Synthesis and Antioxidant Activity of Amido-Linked Benzoxazolyl/Benzothiazolyl/Benzimidazolyl-Pyrazoles and Isoxazoles

Article abstract of DOI:10.1002/jhet.2347

A new class of amido-linked bis heterocycles-benzoxazolyl/benzothiazolyl/benzimidazolyl-pyrazoles and isoxazoles were prepared from benzoxazolyl /benzothiazolyl/benzimidazolyl-cinnamamides and tested for antioxidant activity.

Full text of DOI:10.1002/jhet.2347

738
Synthesis and Antioxidant Activity of Amido-Linked
Vol 53
Benzoxazolyl/Benzothiazolyl/Benzimidazolyl-Pyrazoles and Isoxazoles
*
Suram Durgamma, Putta Ramachandra Reddy, Venkatapuram Padmavathi, and Adivireddy Padmaja
Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India
*
E-mail: adivireddyp@yahoo.co.in
Received July 17, 2014
DOI 10.1002/jhet.2347
Published online 18 May 2015 in Wiley Online Library (wileyonlinelibrary.com).
A new class of amido-linked bis heterocycles-benzoxazolyl/benzothiazolyl/benzimidazolyl-pyrazoles and
isoxazoles were prepared from benzoxazolyl /benzothiazolyl/benzimidazolyl-cinnamamides and tested for
antioxidant activity.
J. Heterocyclic Chem., 53, 738 (2016).
INTRODUCTION
benzoxazolyl/benzothiazolyl/benzimidazolyl-pyrazoles and
isoxazoles has been taken up.
Nitrogen containing five-membered heterocycles has
attracted widespread attention in the field of synthetic
organic chemistry as well as in medicinal chemistry [1].
Amongst them, the prominent classes of compounds
are benzoxazole, benzothiazole, benzimidazole, pyrazole,
isoxazole and their derivatives. Benzoxazoles, benzothiazoles
and benzimidazoles are important fragments in medicinal
chemistry because of their wide range of biological activities
[2–7]. Pyrazoles show pronounced pharmacological applica-
tions as antianxiety [8], antidiabetic [9], antimicrobial
[10,11], herbicidal [12] and anti-inflammatory [13].
Isoxazoles exhibit analgesic [14], anti-inflammatory [14],
ulcerogenic [14], antimicrobial [15], antifungal [15], COX-2
inhibitory [16,17] and anticancer [18] activities. Amongst dif-
ferent methods for the preparation of pyrazolines and
isoxazolines, the 1,3-dipolar cycloaddition is the most impor-
tant and versatile one. The dipolar reagents can be generated
by the dehydrogenation of araldehyde hydrazones and
araldoximes with lead tetraacetate [19], mercury acetate [20],
1-chlorobenzotriazole [21], chloramine-T (CAT) [22–26],
etc. In fact, we have reported novel oxo-linked bis hetero-
cycles by 1,3-dipolar cycloaddition of dipolar reagents
viz., TosMIC, diazomethane, nitrile imines and nitrile oxides
to symmetrical and unsymmetrical bischalcones [27,28]. It is
well known that the combination of two or more heterocy-
cles in a single molecule could afford a novel entity with
increased bioactivities [29,30]. In a continuation quest for
the development of a new class of biologically potent bis
heterocycles from simple substrates, the present work
RESULTS AND DISCUSSION
The synthetic scheme involves the synthesis of a
new class of amide-linked benzoxazolyl/benzothiazolyl/
benzimidazolyl-pyrazoles and isoxazoles from (E)-N-
(benzoxazol-2-yl)cinnamamide (5)/(E)-N-(benzothiazol-2-yl)
cinnamamide (6)/(E)-N-(1H-benzimidazol-2-yl)cinnamamide
(7). In fact, the compounds 5, 6 and 7 were prepared by
the condensation of respective heteroaromatic amines-
benzoxazol-2-amine (1), benzothiazol-2-amine (2) and 1H-
benzimidazol-2-amine (3) with cinnamoyl chloride in toluene
(Scheme 1). The 1H-NMR spectra of 5a, 6a and 7a showed
two doublets at δ 7.84, 7.86, 7.74 and at 6.72, 6.78
6.68 ppm as a result of the olefin protons, HA and HB, respec-
tively. The coupling constant values JAB =16.0Hz (5a),
16.2Hz (6a) and 15.8 Hz (7a) indicated that they possess
trans geometry. Further, a broad singlet was also observed
at δ 8.32 in 5a, at 8.38 in 6a and at 8.18 in 7a ppm as a result
of NH. In addition to these, the compound 7a exhibited
another broad singlet at δ 12.85ppm for NH of benzimidazole
ring. The signals of highly acidic protons disappeared on
deuteration.
The 1,3-dipolar cycloaddition of dipolar reagents to
dipolarophiles is one of the facile techniques for the prep-
aration of pyrazoles and isoxazoles. It was reported that
the cycloaddition of 1,3-dipolar reagents to α,β-unsaturated
systems proceed in such a way that the electron-rich atom
© 2015 HeteroCorporation

May 2016
Pyrazole, Isoxazole, Antioxidant Activity
739
Scheme 1. Synthesis of benzoxazolyl/benzothiazolyl/benzimidazolyl-pyrazoles and isoxazoles.
of 1,3-dipolar species attacks β-carbon of α,β-unsaturated
systems followed by isomerization [31]. In fact, the
cycloaddition of nitrile imine generated from araldehyde
phenylhydrazone and nitrile oxide generated from
araldoxime in the presence of CAT to compound 5/6/7
proceeded regioselectively. Thus, N-(benzoxazol-2-yl)-4′,
5′-dihydro-1′-phenyl-3′,5′-diaryl-1′H-pyrazole-4′-carboxamide
(8), N-(benzothiazol-2-yl)-4′,5′-dihydro-1′-phenyl-3′,5′-diaryl-
1′H-pyrazole-4′-carboxamide (9) and N-(1H-benzimidazol-
2-yl)-4′,5′-dihydro-1′-phenyl-3′,5′-diaryl-1′H-pyrazole-4′-
carboxamide (10) were obtained by the cycloaddition of
nitrile imine generated from araldehyde phenylhydrazone
in the presence of CAT to 5, 6 and 7 (Scheme 1). The 1H-
NMR spectra of 8a, 9a and 10a displayed two doublets at
δ 5.10, 5.16, 5.05 and at 5.28, 5.33, 5.25ppm as a result
of C4′-H and C5′-H of pyrazoline ring. Moreover, a broad
singlet was observed in these compounds at δ 8.37 (8a),
8.40 (9a) and at 8.32 (10a) ppm as a result of NH. Apart
from these, compound 10a exhibited another broad singlet
at δ 12.78ppm that was assigned to NH of benzimidazole
ring. The signals as a result of NH disappeared when D2O
was added.
Adopting similar methodology, the cycloaddition of nitrile
oxide generated from araldoxime in the presence of CAT to
5, 6 and 7 yielded N-(benzoxazol-2-yl)-4′,5′-dihydro-3′,5′-
diarylisoxazole-4′-carboxamide (11), N-(benzothiazol-2-yl)-
4′,5′-dihydro-3′,5′-diarylisoxazole-4′-carboxamide (12) and
N-(1H-benzimidazol-2-yl)-4′,5′-dihydro-3′,5′-diarylisoxazole-
1
4′-carboxamide (13), respectively (Scheme 1). The H-NMR
spectra of 11a, 12a and 13a displayed two doublets
at δ 5.07, 5.11, 4.98 and at 5.42, 5.49, 5.37 ppm that
were attributed to C4′-H and C5′-H. Furthermore, a
broad singlet was observed at δ 8.39 in 11a, at 8.42
in 12a and at 8.37 ppm in 13a as a result of NH. Apart
from these, compound 13a showed another broad signal
at δ 12.82 ppm as a result of NH of benzimidazole
ring. The signals of highly acidic protons disappeared
on deuteration.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

740
S. Durgamma, P. R. Reddy, V. Padmavathi, and A. Padmaja
Vol 53
The oxidation of compounds 8–13 with chloranil in
NH. Furthermore, compounds 16a and 19a exhibited another
broad singlet at δ 12.85 and 12.87ppm as a result of NH of
benzimidazole ring. The signals of NH disappeared when
D2O was added. The structures of all the new compounds
were further confirmed by IR, 13C-NMR, mass spectra
and microanalyses.
xylene produced N-(benzoxazol-2-yl)-1′-phenyl-3′,5′-diaryl-
1′H-pyrazole-4′-carboxamide (14), N-(benzothiazol-2-yl)-
1′-phenyl-3′,5′-diaryl-1′H-pyrazole-4′-carboxamide (15), N-(1H-
benzimidazol-2-yl)-1′-phenyl-3′,5′-diaryl-1′H-pyrazole-4′-
carboxamide (16), N-(benzoxazol-2-yl)-3′,5′-diarylisoxazole-
4′-carboxamide (17), N-(benzothiazol-2-yl)-3′,5′-diarylisoxazole-
4′-carboxamide (18) and N-(1H-benzimidazol-2-yl)-3′,5′-
diarylisoxazole-4′-carboxamide (19) (Scheme 1). The absence
of doublets as a result of pyrazoline and isoxazoline ring pro-
ANTIOXIDANT STUDIES
The compounds 8–19 were tested for antioxidant prop-
erty by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) [32,33],
nitric oxide (NO) [34,35] and hydrogen peroxide (H2O2)
[36] methods at three different concentrations 50, 75 and
100 μg/mL. The Ascorbic acid was used as the standard
1
tons in the H-NMR spectra of compounds 14–19 indicated
1
that aromatization took place. In the H-NMR spectra of
14a, 15a, 16a, 17a, 18a and 19a, a broad singlet was observed
at δ 8.54, 8.56, 8.49, 8.55, 8.60 and 8.52ppm as a result of
Table 1
Table 2
The in vitro antioxidant activity of compounds 8–19 in DPPH method.
The in vitro antioxidant activity of compounds 8–19 in NO method.
Concentration (μg/mL)
Concentration (μg/mL)
Compound
50
75
100
Compound
50
75
100
8a
8b
8c
30.31 0.41
33.98 0.67
—
32.75 0.25
35.42 0.52
—
34.07 0.08
37.58 0.47
—
8a
8b
8c
33.16 0.84
36.74 0.17
—
34.77 0.38
37.26 1.02
—
35.62 0.02
38.53 0.45
—
9a
9b
9c
28.97 0.82
32.64 1.17
—
31.16 0.33
34.49 0.05
—
32.21 0.11
35.54 0.86
—
9a
9b
9c
32.29 0.52
35.84 0.33
—
33.01 0.49
36.25 0.11
—
34.04 1.08
37.79 0.67
—
10a
10b
10c
11a
11b
11c
12a
12b
12c
13a
13b
13c
14a
14b
14c
15a
15b
15c
16a
16b
16c
17a
17b
17c
18a
18b
18c
19a
19b
19c
Ascorbic acid
Blank
—
—
—
10a
10b
10c
11a
11b
11c
12a
12b
12c
13a
13b
13c
14a
14b
14c
15a
15b
15c
16a
16b
16c
17a
17b
17c
18a
18b
18c
19a
19b
19c
Ascorbic acid
Blank
—
—
—
25.48 0.28
—
34.54 0.05
37.79 0.10
—
31.03 0.49
35.91 0.32
—
26.22 0.74
—
36.67 0.86
38.83 0.95
—
33.54 0.17
36.24 0.54
—
27.69 1.09
—
39.82 1.01
41.91 0.07
—
35.42 0.77
39.04 0.13
—
30.07 0.65
—
35.32 0.28
39.54 0.79
—
34.07 0.12
37.65 0.95
—
31.66 0.19
—
36.59 0.52
40.22 0.03
—
35.76 0.98
38.20 0.31
—
32.35 0.07
—
37.81 1.14
42.57 0.46
—
36.74 0.60
39.25 0.18
—
—
—
—
—
—
—
27.65 0.28
—
28.80 0.06
—
30.10 1.02
—
31.72 0.41
—
32.56 1.12
—
33.07 0.97
—
70.33 0.11
77.54 0.85
62.71 1.09
58.29 0.33
64.96 0.52
51.68 0.41
40.03 1.17
44.27 0.32
35.39 0.63
72.34 0.11
80.16 0.69
63.82 0.04
60.54 1.07
66.24 0.75
54.93 1.09
52.44 0.46
59.98 0.54
47.21 0.19
74.37 0.15
—
71.12 0.71
80.64 0.12
64.47 0.25
59.09 0.79
67.38 0.11
52.59 0.65
42.86 0.42
47.62 0.50
38.15 0.25
73.63 0.76
83.47 0.33
65.29 0.64
60.98 0.03
69.32 0.58
55.11 0.97
53.93 0.32
60.54 0.30
49.91 0.75
76.63 0.09
—
73.94 0.38
82.25 0.43
65.12 0.02
61.57 0.96
69.45 0.71
53.09 1.01
43.39 0.05
49.97 0.47
39.84 0.21
75.39 1.05
84.72 0.88
66.58 0.60
62.30 0.37
70.06 0.15
58.81 0.52
55.32 0.22
63.29 0.63
50.57 0.87
79.21 0.45
—
73.42 0.29
81.74 0.06
64.57 0.54
60.19 0.71
66.48 0.04
52.35 0.50
42.10 0.82
47.27 1.15
39.17 0.66
75.54 0.63
83.65 0.12
65.32 0.91
60.61 0.56
68.12 0.09
56.78 0.70
53.35 0.56
62.12 0.08
50.17 0.21
77.20 0.09
—
75.71 0.85
84.06 0.76
66.32 0.08
61.96 0.13
69.51 0.64
54.32 0.97
44.82 0.04
49.14 0.25
40.63 0.09
76.25 1.02
85.42 0.48
68.21 0.44
62.57 0.70
70.92 0.68
57.16 0.83
55.44 0.97
63.23 0.77
51.56 0.56
79.92 022
—
76.01 0.30
87.54 1.11
68.09 0.59
63.37 0.45
71.42 0.10
56.55 0.12
45.75 0.99
52.04 1.21
41.20 0.27
77.97 0.64
88.06 0.01
69.29 0.52
64.63 0.31
72.14 0.17
59.84 0.40
56.05 1.13
64.11 0.12
52.86 1.10
82.24 0.34
—
(—) Showed no scavenging activity.
Values were the means of three replicates SD.
(—) Showed no scavenging activity.
Values were the means of three replicates SD.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2016
Pyrazole, Isoxazole, Antioxidant Activity
741
Table 3
Table 4
The in vitro antioxidant activity of compounds 8–19 in H2O2 method.
Antioxidant activities of compounds 14a, 14b, 17a and 17b at 10 min
time intervals determined by the DPPH radical-scavenging method.
Concentration (μg/mL)
Compound
10 min
20 min
30 min
Compound
50
75
100
14a
14b
17a
17b
71.95
75.01
73.50
79.12
72.02
75.15
73.80
79.28
72.08
75.92
73.98
79.55
8a
8b
8c
31.47 0.41
34.02 0.33
—
34.11 0.57
35.55 1.03
—
35.46 0.11
37.27 0.75
—
9a
9b
9c
30.35 0.65
33.76 0.74
—
32.60 0.97
34.52 0.06
—
34.62 0.38
36.15 0.67
—
17b showed higher radical scavenging activity in all the
three methods when compared with the standard drug ascor-
bic acid. The compounds 14a, 14c, 15b, 17a, 17c, 18a and
18b exhibited good activity whereas the compounds 15a,
15c, 18c, 19a and 19b displayed moderate activity. On the
other hand, the compounds 8a, 8b, 9a, 9b, 10b, 11a, 11b,
12a, 12b, 13b, 16a, 16b, 16c and 19c exhibited low activity.
However, the other compounds showed no activity. The free
radical-scavenging activity of the compounds 14a, 14b, 17a
and 17b was measured at different concentrations, monitored
by the change in absorbance at 10, 20 and 30 min in the DPPH
method (Table 4). It was observed that at these 10min time in-
tervals, the values are very close and the results exemplify that
the antioxidant activity is independent of time.
10a
10b
10c
11a
11b
11c
12a
12b
12c
13a
13b
13c
14a
14b
14c
15a
15b
15c
16a
16b
16c
17a
17b
17c
18a
18b
18c
19a
19b
19c
Ascorbic acid
Blank
—
—
—
25.67 0.30
—
33.51 0.97
38.43 1.06
—
32.68 0.68
35.15 0.30
—
28.01 0.44
—
34.25 1.16
39.82 0.11
—
33.13 0.37
36.91 0.56
—
29.32 0.55
—
36.74 0.13
40.10 0.34
—
35.09 0.72
38.52 0.41
—
—
—
—
27.74 0.05
—
29.82 0.28
—
30.76 0.66
—
71.27 0.49
79.65 0.68
63.01 0.44
59.52 0.65
65.35 0.31
52.19 1.21
41.08 0.86
47.27 0.18
38.81 0.66
72.21 0.39
81.52 0.42
63.96 0.17
60.32 1.18
67.29 0.26
55.04 0.69
52.29 0.26
61.52 0.50
49.90 0.01
76.54 0.32
—
73.37 0.92
83.30 0.13
64.22 0.61
61.11 1.03
69.29 0.96
53.52 0.18
42.97 0.39
49.14 0.57
39.32 0.28
75.07 0.17
84.26 0.50
65.62 0.83
61.96 0.99
70.12 0.01
56.53 0.35
53.32 0.17
63.11 0.32
50.02 0.28
78.12 0.05
—
75.12 1.16
84.99 0.01
65.34 0.09
62.07 0.48
70.56 1.14
55.79 0.76
44.23 0.62
52.04 0.05
40.51 1.02
77.54 0.58
86.75 0.12
66.05 0.09
63.32 0.15
71.17 0.63
59.20 0.71
55.54 0.42
65.92 1.09
51.93 0.54
80.67 0.69
—
CONCLUSION
A
new class of amido-linked bis heterocycles-
benzoxazolyl/benzothiazolyl/benzimidazolyl-pyrazoles and
benzoxazolyl/benzothiazolyl/benzimidazolyl-isoxazoles were
prepared adopting 1,3-dipolar cycloaddition methodology
from the easily accessible building blocks benzoxazol-2-
amine, benzothiazol-2-amine, 1H-benzimidazol-2-amine
and cinnamoyl chloride. All the new compounds were
assayed for antioxidant activity. It was observed that
benzoxazolyl/benzothiazolyl/benzimidazolyl-pyrazoles and
isoxazoles exhibited comparatively greater activity than
the benzoxazolyl/benzothiazolyl/benzimidazolyl-pyrazolines
and isoxazolines. The compounds 14b and 17b showed
greater radical scavenging activity when compared with
the standard drug ascorbic acid.
(—) Showed no scavenging activity.
Values were the means of three replicates SD.
drug. The perusal of the results (Tables 1–3) revealed that
aromatized compounds (14–19) exhibited greater activity
than the corresponding non-aromatized compounds (8–13).
In general, amido-linked benzoxazolyl pyrazoles (14) and
isoxazoles (17) displayed higher radical scavenging activity
than benzothiazolyl pyrazoles (15) and isoxazoles (18),
benzimidazolyl pyrazoles (16) and isoxazoles (19). Further,
it was observed that the compounds with benzothiazolyl
moiety (15, 18) exhibited greater activity than those with
benzimidazolyl moiety (16, 19). It was also observed that
compounds having methyl substituent on the phenyl ring
displayed significant activity than unsubstituted and chloro-
substituted ones. This may be because of electron-donating
effect of the alkyl substituent. In fact, compounds 14b and
EXPERIMENTAL
Melting points were determined in open capillaries on a Mel-
Temp apparatus and are uncorrected. The progress of reaction
was monitored 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 pellets, and the wave numbers were given
in cmꢀ1. The 1H-NMR spectra were recorded in CDCl3 /DMSO-d6
on a Jeol JNM λ 400 MHz. The 13C-NMR spectra were
recorded in CDCl3 /DMSO-d6 on a Jeol JNM spectrometer
operating at λ 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 μA. All chemical shifts are reported
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

742
S. Durgamma, P. R. Reddy, V. Padmavathi, and A. Padmaja
Vol 53
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 [37–39].
(E)-N-(Benzoxazol-2-yl)cinnamamide (5)/(E)-N-(benzothiazol-
2-yl)cinnamamide (6)/(E)-N-(1H-benzimidazol-2-yl)cinnamamide
(7). General procedure. A mixture of 1/2/3 (1 mmol), cinnamoyl
chloride (4) (1.1 mmol) and toluene (10 mL) was heated to reflux for
15–18 h. After completion of the reaction, the contents were cooled
to room temperature. The separated solid was collected and purified
by column chromatography (silica gel, ethyl acetate/hexane, 1.5:3).
C17H14N2OS: C, 69.18; H, 4.69; N, 9.61; Found: C, 69.22; H, 4.67;
N, 9.47%.
(E)-N-(Benzothiazol-2-yl)-3-(4-chlorophenyl)acrylamide (6c). White
solid (0.24 g, 78%); m.p. 161–163°C; IR (KBr): 1605 (C¼N), 1625
(C¼C), 1660 (C¼O), 3331 (NH) cmꢀ1
;
1H-NMR (400 MHz,
CDCl3): δ 6.85 (d, 1H, HB, J= 16.3 Hz), 7.20–8.23 (m, 8H, Ar–H),
7.89 (d, 1H, HA, J= 16.3 Hz), 8.40 (bs, 1H, NH) ppm; 13C-NMR
(100 MHz, CDCl3): δ 118.7 (C-HB), 145.2 (C-HA), 168.6 (C-2),
169.4 (CO), 121.8, 122.1, 124.6, 125.5, 125.9, 127.3, 128.4, 133.0,
133.8, 148.4 (aromatic carbons) ppm; MS (m/z): 314.80 [M+]; Anal.
Calcd. for C16H11ClN2OS: C, 61.03; H, 3.63; N, 9.17; Found: C,
60.94; H, 3.59; N, 8.99%.
(E)-N-(1H-Benzimidazol-2-yl)cinnamamide (7a). Brown solid
(0.22 g, 86%); m.p. 255–257°C; IR (KBr): 1590 (C¼N), 1616
(E)-N-(Benzoxazol-2-yl)cinnamamide (5a).
White solid
(0.17 g, 68%); m.p. 202–204°C; IR (KBr): 1597 (C¼N), 1618
(C¼C), 1653 (C¼O), 3302 (NH) cmꢀ1
;
1H-NMR (400 MHz,
(C¼C), 1654 (C¼O), 3309 (NH) cmꢀ1
;
1H-NMR (400 MHz,
CDCl3): δ 6.68 (d, 1H, HB, J= 15.8 Hz), 7.10–7.64 (m, 9H, Ar–H),
7.74 (d, 1H, HA, J= 15.8 Hz), 8.18 (bs, 1H, NH), 12.85 (bs, 1H,
imidazole-NH) ppm; 13C-NMR (100 MHz, CDCl3): δ 117.4
(C-HB), 141.9 (C-HA), 150.4 (C-2), 167.4 (CO), 119.2, 123.5,
126.4, 128.3, 128.9, 134.3, 138.4 (aromatic carbons) ppm; MS
(m/z): 263.30 [M+]; Anal. Calcd. for C16H13N3O: C, 73.21; H,
5.07; N, 15.97; Found: C, 73.15; H, 5.05; N, 15.84%.
CDCl3): δ 6.72 (d, 1H, HB, J = 16.0 Hz), 7.13–7.35 (m, 9H, Ar–H),
7.84 (d, 1H, HA, J = 16.0 Hz), 8.32 (bs, 1H, NH) ppm; 13C-NMR
(100 MHz, CDCl3): δ 117.8 (C-HB), 143.2 (C-HA), 163.1 (C-2),
168.0 (CO), 117.3, 120.4, 123.5, 124.5, 127.3, 128.1, 128.8, 133.4,
142.5, 150.2 (aromatic carbons) ppm; MS (m/z): 264.28 [M+·];
Anal. Calcd. for C16H12N2O2: C, 72.70; H, 4.59; N, 10.81; Found:
C, 72.64; H, 4.62; N, 10.71%.
(E)-N-(Benzoxazol-2-yl)-3-(4-methylphenyl)acrylamide (5b). White
solid (0.18g, 65%); m.p. 195–197°C; IR (KBr): 1595 (C¼N), 1615
(E)-N-(1H-Benzimidazol-2-yl)-3-(4-methylphenyl)acrylamide
(7b). Brown solid (0.22 g, 80%); m.p. 238–240°C; IR (KBr):
(C¼C), 1651 (C¼O), 3302 (NH) cmꢀ1
;
1H-NMR (400 MHz,
1
1587 (C¼N), 1613 (C¼C), 1650 (C¼O), 3297 (NH) cmꢀ1; H-
CDCl3): δ 2.34 (s, 3H, Ar–CH3), 6.70 (d, 1H, HB, J = 15.9Hz),
7.11–7.31 (m, 8H, Ar–H), 7.79 (d, 1H, HA, J = 15.9Hz), 8.29 (bs,
1H, NH) ppm; 13C-NMR (100 MHz, CDCl3): δ 24.6 (Ar–CH3),
117.5 (C-HB), 142.8 (C-HA), 162.7 (C-2), 167.1 (CO), 117.1,
119.4, 123.4, 125.2, 126.8, 128.3, 133.5, 137.4, 142.4, 149.8
(aromatic carbons) ppm; MS (m/z): 278.31 [M+·]; Anal. Calcd. for
C17H14N2O2: C, 73.34; H, 5.18; N, 10.35; Found: C, 73.21; H,
5.13; N, 10.15%.
NMR (400 MHz, CDCl3): δ 2.32 (s, 3H, Ar–CH3) 6.65 (d, 1H,
HB, J = 15.7 Hz), 7.06–7.62 (m, 8H, Ar–H), 7.70 (d, 1H, HA,
J = 15.7 Hz), 8.14 (bs, 1H, NH), 12.82 (bs, 1H, imidazole-NH)
ppm; 13C-NMR (100 MHz, CDCl3): δ 24.1 (Ar–CH3), 117.2 (C-
HB), 141.5 (C-HA), 150.3 (C-2), 166.6 (CO), 119.0, 123.1,
126.3, 128.2, 128.8, 137.4, 138.1 (aromatic carbons) ppm; MS
(m/z): 277.33 [M+]; Anal. Calcd. for C17H15N3O: C, 73.59; H,
5.56; N, 15.18; Found: C, 73.50; H, 5.52; N, 15.02%.
(E)-N-(Benzoxazol-2-yl)-3-(4-chlorophenyl)acrylamide (5c). White
solid (0.21 g, 72%); m.p. 212–214°C; IR (KBr): 1600 (C¼N), 1620
(E)-N-(1H-Benzimidazol-2-yl)-3-(4-chlorophenyl)acrylamide
(7c).
White solid (0.26 g, 88%); m.p. 272–275°C; IR (KBr):
(C¼C), 1658 (C¼O), 3311 (NH) cmꢀ1
;
1H-NMR (400 MHz,
1598 (C¼N), 1617 (C¼C), 1655 (C¼O), 3305 (NH) cmꢀ1
;
1H-NMR (400 MHz, CDCl3): δ 6.70 (d, 1H, HB, J = 15.9 Hz),
7.12–7.69 (m, 8H, Ar–H), 7.79 (d, 1H, HA, J = 15.9Hz), 8.20 (bs,
1H, NH), 12.90 (bs, 1H, imidazole-NH) ppm; 13C-NMR
(100 MHz, CDCl3): δ 117.7 (C-HB), 142.0 (C-HA), 150.7 (C-2),
167.2 (CO), 119.4, 123.9, 126.6, 128.7, 129.1, 134.5, 138.9
(aromatic carbons) ppm; MS (m/z): 297.74 [M+]; Anal. Calcd. for
C16H12ClN3O: C, 64.57; H, 4.06; N, 14.38; Found: C, 64.44; H,
4.00; N, 14.21%.
CDCl3): δ 6.75 (d, 1H, HB, J = 16.1 Hz), 7.15–7.39 (m, 8H, Ar–H),
7.87 (d, 1H, HA, J = 16.1 Hz), 8.34 (bs, 1H, NH) ppm; 13C-NMR
(100 MHz, CDCl3): δ 118.2 (C-HB), 143.5 (C-HA), 163.5 (C-2),
167.9 (CO), 117.8, 120.3, 123.8, 124.7, 127.4, 128.6, 134.2, 134.8,
140.3, 151.3 (aromatic carbons) ppm; MS (m/z): 298.73 [M+·];
Anal. Calcd. for C16H11ClN2O2: C, 64.62; H, 3.85; N, 9.73;
Found: C, 64.47; H, 3.77; N, 9.46%.
(E)-N-(Benzothiazol-2-yl)cinnamamide (6a).
White solid
N-(Benzoxazol-2-yl)-4′,5′-dihydro-1′-phenyl-3′,5′-diaryl-1′H-
pyrazole-4′-carboxamide (8)/N-(benzothiazol-2-yl)-4′,5′-dihydro-
1′-phenyl-3′,5′-diaryl-1′H-pyrazole-4′-carboxamide (9)/N-(1H-
benzimidazol-2-yl)-4′,5′-dihydro-1′-phenyl-3′,5′-diaryl-1′H-pyrazole-
(0.21 g, 75%); m.p. 148–150°C; IR (KBr): 1601 (C¼N), 1623
(C¼C), 1659 (C¼O), 3318 (NH) cmꢀ1
;
1H-NMR (400 MHz,
CDCl3): δ 6.78 (d, 1H, HB, J = 16.2 Hz), 7.18–8.20 (m, 9H, Ar–H),
7.86 (d, 1H, HA, J = 16.2 Hz), 8.38 (bs, 1H, NH) ppm; 13C-NMR
(100MHz, CDCl3): δ 118.4 (C-HB), 144.8 (C-HA), 166.8 (C-2),
169.2 (CO), 121.3, 121.9, 125.3, 126.0, 126.3, 127.2, 128.7,
129.4, 136.5, 147.3 (aromatic carbons) ppm; MS (m/z): 280.35
[M+·]; Anal. Calcd. for C16H12N2OS: C, 68.74; H, 4.24; N, 10.17;
Found: C, 68.67; H, 4.25; N, 10.08%.
4′-carboxamide (10).
General procedure. The compound 5/6/7
(1.0 mmol), araldehyde phenylhydrazone (1.2 mmol), CAT (0.33 g,
1.2 mmol) and methanol (20 mL) were refluxed for 23–25 h. The
precipitated inorganic salts were filtered off. The filtrate was
concentrated, and the residue was extracted with dichloromethane.
The organic layer was washed with water, brine and dried (an.
Na2SO4). Evaporation of the solvent under reduced pressure
yielded a solid that was purified by column chromatography (silica
gel, 60–120 mesh) using hexane/ethyl acetate (4:1) as eluent.
N-(Benzoxazol-2-yl)-4′,5′-dihydro-1′,3′,5′-triphenyl-1′H-pyrazole-
4′-carboxamide (8a). White solid (0.33 g, 74%); m.p. 218–220°C;
(E)-N-(Benzothiazol-2-yl)-3-(4-methylphenyl)acrylamide (6b). White
solid (0.20 g, 71%); m.p. 137–139°C; IR (KBr): 1585 (C¼N), 1619
(C¼C), 1657 (C¼O), 3315 (NH) cmꢀ1
;
1H-NMR (400 MHz,
CDCl3): δ 2.36 (s, 3H, Ar–CH3), 6.74 (d, 1H, HB, J= 16.0 Hz),
7.16–8.15 (m, 8H, Ar–H), 7.81 (d, 1H, HA, J= 16.0 Hz), 8.26 (bs,
1H, NH) ppm; 13C-NMR (100 MHz, CDCl3): δ 24.8 (Ar–CH3),
117.9 (C-HB), 144.5 (C-HA), 167.6 (C-2), 168.8 (CO), 120.4, 121.1,
124.5, 125.4, 125.8, 126.2, 128.3, 132.4, 136.4, 146.3 (aromatic
carbons) ppm; MS (m/z): 294.38 [M+·]. Anal. Calcd. for
1
IR (KBr): 1567 (C¼N), 1658 (C¼O), 3274 (NH) cmꢀ1; H-NMR
(400 MHz, DMSO-d6): δ 5.10 (d, 1H, C4′-H, J=7.12Hz), 5.28 (d,
1H, C5′-H, J= 7.2 Hz), 6.50–7.60 (m, 19H, Ar–H), 8.37 (bs, 1H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2016
Pyrazole, Isoxazole, Antioxidant Activity
743
NH) ppm; 13C-NMR (100 MHz, DMSO-d6): δ 62.3 (C-4′), 82.5 (C-
5′), 151.9 (C-3′), 162.5 (C-2), 168.2 (CO), 110.5, 113.4, 117.6,
119.3, 123.6, 124.5, 126.4, 127.7, 128.4, 128.8, 129.6, 129.9, 131.3,
134.4, 141.6, 143.5, 144.3, 150.3 (aromatic carbons) ppm; MS (m/z):
458.52 [M+·]; Anal. Calcd. for C29H22N4O2: C, 76.05; H, 4.82; N,
12.33; Found: C, 75.97; H, 4.84; N, 12.22%.
168.9 (CO), 169.7 (C-2), 113.7, 117.8, 121.4, 121.9, 124.7,
125.3, 125.9, 126.7, 127.8, 128.6, 128.8, 129.4, 129.9, 131.9,
134.5, 143.5, 143.9, 149.5 (aromatic carbons) ppm; MS (m/z):
543.49 [M+]; Anal. Calcd. for C29H20Cl2N4OS: C, 64.21; H, 3.70;
N, 10.46; Found: C, 64.09; H, 3.71; N, 10.31%.
N-(1H-Benzimidazol-2-yl)-4′,5′-dihydro-1′,3′,5′-triphenyl-1′
H-pyrazole-4′-carboxamide (10a). Brown solid (0.31 g, 69%);
m.p. 275–277°C; IR (KBr): 1564 (C¼N), 1650 (C¼O), 3264
N-(Benzoxazol-2-yl)-3′,5′-bis(4-methylphenyl)-4′,5′-dihydro-
1′-phenyl-1′H-pyrazole-4′-carboxamide (8b).
White solid
(NH) cmꢀ1 1H-NMR (400 MHz, DMSO-d6): δ 5.05 (d, 1H,
;
(0.32 g, 67%); m.p. 206–208°C; IR (KBr): 1561 (C¼N), 1651
(C¼O), 3262 (NH) cmꢀ1
;
1H-NMR (400 MHz, DMSO-d6): δ
C4′-H, J = 6.8 Hz), 5.25 (d, 1H, C5′-H, J = 6.8 Hz), 6.55–7.71
(m, 19H, Ar–H), 8.32 (bs, 1H, NH), 12.78 (bs, 1H, imidazole-
NH) ppm; 13C-NMR (100 MHz, DMSO-d6): δ 61.7 (C-4′), 81.9
(C-5′), 150.8 (C-3′), 153.9 (C-2), 167.5 (CO), 113.6, 115.5,
117.6, 123.5, 126.5, 127.4, 128.2, 129.4, 130.3, 131.5, 132.7,
134.5, 138.6, 143.5, 144.4 (aromatic carbons) ppm; MS (m/z):
457.53 [M+]; Anal. Calcd. for C29H23N5O: C, 76.23; H, 5.11;
N, 15.50; Found: C, 76.13; H, 5.07; N, 15.31%.
N-(1H-Benzimidazol-2-yl)-3′,5′-bis(4-methylphenyl)-4′,5′-dihydro-
1′-phenyl-1′H-pyrazole-4′-carboxamide (10b). Brown solid (0.32 g,
66%); m.p. 261–263°C; IR (KBr): 1560 (C¼N), 1645 (C¼O), 3255
(NH) cmꢀ1; 1H-NMR (400 MHz, DMSO-d6): δ 2.31 and 2.35 (s, 6H,
Ar–CH3), 5.01 (d, 1H, C4′-H, J= 6.7 Hz), 5.17 (d, 1H, C5′-H,
J=6.7Hz), 6.51–7.66 (m, 17H, Ar–H), 8.28 (bs, 1H, NH), 12.74 (bs,
1H, imidazole-NH) ppm; 13C-NMR (100 MHz, DMSO-d6): δ 23.2
and 24.1 (Ar–CH3), 61.1 (C-4′), 81.4 (C-5′), 150.1 (C-3′), 152.7
(C-2), 167.5 (CO), 113.5, 115.3, 117.1, 123.0, 126.2, 127.3, 128.0,
129.3, 130.2, 131.4, 132.1, 134.3, 138.2, 143.1, 144.0 (aromatic
carbons) ppm; MS (m/z): 485.58 [M+]; Anal. Calcd. for
C31H27N5O: C, 76.81; H, 5.62; N, 14.59; Found: C, 76.68; H,
5.60; N, 14.42%.
2.34 and 2.37 (s, 6H, Ar–CH3), 5.04 (d, 1H, C4′-H, J = 6.9 Hz),
5.24 (d, 1H, C5′-H, J = 6.9 Hz), 6.44–7.53 (m, 17H, Ar–H), 8.34
(bs, 1H, NH) ppm; 13C-NMR (100 MHz, DMSO-d6): δ 23.5
and 24.2 (Ar–CH3), 62.1 (C-4′), 81.9 (C-5′), 151.2 (C-3′),
162.1 (C-2), 168.0 (CO), 110.1, 113.2, 117.4, 119.1, 123.4,
124.1, 126.0, 127.2, 128.1, 128.5, 129.1, 129.5, 131.0, 134.2,
141.3, 143.2, 144.1, 149.8 (aromatic carbons) ppm; MS (m/z):
486.58 [M+]; Anal. Calcd. for C31H26N4O2: C, 76.47; H, 5.39;
N, 11.59; Found: C, 76.52; H, 5.38; N, 11.52%.
N-(Benzoxazol-2-yl)-3′,5′-bis(4-chlorophenyl)-4′,5′-dihydro-
1′-phenyl-1′H-pyrazole-4′-carboxamide (8c). White solid (0.40 g,
77%); m.p. 229–230°C; IR (KBr): 1575 (C¼N), 1667 (C¼O), 3283
(NH) cmꢀ1; 1H-NMR (400 MHz, DMSO-d6): δ 5.12 (d, 1H, C4′-H,
J= 7.3 Hz), 5.32 (d, 1H, C5′-H, J= 7.3 Hz), 6.54–7.67 (m, 17H,
Ar–H), 8.39 (bs, 1H, NH) ppm; 13C-NMR (100 MHz,
DMSO-d6): δ 62.5 (C-4′), 82.7 (C-5′), 152.4 (C-3′), 162.8 (C-2),
168.5 (CO), 110.4, 113.6, 117.7, 119.5, 123.8, 124.7, 126.6,
128.3, 128.5, 128.9, 129.8, 130.2, 131.5, 134.7, 141.8, 143.6,
144.9, 150.7 (aromatic carbons) ppm; MS (m/z): 527.48 [M+];
Anal. Calcd. for C29H20Cl2N4O2: C, 66.12; H, 3.85; N, 10.75;
Found: C, 66.03; H, 3.82; N, 10.62%.
N-(1H-Benzimidazol-2-yl)-3′,5′-bis(4-chlorophenyl)-4′,5′-dihydro-
1′-phenyl-1′H-pyrazole-4′-carboxamide (10c). Brown solid (0.39 g,
76%); m.p. 283–285°C; IR (KBr): 1568 (C¼N), 1658 (C¼O), 3273
N-(Benzothiazol-2-yl)-4′,5′-dihydro-1′,3′,5′-triphenyl-1′H-pyrazole-
4′-carboxamide (9a). White solid (0.38 g, 81%); m.p. 262–264°C; IR
1
(NH) cmꢀ1; H-NMR (400 MHz, DMSO-d6): δ 5.08 (d, 1H, C4′-H,
(KBr): 1579 (C¼N), 1663 (C¼O), 3289 (NH) cmꢀ1
;
1H-NMR
J= 7.0 Hz), 5.28 (d, 1H, C5′-H, J= 7.0 Hz), 6.58–7.75 (m, 17H,
Ar–H), 8.35 (bs, 1H, NH), 12.79 (bs, 1H, imidazole-NH) ppm;
13C-NMR (100 MHz, DMSO-d6): δ 61.9 (C-4′), 82.2 (C-5′), 151.3
(C-3′), 154.3 (C-2), 168.2 (CO), 113.8, 115.7, 117.7, 123.8, 126.9,
127.8, 128.9, 129.5, 130.6, 131.7, 132.9, 134.8, 138.8, 143.8,
144.7 (aromatic carbons) ppm; MS (m/z): 526.43 [M+]; Anal.
Calcd. for C29H21Cl2N5O: C, 66.28; H, 4.07; N, 13.44; Found: C,
66.17; H, 4.02; N, 13.30%.
(400 MHz, DMSO-d6): δ 5.16 (d, 1H, C4′-H, J= 7.4 Hz), 5.33 (d, 1H,
C5′-H, J= 7.4 Hz), 6.61–7.94 (m, 19H, Ar–H), 8.40 (bs, 1H, NH)
ppm; 13C-NMR (100 MHz, DMSO-d6): δ 63.5 (C-4′), 83.5 (C-5′),
152.6 (C-3′), 168.7 (CO), 169.3 (C-2), 113.5, 117.5, 121.1, 121.8,
124.6, 125.2, 125.7, 126.2, 127.5, 128.4, 128.7, 129.3, 129.8, 131.5,
134.2, 143.2, 143.8, 149.2 (aromatic carbons) ppm; MS (m/z): 474.59
[M+]; Anal. Calcd. for C29H22N4OS: C, 73.46; H, 4.69; N, 11.97;
Found: C, 73.39; H, 4.67; N, 11.81%.
N-(Benzothiazol-2-yl)-3′,5′-bis(4-methylphenyl)-4′,5′-dihydro-
N-(Benzoxazol-2-yl)-4′,5′-dihydro-3′,5′-diarylisoxazole-
4′-carboxamide (11)/N-(benzothiazol-2-yl)-4′,5′-dihydro-
3′,5′-diarylisoxazole-4′-carboxamide (12)/N-(1H-benzimi-
dazol-2-yl)-4′,5′-dihydro-3′,5′-diarylisoxazole-4′-carboxamide
1′-phenyl-1′H-pyrazole-4′-carboxamide (9b).
White solid
(0.39 g, 79%); m.p. 245–247°C; IR (KBr): 1571 (C¼N), 1657
(C¼O), 3275 (NH) cmꢀ1
;
1H-NMR (400MHz, DMSO-d6): δ
2.36 and 2.39 (s, 6H, Ar–CH3), 5.13 (d, 1H, C4′-H, J = 7.2 Hz),
5.30 (d, 1H, C5′-H, J = 7.2 Hz), 6.52–7.90 (m, 17H, Ar–H), 8.38
(bs, 1H, NH) ppm; 13C-NMR (100 MHz, DMSO-d6): δ 23.8 and
24.3 (Ar–CH3), 63.0 (C-4′), 83.1 (C-5′), 152.3 (C-3′), 168.2
(CO), 169.1 (C-2), 113.2, 117.3, 120.6, 121.7, 124.3, 125.1,
125.6, 126.1, 127.3, 128.1, 128.4, 129.2, 129.7, 131.2, 134.3,
143.1, 143.5, 148.7 (aromatic carbons) ppm; MS (m/z): 502.65
[M+]; Anal. Calcd. for C31H26N4OS: C, 74.14; H, 5.21; N, 11.27;
Found: C, 74.08; H, 5.22; N, 11.15%.
(13).
General procedure. A mixture of 5/6/7 (1.0 mmol),
araldoxime (1.2 mmol), CAT (0.33 g, 1.2 mmol) and methanol
(20 mL) was refluxed for 17–20 h. The precipitated inorganic
salts were filtered off. The filtrate was concentrated, and the
residue was extracted with dichloromethane. The organic layer
was washed with water, brine and dried (an. Na2SO4). The
solvent was removed under vacuum. The resultant residue was
purified by column chromatography (silica gel, 60–120mesh)
using hexane/ethyl acetate (4:1) as eluent.
N-(Benzothiazol-2-yl)-3′,5′-bis(4-chlorophenyl)-4′,5′-dihydro-
N-(Benzoxazol-2-yl)-4′,5′-dihydro-3′,5′-diphenylisoxazole-4′-
carboxamide (11a). White solid (0.27 g, 72%); m.p. 209–211°C;
IR (KBr): 1570 (C¼N), 1660 (C¼O), 3278 (NH) cmꢀ1; 1H-NMR
(400 MHz, DMSO-d6): δ 5.07 (d, 1H, C4′-H, J = 6.9 Hz), 5.42 (d,
1H, C5′-H, J = 7.4 Hz), 7.01–7.65 (m, 14H, Ar–H), 8.39 (bs, 1H,
NH) ppm; 13C-NMR (100 MHz, DMSO-d6): δ 61.5 (C-4′), 83.6
(C-5′), 153.1 (C-3′), 163.4 (C-2), 168.5 (CO), 110.5, 119.4,
1′-phenyl-1′H-pyrazole-4′-carboxamide (9c).
White solid
(0.45 g, 83%); m.p. 288–290°C; IR (KBr): 1585 (C¼N), 1668
(C¼O), 3307 (NH) cmꢀ1
;
1H-NMR (400MHz, DMSO-d6): δ
5.19 (d, 1H, C4′-H, J = 7.6 Hz), 5.35 (d, 1H, C5′-H, J = 7.6 Hz),
6.67–8.13 (m, 17H, Ar–H), 8.43 (bs, 1H, NH) ppm; 13C-NMR
(100MHz, DMSO-d6): δ 64.1 (C-4′), 83.9 (C-5′), 152.8 (C-3′),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

744
S. Durgamma, P. R. Reddy, V. Padmavathi, and A. Padmaja
Vol 53
123.6, 124.5, 127.2, 127.8, 128.4, 129.5, 129.8, 131.5, 134.5,
140.5, 141.3, 150.8 (aromatic carbons) ppm; MS (m/z): 383.40
[M+]; Anal. Calcd. for C23H17N3O3: C, 72.01; H, 4.49; N, 11.08;
Found: C, 72.05; H, 4.47; N, 10.96%.
N-(Benzoxazol-2-yl)-3′,5′-bis(4-methylphenyl)-4′,5′-dihydroisoxazole-
4′-carboxamide (11b). White solid (0.27 g, 67%); m.p. 194–195°C; IR
N-(1H-Benzimidazol-2-yl)-4′,5′-dihydro-3′,5′-diphenylisoxazole-
4′-carboxamide (13a). Brown solid (0.29 g, 78%); m.p. 268–270°C;
1
IR (KBr): 1568 (C¼N), 1655 (C¼O), 3261 (NH) cmꢀ1; H-NMR
(400 MHz, DMSO-d6): δ 4.98 (d, 1H, C4′-H, J= 6.5 Hz), 5.37 (d, 1H,
C5′-H, J=6.5Hz), 7.19–7.72 (m, 14H, Ar–H), 8.37 (bs, 1H, NH),
12.82 (bs, 1H, imidazole-NH) ppm; 13C-NMR (100 MHz,
DMSO-d6): δ 60.4 (C-4′), 83.1 (C-5′), 152.5 (C-3′), 153.9 (C-2),
168.0 (CO), 115.4, 123.8, 127.1, 127.7, 128.6, 129.2, 129.7, 131.7,
134.5, 138.7, 140.8 (aromatic carbons) ppm; MS (m/z): 382.42 [M+];
Anal. Calcd. for C23H18N4O2: C, 72.33; H, 4.76; N, 14.83; Found: C,
72.24; H, 4.74; N, 14.65%.
(KBr): 1565 (C¼N), 1654 (C¼O), 3265 (NH) cmꢀ1
;
1H-NMR
(400 MHz, DMSO-d6): δ 2.30 and 2.33 (s, 6H, Ar–CH3), 5.03 (d, 1H,
C4′-H, J= 6.8 Hz), 5.39 (d, 1H, C5′-H, J=6.8Hz), 6.94–7.60 (m, 12H,
Ar–H), 8.35 (bs, 1H, NH) ppm; 13C-NMR (100 MHz,
DMSO-d6): δ 24.3 and 25.1 (Ar–CH3), 61.1 (C-4′), 83.4 (C-5′),
152.4 (C-3′), 162.9 (C-2), 168.3 (CO), 110.2, 119.3, 123.1, 124.2,
127.1, 127.6, 128.0, 129.3, 129.4, 131.2, 134.3, 140.1, 141.2,
150.5 (aromatic carbons) ppm; MS (m/z): 411.47 [M+·]; Anal.
Calcd. for C25H21N3O3: C, 73.04; H, 5.15; N, 10.31; Found: C,
72.98; H, 5.14; N, 10.21%.
N-(1H-Benzimidazol-2-yl)-3′,5′-bis(4-methylphenyl)-4′,5′-
dihydroisoxazole-4′-carboxamide (13b).
76%); m.p. 255–257°C; IR (KBr): 1563 (C¼N), 1650 (C¼O),
3254 (NH) cmꢀ1 1H-NMR (400 MHz, DMSO-d6): δ 2.28 and
White solid (0.31 g,
;
2.31 (s, 6H, Ar–CH3), 4.95 (d, 1H, C4′–H, J = 6.3 Hz), 5.31 (d,
1H, C5′-H, J = 6.3 Hz), 7.15–7.64 (m, 12H, Ar–H), 8.32 (bs, 1H,
NH), 12.78 (bs, 1H, imidazole-NH) ppm; 13C-NMR (100 MHz,
DMSO-d6): δ 24.1 and 25.0 (Ar–CH3), 60.1 (C-4′), 82.9 (C-5′),
152.1 (C-3′), 153.2 (C-2), 167.6 (CO), 115.1, 123.2, 126.5, 127.4,
128.4, 129.0, 129.5, 131.2, 134.3, 138.2, 140.3 (aromatic carbons)
ppm; MS (m/z): 410.48 [M+]; Anal. Calcd. for C25H22N4O2: C,
73.21; H, 5.44; N, 13.78; Found: C, 73.15; H, 5.40; N, 13.65%.
N-(1H-Benzimidazol-2-yl)-3′,5′-bis(4-chlorophenyl)-4′,5′-
N-(Benzoxazol-2-yl)-3′,5′-bis(4-chlorophenyl)-4′,5′-dihydroisoxazole-
4′-carboxamide (11c). White solid (0.33 g, 75%); m.p. 216–218°C;
1
IR (KBr): 1580 (C¼N), 1666 (C¼O), 3289 (NH) cmꢀ1; H-NMR
(400 MHz, DMSO-d6): δ 5.09 (d, 1H, C4′-H, J= 7.1 Hz), 5.46 (d,
1H, C5′-H, J= 7.1 Hz), 7.06–7.71 (m, 12H, Ar–H), 8.41 (bs, 1H,
NH) ppm; 13C-NMR (100 MHz, DMSO-d6): δ 62.2 (C-4′), 83.8
(C-5′), 153.6 (C-3′), 163.7 (C-2), 168.8 (CO), 110.7, 119.6,
123.8, 124.7, 127.5, 127.9, 129.1, 129.6, 129.9, 131.8, 134.7,
140.9, 141.6, 151.1 (aromatic carbons) ppm; MS (m/z): 452.30
[M+]; Anal. Calcd. for C23H15Cl2N3O3: C, 61.21; H, 3.31; N,
9.49; Found: C, 61.08; H, 3.34; N, 9.29%.
dihydroisoxazole-4′-carboxamide (13c).
Brown solid (0.37 g,
84%); m.p. 277–279°C; IR (KBr): 1578 (C¼N), 1659 (C¼O),
3275 (NH) cmꢀ1; 1H-NMR (400 MHz, DMSO-d6): δ 5.02 (d, 1H,
C4′-H, J = 6.7 Hz), 5.40 (d, 1H, C5′-H, J = 6.7 Hz), 7.21–7.75 (m,
12H, Ar–H), 8.38 (bs, 1H, NH), 12.84 (bs, 1H, imidazole-NH)
ppm; 13C-NMR (100 MHz, DMSO-d6): δ 61.3 (C-4′), 83.4 (C-5′),
152.7 (C-3′), 154.3 (C-2), 168.3 (CO), 115.7, 123.9, 127.2, 127.9,
128.8, 129.3, 129.8, 131.8, 134.9, 138.8, 141.1 (aromatic carbons)
ppm; MS (m/z): 451.32 [M+]; Anal. Calcd. for C23H16Cl2N4O2:
C, 61.30; H, 3.59; N, 12.56; Found: C, 61.21; H, 3.57; N, 12.41%.
N-(Benzoxazol-2-yl)-1′-phenyl-3′,5′-diaryl-1′H-pyrazole-
4′-carboxamide (14)/N-(benzothiazol-2-yl)-1′-phenyl-3′,5′-
diaryl-1′H-pyrazole-4′-carboxamide (15)/N-(1H-benzimidazol-
2-yl)-1′-phenyl-3′,5′-diaryl-1′H-pyrazole-4′-carboxamide (16)/
N-(benzoxazol-2-yl)-3′,5′-diarylisoxazole-4′-carboxamide (17)/
N-(benzothiazol-2-yl)-3′,5′-diarylisoxazole-4′-carboxamide (18)/
N-(1H-benzimidazol-2-yl)-3′,5′-diarylisoxazole-4′-carboxamide
(19). General procedure: A solution of 8/9/10/11/12/13 (1 mmol)
in xylene (10 mL) and chloranil (1.2 mmol) were refluxed for 24–28 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 was removed in vacuo. The solid obtained was purified
by recrystallization from 2-propanol.
N-(Benzothiazol-2-yl)-4′,5′-dihydro-3′,5′-diphenylisoxazole-4′-
carboxamide (12a). White solid (0.30g, 77%); m.p. 238–240°C;
IR (KBr): 1583 (C¼N), 1665 (C¼O), 3295 (NH) cmꢀ1; 1H-NMR
(400 MHz, DMSO-d6): δ 5.11 (d, 1H, C4′-H, J = 7.2 Hz),
5.49 (d, 1H, C5′-H, J = 7.2 Hz), 6.85–8.10 (m, 14H, Ar–H),
8.42 (bs, 1H, NH) ppm; 13C-NMR (100 MHz, DMSO-d6):
δ 62.9 (C-4′), 83.9 (C-5′), 154.2 (C-3′), 168.9 (CO), 169.6
(C-2), 121.1, 121.6, 124.3, 125.2, 125.7, 126.3, 127.8,
128.5, 129.2, 129.7, 131.5, 134.6, 140.3, 149.3 (aromatic
carbons) ppm; MS (m/z): 399.47 [M+]; Anal. Calcd. for
C23H17N3O2S: C, 69.30; H, 4.34; N, 10.79; Found: C,
69.15; H, 4.29; N, 10.52%.
N-(Benzothiazol-2-yl)-3′,5′-bis(4-methylphenyl)-4′,5′-dihydroisoxazole-
4′-carboxamide (12b). White solid (0.29 g, 70%); m.p. 226–228°C;
1
IR (KBr): 1575 (C¼N), 1661 (C¼O), 3286 (NH) cmꢀ1; H-NMR
(400 MHz, DMSO-d6): δ 2.32 and 2.37 (s, 6H, Ar–CH3), 5.06 (d,
1H, C4′-H, J= 6.9 Hz), 5.44 (d, 1H, C5′-H, J=6.9Hz), 6.81–8.05
(m, 12H, Ar–H), 8.40 (bs, 1H, NH) ppm; 13C-NMR (100 MHz,
DMSO-d6): δ 24.5 and 25.8 (Ar–CH3), 62.4 (C-4′), 83.5 (C-5′),
153.7 (C-3′), 168.4 (CO), 169.2 (C-2), 121.0, 121.4, 124.1, 125.1,
125.4, 126.1, 127.5, 128.2, 129.1, 129.4, 131.2, 134.3, 140.2, 148.7
(aromatic carbons) ppm; MS (m/z): 427.54 [M+]; Anal. Calcd. for
C25H21N3O2S: C, 70.30; H, 5.03; N, 9.74; Found: C, 70.23; H,
4.95; N, 9.83%.
N-(Benzoxazol-2-yl)-1′,3′,5′-triphenyl-1′H-pyrazole-4′-carboxamide
(14a). White solid (0.31 g, 68%); m.p. 210–212°C; IR (KBr): 1570
(C¼N), 1617 (C¼C), 1662 (C¼O), 3283 (NH) cmꢀ1
;
1H-NMR
(400 MHz, DMSO-d6): δ 6.92–7.51 (m, 19H, Ar–H), 8.54 (bs, 1H,
NH) ppm; 13C-NMR (100 MHz, DMSO-d6): δ 137.3 (C-4′), 147.5
(C-5′), 154.6 (C-3′), 163.9 (C-2), 167.6 (CO), 110.5, 119.4, 120.5,
123.8, 124.7, 126.5, 127.3, 127.8, 128.1, 128.6, 129.4, 129.7, 130.2,
133.4, 133.8, 139.6, 141.7, 150.3 (aromatic carbons) ppm; MS
(m/z): 456.51 [M+]; Anal. Calcd. for C29H20N4O2: C, 76.43; H,
4.46; N, 12.38; Found: C, 76.30; H, 4.42; N, 12.27%.
N-(Benzothiazol-2-yl)-3′,5′-bis(4-chlorophenyl)-4′,5′-dihydroisoxazole-
4′-carboxamide (12c). White solid (0.37 g, 81%); m.p. 257–259°C; IR
1
(KBr): 1585 (C¼N), 1670 (C¼O), 3310 (NH) cmꢀ1; H-NMR
(400 MHz, DMSO-d6): δ 5.15 (d, 1H, C4′-H, J = 7.4 Hz), 5.52
(d, 1H, C5′-H, J = 7.4 Hz), 6.90–8.24 (m, 12H, Ar–H), 8.45 (bs,
1H, NH) ppm; 13C-NMR (100 MHz, DMSO-d6): δ 63.3 (C-4′),
84.1 (C-5′), 154.6 (C-3′), 169.1 (CO), 169.9 (C-2), 121.5,
121.9, 124.6, 125.5, 125.9, 126.7, 127.9, 128.8, 129.4, 129.9,
132.5, 134.8, 140.5, 149.7 (aromatic carbons) ppm; MS (m/z):
468.37 [M+]; Anal. Calcd. for C23H15Cl2N3O2S: C, 58.94; H,
3.22; N, 9.11; Found: C, 58.98; H, 3.23; N, 8.97%.
N-(Benzoxazol-2-yl)-3′,5′-bis(4-methylphenyl)-1′-phenyl-1′H-
pyrazole-4′-carboxamide (14b). White solid (0.31 g, 65%); m.p.
197–199°C; IR (KBr): 1567 (C¼N), 1611 (C¼C), 1657 (C¼O),
3279 (NH) cmꢀ1 1H-NMR (400 MHz, DMSO-d6): δ 2.36 and
;
2.39 (s, 6H, Ar–CH3), 6.90–7.48 (m, 17H, Ar–H), 8.51 (bs, 1H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2016
Pyrazole, Isoxazole, Antioxidant Activity
745
NH) ppm; 13C-NMR (100 MHz, DMSO-d6): δ 22.5 and 22.6
(Ar–CH3), 137.0 (C-4′), 147.1 (C-5′), 154.3 (C-3′), 163.4 (C-2),
167.1 (CO), 110.3, 119.2, 120.4, 123.5, 124.4, 126.2, 127.2,
127.5, 128.0, 128.5, 129.2, 129.5, 130.1, 133.0, 133.7, 139.1,
141.3, 149.7 (aromatic carbons) ppm; MS (m/z): 484.56 [M+];
Anal. Calcd. for C31H24N4O2: C, 76.94; H, 5.05; N, 11.74;
Found: C, 76.84; H, 4.99; N, 11.56%.
N-(1H-Benzimidazol-2-yl)-3′,5′-bis(4-methylphenyl)-1′-phenyl-
1′H-pyrazole-4′-carboxamide (16b). Brown solid (0.30 g, 64%);
m.p. 258–260°C; IR (KBr): 1564 (C¼N), 1602 (C¼C), 1649
(C¼O), 3252 (NH) cmꢀ1; 1H-NMR (400 MHz, DMSO-d6): δ 2.35
and 2.37 (s, 6H, Ar–CH3), 7.07–7.67 (m, 17H, Ar–H), 8.45 (bs,
1H, NH), 12.80 (bs, 1H, imidazole-NH) ppm; 13C-NMR
(100 MHz, DMSO-d6): δ 22.1 and 22.4 (Ar–CH3), 136.2 (C-4′),
145.2 (C-5′), 153.8 (C-3′), 154.4 (C-2), 166.9 (CO), 115.1, 120.3,
123.2, 126.1, 127.0, 127.5, 128.1, 128.5, 129.1, 129.4, 129.7,
133.1, 133.9, 138.4, 139.1 (aromatic carbons) ppm; MS (m/z):
483.57 [M+]; Anal. Calcd. for C31H25N5O: C, 77.09; H, 5.23; N,
14.65; Found: C, 77.00; H, 5.21; N, 14.48%.
N-(Benzoxazol-2-yl)-3′,5′-bis(4-chlorophenyl)-1′-phenyl-1′H-
pyrazole-4′-carboxamide (14c). White solid (0.37 g, 71%); m.p.
223–225°C; IR (KBr): 1582 (C¼N), 1619 (C¼C), 1669 (C¼O),
1
3291 (NH) cmꢀ1; H-NMR (400 MHz, DMSO-d6): δ 6.96–7.55
(m, 17H, Ar–H), 8.58 (bs, 1H, NH) ppm; 13C-NMR (100 MHz,
DMSO-d6): δ 137.7 (C-4′), 147.9 (C-5′), 154.9 (C-3′), 164.2
(C-2), 167.8 (CO), 110.8, 119.7, 120.7, 123.9, 124.8, 126.7,
127.4, 127.9, 128.3, 129.1, 129.6, 129.8, 130.7, 133.8, 134.2,
139.9, 142.1, 150.8 (aromatic carbons) ppm; MS (m/z): 525.40
[M+]; Anal. Calcd. for C29H18Cl2N4O2: C, 66.42; H, 3.47; N,
10.86; Found: C, 66.30; H, 3.45; N, 10.66%.
N-(1H-Benzimidazol-2-yl)-3′,5′-bis(4-chlorophenyl)-1′-phenyl-
1′H-pyrazole-4′-carboxamide (16c). Brown solid (0.36 g, 69%);
m.p. 286–288°C; IR (KBr): 1579 (C¼N), 1612 (C¼C), 1663
(C¼O), 3275 (NH) cmꢀ1
;
1H-NMR (400 MHz, DMSO-d6): δ
7.16–7.73 (m, 17H, Ar–H), 8.52 (bs, 1H, NH), 12.88 (bs, 1H,
imidazole-NH) ppm; 13C-NMR (100 MHz, DMSO-d6): δ 136.9
(C-4′), 146.8 (C-5′), 154.7 (C-3′), 155.7 (C-2), 167.6 (CO), 115.8,
120.7, 123.6, 126.7, 127.4, 127.9, 128.4, 128.8, 129.3, 129.8,
130.5, 133.4, 134.5, 138.8, 139.9 (aromatic carbons) ppm; MS
(m/z): 524.41 [M+]; Anal. Calcd. for C29H19Cl2N5O: C, 66.53;
H, 3.69; N, 13.54; Found: C, 66.42; H, 3.65; N, 13.35%.
N-(Benzoxazol-2-yl)-3′,5′-diphenylisoxazole-4′-carboxamide
(17a). White solid (0.27 g, 71%); m.p. 202–204°C; IR (KBr):
N-(Benzothiazol-2-yl)-1′,3′,5′-triphenyl-1′H-pyrazole-4′-carboxamide
(15a). White solid (0.36 g, 77%); m.p. 258–260°C; IR (KBr): 1581
(C¼N), 1623 (C¼C), 1677 (C¼O), 3305 (NH) cmꢀ1
;
1H-NMR
(400 MHz, DMSO-d6): δ 7.25–8.19 (m, 19H, Ar–H), 8.56 (bs, 1H, NH)
ppm; 13C-NMR (100 MHz, DMSO-d6): δ 137.9 (C-4′), 148.7 (C-5′),
155.5 (C-3′), 168.2 (CO), 169.0 (C-2), 120.5, 121.4, 121.9, 124.8, 125.4,
125.8, 126.5, 127.2, 127.7, 128.2, 128.5, 129.3, 129.4, 130.5, 133.2,
133.6, 139.5, 149.3 (aromatic carbons) ppm; MS (m/z): 472.58 [M+];
Anal. Calcd. for C29H20N4OS: C, 73.78; H, 4.30; N, 11.99; Found: C,
73.71; H, 4.27; N, 11.86%.
1580 (C¼N), 1620 (C¼C), 1668 (C¼O), 3285 (NH) cmꢀ1; H-
1
NMR (400 MHz, DMSO-d6): δ 7.14–7.66 (m, 14H, Ar–H), 8.55
(bs, 1H, NH) ppm; 13C-NMR (100 MHz, DMSO-d6): δ 137.1
(C-4′), 151.2 (C-5′), 156.1 (C-3′), 163.8 (C-2), 168.1 (CO),
110.5, 119.6, 123.4, 124.7, 127.2, 127.8, 128.4, 128.7, 129.3,
129.7, 130.7, 133.3, 141.6, 150.4 (aromatic carbons) ppm; MS
(m/z): 381.39 [M+]; Anal. Calcd. for C23H15N3O3: C, 72.49; H,
4.01; N, 11.15; Found: C, 72.43; H, 3.96; N, 11.02%.
N-(Benzothiazol-2-yl)-3′,5′-bis(4-methylphenyl)-1′-phenyl-1′
H-pyrazole-4′-carboxamide (15b). White solid (0.36 g, 73%);
m.p. 236–238°C; IR (KBr): 1572 (C¼N), 1618 (C¼C), 1673
(C¼O), 3298 (NH) cmꢀ1
;
1H-NMR (400 MHz, DMSO-d6): δ
2.39 and 2.41 (s, 6H, Ar–CH3), 7.21–8.16 (m, 17H, Ar–H),
8.54 (bs, 1H, NH) ppm; 13C-NMR (100 MHz, DMSO-d6): δ
22.7 and 22.9 (Ar–CH3), 137.4 (C-4′), 148.2 (C-5′), 155.1 (C-3′),
167.1 (CO), 168.7 (C-2), 120.2, 121.1, 121.7, 124.3, 125.3,
125.6, 126.1, 127.0, 127.3, 128.1, 128.3, 129.1, 129.3, 129.8,
133.0, 133.4, 139.5, 149.1 (aromatic carbons) ppm; MS (m/z):
500.63 [M+]; Anal. Calcd. for C31H24N4OS: C, 74.52; H, 4.84; N,
11.47; Found: C, 74.38; H, 4.83; 11.19%.
N-(Benzoxazol-2-yl)-3′,5′-bis(4-methylphenyl)isoxazole-4′-
carboxamide (17b). White solid (0.26 g, 65%); m.p. 188–190°C;
IR (KBr): 1572 (C¼N), 1615 (C¼C), 1665 (C¼O), 3277 (NH)
1
cmꢀ1; H-NMR (400 MHz, DMSO-d6): δ 2.30 and 2.32 (s, 6H,
Ar–CH3), 7.08–7.60 (m, 12H, Ar–H), 8.53 (bs, 1H, NH) ppm;
13C-NMR (100MHz, DMSO-d6): δ 22.4 and 23.6 (Ar–CH3),
136.4 (C-4′), 150.8 (C-5′), 155.6 (C-3′), 163.4 (C-2), 167.2 (CO),
110.2, 119.4, 123.1, 124.3, 127.1, 127.6, 128.0, 128.5, 129.1,
129.5, 130.2, 133.1, 141.3, 150.1 (aromatic carbons) ppm; MS
(m/z): 409.45 [M+]; Anal. Calcd. for C25H19N3O3: C, 73.26; H,
4.66; N, 10.10; Found: C, 73.34; H, 4.68; N, 10.26%.
N-(Benzothiazol-2-yl)-3′,5′-bis(4-chlorophenyl)-1′-phenyl-1′
H-pyrazole-4′-carboxamide (15c). White solid (0.42 g, 79%);
m.p. 280–282°C; IR (KBr): 1584 (C¼N), 1627 (C¼C), 1681
(C¼O), 3314 (NH) cmꢀ1
;
1H-NMR (400 MHz, DMSO-d6): δ
7.28–8.22 (m, 17H, Ar–H), 8.62 (bs, 1H, NH) ppm; 13C-NMR
(100MHz, DMSO-d6): δ 138.3 (C-4′), 149.3 (C-5′), 156.1 (C-3′),
168.4 (CO), 169.5 (C-2), 120.6, 121.6, 122.2, 124.9, 125.7,
125.9, 126.7, 127.4, 127.9, 128.4, 128.8, 129.5, 129.9, 130.7,
133.5, 133.8, 139.7, 149.9 (aromatic carbons) ppm; MS (m/z):
541.47 [M+]; Anal. Calcd. for C29H18Cl2N4OS: C, 64.49; H, 3.30;
N, 10.60; Found: C, 64.33; H, 3.35; N, 10.35%.
N-(Benzoxazol-2-yl)-3′,5′-bis(4-chlorophenyl)isoxazole-4′-
carboxamide (17c). White solid (0.31 g, 70%); m.p. 215–217°C;
IR (KBr): 1583 (C¼N), 1625 (C¼C), 1670 (C¼O), 3298 (NH)
cmꢀ1 1H-NMR (400 MHz, DMSO-d6): δ 7.18–7.71 (m, 12H,
;
Ar–H), 8.59 (bs, 1H, NH) ppm; 13C-NMR (100 MHz, DMSO-d6):
δ 137.5 (C-4′), 151.8 (C-5′), 156.8 (C-3′), 164.1 (C-2), 168.4
(CO), 110.6, 119.9, 123.5, 124.8, 127.3, 127.9, 128.6, 128.9,
129.4, 129.5, 130.8, 133.9, 141.7, 150.7 (aromatic carbons) ppm;
MS (m/z): 450.28 [M+]; Anal. Calcd. for C23H13Cl2N3O3: C,
61.45; H, 2.94; N, 9.47; Found: C, 61.35; H, 2.91; N, 9.33%.
N-(Benzothiazol-2-yl)-3′,5′-diphenylisoxazole-4′-carboxamide
(18a). White solid (0.32 g, 82%); m.p. 242–244°C; IR (KBr):
N-(1H-Benzimidazol-2-yl)-1′,3′,5′-triphenyl-1′H-pyrazole-4′-
carboxamide (16a). Brown solid (0.30 g, 66%); m.p. 271–273°C;
IR (KBr): 1573 (C¼N), 1607 (C¼C), 1656 (C¼O), 3261 (NH)
cmꢀ1 1H-NMR (400 MHz, DMSO-d6): δ 7.10–7.72 (m, 19H,
;
Ar–H), 8.49 (bs, 1H, NH), 12.85 (bs, 1H, imidazole-NH) ppm;
13C-NMR (100 MHz, DMSO-d6): δ 136.5 (C-4′), 146.4 (C-5′),
154.2 (C-3′), 154.9 (C-2), 167.1 (CO), 115.5, 120.5, 123.3,
126.3, 127.1, 127.8, 128.2, 128.7, 129.2, 129.5, 130.1, 133.3,
134.2, 138.7, 139.5 (aromatic carbons) ppm; MS (m/z): 455.52
[M+]. Anal. Calcd. for C29H21N5O: C, 76.41; H, 4.72; N,
15.48; Found: C, 76.47; H, 4.65; N, 15.37%.
1
1578 (C¼N), 1622 (C¼C), 1680 (C¼O), 3311 (NH) cmꢀ1; H-
NMR (400 MHz, DMSO-d6): δ 7.25–8.05 (m, 14H, Ar–H), 8.60
(bs, 1H, NH) ppm; 13C-NMR (100 MHz, DMSO-d6): δ 137.3
(C-4′), 152.5 (C-5′), 156.7 (C-3′), 168.5 (CO), 169.5 (C-2),
121.3, 121.7, 124.3, 125.2, 125.6, 127.3, 127.8, 128.2, 128.8,
129.1, 129.4, 130.5, 133.4, 149.3 (aromatic carbons) ppm; MS
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

746
S. Durgamma, P. R. Reddy, V. Padmavathi, and A. Padmaja
Vol 53
(m/z): 397.46 [M+]; Anal. Calcd. for C23H15N3O2S: C, 69.57; H,
3.84; N, 10.75; Found: C, 69.50; H, 3.80; N, 10.57%.
REFERENCES AND NOTES
N-(Benzothiazol-2-yl)-3′,5′-bis(4-methylphenyl)isoxazole-4′-
carboxamide (18b). White solid (0.34 g, 80%); m.p. 221–223°C;
IR (KBr): 1576 (C¼N), 1617 (C¼C), 1675 (C¼O), 3304 (NH)
[1] Elguero, J.; Goya, P.; Jagerovic, N.; Silva, A. M. S. Targets
Heterocycl Syst 2002, 6, 52.
[2] Sheng, C.; Xu, H.; Wang, W.; Cao, Y.; Dong, G.; Wang, S.;
Che, X.; Ji, H.; Miao, Z.; Yao, J.; Zhang, W. Eur J Med Chem 2010,
45, 3531.
[3] Satyendra, R. V.; Vishnumurthy, K. A.; Vagdevi, H. M.;
Rajesh, K. P.; Manjunatha, H.; Shruthi, A. Eur J Med Chem 2011, 46,
3078.
[4] Eicher, T.; Hauptmann, S. The Chemistry of Heterocycles,
Wiley-VCH GmbH & Co. KGaA: Weinheim, 2003.
[5] Shi, D. Q.; Rong, S. F.; Dou, G. L. Synth Commun 2010, 40,
2302.
1
cmꢀ1; H-NMR (400 MHz, DMSO-d6): δ 2.35 and 2.39 (s, 6H,
Ar–CH3), 7.18–8.03 (m, 12H, Ar–H), 8.54 (bs, 1H, NH) ppm;
13C-NMR (100 MHz, DMSO-d6): δ 22.7 and 23.8 (Ar–CH3),
136.7 (C-4′), 151.9 (C-5′), 156.2 (C-3′), 168.3 (CO), 169.3 (C-2),
121.2, 121.6, 124.1, 125.0, 125.5, 127.1, 127.4, 128.1, 128.6,
129.0, 129.3, 130.3, 133.2, 149.0 (aromatic carbons) ppm; MS
(m/z): 425.52 [M+]; Anal. Calcd. for C25H19N3O2S: C, 70.70; H,
4.52; N, 10.11; Found: C, 70.57; H, 4.50; N, 9.87%.
[6] Tong, Y. S.; Bouska, J. J.; Ellis, P. A.; Johnson, E. F.;
Leverson, J.; Liu, X. S.; Marcotte, P. A.; Olson, A. M.; Osterling, D. J.;
Przytulinska, M.; Rodriguez, L. E.; Shi, Y.; Soni, N.; Stavropoulos, J.;
Thomas, S.; Donawho, C. K.; Frost, D. J.; Luo, Y.; Giranda, V. L.;
Penning, T. D. J Med Chem 2009, 52, 6803.
N-(Benzothiazol-2-yl)-3′,5′-bis(4-chlorophenyl)isoxazole-4′-
carboxamide (18c). White solid (0.39 g, 85%); m.p. 250–252°C;
IR (KBr): 1584 (C¼N), 1628 (C¼C), 1687 (C¼O), 3328 (NH)
Ar–H), 8.63 (bs, 1H, NH) ppm; 13C-NMR (100 MHz, DMSO-d6):
δ 137.9 (C-4′), 152.7 (C-5′), 157.1 (C-3′), 168.9 (CO), 169.8
(C-2), 121.5, 121.9, 124.7, 125.4, 125.8, 127.6, 127.9, 128.3,
128.9, 129.5, 129.9, 130.9, 133.6, 149.7 (aromatic carbons) ppm;
MS (m/z): 466.35 [M+]; Anal. Calcd. for C23H13Cl2N3O2S: C,
59.28; H, 2.82; N, 9.08; Found: C, 59.24; H, 2.81; N, 9.01%.
N-(1H-Benzimidazol-2-yl)-3′,5′-diphenylisoxazole-4′-carboxamide
(19a). Brown solid (0.29 g, 78%); m.p. 203–205°C; IR (KBr): 1575
cmꢀ1 1H-NMR (400MHz, DMSO-d6): δ 7.26–8.20 (m, 12H,
;
[7] Kalai, T.; Balog, M.; Szabo, A.; Gulyas, G.; Jeko, J.; Sumegi, B.;
Hideg, K. J Med Chem 2009, 52, 1619.
[8] Wustrow, D. J.; Capiris, T.; Rubin, R.; Knobelsdorf, J. A.;
Akunne, H.; Davis, M. D.; MacKenzie, R.; Pugsley, T. A.; Zoski, K. T.;
Heffner, T. G.; Wise, L. D. Bioorg Med Chem Lett 1998, 8, 2067.
[9] Kees, K. L.; Fitzgerald, J. J.; Steiner, K. E. Jr.; Mattes, J. F.;
Mihan, B.; Tosi, T.; Mondoro, D.; McCaleb, M. L. J Med Chem 1996,
39, 3920.
[10] Chen, H. S.; Li, Z. M.; Han, Y. F. J Agric Food Chem 2000,
48, 5312.
[11] Tanitame, A.; Oyamada, Y.; Ofuji, K.; Terauchi, H.;
Kawasaki, M.; Wachi, M.; Yamagishi, J. Bioorg Med Chem Lett 2005,
15, 4299.
[12] Meazz G.; Bettarini F.; La Porta P.; Piccardi P.; Signorini, E.;
Portoso, D.; Fornara L. Pest Manag Sci 2004, 60, 1178.
[13] Penning, T. D.; Talley, J. J.; Bertenshaw, S. R.; Carter, J. S.;
Collins, P. W.; Docter, S.; Graneto, M. J.; Lee, L. F.; Malecha, J. W.;
Miyashiro, J. M.; Rogers, R. S.; Rogier, D. J.; Yu, S. S.; Anderson, G. D.;
Burton, E. G.; Cogburn, J. N.; Gregory, S. A.; Koboldt, C. M.;
Perkins, W. E.; Seibert, K.; Veenhuizen, A. W.; Zhang, Y. Y.;
Isakson, P. C. J Med Chem 1997, 40, 1347.
[14] Daidone, G.; Raffa, D.; Maggio, B.; Plescia, F.; Cutuli, V. M. C.;
Mangano, N. G.; Caruso, A. Arch Pharm Pharm Med Chem 1999, 332, 50.
[15] Tomita, K.; Takahi, Y.; Ishizuka, R.; Kamamura, S.;
Nakagawa, M.; Ando, M.; Nakanishi, T.; Nakamura, T.; Udaira, H. Ann
Sankyo Res Lab 1973, 1, 25; Chem Abstr 1974, 80, 120808.
[16] Talley, J. J. Prog Med Chem 1999, 13, 201.
[17] Talley, J. J.; Brown, D. L.; Carter, J. S.; Graneto, M. J.;
Koboldt, C. M.; Masferrer, J. L.; Perkins, W. E.; Rogers, R. S.; Shaffer,
A. F.; Zhang, Y. Y.; Zweifel, B. S.; Seibert, K. J Med Chem 2000, 43,
775.
[18] Li, W.-T.; Hwang, D.-R.; Chen, C.-P.; Shen, C.-W.; Huang,
C.-L.; Chen, T.-W.; Lin, C.-H.; Chang, Y.-L.; Chang, Y.-Y.; Lo, Y.-K.;
Tseng, H.-Y.; Lin, C.-C.; Song, J.-S.; Chen, H.-C.; Chen, S.-J.; Wu, S.-H.;
Chen, C.-T. J Med Chem 2003, 46, 1706.
(C¼N), 1610 (C¼C), 1664 (C¼O), 3263 (NH) cmꢀ1
;
1H-NMR
(400 MHz, DMSO-d6): δ 7.25–7.77 (m, 14H, Ar–H), 8.52 (bs, 1H,
NH), 12.87 (bs, 1H, imidazole-NH) ppm; 13C-NMR (100 MHz,
DMSO-d6): δ 136.1 (C-4′), 149.5 (C-5′), 155.2 (C-3′), 156.7 (C-2),
167.3 (CO), 115.7, 123.6, 126.5, 127.3, 128.2, 128.8, 129.5, 129.7,
130.4, 133.5, 138.5 (aromatic carbons) ppm; MS (m/z): 380.41 [M+];
Anal. Calcd. for C23H16N4O2: C, 72.74; H, 4.30; N, 14.92; Found: C,
72.62; H, 4.24; N, 14.73%.
N-(1H-Benzimidazol-2-yl)-3′,5′-bis(4-methylphenyl)isoxazole-
4′-carboxamide (19b). Brown solid (0.30 g, 75%); m.p. 197–198°C;
IR (KBr): 1569 (C¼N), 1605 (C¼C), 1651 (C¼O), 3254 (NH) cmꢀ1
;
1H-NMR (400 MHz, DMSO-d6): δ 2.24 and 2.28 (s, 6H, Ar–CH3),
7.20–7.71 (m, 12H, Ar–H), 8.47 (bs, 1H, NH), 12.84 (bs, 1H,
imidazole-NH) ppm; 13C-NMR (100 MHz, DMSO-d6): δ 22.1 and
23.2 (Ar–CH3), 135.8 (C-4′), 149.3 (C-5′), 154.8 (C-3′), 156.2 (C-2),
167.0 (CO), 115.5, 123.3, 126.2, 127.1, 128.1, 128.5, 129.0, 129.4,
130.1, 133.2, 138.3 (aromatic carbons) ppm; MS (m/z): 408.47 [M+];
Anal. Calcd. for C25H20N4O2: C, 73.46; H, 4.97; N, 13.81; Found: C,
73.51; H, 4.94; N, 13.72%.
N-(1H-Benzimidazol-2-yl)-3′,5′-bis(4-chlorophenyl)isoxazole-
4′-carboxamide (19c). White solid (0.36 g, 81%); m.p. 232–234°C;
IR (KBr): 1582 (C¼N), 1614 (C¼C), 1668 (C¼O), 3276 (NH) cmꢀ1
;
1H-NMR (400 MHz, DMSO-d6): δ 7.29–7.80 (m, 12H, Ar–H), 8.56
(bs, 1H, NH), 12.89 (bs, 1H, imidazole-NH) ppm; 13C-NMR
(100 MHz, DMSO-d6): δ 136.3 (C-4′), 150.1 (C-5′), 155.5 (C-3′),
156.9 (C-2), 168.4 (CO), 115.9, 123.7, 126.9, 127.7, 128.4, 128.9,
129.6, 129.8, 130.5, 133.7, 138.9 (aromatic carbons) ppm; MS
(m/z): 449.30 [M+]; Anal. Calcd. for C23H14Cl2N4O2: C, 61.64;
H, 3.21; N, 12.75; Found: C, 61.48; H, 3.14; N, 12.47%.
[19] Just, G.; Dhal, K. Tetrahedron 1968, 24, 5251.
[20] Lokanath Rai, K. M.; Linganna, N.; Hassner, A.; Murthy, C. A.
Org Prep Proc Intl 1992, 24, 91.
[21] Kim, J. N.; Ryu, E. K. Synth Commun 1990, 20, 1373.
[22] Lokanath Rai, K. M.; Hassner, A. Synth Commun 1989, 19,
2799.
[23] Lokanath Rai, K. M.; Hassner, A. Synth Commun 1997, 27,
467.
[24] Hassner, A.; Lokanath Rai, K. M. Synthesis 1989, 57.
[25] Padmavathi, V.; Sumathi, R. P.; Chandrasekhar Babu, N.;
Bhaskar Reddy, D. J Chem Res (S), 1999, 610.
[26] Padmavathi, V.; Sumathi, R. P.; Venugopal Reddy, K.;
Somasekhar Reddy, A.; Bhaskar Reddy, D. Synth Commun 2000, 30,
4007.
Acknowledgments. The author A. Padmaja is thankful to
University Grants Commission (UGC), New Delhi for financial
assistance under major research project. One of the authors, S.
Durgamma, is grateful to UGC-BSR for the sanction of Junior
Research Fellowship. The authors are also thankful to Prof. Ch.
Appa Rao, Department of Biochemistry, S. V. University, Tirupati,
for providing necessary facilities to carry out the antioxidant activity.
[27] Padmavathi, V.; Jagan Mohan Reddy, B.; Venkata Subbaiah,
D. R. C. New J Chem 2004, 28, 1479.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2016
Pyrazole, Isoxazole, Antioxidant Activity
747
[28] Padmavathi, V.; Jagan Mohan Reddy, B.; Chandra Obula
[35] Marcocci, L.; Maguire, J. J.; Droy-Lefaix, M. T.; Packer, L.
Biochem Biophys Res Commun 1994, 201, 748.
[36] Ruch, R. J.; Cheng, S. J.; Klaunig, J. E. Carcinogenesis 1989,
10, 1003.
[37] Saritha, G.; Sarangapani, M.; Prasad, G.; Swathi, C. Der
Pharmacia Let 2011, 3, 427.
Reddy, B.; Padmaja, A. Tetrahedron 2005, 61, 2407.
[29] Zhou, C. H.; Wang Y. Curr Med Chem 2012, 19, 239.
[30] Wang, Y.; Zhou, C. H. Sci Sin Chim 2011, 41, 1429 (in Chinese).
[31] Simovic, D.; Di, M.; Marks, V.; Chatfield, D. C.; Rein, K. S.
J Org Chem 2007, 72, 650.
[38] Robert, W. H. III; Samuel, R.; Catherine, S. R.; Cynthia, B.;
Steven, A. R.; Andrew, T. S.; Christian, M. Bioorg Med Chem 2010,
18, 663.
[32] Burits, M.; Bucar, F. Phytother Res 2000, 14, 323.
[33] Cuendet, M.; Hostettmann, K.; Potterat, O. Helv Chim Acta
1997, 80, 1144.
[39] Vogel’s, A. I. Text Book of Practical Organic Chemistry 5th
edn. Longman Group UK Ltd.: London 1989.
[34] Green, L. C.; Wagner, D. A.; Glogowski, J.; Skipper, P. L.;
Wishnok, J. K. S. R. Anal Biochem 1982, 126, 131.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet