Synthesis and antimicrobial evaluation of novel benzo[b]thiophenes comprising β-lactam nucleus

Article abstract of DOI:10.1007/s00044-011-9669-2

Synthesis, structural characterization, and biological activity studies of benzo[b]thiophene derivatives containing β-lactam nucleus are described. Cycloaddition of azomethines (4a-j) to in situ-generated ketenes from 2,4-dichlorophenoxyacetic acid, in th

Full text of DOI:10.1007/s00044-011-9669-2

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2012) 21:1471–1479
DOI 10.1007/s00044-011-9669-2
ORIGINAL RESEARCH
Synthesis and antimicrobial evaluation of novel
benzo[b]thiophenes comprising b-lactam nucleus
•
Amit R. Trivedi Jignesh M. Desai
•
•
•
Bipin H. Dholariya Dipti K. Dodiya
Viresh H. Shah
Received: 3 October 2009 / Accepted: 10 May 2011 / Published online: 21 May 2011
Ó Springer Science+Business Media, LLC 2011
Abstract Synthesis, structural characterization, and bio-
logical activity studies of benzo[b]thiophene derivatives
containing b-lactam nucleus are described. Cycloaddition
of azomethines (4a–j) to in situ-generated ketenes from
2,4-dichlorophenoxyacetic acid, in the presence of trieth-
ylamine and benzenesulfonyl chloride afforded the title
compounds (5a–j). The stereochemical course of reaction
depends on both the substituents on the ketenes as well as
on the imines. The mechanism for the formation of cis/
trans derivative is presented.
Introduction
Over the recent years, there has been an increasing interest
in the chemistry of thiophenes because of their biological
significance. Many of them have been widely investigated
for several therapeutic uses (Wardakhan et al., 2005). The
b-lactam heterocycles are still the most prescribed anti-
biotics used in medicine. They are considered as an
important contribution of science to humanity (Southgate,
1994; Morin and Gorman, 1982). The most widely used
antibiotics, such as the penicillins, cephalosporins,
carumonam, aztreonam, thienamycine, and the nocardicins
all contain b-lactam rings (Mata et al., 2003). The long-
term use of b-lactam antibiotics exerts selective pressure
on bacteria and permits the proliferation of resistant
organisms (Page, 1992). A comparative study of current
antibiotics with those from previous decades shows an
alarming increase in bacterial resistance to b-lactam
antibiotics (Niccolai et al., 1997; Chu et al., 1996).
The development of several synthetic and semi-synthetic
b-lactam antibiotics by the pharmaceutical industry was
due to the growing resistance of bacteria toward the
b-lactam antibiotics and the need for medicines with a
more specific antibacterial activity (Van der Steen and
Van Koten, 1991).
Keywords Benzo[b]thiophene ꢀ b-Lactam ꢀ
2-Azetidinone ꢀ Antimicrobial activity
Electronic supplementary material The online version of this
article (doi:10.1007/s00044-011-9669-2) contains supplementary
material, which is available to authorized users.
A. R. Trivedi ꢀ J. M. Desai ꢀ B. H. Dholariya ꢀ
D. K. Dodiya ꢀ V. H. Shah (&)
Department of Chemistry, Chemical Research Laboratory,
Saurashtra University, Rajkot 360005, Gujarat, India
e-mail: shah_v_h@yahoo.com
Keeping in mind the biomedical applications, as a
continuation of our previous study (Desai and Shah, 2003),
and with a view to further assess the pharmacological
profile of this class of compounds, it was thought worth-
while to synthesize some new congeners of b-lactam
heterocycles by incorporating the benzo[b]thiophene and
b-lactam in a single molecular framework with a potential
spectrum of bio-responses. The antimicrobial activities of
the newly synthesized compounds against gram-positive
and gram-negative bacteria were studied.
A. R. Trivedi
e-mail: damitdada@gmail.com
J. M. Desai
e-mail: jmdesai@yahoo.com
B. H. Dholariya
e-mail: bipin_dholariya@yahoo.com
D. K. Dodiya
e-mail: diptid85@gmail.com
123

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Med Chem Res (2012) 21:1471–1479
Results and discussion
Chemistry
Several methods are well known for the synthesis of
benzo[b]thiophenes (Radl et al., 2000; Carrington et al.,
1971; Beck, 1972; Beck and Yahner, 1974; Li et al.,
1992). In this study, we have utilized Gewald reaction for
the synthesis of benzo[b]thiophene derivative 3. Synthesis
of 2-(3-((E)-2-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-
yl)vinyl)-5,5-dimethylcyclohex-2-enylidene)malononitrile
2 was accomplished by condensing 2-(3,5,5-trimethylcy-
clohex-2-enylidene)malononitrile 1 with 5-chloro-3-methyl-
1-phenyl-1H-pyrazole-4-carbaldehyde. This 2 on reaction
with sulfur and morpholine furnished 2-amino-5-((E)-2-
(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)vinyl)-6,7-
dihydro-7,7-dimethylbenzo[b]thiophene-3-carbonitrile 3. A
series of azomethines (4a–j) were prepared by condensing
compound 3 with a variety of aromatic aldehydes. Cyclo-
addition of (4a–j) to 2,4-dichlorophenoxy acetic acid, in
the presence of triethylamine and benzenesulfonyl chloride
afforded the title compounds 2-(3-(2,4-dichlorophenoxy)-2-
(aryl)-4-oxoazetidin-1-yl)-5-(2-(5-chloro-3-methyl-1-phe-
nyl-1H-pyrazol-4-yl)vinyl)-6,7-dihydro-7,7-dimethylbenzo[b]
thiophene-3-carbonitriles (5a–j) (Scheme 1; Fig. 1).
Fig. 1 Antibacterial activity of 5a–j
Stereochemistry
The formation of cis or trans 2-azitidinone (b-lactam) takes
place via (2 ? 2) cycloaddition involving a ketene derived
from 2,4-dichlorophenoxyacetic acid and azomethines
(4a–j) obtained by the condensation of aminobenzo[b]thio-
phene derivative with various aromatic aldehydes. The cis–
trans stereochemistry depends mainly upon the substituents
on the ketene parts as the imine (azomethines) is usually
presumed to exist in the more stable E-configuration. The
stereochemical outcome can be explained involving the
Scheme 1 Reaction scheme
H3C
CHO
Cl
N
N
H
C
CN
C
H3C
C
H
CN
CN
CN
N
H3C
Piperidyl acetate
H3C
O
N
Cl
N
Piperidyl acetate
N
2
1
H
C
CN
CN
H3C
CH CH
Cl
H3C
C
H
Sulfur
Morpholine
N
NH2
N
N
R-CHO
S
S
R
C
Cl
N
N
H
3
4a-j
CN
R
Cl
R= Phenyl,
H3C
CH CH
Cl
2-Chlorophenyl,
3-Chlorophenyl,
N
OCH2COOH
Cl
O
Cl
Cl
N
S
3,4-Dichlorophenyl,
N
4-(N,N-Dimethyl)phenyl,
2-Hydroxyphenyl,
O
Benzene sulphonyl chloride
Triethyl amine
4-Methoxyphenyl,
3-Hydroxy-4-methoxyphenyl,
4-Nitrophenyl,
5a-j
3,4,5-Trimethoxyphenyl
123

Med Chem Res (2012) 21:1471–1479
1473
diene intermediate through the concept of torquoselectivity
advanced by Houk and coworkers (Rondan and Houk,
1985), and later utilized by Lopez et al. (Lopez et al.,
1993). Based on this concept, the preference of donor
(alkoxy, aryloxy) or acceptor (thioalkoxy, thioaryloxy,
chloride) groups on the ketene would decide about the
structure of the involved intermediate (A) or (B). The
zwitterionic intermediate (A) forms a cis b-lactam with
phenoxy (donor) group barring ketene, whereas such an
intermediate, which is more stabilized in the resonance
form (B) by sulfur (or any acceptor) on ketene and would
be a major contributor to resonance hybrid, affords trans
b-lactam. The structure of the diene intermediate would be
(A) or (B) resulting from the addition of the imine anti or
syn to the donor or acceptor groups of ketene. Conse-
quently, conrotatory ring closure would then lead to the
formation of cis-or trans-b-lactam. However, in the present
case, the presence of donor aryloxy (phenoxy) group on the
ketene leads to the formation of intermediate (A) and
eventually in the formation of cis b-lactams (5a–j), which
is evident from the values of coupling constants in the
Fig. 2 Antifungal activity of 5a–j
synthesized compounds 5a–j were tested in vitro for their
antibacterial activity against Escherichia coli, Pseudomonas
aeruginosa, Bacillus subtillus, Staphylococcus aureus, and
Micrococcus luteus bacteria by the agar well diffusion
method (Linday, 1962). DMSO was used as a control sol-
vent and, chloramphenicol and cefixime as standard drugs.
After 24-h incubation at 37°C, the zone of inhibition was
measured in mm. The results are depicted in Table 1. The
results showed that all compounds were active against
E. coli. It is worth noting here that compounds 5b and 5f
exhibited significant activity against E. coli and B. subtillus.
The other compounds showed moderate-to-low activity.
The structure–activity relationship (SAR) shows that the
presence of substitution at the 2-position (ortho) of the
phenyl substituent enhanced the antibacterial action of the
compounds (Fig. 1).
1
NMR spectroscopic data. The H NMR spectra of com-
pounds 5a–j shows doublets of two protons on the aze-
tidinonic ring between d 4.99–5.72, with a coupling
constant of J = 5.0–5.8 Hz indicating cis stereochemistry
at the b-lactam ring system (Scheme 2; Fig. 2).
Biological activity
Compounds 5a–j were also screened in vitro for their
antifungal activity against four species using the agar plate
technique (Collins, 1967). The linear growth of the fungus
was obtained by measuring the diameter of the fungal colony
after 7 days. The amount of growth inhibition in each case
was calculated as percentage inhibition. The results shown in
Table 2 indicated that compounds 5b and 5f exhibited sig-
nificant activity against Trichphyton longifusus and Candida
albicans, respectively. It is worth noting that compounds 5b
and 5f exhibited significant (maximum) antibacterial and
antifungal activities, possibly because of the presence of
substitution at the 2-position (ortho) of the phenyl sub-
stituent, in addition to the azetidinone moiety (Fig. 2).
The diverse biological activities of thiophene and fused
derivatives prompted us to test and study the biological
activities of some of the newly synthesized products. Many
antimicrobial agents have been introduced into therapy;
however, the field still needs extensive efforts for the
development of new antimicrobial agents to overcome the
highly resistant strains of microorganisms. The newly
R3
H R2
N+
H
H
PhO
R2
N
C
PhO
H
R2
H
C
N
anti to PhO
-O
R3
O
R3
O
Cis
PhO
(A)
R3
R2
N+
Cl
C-
R2
N
Cl
R2
C
H
H
H
H
N+
R3
Cl
H
syn to Cl
O
R3
-O
C
O
Conclusions
(C)
(B)
In the present article, we report the synthesis, spectral studies,
stereochemistry, and anti-microbial activity of a novel series
of novel benzo[b]thiophenes comprising b-lactam nucleus.
The 1H NMR studies evidenced the formation of cis isomers.
The preliminary in vitro biological activities of the title
compounds 2-(3-(2,4-dichlorophenoxy)-2-(aryl)-4-oxoazeti-
din-1-yl)-5-(2-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)
H
H
R2
R2
Cl
Cl
H
C+
H
N
N
O
R3
trans
-O
R3
(D)
Scheme 2 Mechanism for the formation of 2-azitidinone (b-lactam)
derivatives
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Med Chem Res (2012) 21:1471–1479
Table 1 Antibacterial activity of 5a–j
Compound
R
E.c
P.a
B.s
S.a
M.l
5a
Phenyl
14.19
17.81
13.90
12.00
14.56
17.55
15.56
13.69
13.96
12.95
17.00
30.00
11.65
10.56
11.20
10.85
–
11.70
18.70
12.36
11.25
–
–
–
5b
2-Chlorophenyl
4-Chlorophenyl
3,4-Dichlorophenyl
4-(N,N-Dimethyl)phenyl
2-Hydroxyphenyl
4-Methoxyphenyl
3-Hydroxy-4-methoxyphenyl
4-Nitrophenyl
11.28
10.56
–
13.09
5c
–
5d
–
5e
–
–
5f
11.56
11.90
–
18.86
12.46
–
12.35
11.26
–
–
5g
–
5h
–
5i
12.10
11.68
19.60
17.78
11.23
11.61
18.80
28.70
–
–
5j
3,4,5-Trimethoxyphenyl
–
10.59
16.45
36.12
–
Chlorampenicol
Cefixime (Standard)
17.20
34.11
–
Zone diameter of growth inhibition (mm) after 24 h,\10 mm (-), Concentration 1 mg/mL in DMSO. Microorganisms selected are as follows:
E.c, Escherichia coli; P.a, Pseudomonas aeruginosa; B.s, Bacillus subtillus; S.a, Staphylococcus aureus; M.l, Micrococcus luteus
pre-coated silica gel GF254 plates from E-Merck Co, and
compounds visualized by exposure to UV. Melting points
were determined in open capillaries and are uncorrected.
The IR spectra were recorded on Nicolet Impact 410 FT IR
Table 2 Antifungal activity of 5a–j
Compound
R
T.l
40
C.a
M.c
F.s
5a
5b
5c
5d
5e
5f
Phenyl
–
94
–
50
–
–
40
–
1
spectrophotometer using KBr pellets. H and 13C NMR
2-Chlorophenyl
4-Chlorophenyl
3,4-Dichlorophenyl
4-(N,N-Dimethyl)phenyl
2-Hydroxyphenyl
4-Methoxyphenyl
92
35
–
–
spectra were recorded on Bruker 300-MHz FT NMR
spectrometer in CDCl3 with TMS as internal standard.
Mass spectrum was recorded on Thermo-Finnigan-MAT,
Bremen (Model MAT8200) spectrometer, and elemental
analysis was carried out using Heraus CHN rapid analyzer.
–
–
–
–
–
–
–
89
–
91
30
–
–
–
5g
5h
–
25
–
3-Hydroxy-4-
methoxyphenyl
–
–
Chemistry
5i
5j
4-Nitrophenyl
–
–
–
50
90
–
–
–
–
3,4,5-Trimethoxyphenyl
–
Synthesis of 2-(3,5,5-trimethylcyclohex-2-
enylidene)malononitrile (1)
Miconazole
(Standard)
100
90
90
Conc. of sample 200 lg/mL in DMSO at 27°C, Incubation period
7 days. Microorganisms selected are as follows: T.l, Trichphyton
longifusus; C.a, Candida albicans; M.c, Microsporum canis; F.s,
Fusarium solani
A solution of equimolar quantities of isophorone (0.10 mmol)
and malononitrile (0.10 mmol) wererefluxedindry ethanol in
the presence of piperidyl acetate as a catalyst (2–3 drops) for
3 h. Theproduct separatedout oncoolingwasfiltered, washed
with cold ethanol, dried, and recrystallized from petroleum
ether. Yield: 63%, m.p. 76–78°C.
vinyl)-6,7-dihydro-7,7-dimethylbenzo[b]thiophene-3-carbo-
nitriles revealed that compounds 5b and 5f exhibited signifi-
cant (maximum) antibacterial and antifungal activities. In
summary, we have identified a novel series of benzo[b]thio-
phene derivatives comprising b-lactam nucleus, which may
develop into the potential class of antimicrobial agents.
Synthesis of 2-(3-((E)-2-(5-chloro-3-methyl-1-phenyl-1H-
pyrazol-4-yl)vinyl)-5,5-dimethylcyclohex-2-
enylidene)malononitrile (2)
Experimental
Equimolar quantities of 2-(3,5,5-trimethylcyclohex-2-
enylidene)malononitrile 1 (0.10 mmol) and 5-chloro-3-
methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (0.10 mmol)
was refluxed in dry ethanol in the presence of piperidyl
acetate as a catalyst (2–3 drops) for 5 h. The product sep-
arated out on cooling was filtered, dried and recrystallized
from absolute alcohol. Yield = 83%, m.p. 156–158°C. IR
General
All the research chemicals were purchased from Sigma-
Aldrich and used as such for the reactions. Reactions
were monitored by thin-layer chromatography (TLC) on
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Med Chem Res (2012) 21:1471–1479
1475
(KBr) cm-1: 3045, 2946, 2872, 2232, 1661, 1599, 1540,
692. 1H NMR (300 MHz, CDCl3): 1.09 (s, 6H, CH3), 1.68
(s, 4H, CH2), 2.34 (s, 3H, CH3), 6.03 (s, 1H, CH), 6.32
(d, 1H, CH, J = 14.6 Hz), 6.48 (d, 1H, CH, J = 14.4 Hz),
7.37-7.88 (m, 5H, Ar–H); 13C NMR (CDCl3): 10.1, 11.4,
28.3, 40.7, 43.1, 45.4, 81.7, 112.6, 120.1, 126.1, 127.9,
129.6, 130.9, 136.9, 139.8, 140.7, 149.5, 179.8. MS (m/z):
388; Anal. Calcd. for C23H21ClN4: C, 71.03; H, 5.44; N,
14.41. Found: C, 70.82; H, 5.50; N, 14.26.
2.53 (s, 3H, CH3), 5.22 (s, 1H, CH), 6.19 (s, 1H, CH), 6.29
(d, 1H, CH), 6.40 (d, 1H, CH), 8.09 (s, 1H, CH), 7.22–8.28
(m, 10H, Ar–H); 13C NMR (CDCl3): 11.2, 30.2, 30.6, 49.7,
107.9, 110.1, 115.2, 120.1, 122.7, 126.2, 128.7, 129.1,
129.5, 130.0, 131.2, 132.9, 133.6, 134.9, 137.1, 139.9,
140.7, 149.9, 162.3. MS (m/z): 508; Anal. Calcd. for
C30H25ClN4S: C, 70.78; H, 4.95; N, 11.12. Found: C,
70.48; H, 4.64; N, 10.70.
2-(2-Chlorobenzylideneamino)-5-(2-(5-chloro-3-methyl-1-
phenyl-1H-pyrazol-4-yl)vinyl)-6,7-dihydro-7,
7-dimethylbenzo[b]thiophene-3-carbonitrile (4b)
Synthesis of 2-amino-5-((E)-2-(5-chloro-3-methyl-1-
phenyl-1H-pyrazol-4-yl)vinyl)-6,7-dihydro-7,
7-dimethylbenzo[b]thiophene-3-carbonitrile (3)
Yield = 81%, m.p. 247–249°C. IR (KBr) cm-1: 3043,
2938, 2848, 2204, 1656, 1593, 1549, 740, 699. H NMR
1
2-(3-((E)-2-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)
vinyl)-5,5-dimethylcyclohex-2-enylidene)malononitrile
(300 MHz, CDCl3): 1.33 (s, 6H, CH3), 2.14 (s, 2H, CH2),
2.43 (s, 3H, CH3), 6.09 (s, 1H, CH), 6.24 (d, 1H, CH), 6.40
(d, 1H, CH), 8.12 (s, 1H, CH), 7.31–8.27 (m, 9H, Ar–H);
13C NMR (CDCl3): 11.4, 30.6, 30.9, 50.1, 108.3, 111.9,
115.1, 120.6, 122.7, 126.1, 126.9, 128.8, 129.5, 131.1,
131.2, 132.8, 133.3, 133.6, 134.2, 135.4, 137.3, 139.8,
140.4, 146.2, 150.3, 158.4, 161.0. MS (m/z): 542; Anal.
Calcd. for C30H24Cl2N4S: C, 66.30; H, 4.45; N, 10.31.
Found: C, 66.10; H, 4.26; N, 10.36.
2
(0.10 mmol) was stirred at 60°C with sulfur (0.10 mmol) in
the presence of morpholine (5 ml) in ethanol (20 ml) for
6 h. The mixture was cooled, poured onto crushed ice, and
neutralized with dilute HCl. The product obtained was
filtered, dried, and recrystallized from absolute alcohol.
Yield = 86%, m.p. 206–208°C. IR (KBr) cm-1: 3288,
1
3056, 2954, 2862, 2221, 1656, 1589, 1552, 692. H NMR
(300 MHz, CDCl3): 1.31 (s, 6H, CH3), 2.12 (s, 2H, CH2),
2.62 (s, 3H, CH3), 5.12 (s, 2H, NH2), 6.11 (s, 1H, CH), 6.31
(d, 1H, CH, J = 14.5 Hz), 6.48 (d, 1H, CH, J = 14.4 Hz),
7.12–8.18 (m, 5H, Ar–H); 13C NMR (CDCl3): 11.0, 30.2,
30.9, 50.1, 107.9, 110.2, 114.9, 120.1, 122.4, 126.2, 129.1,
131.1, 133.2, 134.8, 137.0, 139.6, 140.8, 146.1, 149.2. MS
(m/z): 420; Anal. Calcd. for C23H21ClN4S: C, 65.62; H,
5.03; N, 13.31. Found: C, 65.48; H, 4.88; N, 13.16.
2-(4-Chlorobenzylideneamino)-5-(2-(5-chloro-3-methyl-1-
phenyl-1H-pyrazol-4-yl)vinyl)-6,7-dihydro-7,
7-dimethylbenzo[b]thiophene-3-carbonitrile (4c)
Yield = 83%, m.p. 226–228°C. IR (KBr) cm-1: 3041,
2932, 2851, 2209, 1646, 1599, 1552, 735, 694. H NMR
1
(300 MHz, CDCl3): 1.23 (s, 6H, CH3), 2.24 (s, 2H, CH2),
2.33 (s, 3H, CH3), 6.12 (s, 1H, CH), 6.18 (d, 1H, CH), 6.36
(d, 1H, CH), 8.16 (s, 1H, CH), 7.21–8.37 (m, 9H, Ar–H);
13C NMR (CDCl3): 11.4, 30.5, 30.8, 50.0, 107.9, 111.9,
115.4, 120.3, 123.0, 128.8, 129.3, 130.1, 131.0, 132.1,
132.9, 134.8, 136.2, 137.2, 139.1, 140.9, 147.2, 149.4,
157.4, 162.6. MS (m/z): 542; Anal. Calcd. for
C30H24Cl2N4S: C, 66.30; H, 4.45; N, 10.31. Found: C,
66.10; H, 4.36; N, 10.21.
General procedure for the synthesis of 2-(arylideneamino)-
5-(2-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)vinyl)-
6,7-dihydro-7,7-dimethylbenzo[b]thiophene-3-
carbonitriles (4a–j)
A mixture of 2-amino-5-(2-(5-chloro-3-methyl-1-phenyl-
1H-pyrazol-4-yl)vinyl)-6,7-dihydro-7,7-dim-
ethylbenzo[b]thiophene-3-carbonitrile 3 (0.10 mmol) and
appropriate aldehyde (0.10 mmol) was refluxed in absolute
ethanol (15 ml) for 2–3 h. The solid mass that separated
out was filtered, washed with water, and crystallized from
absolute ethanol to give the preferred product (4a–j).
2-(3,4-Chlorobenzylideneamino)-5-(2-(5-chloro-3-methyl-
1-phenyl-1H-pyrazol-4-yl)vinyl)-6,7-dihydro-7,
7-dimethylbenzo[b]thiophene-3-carbonitrile (4d)
Yield = 78%, m.p. 198–200°C. IR (KBr) cm-1: 3049,
2931, 2848, 2212, 1661, 1590, 1549, 736, 694. H NMR
2-(Benzylideneamino)-5-(2-(5-chloro-3-methyl-1-phenyl-
1H-pyrazol-4-yl)vinyl)-6,7-dihydro-7,
7-dimethylbenzo[b]thiophene-3-carbonitrile (4a)
1
(300 MHz, CDCl3): 1.24 (s, 6H, CH3), 2.11 (s, 2H, CH2),
2.31 (s, 3H, CH3), 6.11 (s, 1H, CH), 6.20 (d, 1H, CH), 6.36
(d, 1H, CH), 8.42 (s, 1H, CH), 7.31–8.27 (m, 8H, Ar–H);
13C NMR (CDCl3): 11.7, 30.3, 49.7, 106.7, 110.7, 116.1,
120.7, 122.9, 125.9, 128.4, 129.6, 130.4, 130.8, 131.7,
Yield = 76%, m.p. 255–257°C. IR (KBr) cm-1: 3051,
2945, 2854, 2214, 1646, 1589, 1552, 745, 701. H NMR
1
(300 MHz, CDCl3): 1.29 (s, 6H, CH3), 2.02 (s, 2H, CH2),
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Med Chem Res (2012) 21:1471–1479
132.9, 133.4, 133.7, 135.0, 135.8, 138.1, 139.3, 140.8,
147.1, 150.0, 158.7, 161.4. MS (m/z): 578; Anal. Calcd. for
C30H23Cl3N4S: C, 62.34; H, 4.01; N, 9.69. Found: C,
62.19; H, 4.06; N, 9.57.
MS (m/z): 538; Anal. Calcd. for C31H27ClN4OS: C, 69.07;
H, 5.05; N, 10.39. Found: C, 68.88; H, 5.00; N, 10.26.
2-(3-Hydroxy-4-methoxybenzylideneamino)-5-(2-(5-chloro-3-
methyl-1-phenyl-1H-pyrazol-4-yl)vinyl)-6,7-dihydro-7,7-
dimethylbenzo[b]thiophene-3-carbonitrile (4h)
2-(4-(N,N-dimetylbenzylideneamino)-5-(2-(5-chloro-3-
methyl-1-phenyl-1H-pyrazol-4-yl)vinyl)-6,7-dihydro-7,
7-dimethylbenzo[b]thiophene-3-carbonitrile (4e)
Yield = 70%, m.p. 226–228°C. IR (KBr) cm-1: 3236,
3044, 2926, 2838, 2204, 1652, 1592, 1559, 1131, 722, 702.
1H NMR (300 MHz, CDCl3): 1.19 (s, 6H, CH3), 2.14 (s,
2H, CH2), 2.33 (s, 3H, CH3), 3.52 (s, 3H, OCH3), 5.32 (s,
1H, OH), 6.04 (d, 1H, CH), 6.12 (d, 1H, CH), 8.32 (s, 1H,
CH), 7.20–8.24 (m, 8H, Ar–H); 13C NMR (CDCl3): 11.4,
30.6, 30.9, 54.9, 106.7, 111.2, 115.2, 115.4, 115.9, 120.3,
122.7, 122.9, 126, 127.9, 129.9, 131.0, 133.6, 134.7, 137.2,
139.5, 140.7, 144.9, 146.3, 150.0, 152.4, 158.9, 160.3. MS
(m/z): 554; Anal. Calcd. for C31H27ClN4O2S: C, 67.08; H,
4.90; N, 10.09. Found: C, 66.89; H, 4.84; N, 10.02.
Yield = 67%, m.p. 208–210°C. IR (KBr) cm-1: 3312,
3051, 2934, 2851, 2206, 1656, 1593, 1556, 741, 696. H
1
NMR (300 MHz, CDCl3): 1.18 (s, 6H, CH3), 2.18 (s, 2H,
CH2), 2.25 (s, 3H, CH3), 2.90 (s, 6H, CH3), 6.03 (s, 1H, C),
6.12 (d, 1H, CH), 6.36 (d, 1H, CH), 8.36 (s, 1H, CH), 7.01-
8.12 (m, 9H, Ar–H); 13C NMR (CDCl3): 11.1, 30.4, 30.6,
49.9, 105.6, 110.8, 113.8, 115.9, 121.0, 123.0, 124.9,
126.2, 129.8, 130.7, 131.2, 133.4, 135.1, 137.4, 139.4,
146.2, 149.4, 152.3, 157.9, 160.3. MS (m/z): 551; Anal.
Calcd. for C32H30OClN5S: C, 69.61; H, 5.48; N, 12.68.
Found: C, 69.54; H, 5.32; N, 12.59.
2-(4-Nitrobenzylideneamino)-5-(2-(5-chloro-3-methyl-1-
phenyl-1H-pyrazol-4-yl)vinyl)-6,7-dihydro-7,
7-dimethylbenzo[b]thiophene-3-carbonitrile (4i)
2-(2-Hydroxybenzylideneamino)-5-(2-(5-chloro-3-methyl-
1-phenyl-1H-pyrazol-4-yl)vinyl)-6,7-dihydro-7,
7-dimethylbenzo[b]thiophene-3-carbonitrile (4f)
Yield = 87%, m.p. 157–159°C. IR (KBr) cm-1: 3042,
2926, 2831, 2218, 1654, 1599, 1569, 1119, 745, 712. H
Yield = 69%, m.p. 211–213°C. IR (KBr) cm-1: 3250,
3056, 2929, 2838, 2218, 1655, 1595, 1553, 1112, 742, 696.
1H NMR (300 MHz, CDCl3): 1.19 (s, 6H, CH3), 2.09
(s, 2H, CH2), 2.29 (s, 3H, CH3), 5.12 (s, 1H, OH), 6.13
(s, 1H, CH), 6.29 (d, 1H, CH), 6.42 (d, 1H, CH), 8.34 (s,
1H, CH), 7.31–8.27 (s, 9H, Ar–H); 13C NMR (CDCl3):
11.3, 31.1, 31.3, 50.1, 105.4, 110.4, 114.8, 115.7, 118.4,
121.0, 121.9, 122.8, 125.8, 126.3, 129.2, 130.1, 131.1,
132.4, 133.1, 136.1, 137.4, 139.4, 140.4, 145.9, 148.9,
158.7, 161.0, 162.0. MS (m/z): 524; Anal. Calcd. for
C30H25ClN4OS: C, 68.62; H, 4.80; N, 10.67. Found: C,
68.38; H, 4.81; N, 10.54.
1
NMR (300 MHz, CDCl3): 1.12 (s, 6H, CH3), 2.14 (s, 2H,
CH2), 2.29 (s, 3H, CH3), 6.11 (s, 1H, CH), 6.19 (d, 1H,
CH), 6.24 (d, 1H, CH), 6.70 (s, 2H, CH), 7.12 (d, 2H, CH),
8.36 (s, 1H, CH), 7.30–8.45 (m, 5H, Ar–H); 13C NMR
(CDCl3): 11.7, 30.2, 30.9, 49.4, 170.6, 109.9, 114.9, 121.0,
121.3, 122.4, 126.1, 129.1, 130.2, 131.8, 132.9, 134.9,
137.3, 139.6, 139.8, 140.4, 146.4, 149.4, 150.4, 159.4. MS
(m/z): 569; Anal. Calcd. for C30H24ClN5O3S: C, 63.21; H,
4.24; N, 12.29. Found: C, 63.10; H, 4.09; N, 12.27.
2-(3,4,5-Trimethoxybenzylideneamino)-5-(2-(5-chloro-3-
methyl-1-phenyl-1H-pyrazol-4-yl)vinyl)-6,7-dihydro-7,
7-dimethylbenzo[b]thiophene-3-carbonitrile (4j)
2-(4-Methoxybenzylideneamino)-5-(2-(5-chloro-3-methyl-
1-phenyl-1H-pyrazol-4-yl)vinyl)-6,7-dihydro-7,
7-dimethylbenzo[b]thiophene-3-carbonitrile (4g)
Yield = 72%, m.p. 266–268°C. IR (KBr) cm-1: 3048,
2931, 2844, 2216, 1651, 1602, 1572, 1121, 739, 709. H
1
Yield = 78%, m.p. 185–187°C. IR (KBr) cm-1: 3050,
2932, 2835, 2214, 1658, 1598, 1563, 1123, 732, 706. H
1
NMR (300 MHz, CDCl3): 1.18 (s, 6H, CH3), 2.27 (s, 2H,
CH2), 2.36 (s, 3H, CH3), 3.65 (s, 9H, OCH3), 6.04 (s, 1H,
CH), 6.21 (d, 1H, CH), 6.32 (d, 1H, CH), 6.54 (d, 1H, CH),
8.46 (s, 1H, CH), 7.19–8.15 (m, 5H, Ar–H); 13C NMR
(CDCl3): 10.9, 31.0, 31.4, 50.1, 56.2, 56.6, 106.3, 107.4,
110.4, 115.2, 120.1, 122.7, 126.2, 128.4, 129.2, 131.1,
132.9, 134.8, 137.2, 139.4, 140.3, 141.2, 146.2, 149.4,
150.7, 157.9, 161.4. MS (m/z): 598; Anal. Calcd. for
NMR (300 MHz, CDCl3): 1.21 (s, 6H, CH3), 2.21 (s, 2H,
CH2), 2.36 (s, 3H, CH3), 3.66 (s, 3H, OCH3), 6.03 (s, 1H,
CH), 6.12 (d, 1H, CH), 6.30 (d, 1H, CH), 6.76 (d, 1H, CH),
8.52 (s, 1H, CH), 7.24–8.32 (m, 5H, Ar–H); 13C NMR
(CDCl3): 11.0, 30.8, 31.1, 50.3, 60, 107.6, 111.2, 114.2,
115.4, 120.0, 122.1, 126.0, 126.2, 129.2, 130.4, 131.4, 133.7,
134.8, 137.2, 139.4, 140.7, 149.6, 147.0, 159.0, 163.0, 164.4.
123

Med Chem Res (2012) 21:1471–1479
1477
C33H31ClN4O3S: C, 66.15; H, 5.22; N, 9.35. Found: C,
66.00; H, 5.14; N, 9.30.
120.4, 123.6, 124, 125.6, 126.2, 126.8, 127.4, 127.8, 128.0,
128.4, 128.8, 129.2, 131.2, 132.1, 132.7, 133.2, 134.1, 140.0,
140.9, 143.4, 146.0, 147.2, 149.0, 149.8, 167.0. MS (m/z):
746; Anal. Calcd. for C38H28Cl4N4O2S: C, 61.14; H, 3.78; N,
7.50. Found: C, 61.24; H, 3.64; N, 7.26.
General procedure for the synthesis of 2-(3-(2,4-
dichlorophenoxy)-2-(aryl)-4-oxoazetidin-1-yl)-5-(2-(5-
chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)vinyl)-6,
7-dihydro-7,7-dimethylbenzo[b]thiophene-3-carbonitriles
(5a–j)
2-(3-(2,4-Dichlorophenoxy)-2-(4-chlorophenyl)-4-
oxoazetidin-1-yl)-5-(2-(5-chloro-3-methyl-1-phenyl-1H-
pyrazol-4-yl)vinyl)-6,7-dihydro-7,7-
To a well-stirred solution of the 2-(4-arylideneamino)-5-
(-2-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)vinyl)-
6,7-dihydro-7,7-dimethylbenzo[b]thiophene-3-carbonitrile
(0.10 mmol), 2,4-dichlorophenoxy acetic acid (0.10 mmol)
and triethylamine (0.25 mmol) in dry dioxane (30 ml), a
solution of benzene sulfonyl chloride (0.10 mmol) in dry
dioxane was added dropwise at 0–5°C over a period of
45 min. The stirring was continued at room temperature for
a specific period and the reaction mass was kept at room
temperature for 3 days. The reaction mass was poured onto
crushed ice, filtered, dried, and recrystallized from diox-
ane–methanol (3:1) to yield the preferred product.
dimethylbenzo[b]thiophene-3-carbonitrile (5c)
Yield = 57%, m.p. 297–299°C. IR (KBr) cm-1: 3098,
2973, 2869, 2218, 1741, 1686, 1429, 1261, 759, 656, 628.
1H NMR (300 MHz, CDCl3): 1.40 (s, 6H, CH3), 2.39
(s, 2H, CH2), 2.81 (s, 3H, CH3), 5.22 (d, 1H, CH,
J = 5.3 Hz), 5.79 (d, 1H, CH, J = 5.5 Hz), 6.35 (s, 1H,
CH), 6.45 (d, 1H, CH), 6.66 (d, 1H, CH), 7.26–8.29
(m, 12H, Ar–H); 13C NMR (CDCl3): 11.3, 30.2, 30.9, 49.7,
60.4, 87.1, 95.0, 108.4, 115.2, 117.3, 120.4, 123.6, 124.2,
125.2, 125.9, 126.7, 126.9, 127.8, 128.0, 129.6, 130.2,
131.1, 131.4, 133.2, 134.2, 134.6, 139.8, 140.4, 145.0,
146.0, 147.6, 149.2, 149.8, 166.8. MS (m/z): 746; Anal.
Calcd. for C38H28Cl4N4O2S: C, 61.14; H, 3.78; N, 7.50.
Found: C, 61.14; H, 3.54; N, 7.26.
2-(3-(2,4-Dichlorophenoxy)-2-(phenyl)-4-oxoazetidin-1-
yl)-5-(2-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-
yl)vinyl)-6,7-dihydro-7,7-dimethylbenzo[b]thiophene-3-
carbonitrile (5a)
2-(3-(2,4-Dichlorophenoxy)-2-(3,4-chlorophenyl)-4-
oxoazetidin-1-yl)-5-(2-(5-chloro-3-methyl-1-phenyl-1H-
pyrazol-4-yl)vinyl)-6,7-dihydro-7,7-
Yield = 62%, m.p. 220–222°C. IR (KBr) cm-1: 3105,
2974, 2868, 2854, 2210, 1732, 1684, 1436, 1263, 758, 644,
616. 1H NMR (300 MHz, CDCl3): 1.41 (s, 6H, CH3), 2.30
(s, 2H, CH2), 2.80 (s, 3H, CH3), 5.11 (d, 1H, CH,
J = 5.3 Hz), 5.72 (d, 1H, CH, J = 5.5 Hz), 6.41 (s, 1H,
CH), 6.50 (d, 1H, CH), 6.72 (d, 1H, CH), 7.01–8.19 (m,
13H, Ar–H); 13C NMR (CDCl3): 11.4, 30.3, 30.7, 49.7,
60.1, 65.1, 86.4, 107.6, 115.1, 118.3, 120.3, 123.2, 124.5,
125.3, 126.0, 126.9, 127.2, 127.5, 128.4, 129.5, 130.9,
131.4, 132.8, 134.1, 139.6, 140.4, 143.1, 145.7, 147.2,
149.0, 149.7, 166.6. MS (m/z): 712; Anal. Calcd. for
C38H29Cl3N4O2S: C, 64.09; H, 4.10; N, 7.87. Found: C,
64.00; H, 4.02; N, 7.80.
dimethylbenzo[b]thiophene-3-carbonitrile (5d)
Yield = 63%, m.p. 218–220°C. IR (KBr) cm-1: 3091,
2980, 2860, 2208, 1735, 1689, 1442, 1256, 768, 643, 619.
1H NMR (300 MHz, CDCl3): 1.35 (s, 6H, CH3), 2.32
(s, 2H, CH2), 2.71 (s, 3H, CH3), 5.18 (d, 1H, CH,
J = 5.4 Hz), 5.69 (d, 1H, CH, J = 5.8 Hz), 6.39 (s, 1H,
CH), 6.41 (d, 1H, CH), 6.69 (d, 1H, CH), 7.04–8.23
(m, 11H, Ar–H); 13C NMR (CDCl3): 11.4, 30.2, 30.6, 49.9,
60.6, 87.0, 95.1, 107.6, 115.6, 117.8, 120.4, 123.4, 124.2,
124.9, 126.0, 126.2, 127.1, 127.4, 128.1, 129.2, 130.0,
131.3, 131.5, 132.9, 133.3, 134.3, 139.8, 140.7, 142.9,
146.1, 147.2, 149.0, 149.7, 166.4. MS (m/z): 780; Anal.
Calcd. for C38H27Cl5N4O2S: C, 58.44; H, 3.48; N, 7.17.
Found: C, 58.24; H, 3.33; N, 7.12.
2-(3-(2,4-Dichlorophenoxy)-2-(2-chlorophenyl)-4-
oxoazetidin-1-yl)-5-(2-(5-chloro-3-methyl-1-phenyl-1H-
pyrazol-4-yl)vinyl)-6,7-dihydro-7,7-
dimethylbenzo[b]thiophene-3-carbonitrile (5b)
2-(3-(2,4-Dichlorophenoxy)-2-(4-(N,N-dimethyl)phenyl)-4-
oxoazetidin-1-yl)-5-(2-(5-chloro-3-methyl-1-phenyl-1H-
pyrabol-4-yl)vinyl)-6,7-dihydro-7,7-
Yield = 59%, m.p. 260–262°C. IR (KBr) cm-1: 3103, 2968,
2861, 2214, 1735, 1679, 1423, 1259, 762, 639, 623. 1H NMR
(300 MHz, CDCl3): 1.36 (s, 6H, CH3), 2.23 (s, 2H, CH2),
2.73 (s, 3H, CH3), 4.99 (d, 1H, CH, J = 5.0 Hz), 5.62 (d, 1H,
CH, J = 5.2 Hz), 6.39 (s, 1H, CH), 6.49 (d, 1H, CH), 6.65 (d,
1H, CH), 7.11–8.19 (m, 12H, Ar–H); 13C NMR (CDCl3):
11.2, 30.2, 30.7, 50.1, 50.7, 65.0, 86.0, 107.4, 115.2, 117.4,
dimethylbenzo[b]thiophene-3-carbonitrile (5e)
Yield = 61%, m.p. 198–200°C. IR (KBr) cm-1: 3107, 2972,
2856, 2212, 1740, 1676, 1450, 1332, 1260, 769, 640, 610. 1H
NMR (300 MHz, CDCl3): 1.34 (s, 6H, CH3), 2.26 (s, 2H,
CH2), 2.80 (s, 3H, CH3), 3.12 (s, 6H, CH3), 5.26 (d, 1H, CH,
123

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Med Chem Res (2012) 21:1471–1479
1
J = 5.3 Hz), 5.72 (d, 1H, CH, J = 5.7 Hz), 6.36 (s, 1H, CH),
6.46 (d, 1H, CH), 6.61 (d, 1H, CH), 7.18–8.29 (m, 12H,
Ar–H); 13C NMR (CDCl3): 11.0, 30.2, 30.6, 40.4, 49.7, 60.2,
87.3, 94.7, 107.3, 112.9, 115.3, 116.9, 120.6, 123.4, 124.4,
125.4, 126.2, 127.0, 127.3, 127.6, 127.9, 129.7, 131.2, 131.4,
132.9, 133.1, 134.5, 140.1, 140.7, 146.0, 147.2, 147.6, 149.4,
149.8, 166.2. MS (m/z): 755; Anal. Calcd. for C40H34Cl3N5O2S:
C, 63.62; H, 4.54; N, 9.27. Found: C, 63.46; H, 4.50; N, 9.21.
761, 626. H NMR (300 MHz, CDCl3): 1.46 (s, 6H, CH3),
2.24 (s, 2H, CH2), 2.76 (s, 3H, CH3), 3.81 (s, 1H, OCH3),
5.12 (d, 1H, OH), 5.32 (d, 1H, CH, J = 5.2 Hz), 5.71 (s,
1H, CH, J = 5.4 Hz), 6.32 (s, 1H, CH), 6.50 (d, H, CH),
6.61 (d, H, CH), 7.12–8.329 (s, 11H, Ar–H); 13C NMR
(CDCl3): 11.6, 30.2, 30.7, 49.9, 57.1, 62.3, 86.9, 95.0,
107.3, 113.2, 115.4, 115.6, 117.3, 120.0, 120.4, 123.7,
124.2, 125.3, 126.6, 127.2, 127.7, 129.6, 131.1, 131.4,
133.3, 134.7, 137.8, 139.6, 140.4, 145.8, 147.6, 149.0,
149.2, 149.7, 165.7. MS (m/z): 758; Anal. Calcd. for
C39H31Cl3N4O4S: C, 61.79; H, 4.12; N, 7.39. Found: C,
61.50; H, 4.22; N, 7.29.
2-(3-(2,4-Dichlorophenoxy)-2-(2-hydroxyphenyl)-4-
oxoazetidin-1-yl)-5-(2-(5-chloro-3-methyl-1-phenyl-1H-
pyrazol-4-yl)vinyl)-6,7-dihydro-7,7-
dimethylbenzo[b]thiophene-3-carbonitrile (5f)
2-(3-(2,4-Dichlorophenoxy)-2-(4-nitrophenyl)-4-
oxoazetidin-1-yl)-5-(2-(5-chloro-3-methyl-1-phenyl-1H-
pyrazol-4-yl)vinyl)-6,7-dihydro-7,7-
Yield = 57%, m.p. 171–173°C. IR (KBr) cm-1: 3290,
3108, 2976, 2872, 2213, 1729, 1687, 1439, 1260, 766, 649,
612. 1H NMR (300 MHz, CDCl3): 1.36 (s, 6H, CH3), 2.24
(s, 2H, CH2), 2.92 (s, 3H, CH3), 5.11 (s, 1H, OH), 5.19 (d,
1H, CH, J = 5.4 Hz), 5.80 (d, 1H, CH, J = 5.1 Hz), 6.42
(s, 1H, CH), 6.51 (d, 1H, CH), 6.69 (d, 1H, CH), 7.12–8.42
(m, 12H, Ar–H); 13C NMR (CDCl3): 11.4, 30.3, 30.9, 49.5,
50.4, 86.9, 95.0, 107.6, 115.8, 116.0, 117.4, 119.8, 121.3,
123.3, 124.4, 125.0, 126.1, 127.2, 127.8, 128.0, 128.3,
129.7, 130.8, 131.1, 131.4, 133.2, 134.6, 139.8, 140.7,
146.0, 147.2, 150.0, 154.3, 156.3, 166.4. MS (m/z): 728;
Anal. Calcd. for C38H29Cl3N4O3S: C, 62.69; H, 4.01; N,
7.70. Found: C, 62.48; H, 4.20; N, 7.55.
dimethylbenzo[b]thiophene-3-carbonitrile (5i)
Yield = 62%, m.p. 181–183°C. IR (KBr) cm-1: 3099,
2969, 2866, 2211, 1732, 1674, 1438, 1265, 1342, 1265,
1
749, 640, 612. H NMR (300 MHz, CDCl3): 1.33 (s, 6H,
CH3), 2.19 (s, 2H, CH2), 2.80 (s, 3H, CH3), 5.22 (d, 1H,
CH, J = 5.2 Hz), 5.54 (d, 1H, CH, J = 5.2 Hz), 6.31 (s,
1H, CH), 6.46 (d, 1H, CH), 6.81 (d, 1H, CH), 7.43–8.69
(m, 12H, Ar–H); 13C NMR (CDCl3): 11.2, 30.3, 30.8, 50.1,
60.9, 87.0, 95.1, 106.9, 115.8, 117.1, 120.1, 120.8, 124.0,
124.3, 125.1, 126.2, 127.4, 127.7, 127.9, 129.3, 131.2,
131.6, 133.1, 134.6, 139.8, 140.8, 146.2, 146.9, 147.3,
149.1, 149.7, 166.0. MS (m/z): 757; Anal. Calcd. for
C38H28Cl3N5O4S: C, 60.28; H, 3.73; N, 9.25. Found: C,
59.28; H, 4.13; N, 9.45.
2-(3-(2,4-Dichlorophenoxy)-2-(4-methoxyphenyl)-4-
oxoazetidin-1-yl)-5-(2-(5-chloro-3-methyl-1-phenyl-1H-
pyrazol-4-yl)vinyl)-6,7-dihydro-7,7-
dimethylbenzo[b]thiophene-3-carbonitrile (5g)
2-(3-(2,4-Dichlorophenoxy)-2-(3,4,5-methoxyphenyl)-4-
oxoazetidin-1-yl)-5-(2-(5-chloro-3-methyl-1-phenyl-1H-
pyrazol-4-yl)vinyl)-6,7-dihydro-7,7-
Yield = 68%, m.p. 175–177°C. IR (KBr) cm-1: 3103, 2970,
2871, 2220, 1733, 1680, 1442, 1268, 756, 649, 621. 1H NMR
(300 MHz, CDCl3): 1.21 (s, 6H, CH3), 2.21 (s, 2H, CH2),
2.81 (s, 3H, CH3), 3.79 (s, 3H, OCH3), 5.31 (d, 1H, CH,
J = 5.0 Hz), 5.81 (d, 1H, CH, J = 5.4 Hz), 6.46 (s, 1H,
CH), 6.56 (d, 1H, CH), 6.69 (d, 1H, CH), 7.02–8.16 (m, 12H,
Ar–H); 13C NMR (CDCl3): 11.3, 30.2, 31.0, 49.8, 54.9, 61.2,
87.1, 95.2, 107.4, 112.9, 115.6, 117.4, 120.3, 124.0, 124.4,
125.3, 126.1, 127.6, 127.9, 128.2, 129.6, 131.2, 131.8, 133.3,
134.7, 135.9, 140.0, 140.8, 144.8, 147.2, 148.9, 149.8, 158.6,
166.7. MS (m/z): 742; Anal. Calcd. for C39H31Cl3N4O3S: C,
63.12; H, 4.21; N, 7.55. Found: C, 62.99; H, 4.04; N, 7.46.
dimethylbenzo[b]thiophene-3-carbonitrile (5j)
Yield = 58%, m.p. 231–233°C. IR (KBr) cm-1: 3088,
2964, 2861, 2210, 1736, 1671, 1446, 1243, 756, 640, 623.
1H NMR (300 MHz, CDCl3): 1.49 (s, 6H, CH3), 2.40 (s,
2H, CH2), 2.72 (s, 3H, CH3), 3.72 (s, 9H, OCH3), 5.31 (d,
1H, CH, J = 5.3 Hz), 5.70 (d, 1H, CH, J = 5.1 Hz), 6.12
(s, 1H, CH), 6.29 (d, 1H, CH), 6.56 (d, 1H, CH), 6.98–7.67
(m, 10H, Ar–H); 13C NMR (CDCl3): 11.4, 30.2, 30.6, 49.6,
56.5, 56.8, 61.2, 94.5, 103.0, 104.5, 108.3, 115.1, 117.1,
120.4, 123.5, 124.4, 125.3, 126.1, 127.1, 127.4, 129.1,
131.0, 131.4, 133.3, 134.1, 137.4, 137.5, 139.5, 140.4,
145.7, 147.1, 149.3, 150.3, 165.3. MS (m/z): 802; Anal.
Calcd. for C41H35Cl3N4O5S: C, 61.39; H, 4.40; N, 6.98.
Found: C, 61.09; H, 4.16; N, 7.08.
2-(3-(2,4-Dichlorophenoxy)-2-(3-hydroxy-4-
methoxyphenyl)-4-oxoazetidin-1-yl)-5-(2-(5-chloro-3-
methyl-1-phenyl-1H-pyrazol-4-yl)vinyl)-6,7-dihydro-7,
7-dimethylbenzo[b]thiophene-3-carbonitrile (5h)
Yield = 64%, m.p. 201–203°C. IR (KBr) cm-1: 3308,
3111, 2972, 2838, 2874, 2212, 1742, 1684, 1448, 1251,
Acknowledgements The authors are grateful to the Professor and
Head, Department of Chemistry, Saurashtra University, Rajkot for
123

Med Chem Res (2012) 21:1471–1479
1479
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