Synthesis of benzo[b]thiophene substituted carbamates, ureas, semicarbazides, and pyrazoles and their antimicrobial and analgesic activity

Article abstract of DOI:10.1080/10426500802388433

2-Azidocarbonyl-3-chlorobenzo[b]thiophene 3 was obtained from 3-chloro-benzo[b]thiophene-2-carbonyl chloride 1 and 3-chloro-benzo[b]thiophene- 2-carboxy hydrazide 2. The compound 3 on Curtius rearrangement with various alcohols, amines, and hydrazines afforded the corresponding carbamates 4a-b, ureas 5a-j, and semicarbazides 6a-g, respectively. Compound 2 was also utilized for the synthesis of pyrazoles 7a-c by treatment with various chalcones. The structures of the newly synthesized compounds were elucidated on the basis of IR, 1H NMR, and mass spectral data and have been screened for antimicrobial and analgesic activities.

Full text of DOI:10.1080/10426500802388433

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Synthesis of
Benzo[b]thiophene Substituted
Carbamates, Ureas,
Semicarbazides, and Pyrazoles
and Their Antimicrobial and
Analgesic Activity
Tholappanavara H. Suresha Kumara a , Kittappa
M. Mahadevan a , Hosanagara N. Harishkumar a
,
Basavaraj Padmashali b & Gadada Naganagowda b
a Department of Post Graduate Studies and Research
in Chemistry , Kuvempu University , Shankaraghatta,
Karnataka, India
b Department of Chemistry , Sahyadri Science
College (Autonomous) , Shimoga, Karnataka, India
Published online: 22 Jun 2009.
To cite this article: Tholappanavara H. Suresha Kumara , Kittappa M. Mahadevan ,
Hosanagara N. Harishkumar , Basavaraj Padmashali & Gadada Naganagowda
(2009) Synthesis of Benzo[b]thiophene Substituted Carbamates, Ureas,
Semicarbazides, and Pyrazoles and Their Antimicrobial and Analgesic Activity,
Phosphorus, Sulfur, and Silicon and the Related Elements, 184:7, 1866-1879, DOI:
10.1080/10426500802388433
To link to this article: http://dx.doi.org/10.1080/10426500802388433
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Phosphorus, Sulfur, and Silicon, 184:1866–1879, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802388433
Synthesis of Benzo[b]thiophene Substituted Carbamates,
Ureas, Semicarbazides, and Pyrazoles and Their
Antimicrobial and Analgesic Activity
Tholappanavara H. Suresha Kumara,1 Kittappa M.
Mahadevan,1 Hosanagara N. Harishkumar,1
Basavaraj Padmashali,2 and Gadada Naganagowda2
1Department of Post Graduate Studies and Research in Chemistry,
Kuvempu University, Shankaraghatta, Karnataka, India
2Department of Chemistry, Sahyadri Science College (Autonomous),
Shimoga, Karnataka, India
2-Azidocarbonyl-3-chlorobenzo[b]thiophene
3
was obtained from 3-chloro-
benzo[b]thiophene-2-carbonyl chloride 1 and 3-chloro-benzo[b]thiophene-2-carboxy
hydrazide 2. The compound 3 on Curtius rearrangement with various alcohols,
amines, and hydrazines afforded the corresponding carbamates 4a–b, ureas 5a–
j, and semicarbazides 6a–g, respectively. Compound 2 was also utilized for the
synthesis of pyrazoles 7a–c by treatment with various chalcones. The structures
1
of the newly synthesized compounds were elucidated on the basis of IR, H NMR,
and mass spectral data and have been screened for antimicrobial and analgesic
activities.
Keywords
Analgesic
activity;
antimicrobial
activity;
2-azidocarbonyl-3-
chlorobenzo[b]thiophene; Curtius rearrangement
INTRODUCTION
The acyl azido group is most useful in organic synthesis, due to its
ready conversion to amino groups or due to its photochemical or cy-
cloaddition reactions or Curtius rearrangement in the presence of nu-
cleophiles. Curtius rearrangement describes the degradation of an acyl
azide into an isocyanate through a concerted mechanism.1 Trapping
the isocyanates with nucleophiles is a most widely used method for
synthesizing amine derivatives. Acyl azides can be prepared from car-
boxylic acid derivatives such as hydrazides,2 acyl chlorides,3and mixed
Received 17 March 2008; accepted 3 August 2008.
Address correspondence to Basavaraj Padmashali, Department of Chemistry,
Sahyadri Science College (Autonomous), Shimoga–577 203, Karnataka, India. E-mail:
basavarajpadmashali@yahoo.com
1866

Synthesis of Benzo[b]thiophene Substituted Carbamates
1867
anhydrides.4,5 These acyl azides can be isolated, and Curtius rearrange-
ment is then performed in a separate step. The literature is rich with
references related to Curtius rearrangements that involve the synthe-
sis of carbamates and ureas.6,7
The benzo[b]thiophene derivatives have been found to exhibit
analgesic activity,8 anti-inflammatory activity,9 serotonine N-
acetyltransferase inhibitor activity,10 antitubercular activity, and
antimicrobial activity.11 It was also thought to be of interest to
synthesize some benzo[b]thiophene derivatives containing other bi-
ologically potent moieties. In view of the diverse and remarkable
biological properties of several heterocyclic systems with pendant
carbamates12–13 and diphenylureas,14–16 we thought of coupling these
moieties with benzo[b]thiophene. Pyrazoles are well documented to pos-
sess antihypertensive,17 antibacterial,18,19 anti-inflammatory,20,21 and
anti-tumor activities,22 and they have wide applications as pharmaceu-
ticals and agrochemical agents.23,24 Hence, in the third series of com-
pounds, the synthesis of the pyrazole derivatives of benzo[b]thiophene
is reported.
In this context, it was contemplated to synthesize benzo[b]thiophene
substituted carbamates, ureas, semicarbazides, and pyrazoles, as
shown in Scheme 1.
RESULTS AND DISCUSSION
In this article, we report the synthesis and biological properties of
some carbamates 4a–b, ureas 5a–j, semicarbazides 6a–g incorpo-
rated with the benzo[b]thiophene ring, using the well-known Curtius
rearrangement. The starting material, 2-acylazidobenzo[b]thiophene-
3-chloride 3, was prepared by reacting 3-chlorobenzo[b]thiophene-2-
carbonyl chloride25 1 with sodium azide in acetone medium. The acyl
azide 3 can also be prepared by treating the carbonyl chloride 1 with
hydrazine to get 3-chloro-benzo[b]thiophene-2-carboxy hydrazide26
2
followed by diazotization. The IR spectrum of 3 showed a peak at
1
2184 cm−1 due to an azido group. The H NMR spectrum showed a
multiplet in the aromatic region due to four protons. The formation of 3
was also proved by the mass spectrum data, which showed a molecular
ion peak at 244.
The acyl azide 3, upon refluxing with various alcohols, produced
3-chlorobenzo[b]thiophene-2-carbamates 4a–b in good yields. The ab-
–1
sence of an azide band at 2184 cm and the presence of an N–H band
–1
at 3240 cm in IR spectrum of 4a was the evidence for the rearrange-
ment of azide to carbamates. The 1H NMR (300 MHz) spectrum showed

1868
T. H. S. Kumara et al.
O
Cl
Cl
Cl
O
O
N
O
R
NH2NH2
S
S
S
NH
Cl
HN
1
2
7a-c
NH2
NaNO2/HCl
NaN3
R
Cl
O
Cl
Alcohols
NH
S
S
N3
O
O
3
4a-b
R
NHNH2
NH2
R1
R3
R3
R1
Cl
R2
Cl
R2
NH
O
NH
R1
R2
S
NH
S
NH R1
O
6a-f
5a-j
HN
R3
R2
R3
SCHEME 1 General synthetic procedure for 3-chlorobenzo[b]thiophene sub-
stituted carbamates 4a–b, ureas 5a–j, semicarbazides 6a–g, and pyrazoles
7a–c.
a multiplet in the region δ 7.27–7.74 due to four aromatic protons, a
broad peak at δ 7.40 corresponding to an NH proton, a quartet at δ
4.31–4.37 corresponding to CH2 protons, and a triplet at δ 1.36–1.58
corresponding to CH3 protons. This was further confirmed by its mass
spectrum, which showed a molecular ion peak m/z at 255, which agrees
with the molecular weight of the compound. In this series, another car-
bamate 4b was also prepared by using methanol, and it was also well
characterized through spectral data.
The treatment of acyl azide 3 with various anilines afforded 3-
chlorobenzo[b]thiophene substituted ureas 5a–j. The IR spectra of all
–1
these compounds showed two sharp bands at 3275–3320 cm due to
N–H groups and the sharp bands at 1628 cm–1 due to C O groups. The
–1
absence of the azide band at 2184 cm also confirms the formation
1
of compounds 5a–j. The H NMR spectrum of compound 5a showed a
multiplet in the region δ 6.80–7.70 corresponding to eight aromatic pro-
tons, a peak at δ 7.40 corresponding to two protons of two NH groups,
and a singlet at δ 3.50 corresponding to CH3protons. This was further

Synthesis of Benzo[b]thiophene Substituted Carbamates
1869
confirmed by its mass spectrum, which showed a molecular ion peak m/z
at 317, and which agrees with the molecular weight of the compound. In
this series, the other compounds 5b–j were prepared by using various
phenyl hydrazines, and they were also characterized by their spectral
data.
The acyl azide 3 also underwent smooth rearrangement with various
phenyl hydrazines to produce 3-chlorobenzo[b]thiophene substituted
semicarbazides 6a–g. The IR spectra of all these compounds showed
two sharp bands at 3290–3320 due to CONH groups, 3335–3350 due to
–1
N-H groups, and a sharp band at 1628 cm due to C O groups. The
–1
absence of the azide band at 2184 cm also confirmed the formation
of compounds 6a–g. The H NMR spectrum of compound 6a showed a
1
singlet at δ 8.90 corresponding to two protons of CONH, a multiplet in
the region δ 7.30–7.90 due to the nine aromatic protons, and a singlet at
δ 6.80 corresponding to one proton of NH. This was further confirmed
by its mass spectrum, which showed molecular ion peak m/z at 318,
and which agrees with the molecular weight of the compound. In this
series, the other compounds 6b–g were also prepared by using various
phenyl hydrazines, and they were also characterized by their spectral
data.
The intermediate 3-chloro benzo[b]thiophene-2-carboxyhydrazide 2
was utilized for the synthesis of pyrazoles 7a–c by reacting it with
various chalcones. The IR spectra of all these compounds showed 3320
(singlet) corresponds to N-H and sharp signal at 1628 cm−1 due to C O.
The 1H-NMR spectrum (compound 7a) showed a signal at 10.0 (singlet)
due to pyrazole proton, 7.20–8.0 corresponding to fifteen aromatic pro-
tons, and the signal at 6.50 corresponding to one proton of CH. This
was further confirmed by its mass spectrum, which showed molecular
ion peak m/z at 418, and which agrees with the molecular weight of the
compound. In this series, other pyrazoles 7b–c were prepared by using
different chalcones, and they were also characterized by their spectral
data.
The physical properties of the synthesized compounds are shown in
Table I and have been screened for antimicrobial and analgesic activi-
ties.
ANTIBACTERIAL ACTIVITY
All the synthesized compounds were screened for their antibacterial
activity against Staphylococcus aureus, Escherichia coli, S. paratyphi-
A, and Bacillus subtilis. The activity was carried out using the cup
plate agar diffusion method.27 The zone of inhibition was measured in

1870
T. H. S. Kumara et al.
TABLE I Characterization Data of the Compounds
Sl. No Comp
R
R1
R2
R3
Nature
Yield (%) Mp (◦C)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
3
—
CH2CH3
CH3
—
—
—
—
H
H
CH3
H
OCH3
H
H
H
H
F
H
H
H
CH3
H
H
—
—
—
—
H
CH3
H
OCH3
H
H
H
Cl
H
H
H
H
CH3
H
H
H
—
—
—
—
—
CH3
H
H
Crystalline
Amorphous
Amorphous
Crystalline
Crystalline
Crystalline
Crystalline
Crystalline
85
40
38
96
92
90
86
95
92
90
85
92
80
88
96
90
86
91
80
65
60
50
101–105
68–71
65–68
4a
4b
5a
5b
5c
5d
5e
5f
218–220
214–218
213–216
235–238
229–231
238–240
221–225
220–223
206–210
245–250
190–195
203–205
201–203
203–206
207–210
205–208
142–145
148–150
157–159
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
H
H
H
OCH3 Crystalline
Cl
H
H
NO2
H
CH3
H
H
Cl
F
—
5g
5h
5i
Crystalline
Crystalline
Crystalline
Crystalline
Crystalline
Crystalline
Crystalline
Crystalline
Crystalline
Crystalline
Amorphous
Amorphous
Amorphous
5j
6a
6b
6c
6d
6e
6f
7a
7b
7c
Cl
NO2
—
—
—
—
—
millimeters. DMF was used as a vehicle. Choramphenicol and Strep-
tomycin were used as standard drugs for comparison. The compounds
were tested at 40 µg/mL concentration. All the synthesized compounds
were found to show moderate to poorly active against all bacteria. The
zones of inhibition are presented in Table II.
ANALGESIC ACTIVITY
Albino mice of either sex (20–30 g) were subjected to acetic acid in-
duced writhing to test for analgesic activity.28 Acetic acid solution (0.6%,
10 mL/kg) was used to induce writhing in mice. The mice were divided
into 13 groups, each consisting of six animals. The analgesic response
was assessed by counting the number of abdominal constrictions for 20
min starting 3 min after the injection of acetic acid solution. Groups 1 to
12 received the suspension of test compounds (100 mg/kg dose), respec-
tively, and group 13 received the standard drug suspension (Ibuprofen)
at the dose of 100 mg/kg. After 1 h, acetic acid solution was admin-
istered intraperitoneally and number of abdominal constrictions was

Synthesis of Benzo[b]thiophene Substituted Carbamates
1871
TABLE II Antibacterial Activity of the Compounds
Diameter of zone of inhibition (mm)
Staphylococcus
aureus
Escherichia
coli
S.
Bacillus
subtilis
Compound
Paratyphi-A
4a
4b
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
6a
6b
6c
6d
14
13
11
11
12
12
13
15
12
13
14
11
14
14
15
13
14
15
11
13
11
00
20
08
12
12
13
11
12
10
12
12
09
13
10
09
09
08
13
12
11
12
10
11
00
14
10
15
14
15
16
12
14
13
15
10
14
16
13
17
11
13
15
16
14
16
15
00
18
12
17
18
15
16
15
17
17
14
11
18
17
14
17
15
17
16
17
17
15
16
00
22
6e
6f
7a
7b
7c
DMF
Chloramphenicol
recorded for 20 min starting 3 min after the injection of acetic acid so-
lution. Analgesic activity was calculated as the percentage maximum
possible effect (%MPE), and the results are given in Table III.
EXPERIMENTAL SECTION
Melting points were determined in an open capillary and are uncor-
rected. 1H NMR (300 MHz) spectra were run in CDCl3 and DMSO
solutions. Chemical shifts are expressed in δ ppm. Mass spectra were
performed on a Joel JMS-D 300 mass spectrometer operating at 70 eV.
IR spectra were recorded by using JASCO FT/IR-300 E spectrometer
from a KBr pelleted sample. Elemental analysis was done by a Perkin-
Elmer auto analyzer at IISc Bangalore. The purity of the compounds
was checked by TLC, and further purification was done by column chro-
matography.

1872
T. H. S. Kumara et al.
TABLE III Analgesic Activity of the Compounds
Mean number of abdominal constrictions
occurred between 3 and 20 min
Compound
Dose mg/kg
Before drug
After drug
% MPE
4a
4b
5a
5b
5c
5d
5e
5f
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
40.6 2.1
52.4 2.5
26.4 1.5
24.8 1.2
40.1 2.0
23.1 1.6
26.4 1.5
24.8 1.2
39.6 2.1
40.1 2.0
28.6 1.7
40.6 2.1
52.4 2.5
26.4 1.5
24.8 1.2
34.1 2.0
23.1 1.5
26.4 1.6
23.8 1.0
33.1 2.0
28.4 1.3
22.1 1.3
47.1 2.5
15.8 1.43
17.2 3.61
10.1 0.89
8.4 0.92
15.2 1.40
8.9 0.79
10.1 0.89
8.4 0.92
14.8 1.43
15.2 1.40
12.2 1.21
13.8 0.43
17.2 2.61
10.4 1.89
8.5 1.92
15.1 0.40
8.9 0.82
10.4 1.3
8.3 1.2
61.1∗
67.3∗
62.1∗
66.1∗
60.1∗
63.4∗
62.1∗
66.1∗
61.7∗
60.1∗
64.1∗
61.3∗
60.3∗
68.3∗
68.5∗
60.1∗
66.4∗
62.2∗
61.7∗
60.1∗
67.4∗
64.0∗
75.1∗
5g
5h
5i
5j
6a
6b
6c
6d
6e
6f
6g
7a
7b
7c
13.9 0.60
12.8 1.20
8.9 0.79
11.8 1.27
Ibuprofen
Analgesic activity, ∗P < 0.001 vs. control; student’s t-test, n = 6.
Preparation of 3-Chlorobenzothiophene-2-carbonyl Azide (3)
Method A: To a stirred solution of 3-chloro-benzo[b]thiophene-2-
carbonyl chloride 1 (2.0 g, 8.0 mmol) in anhydrous acetone (50 mL),
a solution of sodium azide (0.52 g, 8.0 mmol) in water (2 mL) was
added dropwise at 0◦C. After the complete addition of sodium azide,
the temperature of the reaction mixture was raised to 25◦C, and this
temperature was maintained for 30 min. to ensure the completion of the
reaction. The reaction mixture was diluted with cold water (100 mL),
and then the pale yellow solid obtained was filtered, washed thoroughly
with cold water, and dried over phosphorous pentoxide in vacuum to
get (2.08 g) 85% of the pure 3.
Method B: 3-Chlorobenzo[b]thiophene-2-carboxyhydrazide 2 (10 g,
44.0 mmol) was suspended in 1,4-dioxane (60 mL) and acetic acid (60
mL) and cooled to 0◦C. An ice cold solution of sodium nitrite (4.85 g,

Synthesis of Benzo[b]thiophene Substituted Carbamates
1873
71.0 mmol) in water (18 mL) was introduced into it in small portions
with vigorous stirring. Meanwhile the temperature of the reaction mix-
ture was maintained below 5◦C, then it was allowed to stay at room
temperature for 30 min. The pale yellow solid that was obtained was
filtered, washed thoroughly with cold water, and dried over phospho-
rous pentoxide in vacuum to obtain (9 g) 85% of pure 3.
3-Chlorobenzothiophene-2-carbonyl Azide (3)
IR (KBr) ν (cm−1): 2184 (N3), 1712 (C O), 1572 (N N), 781 (C-S-C),
752 (C-Cl); 1H NMR (300 MHz, CDCl3) δ (ppm): 7.20-7.90 (4H, m, ArH);
MS (M+): 244. Calcd. (%) for (C9H4ClN3OS): C, 45.48; N, 17.68; S, 13.38;
H, 4.20. Found: C, 45.25; N, 17.35; S, 13.11; H, 4.01.
Preparation of Ethyl-3-chloro-1-benzothien-2-ylcarbamate (4)
A suspension of 3-chlorobenzothiophene-2-carbonyl azide 3 (2 g,
8.2 mmol) in absolute ethanol (15 mL) was refluxed on steam bath for 3
h. The reaction mixture was concentrated under reduced pressure, and
then it was diluted with cold water with stirring. The product that sep-
arated was filtered, washed with water, dried, and purified from column
chromatography by using petroleum ether, and ethyl acetate (0.5:9.5)
was used as an elutent to get pure 4a. Similarly, the compound 4b was
prepared.
Ethyl-3-chloro-1-benzothien-2-ylcarbamate (4a)
IR (KBr) ν (cm−1): 3240 (N-H), 1712 (C O), 781 (C-S-C), 752 (C-Cl);
1H NMR (300 MHz, CDCl3) δ (ppm): 7.27–7.74 (4H, m, ArH), 7.40 (1H,
b, NH), 4.31–4.37 (2H, q, CH2), 1.36–1.58 (3H, t, CH3); MS (M+): 255,
210. Calcd. (%) for C10H8ClNO2S: C, 49.69; H, 3.34; N, 5.80; S, 13.27.
Found: C, 49.35; S, 13.27; N, 5.80; H, 3.18.
Methyl-3-chloro-1-benzothien-2-ylcarbamate (4b)
IR (KBr) ν (cm−1): 3240 (N-H), 1712 (C O), 781(C-S-C), 752 (C-Cl);
1H NMR (300 MHz, CDCl3) δ (ppm): 7.27–7.74, (4H, m, ArH), 7.40
(1H, broad, NH), 3.60 (3H, s, OCH3); MS (M+): 242. Calcd. (%) for
C10H8ClNO2S: C, 60.64; S, 13.27; N, 5.89; H, 3.34. Found: C, 60.36; S,
13.27; N, 5.52; H, 3.34.
Preparation of N-(3-Chloro-1-benzothien-2-yl)-N’-
(4-methylphenyl) Urea (5)
A suspension of 3-chlorobenzothiophene-2-carbonyl azide 3 (2 g,
8.2 mmol) and p-toludine (0.878 g, 8.2 mmol) in anhydrous toluene

1874
T. H. S. Kumara et al.
(15 mL) was heated under gentle reflux (110◦C) in an oil bath for 4
h. The crystalline product that separated on cooling was filtered and
washed with toluene and petroleum ether. The analytical sample was
obtained by crystallization from chloroform. Similarly, the compounds
5b–j were prepared.
N-(3-Chloro-1-benzothien-2-yl)-N’-(4-methylphenyl)urea (5a)
IR (KBr) ν (cm−1): 3300 (N-H), 1628 (C O), 781 (C-S-C), 752 (C-
1
Cl); H NMR (300 MHz, CDCl3) δ (ppm): 7.40 (2H, s, NH), 6.80–7.70
(8H, m, Ar H), 3.50 (3H, s, CH3); MS (M+): 317, 302. Calcd. (%) for
C16H13ClN2OS: C, 60.66; S, 10.12; N, 8.84; H, 4.14. Found: C, 60.26 S,
10.01; N, 8.57; H, 3.86.
N-(3-Chloro-1-benzothien-2-yl)-N’-(3-methylphenyl)urea (5b)
IR (KBr) ν (cm−1): 3310 (N-H), 1628 (C O), 781 (C-S-C), 752 (C-
1
Cl); H NMR (300 MHz, CDCl3) δ (ppm): 7.40 (2H, s, NH), 6.80–7.70
(8H, m, Ar H), 3.50 (3H, s, CH3); MS (M+): 317, 302. Calcd. (%) for
C16H13ClN2OS: C, 60.66; S, 10.12; N, 8.84; H, 4.14. Found: C, 60.30; S,
10.00; N, 8.56; H, 3.98.
N-(3-Chloro-1-benzothien-2-yl)-N’-(2-methylphenyl)urea (5c)
IR (KBr) ν (cm−1): 3290 (N-H), 1628 (C O), 781 (C-S-C), 752 (C-
Cl); 1H NMR (300 MHz, CDCl3) δ (ppm): 6.70–7.70 (8H, m, Ar H),
7.40 (2H, s, NH), 3.50 (3H, s, CH3); MS (M+): 317, 302; Calcd. (%) for
C16H13ClN2OS: C, 60.66; S, 10.12; N, 8.84; H, 4.14. Found: C, 60.34; S,
10.01; N, 8.54; H, 3.77.
N-(3-Chloro-1-benzothien-2-yl)-N’-(3-methoxyphenyl)urea (5d)
IR (KBr) ν (cm−1): 3315 (N-H), 1628 (C O), 781 (C-S-C), 752 (C-Cl)):
1H NMR (300 MHz, CDCl3) δ (ppm): 6.70–7.70 (8H, m, Ar H), 7.40
(2H, s, NH), 3.80 (3H, s, OCH3); MS (M+): 333, 332, 302. Calcd. (%) for
C16H13ClN2O2S: C, 57.74; S, 9.64; N, 8.42; H, 3.94. Found: C, 57.55; S,
9.43; N, 8.17; H, 3.69.
N-(3-Chloro-1-benzothien-2-yl)-N’-(2-methoxyphenyl)urea (5e)
IR (KBr) ν (cm−1): 3320 (N-H), 1628 (C O), 781 (C-S-C), 752 (C-Cl));
1H NMR (300 MHz, CDCl3) δ (ppm): 6.70–7.70 (8H, m, Ar H), 7.40
(2H, s, NH), 3.80 (3H, s, OCH3); MS (M+): 333, 332, 302. Calcd. (%) for
C16H13ClN2O2S: C, 57.74; S, 9.64; N, 8.42; H, 3.94. Found: C, 52.55; S,
9.45; N, 8.22; H, 3.67.

Synthesis of Benzo[b]thiophene Substituted Carbamates
1875
N-(3-Chloro-1-benzothien-2-yl)-N’-(4-methoxyphenyl)urea (5f)
IR (KBr) ν (cm−1): 3280 (N-H), 1628 (C O), 781 (C-S-C), 752 (C-Cl);
1H NMR (300 MHz, CDCl3) δ (ppm): 6.70–7.70 (8H, m, Ar H), 7.40
(2H, s, NH), 3.80 (3H, s, OCH3); MS (M+): 333, 332, 302. Calcd. (%) for
C16H13ClN2O2S: C, 57.74; S, 9.64; N, 8.42; H, 3.94. Found: C, 57.58; S,
9.40; N, 8.16; H, 3.65.
N-(3-Chloro-1-benzothien-2-yl)-N’-(4-chlorophenyl)urea (5g)
IR (KBr) ν (cm−1): 3275 (N-H), 1628 (C O), 781 (C-S-C), 752 (C-Cl);
1H NMR (300 MHz, CDCl3) δ (ppm): 6.80–7.70 (8H, m, Ar H), 7.40 (2H,
s, NH); MS (M+): 338, 301, 302. Calcd. (%) for C15H10Cl2N2OS: C, 53.42;
S, 9.51, N, 8.31; H, 2.99. Found: C, 53.12; S, 9.29, N, 8.01; H, 2.77.
N-(3-Chloro-1-benzothien-2-yl)-N’-(3-chlorophenyl)urea (5h)
IR (KBr) ν (cm−1): 3320 (N-H), 1628 (C O), 781 (C-S-C), 752 (C-Cl);
1H NMR (300 MHz, CDCl3) δ (ppm): 6.80–7.70 (8H, m, Ar H), 7.40 (2H,
s, NH); MS (M+): 338, 301. Calcd. (%) for C15H10Cl2N2OS: C, 53.42; S,
9.51, N, 8.31; H, 2.99. Found: C, 53.12; S, 9.27, N, 8.01; H, 2.75.
N-(3-Chloro-1-benzothien-2-yl)-N’-phenylurea (5i)
IR (KBr) ν (cm−1): 3300 (N-H), 1628 (C O), 781 (C-S-C), 752 (C-Cl);
1H NMR (300 MHz, CDCl3) δ (ppm): 6.80–7.70 (8H, m, Ar H), 7.40 (2H,
s, NH); MS (M+): 303, 211. Calcd. (%) for C15H11ClN2OS: C, 59.50; S,
10.59; N, 9.25; H, 3.66. Found: C, 59.22; S, 10.37; N, 9.03; H, 3.55.
N-(3-Chloro-1-benzothien-2-yl)-N’-(2-fluoro-4-nitrophenyl)urea
(5j)
IR (KBr) ν (cm−1): 3310 (N-H), 1628 (C O), 781 (C-S-C), 752 (C-Cl);
1H NMR (300 MHz, CDCl3) δ (ppm): 9.20–9.40 (2H, s, NH), 7.20–8.20
(7H, m, Ar H); MS (M+): 366, 348. Calcd. (%) for C15H9ClFN3O3S: C,
49.26; N, 11.49; S, 8.77; H, 2.48. Found: C, 49.00; N, 11.19; S, 8.68; H,
2.32.
Preparation of N-(3-Chloro-1-benzothien-2-yl)-2-
phenylhydrazinecarboxamide (6)
A suspension of 3-chlorobenzothiophene-2-carbonyl azide 3 (2 g,
8.2 mmol) and phenyl hydrazine (0.88 g, 8.2 mmol) in anhydrous
toluene (15 mL) was refluxed on an oil bath for about 6 h. Then re-
action mixture was cooled to room temperature, and the solid that

1876
T. H. S. Kumara et al.
separated was filtered, washed with toluene, and then with petroleum
ether. It was recrystallized by methanol to get pure 6a. Similarly, the
compounds 6b–f were prepared.
N-(3-Chloro-1-benzothien-2-yl)-2-
phenylhydrazinecarboxamide (6a)
IR (KBr) ν (cm−1): 3290 (CON-H), 3330 (N-H), 1628 (C O), 781 (C-S-
C), 752 (C-Cl); 1H NMR (300 MHz, CDCl3) δ (ppm): 8.90 (2H, s, CONH),
7.30–7.90 (9H, m, Ar H), 6.80 (1H,s, NH); MS (M+): 318, 282, 178. Calcd.
(%) for C15H12Cl N3OS: C, 56.69; N, 13.22; S, 10.09; H, 3.81, Found: C,
56.22; N, 13.11; S, 9.88; H, 3.66.
N-(3-Chloro-1-benzothien-2-yl)-2-(4-methylphenyl)-
hydrazinecarboxamide (6b)
IR (KBr) ν (cm−1): 3310 (CON-H), 3340 (N-H), 1628 (C O), 781 (C-S-
C), 752 (C-Cl); 1H NMR (300 MHz, CDCl3) δ (ppm): 8.90 (2H, s, CONH),
7.30–7.90 (8H, m, Ar H), 6.80 (1H,s, NH), 3.40 (3H, s, CH3); MS (M+):
332, 317. Calcd. (%) for C16H14ClN3OS: C, 57.91; N, 12.66; S, 9.66; H,
4.25. Found: C, 57.41, N, 12.32; S, 9.66; H, 4.25.
N-(3-Chloro-1-benzothien-2-yl)-2-(3-methylphenyl)-
hydrazinecarboxamide (6c)
IR (KBr) ν (cm−1): 3300 (CON-H), 3335 (N-H), 1628(C O), 781(C-S-
C), 752(C-Cl); 1H NMR (300 MHz, CDCl3) δ (ppm): 8.80 (2H, s, CONH),
7.20–7.90 (8H, m, Ar H), 6.90 (1H,s, NH), 3.5(3H, s, CH3); MS (M+):
332, 318. Calcd. (%) for C16H14ClN3OS: C, 57.91; N, 12.66; S, 9.66; H,
4.25. Found: C, 57.39, N, 12.33; S, 9.66; H, 4.27.
N-(3-Chloro-1-benzothien-2-yl)-2-(2-methylphenyl)-
hydrazinecarboxamide (6d)
IR (KBr) ν (cm−1): 3315 (CON-H), 3350 (N-H), 1628(C O), 781 (C-
1
S-C), 752 (C-Cl);); H NMR (300 MHz, CDCl3) δ (ppm): 8.90 (2H, s,
CONH), 7.30–7.90 (8H, m, Ar H), 6.80 (1H,s, NH), 3.60 (3H, s, CH3);
MS (M+): 332, 318. Calcd. (%) for C16H14ClN3OS: C, 57.91; N, 12.66; S,
9.66; H, 4.25. Found: C, 57.40, N, 12.31; S, 9.65; H, 4.24.
N-(3-Chloro-1-benzothien-2-yl)-2-(4-chlorophenyl)-
hydrazine Carboxamide (6e)
IR (KBr) ν (cm−1): 3290 (CON-H), 3345 (N-H), 1628 (C O), 781 (C-S-
C), 752 (C-Cl); 1H NMR (300 MHz, CDCl3) δ (ppm): 9.0 (2H, s, CONH),
7.40–8.0 (8H, m, Ar H), 6.90 (1H, s, NH); MS (M+): 353, 316. Calcd.

Synthesis of Benzo[b]thiophene Substituted Carbamates
1877
(%) for C15H11Cl2N3OS: C, 51.15; N, 11.93; S, 9.10; H, 3.15. Found: C,
51.01; N, 11.52; 9.01; H, 2.89.
N-(3-Chloro-1-benzothien-2-yl)-2-(4-flurophenyl)hydrazine
Carboxamide (6f)
IR (KBr) ν (cm−1): 3320 (CON-H), 3330 (N-H), 1628 (C O), 781 (C-S-
C), 752 (C-Cl); 1H NMR (300 MHz, CDCl3) δ (ppm): 9.0 (2H, s, CONH),
7.30–8.0 (8H, m, Ar H), 6.80 (1H, s, NH); MS (M+): 337, 318; Calcd.
(%) for C15H11ClFN3OS: C, 53.65; N, 12.51; S, 9.55; H, 3.30. found: C,
53.32; N ,12.25; S, 9.33; H, 3.19.
Preparation of 1-[(3-Chloro-1-benzothien-2-yl)carbonyl]-3,5-
diphenyl-2,3-dihydro-1H-pyrazole (7)
A hot mixture of 1,3-diphenylprop-2-en-1-one (2.08 g, 10 mmol)
and a catalytic amount of acetic acid in 1,4-dioxane (40 mL) was
stirred for 15 min, and then powdered 3-chloro benzo[b]thiophene-2-
carboxyhydrazide 2 (2.265 g, 10 mmol) was added. Then the reaction
mixture was refluxed for about 26 h at reflux temperature, and the com-
pletion of the reaction was monitored through TLC. After completion
of the reaction, the reaction mixture was cooled to room temperature
and poured into 200 g crushed ice taken in 500 mL beaker with stirring
for about 10 min. The solid that separated was filtered and washed
thoroughly with water, dried, and purified through column chromatog-
raphy by using ethyl acetate and petroleum ether (1:9) as an elutent to
get pure sample of 7a. Similarly, the compounds 7b–c were prepared.
1-[(3-Chloro-1-benzothien-2-yl)carbonyl]-3,5-diphenyl-2,3-
dihydro-1H-pyrazole (7a)
IR (KBr) ν (cm−1): 3320 (N-H), 1628 (C O), 781 (C-S-C), 752 (C-Cl);
1H NMR (300 MHz, CDCl3) δ (ppm): 10.0 (1H, s, NH), 7.20–8.0 (15H,
m, Ar H), 6.50 (1H, d, CH); MS (M+): 418, 417, 340. Calcd. (%) for
C24H17ClN2OS: C. 69.14,; N, 6.72; S, 7.69; H, 4.11. Found: C, 69.01; N,
6.36; S, 7.55; H, 4.01.
2-[(3-Chloro-1-benzothien-2-yl)carbonyl]-5-(4-chlorophenyl)-3-
phenyl-2,3-dihydro-1H-pyrazole (7b)
IR (KBr) ν (cm−1): 3320 (N-H), 1628 (C O), 781 (C-S-C), 752 (C-
1
Cl); H NMR (300 MHz, CDCl3) δ (ppm): 10.20 (1H, s, NH), 7.20–8.0
(14H, m, Ar H), 6.50 (1H, d, CH); MS (M+): 453, 417. Calcd. (%) for
C24H16Cl2N2OS: C, 63.86; N, 6.21; S, 7.10; H, 3.57. Found: C, 63.42; N,
6.03; S, 6.90; H, 3.23.

1878
T. H. S. Kumara et al.
1-[(3-Chloro-1-benzothien-2-yl)carbonyl]-3-(4-nitrophenyl)-5-
phenyl-2,3-dihydro-1H-pyrazole (7c)
IR (KBr) ν (cm−1): 3320 (N-H), 1628 (C O), 1349 (N O), 781 (C-S-
C), 752 (C-Cl); 1H NMR (300 MHz, CDCl3) δ (ppm): 10.10 (1H, s, NH),
7.10–8.0 (14H, m, Ar H), 6.60 (1H, d, CH); MS (M+): 463, 417. Calcd.
(%) for C24H16ClN3O3S: C, 62.40; N, 9.10; S, 6.94; H, 3.49. Found: C,
62.22; N, 8.77; S, 6.74; H, 3.19.
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