Convenient Synthesis of Novel Chalcone and Pyrazoline Sulfonamide Derivatives as Potential Antibacterial Agents

Article abstract of DOI:10.1134/S1068162020030048

Abstract: Novel chalcone sulfonamide derivatives were synthesized starting from benzophenones and aldehydes in 3 steps. Also, (E)-3-(4-chlorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one was converted to different pyrazoline in four steps. The synthesis of s

Full text of DOI:10.1134/S1068162020030048

ISSN 1068-1620, Russian Journal of Bioorganic Chemistry, 2020, Vol. 46, No. 3, pp. 371–381. © Pleiades Publishing, Ltd., 2020.
Convenient Synthesis of Novel Chalcone and Pyrazoline Sulfonamide
Derivatives as Potential Antibacterial Agents
A. P. S. Bonakdara, A. Sadeghia, H. R. Aghaeia, K. Beheshtimaalb, S. M. R. Nazific, and A. R. Massaha, 1
aDepartment of Chemistry, Shahreza Branch, Islamic Azad University, Shahreza, 86145-311 Iran
bDepartment of Microbiology, Falavarjan Branch, Islamic Azad University, Falavarjan, Isfahan, Iran
cDepartment of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical
Sciences, Isfahan, 81746-73461 Iran
Received November 11, 2019; revised November 25, 2019; accepted December 17, 2019
Abstract—Novel chalcone sulfonamide derivatives were synthesized starting from benzophenones and alde-
hydes in 3 steps. Also, (E)-3-(4-chlorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one was converted to dif-
ferent pyrazoline in four steps. The synthesis of sulfonamides was carried out under solvent-free conditions
at room temperature and the products were obtained in high purity after a simple work-up without using any
chromatography method for purification. All of the products were evaluated for their in vitro antibacterial
activity against Staphylococcus aureus and Escherichia coli.
Keywords: chalcone, pyrazoline, sulfonamide, solvent-free, antibacterial activity
DOI: 10.1134/S1068162020030048
INTRODUCTION
including anti-inflammatory, antimicrobial [9, 10],
anticancer [11], antiepileptic, antidepressant, antioxi-
dant activity [12] and antimicrobial activity [13].
Sulfonamides possess many biological activities,
such as antibacterial [14, 15], antimalarial [16], selec-
tive adenosine A2B receptor antagonists [17], antican-
cer, anti-inflammatory and antiviral activity [18].
Antibacterial agents with a sulfonamide structure, e.g.
sulfadiazine, and diuretics, such as hydrochlorothia-
Chalcones, are one of the major classes of natural
products with pharmacological activity. Chemically they
consist of open-chain flavonoids in which the two aro-
matic rings are joined by a three-carbon α,β-unsaturated
carbonyl system [1]. Chalcones have been reported to
possess many useful properties including antibacterial
[2], antifungal [3], anti-inflammatory [4], antimalarial
[5], anti-diabetic [6], and anticancer activity [7].
Also, chalcones are well known intermediates in zide, have been therapeutically used for many decades
the synthesis of various heterocyclic compounds, such [19, 20]. In continuation of our interest in the synthe-
as pyrazolines, isoxazolines, pyrimidines and pyri- sis and biological study of sulfonamide derivatives [14,
dines [8]. Pyrazolines are prominent nitrogen con- 21, 22], we report in the present work the synthesis and
taining five-membered heterocyclic compounds also biological activity of a series of novel chalcones and
possessing a broad spectrum of biological activities pyrazolines bearing sulfonamide groups (Scheme 1).
O
H
N
O
O
CH3
Ar
S
N
H
N
O
N
O
Cl
Ar
S
H3CO
Y
X
O
X = −Cl, −NO2; Y = −Cl, −H
H3CO
O
O
H
S N Ar
O
−
O
O
N+
O
CH3
Scheme 1. Synthesized chalcone sulfonamides.
1 Corresponding author: phone: +98–321-3292522; e-mail: Massah@iaush.ac.ir.
371

372
BONAKDAR et al.
treated with chlorosulfonic acid at 0–5°C to give
RESULTS AND DISCUSSION
the corresponding sulfonyl chlorides. Finally, the
reaction of chalcone sulfonyl chlorides (IIIa–IIIc)
with aromatic substituted amines in the presence of
K2CO3 produced chalcone sulfonamides (IV–XV)
in good to high yield (Table 1) under solvent-free
The synthesis of chalcone sulfonamide (IV–XV)
followed the general pathway outlined in Scheme 2.
Firstly, the chalcones were synthesized by conden-
sation of aromatic aldehydes with 4–methoxy ace-
tophenone (1 : 1), using 40% potassium hydroxide
in ethanol [4]. Then compounds (IIa–IIc) was conditions [23].
O
CH3
+
H
O
O
Y
Y
KOH 40%, EtOH
35 2°C
H3CO
X
OCH3
X
(Ia−Ic)
(IIa−IIc)
H
O
O
O
O
N
Ar
Cl
Aromatic
substituted amines
S
S
ClSO3H
O
O
K2CO3
H3CO
Y
X
H3CO
Y
X
Solvent-free, r.t
(IIIa−IIIc)
(IV−XV)
X = −Cl, Y = −H (a); X,Y = −Cl (b);
X = −NO2, Y = −H (c)
Scheme 2. Synthetic route for target compounds (IV–XV).
Chalcone sulfonamides (XVIII–XXVI) incorpo- 0–5°C to give the corresponding sulfonyl chloride
rating a furan, were synthesized following the general (XVII) in high yield. Finally, the reaction of chalcone
sulfonyl chloride (XVII) with aromatic and het-
eroaromatic substituted amines in the presence of
NaHCO3 produced chalcone sulfonamides (XVIII–
pathway outlined in Scheme 3. Firstly, the chalcone
was synthesized by the reaction of 5-methylfurfural
with 4-nitro acetophenone (1 : 1), in the presence of
20% sodium hydroxide in ethanol. The obtained XXVI) in good to high yields under solvent-free con-
chalchone (XVI) reacted with chlorosulfonic acid at ditions (Table 2).
O
CH3
O
O
NaOH 20%, EtOH
r.t
+
−
H3C
O
O
O
N+
O
H
(XVI)
CH3
N+
O−
O
O
O
Aromatic
O
O
H
N
ClSO3H
substituted amines
S Cl
O
CH3
S
O
CH3
Ar
−
−
O
O
O
O
N+
O
N+
O
NaHCO3
Solvent-free, r.t
(XVII)
(XVIII−XXVI)
Scheme 3. Synthetic route for target compounds (XVIII–XXVI).
In addition, the synthesis of pyrazoline sulfon- reacted with hydrazine hydrate in ethanol under
amides (XXIX–XXXII) followed the general pathway reflux conditions [8]. The resulting pyrazoline was
outlined in Scheme 4. Firstly, chalcone (IIa) was acylated with acetyl chloride to produce the corre-
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CONVENIENT SYNTHESIS OF NOVEL CHALCONE
373
Table 2. Synthesis of new chalcone sulfonamides (XVIII–
XXVI)
Table 1. Synthesis of new chalcone sulfonamides (IV–XV)
R1
H
N
O
O
O
S
O
H
O
S N Ar
R2
−
O
O
H3CO
Y
X
O
N+
O
CH3
Yielda,
%
Time,
min
R1
R2
Compound
X
Y
Yielda, %
Compound
Ar
Time, min
(IV)
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
H
H
H
H
H
Cl
Cl
Cl
H
H
H
H
H
OCH3 30
88
78
89
80
71
86
85
75
78
76
81
85
(XVIII)
(V)
OCH3
H
H
35
35
30
40
30
25
20
4-Cl–C6H4
4-Me–C6H4
4-Br–C6H4
2-Cl–C6H4
2,4-Me2–C6H3
C6H5
135
130
145
150
144
125
61
65
84
73
61
60
58
88
75
70
(VI)
CH3
(XIX)
(VII)
(VIII)
(IX)
CH3 CH3
(XX)
H
OCH3
H
Br
H
(XXI)
(X)
CH3
(XXII)
(XXIII)
(XXIV)
(XXV)
(XXVI)
(XI)
CH3 CH3
(XII)
(XIII)
(XIV)
(XV)
NO2
NO2
NO2
NO2
H
OCH3 30
4-OMe–C6H4
2-OMe–C6H4
C5H4N
OCH3
H
H
35
35
30
73
CH3
CH3 CH3
30
a Isolated yield of the final step.
a Isolated yield of the final step.
sponding acetyl pyrazoline (XXVII) in high yield.
Then compound (XXVII) reacted with chlorosul- compound (XXVIII) with aromatic substituted
(XXIX–XXXII) were synthesized by the reaction of
amines in the presence of K2CO3 under solvent–free
fonic acid to give the corresponding sulfonyl chlo-
rides (XXVIII). Finally, the pyrazoline sulfonamides conditions.
O
CH3
O
1. N2H4 · H2O, EtOH
N
N
reflux, 8 h
Cl
2. Acetyl chloride
H3CO
Cl
CHCl3, r.t
(XXVII)
(IIa)
H3CO
O
O
CH3
CH3
N
N
H
N
Aromatic
substituted amines
N
N
O
O
Cl
Cl
Cl
Ar
ClSO3H
CHCl3
S
S
K2CO3
O
O
Solvent-free, r.t
H3CO
H3CO
(XXVIII)
(XXIX−XXXII)
Scheme 4. Synthetic route for target compounds (XXIX–XXXII).
The results indicate that, the synthesis of chalcone
A careful study revealed that most of the tested
and pyrazoline sulfonamide derivatives from the cor- compounds showed moderate to good antibacterial
responding sulfonyl chlorides proceeds in the absence activity against S. aureus and E. coli. Among them,
of solvent, with good yields and high purity in rela- compounds (XIX, XX, XI, XXIII, and XXVI) showed
tively short reaction times (Tables 1, 2 and 3).
better antibacterial activities than other compounds,
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374
BONAKDAR et al.
Table 3. Synthesis of new pyrazoline sulfonamides (XXIX–
XXXII)
yser for CHN (Perkin Elmer). Column
chromatography was performed using silica gel 60
(230–400 mesh). All reactions were conducted open
to the atmosphere and the yields refer to the isolated
products.
O
CH3
N
H
N
N
O
Synthesis of chalcone derivatives (IIa–IIc); General
procedure. Potassium hydroxide (40%, 20 mL) was
added dropwise to a mixture of 4-methoxy acetophe-
none (13 mmol) and aromatic aldehydes (13 mmol) in
ethanol, over 2–3 min under constant stirring using
magnetic stirrer. The reaction mixture was stirred at
35 2°C for 4.5–5.0 h. The progress of the reaction
was monitored by TLC. After completion of the reac-
tion, the mixture was poured into chilled water
(100 mL) and neutralized with hydrochloric acid. The
temperature of the chilled water was in the range of 2–
5°C. The product was filtered, dried at 60°C for 4 h
and recrystallized from ethanol. Mp (IIa): 126–128°C
(128–131°C) [24]; (IIb): 133–135°C (134–137) [24];
(IIc): 168–170°C (172) [24].
Cl
S
O
R
H3CO
Yielda, %
Compound
R
Time, min
(XXIX)
OCH3
CH3
Cl
20
25
35
30
76
79
73
70
(XXX)
(XXXI)
(XXXII)
Br
a Isolated yield of the final step.
against S. aureus and compounds (XX) and (XXII–
XXV) showed better antibacterial activity than other
compounds, against E. coli. Amongst the chalcone
sulfonamides, compound (XXIII) exhibited the lowest
MIC of 0.156 and 2.5 mg/mL against S. aureus and
E. coli respectively. Amongst the pyrazoline sulfon-
amides, compound (XXXI) exhibited the lowest MIC
of 22 and 11 mg/mL against S. aureus and E. coli respec-
tively. The mechanism of the antibacterial activity of
tested compounds is not known at the moment. How-
ever, it can be interference with the cell wall synthesis
or inhibition of cellular enzymes leading to cell death.
As a result of the study, we synthesized a number of
novel chalcone and pyrazoline sulfonamide deriva-
tives by the reaction of chalcone and pyrazoline sulfo-
nyl chlorides with different aromatic substituted
amines in the presence of K2CO3 and NaHCO3 under
solvent-free conditions at room temperature. All the
newly synthesized compounds were assayed for their
in vitro antibacterial activity against S. aureus and
E. coli. In this regard, the chalcone sulfonamides con-
taining furan ring (XVIII–XXVI) showed better anti-
bacterial activity than the other chalcones. Moreover,
pyrazoline sulfonamides (XXIX–XXXII) exhibited
more antibacterial activity than the similar chalcone
sulfonamides (IX, VI, VIII).
(E)-3-(4-Chlorophenyl)-1-(4-methoxyphenyl)prop-
2-en-1-one (IIa). Mp 126–128°C; yield 85%; IR
(KBr, ν cm–1): 3067 (Ar–H), 1657 (C=O), 1604
1
(C=C). H NMR (400 MHz, CDCl3): δ 3.93 (s, 3H,
OCH3), 7.02 (d, J = 8.8 Hz, 2H, Ar–H), 7.42 (d, J =
8.4 Hz, 2H, Ar–H), 7.55 (d, J = 15.6 Hz, 1H,
COCH=CH), 7.60 (d, J = 8.4 Hz, 2H, Ar–H), 7.78
(d, J = 15.6 Hz, 1H, COCH=CH), 8.07 (d, J = 8.8 Hz,
2H, Ar–H).
Synthesis of chalcone sulfonyl chloride derivatives
(IIIa–IIIc); General procedure. Cold chlorosulfonic
acid (9 mmol) was added to compound (IIa–IIc)
(1 mmol), with stirring for 1h while maintaining the
temperature at 0–5°C. Then, the reaction mixture was
stirred at 35–37°C for 1h. The progress of the reaction
was monitored by TLC. After completion of the reac-
tion, the mixture was cooled to 0–5°C and poured into
ice water gradually with vigorous stirring. The crystal-
line product was separated by filtration and used in the
next step without any purification.
(E)-5-(3-(4-Chlorophenyl)acryloyl)-2-methoxy-
benzene-1-sulfonyl chloride (IIIa). Mp 185–187°C;
yield 94%; IR (KBr, ν cm–1): 3093 (Ar–H), 1662
1
(C=O), 1600 (C=C), 1368, 1169 (SO2). H NMR
(400 MHz, CDCl3): δ 4.20 (s, 3H, OCH3), 7.29 (d,
J = 8.4 Hz, 1H, Ar–H), 7.45 (d, J = 8.4 Hz, 2H, Ar–
H), 7.51 (d, J = 15.6 Hz, 1H, COCH=CH), 7.64 (d,
J = 8.4 Hz, 2H, Ar–H), 7.86 (d, J = 15.6 Hz, 1H,
COCH=CH), 8.45 (dd, J = 8.4, 2.0 Hz, 1H, Ar–H),
8.65 (d, J = 2.0 Hz, 1H, Ar–H); 13C NMR (100 MHz,
CDCl3): 57.2, 113.5, 120.6, 129.4, 129.9, 130.3, 130.4,
131.7, 132.9, 137.0, 137.6, 144.6, 160.5, 186.3; Anal.
calcd. for C16H12Cl2O4S, %: C, 51.77; H, 3.26. Found,
%: C, 51.82; H, 3.12.
EXPERIMENTAL
All chemicals were purchased from Merck and
Fluka chemical companies. Melting points were taken
in open capillary tubes and are uncorrected. Infrared
spectra were recorded on a Perkin-Elmer V IR spec-
1
trophotometer. H NMR and 13C NMR spectra were
recorded either in pure CDCl3 on Bruker NMR spec-
trometers at 400 and 500, 100 and 125 MHz, respec-
tively. Chemical shifts are expressed in δ, ppm. Ele-
(E)-5-(3-(2,4-Dichlorophenyl)acryloyl)-2-methoxy-
benzene-1-sulfonyl chloride (IIIb). Mp 197–199°C;
mental analysis was carried out using Elemental Anal- yield 96%; IR (KBr, ν cm–1): 3091 (Ar–H), 1664
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CONVENIENT SYNTHESIS OF NOVEL CHALCONE
375
(C=O), 1601 (C=C), 1368, 1169 (SO2). 1H NMR (400
MHz, CDCl3): δ 4.17 (s, 3H, OCH3), 7.26 (d, J = 8.8
Hz, 1H, Ar–H), 7.33 (dd, J = 8.4, 2.0 Hz, 1H, Ar–
H), 7.45 (d, J = 15.6 Hz, 1H, COCH=CH), 7.48 (d,
J = 2.0 Hz, 1H, Ar–H), 7.72 (d, J = 8.4 Hz, 1H, Ar–
(E)-5-(3-(4-Chlorophenyl)acryloyl)-2-methoxy-N-
(2-methoxyphenyl)benzene sulfonamide (V). Mp 207–
209°C; yield 78%; IR (KBr, ν cm–1): 3309 (N–H),
3079 (Ar–H), 1661 (C=O), 1602 (C=C), 1342, 1161
1
(SO2). H NMR (400 MHz, CDCl3): δ 3.81 (s, 3H,
H), 8.17 (d, J = 15.6 Hz, 1H, COCH=CH), 8.41 (dd, OCH3), 4.08 (s, 3H, OCH3), 6.79 (dd, J = 8.0, 1.6 Hz,
J = 8.8, 2.0 Hz, 1H, Ar–H), 8.61 (d, J = 2.0 Hz, 1H,
1H, Ar–H), 6.88 (dt, J = 8.0, 1.6 Hz, 1H, Ar–H), 7.02
Ar–H); 13C NMR (100 MHz, CDCl3): 57.3, 113.5, (dt, J = 8.0, 1.6 Hz, 1H, Ar–H), 7.10 (d, J = 8.8 Hz,
1H, Ar–H), 7.44 (d, J = 8.4 Hz, 2H, Ar–H), 7.47 (d,
J = 15.6 Hz, 1H, COCH=CH), 7.56 (dd, J = 8.0,
1.6 Hz, 1H, Ar–H), 7.60 (s, 1H, N–H), 7.61 (d, J =
8.4 Hz, 2H, Ar–H), 7.78 (d, J = 15.6 Hz, 1H,
COCH=CH), 8.25 (dd, J = 8.8, 2.0 Hz, 1H, Ar–H),
8.54 (d, J = 2.0 Hz, 1H, Ar–H); 13C NMR (100 MHz,
CDCl3): 55.8, 56.6, 110.6, 112.1, 120.5, 121.2, 121.3,
125.0, 125.9, 126.9, 129.3, 129.8, 130.4, 131.4, 133.1,
135.5, 136.7, 143.9, 149.1, 159.9, 187.1; Anal. calcd. for
C23H20ClNO5S, %: C, 60.33; H, 4.40; N, 3.06.
Found, %: C, 60.58; H, 4.29; N, 3.14.
123.2, 127.7, 128.7, 130.1, 130.2, 130.5, 131.4, 131.7,
136.3, 137.0, 137.7, 140.5, 160.6, 186.3; Anal. calcd. for
C16H11Cl3O4S, %: C, 47.37; H, 2.73. Found, %: C,
47.15; H, 2.67.
(E)-2-Methoxy-5-(3-(4-nitrophenyl)acryloyl)ben-
zene-1-sulfonyl chloride (IIIc). Mp 219–221°C; yield
95%; IR (KBr, ν cm–1): 3100 (Ar–H), 1665 (C=O),
1
1596 (C=C), 1342, 1169 (SO2). H NMR (400 MHz,
CDCl3): δ 4.18 (s, 3H, OCH3), 7.28 (d, J = 8.8 Hz,
1H, Ar–H), 7.62 (d, J = 15.6 Hz, 1H, COCH=CH),
7.82 (d, J = 8.4 Hz, 2H, Ar–H), 7.89 (d, J = 15.6 Hz,
1H, COCH=CH), 8.30 (d, J = 8.4 Hz, 2H, Ar–H),
8.44 (dd, J = 8.8, 2.4 Hz, 1H, Ar–H), 8.64 (d, J = 2.0 Hz,
1H, Ar–H); 13C NMR (100 MHz, CDCl3): 57.4,
113.6, 123.9, 124.3, 129.2, 129.8, 130.5, 131.8, 137.6,
140.5, 142.8, 148.8, 160.8, 185.8; Anal. calcd. for
C16H12ClNO6S, %: C, 50.33; H, 3.17; N, 3.67. Found,
%: C, 50.42; H, 3.30; N, 3.55.
(E)-5-(3-(4-Chlorophenyl)acryloyl)-2-methoxy-
N-(p-tolyl)benzene sulfonamide (VI). Mp 208–210°C;
yield 89%; IR (KBr, ν cm–1): 3243 (N–H), 3037 (Ar–
1
H(, 1665 (C=O), 1599 (C=C), 1332, 1155 (SO2). H
NMR (400 MHz, CDCl3): δ 2.25 (s, 3H, CH3), 4.17
(s, 3H, OCH3), 7.01 (m, 4H, Ar–H), 7.13 (s, 1H, N–
H), 7.16 (d, J = 8.8 Hz, 1H, Ar–H), 7.42 (d, J = 8.4 Hz,
2H, Ar–H), 7.45 (d, J = 15.6 Hz, 1H, COCH=CH),
7.59 (d, J = 8.4 Hz, 2H, Ar–H), 7.76 (d, J = 15.6 Hz,
1H, COCH=CH), 8.26 (dd, J = 8.8, 2.4 Hz, 1H, Ar–H),
8.47 (d, J = 2.4 Hz, 1H, Ar–H); 13C NMR (100 MHz,
CDCl3): 20.8, 56.9, 112.4, 121.1, 122.1, 122.2, 126.4,
129.3, 129.8, 129.9, 130.8, 131.5, 133.1, 133.4, 135.7,
135.9, 136.8, 143.9, 159.5, 187.1; Anal. calcd. for
C23H20ClNO4S, %: C, 62.51; H, 4.56; N, 3.17. Found,
%: C, 62.65; H, 4.42; N, 3.27.
Synthesis of chalcone sulfonamide derivatives (IV–
XV). General procedure. Amine (1 mmol) and anhy-
drous K2CO3 (4 mmol) were ground together into fine
powder in a mortar. Then, chalcone sulfonyl chloride
derivatives (1 mmol) were added to the mixture under
vigorous stirring using magnetic stirrer at room tem-
perature. 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. Upon completion of the reaction, water was
added and the mixture was stirred for a few minutes.
The precipitate was collected by filtration, washed
with water, dried and crystallized from ethanol.
(E)-5-(3-(4-chlorophenyl)acryloyl)-N-(2,4-dimeth-
ylphenyl)-2-methoxybenzene sulfonamide (VII). Mp
200–202°C; yield 80%; IR (KBr, ν cm–1): 3279 (N–
H), 3030 (Ar–H(, 1661 (C=O), 1601 (C=C), 1330,
1
1160 (SO2). H NMR (400 MHz, CDCl3): δ 2.21 (s,
(E)-5-(3-(4-Chlorophenyl)acryloyl)-2-methoxy-N-
(4-methoxyphenyl)benzenesulfonamide (IV). Mp 180–
182°C; yield 88%; IR (KBr, ν cm–1): 3268 (N–H),
3083 (Ar–H), 1666 (C=O), 1600 (C=C), 1334, 1153
3H, CH3), 2.24 (s, 3H, CH3), 4.12 (s, 3H, OCH3),
6.70 (s, 1H, N–H), 6.83 (dd, J = 8.4, 1.6 Hz, 1H, Ar–
H), 6.95 (s, 1H, Ar–H), 6.96 (d, J = 8.4 Hz, 1H, Ar–
H), 7.17 (d, J = 8.8 Hz, 1H, Ar–H), 7.39 (d, J =
8.4 Hz, 2H, Ar–H), 7.43 (d, J = 15.6 Hz, 1H,
COCH=CH), 7.56 (d, J = 8.4 Hz, 2H, Ar–H), 7.74
(d, J = 15.6 Hz, 1H, COCH=CH), 8.28 (dd, J = 8.8,
2.0 Hz, 1H, Ar–H), 8.45 (d, J = 2.0 Hz, 1H, Ar–H);
13C NMR (100 MHz, CDCl3): 17.7, 20.8, 56.9, 112.4,
121.2, 123.8, 127.5, 127.7, 129.3, 129.8, 130.7, 131.2,
131.6, 131.8, 132.3, 133.1, 135.6, 136.3, 136.7, 143.9,
159.5, 187.1; Anal. calcd. for C24H22ClNO4S, %: C,
63.22; H, 4.86; N, 3.07. Found, %: C, 63.38; H, 4.73;
N, 3.19.
1
(SO2). H NMR (400 MHz, CDCl3): δ 3.73 (s, 3H,
OCH3), 4.19 (s, 3H, OCH3), 6.75 (d, J = 8.8 Hz, 2H,
Ar–H), 6.92 (s, 1H, N–H), 7.03 (d, J = 8.8 Hz, 2H,
Ar–H), 7.19 (d, J = 8.8 Hz, 1H, Ar–H), 7.42 (d, J =
8.4 Hz, 2H, Ar–H), 7.44 (d, J = 15.6 Hz, 1H,
COCH=CH), 7.59 (d, J = 8.4 Hz, 2H, Ar–H), 7.76
(d, J = 15.6 Hz, 1H, COCH=CH), 8.29 (dd, J = 8.8,
2 Hz, 1H, Ar–H), 8.42 (d, J = 2.0 Hz, 1H, Ar–H);
13C NMR (100 MHz, CDCl3): 55.4, 57.0, 112.4, 114.5,
121.1, 124.9, 126.4, 128.6, 129.3, 129.8, 130.8, 131.4,
133.1, 135.7, 136.7, 143.9, 158.1, 159.4, 187.1; Anal.
calcd. for C23H20ClNO5S, %: C, 60.33; H, 4.40; N,
3.06. Found, %: C, 60.52; H, 4.12; N, 3.21.
(E)-N-(4-Bromophenyl)-5-(3-(4-chlorophenyl)acry-
loyl)-2-methoxybenzene sulfonamide (VIII). Mp 255–
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(s, 3H, CH3), 2.27 (s, 3H, CH3), 4.16 (s, 3H, OCH3),
257°C; yield 71%; IR (KBr, ν cm–1): 3247 (N–H),
3027 (Ar–H), 1663 (C=O), 1600 (C=C), 1334, 1159 6.73 (s, 1H, N–H), 6.83 (d, J = 8.4 Hz, 1H, Ar–H),
1
6.98 (d, J = 8.4 Hz, 2H, Ar–H), 7.20 (d, J = 8.8 Hz,
1H, Ar–H), 7.32 (dd, J = 8.4, 2.0 Hz, 1H, Ar–H),
7.42 (d, J = 15.6 Hz, 1H, COCH=CH), 7.48 (d, J =
2.0 Hz, 1H, Ar–H), 7.71 (d, J = 8.4 Hz, 1H, Ar–H),
8.13 (d, J = 15.6 Hz, 1H, COCH=CH), 8.31 (dd, J =
8.8, 2.4 Hz, 1H, Ar–H), 8.47 (d, J = 2.4 Hz, 1H, Ar–
H); 13C NMR (125 MHz, CDCl3): 17.7, 20.8, 56.9,
112.5, 123.7, 123.9, 127.5, 127.6, 127.8, 128.7, 130.1,
130.5, 131.2, 131.5, 131.6, 131.8, 132.3, 135.7, 136.2,
136.3, 136.7, 139.8, 159.6, 187.0; Anal. calcd. for
C24H21Cl2NO4S, %: C, 58.78; H, 4.32; N, 2.86.
Found, %: C, 58.83; H, 4.63; N, 2.44.
(SO2). H NMR (400 MHz, CDCl3): δ 4.13 (s, 3H,
OCH3), 6.98 (d, J = 8.8 Hz, 2H, Ar–H), 7.02 (s, 1H,
N–H), 7.14 (d, J = 8.8 Hz, 1H, Ar–H), 7.33 (d, J =
8.8 Hz, 2H, Ar–H), 7.41 (d, J = 8.4 Hz, 2H, Ar–H),
7.43 (d, J = 15.6 Hz, 1H, COCH=CH), 7.58 (d, J =
8.4 Hz, 2H, Ar–H), 7.75 (d, J = 15.6 Hz, 1H,
COCH=CH), 8.25 (dd, J = 8.8, 2.0 Hz, 1H, Ar–H),
8.46 (d, J = 2.0 Hz, 1H, Ar–H); 13C NMR (100 MHz,
CDCl3): 57.0, 112.5, 119.0, 121.1, 123.2, 129.3, 129.7,
129.8, 130.9, 131.5, 132.5, 133.7, 135.3, 135.9, 136.8,
144.2, 159.3, 186.9; Anal. calcd. for C22H17BrClNO4S,
%: C, 52.14; H, 3.38; N, 2.76. Found, %: C, 52.37; H,
3.19; N, 2.64.
(E)-2-Methoxy-N-(4-methoxyphenyl)-5-(3-(4-
nitrophenyl)acryloyl)benzene sulfonamide (XII). Mp
210–212°C; yield 78%; IR (KBr, ν cm–1): 3261 (N–
H), 3078 (Ar–H(, 1666 (C=O), 1598 (C=C), 1341,
(E)-5-(3-(2,4-Dichlorophenyl)acryloyl)-2-methoxy-
N-(2-methoxyphenyl)benzene sulfonamide (IX). Mp
178–180°C; yield 86%; IR (KBr, ν cm–1): 3309 (N–
H), 3080 (Ar–H), 1663 (C=O), 1601 (C=C), 1342,
1
1156 (SO2). H NMR (400 MHz, CDCl3): δ 3.71 (s,
1
3H, OCH3), 4.18 (s, 3H, OCH3), 6.73 (d, J = 8.8 Hz,
2H, Ar–H), 6.85 (s, 1H, N–H), 7.00 (d, J = 8.8 Hz,
2H, Ar–H), 7.21 (d, J = 8.8 Hz, 1H, Ar–H), 7.54 (d,
J = 15.6 Hz, 1H, COCH=CH), 7.78 (m, 3H,
COCH=CH, Ar–H), 8.27 (d, 3H, Ar–H), 8.40 (d,
J = 1.2 Hz, 1H, Ar–H); 13C NMR (100 MHz,
CDCl3): 55.4, 57.0, 112.5, 114.5, 124.2, 125.1, 126.7,
128.4, 129.1, 130.4, 131.5, 135.7, 140.6, 142.1, 148.7,
158.1, 148.7, 159.7, 186.6; Anal. calcd. for
C23H20N2O7S, %: C, 58.97; H, 4.30; N, 5.98. Found,
%: C, 58.88; H, 4.51; N, 5.86.
1167 (SO2). H NMR (500 MHz, CDCl3): δ 3.79 (s,
3H, OCH3), 3.97 (s, 3H, OCH3), 6.68 (dd, J = 8.0, 1.6 Hz,
1H, Ar–H), 6.76 (td, J = 8.0, 1.6 Hz, 1H, Ar–H),
6.90 (td, J = 8.0, 1.6 Hz, 1H, Ar–H), 6.99 (d, J =
8.8 Hz, 1H, Ar–H), 7.24 (dd, J = 8.4, 2.0 Hz, 1H,
Ar–H), 7.33 (d, J = 15.6 Hz, 1H, COCH=CH), 7.38
(d, J = 2.0 Hz 1H, Ar–H), 7.44 (dd, J = 8.0, 1.6 Hz,
1H, Ar–H), 7.52 (s, 1H, N–H), 7.63 (d, J = 8.4 Hz,
1H, Ar–H), 8.02 (d, J = 15.6 Hz, 1H, COCH=CH),
8.13 (dd, J = 8.8, 2.4 Hz, 1H, Ar–H), 8.43 (d, J =
2.4 Hz, 1H, Ar–H); 13C NMR (125 MHz, CDCl3):
55.8, 56.6, 110.6, 112.2, 120.5, 121.3, 123.8, 125.1,
125.9, 127.0, 127.6, 128.0, 128.7, 130.1, 131.5, 131.6,
135.7, 136.2, 136.7, 139.7, 149.1, 160.0, 187.0; Anal.
calcd. for C23H19Cl2NO5S, %: C, 56.11; H, 3.89; N,
2.84. Found, %: C, 56.24; H, 3.78; N, 2.77.
(E)-2-Methoxy-N-(2-methoxyphenyl)-5-(3-(4-
nitrophenyl)acryloyl)benzene sulfonamide (XIII). Mp
204–206°C; yield 76%; IR (KBr, ν cm–1): 3355 (N–
H), 3080 (Ar–H), 1667 (C=O), 1599 (C=C), 1340,
1
1159 (SO2). H NMR (400 MHz, CDCl3): δ 3.81 (s,
(E)-5-(3-(2,4-Dichlorophenyl)acryloyl)-2-methoxy-
N-(p-tolyl)benzene sulfonamide (X). Mp 226–228°C;
yield 85%; IR (KBr, ν cm–1): 3324 (N–H), 3093 (Ar–
H(, 1658 (C=O), 1600 (C=C), 1332, 1160 (SO2).
3H, OCH3), 4.10 (s, 3H, OCH3), 6.80 (dd, J = 8.0,
1.6 Hz, 1H, Ar–H), 6.88 (td, J = 8.0, 1.6 Hz, 1H, Ar–
H), 7.03 (td, J = 8.0, 1.6 Hz, 1H, Ar–H), 7.12 (d, J =
8.8 Hz, 1H, Ar–H), 7.56 (dd, J = 8.0, 1.6 Hz, 1H, Ar–
H), 7.60 (d, J = 15.6 Hz, 1H, COCH=CH), 7.61 (s,
1H, N–H), 7.82 (d, J = 8.4 Hz, 2H, Ar–H), 7.84 (d,
J = 15.6 Hz, 1H, COCH=CH), 8.27 (dd, J = 8.8,
2.4 Hz, 1H, Ar–H), 8.32 (d, J = 8.4 Hz, 2H, Ar–H),
8.55 (d, J = 2.4 Hz, 1H, Ar–H); 13C NMR (100 MHz,
CDCl3): 55.8, 56.7, 110.6, 112.3, 120.6, 121.3, 124.3,
124.5, 125.1, 125.8, 127.1, 129.2, 129.9, 131.5, 135.7,
140.7, 142.1, 148.7, 149.2, 160.2, 186.7; Anal. calcd. for
C23H20N2O7S, %: C, 58.97; H, 4.30; N, 5.98. Found,
%: C, 58.78; H, 4.46; N, 5.84.
1H NMR (400 MHz, CDCl3): δ 2.25 (s, 3H, CH3),
4.18 (s, 3H, OCH3), 6.91 (s, 1H, N–H), 7.01 (m, 4H, Ar–
H), 7.17 (d, J = 8.8 Hz, 1H, Ar–H), 7.34 (d, J = 8.4 Hz,
1H, Ar–H), 7.41 (d, J = 15.6 Hz, 1H, COCH=CH),
7.50 (s, 1H, Ar–H), 7.72 (d, J = 8.4 Hz, 1H, Ar–H),
8.12 (d, J = 15.6 Hz, 1H, COCH=CH), 8.27 (d, J =
8.8 Hz, 1H, Ar–H), 8.46 (s, 1H, Ar–H); 13C NMR
(100 MHz, CDCl3): 20.8, 57.0, 112.5, 122.2, 112.3,
123.7, 126.5, 127.6, 128.7, 130.0, 130.2, 130.6, 131.5,
133.3, 135.8, 135.9, 136.2, 136.8, 139.9, 159.5, 187.0;
Anal. calcd. for C23H19Cl2NO4S, %: C, 57.99; H, 4.02;
N, 2.94. Found, %: C, 57.85; H, 4.17; N, 2.79.
(E)-2-Methoxy-5-(3-(4-nitrophenyl)acryloyl)-N-
(p-tolyl)benzene sulfonamide (XIV). Mp 236–237°C;
yield 81%; IR (KBr, ν cm–1): 3250 (N–H), 3112 (Ar–
H(, 1666 (C=O), 1599 (C=C), 1341, 1159 (SO2).
(E)-5-(3-(2,4-Dichlorophenyl)acryloyl)-N-(2,4-
dimethylphenyl)-2-methoxybenzene sulfonamide (XI).
Mp 187–189°C; yield 75%; IR (KBr, ν cm–1): 3324 1H NMR (400 MHz, CDCl3): δ 2.26 (s, 3H, CH3),
(N–H), 3090 (Ar–H(, 1657 (C=O), 1605 (C=C),
4.19 (s, 3H, OCH3), 6.89 (s, 1H, N–H), 6.99 (d, J =
8.4 Hz, 2H, Ar–H), 7.02 (d, J = 8.4 Hz, 2H, Ar–H),
1330, 1162 (SO2). 1H NMR (500 MHz, CDCl3): δ 2.23
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7.19 (d, J = 8.8 Hz, 1H, Ar–H), 7.58 (d, J = 15.6 Hz, 0–5°C and poured into ice water gradually with vigor-
1H, COCH=CH), 7.81 (d, J = 8.4 Hz, 2H, Ar–H), ous stirring. The crystalline product was separated by
7.83 (d, J = 15.6 Hz, 1H, COCH=CH), 8.29 (dd, J = filtration and used in the next step.
8.8, 2.0 Hz, 1H, Ar–H), 8.32 (d, J = 8.4 Hz, 2H, Ar–
H), 8.48 (d, J = 2.0 Hz, 1H, Ar–H); 13C NMR (100
MHz, CDCl3): 20.9, 57.1, 112.5, 122.4, 124.3, 124.4,
126.7, 129.2, 130.0, 130.3, 131.6, 133.3, 135.8, 136.0,
140.7, 142.2, 148.7, 159.7, 186.6; Anal. calcd. for
C23H20N2O6S, %: C, 61.05; H, 4.46; N, 6.19. Found,
%: C, 61.22; H, 4.32; N, 6.04.
(E)-2-Methyl-5-(3-(4-nitrophenyl)-3-oxoprop-1-
en-1-yl)furan-3-sulfonyl chloride (XVII). Mp 160–
162°C; yield 92%; IR (KBr, ν cm–1): 3118 (Ar–H),
1668 (C=O), 1609 (C=C), 1347, 1171 (SO2). 1H NMR
(400 MHz, DMSO): δ 2.55 (s, 3H, CH3), 7.17 (s, 1H,
Ar–H), 7.49 (d, J = 16.0 Hz, 1H, COCH=CH), 7.62
(d, J = 16.0 Hz, 1H, COCH=CH), 8.33 (d, J =
8.0 Hz, 2H, Ar–H), 8.41 (d, J = 8.0 Hz, 2H, Ar–H);
13C NMR (100 MHz, DMSO): 12.8, 117.2, 119.0,
123.8, 129.6, 131.6, 142.4, 147.4, 149.6, 153.4, 187.4;
Anal. calcd. for C14H10ClNO6S, %: C, 47.27; H, 2.83;
Cl, 9.97; N, 3.94; O, 26.98; S, 9.01. Found, %: C,
47.01; H, 3.13; Cl, 10.31; N, 3.15; O, 27.22; S, 8.75.
(E)-N-(2,4-Dimethylphenyl)-2-methoxy-5-(3-(4-
nitrophenyl)acryloyl)benzene sulfonamide (XV). Mp
214–216°C; yield 85%; IR (KBr, ν cm–1): 3323 (N–
H), 3090 (Ar–H(, 1659 (C=O), 1598 (C=C), 1339,
1
1159 (SO2). H NMR (500 MHz, CDCl3): δ 2.22 (s,
3H, CH3), 2.28 (s, 3H, CH3), 4.14 (s, 3H, OCH3),
6.73 (s, 1H, N–H), 6.86 (d, J = 8.4 Hz, 1H, Ar–H),
Synthesis of chalcone sulfonamide derivatives (XVIII–
6.98 (m, 2H, Ar–H), 7.22 (d, J = 8.8 Hz, 1H, Ar–H), XXVI); General procedure. An amine (1 mmol) and
7.59 (d, J = 15.6 Hz, 1H, COCH=CH), 7.80 (d, J = anhydrous NaHCO3 (2 mmol) were ground together
8.4 Hz, 2H, Ar–H), 7.83 (d, J = 15.6 Hz, 1H,
COCH=CH), 8.29 (d, J = 8.4 Hz, 2H, Ar–H), 8.33
(dd, J = 8.8, 2.0 Hz, 1H, Ar–H), 8.49 (d, J = 2.0 Hz,
into fine powder in a mortar and chalcone sulfonyl
chloride derivative (1 mmol) was added under vigor-
ous stirring with a magnetic stirrer at room tempera-
1H, Ar–H); 13C NMR (125 MHz, CDCl3): 17.7, 20.8, ture. 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.
Upon completion of the reaction, water was added and
the mixture was stirred for a few minutes. The precip-
itate was collected by filtration, washed with water and
dried. All of the products were obtained in high purity.
56.9, 112.6, 114.7, 124.0, 124.2, 124.5, 127.5, 129.2,
130.3, 131.3, 131.6, 131.8, 132.5, 135.7, 136.5, 140.7,
142.1, 148.7, 159.8, 186.6; Anal. calcd. for
C24H22N2O6S, %: C, 61.79; H, 4.75; N, 6.00. Found,
%: C, 61.90; H, 4.54; N, 6.19.
Synthesis of furan derived chalcones (XVI); General
procedure. Sodium hydroxide (20%, 15 mL) was
added dropwise to a mixture of 4-nitroacetophenone
(3 mmol) and 5-methylfurfural (3 mmol) in ethanol,
over 2–3 min under constant stirring using magnetic
stirrer. The reaction mixture was stirred at room tem-
(E)-N-(4-Chlorophenyl)-2-methyl-5-(3-(4-nitrophe-
nyl)-3-oxoprop-1-en-1-yl)furan-3-sulfonamide
(XVIII).
Mp 183–185°C; yield 65%; IR (KBr, ν cm–1): 3231
(N–H), 3108 (Ar–H(, 1660 (C=O), 1590 (C=C),
1
1342, 1158 (SO2). H NMR (400 MHz, DMSO): δ
perature for 2 h. The progress of the reaction was mon- 2.47 (s, 3H, CH3), 7.16 (dd, J = 6.8, 2.0 Hz, 2H, Ar–
itored by TLC. After completion of the reaction, the
mixture was poured into chilled water (100 mL) and
neutralized with hydrochloric acid. The temperature
of the chilled water was kept in the range of 2–5°C.
The product was obtained by simple filtration and
used in the next step without any purification.
(E)-3-(5-Methylfuran-2-yl)-1-(4-nitrophenyl)prop-
2-en-1-one (XVI). Mp 155–157°C; yield 90%; IR
(KBr, ν cm–1): 3111 (Ar–H), 1660 (C=O), 1606
(C=C). 1H NMR (400 MHz, DMSO): δ 2.40 (s, 3H,
CH3), 6.3 (d, J= 4.0 Hz, 1H, Ar–H), 7.08 (d, J = 4.0 Hz,
1H, Ar–H), 7.40 (d, J = 16 Hz, 1H, COCH=CH),
7.57 (d, J = 16 Hz, 1H, COCH=CH), 8.26 (d, J =
8.0 Hz, 2H, Ar–H), 8.36 (d, J = 8.0 Hz, 2H, Ar–H).
H), 7.23 (s, 1H, Ar–H), 7.36 (dd, J = 6.8, 2.0 Hz, 2H,
Ar–H), 7.51 (d, J = 15.6 Hz, 1H, COCH=CH), 7.56
(d, J = 15.6 Hz, 1H, COCH=CH), 8.26 (dd, J = 6.8,
2.0 Hz, 2H, Ar–H), 8.35 (dd, J = 6.8, 2.0 Hz, 2H,
Ar–H), 10.55(s, 1H, N–H); 13C NMR (100 MHz,
DMSO): 13.4, 116.6, 120.6, 122.7, 123.9, 124.3, 129.2,
129.7, 129.8, 130.2, 130.9, 136.7, 142.4, 149.6, 150.3,
158.8, 188.1; Anal. calcd. for C20H15ClN2O6S, %: C,
53.76; H, 3.38; Cl, 7.93; N, 6.27; O, 21.48; S, 7.18.
Found, %: C, 53.41; H, 3.98; Cl, 7.11; N, 6.85; O,
21.97; S, 6.82.
(E)-2-Methyl-5-(3-(4-nitrophenyl)-3-oxoprop-1-
en-1-yl)-N-(p-tolyl)furan-3-sulfonamide (XIX). Mp
179–181°C; yield 84%; IR (KBr, ν cm–1): 3237 (N–
H), 3103 (Ar–H), 1662 (C=O), 1600 (C=C), 1339,
Synthesis of chalcone sulfonyl chloride (XVII); Gen-
eral procedure. Cold chlorosulfonic acid (22.5 mmol)
was added to compound (XVI) (1 mmol, 0.257 g), with
stirring for 1h while maintaining the temperature at 0–
5°C. The reaction mixture was stirred at room tempra-
ture for 1h and it was stirred at 35–37°C for 2 h. The
progress of the reaction was monitored by TLC. After
1
1157 (SO2). H NMR (400 MHz, CDCl3): δ 2.34 (s,
3H, CH3), 2.37 (s, 3H, CH3), 6.48 (s, 1H, N–H), 6.81
(s, 1H, Ar–H), 7.03 (dd, J = 8.0, 2.0 Hz, 2H, Ar–H),
7.13 (dd, J = 8.0, 2.0 Hz, 2H, Ar–H), 7.39 (d, J =
15.6 Hz, 1H, COCH=CH), 7.49 (d, J = 15.6 Hz, 1H,
COCH=CH), 8.16 (dd, J = 7.2, 2.0 Hz, 2H, Ar–H),
completion of the reaction, the mixture was cooled to 8.36 (dd, J = 7.2, 2.0 Hz, 2H, Ar–H); 13C NMR
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BONAKDAR et al.
(100 MHz, CDCl3): 13.2, 20.9, 115.7, 119.7, 123.3,
123.4, 123.9, 129.3, 130.0, 130.6, 132.9, 136.6, 142.4,
(E)-2-Methyl-5-(3-(4-nitrophenyl)-3-oxoprop-1-
en-1-yl)-N-phenylfuran-3-sulfonamide (XXIII). Mp
149.2, 159.3, 187.6; Anal. calcd. for C21H18N2O6S, %: 168–170°C; yield 58%; IR (KBr, ν cm–1): 3250 (N–
H), 3121 (Ar–H(, 1663 (C=O), 1594 (C=C), 1343,
C, 59.15; H, 4.25; N, 6.57; O, 22.51; S, 7.52. Found,
%: C, 59.40; H, 4.95; N, 6.02; O, 22.77; S, 7.96.
1
1158 (SO2). H NMR (400 MHz, DMSO): δ 2.42 (s,
3H, CH3), 7.13 (dd, J = 7.6, 3.2 Hz, 3H, Ar–H), 7.24
(s, 1H, Ar–H), 7.29 (dd, J = 7.6, 3.2 Hz, 2H, Ar–H),
7.51 (d, J = 15.6 Hz, 1H, COCH=CH), 7.56 (d, J =
15.6 Hz, 1H, COCH=CH), 8.26 (dd, J = 6.8, 2.0 Hz,
2H, Ar–H), 8.35 (dd, J = 6.8, 2.0 Hz, 2H, Ar–H),
10.39 (s, 1H, N–H); 13C NMR (100 MHz, DMSO):
13.3, 116.8, 120.5, 121.3, 124.2, 124.3, 125.1, 129.7,
130.1, 130.2, 130.9, 137.6, 142.4, 149.5, 150.3, 158.6,
188.1; Anal. calcd. for C20H16N2O6S, %: C, 58.25; H,
3.91; N, 6.79; O, 23.28; S, 7.77. Found, %: C, 58.33;
H, 3.47; N, 6.56; O, 23.98; S, 7.24.
(E)-N-(4-Bromophenyl)-2-methyl-5-(3-(4-nitro-
phenyl)-3-oxoprop-1-en-1-yl)furan-3-sulfonamide (XX).
Mp 166–168°C; yield 73%; IR (KBr, ν cm–1): 3223
(N–H), 3108 (Ar–H), 1659 (C=O), 1604 (C=C),
1
1341, 1159 (SO2). H NMR (400 MHz, DMSO): δ
2.47 (s, 3H, CH3), 7.09 (dd, J = 8.8, 2.0 Hz, 2H, Ar–
H), 7.23 (s, 1H, Ar–H), 7.49 (dd, J = 8.8, 2.0 Hz, 2H,
Ar–H), 7.51 (d, J = 15.6 Hz, 1H, COCH=CH), 7.56
(d, J = 15.6 Hz, 1H, COCH=CH), 8.26 (dd, J = 8.4,
2.0 Hz, 2H, Ar–H), 8.33 (dd, J = 8.4, 2.0 Hz, 2H,
Ar–H), 10.56 (s, 1H, N–H); 13C NMR (100 MHz,
DMSO): 13.4, 116.6, 117.2, 120.6, 122.9, 123.9, 124.3,
130.2, 130.9, 132.5, 132.6, 137.1, 142.4, 149.6, 150.3,
(E)-N-(4-Methoxyphenyl)-2-methyl-5-(3-(4-nitro-
phenyl)-3-oxoprop-1-en-1-yl)furan-3-sulfonamide (XXIV).
158.8, 188.1; Anal. calcd. for C20H15BrN2O6S, %: C, Mp 158–160°C; yield 88%; IR (KBr, ν cm–1): 3247
(N–H), 3105 (Ar–H), 1659 (C=O), 1601 (C=C),
48.89; H, 3.08; Br, 16.62; N, 5.70; O, 19.54; S, 6.53.
Found, %: C, 48.36; H, 2.71; Br, 16.32; N, 5.99; O, 1337, 1158 (SO2). 1H NMR (400 MHz, CDCl3): δ 2.31
19.03; S, 6.12.
(s, 3H, CH3), 3.80 (s, 3H, OCH3), 6.73 (s, 1H, N–H),
6.83 (s, 1H, Ar–H), 6.84 (dd, J = 6.8, 2.4 Hz, 2H, Ar–
H), 7.08 (dd, J = 6.8, 2.4 Hz, 2H, Ar–H), 7.36 (d, J =
15.6 Hz, 1H, COCH=CH), 7.50 (d, J = 15.6 Hz, 1H,
COCH=CH), 8.16 (dd, J = 6.8, 2.0 Hz, 2H, Ar–H),
8.35 (dd, J = 6.8, 2.0 Hz, 2H, Ar–H); 13C NMR
(100 MHz, CDCl3): 13.1, 55.4, 114.6, 114.8, 115.8,
119.7, 123.1, 123.9, 126.2, 128.0, 129.3, 130.7, 142.4,
149.3, 150.2, 158.6, 159.3, 187.7; Anal. calcd. for
C21H18N2O7S, %: C, 57.01; H, 4.10; N, 6.33; O, 25.31;
S, 7.25. Found, %: C, 57.24; H, 4.68; N, 6.99; O,
25.74; S, 7.64.
(E)-N-(2-Chlorophenyl)-2-methyl-5-(3-(4-nitro-
phenyl)-3-oxoprop-1-en-1-yl)furan-3-sulfonamide (XXI).
Mp 146–148°C; yield 61%; IR (KBr, ν cm–1): 3206
(N–H), 3117 (Ar–H), 1664 (C=O), 1601 (C=C),
1
1344, 1164 (SO2). H NMR (400 MHz, DMSO): δ
2.32 (s, 3H, CH3), 7.21 (s, 1H, Ar–H), 7.27–7.37 (m,
3H, Ar–H), 7.47 (d, J = 7.6 Hz, 1H, Ar–H), 7.55 (d,
J = 18.0 Hz, 1H, COCH=CH), 7.59 (d, J = 18.0 Hz,
1H, COCH=CH), 8.28 (d, J = 8.8 Hz, 2H, Ar–H),
8.36 (d, J = 8.8 Hz, 2H, Ar–H), 10.20 (s, 1H, N–H);
13C NMR (100 MHz, DMSO): 13.2, 117.0, 120.3,
124.3, 125.2, 128.3, 128.9, 129.3, 130.2, 130.4, 130.4,
(E)-N-(2-Methoxyphenyl)-2-methyl-5-(3-(4-nitro-
131.1, 133.4, 142.4, 149.5, 150.3, 158.4, 188.0; Anal. phenyl)-3-oxoprop-1-en-1-yl)furan-3-sulfonamide (XXV).
Mp 167–169°C; yield 75%; IR (KBr, ν cm–1): 3254
calcd. for C20H15ClN2O6S, %: C, 53.76; H, 3.38; Cl,
7.93; N, 6.27; O, 21.48; S, 7.18. Found, %: C, 53.45; (N–H), 3116 (Ar–H(, 1670 (C=O), 1615 (C=C),
1
H, 3.91; Cl, 7.12; N, 6.89; O, 21.92; S, 6.87.
1342, 1161 (SO2). H NMR (400 MHz, DMSO): δ
2.31 (s, 3H, CH3), 3.57 (s, 3H, OCH3), 6.92 (dd, J =
8.0, 8.0 Hz, 1H, Ar–H), 6.96 (dd, J = 8.4, 2.0 Hz, 1H,
Ar–H), 7.17 (s, 1H, Ar–H), 7.21 (dd, J = 8.0, 8.0 Hz,
1H, Ar–H), 7.24 (dd, J = 8.0, 2.0 Hz, 1H, Ar–H),
7.53 (d, J = 15.6 Hz, 1H, COCH=CH), 7.58 (d, J =
15.6 Hz, 1H, COCH=CH), 8.27 (dd, J = 8.8, 2.0 Hz,
2H, Ar–H), 8.35 (dd, J = 8.8, 2.0 Hz, 2H, Ar–H),
9.60 (s, 1H, N–H); 13C NMR (100 MHz, DMSO):
13.1, 55.9, 112.2, 117.3, 120.0, 120.9, 124.3, 124.9,
125.1, 127.3, 128.1, 130.2, 131.1, 142.5, 149.1, 150.3,
153.7, 158.4, 188.0; Anal. calcd. for C21H18N2O7S, %:
C, 57.01; H, 4.10; N, 6.33; O, 25.31; S, 7.25. Found,
%: C, 57.29; H, 4.71; N, 7.00; O, 25.70; S, 7.69.
(E)-N-(2,4-Dimethylphenyl)-2-methyl-5-(3-(4-
nitrophenyl)-3-oxoprop-1-en-1-yl)furan-3-sulfon-
amide (XXII). Mp 171–173°C; yield 60%; IR (KBr,
ν cm–1): 3120 (N–H), 3108 (Ar–H(, 1657 (C=O),
1
1595 (C=C), 1342, 1159 (SO2). H NMR (400 MHz,
CDCl3): δ 2.14 (s, 3H, CH3), 2.30 (s, 3H, CH3), 2.31
(s, 3H, CH3), 6.43 (s, 1H, N–H), 6.85 (s, 1H, Ar–H),
6.98 (s, 1H, Ar–H), 7.00 (s, 1H, Ar–H), 7.16 (d, J =
8.0 Hz, 1H, Ar–H), 7.40 (d, J = 15.6 Hz, 1H,
COCH=CH), 7.50 (d,
J
=
15.6 Hz, 1H,
COCH=CH), 8.16 (dd, J = 8.0, 2.0 Hz, 2H, Ar–H),
8.35 (dd, J = 8.0, 2.0 Hz, 2H, Ar–H); 13C NMR
(100 MHz, CDCl3): 13.0, 17.7, 20.9, 115.8, 119.7,
123.9, 124.0, 125.8, 127.6, 129.3, 130.6, 130.9, 131.7,
132.8, 137.2, 142.4, 149.2, 150.2, 159.2, 187.6; Anal.
calcd. for C22H20N2O6S, %: C, 59.99; H, 4.58; N,
6.36; O, 21.79; S, 7.28. Found, %: C, 59.55; H, 4.36;
N, 6.88; O, 21.24; S, 7.52.
(E)-2-Methyl-5-(3-(4-nitrophenyl)-3-oxoprop-1-
en-1-yl)-N-(pyridin-3-yl)furan-3-sulfonamide (XXVI).
Mp 158–160°C; yield 70%; IR (KBr, ν cm–1): 3202
(N–H), 3145 (Ar–H), 1660 (C=O), 1604 (C=C),
1
1346, 1162 (SO2). H NMR (400 MHz, DMSO): δ
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Table 4. In vitro antibacterial activity of compounds (IV–XV), (XVIII–XXVI), and (XXIX–XXXII) using agar well diffu-
sion method
Diameter of zone of inhibition, mm
Antibacterial strains
Antibacterial strains
Compounds
(IV)
(V)
(VI)
(VII)
(VIII)
(IX)
(X)
(XI)
(XII)
(XIII)
(XIV)
(XV)
(XVIII)
(XIX)
Compounds
(XX)
(XXI)
(XXII)
(XXIII)
(XXIV)
(XXV)
(XXVI)
(XXIX)
(XXX)
(XXXI)
(XXXII)
Control (DMSO)
Ampicillin
S. aureus
E. coli
S. aureus
E. coli
– (>22)
– (>22)
9 (22)
– (>22)
9 (22)
– (>22)
9 (22)
– (>22)
– (>22)
9 (22)
11 (0.625)
10 (0.625)
10 (1.25)
10 (0.156)
10 (1.25)
11 (2.5)
11 (0.625)
9 (22)
11 (2.5)
10 (5)
11 (2.5)
12 (2.5)
11 (2.5)
11 (2.5)
12 (5)
11 (11)
– (>44)
11 (11)
10 (11)
–
9 (22)
10 (22)
10 (44)
– (>22)
10 (22)
9 (22)
– (>22)
– (>22)
– (>22)
9 (22)
10 (44)
10 (22)
9 (22)
9 (22)
– (>22)
– (>22)
10 (5)
– (>22)
11 (2.5)
11 (0.625)
–
16 (0.156)
18 (0.156)
12 (5)
–, No activity.
Values in parentheses; MIC (mg/mL), minimum inhibitory concentration.
Values, including diameter of the well (6 mm).
2.46 (s, 3H, CH3), 7.26 (s, 1H, Ar–H), 7.40-7.60 (m, (dd, J = 17.6, 4.4 Hz 1H, pyrazoline–H), 3.75 (dd, J
= 17.6, 11.6 Hz, 1H, pyrazoline–H), 3.88 (s, 3H,
OCH3), 5.56 (dd, J = 11.6, 4.4 Hz, 1H, pyrazoline–
H), 6.97 (d, J = 8.8 Hz, 2H, Ar–H), 7.20 (d, J = 8.4
Hz, 2H, Ar–H), 7.31 (d, J = 8.4 Hz, 2H, Ar–H), 7.71
3H, COCH=CH, Ar–H), 7.61 (d, J = 8.0 Hz, 1H,
Ar–H), 8.26 (d, J = 8.0 Hz, 2H, Ar–H), 8.32-8.41 (m,
4H, Ar–H), 10.76 (s, 1H, N–H); 13C NMR
(100 MHz, DMSO): 13.4, 116.5, 120.7, 123.7, 124.3,
124.9, 129.3, 130.2, 130.8, 134.7, 141.9, 142.3, 145.5, (d, J = 8.8 Hz, 2H, Ar–H); 13C NMR (100 MHz,
149.7, 150.3, 158.9, 188.1; Anal. calcd. for CDCl3): 22.0, 42.3, 55.4, 59.2, 114.2, 123.8, 127.1,
C19H15N3O7S, %: C, 55.20; H, 3.66; N, 10.16; O,
128.2, 129.0, 133.4, 140.5, 153.6, 161.4, 168.7; Anal.
23.22; S, 7.76. Found, %: C, 55.98; H, 3.10; N, 10.63; calcd. for C18H17ClN2O2, %: C, 65.75; H, 5.21; N,
O, 23.84; S, 8.11.
8.52. Found, %: C, 65.63; H, 5.44; N, 8.35.
Synthesis of acetyl pyrazoline; General procedure.
To an ethanolic solution of chalcone (IIa) (10 mmol),
hydrazine hydrate (15 mmol) was added dropwise.
The reaction mixture was heated under reflux for 8 h.
after the completion of the reaction, as it was shown by
TLC, the reaction mixture was cooled, poured into the
crushed ice, filtered and dried at room temperature.
To the obtained product in CHCl3 (10 mL), acetyl
chloride (10 mmol) was added slowly under vigorous
stirring at room temperature. The progress of the reac-
tion was monitored by TLC. After completion of the
reaction, the solvent was evaporated and the solid
product was washed with water and recrystallized from
n-hexane–ethyl acetate mixed solvent.
Synthesis of acetyl pyrazoline sulfonyl chloride
derivatives (XXVIII–XXXII); General procedure.
Chlorosulphonic acid (9 mmol) was added dropwise
to a cooled and stirred solution of acetyl pyrazoline
(XXVII) (1 mmol, 0.328 g) in 5 mL chloroform. The
reaction mixture was stirred at 0–5°C for 1h and then
the mixture was stirred at 35–37°C for 1h. The prog-
ress of the reaction was monitored by TLC. After com-
pletion of the reaction, the mixture was cooled to 0–
5°C and poured into ice water gradually with vigorous
stirring. The solid product was separated by filtration
in high purity.
5-(1-Acetyl-5-(4-chlorophenyl)-4,5-dihydro-1H-
pyrazol-3-yl)-2-methoxybenzene-1-sulfonyl chloride
(XXVIII). Mp 238–240°C; yield 53%; IR (KBr, ν cm–1):
1-(5-(4-Chlorophenyl)-3-(4-methoxyphenyl)-4,5-
dihydro-1H-pyrazol-1-yl)ethanone (XXVII). Mp 173– 3091 (Ar–H), 2847 (CH2), 1655 (C=O), 1602 (C=C),
180°C; yield 80%; IR (KBr, ν cm–1): 3052 (Ar–H),
2841 (CH2), 1654 (C=O), 1602 (pyrazoline C=N). 1H
NMR (400 MHz, CDCl3): δ 2.43 (s, 3H, CH3), 3.12
1367, 1175 (SO2). 1H NMR (400 MHz, CDCl3): δ 2.42
(s, 3H, CH3), 3.12 (dd, J = 17.6, 4.8 Hz, 1H, pyrazo-
line-H), 3.76 (dd, J = 17.6, 12.0 Hz, 1H, pyrazoline-
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380
BONAKDAR et al.
H), 4.12 (s, 3H, OCH3), 5.60 (dd, J = 12.0, 4.8 Hz, OCH3), 5.54 (dd, J = 12.0, 4.8 Hz, 1H, pyrazoline-H),
1H, pyrazoline-H), 7.15 (d, J = 8.4 Hz, 2H, Ar–H), 7.02 (d, J = 8.8 Hz, 2H, Ar–H), 7.06 (d, J = 8.8 Hz, 1H,
7.19 (d, J = 8.8 Hz, 1H, Ar–H), 7.29 (d, J = 8.4 Hz, Ar–H), 7.13 (d, J = 8.8 Hz, 2H, Ar–H), 7.14 (s, 1H,
2H, Ar–H), 8.10 (dd, J = 8.8, 2.4 Hz, 1H, Ar–H), N–H), 7.17 (d, J = 8.8 Hz, 2H, Ar–H), 7.28 (d, J =
8.22 (d, J = 2.4 Hz, 1H, Ar–H); 13C NMR (100 MHz,
128.0, 129.2, 130.0, 132.2, 133.7, 139.8, 151.4, 158.4,
8.8 Hz, 2H, Ar–H), 7.92 (dd, J = 8.8, 2.0 Hz, 1H, Ar–
CDCl3): 21.9, 42.1, 57.0, 59.7, 113.6, 124.0, 127.0, H), 8.05 (d, J = 2.0 Hz, 1H, Ar–H); 13C NMR
(100 MHz, CDCl3): 21.9, 42.1, 56.9, 59.5, 112.5,
169.1; Anal. calcd. for C18H16Cl2N2O4S, %: C, 50.59; 123.0, 124.5, 126.7, 127.0, 127.1, 129.1, 129.4, 131.2,
132.9, 133.5, 134.9, 140.0, 151.7, 157.3, 168.9; Anal.
calcd. for C24H21Cl2N3O4S, %: C, 55.60; H, 4.08; N,
8.11. Found, %: C, 55.74; H, 4.16; N, 8.32.
H, 3.77; N, 6.56. Found, %: C, 50.64; H, 3.88; N,
6.81.
5-(1-Acetyl-5-(4-chlorophenyl)-4,5-dihydro-1H-
pyrazol-3-yl)-2-methoxy-N-(4-methoxyphenyl) ben-
zene sulfonamide (XXIX). Mp 239–241°C; yield 76%;
IR (KBr, ν cm–1): 3180 (N–H), 3071 (Ar–H(, 2837
(CH2(, 1645 (C=O), 1603 (C=N), 1331, 1157 (SO2).
5-(1-Acetyl-5-(4-chlorophenyl)-4,5-dihydro-1H-
pyrazol-3-yl)-N-(4-bromophenyl)-2-methoxybenzene
sulfonamide (XXXII). Mp 160–162°C; yield 70%; IR
(KBr, ν cm–1): 3350 (N–H), 3050 (Ar–H(, 2849
(CH2(, 1655 (C=O), 1601 (C=N), 1332, 1160 (SO2).
1H NMR (400 MHz, CDCl3): δ 2.41 (s, 3H, CH3),
3.06 (dd, J = 17.6, 4.4 Hz, 1H, pyrazoline-H), 3.69
(dd, J = 17.6, 11.6 Hz, 1H, pyrazoline-H), 3.75 (s, 3H,
OCH3), 4.16 (s, 3H, OCH3), 5.55 (dd, J = 11.6, 4.4
Hz, 1H, pyrazoline-H), 6.76 (d, J = 8.8 Hz, 2H, Ar–
H), 6.87 (s, 1H, N–H), 7.02 (d, J = 8.8 Hz, 2H, Ar–
H), 7.12 (d, J = 8.8 Hz, 1H, Ar–H), 7.15 (d, J = 8.8
Hz, 2H, Ar–H), 7.30 (d, J = 8.8 Hz, 2H, Ar–H), 7.97
(d, J = 8.8 Hz, 1H, Ar–H), 8.00 (s, 1H, Ar–H); 13C
NMR (100 MHz, CDCl3): 22.0, 42.1, 55.4, 56.9, 59.5,
112.5, 114.5, 124.5, 125.1, 127.0, 127.2, 128.7, 129.1,
129.2, 132.6, 133.5, 140.0, 151.8, 157.3, 158.1, 168.9;
Anal. calcd. for C25H24ClN3O5S, %: C, 58.42; H, 4.71;
N, 8.18. Found, %: C, 58.18; H, 4.59; N, 8.43.
1H NMR (400 MHz, CDCl3): δ 2.37 (s, 3H, CH3),
3.02 (dd, J = 15.0, 6.0 Hz, 1H, pyrazoline-H), 3.71
(dd, J = 15.0, 11.0 Hz, 1H, pyrazoline-H), 3.99 (s, 3H,
OCH3), 5.56 (dd, J = 11.0, 6.0 Hz, 1H, pyrazoline-
H), 6.90 (d, J = 8.0 Hz, 2H, Ar–H), 7.00 (s, 1H, N–
H), 7.11 (d, J = 8.0 Hz, 2H, Ar–H), 7.15 (d, J = 8.8
Hz, 1H, Ar–H), 7.22 (d, J = 8.8 Hz, 2H, Ar–H), 7.26
(d, J = 8.8 Hz, 2H, Ar–H), 7.87 (d, J = 8.8 Hz, 1H,
Ar–H), 8.05 (s, 1H, Ar–H); 13C NMR (100 MHz,
CDCl3): 21.9, 42.1, 56.7, 59.5, 112.6, 116.7, 123.1,
124.3, 127.0, 129.0, 129.1, 130.4, 131.7, 132.0, 132.2,
133.5, 140.0, 151.8, 157.3, 168.9; Anal. calcd. for
C24H21BrClN3O4S, %: C, 51.21; H, 3.76; N, 7.47.
Found, %: C, 51.45; H, 3.68; N, 7.62.
5-(1-Acetyl-5-(4-chlorophenyl)-4,5-dihydro-1H-
pyrazol-3-yl)-2-methoxy-N-(p-tolyl) benzene sulfon-
amide (XXX). Mp 274–276°C; yield 79%; IR (KBr, ν
cm–1): 3198 (N–H), 3070 (Ar–H(, 2848 (CH2(, 1644
Antibacterial activity. All the target compounds
(IV–XV), (XVIII–XXVI), and (XXIV–XXXII) were
evaluated for their antibacterial activity against Staph-
ylococcus aureus ATCC 25923 as the representative of
gram-positive bacteria and Escherichia coli ATCC
25922 as the representative of gram-negative bacteria,
1
(C=O), 1605 (C=N), 1332, 1159 (SO2). H NMR
(400 MHz, CDCl3): δ 2.27 (s, 3H, CH3), 2.41 (s, 3H,
CH3), 3.07 (dd, J = 17.6, 4.4 Hz, 1H, pyrazoline-H),
3.71 (dd, J = 17.6, 11.6 Hz, 1H, pyrazoline-H), 4.14 (s, using the agar diffusion method [9, 10, 25]. Suspen-
3H, OCH3), 5.56 (dd, J = 11.6, 4.4 Hz, 1H, pyrazo-
line-H), 6.89 (s, 1H, N–H), 6.99 (d, J = 8.0 Hz, 2H,
Ar–H), 7.04 (d, J = 8.0 Hz, 2H, Ar–H), 7.10 (d, J =
8.8 Hz, 1H, Ar–H), 7.15 (d, J = 8.0 Hz, 2H, Ar–H),
7.31 (d, J = 8.0 Hz, 2H, Ar–H), 7.96 (d, J = 8.8 Hz,
1H, Ar–H), 8.05 (s, 1H, Ar–H); 13C NMR
(100 MHz, CDCl3): 20.9, 22.0, 42.2, 56.9, 59.5, 112.5,
122.4, 124.5, 127.0, 127.2, 129.1, 129.2, 129.9, 132.6,
133.5, 133.6, 135.8, 140.0, 151.8, 157.3, 168.9; Anal.
calcd. for C25H24ClN3O4S, %: C, 60.30; H, 4.86; N,
8.44. Found, %: C, 60.21; H, 4.55; N, 8.63.
sion of bacteria in sterile peptone water was adjusted to
0.5 McFarland as standard in order to achieve a con-
centration of 1.58 × 108 bacterial colony forming units
(CFU)/mL. The target compounds were dissolved in
DMSO (1 mL) and the solution was diluted with
nutrient broth (4 mL) to get a stock solution of 2000
µg/mL of each compound. The test cultures were
incubated at 37°C until they were visibly turbid. After
incubation, the growth inhibition zone around the
disc was observed indicating that the examined com-
pounds inhibit the growth of microorganisms. To
ensure that the solvent had no effect on the bacterial
growth, a control test was performed with a test
medium supplemented with DMSO at the same dilu-
tions as used in the experiment. The standard antibi-
otic (ampicillin) was also diluted in the same manner.
The diameters of the zones of inhibition and mini-
mum inhibitory concentrations (MIC) for compounds
5-(1-Acetyl-5-(4-chlorophenyl)-4,5-dihydro-1H-
pyrazol-3-yl)-N-(4-chlorophenyl)-2–methoxy benzene
sulfonamide (XXXI). Mp 158–160°C; yield 73%; IR
(KBr, ν cm–1): 3263 (N–H), 3053 (Ar–H(, 2847
(CH2(, 1664 (C=O), 1601 (C=N), 1331, 1161 (SO2).
1H NMR (400 MHz, CDCl3): δ 2.39 (s, 3H, CH3),
3.05 (dd, J = 17.6, 4.8 Hz, 1H, pyrazoline-H), 3.69 are summarized in Table 4 and compared with those of
(dd, J = 17.6, 12.0 Hz, 1H, pyrazoline-H), 4.08 (s, 3H, reference standards ampicillin.
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CONVENIENT SYNTHESIS OF NOVEL CHALCONE
381
ACKNOWLEDGMENTS
9. Sharma, P.K., Kumar, S., Kumar, P., Kaushik, P.,
Sharma, C., Kaushik, D., and Aneja, K. R., Med.
Chem. Res., 2012, vol. 21, pp. 2945–2954.
10. Samshuddin, S., Narayana, B., Sarojini, B.K.,
Khan, M.T.H., Yathirajan, H.S., Raj, C.G.D., and Ra-
ghavendra, R., Med. Chem. Res., 2012, vol. 21,
pp. 2012–2022.
We acknowledge financial support from the Shahreza
Branch, Islamic Azad University (IAUSH) Research
Council. Also, we thank Professor R. F. W. Jackson
(Department of Chemistry, The University of Sheffield
UK) for helpful comments on the manuscript and S. Brad-
shaw (Department of Chemistry, The University of Shef-
field UK) for recording NMR spectra.
11. Lv, P.-C., Li, H.-Q., Sun, J., Zhou, Y., and Zhu, H.-L.,
Bioorg. Med. Chem., 2010, vol. 18, pp. 4606–4614.
12. Rahman, M.A., and Siddiqui, A.A., Int. J. Pharm. Sci.
Drug Res., 2010, vol. 2, pp. 165–175.
COMPLIANCE WITH ETHICAL STANDARDS
13. Lv, P.-C., Sun, J., Luo, Y., Yang, Y., and Zhu, H.-L.,
The authors declare that they have no conflict of interest.
This article does not contain any studies involving animals or
human participants performed by any of the authors.
Bioorg. Med. Chem. Lett., 2010, vol. 20, pp. 4657–4660.
14. Massah, A.R., Adibi, H., Khodarahmi, R., Abiri, R.,
Majnooni, M.B., Shahidi, S., Asadi, B., Mehrabi, M.,
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