M.J.C. Long, H.S. Lee,
M.S. Yang and K.H. Park, Bioorg. Med. Chem. Lett., 15, 5514 (2005).
0. J.N. Domínguez, C. León, J. Rodrigues, N.G. de Domínguez, J. Gut and
P. J. Rosenthal, Farmaco, 60, 307 (2005).
7
8
9
1
1
1
1
.
.
.
H.H. Ko, L.T. Tsao, K.L. Yu, C.T. Liu, J.P. Wang and C.N. Lin, Bioorg.
Med. Chem., 11, 105 (2003).
A.M. Deshpande, N.P. Argade, A.A. Natu and J. Eckman, Bioorg. Med.
Chem., 7, 1237 (1999).
1. V. Shettigar, J. B.-J. Teh, H.-K. Fun, I. A. Razak, P. S. Patil and S. M.
Dharmaprakash, Acta Cryst., E62, o4646 (2006).
J. Rajas, J.M. Paya, J.N. Dominguez and M.L. Ferrandiz, Bioorg. Med.
Chem. Lett., 12, 1951 (2002).
2. J.G. Colle, J.P. Duguid, A.G. Fraser and B.P. Marmion, in eds.: T.J.
Mackie and J.E. McCartney, Practical Medical Biology, Churchill
Livingstone, London, UK, Vol. 13 (1989).
0. S. Khatib, O. Nerya, R. Musa, M. Shmnel, S. Tamir and J. Vaya, Bioorg.
Med. Chem., 13, 433 (2005).
1. F. Severi, S. Benvenuti, L. Costantino, G. Vampa, M. Melegari and L.
Antolini, Eur. J. Med. Chem., 33, 859 (1998).
2. S. Padhye, A. Ahmad, N. Oswal and F. H Sarkar, J. Hematol. Oncol.,
2
2
3. H. Hanel and W. Raether, Mycoses, 31, 148 (1988).
4. C. Booth, in eds.: J.R. Norris and D.W. Ribbons, Methods in Microbiology,
Academic Press, London, New York, Vol. IV, p. 49-94 (1977).
2, 38 (2009).
3. Y. Satomi, Int. J. Cancer, 55, 506 (1993).