Design and Synthesis of 2,5-Disubstituted-1,3,4-Oxadiazole Hybrids Bearing Pyridine and 1,2,3-Triazole Pharmacophores

Article abstract of DOI:10.1002/jhet.2672

A novel series of 2,5-disubstituted-1,3,4-oxadiazoles decorated with two biodynamic moieties pyridine and 1,2,3-triazole have been successfully synthesized in good yields under mild reaction conditions. The synthesized compounds are valuable for biological activity exploration since three biodynamic moieties are covalently linked together in a single molecular framework. All the synthesized compounds were fully characterized by their detailed spectral studies IR, ¹HNMR, ¹³C NMR and Mass.

Full text of DOI:10.1002/jhet.2672

Month 2016
Design and Synthesis of 2,5-Disubstituted-1,3,4-Oxadiazole Hybrids
Bearing Pyridine and 1,2,3-Triazole Pharmacophores
Reena Kaushik, Khushbu Kushwaha, Mahesh Chand, Monika Vashist, and Subhash C. Jain*
Department of Chemistry, University of Delhi, Delhi 110 007, India
*
E-mail: jainsc48@hotmail.com
Additional Supporting Information may be found in the online version of this article.
Received November 25, 2015
DOI 10.1002/jhet.2672
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
A novel series of 2,5-disubstituted-1,3,4-oxadiazoles decorated with two biodynamic moieties pyridine
and 1,2,3-triazole have been successfully synthesized in good yields under mild reaction conditions. The
synthesized compounds are valuable for biological activity exploration since three biodynamic moieties
are covalently linked together in a single molecular framework. All the synthesized compounds were fully
1
13
characterized by their detailed spectral studies IR, HNMR, C NMR and Mass.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
such as antimicrobial [15], antimalarial [16], anti-HIV
17], anti-tuberculosis [18], anticancer [19–21] and herbi-
[
The convenient, rapid and high yielding synthesis of
small heterocycles in drug discovery is gaining importance
these days as this can provide novel molecules for high
throughput screening. The trend is to construct new mole-
cules, containing two or more small privileged heterocyclic
moieties linked by a covalent bond, using simple chemis-
try. These privileged molecules can be triazole, oxadiazole,
pyrazole, thiazole or pyridine, as each of them is biologi-
cally active moiety and when present in tandem might
result in a new hybrid molecule possessing varied and
enhanced biological activity than that of an individual mol-
ecule. Earlier many such hybrids possess antimicrobial [1],
antimycobacterial [2], antituberculosis [3], antileishmenial
cidal [22]. Some 1,2,3-triazoles have also shown applica-
tion as potassium channel activators [23], cannabinoid
CB1 receptor antagonists [24], organocatalysts [25] and
chemosensors [26]. This heterocycle possesses high dipole
moment and is able to participate actively in the hydrogen
bond formation as well as in dipole–dipole and Π stacking
interactions which may be helpful for its binding with
bimolecular targets [27].
1,3,4-Oxadiazoles, on the other hand, are well known in
literature for their versatile biological activities such as
anti-inflammatory [28], vasodialatory [29], antibacterial
[30,31], antifungal [32,33], antitumor [34–36], anticon-
vulsant [37], insecticidal [38] and herbicidal [39].
1,3,4-Oxadiazoles are also known as surrogates for
carboxamides, esters and carboxylic acids to improve the
biological activities of consequent molecules [40].
Raltegravir, Furamizole and Nesapidil are well known
examples of antiretroviral, antibacterial and anti-arrhythmic
drugs which are available in the market. Beside the biological
activities, 1,3,4-oxadiazoles have also many industrial
applications in material sciences [41–44].
[
4] or antiprotozoal [5] activities and some are also avail-
able in market as drugs e.g. fluconazole, miridazole,
losartan, nitrofurantoin, methapyrilene and rosiglitazone.
Pyridine is a privileged heterocycle and is present in major
marketed drugs. Compounds containing this nucleus are
endowed with diverse biological activities such as antitumor
[
[
6,7], anti-inflammatory [8], antimalarial [9,10], anti-HIV
11], anti-tuberculosis [12], antimicrobial [13] or anti-
mycobacterial [14]. So we have chosen pyridine as our core
molecule and thought of constructing 1,2,3-triazole at posi-
tion 3 on it and further linking the triazole to another biody-
namic moiety 1,3,4-oxadiazole by a covalent bond to create
novel hybrids for biological activity exploration.
Besides the individual activity of above mentioned
molecules, few compounds that contain both pyridine and
1,3,4-oxadiazole moieties are also known to possess anti-
microbial [45], anticancer [46,47], anti-inflammatory and
analgesic [48] or anti-tuberculosis [49] activities.
1
,2,3-Triazoles also owes a huge importance in medici-
Thus we, in continuation to our research work that is pri-
marily focused on the synthesis of new bioactive molecules
nal chemistry due to their numerous biological activities
©
2016 Wiley Periodicals, Inc.

R. Kaushik, K. Kushwaha, M. Chand, M. Vashist, and S. C. Jain
Vol 000
[
50], have now planned to obtain a series of new hybrid
disubstituted-1,3,4-oxadiazoles. Formation of compound
8h was confirmed on the basis of presence of two doublets
each integrating for two protons at δ 8.11 and 7.35
(J=8.04Hz) in addition to the presence of multiplet at δ
8.86-8.85 integrated for two protons, doublet at δ 7.95
(J=8.08Hz) for one proton and double doublet at δ 7.60
(J=8.04 & 5.12Hz) for one proton for the pyridyl ring.
Final confirmation came from its mass spectrum which shows
molecules by combining covalently three pharmacologically
active moieties pyridine, 1,2,3-triazole and 1,3,4-oxadiazole
in a suitable frame on the promise that these pharmacophores
when present in tandem will contribute significantly to the
biological activity of the resulting hybrid. To achieve this,
1
,2,3-triazole is used as a biodynamic linker between pyri-
dine and 1,3,4-oxadiazole which will help in amending the
biological properties of the resulting new molecule. Cepha-
losporins endowed with good oral availability, were earlier
similarly obtained by linking the triazole moiety to the
cephalosporin core [51].
+
its (M +1) peak at m/z 319 corresponding to the molecular
formula C H N O. Elemental analysis also confirmed the
17 14 6
structure of compound 8 h as 2-(4-methylphenyl)-5-(5-
methyl-1-(pyridin-3-yl)-1H-1,2,3-triazol-4-yl)-1,3,4-oxadiazole.
Compound 8j was synthesized by the reaction of
carbohydrazide 6 with 2-phenylquinoline-4-carboxylic acid
(
7j) using the same methodology. Compound 7j was
RESULTS AND DISCUSSION
synthesized separately using indolin-2,3-dione (9) and
acetophenone (10) under basic conditions [53]. All the syn-
thesized compounds 8a-j were characterized on the basis of
their detailed spectral studies and elemental analysis.
Synthesis of target molecules was initiated by diazotiza-
tion of 3-aminopyridine (1) with sodium nitrite and sulfuric
acid to give diazonium salt which on treatment with sodium
azide gave 3-azidopyridine (2). Compound 2 was mainly
characterized by the presence of absorption band at 2134
-
1
CONCLUSIONS
&
2096cm for azido functionality in IR spectrum [52].
In the next step, 2 was cyclized with ethylacetoacetate (3)
using sodium methoxide in dry methanol to obtain
In summary, a novel series of heterocyclic hybrids 8a-j
containing 1,3,4-oxadiazole, pyridine and 1,2,3-triazole moi-
eties was designed and synthesized under simple reaction
conditions in good yields. Synthesized compounds contain
three biodynamic moieties, each having its own characteris-
tic biological and physiological properties, will certainly
possess varied enhanced biological activity as compared to
the individual species and hence would be interesting for fur-
ther exploration as drug like molecules/compounds.
5
-methyl-1-(pyridin-3-yl)-1H-1,2,3-triazole-4-carboxylic
acid (4) in 85% yield. Cyclization was confirmed by the
-
1
presence of absorption bands at 3435 & 1704 cm for –
OH and –C= O stretching respectively and supported by
-
1
the absence of absorption bands at 2134 & 2096 cm for
azido group. Further, a D O exchangeable singlet at δ
2
1
1
3.21 in H NMR confirmed the presence of carboxylic
group. A singlet at δ 2.52 in H NMR and carbon peak at
δ 9.62 in C NMR confirmed the presense of methyl
substituted triazole ring. Esterification of 4 was done in
absolute ethanol to obtain ethyl 5-methyl-1-(pyridin-3-yl)-
1
13
EXPERIMENTAL
1
H-1,2,3-triazole-4-carboxylate (5). Esterification was con-
firmed by a characteristic quartet for two protons at δ 4.47
and a triplet for three protons at δ 1.45 in H NMR and their
General: All chemicals and solvents used in this work
were of analytical reagent grade (anhydrous). Melting
points were recorded with open capillary on Tropical Lab
equip apparatus and are uncorrected. Infra-red spectras
were recorded on Shimadzu model 435 spectrophotometer
as films or using KBr discs and only major absorption
1
corresponding carbon peaks appeared at δ 61.13 and 14.21
13
in C NMR for the ethoxy group. Compound 5 on treat-
ment with hydrazine hydrate in absolute ethanol gave
5
-methyl-1-(pyridin-3-yl)-1H-1,2,3-triazole-4-
-
1
carbohydrazide (6) (Scheme 1). Its formation was con-
bands are quoted in cm . Proton nuclear magnetic reso-
1
firmed by the presence of two D O exchangeable singlets
nance ( H NMR) spectra were recorded on Jeol
2
1
at δ 9.81 and 4.50 for –NH and –NH in H NMR. Also a
mark deviation in absorption band from 1720 cm to
654 cm for the carbonyl group, showed the consumption
(400 MHz) spectrometers using CDCl /DMSO-d as sol-
2
3
6
-
1
vent. Chemical shifts are reported as δ (ppm) relative to
-
1
1
TMS (tetramethylsilane) as internal standard and coupling
13
of ester and the formation of carbohydrazide. Target com-
pounds 8a-j were finally synthesized by the cyclization of
carbohydrazide 6 with different aromatic carboxylic acids
constants J are expressed in Hertz. C NMR spectra were
recorded on Jeol (100.5 MHz) spectrometer. The Mass
spectra were recorded on a Waters micromass LCT Mass
Spectrometer TOF MS on LCT micromass and only the
major peaks are quoted.
7
a-j (Schemes 2 and 3). Consumption of carbohydrazide 6
was confirmed by absence of D O exchangeable singlets
2
1
for –NH and –NH in H NMR along with the absence of
General Procedure for the Synthesis of 3-Azidopyridine (2)
2
carbonyl absorption band in IR spectrum of the 2,5-
[52].
3-Aminopyridine (1) (2.0 g, 21.28 mmol) was
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
1,3,4-Oxadiazole, Pyridine, 1,2,3-Triazole, Diazotization, Cyclization,
Pharmacologically Active Moieties
Scheme 1. Synthesis of carbohydrazide 6 from 3-aminopyridine.
dissolved in a solution of concentrated sulfuric acid
2.4 mL) and water (14 mL). The resultant solution was
cooled to 0°C and a solution of sodium nitrite (1.76g,
5.53 mmol) in water (10 mL) was added dropwise, with
stirring. The solution was stirred at this temperature for
in 2.90g (85%) yield. Colour: white solid; mp 211-213°C;
(
IR (KBr): 3435, 3066, 2454, 1885, 1704, 1438, 1276,
-
1 1
1122, 1008, 785 cm ; H NMR (δ, DMSO-d , 400 MHz):
6
2
13.21 (brs, 1H, -COOH, D O exchangeable), 8.87-8.81
2
(m, 2H), 8.14 (d, 1H, J = 8.80Hz), 7.70 (dd, 1H, J = 8.04
13
1
3
5min and then a solution of sodium azide (2.35g,
6.17 mmol) in water (8mL) was added to it with
& 4.40Hz), 2.52 (s, 3H, -CH3); C NMR (δ, DMSO-d6,
100.5 MHz): 162.54 (C = O), 151.02, 146.04, 139.69,
vigorous stirring. The mixture was stirred for 1 h at 0°C
and then kept overnight at room temperature. The
136.98, 133.33, 132.30, 124.57, 9.62 (CH ); TOF ES+
m/z : 205 (M +1).
3
+
reaction mixture was then treated with saturated Na CO3
General Procedure for the Synthesis of Ethyl 5-Methyl-1-
2
solution, and extracted thrice with dichloromethane. The
combined extracts were washed with water, dried over
sodium sulfate and solvent was removed in vacuum to
obtain 3-azidopyridine (2) in 2.29 g (90%) yield. Colour:
light yellow oil; IR (Film): 2924, 2363, 2134, 2096,
(Pyridin-3-yl)-1H-1,2,3-Triazole-4-Carboxylate (5).
A
round bottom flask was charged with 5-methyl-
1-(pyridin-3-yl)-1H-1,2,3-triazole-4-carboxylic acid (4)
(2.0 g, 9.80mmol) in absolute ethanol (50 mL), followed
by addition of 1 mL of conc. H SO . The resulting
2
4
-1 1
1
4
7
1
474, 1420, 1305, 1219, 772cm ; H NMR (δ, CDCl ,
mixture was refluxed for 5 h and reaction was monitored
on TLC. After completion, ethanol was evaporated
under reduced pressure and the residue left was treated
with ice cold water. The resulting contents were
rendered alkaline by adding sufficient amount of
ammonia solution. The mixture was then extracted with
dichloromethane (3 x 50mL). The combined organic
layer was dried over anhydrous sodium sulfate and the
solvent was removed under vacuum to obtain the
desired compound in 2.02g (89%) yield. Colour:
creamish liquid; IR (Film): 2983, 2925, 1720, 1568,
3
00MHz): 8.35-8.31 (m, 2H), 7.32-7.28 (m, 1H), 7.26-
13
.22 (m, 1H); C NMR (δ, CDCl , 100.5MHz): 145.86,
3
41.14, 136.93, 125.75, 123.99.
General Procedure for the Synthesis of 5-Methyl-1-
(
Pyridin-3-yl)-1H-1,2,3-Triazole-4-Carboxylic Acid (4). To
a
1
cooled solution of sodium methoxide (0.90g,
6.67 mmol) in 20 mL of dry methanol, a solution of
ethylacetoacetate (3) (2.17g, 16.67 mmol) in 10mL of
dry methanol was added dropwise under inert atmosphere
of nitrogen. The contents were stirred at 0°C for
-
1 1
1
(
5minutes and then a solution of 3-azidopyridine (2)
2.0 g, 16.67 mmol) in methanol (10 mL) was added to it
dropwise. Stirring was continued for additional
0minutes at 0°C and then at room temperature for
1491, 1431, 1375, 1248, 1112, 981, 709cm ; H NMR
(δ, CDCl , 400MHz): 8.82 (d, 1H, J = 5.16Hz), 8.78 (d,
3
1H, J= 2.20 Hz), 7.91-7.88 (m, 1H), 7.59 (dd, 1H,
2
J = 8.04 & 5.12 Hz), 4.47 (q, 2H, -COOCH CH ), 2.65
2
3
another 6 h. Completion of reaction was monitored on
TLC. The solvent was then evaporated and the residue
left was treated with ice cold water and neutralized with
acetic acid. The precipitated solid was filtered, washed
with water and recrystallized from methanol to obtain 4
(s, 3H, -CH ), 1.45 (t, 3H, J = 7.72 Hz, -COOCH CH );
C NMR (δ, CDCl , 100.5 MHz): 161.29 (C = O), 151.02,
3
3
2
3
1
3
145.74, 138.99, 136.97, 132.72, 132.16, 124.14, 61.13
(OCH ), 14.21 (OCH CH ), 9.80 (CH ); TOF ES+ m/z :
2
2
3
3
+
233 (M +1).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Kaushik, K. Kushwaha, M. Chand, M. Vashist, and S. C. Jain
Vol 000
Scheme 2. Synthesis of 2,5-disubstituted-1,3,4-oxadiazoles 8a-i from carbohydrazide 6.
General Procedure for the Synthesis of 5-Methyl-1-
Pyridin-3-yl)-1H-1,2,3-Triazole-4-Carbohydrazide (6). To
Yield: 0.17g (56%); mp 174-176°C; IR (KBr): 2923, 1549,
1425, 1078, 1004, 706cm ; H NMR (δ, CDCl3,
400MHz): 8.90 (brs, 2H), 8.20 (dd, 2H, J=7.76 &
-
1
1
(
a solution of ethyl 5-methyl-1-(pyridin-3-yl)-1H-1,2,3-
triazole-4-carboxylate (5) (2.0 g, 8.62mmol) in absolute
ethanol (20 mL), hydrazine hydrate (0.86 g, 17.24mmol)
was added and the reaction mixture was refluxed for 14h.
Progress of the reaction was monitored on TLC and after
completion, contents were cooled at room temperature.
Solid that precipitated out was filtered and washed with
ethanol to obtain the desired compound in 1.52g (81%)
yield. Colour: white crystalline solid; mp 189-191°C; IR
1.84Hz), 7.96 (d, 1H, J=8.28Hz), 7.63-7.51 (m, 4H),
+
2.84 (s, 3H, -CH ); TOF ES+ m/z : 305 (M +1). Anal.
3
Calcd. For C H N O: C, 63.15; H, 3.97; N, 27.62;
16 12 6
Found: C, 63.20; H, 3.99; N, 27.58.
2-(2-Fluorophenyl)-5-(5-Methyl-1-(Pyridin-3-yl)-1H-1,2,3-
Triazol-4-yl)-1,3,4-Oxadiazole (8b).
It was obtained as
light brown solid; Yield: 0.20 g (62%); mp 166-168°C;
IR (KBr): 2924, 2853, 2371, 1617, 1461, 1272, 1231,
-
1
1
(
1
4
(
KBr): 3312, 3248, 3096, 1654, 1572, 1432, 1279, 1194,
1057, 909, 811, 747 cm ; H NMR (δ, CDCl3,
400 MHz): 8.88 (brs, 2H), 8.20 (t, 1H, J = 6.96 Hz), 7.97
(d, 1H, J = 8.08 Hz), 7.63-7.56 (m, 2H), 7.37-7.28 (m,
-1
1
083, 954, 806,703 cm ; H NMR (δ, DMSO-d6,
00MHz): 9.81 (s, 1H, -NH, D O exchangeable), 8.87
2
1
3
d, 1H, J =2.20 Hz), 8.80-8.79 (m, 1H), 8.16-8.13 (m,
2H), 2.82 (s, 3H, -CH3);
C NMR (δ, CDCl3,
1
H), 7.69 (dd, 1H, J =8.08 & 5.12Hz), 4.50 (s, 2H, -
100.5 MHz): 161.52-111.67 (C-Aromatic), 158.48 (C-F),
13
+
NH , D O exchangeable), 2.54 (s, 3H, -CH ); C NMR
10.07 (CH ); TOF ES+ m/z : 323 (M +1). Anal. Calcd.
2
2
3
3
(
δ, DMSO-d , 100.5 MHz): 160.06 (C = O), 150.87,
For C H FN O: C, 59.63; H, 3.44; N, 26.08; Found:
6
16 11
6
1
45.86, 137.74, 136.86, 133.13, 132.27, 124.49, 9.07
C, 59.68; H, 3.41; N, 26.12.
+
(CH ); TOF ES+ m/z : 219 (M +1).
2-(4-Fluorophenyl)-5-(5-Methyl-1-(Pyridin-3-yl)-1H-1,2,3-
3
General Procedure for the Synthesis of Compounds 8a-j.
Triazol-4-yl)-1,3,4-Oxadiazole (8c).
It was obtained as
An equimolar mixture of 5-methyl-1-(pyridin-3-yl)-1H-
,2,3-triazole-4-carbohydrazide (6) (0.22 g, 1mmol) and
substituted aromatic/heterocyclic carboxylic acids 7a-j
1 mmol) in phosphorus oxychloride (5mL) was heated at
0-80°C for 6 h and progress of the reaction was
monitored on TLC. After completion of the reaction,
phosphorus oxychloride was distilled and ice cold water
was added to it. Reaction mixture was neutralized by
adding a saturated sodium bicarbonate solution. Solid that
separated out was filtered, washed with water, dried and
purified by column chromatography using silica gel (60-
brown solid; Yield: 0.18 g (57%); mp 204-206°C; IR
1
(KBr): 3107, 2927, 1608, 1510, 1425, 1223, 1074, 850,
-
1
1
817, 707 cm ; H NMR (δ, CDCl , 400 MHz): 8.87
3
(
7
(brs, 2H), 8.25-8.21 (m, 2H), 7.96 (d, 1H, J = 7.32 Hz),
7.62 (dd, 1H, J = 8.04 & 5.12 Hz), 7.25-7.23 (m, 2H),
1
3
2.82 (s, 3H, -CH3); C NMR (δ, CDCl , 100.5 MHz):
3
163.71 (C-F), 151.27-116.39 (C-Aromatic), 9.94 (CH );
3
+
TOF ES+ m/z : 323 (M +1). Anal. Calcd. For
C H FN O: C, 59.63; H, 3.44; N, 26.08; Found: C,
1
6
11
6
59.70; H, 3.48; N, 26.03.
2-(2-Chlorophenyl)-5-(5-Methyl-1-(Pyridin-3-yl)-1H-1,2,3-
1
(
20mesh) as an adsorbent using hexane/ethylacetate
80:20) as eluent and the desired compounds 8a-j were
obtained.
Triazol-4-yl)-1,3,4-Oxadiazole (8d).
light brown solid; Yield: 0.20g (58%); mp 141-143°C; IR
It was obtained as
(KBr): 2961, 2925, 2854, 1598, 1542, 1432, 1261, 1088,
-
1 1
2
-(5-Methyl-1-(Pyridin-3-yl)-1H-1,2,3-Triazol-4-yl)-5-Phenyl-
1041, 810, 745cm ; H NMR (δ, CDCl , 400MHz): 8.80
3
1
,3,4-Oxadiazole (8a). It was obtained as light brown solid;
(brs, 2H), 8.07 (d, 1H, J=7.36Hz), 7.88 (d, 1H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
1,3,4-Oxadiazole, Pyridine, 1,2,3-Triazole, Diazotization, Cyclization,
Pharmacologically Active Moieties
Scheme 3. Synthesis of 2-(5-Methyl-1-(pyridin-3-yl)-1H-1,2,3-triazol-4-yl)-5-(2-phenylquinolin-4-yl)-1,3,4-oxadiazole (8j) from carbohydrazide 6 and
-phenylquinoline-4-carboxylic acid (7j).
2
J=8.04Hz), 7.53 (d, 2H, J=7.32Hz), 7.44 (t, 1H,
(m, 1H), 2.84 (s, 3H, -CH ); TOF ES+ m/z : 350
3
+
J=6.60Hz), 7.39 (t, 1H, J=8.04Hz), 2.75 (s, 3H, -CH );
(M +1). Anal. Calcd. For C H N O : C, 55.02; H,
3
16 11 7 3
13
C NMR (δ, CDCl , 100.5MHz): 162.76--124.32 (C-
3.17; N, 28.07; Found: C, 54.95; H, 3.15; N, 28.11.
3
Aromatic), 132.28 (C-Cl), 10.09 (CH ); TOF ES+ m/z :
2-(4-Methylphenyl)-5-(5-Methyl-1-(Pyridin-3-yl)-1H-1,2,3-
3
+
+
3
5
38 (M ), 340 (M +2). Anal. Calcd. For C H ClN O: C,
6.73; H, 3.27; N, 24.81; Found: C, 56.65; H, 3.31; N, 24.89.
Triazol-4-yl)-1,3,4-Oxadiazole (8h).
It was obtained as
1
6
11
6
light brown solid; Yield: 0.19 g (60%); mp 143-145°C;
2
-(4-Chlorophenyl)-5-(5-Methyl-1-(Pyridin-3-yl)-1H-1,2,3-
IR (KBr): 3079, 2923, 2853, 1612, 1539, 1497, 1481,
1437, 1284, 1072, 823, 808, 705 cm ; H NMR (δ,
-
1
1
Triazol-4-yl)-1,3,4-Oxadiazole (8e). It was obtained as
white solid; Yield: 0.21 g (62%); mp 183-185°C; IR
KBr): 2926, 2854, 1599, 1461, 1270, 1093, 836, 705cm ;
H NMR (δ, CDCl , 400MHz): 8.88 (brs, 2H), 8.17 (d,
H, J =8.08 Hz), 7.98 (d, 1H, J = 9.52Hz), 7.65-7.61 (m,
H), 7.54 (d, 2H, J =8.76 Hz), 2.82 (s, 3H, -CH ); TOF
ES+ m/z : 338 (M ), 340 (M +2). Anal. Calcd. For
CDCl , 400 MHz): 8.86-8.85 (m, 2H), 8.11 (d, 2H,
3
-1
(
J = 8.04 Hz), 7.95 (d, 1H, J = 8.08 Hz), 7.60 (dd, 1H,
J = 8.04 & 5.12 Hz), 7.35 (d, 2H, J = 8.04 Hz), 2.81 &
1
3
1
3
2
1
2.45 (s, 3H each, 2x-CH3); C NMR (δ, CDCl3,
100.5 MHz): 164.68-120.62 (C-Aromatic), 21.68
(Phenyl-CH ), 10.11 (Triazole-CH ); TOF ES+ m/z :
3
+
+
3
3
+
C H ClN O: C, 56.73; H, 3.27; N, 24.81; Found: C,
319 (M +1). Anal. Calcd. For C H N O: C, 64.14; H,
17 14 6
16
11
6
56.79; H, 3.32; N, 24.74.
4.43; N, 26.40; Found: C, 64.10; H, 4.48; N, 26.47.
2
-(5-Methyl-1-(Pyridin-3-yl)-1H-1,2,3-Triazol-4-yl)-5-
2-(5-Methyl-1-(Pyridin-3-yl)-1H-1,2,3-Triazol-4-yl)-5-
(
3-Nitrophenyl)-1,3,4-Oxadiazole (8f). It was obtained
(Pyridin-3-yl)-1,3,4-Oxadiazole (8i).
It was obtained as
as brown solid; Yield: 0.20 g (58%); mp 184-186°C;
light yellow solid; Yield: 0.19 g (62%); mp 168-170°C;
IR (KBr): 2923, 2852, 1524, 1342, 1284, 1107, 1074,
IR (KBr): 2924, 1597, 1430, 1274, 1192, 1079, 1023,
-
1
1
-1 1
8
9
8
7
5
1
56, 802, 707 cm ; H NMR (δ, CDCl , 400 MHz):
820, 745, 709 cm ; H NMR (δ, CDCl
, 400 MHz): 9.45
3
3
.07 (s, 1H), 8.88 (brs, 2H), 8.56 (d, 1H, J = 7.32 Hz),
.44 (d, 1H, J = 8.76 Hz), 7.97 (d, 1H, J = 8.04 Hz),
.93 (t, 1H, J = 7.68 Hz), 7.62 (dd, 1H, J = 8.04 &
(s, 1H), 8.85-8.81 (m, 3H), 8.57-8.55 (m, 1H), 7.95-7.93
13
(m, 1H), 7.61-7.56 (m, 2H), 2.80 (s, 3H, -CH
NMR (δ, CDCl , 100.5 MHz): 162.41-119.99 (C-Aromatic),
10.11 (CH ); TOF ES+ m/z : 306 (M +1). Anal. Calcd.
For C15 O: C, 59.01; H, 3.63; N, 32.12; Found: C,
59.08; H, 3.66; N, 32.17.
);
C
3
3
1
3
+
.12 Hz), 2.84 (s, 3H, -CH ); C NMR (δ, CDCl3,
3
3
00.5 MHz): 162.58-122.16 (C-Aromatic), 10.00
H N
11 7
+
(
CH ); TOF ES+ m/z : 350 (M +1). Anal. Calcd. For
3
C H N O : C, 55.02; H, 3.17; N, 28.07; Found: C,
General
Procedure
for
the
Synthesis
of
1
6
11
7
3
5
5.10; H, 3.20; N, 28.12.
2-Phenylquinoline-4-Carboxylic Acid (7j).
It was
2
-(5-Methyl-1-(Pyridin-3-yl)-1H-1,2,3-Triazol-4-yl)-5-(4-
synthesized using the same procedure as mentioned in
Reference [53].
Nitrophenyl)-1,3,4-Oxadiazole (8 g). It was obtained as
creamish solid; Yield: 0.21g (61%); mp 294-296°C; IR
2-(5-Methyl-1-(Pyridin-3-yl)-1H-1,2,3-Triazol-4-yl)-5-(2-
(
9
(
KBr): 3104, 2922, 2851, 1521, 1343, 1285, 1107, 1074,
Phenylquinolin-4-yl)-1,3,4-Oxadiazole (8j).
obtained as light yellow solid; Yield: 0.115g (58%); mp
188-190°C; IR (KBr): 2925, 2854, 1600, 1474, 1262,
It was
-1 1
77, 856, 708cm ; H NMR (δ, CDCl , 400MHz): 8.88
3
brs, 2H), 8.43 (brs, 4H), 7.97-7.95 (m, 1H), 7.64-7.61
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Kaushik, K. Kushwaha, M. Chand, M. Vashist, and S. C. Jain
Vol 000
-
1
1
1
4
8
4
4
1
176, 1105, 836, 812, 710cm ; H NMR (δ, CDCl ,
[19] Pertino, M. W.; Theoduloz, C.; Butassi, E.; Zacchino, S.;
Schmeda-Hirschmann, G. Molecules 2015, 20, 8666.
3
00MHz): 10.91 (s, 1H, H-3’), 10.52-10.48 (m, 1H),
.88 (brs, 1H), 8.51 (d, 1H, J = 8.24Hz), 8.28-8.22 (m,
H), 8.03-8.01 (m, 1H), 7.85-7.78 (m, 1H), 7.68-7.53 (m,
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Acknowledgments. Authors Reena Kaushik and Khushbu
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet