Synthesis and antioxidant activity of amido-linked benzoxazolyl/ benzothiazolyl/benzimidazolyl-pyrroles and pyrazoles

Article abstract of DOI:10.1007/s00044-013-0884-x

The amido-linked benzoxazolyl/benzothiazolyl/benzimidazolyl-pyrroles and benzoxazolyl/benzothiazolyl/benzimidazolyl-pyrazoles were prepared from the synthetic intermediates (E)-N-(benzoxazol-2-yl)cinnamamide/(E)-N-(benzothiazol- 2-yl)cinnamamide/(E)-N-(1H

Full text of DOI:10.1007/s00044-013-0884-x

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res
DOI 10.1007/s00044-013-0884-x
ORIGINAL RESEARCH
Synthesis and antioxidant activity of amido-linked benzoxazolyl/
benzothiazolyl/benzimidazolyl-pyrroles and pyrazoles
•
Suram Durgamma Akkarapalli Muralikrishna
•
•
Venkatapuram Padmavathi Adivireddy Padmaja
Received: 19 August 2013 / Accepted: 15 November 2013
Ó Springer Science+Business Media New York 2013
Abstract The amido-linked benzoxazolyl/benzothiazolyl/
benzimidazolyl-pyrroles and benzoxazolyl/benzothiazolyl/
benzimidazolyl-pyrazoles were prepared from the synthetic
intermediates (E)-N-(benzoxazol-2-yl)cinnamamide/(E)-N-
(benzothiazol-2-yl)cinnamamide/(E)-N-(1H-benzimidazol-
2-yl)cinnamamides adopting simple and versatile synthetic
methodologies. All the new compounds were tested for
antioxidant activity. The compounds 5b, 8b and 14b dis-
played greater antioxidant activity when compared with the
standard drug ascorbic acid. It was also observed that
benzoxazolyl amido-linked derivatives displayed greater
radical scavenging activity than the benzothiazolyl and
benzimidazolyl amido-linked derivatives.
possess diverse chemotherapeutic activities viz., antimicro-
bial (Oren et al., 1997; Oren et al., 1999; Temiz-Arpaci et al.,
2002, 2005; Vinsova et al., 2005), antiviral (Akbay et al.,
2003) and antitumour (Ukei and Taniguchi, 1997; Varga
et al., 2005). Benzothiazoles display a wide range of biolog-
ical activities viz., antitumour (Chua et al., 1999), anti-
inflammatory (Paramashivappa et al., 2003), analgesic
(Westaway et al., 2008), antimicrobial (Yildiz-Oren et al.,
2004), anticonvulsant (Ucar et al., 1998) and antimalarial
(Takasu et al., 2002). The benzimidazole exhibits clinical
value towards breast cancer (Andrzejewska et al., 2002; Gu-
mus et al., 2003; Kamal et al., 2004; Chauhan et al., 2005),
leukaemia (Garuti et al., 2000; Demirayak et al., 2002),
tumour cells (Lukevics et al., 2001; Handratta et al., 2005),
etc. Pyrroles are the fundamental structural motifs in various
classes of natural and biologically important molecules like
porphyrins, bile pigments, coenzymes and alkaloids (Boger
et al., 1999; Fan et al., 2008). Nitropsin and distamycin are
pyrrole polyamides and are naturally occurring anticancer
antibiotics (Wemmer, 1999). In the literature, multistep syn-
thetic routes of 3,4-disubstituted pyrroles have been reported
either by coupling of imines and nitroalkanes or using Fri-
edel–Craft’s acylation with an electron-withdrawing group on
the pyrrole nitrogen or 3,4-silylated precursors (Shiraishi
et al., 1999; Zelikin et al., 1999; Liu et al., 2000). 3,4-
Disubstituted pyrroles have also been synthesized from
Michael acceptors with tosyl methyl isocyanide (TosMIC)
(Van Leusen et al., 1972; Pavri and Trudell, 1997; Padmav-
athi et al., 2004). Several pyrazole derivatives exhibit a wide
range of biological activities such as potential HIV-1 inhibi-
tors (Larsen et al., 1999), insecticides (Arrieta et al., 1998),
fungicides (Arrieta et al., 1998), antiviral (Rashad et al.,
2008), antihyperglycemic (Kees et al., 1996), anti-inflam-
matory (Penning et al., 1997), antiobesity (Rinaldi-Carmona
et al., 1994) and anticancer (Bouabdallah et al., 2006). The
Keywords Benzoxazole ꢀ Benzothiazole ꢀ
Benzimidazole ꢀ Pyrrole ꢀ Pyrazole ꢀ Antioxidant activity
Introduction
Scientific efforts have continuously been directed towards the
synthesis of five membered heterocycles because of their vital
role as drugs and pharmaceutical agents. Benzoxazole, ben-
zothiazole and benzimidazole motifs are found in several
important natural products (Easmon et al., 2006; Kumar et al.,
2002) and have many applications in the field of medicinal
chemistry (Ajay and Govindasamy, 2010; Venkatesh and
Pandeya, 2009; Padmavathi et al., 2012; Akhilesh and Swati,
2010; Hanan, 2010; Heba, 2011). Substituted benzoxazoles
S. Durgamma ꢀ A. Muralikrishna ꢀ V. Padmavathi ꢀ
A. Padmaja (&)
Department of Chemistry, Sri Venkateswara University,
Tirupati 517 502, Andhra Pradesh, India
e-mail: adivireddyp@yahoo.co.in
123

Med Chem Res
Scheme 1 Synthesis of
benzoxazolyl/benzothiazolyl/
benzimidazolyl-pyrroles and
pyrazoles
O
N
X
+
Cl
NH2
R
4
1/2/3
i
O
HA
N
2
1
X
4
5
6
3
9
8
2''
N
7
1''
3''
4''
H
HB
R
5(a-c)/6(a-c)/7(a-c)
iii
ii
R
R
O
O
N
N
3
4
4
7
5
6
HA
5
6
3
9
8
9
8
2
2
1
1
N
N
7
3' 4'
3'
4'
X
X
HM
HX
H
H
5'
2'
2'
5'
N
1'
1'
N
H
N
H
8(a-c)/9(a-c)/10(a-c)
11(a-c)/12(a-c)/13(a-c)
iv
R
O
N
4
7
5
3
2
9
8
6
(i) Toluene
1
N
3' 4'
X
H
(ii) TosMIC/NaH/DMSO/Et2O
(iii) CH2N2/Et3N/Et2O/-20 to -15 oC
(iv) Chloranil/Xylene
2'
5'
N
1'
N
H
14(a-c)/15(a-c)/16(a-c)
R a= H
b= Me
c= Cl
1, 5(a-c), 8(a-c), 11(a-c), 14(a-c) : X = O
2, 6(a-c), 9(a-c), 12(a-c), 15(a-c) : X = S
3, 7(a-c), 10(a-c), 13(a-c), 16(a-c) : X = NH
1,3-dipolar cycloaddition methodology is widely used for the
synthesis of pyrazoles using diverse synthons viz., nitrile
imines and alkynes (Conti et al., 2007), hydrazones and nitro
olefins (Palazzino et al., 1987; Deng and Mani, 2006), diazo
compounds and alkynes (Aggarwal et al., 2003) and azome-
thine imines and alkynes (Washizuka et al., 1999; Komatsu
et al., 2006). Recently, we have studied the antioxidant
activity of pyrazolyl oxadiazoles (Mallikarjuna Reddy et al.,
2013). Prompted by these findings and our continued interest
in the synthesis of biologically potent heterocycles (Padmaja
et al., 2009; Padmaja et al., 2011; Muralikrishna et al., 2012),
it is proposed to synthesize the molecules having different
pharmacophore units and to study their antioxidant activity.
benzimidazolyl-pyrroles and pyrazoles from benzoxazolyl/
benzothiazolyl/benzimidazolyl-styryl amides as depicted in
Scheme 1. The starting compounds, benzoxazol-2-amine (1)/
benzothiazol-2-amine (2)/1H-benzimidazol-2-amine (3),
were prepared by the cyclocondensation of 2-aminophenol/2-
aminothiophenol/1,2-phenylenediamine with cyanogen bro-
mide in methanol (Saritha et al., 2011; Robert et al., 2010).
Besides, the cinnamoyl chloride (4) was obtained by the
chlorination of cinnamic acid with thionyl chloride (Vogel,
1989).
The synthetic intermediates (E)-N-(benzoxazol-2-yl)cinn-
amamide (5a–5c), (E)-N-(benzothiazol-2-yl)cinnamamide
(6a–6c) and (E)-N-(1H-benzimidazol-2-yl)cinnamamide (7a–
7c) were prepared by the condensation of compounds 1, 2 and 3
with cinnamoyl chloride in toluene. The 1H NMR spectra of 5a,
6a and 7a showed two doublets at d 6.72, 6.78, 6.68 and 7.85,
7.86, 7.74 ppm which were assigned to olefin protons (HA and
HB). The downfield signal was attributed to HA. The coupling
constant, J & 16.0 Hz indicated that they are in trans geom-
etry. A broad singlet was also observed at d 8.32, 8.38 and
8.18 ppm due to NH in 5a, 6a and 7a, respectively.
Results and discussion
Chemistry
The present communication deals with the synthesis of a
new class of amido-linked benzoxazolyl/benzothiazolyl/
123

Med Chem Res
Table 1 The in vitro antioxidant activity of compounds 5(a–c)–16(a–c) in DPPH method
Compounds
Concentration
IC50 (lmol/ml)
50 lg/ml
75 lg/ml
100 lg/ml
5a
71.45 0.17
79.12 0.08
60.58 0.37
57.40 0.43
63.83 0.33
50.53 0.57
38.12 0.74
44.37 0.67
35.23 0.97
65.74 0.28
75.18 0.11
58.15 0.41
52.72 0.54
62.20 0.30
45.36 0.65
36.67 0.77
41.78 0.71
32.71 1.06
28.65 1.17
31.36 1.09
–
73.48 0.16
81.79 0.06
62.18 0.32
58.81 0.46
67.69 0.25
52.75 0.52
42.31 0.68
46.72 0.63
38.46 0.82
68.52 0.23
79.67 0.08
59.53 0.40
55.24 0.45
64.75 0.27
48.24 0.61
39.70 0.71
44.04 0.66
35.09 0.97
31.75 1.09
34.51 0.99
–
76.59 0.11
83.56 0.03
64.72 0.27
60.11 0.38
68.24 0.22
56.80 0.47
44.41 0.67
49.81 0.60
40.69 0.75
70.98 0.15
82.35 0.05
61.87 0.35
58.04 0.41
66.24 0.24
50.52 0.55
41.07 0.69
46.28 0.64
37.34 0.86
32.57 1.06
36.42 0.91
–
0.105 0.78
0.111 0.63
0.119 0.58
0.112 0.61
0.118 0.57
0.126 0.42
0.105 0.78
0.110 0.62
0.119 0.58
0.121 0.44
0.127 0.41
0.135 0.34
0.128 0.40
0.133 0.36
0.141 0.28
0.120 0.45
0.126 0.42
0.134 0.35
0.122 0.43
0.128 0.40
–
5b
5c
6a
6b
6c
7a
7b
7c
8a
8b
8c
9a
9b
9c
10a
10b
10c
11a
11b
11c
12a
12b
12c
13a
13b
13c
14a
14b
14c
15a
15b
15c
16a
16b
16c
Ascorbic acid
Blank
27.32 1.19
30.14 1.14
–
30.89 1.14
32.37 1.06
–
31.73 1.09
34.26 1.01
–
0.129 0.39
0.134 0.35
–
–
–
–
–
25.87 1.21
–
28.62 1.17
–
30.05 1.14
–
0.128 0.40
–
67.31 0.25
78.26 0.12
59.15 0.42
55.26 0.48
62.62 0.32
48.07 0.63
37.93 0.76
42.02 0.69
33.58 1.02
72.58 0.17
–
70.64 0.18
82.56 0.05
61.36 0.35
57.06 0.42
65.43 0.27
50.12 0.56
40.05 0.70
45.45 0.64
36.12 0.86
75.32 0.11
–
73.46 0.16
84.91 0.03
63.54 0.31
59.23 0.39
67.68 0.25
52.37 0.40
43.85 0.66
48.19 0.62
39.85 0.73
78.46 0.09
–
0.121 0.39
0.127 0.37
0.135 0.34
0.128 0.40
0.134 0.36
0.142 0.26
0.121 0.38
0.127 0.46
0.135 0.34
0.256 0.21
–
(–) Showed no scavenging activity. Values were the mean of three replicates SD
Furthermore, the compound 7a exhibited another broad singlet
at d12.85 ppm due to NH of benzimidazole ring. The signals of
highly acidic protons disappeared on deuteration.
of sodium hydride in a mixture of dimethyl sulphoxide and
ether produced N-(benzoxazol-2-yl)-40-aryl-10H-pyrrole-30-
carboxamide (8a–8c), N-(benzothiazol-2-yl)-40-aryl-10H-
pyrrole-30-carboxamide (9a–9c) and N-(1H-benzimidazol-2-
yl)-40-aryl-10H-pyrrole-30-carboxamide (10a–10c), respec-
tively. The 1H NMR spectra of 8a displayed two singlets at d
6.80, 7.07, 9a at 6.84, 7.13 and 10a at 6.78, 7.03 ppm due to
The olefin moiety present in compounds 5(a–c), 6(a–
c) and 7(a–c) was utilised to develop pyrrole and pyrazole
rings. Thus, the treatment of compounds 5(a–c), 6(a–c) and
7(a–c) with tosylmethyl isocyanide (TosMIC) in the presence
123

Med Chem Res
Table 2 The in vitro antioxidant activity of compounds 5(a–c)–
16(a–c) in NO method
Table 3 The in vitro antioxidant activity of compounds 5(a–c)–
16(a–c) in H2O2 method
Compounds
Concentration
Compounds
Concentration
50 lg/ml
75 lg/ml
100 lg/ml
50 lg/ml
75 lg/ml
100 lg/ml
5a
74.52 0.12
82.47 0.05
61.30 0.32
57.54 0.43
66.46 0.27
53.85 0.50
43.69 0.68
48.12 0.63
38.04 0.83
69.72 0.23
77.09 0.10
58.62 0.40
54.10 0.49
62.73 0.30
50.44 0.56
39.53 0.81
45.57 0.67
36.75 0.91
32.39 1.06
34.82 0.99
–
76.97 0.11
85.23 0.03
63.19 0.28
59.13 0.39
70.08 0.15
55.70 0.46
46.95 0.66
51.45 0.57
42.25 0.77
72.94 0.16
79.83 0.08
60.35 0.38
56.23 0.44
66.89 0.24
52.27 0.51
43.87 0.72
48.63 0.63
39.65 0.73
34.41 1.01
36.93 0.95
–
79.62 0.09
87.56 0.01
65.88 0.26
61.70 0.35
72.19 0.17
57.42 0.43
49.03 0.54
54.24 0.48
45.48 0.70
75.28 0.12
83.21 0.03
62.31 0.32
58.37 0.42
69.92 0.21
55.58 0.47
46.12 0.69
51.72 0.51
42.61 0.68
39.82 0.84
41.37 0.73
–
5a
74.15 0.12
80.43 0.07
60.79 0.36
57.12 0.45
65.43 0.29
52.75 0.54
42.14 0.76
47.26 0.68
37.28 0.84
68.48 0.24
76.70 0.11
57.41 0.43
53.80 0.50
61.76 0.34
49.13 0.65
38.50 0.82
44.93 0.71
34.65 0.99
31.32 1.09
33.14 1.02
–
76.68 0.11
84.87 0.03
62.95 0.32
59.01 0.38
67.02 0.25
54.10 0.49
44.95 0.71
49.57 0.64
41.53 0.71
71.93 0.17
78.76 0.09
59.93 0.37
55.92 0.47
63.06 0.31
50.97 0.56
42.64 0.77
47.46 0.69
39.37 0.73
34.19 1.01
37.63 0.86
–
78.85 0.10
86.31 0.02
65.02 0.30
61.36 0.35
69.76 0.23
55.25 0.48
46.15 0.69
50.61 0.55
43.36 0.67
73.82 0.13
80.14 0.07
61.98 0.34
58.07 0.42
67.53 0.23
52.09 0.51
44.81 0.72
48.85 0.68
40.49 0.74
37.03 0.88
39.24 0.73
–
5b
5b
5c
5c
6a
6a
6b
6b
6c
6c
7a
7a
7b
7b
7c
7c
8a
8a
8b
8b
8c
8c
9a
9a
9b
9b
9c
9c
10a
10b
10c
11a
11b
11c
12a
12b
12c
13a
13b
13c
14a
14b
14c
15a
15b
15c
16a
16b
16c
Ascorbic acid
Blank
10a
10b
10c
11a
11b
11c
12a
12b
12c
13a
13b
13c
14a
14b
14c
15a
15b
15c
16a
16b
16c
Ascorbic acid
Blank
31.43 1.09
33.67 1.02
–
33.50 1.03
35.18 0.98
–
37.28 0.91
40.53 0.80
–
30.21 1.14
32.56 1.06
–
33.46 1.03
35.02 0.98
–
36.77 0.91
38.67 0.82
–
–
–
–
–
–
–
30.61 1.14
–
32.79 1.08
–
35.94 0.99
–
29.83 1.17
–
32.28 1.08
–
34.95 0.99
–
72.64 0.17
80.34 0.06
60.42 0.33
56.89 0.45
64.17 0.28
51.56 0.52
42.20 0.79
47.33 0.65
37.98 0.85
76.69 0.11
–
74.75 0.19
83.61 0.04
61.65 0.31
57.95 0.42
67.58 0.26
54.92 0.49
45.76 0.70
49.26 0.61
40.92 0.79
78.34 0.09
–
77.06 0.10
86.78 0.02
64.67 0.28
60.21 0.39
70.43 0.19
56.14 0.45
48.05 0.67
53.08 0.49
44.74 0.75
80.45 0.05
–
71.52 0.17
79.51 0.08
59.63 0.41
55.85 0.47
63.90 0.31
50.44 0.60
41.89 0.78
46.31 0.69
35.41 0.97
75.64 011
–
73.79 0.12
83.45 0.04
61.64 0.34
57.61 0.41
66.14 0.27
51.27 0.52
43.14 0.75
48.22 0.68
40.24 0.75
77.62 0.10
–
75.60 0.11
85.63 0.03
63.87 0.31
59.58 0.37
68.47 0.22
53.58 0.50
45.28 0.70
49.78 0.57
42.11 0.68
79.86 0.08
–
(–) Showed no scavenging activity. Values were the mean of three
replicates SD
(–) Showed no scavenging activity. Values were the mean of three
replicates SD
0
0
C2 -H and C5 -H. Furthermore, two broad singlets were
observed in these compounds at d 8.25, 8.29, 8.22 due to
CONH and at 8.84, 8.92, 8.61 ppm due to NH of pyrrole ring.
Apart from these, compound 10a exhibited another broad
singlet at d 12.68 ppm due to NH of benzimidazole ring. The
signals of NH disappeared when D2O was added.
On the other hand, the reaction of compounds 5(a–c), 6(a–
c) and 7(a–c) with diazomethane in ether in the presence of
triethylamine at -20 to -15 °C for 40–48 h resulted in
N-(benzoxazol-2-yl)-40,50-dihydro-40-aryl-10H-pyrazole-30-
carboxamide (11a–11c), N-(benzothiazol-2-yl)-40,50-dihy-
dro-40-aryl-10H-pyrazole-30-carboxamide (12a–12c) and
123

Med Chem Res
Fig. 1 The in vitro antioxidant
activity of 5b, 8b and 14b in all
the three methods
90
80
70
60
50
40
30
20
10
0
Concentration of
50 µg/ml (%)
Concentration of
75 µg/ml (%)
Concentration of
100 µg/ml (%)
5b
8b
5b
8b
5b
8b
14b
14b
14b
Blank
Blank
Blank
NO Method
Ascorbic acid
Ascorbic acid
Ascorbic acid
H2O2 Method
DPPH Method
Tested Compounds
N-(1H-benzimidazol-2-yl)-40,50-dihydro-40-aryl-10H-pyra-
zole-30-carboxamide (13a–13c), regioselectively. The H
Bucar, 2000; Cuendet et al., 1997), nitric oxide (NO) (Green
et al., 1982; Marcocci et al., 1994) and hydrogen peroxide
(H2O2) (Ruch et al., 1989) methods. The observed data on the
antioxidant activity of the compounds and control drug are
presented in Tables 1, 2 and 3. The aim of this study is to
identify the potential heterocyclic compound as antioxidant
agent. The compounds 5b, 8b and 14b showed excellent radical
scavenging activity in all the three methods (Fig. 1) when
compared with the standard drug Ascorbic acid. The com-
pounds 5a, 6b, 8a, 9b, 14a and 15b exhibited good activity
whereas the compounds 6a, 6c, 8c, 9a, 14c and 15a displayed
moderate activity. However, the compounds 11c, 12c, 13a and
13c showed no activity, while the compounds 5c, 7a, 7b, 7c, 9c,
10a, 10b, 10c, 11a, 11b, 12a, 12b, 13b, 15c, 16a, 16b and 16c
exhibited least activity. It was also observed that compounds
having methyl substituent on the phenyl ring displayed signifi-
cant activity than unsubstituted and chloro-substituted com-
pounds. Amongst the tested compounds amido-linked styryl
(5a–5c), pyrrolyl (8a–8c) and pyrazolyl (14a–14c) compounds
exhibited greater activity than the pyrazolinyl (11a–11c)
derivatives. In fact, the unsaturated compounds (5a–5c) showed
comparatively higher activity than the pyrrolyl (8a–8c) and
pyrazolyl (14a–14c) derivatives. This may be due to effective
conjugation of styryl moiety attached to the amido group. It was
also noticed that benzoxazolyl amido-linked derivatives dis-
played greater activity than the benzothiazolyl and benzimi-
dazolyl amido-linked ones. Besides, the perusal of Tables 1, 2
and 3 indicated that radical scavenging activity increases with
increase in concentration in all the three methods.
1
NMR spectra of 11a, 12a and 13a exhibited an AMX
splitting pattern due to the methine and methylene protons of
pyrazoline ring. The three double doublets observed at d
3.62, 4.00, 4.42 in 11a, at 3.63, 4.04, 4.64 in 12a and at 3.59,
3.97, 4.38 ppm in 13a were assigned to HX, HM and HA,
respectively. The coupling constant values JAM = 12.6 Hz,
JAX = 6.6 Hz, JMX = 10.5 Hz in 11a, JAM = 12.8 Hz,
JAX = 6.8 Hz, JMX = 10.8 Hz in 12a and JAM = 12.4 Hz,
JAX = 6.3 Hz, JMX = 10.2 Hz in 13a indicated that HA,
H
M are cis, HA, HX are trans while HM, HX are geminal. In
addition, two broad singlets were appeared at d 8.40, 9.94 in
11a, at 8.42, 9.98 in 12a and at 8.37, 9.83 ppm in 13a due to
CONH and NH of pyrazoline, respectively. Besides, the
compound 13a showed another broad singlet at d 12.80 ppm
due to NH of benzimidazole. The signals due to NH disap-
peared when D2O was added.
The oxidation of compounds 11(a–c), 12(a–c) and 13(a–
c) with chloranil in xylene produced N-(benzoxazol-2-yl)-
40-aryl-10H-pyrazole-30-carboxamide (14a–14c), N-(ben-
zothiazol-2-yl)-40-aryl-10H-pyrazole-30-carboxamide (15a–
15c) and N-(1H-benzimidazol-2-yl)-40-aryl-10H-pyrazole-30-
carboxamide (16a–16c). The absence of an AMX splitting
pattern in compounds 14(a–c), 15(a–c) and 16(a–c) indicated
that aromatisation took place. The structures of all the new
compounds were further characterised by IR, 13C NMR and
elemental analyses.
Biological evaluation
Conclusion
Antioxidant activity
The amido-linked benzoxazolyl/benzothiazolyl/benzimi-
dazolyl-pyrroles and benzoxazolyl/benzothiazolyl/benzi-
midazolyl-pyrazoles were prepared from the synthetic
The compounds 5(a–c)–16(a–c) were evaluated for antioxidant
property by 2,2,-diphenyl-1-picrylhydrazyl (DPPH) (Burits and
123

Med Chem Res
intermediates (E)-N-(benzoxazol-2-yl)cinnamamide/(E)-N-
(benzothiazol-2-yl)cinnamamide/(E)-N-(1H-benzimidazol-
2-yl)cinnamamides adopting simple and versatile synthetic
methodologies. All the new compounds were tested for
antioxidant activity. The compounds 5b, 8b and 14b dis-
played greater antioxidant activity when compared with the
standard drug ascorbic acid. It was also observed that
benzoxazolyl amido-linked derivatives displayed greater
activity than the benzothiazolyl and benzimidazolyl amido-
linked derivatives.
(CDCl3, 100 MHz): d = 168.0 (CO), 163.1 (C-2), 150.2
(C, C-8), 143.2 (C-HA), 142.5 (C, C-9), 133.4 (C, C-100),
128.8 (CH, C-300), 128.1 (CH, C-400), 127.3 (CH, C-200),
124.5 (CH, C-5), 123.5 (CH, C-6), 120.4 (CH, C-4), 117.8
(C-HB), 117.3 (CH, C-7); MS (m/z): 264.28 [M?ꢀ]. Anal.
Calcd. for C16H12N2O2: C, 72.72; H, 4.57; N, 10.60.
Found: C, 72.64; H, 4.62; N, 10.71.
(E)-N-(Benzoxazol-2-yl)-3-(400-methylphenyl)acrylamide
(5b)
Mp 195–197 °C; yield 68 %; IR (KBr) mmax 3302, 1651,
1
1615, 1595 cm-1; H NMR (CDCl3, 400 MHz): d = 8.29
Experimental
(bs, 1H, NH), 7.79 (d, 1H, HA, J = 15.9 Hz), 7.11–7.31
(m, 8H, Ar–H), 6.70 (d, 1H, HB, J = 15.9 Hz), 2.34 (s, 3H,
Ar-CH3); 13C NMR (CDCl3, 100 MHz): d = 167.1 (CO),
162.7 (C-2), 149.8 (C, C-8), 142.8 (C-HA), 142.4 (C, C-9),
137.4 (C, C-400), 133.5 (C, C-100), 128.3 (CH, C-300), 126.8
(CH, C-200), 125.2 (CH, C-5), 123.4 (CH, C-6), 119.4 (CH,
C-4), 117.5 (C-HB), 117.1 (CH, C-7), 24.6 (Ar-CH3); MS
(m/z): 278.31 [M?ꢀ]. Anal. Calcd. for C17H14N2O2: C,
73.37; H, 5.07; N, 10.06. Found: C, 73.21; H, 5.13; N,
10.15.
Melting points were determined in open capillaries on a
Mel-Temp apparatus and are uncorrected. The purity of the
compounds was checked by TLC (silica gel H, BDH,
hexane/ethyl acetate, 3:1). The IR spectra were recorded on
a Thermo Nicolet IR 200 FT-IR spectrometer as KBr
1
pellets and the wavenumbers were given in cm-1. The H
NMR spectra were recorded in CDCl3/DMSO-d6 on a Jeol
JNM k-400 MHz. The 13C NMR spectra were recorded in
CDCl3/DMSO-d6 on a Jeol JNM spectrometer operating at
k-100 MHz. The mass spectra were recorded on Jeol JMS-
D 300 and Finnigan Mat 1210 B at 70 eV with an emission
current of 100 lA. All chemical shifts are reported in ppm
using TMS as an internal standard. The microanalyses were
performed on a Perkin-Elmer 240C elemental analyzer.
The compounds benzoxazol-2-amine (1)/benzothiazol-2-
amine (2)/1H-benzimidazol-2-amine (3) and cinnamoyl
chloride (4) were prepared as per the literature precedent
(Saritha et al., 2011; Robbert et al., 2010; Vogel, 1989).
(E)-N-(Benzoxazol-2-yl)-3-(400-chlorophenyl)acrylamide
(5c)
Mp 212–214 °C; yield 72 %; IR (KBr) mmax 3311, 1658,
1
1620, 1600 cm-1; H NMR (CDCl3, 400 MHz): d = 8.34
(bs, 1H, NH), 7.87 (d, 1H, HA, J = 16.1 Hz), 7.15–7.39
(m, 8H, Ar–H), 6.75 (d, 1H, HB, J = 16.1 Hz); 13C NMR
(100 MHz, CDCl3): d = 167.9 (CO), 163.5 (C-2), 151.3
(C, C-8), 143.5 (C-HA), 140.3 (C, C-9), 134.8 (C, C-400),
134.2 (C, C-100), 128.6 (CH, C-300), 127.4 (CH, C-200), 124.7
(CH, C-5), 123.8 (CH, C-6), 120.3 (CH, C-4), 118.2 (C-
HB), 117.8 (CH, C-7); MS (m/z): 298.73 [M?ꢀ]. Anal.
Calcd. for C16H11ClN2O2: C, 64.33; H, 3.71; N, 9.38.
Found: C, 64.47; H, 3.77; N, 9.46.
General procedure for the synthesis of (E)-N-
(benzoxazol-2-yl)cinnamamide (5a–5c), (E)-N-
(benzothiazol-2-yl)cinnamamide (6a–6c) and (E)-N-
(1H-benzimidazol-2-yl)cinnamamide (7a–7c)
A mixture of compound 1/2/3 (1 mmol), cinnamoyl chloride
(4) (1.1 mmol) and toluene (10 ml) were heated to reflux for
15–18 h. After completion of the reaction, the contents were
cooled to room temperature. The separated solid was purified
by column chromatography (silica gel, ethyl acetate/hexane,
1.5:3).
(E)-N-(Benzothiazol-2-yl)cinnamamide (6a)
Mp 148–150 °C; yield 78 %; IR (KBr) mmax 3318, 1659,
1
1623, 1601 cm-1; H NMR (CDCl3, 400 MHz): d = 8.38
(bs, 1H, NH), 7.86 (d, 1H, HA, J = 16.2 Hz), 7.18–8.20
(m, 9H, Ar–H), 6.78 (d, 1H, HB, J = 16.2 Hz); 13C NMR
(CDCl3, 100 MHz): d = 169.2 (CO), 166.8 (C-2), 147.3
(C, C-9), 144.8 (C-HA), 136.5 (C, C-100), 129.4 (CH, C-300),
128.7 (CH, C-400), 127.2 (CH, C-200), 126.3 (CH, C-6),
126.0 (CH, C-5), 125.3 (C, C-8), 121.9 (CH, C-7), 121.3
(CH, C-4), 118.4 (C-HB); MS (m/z): 280.35 [M?ꢀ]. Anal.
(E)-N-(Benzoxazol-2-yl)cinnamamide (5a)
Mp 202–204 °C; yield 65 %; IR (KBr) mmax 3309, 1654,
1
1618, 1597 cm-1; H NMR (CDCl3, 400 MHz): d = 8.32
(bs, 1H, NH), 7.85 (d, 1H, HA, J = 16.0 Hz), 7.13–7.35
(m, 9H, Ar–H), 6.72 (d, 1H, HB, J = 16.0 Hz); 13C NMR
123

Med Chem Res
Calcd. for C16H12N2OS: C, 68.55; H, 4.31; N, 9.99. Found:
C, 68.67; H, 4.25; N, 10.08.
1H, HA, J = 15.7 Hz), 7.06–7.62 (m, 8H, Ar–H), 6.65 (d,
1H, HB, J = 15.7 Hz), 2.32 (s, 3H, Ar-CH3); 13C NMR
(CDCl3, 100 MHz): d = 166.6 (CO), 150.3 (C-2), 141.6
(C-HA), 138.1 (C, C-8, C-9), 137.4 (C, C-400), 128.8 (C,
C-100), 128.1 (CH, C-300), 126.3 (CH, C-200), 123.1 (CH,
C-5, C-6), 119.0 (CH, C-4, C-7), 117.2 (C-HB), 24.1 (Ar-
CH3); MS (m/z): 277.33 [M?ꢀ]. Anal. Calcd. for
C17H15N3O: C, 73.63; H, 5.45; N, 15.15. Found: C, 73.50;
H, 5.52; N, 15.02.
(E)-N-(Benzothiazol-2-yl)-3-(400-methylphenyl)acrylamide
(6b)
Mp 137–139 °C; yield 75 %; IR (KBr) mmax 3315, 1657,
1
1619, 1585 cm-1; H NMR (CDCl3, 400 MHz): d = 8.26
(bs, 1H, NH), 7.81 (d, 1H, HA, J = 16.0 Hz), 7.16–8.15
(m, 8H, Ar–H), 6.74 (d, 1H, HB, J = 16.0 Hz), 2.36 (s, 3H,
Ar-CH3); 13C NMR (CDCl3, 100 MHz): d = 168.8 (CO),
167.6 (C-2), 146.3 (C, C-9), 144.5 (C-HA), 136.4 (C, C-400),
132.4 (C, C-100), 128.3 (CH, C-300), 126.2 (CH, C-200), 125.8
(CH, C-6), 125.4 (CH, C-5), 124.5 (C, C-8), 121.1 (CH,
C-7), 120.4 (CH, C-4), 117.9 (C-HB), 24.8 (Ar-CH3); MS
(m/z): 294.38 [M?ꢀ]. Anal. Calcd. for C17H14N2OS: C,
69.36; H, 4.79; N, 9.52. Found: C, 69.22; H, 4.67; N, 9.47.
(E)-N-(1H-Benzimidazol-2-yl)-3-(400-
chlorophenyl)acrylamide (7c)
Mp 272–275 °C; yield 88 %; IR (KBr) mmax 3305, 1655,
1617, 1598 cm-1; 1H NMR (CDCl3, 400 MHz): d = 12.90
(bs, 1H, imidazole-NH), 8.20 (bs, 1H, CO–NH), 7.79 (d,
1H, HA, J = 15.9 Hz), 7.12–7.69 (m, 8H, Ar–H), 6.70 (d,
1H, HB, J = 15.9 Hz); 13C NMR (CDCl3, 100 MHz):
d = 167.2 (CO), 150.7 (C-2), 142.0 (C-HA), 139.1 (C, C-8,
C-9), 134.5 (C, C-400), 129.1 (C, C-100), 128.7 (CH, C-300),
126.6 (CH, C-200), 123.9 (CH, C-5, C-6), 119.4 (CH, C-4,
C-7), 117.7 (C-HB); MS (m/z): 297.74 [M?ꢀ]. Anal. Calcd.
for C16H12ClN3O: C, 64.55; H, 4.06; N, 14.11. Found: C,
64.44; H, 4.00; N, 14.21.
(E)-N-(Benzothiazol-2-yl)-3-(400-chlorophenyl)acrylamide
(6c)
Mp 161–163 °C; yield 71 %; IR (KBr) mmax 3331, 1660,
1
1625, 1605 cm-1; H NMR (CDCl3, 400 MHz): d = 8.40
(bs, 1H, NH), 7.89 (d, 1H, HA, J = 16.3 Hz), 7.20–8.23
(m, 8H, Ar–H), 6.85 (d, 1H, HB, J = 16.3 Hz); 13C NMR
(CDCl3, 100 MHz): d = 169.4 (CO), 168.6 (C-2), 148.4
(C, C-9), 145.2 (C-HA), 133.8 (C, C-400), 133.0 (C, C-100),
128.4 (CH, C-300), 127.3 (CH, C-200), 125.9 (CH, C-6),
125.5 (CH, C-5), 124.6 (C, C-8), 122.1 (CH, C-7), 121.8
(CH, C-4), 118.7 (C-HB); MS (m/z): 314.80 [M?ꢀ]. Anal.
Calcd. for C16H11ClN2OS: C, 61.05; H, 3.52; N, 8.90.
Found: C, 60.94; H, 3.59; N, 8.99.
General procedure for the synthesis of N-(benzoxazol-
2-yl)-40-aryl-10H-pyrrole-30-carboxamide (8a–8c), N-
(benzothiazol-2-yl)-40-aryl-10H-pyrrole-30-carboxamide
(9a–9c) and N-(1H-benzimidazol-2-yl)-40-aryl-10H-
pyrrole-30-carboxamide (10a–10c)
An equimolar (1 mmol) mixture of compound 5(a–c)/6(a–
c)/7(a–c) and TosMIC in dimethyl sulphoxide (8 ml) and
dry ether (16 ml) was added dropwise via a syringe to a
stirred suspension of sodium hydride (50 mg) in dry ether
(20 ml). The stirring was continued for 18–21 h at room
temperature. After completion of the reaction, the contents
were diluted with water and extracted with ether. The
ethereal layer was dried (an. Na2SO4) and removed in
vacuo. The resultant sample was purified by column
chromatography (silica gel, ethyl acetate/hexane, 1:3).
(E)-N-(1H-Benzimidazol-2-yl)cinnamamide (7a)
Mp 255–257 °C; yield 86 %; IR (KBr) mmax 3302, 1653,
1616, 1590 cm-1
;
1H NMR (CDCl3, 400 MHz,):
d = 12.85 (bs, 1H, imidazole-NH), 8.18 (bs, 1H, CO–NH),
7.74 (d, 1H, HA, J = 15.8 Hz), 7.10–7.64 (m, 9H, Ar–H),
6.68 (d, 1H, HB, J = 15.8 Hz); 13C NMR (CDCl3,
100 MHz): d = 167.4 (CO), 150.4 (C-2), 141.9 (C-HA),
138.4 (C, C-8, C-9), 134.3 (C, C-100), 128.9 (CH, C-300),
128.3 (CH, C-400), 126.4 (CH, C-200), 123.5 (CH, C-5, C-6),
119.2 (CH, C-4, C-7), 117.4 (C-HB); MS (m/z): 263.30
[M?ꢀ]. Anal. Calcd. for C16H13N3O: C, 73.01; H, 4.98; N,
15.96. Found: C, 73.15; H, 5.05; N, 15.84.
N-(Benzoxazol-2-yl)-40-phenyl-10H-pyrrole-30-
carboxamide (8a)
Mp 215–217 °C; yield 69 %; IR (KBr) mmax 3245, 1674,
1
1620, 1580 cm-1; H NMR (CDCl3, 400 MHz): d = 8.84
(E)-N-(1H-Benzimidazol-2-yl)-3-(400-
(bs, 1H, NH), 8.25 (bs, 1H, CO–NH), 7.25–7.76 (m, 9H,
methylphenyl)acrylamide (7b)
Ar–H), 7.07 (s, 1H, C5 -H), 6.80 (s, 1H, C2 -H); 13C NMR
(CDCl3, 100 MHz): d = 166.2 (CO), 162.5 (C-2), 149.1
(C, C-8), 140.5 (C, C-9), 137.4 (C, C-100), 132.0 (CH,
C-300), 131.6 (CH, C-400), 130.4 (CH, C-200), 129.1 (CH,
0
0
Mp 238–240 °C; yield 80 %; IR (KBr) mmax 3297, 1650,
1613, 1587 cm-1; 1H NMR (CDCl3, 400 MHz): d = 12.82
(bs, 1H, imidazole-NH), 8.14 (bs, 1H, CO–NH), 7.70 (d,
123

Med Chem Res
N-(Benzothiazol-2-yl)-40-(400-methylphenyl)-10H-pyrrole-
30-carboxamide (9b)
C-5), 128.3 (C-40), 127.2 (CH, C-6), 126.4 (CH, C-4),
121.9 (C-20), 117.4 (CH, C-7), 116.7 (C-50), 109.1 (C-30);
MS (m/z): 303.32 [M?ꢀ]. Anal. Calcd. for C18H13N3O2: C,
71.28; H, 4.32; N, 13.85. Found: C, 71.63; H, 4.56; N,
13.62.
Mp 155–157 °C; yield 60 %; IR (KBr) mmax 3247, 1676,
1
1616, 1590 cm-1; H NMR (CDCl3, 400 MHz): d = 8.90
(bs, 1H, NH), 8.22 (bs, 1H, CO–NH), 7.21–8.06 (m, 8H,
0
0
Ar–H), 7.09 (s, 1H, C5 -H), 6.82 (s, 1H, C2 -H), 2.39 (s, 3H,
Ar-CH3); 13C NMR (100 MHz, CDCl3): d = 169.3 (CO),
166.8 (C-2), 148.4 (C, C-9), 138.2 (C, C-400), 133.2 (C,
C-100), 129.4 (CH, C-300), 128.2 (C-40), 127.3 (CH, C-200),
125.7 (CH, C-6), 125.4 (CH, C-5), 123.9 (C, C-8), 122.8
(CH, C-7), 122.2 (C-20), 121.8 (CH, C-4), 116.8 (C-50),
110.5 (C-30), 24.4 (Ar-CH3); MS (m/z): 333.42 [M?ꢀ].
Anal. Calcd. for C19H15N3OS: C, 68.45; H, 4.53; N, 12.60.
Found: C, 68.60; H, 4.76; N, 12.79.
N-(Benzoxazol-2-yl)-40-(400-methylphenyl)-10H-pyrrole-30-
carboxamide (8b)
Mp 204–206 °C; yield 65 %; IR (KBr) mmax 3242, 1665,
1
1610, 1572 cm-1; H NMR (CDCl3, 400 MHz): d = 8.78
(bs, 1H, NH), 8.20 (bs, 1H, CO–NH), 7.18–7.71 (m, 8H, Ar–
0
0
H), 7.03 (s, 1H, C5 -H), 6.78 (s, 1H, C2 -H), 2.37 (s, 3H, Ar-
CH3); 13C NMR (100 MHz, CDCl3): d = 166.0 (CO), 161.7
(C-2), 149.0 (C, C-8), 140.8 (C, C-9), 137.2 (C, C-400), 132.7
(C, C-100), 131.8 (CH, C-300), 130.1 (CH, C-200), 129.5 (CH,
C-5), 127.6 (C-40), 127.1 (CH, C-6), 126.2 (CH, C-4), 121.3
(C-20), 117.3 (CH, C-7), 116.5 (C-50), 108.7 (C-30), 23.9 (Ar-
CH3); MS (m/z): 317.35 [M?ꢀ]. Anal. Calcd. for C19H15N3O2:
C, 71.91; H, 4.76; N, 13.24. Found: C, 72.34; H, 4.91; N,
13.69.
N-(Benzothiazol-2-yl)-40-(400-chlorophenyl)-10H-pyrrole-30-
carboxamide (9c)
Mp 186–188 °C; yield 64 %; IR (KBr) mmax 3256, 1685,
1630, 1600 cm-1; H NMR (CDCl3, 400 MHz): d = 8.95
1
(bs, 1H, NH), 8.32 (bs, 1H, CO–NH), 7.29–8.15 (m, 8H, Ar–
H), 7.14 (s, 1H, C5 -H), 6.88 (s, 1H, C2 -H); 13C NMR
(CDCl3, 100 MHz): d = 170.2 (CO), 167.4 (C-2), 149.4 (C,
C-9), 134.8 (C, C-100), 134.3 (C, C-400), 129.3 (C-40), 128.8
(CH, C-300), 127.9 (CH, C-200), 125.9 (CH, C-6), 125.5 (CH,
C-5), 124.4 (C, C-8), 122.6 (C-20), 121.7 (CH, C-7), 120.9
(CH, C-4), 117.4 (C-50), 111.3 (C-30); MS (m/z): 353.83
[M?ꢀ]. Anal. Calcd. for C18H12ClN3OS: C, 61.10; H, 3.42; N,
11.88. Found: C, 61.01; H, 3.59; N, 12.18.
0
0
N-(Benzoxazol-2-yl)-40-(400-chlorophenyl)-10H-pyrrole-30-
carboxamide (8c)
Mp 220–222 °C; yield 71 %; IR (KBr) mmax 3258, 1678,
1
1622, 1597 cm-1; H NMR (CDCl3, 400 MHz): d = 8.86
(bs, 1H, NH), 8.27 (bs, 1H, CO–NH), 7.29–7.78 (m, 8H, Ar–
H), 7.12 (s, 1H, C5 -H), 6.82 (s, 1H, C2 -H); 13C NMR (CDCl3,
100 MHz): d = 166.9 (CO), 162.8 (C-2), 149.3 (C, C-8),
140.9 (C, C-9), 137.9 (C, C-100), 132.5 (C, C-400), 131.7 (CH,
C-300), 130.5 (CH, C-200), 129.6 (CH, C-5), 128.5 (C-40), 127.8
(CH, C-6), 126.7 (CH, C-4), 122.1 (C-20), 117.7 (CH, C-7),
117.0 (C-50), 109.5 (C-30); MS (m/z): 337.76 [M?ꢀ]. Anal.
Calcd. for C18H12ClN3O2: C, 64.01; H, 3.58; N, 12.44. Found:
C, 63.89; H, 3.79; N, 12.82.
0
0
N-(1H-Benzimidazol-2-yl)-40-phenyl-10H-pyrrole-30-
carboxamide (10a)
Mp 284–286 °C; yield 71 %; IR (KBr) mmax 3241, 1666,
1618, 1576 cm-1; 1H NMR (CDCl3, 400 MHz): d = 12.68
(bs, 1H, imidazole-NH), 8.61 (bs, 1H, NH), 8.22 (bs, 1H,
0
CO–NH), 7.22–7.70 (m, 9H, Ar–H), 7.03 (s, 1H, C5 -H),
N-(Benzothiazol-2-yl)-40-phenyl-10H-pyrrole-30-
0
6.78 (s, 1H, C2 -H); 13C NMR (CDCl3, 100 MHz):
carboxamide (9a)
d = 164.5 (CO), 152.2 (C-2), 138.5 (C, C-8, C-9), 135.8
(C, C-100), 129.5 (CH, C-300), 128.7 (CH, C-400), 127.8 (C-
40), 127.4 (CH, C-200), 122.8 (CH, C-5, C-6), 121.5 (C-20),
118.9 (CH, C-4, C-7), 115.2 (C-50), 108.8 (C-30); MS (m/z):
302.34 [M?ꢀ]. Anal. Calcd. for C18H14N4O: C, 71.51; H,
4.67; N, 18.53. Found: C, 71.87; H, 4.60; N, 18.32.
Mp 168–170 °C; yield 62 %; IR (KBr) mmax 3250, 1681,
1624, 1595 cm-1; H NMR (CDCl3, 400 MHz): d = 8.92
1
(bs, 1H, NH), 8.29 (bs, 1H, CO–NH), 7.26–8.11 (m, 9H,
Ar–H), 7.13 (s, 1H, C5 -H), 6.84 (s, 1H, C2 -H); 13C NMR
(CDCl3, 100 MHz): d = 169.5 (CO), 167.1 (C-2), 148.6
(C, C-9), 136.2 (C, C-100), 129.8 (CH, C-300), 129.0 (C-40),
128.5 (CH, C-400), 127.4 (CH, C-200), 125.8 (CH, C-6),
125.2 (CH, C-5), 124.3 (C, C-8), 122.3 (C-20), 121.4 (CH,
C-7), 120.8 (CH, C-4), 117.1 (C-50), 111.1 (C-30); MS (m/z):
319.39 [M?ꢀ]. Anal. Calcd. for C18H13N3OS: C, 67.69; H,
4.10; N, 13.16. Found: C, 67.98; H, 3.91; N, 13.46.
0
0
N-(1H-Benzimidazol-2-yl)-40-(400-methylphenyl)-10H-
pyrrole-30-carboxamide (10b)
Mp 270–272 °C; yield 64 %; IR (KBr) mmax 3239, 1659,
1615, 1573 cm-1; 1H NMR (CDCl3, 400 MHz): d = 12.64
(bs, 1H, imidazole-NH), 8.58 (bs, 1H, NH), 8.16 (bs, 1H,
123

Med Chem Res
0
CO–NH), 7.19–7.67 (m, 8H, Ar–H), 7.01 (s, 1H, C5 -H),
124.4 (CH, C-5), 123.8 (CH, C-6), 119.3 (CH, C-4), 117.4
(CH, C-7), 57.9 (C-50), 48.3 (C-40); MS (m/z): 306.33
[M?ꢀ]. Anal. Calcd. for C17H14N4O2: C, 66.66; H, 4.61; N,
18.29. Found: C, 67.01; H, 4.60; N, 18.69.
6.73 (s, 1H, C2 -H), 2.35 (s, 3H, Ar-CH3); 13C NMR
0
(CDCl3, 100 MHz): d = 163.9 (CO), 151.5 (C-2), 139.1
(C, C-8, C-9), 138.2 (C, C-400), 133.4 (C, C-100), 129.7 (CH,
C-300), 127.8 (CH, C-200), 127.1 (C-40), 122.7 (CH, C-5,
C-6), 121.2 (C-20), 118.2 (CH, C-4, C-7), 115.1 (C-50),
108.6 (C-30), 23.7 (Ar-CH3); MS (m/z): 316.37 [M?ꢀ].
Anal. Calcd. for C19H16N4O: C, 72.13; H, 5.10; N, 17.71.
Found: C, 72.23; H, 5.19; N, 18.01.
N-(Benzoxazol-2-yl)-40,50-dihydro-40-(400-methylphenyl)-
10H-pyrazole-30-carboxamide (11b)
Mp 218–220 °C; yield 66 %; IR (KBr) mmax 3265, 1654,
1
1565 cm-1; H NMR (CDCl3, 400 MHz): d = 9.91 (bs,
N-(1H-Benzimidazol-2-yl)-40-(400-chlorophenyl)-10H-
pyrrole-30-carboxamide (10c)
1H, NH), 8.38 (bs, 1H, CO–NH), 7.08–7.39 (m, 8H, Ar–
H), 4.41 (dd, 1H, HA, JAM = 12.4 Hz, JAX = 6.4 Hz),
3.97 (dd, 1H, HM, JAM = 12.4 Hz, JMX = 10.3 Hz), 3.61
(dd, 1H, HX, JAX = 6.4 Hz, JMX = 10.3 Hz), 2.33 (s, 3H,
Ar-CH3); 13C NMR (CDCl3, 100 MHz): d = 165.5 (CO),
163.1 (C-2), 150.1 (C, C-8), 149.1 (C-30), 140.8 (C, C-9),
137.3 (C, C-100), 135.2 (C, C-400), 128.7 (CH, C-300), 127.3
(CH, C-200), 124.7 (CH, C-5), 123.6 (CH, C-6), 119.0 (CH,
C-4), 117.2 (CH, C-7), 57.6 (C-50), 47.7 (C-40), 24.3 (Ar-
CH3); MS (m/z): 320.36 [M?ꢀ]. Anal. Calcd. for
C18H16N4O2: C, 67.49; H, 5.03; N, 17.49. Found: C, 67.71;
H, 5.20; N, 17.84.
Mp 292–294 °C; yield 68 %; IR (KBr) mmax 3250, 1672,
1625, 1587 cm-1; 1H NMR (CDCl3, 400 MHz): d = 12.71
(bs, 1H, imidazole-NH), 8.63 (bs, 1H, NH), 8.25 (bs, 1H,
0
CO–NH), 7.26–7.73 (m, 8H, Ar–H), 7.06 (s, 1H, C5 -H),
6.79 (s, 1H, C2 -H); 13C NMR (100 MHz, CDCl3):
0
d = 164.9 (CO), 152.8 (C-2), 138.6 (C, C-8, C-9), 134.6
(C, C-100), 134.2 (C, C-400), 129.4 (CH, C-300), 128.9 (CH,
C-200), 127.9 (C-40), 123.1 (CH, C-5, C-6), 121.9 (C-20),
119.7 (CH, C-4, C-7), 115.5 (C-50), 109.1 (C-30); MS (m/z):
336.78 [M?ꢀ]. Anal. Calcd. for C18H13ClN4O: C, 64.19; H,
3.89; N, 16.64. Found: C, 64.36; H, 4.01; N, 16.39.
N-(Benzoxazol-2-yl)-40,50-dihydro-40-(400-chlorophenyl)-
10H-pyrazole-30-carboxamide (11c)
General procedure for the synthesis of N-(benzoxazol-
2-yl)-40,50-dihydro-40-aryl-10H-pyrazole-30-
carboxamide (11a–11c), N-(benzothiazol-2-yl)-40,50-
dihydro-40-aryl-10H-pyrazole-30-carboxamide (12a–
12c) and N-(1H-benzimidazol-2-yl)-40,50-dihydro-40-
aryl-10H-pyrazole-30-carboxamide (13a–13c)
Mp 233–235 °C; yield 74 %; IR (KBr) mmax 3300, 1663,
1
1580 cm-1; H NMR (CDCl3, 400 MHz): d = 9.96 (bs,
1H, NH), 8.45 (bs, 1H, CO–NH), 7.15–7.47 (m, 8H, Ar–
H), 4.45 (dd, 1H, HA, JAM = 12.7 Hz, JAX = 6.7 Hz),
4.02 (dd, 1H, HM, JAM = 12.7 Hz, JMX = 10.6 Hz), 3.67
(dd, 1H, HX, JAX = 6.7 Hz, JMX = 10.6 Hz); 13C NMR
(CDCl3, 100 MHz): d = 165.9 (CO), 163.6 (C-2), 149.7
(C-30), 149.7 (C, C-8), 141.2 (C, C-9), 138.7 (C, C-100),
131.2 (C, C-400), 129.0 (CH, C-200), 128.3 (CH, C-300), 124.8
(CH, C-5), 123.7 (CH, C-6), 119.5 (CH, C-4), 117.7 (CH,
C-7), 58.2 (C-50), 48.9 (C-40); MS (m/z): 340.77 [M?ꢀ].
Anal. Calcd. for C17H13ClN4O2: C, 59.92; H, 3.84; N,
16.44. Found: C, 60.22; H, 3.99; N, 16.75.
An ice-cold ethereal solution of diazomethane (40 ml,
0.4 M) and triethylamine (0.1 ml) were added to a
well-cooled solution of compound 5(a–c)/6(a–c)/7(a–
c) (5 mmol) in dichloromethane (20 ml). The reaction
mixture was kept at -20 to -15 °C for 42–48 h. The
solvent was removed on a rotary evaporator. The resultant
residue was purified by column chromatography (silica gel,
ethyl acetate/hexane, 1:4).
N-(Benzothiazol-2-yl)-40,50-dihydro-40-phenyl-10H-
pyrazole-30-carboxamide (12a)
N-(Benzoxazol-2-yl)-40,50-dihydro-40-phenyl-10H-pyrazole-
30-carboxamide (11a)
Mp 180–182 °C; yield 65 %; IR (KBr) mmax 3295, 1665,
Mp 225–227 °C; yield 69 %; IR (KBr) mmax 3278, 1660,
1
1583 cm-1; H NMR (CDCl3, 400 MHz): d = 9.98 (bs,
1
1570 cm-1; H NMR (CDCl3, 400 MHz): d = 9.94 (bs,
1H, NH), 8.42 (bs, 1H, CO–NH), 7.20–7.58 (m, 9H, Ar–
H), 4.64 (dd, 1H, HA, JAM = 12.8 Hz, JAX = 6.8 Hz),
4.04 (dd, 1H, HM, JAM = 12.8 Hz, JMX = 10.8 Hz), 3.63
(dd, 1H, HX, JAX = 6.8 Hz, JMX = 10.8 Hz); 13C NMR
(CDCl3, 100 MHz): d = 168.8 (CO), 166.7 (C-2), 150.1
(C-30), 148.1 (C, C-9), 138.8 (C, C-100), 137.4 (CH, C-300),
136.9 (CH, C-200), 135.0 (CH, C-400), 129.8 (CH, C-6),
1H, NH), 8.40 (bs, 1H, CO–NH), 7.10–7.42 (m, 9H, Ar–
H), 4.42 (dd, 1H, HA, JAM = 12.6 Hz, JAX = 6.6 Hz),
4.00 (dd, 1H, HM, JAM = 12.6 Hz, JMX = 10.5 Hz), 3.62
(dd, 1H, HX, JAX = 6.6 Hz, JMX = 10.5 Hz); 13C NMR
(CDCl3, 100 MHz): d = 165.8 (CO), 163.5 (C-2), 149.6
(C, C-8), 149.5 (C-30), 140.1 (C, C-9), 139.4 (C, C-100),
128.4 (CH, C-300), 127.0 (CH, C-200), 126.5 (CH, C-400),
123

Med Chem Res
129.2 (CH, C-5), 128.2 (C, C-8), 124.6 (CH, C-7), 120.7
(CH, C-4), 58.6 (C-50), 48.5 (C-40); MS (m/z): 322.40
[M?ꢀ]. Anal. Calcd. for C17H14N4OS: C, 63.33; H, 4.38; N,
17.38. Found: C, 63.58; H, 4.49; N, 17.82.
118.7 (CH, C-4, C-7), 57.7 (C-50), 47.8 (C-40); MS (m/z):
305.34 [M?ꢀ]. Anal. Calcd. for C17H15N5O: C, 66.87; H,
4.95; N, 22.94. Found: C, 67.29; H, 5.07; N, 23.43.
N-(1H-Benzimidazol-2-yl)-40,50-dihydro-40-(400-
N-(Benzothiazol-2-yl)-40,50-dihydro-40-(400-methylphenyl)-
10H-pyrazole-30-carboxamide (12b)
methylphenyl)-10H-pyrazole-30-carboxamide (13b)
Mp 249–251 °C; yield 62 %; IR (KBr) mmax 3250, 1650,
1
Mp 168–170 °C; yield 63 %; IR (KBr) mmax 3286, 1661,
1563 cm-1; H NMR (CDCl3, 400 MHz): d = 12.78 (bs,
1
1575 cm-1; H NMR (CDCl3, 400 MHz): d = 9.95 (bs,
1H, imidazole-NH), 9.80 (bs, 1H, NH), 8.32 (bs, 1H, CO–
NH), 7.27–7.64 (m, 8H, Ar–H), 4.35 (dd, 1H, HA,
JAM = 12.3 Hz, JAX = 6.2 Hz), 3.94 (dd, 1H, HM,
JAM = 12.3 Hz, JMX = 10.1 Hz), 3.53 (dd, 1H, HX,
1H, NH), 8.40 (bs, 1H, CO–NH), 7.19–7.54 (m, 8H, Ar–
H), 4.62 (dd, 1H, HA, JAM = 12.5 Hz, JAX = 6.4 Hz),
4.01 (dd, 1H, HM, JAM = 12.5 Hz, JMX = 10.5 Hz), 3.60
(dd, 1H, HX, JAX = 6.4 Hz, JMX = 10.5 Hz), 2.37 (s, 3H,
Ar-CH3); 13C NMR (CDCl3, 100 MHz): d = 168.4 (CO),
166.2 (C-2), 149.8 (C-30), 148.7 (C, C-9), 138.4 (C, C-100),
137.8 (C, C-400), 137.1 (CH, C-300), 135.3 (CH, C-200), 129.7
(CH, C-6), 129.1 (CH, C-5), 128.5 (C, C-8), 124.8 (CH,
C-7), 120.1 (CH, C-4), 58.4 (C-50), 48.4 (C-40), 24.6 (Ar-
CH3); MS (m/z): 336.43 [M?ꢀ]. Anal. Calcd. for
C18H16N4OS: C, 64.26; H, 4.79; N, 16.65. Found: C, 64.16;
H, 4.96; N, 16.87.
JAX = 6.2 Hz, JMX = 10.1 Hz), 2.31 (s, 3H, Ar-CH3); 13
C
NMR (CDCl3, 100 MHz): d = 164.9 (CO), 153.1 (C-2),
148.5 (C-30), 138.3 (C, C-8, C-9), 137.6 (C, C-100), 135.2
(C, C-400), 129.2 (CH, C-300), 127.5 (CH, C-200), 123.3 (CH,
C-5, C-6), 118.0 (CH, C-4, C-7), 57.5 (C-50), 47.4 (C-40),
24.1 (Ar-CH3); MS (m/z): 319.36 [M?ꢀ]. Anal. Calcd. for
C18H17N5O: C, 67.70; H, 5.36; N, 21.93. Found: C, 67.97;
H, 5.54; N, 22.27.
N-(1H-Benzimidazol-2-yl)-40,50-dihydro-40-(400-
chlorophenyl)-10H-pyrazole-30-carboxamide (13c)
N-(Benzothiazol-2-yl)-40,50-dihydro-40-(400-chlorophenyl)-
10H-pyrazole-30-carboxamide (12c)
Mp 297–299 °C; yield 75 %; IR (KBr) mmax 3295, 1659,
Mp 197–199 °C; yield 67 %; IR (KBr) mmax 3310, 1670,
1590 cm-1; 1H NMR (CDCl3, 400 MHz): d = 9.99 (bs, 1H,
NH), 8.44 (bs, 1H, CO–NH), 7.27–7.60 (m, 8H, Ar–H), 4.69
(dd, 1H, HA, JAM = 12.9 Hz, JAX = 6.9 Hz), 4.06 (dd, 1H,
HM, JAM = 12.9 Hz, JMX = 10.9 Hz), 3.74 (dd, 1H, HX,
JAX = 6.9 Hz, JMX = 10.9 Hz); 13C NMR (CDCl3,
100 MHz): d = 169.6 (CO), 166.9 (C-2), 150.5 (C-30), 148.9
(C, C-9), 138.9 (C, C-100), 138.1 (C, C-400), 137.6 (CH, C-200),
135.7 (CH, C-300), 130.2 (C, C-8), 129.9 (CH, C-5), 128.6
(CH, C-6), 124.7 (CH, C-7), 120.9 (CH, C-4), 59.5 (C-50),
49.1 (C-40); MS (m/z): 356.84 [M?ꢀ]. Anal. Calcd. for
C17H13ClN4OS: C, 57.22; H, 3.67; N, 15.70. Found: C, 57.58;
H, 3.65; N, 16.11.
1
1578 cm-1; H NMR (CDCl3, 400 MHz): d = 12.85 (bs,
1H, imidazole-NH), 9.87 (bs, 1H, NH), 8.38 (bs, 1H,
CO–NH), 7.32–7.75 (m, 8H, Ar–H), 4.40 (dd, 1H, HA,
JAM = 12.5 Hz, JAX = 6.4 Hz), 4.02 (dd, 1H, HM,
JAM = 12.5 Hz, JMX = 10.3 Hz), 3.64 (dd, 1H, HX,
JAX = 6.4 Hz, JMX = 10.3 Hz); 13C NMR (CDCl3,
100 MHz): d = 165.8 (CO), 153.9 (C-2), 149.4 (C-30),
138.8 (C, C-8, C-9), 138.4 (C, C-100), 131.4 (C, C-400),
129.4 (CH, C-200), 128.4 (CH, C-300), 122.8 (CH, C-5,
C-6), 119.2 (CH, C-4, C-7), 58.2 (C-50), 48.3 (C-40); MS
(m/z): 339.78 [M?ꢀ]. Anal. Calcd. for C17H14ClN5O: C,
60.09; H, 4.15; N, 20.61. Found: C, 60.00; H, 4.24; N,
20.80.
N-(1H-Benzimidazol-2-yl)-40,50-dihydro-40-phenyl-10H-
pyrazole-30-carboxamide (13a)
General procedure for the synthesis of N-(benzoxazol-
2-yl)-40-aryl-10H-pyrazole-30-carboxamide (14a–14c),
N-(benzothiazol-2-yl)-40-aryl-10H-pyrazole-30-
Mp 261–262 °C; yield 70 %; IR (KBr) mmax 3254, 1653,
1
1568 cm-1; H NMR (CDCl3, 400 MHz): d = 12.80 (bs,
carboxamide (15a–15c) and N-(1H-benzimidazol-2-yl)-
40-aryl-10H-pyrazole-30-carboxamide (16a–16c)
1H, imidazole-NH), 9.83 (bs, 1H, NH), 8.37 (bs, 1H, CO–
NH), 7.30–7.70 (m, 9H, Ar–H), 4.38 (dd, 1H, HA,
JAM = 12.4 Hz, JAX = 6.3 Hz), 3.97 (dd, 1H, HM,
JAM = 12.4 Hz, JMX = 10.2 Hz), 3.59 (dd, 1H, HX,
JAX = 6.3 Hz, JMX = 10.2 Hz); 13C NMR (CDCl3,
100 MHz): d = 165.2 (CO), 153.6 (C-2), 148.8 (C-30),
139.7 (C, C-100), 138.5 (C, C-8, C-9), 129.5 (CH, C-300),
127.7 (CH, C-200), 123.4 (CH, C-400), 122.4 (CH, C-5, C-6),
The compound 11(a–c)/12(a–c)/13(a–c) (1 mmol),
chloranil (1.2 mmol) and xylene (10 ml) were taken and
refluxed for 23–25 h. Then it was treated with 5 % NaOH
solution. The organic layer was separated and repeatedly
washed with water and dried (an. Na2SO4). The solvent
123

Med Chem Res
was removed in vacuo. The solid obtained was purified by
recrystallization from 2-propanol.
(bs, 1H, CO–NH), 7.30–7.95 (m, 9H, Ar–H), 6.57 (bs, 1H,
NH), 6.32 (s, 1H, C5 -H); 13C NMR (CDCl3, 100 MHz):
0
d = 169.1 (CO), 165.6 (C-2), 148.5 (C, C-9), 147.2 (C-30),
136.6 (C-50), 135.7 (C, C-100), 129.4 (CH, C-300), 128.3
(CH, C-400), 127.3 (CH, C-200), 126.2 (C-40), 125.4 (CH,
C-6), 125.2 (CH, C-5), 123.8 (C, C-8), 121.9 (CH, C-7),
121.7 (CH, C-4); MS (m/z): 320.38 [M?ꢀ]. Anal. Calcd. for
C17H12N4OS: C, 63.73; H, 3.77; N, 17.49. Found: C, 64.18;
H, 3.90; N, 17.80.
N-(Benzoxazol-2-yl)-40-phenyl-10H-pyrazole-30-
carboxamide (14a)
Mp 232–234 °C; yield 72 %; IR (KBr) mmax 3285, 1668,
1
1620, 1580 cm-1; H NMR (CDCl3, 400 MHz): d = 8.56
(bs, 1H, CO–NH), 7.24–7.56 (m, 9H, Ar–H), 6.55 (bs, 1H,
NH), 6.25 (s, 1H, C5 -H); 13C NMR (CDCl3, 100 MHz):
0
d = 165.3 (CO), 163.8 (C-2), 150.1 (C, C-8), 146.8 (C-30),
142.0 (C, C-9), 136.2 (C, C-100), 135.7 (C-50), 129.5 (CH,
C-300), 128.3 (CH, C-400), 127.0 (CH, C-200), 124.9 (C-40),
124.1 (CH, C-5), 123.7 (CH, C-6), 119.7 (CH, C-4), 117.6
(CH, C-7); MS (m/z): 304.31 [M?ꢀ]. Anal. Calcd. for
C17H12N4O2: C, 67.10; H, 3.97; N, 18.41. Found: C, 67.47;
H, 4.00; N, 18.81.
N-(Benzothiazol-2-yl)-40-(400-methylphenyl)-10H-pyrazole-
30-carboxamide (15b)
Mp 172–174 °C; yield 62 %; IR (KBr) mmax 3304, 1675,
1
1617, 1588 cm-1; H NMR (CDCl3, 400 MHz): d = 8.56
(bs, 1H, CO–NH), 7.26–7.92 (m, 8H, Ar–H), 6.55 (bs, 1H,
NH), 6.30 (s, 1H, C5 -H), 2.39 (s, 3H, Ar-CH3); 13C NMR
0
(CDCl3, 100 MHz): d = 169.0 (CO), 165.3 (C-2), 148.3
(C, C-9), 147.0 (C-30), 137.8 (C, C-400), 136.1 (C-50), 135.3
(C, C-100), 133.2 (CH, C-300), 129.6 (CH, C-200), 127.1 (CH,
C-6), 126.0 (C-40), 125.0 (CH, C-5), 124.8 (C, C-8), 121.8
(CH, C-7), 121.3 (CH, C-4), 24.3 (Ar-CH3); MS (m/z):
334.41 [M?ꢀ]. Anal. Calcd. for C18H14N4OS: C, 64.65; H,
4.22; N, 16.75. Found: C, 64.84; H, 4.38; N, 16.99.
N-(Benzoxazol-2-yl)-40-(400-methylphenyl)-10H-pyrazole-30-
carboxamide (14b)
Mp 226–228 °C; yield 61 %; IR (KBr) mmax 3277, 1665,
1
1615, 1572 cm-1; H NMR (CDCl3, 400 MHz): d = 8.53
(bs, 1H, CO–NH), 7.15–7.54 (m, 8H, Ar–H), 6.51 (bs, 1H,
NH), 6.17 (s, 1H, C5 -H), 2.32 (s, 3H, Ar-CH3); 13C NMR
0
(CDCl3, 100 MHz): d = 165.1 (CO), 163.5 (C-2), 149.4
(C, C-8), 146.3 (C-30), 140.3 (C, C-9), 135.4 (C-50), 133.8
(C, C-400), 129.3 (C, C-100), 127.1 (CH, C-300), 124.9 (CH,
C-200), 124.1 (C-40), 123.4 (CH, C-5), 120.1 (CH, C-6),
119.6 (CH, C-4), 117.2 (CH, C-7), 23.7 (Ar-CH3); MS (m/
z): 318.34 [M?ꢀ]. Anal. Calcd. for C18H14N4O2: C, 67.91;
H, 4.43; N, 17.60. Found: C, 68.20; H, 4.60; N, 17.92.
N-(Benzothiazol-2-yl)-40-(400-chlorophenyl)-10H-pyrazole-
30-carboxamide (15c)
Mp 204–206 °C; yield 68 %; IR (KBr) mmax 3328, 1687,
1
1628, 1598 cm-1; H NMR (CDCl3, 400 MHz): d = 8.61
(bs, 1H, CO–NH), 7.32–8.02 (m, 8H, Ar–H), 6.60 (bs, 1H,
NH), 6.38 (s, 1H, C5 -H); 13C NMR (CDCl3, 100 MHz):
0
N-(Benzoxazol-2-yl)-40-(400-chlorophenyl)-10H-pyrazole-30-
d = 169.4 (CO), 166.2 (C-2), 148.6 (C, C-9), 147.8 (C-30),
137.9 (C, C-100), 136.8 (C-50), 134.1 (C, C-400), 133.1 (CH,
C-300), 129.0 (CH, C-200), 128.4 (CH, C-6), 126.7 (C-40),
125.6 (CH, C-5), 123.7 (C, C-8), 121.5 (CH, C-7), 120.4
(CH, C-4); MS (m/z): 354.83 [M?ꢀ]. Anal. Calcd. for
C17H11ClN4OS: C, 57.55; H, 3.13; N, 15.71. Found: C,
57.80; H, 3.23; N, 16.09.
carboxamide (14c)
Mp 253–255 °C; yield 70 %; IR (KBr) mmax 3298, 1670,
1
1625, 1593 cm-1; H NMR (CDCl3, 400 MHz): d = 8.57
(bs, 1H, CO–NH), 7.28–7.69 (m, 8H, Ar–H), 6.58 (bs, 1H,
NH), 6.29 (s, 1H, C5 -H); 13C NMR (CDCl3, 100 MHz):
0
d = 165.7 (CO), 163.9 (C-2), 150.4 (C, C-8), 146.9 (C-30),
140.6 (C, C-9), 135.9 (C-50), 134.1 (C, C-100), 129.0 (C,
C-400), 128.6 (CH, C-300), 125.2 (C-40), 124.3 (CH, C-200),
123.8 (CH, C-5), 120.6 (CH, C-6), 119.9 (CH, C-4), 117.9
(CH, C-7); MS (m/z): 338.76 [M?ꢀ]. Anal. Calcd. for
C17H11ClN4O2: C, 60.28; H, 3.27; N, 16.54. Found: C,
60.49; H, 3.33; N, 16.82.
N-(1H-Benzimidazol-2-yl)-40-phenyl-10H-pyrazole-30-
carboxamide (16a)
Mp 286–288 °C; yield 72 %; IR (KBr) mmax 3263, 1660,
1610, 1575 cm-1; 1H NMR (CDCl3, 400 MHz): d = 12.86
(bs, 1H, imidazole-NH), 8.54 (bs, 1H, CO–NH), 7.19–7.87
(m, 9H, Ar–H), 6.50 (bs, 1H, NH), 6.18 (s, 1H, C5 -H); 13C
N-(Benzothiazol-2-yl)-40-phenyl-10H-pyrazole-30-
0
NMR (CDCl3, 100 MHz): d = 164.9 (CO), 154.6 (C-2),
145.3 (C-30), 139.3 (C, C-8, C-9), 137.8 (C, C-100), 137.7
(CH, C-300), 135.5 (C-50), 130.2 (CH, C-400), 128.9 (CH,
C-200), 128.6 (CH, C-5, C-6), 124.0 (C-40), 119.1 (CH, C-4,
carboxamide (15a)
Mp 187–188 °C; yield 65 %; IR (KBr) mmax 3311, 1680,
1
1622, 1596 cm-1; H NMR (CDCl3, 400 MHz): d = 8.59
123

Med Chem Res
C-7); MS (m/z): 303.32 [M?ꢀ]. Anal. Calcd. for
C17H13N5O: C, 67.32; H, 4.32; N, 23.09. Found: C, 67.77;
H, 4.47; N, 23.48.
the standard. The percent of inhibition (I%) of free radical
production from DPPH was calculated by the following
equation
I % ¼ ½ðAcontrol ꢁ AsampleÞ=Ablankꢂ ꢃ 100;
N-(1H-Benzimidazol-2-yl)-40-(400-methylphenyl)-10H-
pyrazole-30-carboxamide (16b)
where Acontrol is the absorbance of the control reaction
(containing methanolic DPPH and ascorbic acid), Asample is
the absorbance of the test compound (containing metha-
nolic DPPH and test compound) and Ablank is the absor-
bance of the blank (containing only methanolic DPPH).
Tests were carried out in triplicate.
Mp 275–276 °C; yield 66 %; IR (KBr) mmax 3252, 1651,
1600, 1569 cm-1; 1H NMR (CDCl3, 400 MHz): d = 12.84
(bs, 1H, imidazole-NH), 8.45 (bs, 1H, CO–NH), 7.15–7.85
0
(m, 8H, Ar–H), 6.47 (bs, 1H, NH), 6.12 (s, 1H, C5 -H), 2.28
(s, 3H, Ar-CH3); 13C NMR (CDCl3, 100 MHz): d = 163.8
(CO), 153.7 (C-2), 145.1 (C-30), 139.1 (C, C-8, C-9), 137.6
(C, C-400), 137.2 (C, C-100), 135.1 (C-50), 130.7 (CH, C-300),
128.5 (CH, C-200), 128.1 (CH, C-5, C-6), 123.6 (C-40),
119.4 (CH, C-4, C-7), 23.6 (Ar-CH3); MS (m/z): 317.35
[M?ꢀ]. Anal. Calcd. for C18H15N5O: C, 68.13; H, 4.75; N,
22.39. Found: C, 68.62; H, 4.76; N, 22.07.
Nitric oxide (NO) scavenging activity
NO scavenging activity was measured by slightly modified
methods of Green et al. and Marcocci et al. NO radicals
were generated from sodium nitroprusside. 1 ml of sodium
nitroprusside (10 mm) and 1.5 ml of phosphate buffer
saline (0.2 M, pH 7.4) were added to different concentra-
tions (50, 75 and 100 lg/ml) of the test compounds and
incubated for 150 min at 25 °C. After incubation 1 ml of
the reaction mixture was treated with 1 ml of Griess
reagent (1 % sulphanilamide, 2 % H3PO4 and 0.1 %
naphthylethylenediamine dihydrochloride). The absor-
bance of the chromatophore was measured at 546 nm.
Ascorbic acid was used as standard. NO scavenging
activity was calculated by the following equation:
N-(1H-Benzimidazol-2-yl)-40-(400-chlorophenyl)-10H-
pyrazole-30-carboxamide (16c)
Mp 298–300 °C; yield 75 %; IR (KBr) mmax 3276, 1668,
1614, 1582 cm-1; 1H NMR (CDCl3, 400 MHz): d = 12.88
(bs, 1H, imidazole-NH), 8.56 (bs, 1H, CO–NH), 7.25–7.90
(m, 8H, Ar–H), 6.52 (bs, 1H, NH), 6.20 (s, 1H, C5 -H); 13C
0
NMR (CDCl3, 100 MHz): d = 165.1 (CO), 154.8 (C-2),
145.8 (C-30), 139.9 (C, C-8, C-9), 138.4 (C, C-100), 137.9
(C, C-400), 135.8 (C-50), 130.3 (CH, C-300), 128.8 (CH,
C-200), 127.7 (CH, C-5, C-6), 124.5 (C-40), 119.8 (CH, C-4,
C-7); MS (m/z): 337.76 [M?ꢀ]. Anal. Calcd. for
C17H12ClN5O: C, 60.45; H, 3.58; N, 20.73. Found: C,
60.55; H, 3.69; N, 20.95.
% of scavenging ¼ ½ðAcontrol ꢁ AsampleÞ=Ablankꢂ ꢃ 100;
where Acontrol is the absorbance of the control reaction
(containing all reagents and ascorbic acid), Asample is the
absorbance of the test compound (containing all reagents
and test compound) and Ablank is the absorbance of the
blank (containing only reagents). Tests were carried out in
triplicate.
Antioxidant activity
The compounds 5(a–c)–16(a–c) were tested for antioxidant
property by DPPH (Burits and Bucar, 2000; Cuendet et al.,
1997), NO (Green et al., 1982; Marcocci et al., 1994) and
H2O2 (Ruch et al., 1989) methods at three different con-
centrations 50, 75 and 100 lg/ml.
Hydrogen peroxide (H2O2) scavenging activity
The H2O2 scavenging ability of the test compound was
determined according to the method of Ruch et al. A
solution of H2O2 (40 mm) was prepared in phosphate
buffer (pH 7.4). 50, 75 and 100 lg/ml concentrations of the
test compounds in 3.4 ml phosphate buffer were added to
H2O2 solution (0.6 ml, 40 mm). The absorbance value of
the reaction mixture was recorded at 230 nm. The percent
of scavenging of H2O2 was calculated by the following
equation:
DPPH radical scavenging activity
The hydrogen atom or electron donation ability of the
compounds was measured from the bleaching of the pur-
ple-coloured methanol solution of DPPH radical. This
property makes it suitable for spectrophotometric studies.
To 4 ml of 0.004 % (w/v) methanol solution of DPPH,
1 ml of various concentrations of the test compounds (50,
75 and 100 lg/ml) in methanol were added. After a 30-min
incubation period at room temperature, the absorbance was
read against blank at 517 nm. Ascorbic acid was used as
% of scavenging ¼ ½ðAcontrol ꢁ AsampleÞ=Ablankꢂ ꢃ 100;
where Acontrol is the absorbance of the control reaction
(containing all reagents and ascorbic acid), Asample is the
absorbance of the test compound (containing all reagents
123

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and test compound) and Ablank is the absorbance of the
blank (containing only reagents). Tests were carried out in
triplicate.
Acknowledgments One of the aurhors (A. Padmaja) is thankful to
University Grants Commission (UGC), New Delhi, for financial
assistance under a major research project. The authors are also
thankful to Prof. Ch. Apparao, Department of Bio-Chemistry, S.
V. University, Tirupati, for providing necessary facilities to carry out
the antioxidant activity of the compounds.
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