Synthesis of some new 4-styryltetrazolo[1,5-a]quinoxaline and 1-substituted-4-styryl[1,2,4]triazolo[4,3-a]quinoxaline derivatives as potent anticonvulsants

Article abstract of DOI:10.1016/j.ejmech.2008.06.006

4-Methyltetrazolo[1,5-a]quinoxaline (3) was prepared by the azide cyclocondensation of 2-chloro-3-methylquinoxaline (2). The reaction of 3 with aromatic aldehydes furnished 4-styryltetrazolo[1,5-a]quinoxalines (4a-f). Compound 2, on treatment with hydrazi

Full text of DOI:10.1016/j.ejmech.2008.06.006

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European Journal of Medicinal Chemistry 44 (2009) 1135e1143
http://www.elsevier.com/locate/ejmech
Original article
Synthesis of some new 4-styryltetrazolo[1,5-a]quinoxaline and
1-substituted-4-styryl[1,2,4]triazolo[4,3-a]quinoxaline
derivatives as potent anticonvulsants
c
Shivananda Wagle a, Airody Vasudeva Adhikari b, , Nalilu Suchetha Kumari
*
a Strides Research and Specialty Chemicals Ltd., New Mangalore 575 011, India
b Department of Chemistry, National Institute of Technology Karnataka, Surathkal, Srinivasnagar 575 025, Karnataka, India
c Department of Biochemistry, Justice K.S. Hegde Medical Academy, Deralakatte, Mangalore, India
Received 13 September 2007; received in revised form 5 June 2008; accepted 13 June 2008
Available online 20 June 2008
Abstract
4-Methyltetrazolo[1,5-a]quinoxaline (3) was prepared by the azide cyclocondensation of 2-chloro-3-methylquinoxaline (2). The reaction of
3 with aromatic aldehydes furnished 4-styryltetrazolo[1,5-a]quinoxalines (4aef). Compound 2, on treatment with hydrazine hydrate gave
2-hydrazino-3-methylquinoxaline (5). The ring closure of 5 was achieved by the reaction of orthoesters and trifluoroacetic acid to yield 4-
methyl-1-(substituted)[1,2,4]triazolo[4,3-a]quinoxalines (7aec). Further, reaction of 7aec with different aromatic aldehydes furnished the title
compounds, 4-styryl-1-(substituted)[1,2,4]triazolo[4,3-a]quinoxalines (8aei) in good yield. In another scheme, the hydrazino compound 5 was
treated with different aromatic aldehydes to yield corresponding N-arylidenehydrazino quinoxalines (6aed). Further, the oxidative cyclization of
hydrazones by nitrobenzene yielded 1-aryl-4-methyl[1,2,4]triazolo[4,3-a]quinoxalines (7deg), which on condensation with aromatic aldehydes
gave the title compounds, 1-aryl-4-styryl[1,2,4]triazolo[4,3-a]quinoxalines (8jeu). The newly synthesized compounds have been characterized
1
by FTIR, H NMR, 13C NMR and mass spectral data, followed by elemental analysis. Some of the compounds were screened for in vivo
anticonvulsant activity. Few of them exhibited promising results.
Ó 2008 Elsevier Masson SAS. All rights reserved.
Keywords: Quinoxaline; 1,2,4-Triazolo; Styryl; Tetrazolo; Hydrazones; Anticonvulsant activity
1. Introduction
from 1,2,4-triazoles have been shown to display awide spectrum
of biological activities. Moreover, a few fused triazoles to
different heterocycles have been found to be significant anticon-
vulsant [11e15] and tranquillizing agents [16]. Also, 1,2,4-
triazolo quinoxalines have been reported as antidepressant,
cardiotonic and antifatigue agents [17]. Further, hydrazino
quinoxalines and their cyclic analogues were reported as antimi-
crobial agents [18]. Keeping this in view, it was thought worth-
while to design the synthesis of title compounds wherein the
biologically active triazole and tetrazole moieties are fused to
potent quinoxaline ring at 1,2 positions. The present com-
munication reports the multistep synthesis of hitherto unknown
4-styryltetrazolo[1,5-a]quinoxalines (4aef), 4-styryl-1-(substi-
tuted)[1,2,4]triazolo[4,3-a]quinoxalines (8aei) and 1-aryl-4-
styryl[1,2,4]triazolo[4,3-a]quinoxalines (8jeu) starting from
The tetrazolegroup which is considered analogous to carbox-
ylic group [1] as a pharmacore possesses wide range of biolog-
ical activities. Several substituted tetrazoles have been shown to
possess anticonvulsant [2], anti-inflammatory [3], CNS depres-
sant [4], antimicrobial [5], anti-aids [6] and antifertility [7,8]
agents. Similarly tetrazolo quinoxalines have been reported
for their antibacterial, antifungal or algicidal activities [9]. Ear-
lier studies revealed [10] that most of the compounds derived
* Corresponding author. Tel.: þ91 824 2474000x3203; fax: þ91 824
2474033.
E-mail addresses: avchem@nitk.ac.in, avadhikari123@yahoo.co.in (A.V.
Adhikari).
0223-5234/$ - see front matter Ó 2008 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2008.06.006

1136
S. Wagle et al. / European Journal of Medicinal Chemistry 44 (2009) 1135e1143
N
N
H
N
O
N
N
N
Cl
NaN3/ AcOH
N
POCl3
N,N-DMA
N
CH3
N
CH3
CH3
1
2
3
R1-CHO
MeOH
N
MeOH
NH2NH2
N
R
N
N
N
N
NH
N
N
NH
NH2
N
R-CHO
N
R1
CH3
CH3
5
4a-f
6a-d
CF3COOH or
R-C(OC2H5)3
R1= Phenyl, substituted phenyl
6a, R = Biphenyl
b, R = 4(OCH3)C6H4
Nitrobenzene
Reflux
(R=H,CH3)
R
c, R = 3(OH)4(OC2H5)C6H3
d, R = 4(F)C6H4
N
N
N
N
CH3
7a-g
R1-CHO
MeOH
R
N
N
N
N
R1
8a-u
R= H, CH3, CF3 , (un) Substitutedphenyl
R1= (un) Substitutedphenyl
Scheme 1.
1,2 diaminobenzene and pyruvic acid via quinoxaline ring
build-up. Eighteen title compounds have been evaluated for
their anticonvulsant activity following PTZ model.
2-hydrazino-3-methylquinoxaline (5). The cyclization of 5 was
achieved by the reaction of orthoesters and trifluoroacetic acid
to yield 4-methyl-1-(substituted)[1,2,4]triazolo[4,3-a]quinoxa-
lines (7aec). Further, compounds 7aec were condensed with
different aromatic aldehydes to give the title compounds 4-
styryl-1-(substituted)[1,2,4]triazolo[4,3-a]quinoxalines (8aei)
in good yield. Another series of title compounds, 1-aryl-4-
styryl[1,2,4]triazolo[4,3-a]quinoxalines (8jeu) were prepared
from the intermediate 5 in three steps. Compound 5 was treated
with different aromatic aldehydes to yield corresponding N-
arylidenehydrazino quinoxalines (6aed) which on oxidative
cyclization by nitrobenzene gave 1-aryl-4-methyl[1,2,4]triazolo
[4,3-a]quinoxalines (7deg). Finally, compounds 7deg were
condensed with different aromatic aldehydes to obtain 8jeu.
The structural assignments to the new compounds were based
2. Results and discussion
2.1. Chemistry
The target compounds were synthesized according to the
representative scheme-1 (Scheme 1). The required starting ma-
terial, 2-chloro-3-methylquinoxaline (2) was prepared in good
yield from 3-methyl quinoxaline-2-one by the treatment of phos-
phorousoxychloride. The azide cyclocondensation of 2 with so-
dium azide, yielded 4-methyltetrazolo[1,5-a]quinoxaline (3),
which on treatment with different aromatic aldehydes furnished
4-styryltetrazolo[1,5-a]quinoxaline (4aef). The reaction of 2-
chloro-3-methylquinoxaline (2) with hydrazine hydrate gave
1
on their elemental analysis and spectral (FTIR, H NMR, 13C
NMR and mass) data.

S. Wagle et al. / European Journal of Medicinal Chemistry 44 (2009) 1135e1143
1137
The formation of 4-methyltetrazolo[1,5-a]quinoxaline (3)
from 2 was confirmed by its mass spectrum. In its mass spec-
trum, molecular ion peak appeared at m/z 186 (100%), which
matches with its molecular formula C9H7N5. Further, conden-
sation of aromatic aldehydes with compounds 3 was confirmed
by the absence of three methyl protons and appearance of two
strain) weighing between 20 and 30 g were used for the study.
They were housed in groups of three mice per cage under stan-
dard laboratory conditions for 1 week before the experiments.
The housing conditions were maintained at controlled temper-
ature (23 ꢁC) and humidity (50%). They received standard diet
and water ad libitum. The animals were transferred to the lab-
oratory 1 h before the start of the experiment. The institutional
ethical committee approved the study. All the results were sta-
tistically analyzed and are expressed as the mean ꢂ S.E.M.
Pentylenetetrazole (PTZ, Sigma Chemicals, USA) was used
as convulsant and diazepam (Ranbaxy Laboratories, India) was
used as standard drug. PTZ was dissolved in normal saline. Test
compounds and standard drug were dissolved in 2% acacia sus-
pension. The mice were divided into 20 groups of three each.
Group-1 received diazepam at a dose of 4 mg/kg, group-2 re-
ceived 4b, group-3 received4c, group-4 received 4d, group-5 re-
ceived 4e, group-6 received 4f, group-7 received 8a, group-8
received 8b, group-9 received 8c, group-10 received 8d,
group-11 received 8e, group-12 received 8f, group-13 received
8g, group-14 received 8h, group-15 received 8i, group-16 re-
ceived 8k, group-17 received 8n, group-18 received 8q and
group-19 received 8t, at a dose of 10 mg/kg. Each dose was dis-
solved in 2% gum acacia and delivered orally in a volume of
0.1 ml/10 g body weight. The control group, i.e. group-20 re-
ceived 0.1 ml/10 g of 2% gum acacia orally by gavage feeding.
Convulsion was induced 1 h after the administration of the stan-
dard drug or the test compounds by i.p. injection of PTZ (80 mg/
kg), dissolved in saline to a volume of 0.1 ml/10 g body weight.
The time needed for the development of unequivocal sustained
clonic seizure activity involving the limbs (isolated myoclonic
jerks or other preconvulsive chewing behavior were not
counted) was carefully noted. Duration of seizure was also
noted. Seizure-free duration for a period of 1 h was taken as pro-
tection. The number of animals protected in each group was re-
corded and percent protection was calculated. The animals in the
control group exhibited seizures at the dose of PTZ used in the
study. The onset of seizure was found to be 119 ꢂ 0.577 s and
the mean seizure duration was 311 ꢂ 0.577 s for the control
group. Diazepam (4 mg/kg), 4c, 4f, 8b, 8c, 8f, 8i and 8t pro-
tected the animals from developing convulsions at the dose of
10 mg/kg body weight in comparison with control group. For
these compounds, all three mice in the group failed to have sei-
zure and thus went for the maximal defined time of 3600 s. An-
imals were less active after receiving all of the test compounds
than the control mice and enhanced effect was exhibited when
compounds 4c, 4f, 8b, 8c, 8f, 8i and 8t were administered.
Amongst the tested compounds, 4c, 4f, 8b, 8c, 8f, 8i and 8t ex-
hibited promising anticonvulsant activity against PTZ induced
seizure in mice at a dose of 10 mg/kg in comparison with diaz-
epam at 4 mg/kg dose. The results are tabulated in Table 2.
A study of structureeactivity relationship from the results
tabulated in Table 2 reveals that compounds bearing CF3, H
or CH3 group in position-1 and 4-fluorophenyl moiety (4c,
4f, 8c, 8f, 8i and 8t) or 4-methoxyphenyl (8b and 8t) substit-
uents at C-4 of the title compounds have shown good anticon-
vulsant activity in comparison with standard drug diazepam.
The increase in activity may be due to their easier transport
1
vinylic protons as two doublets around aromatic region in H
NMR spectra of title compounds. Their structures were also
confirmed by recording their FAB MASS spectra, which are
consistent with their molecular formula. The synthesis of
2-hydrazino-3-methylquinoxaline (5) from 2 was confirmed
by its NMR and FTIR spectra. Its FTIR spectrum showed
strong peaks at 3188 and 2943 cmꢀ1 indicating the presence
1
of eNHNH2 group, while H NMR spectrum was in accor-
dance with its structure. The mass spectrum of it showed
a molecular ion peak at m/z 175 (50%), which tallies with
its molecular formula C9H10N4. The cyclization of compound
5 to triazoles (7aec) was confirmed by recording its FTIR,
NMR and mass spectra. In FTIR spectrum of 7aec, disappear-
ance of strong peaks at 3188 and 2943 cmꢀ1 indicates the
absence of eNHNH2 group. This confirms the cyclization.
The mass spectrum of 7a showed a molecular ion peak at m/
z 253 (100%), which conforms to its molecular formula
C11H7F3N4. In the 1H NMR spectrum of 7b, a singlet appeared
at d 9.3 integrating for one proton of triazolo ring. Appearance
of molecular ion at m/z 185 (100%) in its mass spectrum con-
1
firms its molecular formula, C10H8N4. Similarly the H NMR
spectrum of 7c showed an additional singlet at d 3.2 account-
ing for three protons of methyl group of triazole ring. The
smooth cyclization of 5 was further confirmed by its mass
spectrum, which showed a molecular ion peak at m/z
199(100%) corresponding to C11H10N4.
The FTIR spectra of hydrazones 6aed displayed strong ab-
sorption bands between 1650 and 1420 cmꢀ1 in the aromatic
region. On cyclization of hydrazones to triazoles (7deg),
these bands shifted towards shorter wavelengths indicating
complete aromatization of 6aed. In the FTIR spectrum, 5 ex-
hibited a broad band at 3188 cmꢀ1 due to NH stretching while
compounds 6aed showed sharp band at 3320 cmꢀ1. The dis-
appearance of these bands in the spectra of 7deg indicates
cyclization. The mass spectrum of 7e showed a molecular
ion peak at m/z 321 (100%), which matches with its molecular
formula C18H16N4O2. Finally, the formation of title com-
pounds 8aeu from 7aeg was confirmed by the absence of
three methyl protons and appearance of two vinylic protons
1
as two doublets in aromatic region of their H NMR spectra.
Their structures were also confirmed by recording their FAB
MASS spectra, which are in consistent with their molecular
formulae. The results of physical and elemental analyses
data are shown in Table 1.
3. Biological activity
3.1. Anticonvulsant activity
Anticonvulsant studies were carried out by PTZ animal
model [19]. In the method, inbred male albino mice (Swiss

1138
S. Wagle et al. / European Journal of Medicinal Chemistry 44 (2009) 1135e1143
Table 1
Characterization data of compounds 4aef and 8aeu
Compound
R
R1
Molecular
formula/Molecular Crystallization
M.p. (ꢁC)/
Yield % Analysis (%)
Found (Calc.)
C
weight
solvent
H
N
4a
4b
4c
4d
4e
4f
e
Biphenyl
C22H15N5
349.38
250e252
Chloroform
196e198
Chloroform
204e206
65
67
75
64
78
75
62
68
73
73
78
61
70
78
65
75.60 (75.64) 4.34(4.29)
67.29 (67.32) 4.25 (4.29)
65.90 (65.97) 3.38 (3.43)
60.30 (60.32) 3.09 (3.14)
71.35 (71.38) 4.20 (4.24)
70.23 (70.25) 3.98 (4.02)
62.55 (65.66) 3.59 (3.56)
61.54 (61.56) 3.50 (3.51)
60.25 (60.28) 2.84 (2.79)
65.23 (65.19) 3.95 (3.92)
72.10 (72.07) 5.00 (5.05)
70.94 (70.97) 4.25 (4.27)
64.25 (64.29) 3.50 (3.46)
71.42 (71.44) 4.65 (4.63)
70.24 (70.27) 3.80 (3.78)
83.85 (83.90) 4.75 (4.79)
78.61 (78.64) 4.25 (4.29)
74.08 (74.12) 4.08 (4.04)
75.85 (75.89) 4.77 (4.79)
69.73 (69.75) 4.10 (4.11)
76.07 (76.10) 4.73 (4.75)
66.10 (66.15) 4.20 (4.19)
67.70 (67.73) 4.26 (4.29)
73.48 (73.44) 4.90 (4.89)
67.12 (67.09) 3.44 (3.40)
20.11 (20.05)
e
4(OCH3)C6H4
4-(F)C6H4
C17H13N5O
303.33
23.13 (23.10)
23.98 (24.05)
26.35 (26.41)
19.80 (19.83)
25.63 (25.61)
13.27 (13.32)
15.15 (15.12)
15.65 (15.62)
21.15 (21.12)
17.68 (17.70)
18.43 (18.40)
22.04 (22.06)
18.50 (18.52)
19.26 (19.29)
11.15 (11.18)
12.68 (12.65)
14.96 (14.90)
12.18 (12.21)
13.60 (13.56)
14.82 (14.79)
15.40 (15.43)
12.60 (12.64)
13.70 (13.71)
16.99 (17.01)
e
C16H10FN5
291.26
Chloroform
218e220
Chloroform
210e212
e
3-(NO2)C6H4
C16H10N6O2
318.29
e
6-Methoxy-2-naphthyl C21H15N5O
353.37
Chloroform
180e184
Chloroform
250e252
e
C6H5
C16H11N5
273.29
8a
8b
8c
8d
8e
8f
CF3
6-Methoxy-2-naphthyl C23H15F3N4O
420.38
Chloroform
208e210
CF3
4-(OCH3)C6H4
C19H13F3N4O
370.32
Chloroform
190e192
CF3
4-(F)C6H4
C18H10F4N4
358.29
Chloroform
198e200
CH3
3-(NO2)C6H4
4-(OCH3)C6H4
4-(F)C6H4
C18H13N5O2
331.32
Chloroform
210e212
CH3
C19H16N4O
316.35
Chloroform
240e242
CH3
C18H13FN4
304.32
Chloroform
260e262
Chloroform
240e242
8g
8h
8i
H
3-(NO2)C6H4
4-(OCH3)C6H4
4-(F)C6H4
C17H11N5O2
317.30
H
C18H14N4O
302.33
Chloroform
206e208
Chloroform
218e220
H
C17H11FN4
290.29
8j
Biphenyl
Biphenyl
Biphenyl
4(OCH3)C6H4
4(OCH3)C6H4
4(OCH3)C6H4
Biphenyl
C35H24N4
500.59
Chloroform
260e262
Chloroform
280e282
8k
8l
4-(F)C6H4
C29H19FN4
442.48
71
71
70
72
82
68
68
68
74
74
74
3-(NO2)C6H4
C29H19N5O2
469.49
Chloroform
294e296
Chloroform
250e252
8m
8n
8o
8p
8q
8r
8s
6-Methoxy-2-naphthyl C29H22N4O2
458.51
4-(Cl)C6H4
C24H17ClN4O
412.87
Chloroform
230e233
C6H5
C24H18N4O
378.42
Chloroform
158e160
3-(OH)-4-(OC2H5)-C6H3 3-(NO2)C6H4
3-(OH)-4-(OC2H5)-C6H3 4-(Cl)C6H4
3-(OH)-4-(OC2H5)-C6H3 C6H5
C25H19N5O4
453.45
Chloroform
248e250
C25H19ClN4O2
442.89
Chloroform
238e240
C25H20N4O2
408.45
Chloroform
274e276
4-(F)C6H4
4-(F)C6H4
4-(F)C6H4
3-(NO2)C6H4
4-(OCH3)C6H4
C6H5
C23H14FN5O2
411.38
Chloroform
220e222
Chloroform
244e246
Chloroform
8t
C24H17FN4O
396.41
72.62 (72.65) 4.30 (4.28) 14.151 (14.12)
75.30 (75.32) 4.11 (4.09) 15.23 (15.28)
8u
C23H15FN4
366.39
across biological membranes after the introduction of the styr-
ylphenyl group at the position 4 of quinoxaline ring [20]. It
can be inferred that presence of fluoro, trifluoromethyl, me-
thoxy and methyl groups on the condensed heterocyclic sys-
tem containing quinoxaline, fused with triazole or tetrazole
at positions 1,2 in the backbone structure, influenced the
activity to the greater extent, which may be attributed to
the electronic factors exerted by the substituents and the hy-
drophobic nature of phenyl nucleus in the structure. This ob-
servation is in accordance with the structural requirements of

S. Wagle et al. / European Journal of Medicinal Chemistry 44 (2009) 1135e1143
1139
Table 2
Anticonvulsant activity of the tested compounds (PTZ animal mode)
Group
Drug/test compound
Dose (mg/kg)
Latency (s) (mean ꢂ S.E.M)
3600
Protection (%)
Duration of seizure (s) (mean ꢂ S.E.M)
0
1
Diazepam
4b
4
10
100
0
2
110 ꢂ 2.866
3600
11 ꢂ 0.577
0
3
4c
4d
10
10
100
0
4
110 ꢂ 2.866
100 ꢂ 2.866
3600
11 ꢂ 0.577
8 ꢂ 0.577
0
5
4e
10
10
0
6
4f
8a
100
0
7
10
10
110 ꢂ 2.866
3600
3600
12 ꢂ 0.842
0
8
8b
8c
100
100
0
9
10
10
0
10
11
12
13
14
15
16
17
18
19
20
8d
8e
110 ꢂ 2.866
100 ꢂ 2.866
3600
11 ꢂ 0.577
14 ꢂ 0.842
0
10
10
0
8f
8g
100
0
10
10
110 ꢂ 2.866
123 ꢂ 1.666
3600
12 ꢂ 0.842
14 ꢂ 0.842
0
8h
0
8i
8k
10
10
100
0
125 ꢂ 0.577
110 ꢂ 2.866
110 ꢂ 2.866
3600
8 ꢂ 0.577
12 ꢂ 0.842
12 ꢂ 0.842
0
8n
8q
10
10
0
0
8t
2% Gum acacia (control)
10
0.1 ml/10 g
100
0
119 ꢂ 0.577
311 ꢂ 0.577
N ¼ 3 in each group.
CNS depressant drugs, as reported [21]. Since our preliminary
studies were carried out only at one concentration, further
studies using larger concentrations should be conducted for
obtaining conclusive results. Therefore, the above seven com-
pounds could be recommended for further studies including
behavioral effect and concentration response studies to find
out the advantages of these compounds over known
anticonvulsants.
the resulting slurry N,N-dimethyl aniline (4.4 g, 36.3 mmol)
was added dropwise below 15 ꢁC. The brick red mixture
was refluxed (at z105 ꢁC) for 15 min and the resulting dark
brown clear solution was then cooled to ambient temperature.
It was added to ice cold water (1250 mL) and basified slowly
under cooling with 40% aq. NaOH to pH 8. The brick red
solid, thus separated was filtered, washed with water
(2 ꢃ 250 mL) and dried to obtain crude 2. The crude product
was dissolved in hot hexane (400 ml), treated with activated
charcoal and filtered. The filtrate on concentration to a small
volume (25 mL) gave pure 2, as brick red crystals, 20.0 g
(72%), m.p. 82e84 ꢁC (Lit. 84e86 ꢁC). This is a more conve-
nient and better method compared to the reported procedure
[22]. IR (KBr) cmꢀ1: 1578.6, 1540, 1405, 1368, 1329, 978,
892, 736, 620 (AreH). MS (m/z, %): 179 (M þ 1, 100), 178
(Mþ, 30), 164 (40), 144 (15), 130 (40), 121 (20), 102 (40).
1H NMR (DMSO-d6) d: 2.72 (s, 3H, CH3), 7.59 (m, 2H,
CH), 7.89 (m, 2H, CH). 13C NMR (DMSO-d6): 19.88 (eCH3),
128.59, 129.02, 129.20, 129.98, 140.01, 140.56, 140.90
(aromatic carbons), 146.70 (N]CeCH3). Anal. Calcd. for
C9H7ClN2: C, 60.47; H, 3.91; N, 15.67; Found: C, 60.40; H,
3.87; N, 15.69%.
4. Experimental
4.1. General
Melting points were determined by open capillary and are
uncorrected. The IR spectra (in KBr pellets) were recorded
on a Shimadzu FT-IR 157 spectrophotometer. 1H NMR spectra
were recorded either on PerkineElmer EM-390 (300 MHz) or
on Bruker WH-200 (400 MHz) spectrometer using TMS as an
internal standard. 13C NMR spectra were obtained on a Per-
kineElmer (Model RB-12, 100 MHz) spectrometer. All chem-
ical shifts are reported in ppm downfield from
tetramethylsilane. The mass spectra were recorded on a Jeol
JMS-D 300 mass spectrometer (FAB) operating at 70 eV. Ele-
mental analysis was performed on Flash EA 1112 Thermo
Electron Corporation CHNS analyzer. The purity of the com-
pounds was checked by thin layer chromatography (TLC) on
Merck silica gel 60 F254 precoated sheets. Starting materials
were purchased from Aldrich Chemical Company or Spectro-
chem Chemical Company and used without further purifica-
tion. All solvents were of analytical grade and freshly
distilled prior to use.
4.1.2. Preparation of 4-methyltetrazolo[1,5-a]
quinoxaline (3)
A
mixture of 2-chloro-3-methylquinoxaline 2 (10 g
0.056 mol), sodium azide (4.4 g, 0.067 mol) in water
(15 mL), acetic acid (10 mL) and dimethylsulphoxide
(200 mL) was stirred at 40 ꢁC for 3 h. Completion of the reac-
tion was monitored by TLC (hexane:ethyl acetate, 4:1 v/v). It
was then cooled to room temperature and added to cold water
(500 mL). A crystalline solid separated was filtered off,
washed with water, dried and recrystallized from chloroform
as light yellow crystals, 9.5 g (92%), m.p. 134e136 ꢁC. IR
(KBr) cmꢀ1: 1570.6, 1546, 1400, 1362, 1329, 898, 734, 620
4.1.1. 2-Chloro-3-methylquinoxaline (2)
Compound 1 (25.0 g, 143.6 mmol) was added to cold phos-
phorousoxychloride (125 mL) in portions to get a slurry. To

1140
S. Wagle et al. / European Journal of Medicinal Chemistry 44 (2009) 1135e1143
(AreH). MS (m/z, %): 186 (M þ 1, 100), 185 (Mþ, 80), 164
(20), 131 (15), 107 (40), 121 (20), 102 (15). 1H NMR
(CDCl3) d: 3.16 (s, 3H, CH3), 7.78 (m, 2H), 8.23 (d, 1H),
8.62 (d, 1H). 13C NMR (DMSO-d6): 21.71 (eCH3), 116.29,
124.52, 129.71, 129.85, 130.36, 136.80, 142.89, 151.09.
Anal. Calcd. for C9H7N5: C, 58.34; H, 3.78; N, 37.81; Found:
C, 58.30; H, 3.73; N, 37.88%.
Compound 4e: IR (KBr) cmꢀ1: 3058, 2930, 1620, 1528,
1471, 1452, 1388, 1360, 1324, 893 (AreH). MS (m/z, %):
354 (M þ 1, 40), 353 (Mþ, 20), 289 (20), 242 (15), 120
(10), 105 (10), 73 (15).
4.1.4. Preparation of 2-hydrazino-3-methylquinoxaline (5)
A mixture of 20 g (0.112 mol) of 2-chloro-3-methylqui-
noxaline (2) and 9.0 g (0.28 mol) of hydrazine hydrate in
150 mL of methanol was stirred for 16 h at room temperature.
The reaction mixture was filtered, and the solids were washed
with methanol and air dried to give 17 g (87.6%) of product,
m.p. 180e182 ꢁC. MS (m/z, %): 175 (M þ 1, 100), 174
4.1.3. 3-[(E )-2-Arylvinyl]tetrazolo[1,5-a]quinoxaline
(4aef)
General procedure: A mixture of compound 3 (1.5 g,
0.008 mol), an appropriate aldehyde (0.0097 mol), acetic
acid (10 mL) and catalytic amount (0.2 mL) of conc. sulfuric
acid was refluxed (118 ꢁC) for 1 h. The reaction mass was
cooled to room temperature; the separated solid was filtered,
washed with water (2 ꢃ 20 mL) and finally with cold methanol
to obtain compounds 4aef. They were recrystallized from ap-
propriate solvents.
1
(Mþ, 80), 149 (50), 107(20), 95(10). H NMR (DMSO-d6)
d: 2.43 (s, 3H, CH3), 7.28 (t, 1H), 7.48 (t, 1H), 7.56 (d, 1H,
J ¼ 8.50 Hz), 7.69 (d, 1H, J ¼ 8.20 Hz). 13C NMR (DMSO-
d6): 21.27 (eCH3), 123.64, 124.68, 128.03, 128.94, 136.21,
140.48, 146.74, 146.95. Anal. Calcd. for C9H10N4: C, 61.99;
H, 5.74; N, 32.14; Found: C, 62.06; H, 5.70; N, 32.18%.
Compound 4a: IR (KBr) cmꢀ1: 3054, 2929, 1625, 1540,
1475, 1392, 1360, 1315, 1255. 1H NMR (CDCl3) d: 7.50
(complex m, 12H), 8.58 (d, 1H, J ¼ 8.6 Hz). 13C NMR
(DMSO-d6): 116.62, 123.36, 124.41, 125.10, 125.56, 126.55,
127.99, 128.15, 128.20, 129.60, 130.91, 136.54, 136.65,
136.93, 137.91, 139.99, 141.58, 143.57.
4.1.5. Preparation of 2-(N-arylidenehydrazino)-3-
methylquinoxalines (6aed)
General procedure: A mixture of 5.0 g (0.028 mol) of 2-hy-
drazino-3-methylquinoxaline (5) and, an aromatic aldehyde
(0.029 mol), methanol (10 mL) and glacial acetic acid
(2 mL) was refluxed for 3e4 h. The reaction mass was then
cooled to room temperature, and kept overnight. The separated
solid was filtered, washed with methanol (5 mL), dried and
crystallized from a mixture of ethanol and acetic acid to obtain
compounds 6aed.
Compound 4b: IR (KBr) cmꢀ1: 3050, 2925, 1625, 1537,
1475, 1390, 1356, 1312, 1254. MS (m/z, %): 304 (M þ 1,
50), 303 (Mþ, 20), 245 (20), 244 (15), 107 (40), 102 (15),
1
75 (10). H NMR (CDCl3) d: 3.80 (s, 3H, OCH3), 7.18 (m,
2H), 7.23 (d, 1H, vinylic proton, J ¼ 16.6 Hz), 7.39 (m, 2H),
7.56 (t, 1H, J ¼ 8.38 Hz), 7.60 (d, 1H, J ¼ 8.38 Hz), 7.92 (d,
1H, vinylic proton, J ¼ 16.6 Hz), 7.95 (t, 1H, J ¼ 8.5 Hz),
8.65 (d, 1H, J ¼ 8.5 Hz). 13C NMR (DMSO-d6): 57.60
(eOCH3), 115.74, 116.40, 123.36, 124.41, 125.08, 125.55,
126.55, 127.89, 128.06, 133.65, 136.54, 137.91, 141.58,
160.32.
Compound 6a: Yield 7.5 g (78.9%), m.p. 238e240 ꢁC. IR
(KBr) cmꢀ1: 3320, 2930, 1650, 1528, 1471, 1420, 1380,
1
1362, 1326, 893 (AreH). H NMR (CDCl3) d: 2.41 (s, 3H,
eCH3), 6.90 (m, 2H), 7.21 (m, 3H), 7.57 (m, 5H), 7.85 (m,
2H), 7.96 (d, 1H, J ¼ 8.50), 8.19 (s, 1H). 13C NMR (DMSO-
d6): 19.32 (CH3), 114.55, 127.27, 127.40, 127.81, 127.97,
128.42, 128.79, 131.75, 132.79, 133.50, 136.33, 137.24,
138.21, 142.45, 142.92. Anal. Calcd. for C22H18N4: C,
78.01; H, 5.31; N, 16.54; Found: C, 78.12; H, 5.38; N,
16.50%.
Compound 6b: Yield 5.0 g (61.7%), m.p. 208e210 ꢁC. IR
(KBr) cmꢀ1: 3318, 2931, 1628, 1521, 1476, 1450, 1379,
1355, 1324, 890 (AreH). Anal. Calcd. for C17H16N4O: C,
69.78; H, 5.47; N, 19.15; Found: C, 69.75; H, 5.52; N,
19.08%.
Compound 6c: Yield 6.5 g (72.2%), m.p. 230e232 ꢁC. IR
(KBr) cmꢀ1: 3324, 2930, 1616, 1532, 1475, 1448, 1369,
1355, 1317, 896 (AreH). Anal. Calcd. for C18H18N4O2: C,
67.00; H, 5.58; N, 17.37; Found: C, 67.11; H, 5.62; N,
17.41%.
Compound 6d: Yield 6.2 g (79.5%), m.p. 194e496 ꢁC. IR
(KBr) cmꢀ1: 3323, 2924, 1620, 1524, 1473, 1450, 1380,
1
1361, 1318, 879 (AreH). H NMR (CDCl3) d: 2.60 (s, 3H,
eCH3), 7.32 (m, 2H), 7.57 (t, 1H, J ¼ 6.86), 7.67 (m, 4H),
7.96 (d, 1H, J ¼ 8.52), 8.19 (s, 1H). 13C NMR (DMSO-d6):
20.2 (CH3), 114.25, 115.75, 116.41, 127.27, 127.81, 127.97,
129.13, 131.79, 132.75, 133.56, 137.24, 142.45, 145.52,
Compound 4c: IR (KBr) cmꢀ1: 3075, 1625, 1600, 1525,
1510, 1410, 1305, 1225, 736, 620 (AreH). MS (m/z, %):
292 (M þ 1, 40), 291 (Mþ, 20), 125 (20), 120 (15), 75(10).
1H NMR (CDCl3) d: 7.20 (m, 2H), 7.23 (d, 1H, vinylic proton,
J ¼ 16.5 Hz), 7.39 (m, 2H), 7.59 (t, 1H, J ¼ 8.38 Hz), 7.63 (d,
1H, J ¼ 8.38 Hz), 7.92 (d, 1H, vinylic proton, J ¼ 16.5 Hz),
7.96 (t, 1H, J ¼ 8.5 Hz), 8.63 (d, 1H, J ¼ 8.5 Hz). 13C NMR
(DMSO-d6): 116.40, 117.79, 118.49, 123.36, 124.41, 125.55,
126.55, 129.70, 129.87, 131.79, 133.65, 136.54, 137.91,
141.58, 159.28, 165.78.
Compound 4d: IR (KBr) cmꢀ1: 3050, 2925, 1625, 1537,
1475, 1450, 1390, 1362, 1329, 890 (AreH). MS (m/z, %):
319 (M þ 1, 50), 289(20), 273 (10), 245 (10), 244 (10), 165
1
(10), 120 (15), 107 (20), 89 (20), 75 (10). H NMR (CDCl3)
d: 7.70 (d, 1H, vinylic proton, J ¼ 16.4 Hz), 7.79 (t, 1H,
J ¼ 8.50 Hz), 7.88 (t, 1H, J ¼ 6.86 Hz), 7.94 (d, 1H,
J ¼ 8.30 Hz), 7.99 (d, 1H, J ¼ 7.70 Hz), 8.12 (d, 1H, vinylic
proton, J ¼ 16.4 Hz), 8.24 (d, 1H, J ¼ 6.86 Hz), 8.29 (d, 1H,
J ¼ 8.50 Hz), 8.60 (s, 1H), 8.63 (d, 1H, J ¼ 8.50 Hz). 13C
NMR (DMSO-d6): 116.60, 124.73, 125.22, 128.72, 129.20,
130.28, 130.39, 130.49, 131.22, 131.73, 134.35, 136.23,
137.15, 142.62, 147.07 and 149.06.

S. Wagle et al. / European Journal of Medicinal Chemistry 44 (2009) 1135e1143
1141
151.96. Anal. Calcd. for C16H13FN4: C, 68.49; H, 4.63; N,
19.97; Found: C, 68.46; H, 4.60; N, 19.94%.
66.59; H, 5.04; N, 28.25; Found: C, 66.63; H, 5.14; N,
28.22%.
4.1.6. Preparation of 4-methyl-1-(trifluoromethyl)
[1,2,4]triazolo[4,3-a]quinoxaline (7a)
4.1.9. Preparation of 1-aryl-4-methyl[1,2,4]triazolo[4,3-
a]quinoxalines (7deg)
2-Hydrazino-3-methylquinoxaline (5, 5.0 g, 0.028 mol)
was added to 32.72 g (0.28 mol) of trifluoroacetic acid taken
in a dry flask, at 5e10 ꢁC with stirring under nitrogen atmo-
sphere. The mixture was then heated to 100 ꢁC for 3 h and
poured over ice/H2O. The separated solid was filtered, washed
well with water and dried at 60 ꢁC under vacuum. It was re-
crystallized from chloroform to give 5.0 g (70%) of product,
m.p. 130e132 ꢁC. IR (KBr) cmꢀ1: 3026, 1517, 1493, 1457,
1420, 1376, 1353, 1285, 1214, 1179, 1141, 1070, 988. MS
(m/z, %): 253 (M þ 1, 100), 252 (70), 234 (20), 137 (80),
2H, J ¼ 8.50 Hz), 8.17 (t, 2H, J ¼ 8.70 Hz). 13C NMR
(DMSO-d6): 21.18, 116.73, 117.78, 120.46, 121.48, 124.25,
129.02, 129.78, 130.75, 136.72, 145.98, 149.10, 152.48,
160.19. Anal. Calcd. for C11H7F3N4: C, 52.34; H, 2.77; N,
22.20; Found: C, 52.30; H, 2.82; N, 22.26%.
General procedure: Compound 6 (0.009 mol) was added to
nitrobenzene (10e15 mL) and the mixture was refluxed for 3e
4 h in an oil bath. When the reaction was over, nitrobenzene
was removed by applying high vacuum. The resulting residue
was triturated with water and filtered. The dry product was
then recrystallized from chloroform to give 7deg.
Compound 7d: Yield 6.0 g (81.0%), m.p. 245e247 ꢁC.
3024, 1520, 1488, 1450, 1374, 1351, 1281, 1210, 1179,
1
1141, 1070, 981. H NMR (CDCl3) d: 2.72 (s, 3H, eCH3),
7.21 (m, 5H), 7.43 (m, 3H), 7.62e7.71 (m, 2H), 7.96 (d,
1H, J ¼ 8.50), 8.19 (s, 1H), 8.26 (d, 2H, J ¼ 8.35). 13C
NMR (DMSO-d6): 18.24 (CH3), 116.74, 123.31, 127.40,
127.59, 128.22, 128.79, 129.17, 131.03, 131.22, 131.61,
132.94, 137.46, 138.08, 140.34, 145.59, 146.12, 147.86.
Anal. Calcd. for C22H16N4: C, 78.48; H, 4.75; N, 16.64;
Found: C, 78.53; H, 4.78; N, 16.60%.
1
107 (30). H NMR (CDCl3) d: 3.10 (s, 3H, CH3), 7.73 (d,
Compound 7e: Yield 4.0 g (81.6%), m.p. 215e217 ꢁC.
3026, 1520, 1497, 1452, 1371, 1348, 1280, 1209, 1074, 990.
Anal. Calcd. for C17H14N4O: C, 70.26; H, 4.82; N, 19.28;
Found: C, 70.20; H, 4.80; N, 19.23%.
4.1.7. Preparation of 4-methyl[1,2,4]triazolo[4,3-a]
quinoxaline (7b)
A mixture of 5.0 g (0.028 mol) of 2-hydrazino-3-methyl-
quinoxaline (5) and 50 mL of triethyl orthoformate was stirred
at 100 ꢁC for 1 h. The reaction mass was then cooled to room
temperature and the solid separated was filtered, washed with
hexane, dried and finally recrystallized from chloroform to
give 4.5 g (85.2%), m.p. 168e170 ꢁC. IR (KBr) cmꢀ1: 3026,
1517, 1493, 1457, 1420, 1376, 1353, 1285, 1214, 1179,
1141, 1070, 988. MS (m/z, %): 185 (M þ 1, 100), 184 (Mþ,
Compound 7f: Yield 5.8 g (90%), m.p. 238e240 ꢁC. MS
(m/z, %): 321 (M þ 1, 100), 320 (Mþ, 20), 307 (20), 273
1
(10), 180 (5), 120 (10), 107 (25). H NMR (CDCl3) d: 1.45
(t, 3H, CH3), 3.05 (s, 3H, CH3), 4.1 (q, 2H, eOCH2), 7.1
(m, 4H), 7.32 (t, 1H, J ¼ 8.50), 7.50 (t, 1H, J ¼ 8.20), 7.65
(d, 1H, J ¼ 8.50), 8.41 (d, 1H, J ¼ 8.48). 13C NMR (DMSO-
d6): 14.76 (CH3), 20.60 (CH3), 65.02 (OCH2), 113.27,
115.29, 116.08, 118.81, 123.51, 125.82, 128.03, 128.69,
129.43, 135.38, 144.57, 146.47, 148.60, 150.44, 153.13.
Anal. Calcd. for C18H16N4O2: C, 67.42; H, 4.99; N, 17.48;
Found: C, 67.40; H, 4.94; 17.43%.
Compound 7g: Yield 5.75 g (94%), m.p. 212e214 ꢁC.
3025, 1522, 1493, 1450, 1373, 1359, 1285, 1218, 1179,
1141, 1070, 975, 830. Anal. Calcd. for C16H11FN4: C,
68.99; H, 3.95; N, 20.12; Found: C, 68.96; H, 3.98; N,
20.08%.
1
80), 131 (20), 107 (15). H NMR (CDCl3) d: 3.05 (s, 3H, e
CH3), 7.60 (m, 2H), 7.90 (d, 1H, J ¼ 8.60 Hz), 8.05 (d, 1H,
J ¼ 8.60 Hz), 9.3 (s, 1H, proton on triazole ring). 13C NMR
(DMSO-d6): 21.17, 116.11, 123.50, 129.19, 130.90, 131.94,
137.47, 138.33, 140.29, 147.40. Anal. Calcd. for C10H8N4:
C, 65.15; H, 4.34; N, 30.40; Found: C, 65.20; H, 4.38; N,
30.38%.
4.1.8. Preparation of 1,4-dimethyl[1,2,4]triazolo[4,3-a]
quinoxaline (7c)
A mixture of 5.0 g (0.028 mol) of 2-hydrazino-3-methyl-
quinoxaline (5) and 50 mL of triethyl orthoacetate was stirred
at 100 ꢁC for 3 h. The reaction mass was then cooled to room
temperature and quenched into 250 mL of ice cold water. The
resulting product was filtered, washed with hexane, dried and
finally recrystallized from chloroform to give 5.0 g (88%),
m.p. 82e84 ꢁC. IR (KBr) cmꢀ1: 3026, 1517, 1493, 1457,
1420, 1376, 1353, 1285, 1214, 1179, 1141, 1070, 988. MS
(m/z, %): 199 (M þ 1, 100), 196 (10), 179 (10), 169 (20),
148 (20), 147 (10), 131 (10), 117 (5), 113 (10), 106 (5), 97
4.1.10. Preparation of 1-substituted-4-[(E )-2-arylvinyl]
[1,2,4]triazolo[4,3-a]quinoxaline (8aeu)
General procedure: A mixture of compounds 7aeg
(0.10 mol), an appropriate aldehyde (0.11 mol), methanol
(10 mL) and catalytic amount (0.2 mL) of conc. sulfuric acid
was refluxed (65 ꢁC) for 8 h. The reaction mass was cooled
to room temperature, and kept in deep-freezer for 8 h. The
separated solid was filtered, washed with cold methanol
(5 mL) to obtain compounds 8aeu. They were crystallized
from appropriate solvents.
Compound 8a: IR (KBr) cmꢀ1: 3020, 1519, 1490, 1457,
1380, 1353, 1285, 1214, 1179, 1070, 988. MS (m/z, %): 421
(M þ 1, 40), 420 (10), 365 (20), 245 (10), 179 (10), 148
(20), 131 (10), 113 (10), 106 (5), 97 (10), 77 (10). 1H
NMR (CDCl3) d: 3.90 (s, 3H, eOCH3), 7.2 (m, 3H), 7.8
1
(10). H NMR (CDCl3) d: 3.0 (s, 3H, eCH3), 3.20 (s, 3H, e
CH3), 7.6 (m, 2H), 8.00 (d, 1H, J ¼ 8.70 Hz), 8.15 (d, 1H,
J ¼ 8.70 Hz). 13C NMR (DMSO-d6): 12.45 (eCH3), 18.24
(eCH3), 116.17, 123.55, 130.56, 131.78, 132.47, 137.51,
138.05, 148.29, 148.68. Anal. Calcd. for C11H10N4: C,

1142
S. Wagle et al. / European Journal of Medicinal Chemistry 44 (2009) 1135e1143
(complex m, 6H), 8.2 (d, 1H), 8.30 (s, 1H), 8.67 (d, 1H,
J ¼ 8.50 Hz). 13C NMR (DMSO-d6): 55.43, 106.17, 108.40,
115.53, 116.39, 119.53, 121.84, 122.66, 123.02, 124.06,
125.00, 125.36, 129.70, 130.41, 131.13, 131.53, 131.83,
131.85, 132.73, 132.84, 133.73, 134.38, 135.87, 136.91,
137.44, 139.08, 141.08, 141.15, 141.22, 159.00.
Compound 8p: IR (KBr) cmꢀ1: 3020, 1519, 1490, 1380,
1353, 1285, 1214, 1179, 1070, 978, 875. MS (m/z, %): 454
(M þ 1, 90), 453 (Mþ, 10), 438 (10), 307 (20), 281 (10),
1
221 (10), 167 (20), 107 (30), 91 (20), 89 (20), 73 (10). H
NMR (CDCl3) d: 1.28 (t, 3H, CH3), 4.00 (q, 2H, OCH2),
7.50 (complex m, 12H), 8.94 (d, 1H, J ¼ 7.80), 9.71 (s, 1H,
OH).
Compound 8b: IR (KBr) cmꢀ1: 3023, 1512, 1496, 1451,
1
1387, 1350, 1284, 1214, 1179, 1073. H NMR (CDCl3) d:
Compound 8u: IR (KBr) cmꢀ1: 3018, 1512, 1494, 1449,
1
1383, 1350, 1280, 1210, 1175, 1076, 975. H NMR (CDCl3)
3.80 (s, 3H, eOCH3), 6.89 (d, 2H), 7.19 (d, 2H, vinylic pro-
tons), 7.45 (d, 2H, vinylic protons, J ¼ 16.40 Hz), 7.53 (com-
plex m, 2H), 7.72 (t, 1H, J ¼ 8.20 Hz), 7.91 (t, 1H,
J ¼ 6.86 Hz), 8.66 (d, 1H, J ¼ 8.50 Hz).
d: 6.99 (t, 1H, J ¼ 7.30), 7.19 (d, 1H, vinylic proton,
J ¼ 16.40 Hz), 7.36 (m, 8H), 7.68 (d, 2H, J ¼ 7.58), 7.82 (t,
1H, J ¼ 6.86), 8.32 (d, 1H, J ¼ 8.66), 8.49 (d, 1H, J ¼ 8.50).
13C NMR (DMSO-d6): 117.03, 117.93, 118.63, 123.02,
123.06, 123.78, 123.84, 127.30, 128.70, 129.10, 129.28,
129.73, 131.05, 131.63, 132.95, 135.87, 136.84, 137.54,
138.66, 139.35, 143.85, 161.08, 167.58.
Compound 8d: IR (KBr) cmꢀ1: 3018, 1519, 1490, 1449,
1376, 1350, 1282, 1218, 1180, 1068, 980. MS (m/z, %): 332
1
(M þ 1, 60), 331 (50), 245 (10), 113 (10), 97 (10). H NMR
(CDCl3) d: 2.79 (s, 3H, CH3), 7.33 (d, 1H, vinylic protons,
J ¼ 16.50), 7.45 (t, 1H, J ¼ 8.20), 7.46 (d, 1H, vinylic protons,
J ¼ 16.50), 7.50 (t, 1H, J ¼ 7.70), 7.59 (d, 1H, J ¼ 8.20), 7.82
(t, 1H, J ¼ 6.86), 7.90 (d, 1H, J ¼ 7.70), 8.05 (d, 1H), 8.39 (d,
1H, J ¼ 8.48), 8.54 (s, 1H). 13C NMR (DMSO-d6): 12.45
(CH3), 116.42, 122.59, 123.86, 124.48, 130.56, 131.78,
131.80, 132.50, 132.69, 133.18, 136.97, 137.53, 138.80,
139.08, 139.96, 146.40, 151.54.
5. Conclusion
In the present investigation, 27 new 4-styryltetrazolo[1,5-
a]quinoxaline and 1-substituted-4-styryl[1,2,4]triazolo[4,3-
a]quinoxaline derivatives were synthesized and characterized
by spectral analysis. They were screened for preliminary anti-
convulsant activity by PTZ animal model. Compounds 4c, 4f,
8b, 8c, 8f, 8i and 8t exhibited promising activity, which is
comparable to the standard. The activity was attributed to
the presence of fluoro, trifluoromethyl, methoxy and methyl
groups on the condensed heterocyclic system containing qui-
noxaline, fused to triazole or tetrazole at 1,2 positions in the
backbone structure of title compounds. The electronic factors
exerted by the substituents and the hydrophobic nature of phe-
nyl nucleus in the title compounds influenced the activity.
Compound 8f: IR (KBr) cmꢀ1: 3028, 1520, 1487, 1451,
1379, 1280, 1220, 1176, 1070, 975. 1H NMR (CDCl3) d:
2.84 (s, 3H, CH3), 7.20 (d, 2H, J ¼ 8.80), 7.39 (m, 2H), 7.44
(t, 1H, J ¼ 6.80), 7.46 (d, 1H, J ¼ 8.20), 7.49 (d, 1H, vinylic
proton, J ¼ 16.20), 7.59 (d, 1H, J ¼ 8.20), 7.82 (t, 1H,
J ¼ 6.80), 8.40 (d, 1H, J ¼ 8.40). 13C NMR (DMSO-d6):
12.52 (CH3), 116.40, 117.81, 118.51, 123.06, 123.80,
128.99, 129.17, 130.56, 131.63, 131.82, 132.50, 135.87,
139.10, 139.97, 146.44, 159.33, 165.80.
Compound 8h: IR (KBr) cmꢀ1: 3020, 1519, 1490, 1457,
1
1380, 1353, 1285, 1214, 1179, 1070, 988. H NMR (CDCl3)
Acknowledgments
d: 3.82 (s, 3H, eOCH3), 6.89 (d, 2H, J ¼ 8.40), 7.19 (d, 1H,
vinylic proton, J ¼ 16.00), 7.45 (d, 1H, vinylic proton
J ¼ 16.00), 7.50 (m, 5H), 8.43 (d, 1H, J ¼ 8.58), 10.19 (s,
1H, triazolo proton). 13C NMR (DMSO-d6): 57.60 (OCH3),
115.74, 116.40, 123.08, 123.84, 127.35, 127.80, 129.20,
130.92, 131.92, 135.87, 136.93, 138.06, 138.28, 140.26,
160.38.
The authors are grateful to Head, SAIF, CDRI, Lucknow
and Head, NMR Research Centre, IISc, Bangalore, for provid-
1
ing H NMR and mass spectral data.
References
Compound 8j: IR (KBr) cmꢀ1: 3022, 1514, 1478, 1439,
1383, 1342, 1279, 1210, 1170, 1067, 960. MS (m/z, %): 501
(M þ 1, 50), 500 (Mþ, 20), 486 (10), 379 (10), 376 (10),
361 (25), 307 (30), 253 (50), 242 (10), 226 (10), 165 (20),
120 (20), 107 (30), 105 (20).
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