A facile approach for the synthesis of novel 1,2,4-triazolo[4,3-a] pyridine derivatives in single step

Article abstract of DOI:10.1002/jhet.1977

A series of novel substituted 4-trifluoromethyl-pyridin-2-yl hydrazide derivatives 5 and 7-trifluoromethyl- 1,2,4-triazolo[4,3-a]pyridine derivatives 6 were synthesized through a facile method in single step from 2-hydrazino-pyridine derivatives 4 and their reaction with aliphatic/aromatic acids in the presence of POCl3 and PCl5. In each reaction, an intermediate 5 and product 6 were formed in definite proportion except in 5a, 5d, and 6e and were independent of reaction time and temperature.

Full text of DOI:10.1002/jhet.1977

Month 2014
A Facile Approach for the Synthesis of Novel 1,2,4-Triazolo[4,3-a]
Pyridine Derivatives in Single Step
*
G. Santhosh Kumar, C. Kurumurthy, P. Sambasiva Rao, B. Veeraswamy, P. Shanthan Rao, and B. Narsaiah
Fluoroorganic Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India
*
E-mail: narsaiahbanda84@gmail.com
Received October 10, 2012
DOI 10.1002/jhet.1977
Published online in Wiley Online Library (wileyonlinelibrary.com).
A series of novel substituted 4-trifluoromethyl-pyridin-2-yl hydrazide derivatives 5 and 7-trifluoromethyl-
1,2,4-triazolo[4,3-a]pyridine derivatives 6 were synthesized through a facile method in single step from
2-hydrazino-pyridine derivatives 4 and their reaction with aliphatic/aromatic acids in the presence of
POCl3 and PCl5. In each reaction, an intermediate 5 and product 6 were formed in definite proportion
except in 5a, 5d, and 6e and were independent of reaction time and temperature.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
cyclized product, we reacted compound 4 with aliphatic/ar-
omatic acids in POCl3/PCl5, and obtained N-acylated prod-
uct 5 and cyclized product 6 in definite proportions. The
sequence of reaction is mainly acylation, then chlorination
followed by cyclization. Specifically, with compound 4 on
reaction with formic acid or trifluoroacetic acid, exclu-
sively N-formyl or N-trifluoroacetyl products 5 are formed,
irrespective of long reaction time at reflux temperature, and
it is attributed to no-enol form as a result of the abscence of
chlorination. Thereby, there was no cyclization. The infra-
red spectrum of compound 5 shows the presence of amide
peak for NH at 3420 Cmꢀ1 and amide carbonyl peak at
1660 Cmꢀ1. In all other cases, the acyl product is in
keto–enol equilibrium form, and enol form promoted chlo-
rination and formed product 6, whereas keto form retained
to have product 5 only. On the other hand, compound 4 on
reaction with benzoic acid gave exclusively product 6e,
which is assumed to be the formation of benzoyl derivative
in enol form followed by chlorination and cyclization. The
sequence of reactions outlined in Schemes 1 and 2, mech-
anism in Scheme 3, and products are presented in Table 1.
The 1,2,4-triazolo[4,3-a]pyridine ring system is known
since 1903 [1]; however, extensive studies have not been ini-
tiated even though they have interesting pharmacological
properties [2–5] such as use in cancer chemotherapy [6].
The 1,2,4-triazole-fused heterocycles were reviewed more
recently [7], some of them found to show anti-inflammatory
[8], bactericidal [9], fungicidal [10], analgesic [11–13],
and anxiolytic [14] activity. The method of synthesis of
1,2,4-triazolo[4,3-a]pyridines is mainly from 2-pyridyl
hydrazine by cyclodehydration agents [15–22]. On the
basis of the importance and continuation of our efforts
[23–25] to synthesize potential molecules, we have devel-
oped a convenient method for the synthesis of novel
1,2,4-triazolo[4,3-a]pyridine derivatives, and are reporting
here for the first time.
RESULTS AND DISCUSSION
The 2-hydrazino-4-trifluoromethyl-6-phenyl pyridine 4
was prepared from 1,1,1-trifluoro-4-phenyl-butane-2,4-
dione on reaction with cyanoacetamide to form exclusively
3-cyano-4-trifluoromethyl-6-phenyl 2(1H)pyridone 1 [26].
Compound 1 on hydrolysis followed by decarboxylation
resulted in 4-trifluoro-methyl-6-phenyl 2(1H)pyridone 2
[27]. Compound 2 on reaction with POCl3 formed 2-
chloro-4-trifluoromethyl-6-phenyl pyridine 3 [27] followed
by reaction with hydrazine hydrate, which resulted in the
formation of compound 4 [27]. The 2-hydrazino-4-
trifluoromethyl-6-phenyl pyridine 4 was further reacted
with acetic acid under different set of conditions by using
H2SO4, ZnCl2, PTSA, POCl3, high temperature, and
under-microwave-irradiation conditions. In all the cases,
the acylation product was found to be formed. To have
CONCLUSION
A series of novel substituted 4-trifluoromethyl-pyridin-
2-yl hydrazides 5 and 7-trifluoromethyl-1,2,4-triazolo
[4,3-a]pyridine derivatives 6 were prepared in a single step
by facile method and is applicable to the synthesis of di-
verse functionalized pyridine derivatives.
EXPERIMENTAL
Melting points were recorded using open glass capillaries on
Casia-siamia (VMP-AM) melting point apparatus and were
uncorrected. Infrared spectra were recorded on a Perkin-Elmer
© 2014 HeteroCorporation

G. Santhosh Kumar, C. Kurumurthy, P. Sambasiva Rao, B. Veeraswamy,
P. Shanthan Rao, and B. Narsaiah
Vol 000
Scheme 1
Scheme 2
Scheme 3
FT-IR 240-C spectrophotometer using KBr optics. 1H NMR
spectra were recorded on Avance (Bruker, Switzerland) 300-
MHz spectrometer in CDCl3 and DMSO-d6 using TMS as an inter-
nal standard. EI and chemical ionization mass spectra were recorded
on VG-7070 H instrument at 70eV. All reactions were monitored
by TLC on pre-coated silica gel 60 F254 (mesh). Spots were visual-
ized with UV light. Merck silica gel (100–200 mesh) was used for
column chromatography. CHN analyses were recorded on a Vario
EL analyzer.
Preparation of 3-cyano-4-trifluoromethyl-2(1H)pyridone (1) [26]
Preparation of 4-trifluoromethyl-2(1H)pyridone (2) [27]
Preparation of 2-chloro-6-phenyl-4-(trifluoromethyl)pyridine (3) [27]
Preparation of 1-(6-phenyl-4-(trifluoromethyl)pyridin-
2-yl)hydrazine (4) [27]
for 6–8 h, at 120ꢁC and cooled to room temperature. The excess
POCl3 was distilled under vacuum, and the residue was treated
with crushed ice. The aqueous solution was extracted with ethyl
acetate twice (30 mL each), and combined extract was washed
with saturated sodium bicarbonate solution followed by distilled
water till washings were neutral in pH. The organic layer was
separated, dried over sodium sulfate, and concentrated. The
crude product was purified by passing it through a column
packed with silica gel and ethyl acetate–n-hexane used as
eluents.
Spectral data
N0-(6-Phenyl-4-(trifluoromethyl)pyridin-2-yl)formohydrazide
(5a). IR (KBr, cmꢀ1): 3420 (-CONH-), 1660 (-CONH-), 1168,
1
1125 (C-F); H NMR (CDCl3, 300 MHz): d 7.42-7.58(m, 4H,
Ar-H), 7.99-8.03(m, 2H, Ar-H), 8.18(s, 1H, Ar-H), 8.68
(br, 1H,-NH-) 8.99 (s, 1H, Ar-H), 10.21(br, 1H,-NH-); MS
(ESI): m/z [(M + H)+]: 382, [(M + Na)+]: 304; Anal. Calcd
for C13H10F3N4O: C 55.52, H 3.58, N 14.94%. Found:
C 55.21, H 3.47, N 14.82%.
Preparation of 4-trifluoromethyl-6-phenyl-pyridine-2-yl
hydrazide (5)/substituted 7-trifluoromethyl-1,2,4-triazolo
[4,3-a]pyridine derivatives (6): General procedure.
The 2-hydrazino-4-trifluoromethyl-6-phenyl pyridine 4 (0.2 g,
0.7 mmol) and aliphatic/aromatic acid (1.1 mmol) were taken
in a clean and dry round bottom flask having POCl3 (6–8 mL),
and PCl5 (0.05 g) was added. The reaction mixture was refluxed
N0-(6-Phenyl-4-(trifluoromethyl)pyridin-2-yl)acetohydrazide
(5b). IR (KBr, cmꢀ1): 3421 (-CONH-), 1658 (-CONH-), 1172,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
A Facile Approach for the Synthesis of Novel 1,2,4-Triazolo[4,3-a]
Pyridine Derivatives in Single Step
Table 1
Preparation of substituted 4-trifluoromethyl-pyridine-2-yl hydrazide derivatives 5 and 7-trifluorormethyl-1,2,4-triazolo[4,3-a]pyridine derivatives 6.
Compound
No.
mp
ꢁC
Yield
%
Compound
No.
mp
ꢁC
Yield
%
R
H
CH3
CH2CH3
CF3
C6H5
4-CH3-C6H4
4-OCH3-C6H4
3-OCH3-C6H4
4-F-C6H4
3-F-C6H4
4-Cl-C6H4
3-Cl-C6H4
3-Br-C6H4
3-CN-C6H4
3-pyridyl
2-furyl
5a
5b
5c
5d
—
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
255–257
262–264
260–262
256–257
—
268–270
250–252
245–247
240–242
252–254
268–270
261–262
278–280
258–261
251–252
238–242
78
61
68
82
—
32
28
31
38
35
28
29
31
28
45
30
—
6b
6c
—
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
—
—
31
27
—
69
56
50
48
42
45
41
40
48
45
38
39
171–173
178–180
—
194–196
201–204
207–209
201–203
198–200
191–193
220–221
211–213
232–234
228–232
200–202
209–212
1128 (C-F); 1H NMR (CDCl3, 300MHz): d 2.21(s, 1H,-CH3),
6.82(s, 1H, Ar-H), 7.00(br, 1H,-NH-), 7.42(s, 1H, Ar-H),
7.48–7.52(m, 3H, Ar-H), 7.60(br, 1H,-NH-), 7.90–7.96(m,
2H, Ar-H); MS (ESI): m/z [(M + H)+]: 296, [(M + Na)+]: 318;
Anal. Calcd for C14H12F3N4O: C 56.95, H 4.10, N 14.23%.
Found: C 56.72, H 4.05, N 14.10%.
3-Methyl-5-phenyl-7-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]
pyridine (6b). IR (KBr, cmꢀ1): 1648 (C═N), 1172, 1139 (C-F);
1H NMR (CDCl3, 300 MHz): d 2.12(s, 3H,-CH3), 6.78(s, 1H,
Ar-H), 7.42–7.48(m, 2H, Ar-H), 7.52–7.60(m, 3H, Ar-H), 8.05
(s, 1H, Ar-H); MS (ESI): m/z [(M + H)+]: 278, [(M + Na)+]:
300; Anal. Calcd for C13H10F3N3: C 60.65, H 3.64, N 15.16%.
Found: C 60.42, H 3.69, N 15.08%.
N’-(6-Phenyl-4-(trifluoromethyl)pyridin-2-yl)propionohydrazide
(5c). IR (KBr, cmꢀ1): 3422 (-CONH-), 1660 (-CONH-), 1174,
1138 (C-F); 1H NMR (CDCl3, 300 MHz): d 1.38(t, 3H,-CH3), 2.41
(q, 2H,-CH2-), 6.80(s, 1H, Ar-H), 7.02(br, 1H,-NH-), 7.42(s, 1H,
Ar-H), 7.48–7.51(m, 3H, Ar-H), 7.61(br, 1H,-NH-), 7.89–7.96
(m, 2H, Ar-H); MS (ESI): m/z [(M + H)+]: 310, [(M + Na)+]:
332; Anal. Calcd for C15H14F3N3O: C 58.25, H 4.56, N 13.59%.
Found: C 57.95, H 4.49, N 13.09%.
7.19–7.24(m, 2H, Ar-H), 8.26(s, 1H, Ar-H); MS (ESI): m/z
[(M + H)+]: 340, [(M + Na)+]: 362; Anal. Calcd for C19H12F3N3:
C 67.25, H 3.56, N 12.38%. Found: C 67.02, H 3.49, N 12.23%.
4-Methyl-N’-(6-phenyl-4-(trifluoromethyl)pyridin-2-yl)
benzohydrazide (5f).
IR (KBr, cmꢀ1): 3420 (-CONH-),
1656 (-CONH-), 1168, 1130 (C-F); 1H NMR (CDCl3,
300 MHz): d 2.30(s, 3H,-CH3), 7.02(s, 1H, Ar-H), 7.12
(br, 1H,-NH-), 7.31–7.49(m, 7H, Ar-H), 7.51–7.52(m, 3H,
Ar-H), 8.41(br, 1H,-NH-); MS (ESI): m/z [(M + H)+]:
372; Anal. Calcd for C20H16F3N3O: C 64.69, H 4.34,
N 11.32%. Found: C 64.32, H 4.39, N 11.41%.
5-Phenyl-3-p-tolyl-7-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]
pyridine (6f). IR (KBr, cmꢀ1): 1659 (C═N) 1172, 1128 (C-F);
1H NMR (CDCl3, 300 MHz): d 2.27(s, 3H,-CH3), 6.84–6.96
(m, 5H, Ar-H), 7.06–7.12(m, 4H, Ar-H), 7.23(s, 1H, Ar-H), 8.18
(s, 1H, Ar-H); MS (ESI): m/z [(M + H)+]: 354, [(M + Na)+]: 376;
Anal. Calcd for C20H14F3N3: C 67.98, H 3.99, N 11.89%. Found:
C 67.77, H 3.89, N 11.80%.
4-Methoxy-N’-(6-phenyl-4-(trifluoromethyl)pyridin-2-yl)
benzohydrazide (5g).
IR (KBr, cmꢀ1): 3423 (-CONH-), 1660
1
(-CONH-),1171, 1125 (C-F); H NMR (CDCl3, 300 MHz): d 3.91
(s, 3H,-OCH3), 6.90(s, 1H, Ar-H), 7.12(br, 1H,-NH-), 7.31–7.49
(m, 7H, Ar-H), 7.51–7.52(m, 3H, Ar-H), 8.41(br, 1H,-NH-);
MS (ESI): m/z [(M + H)+]: 388, [(M + Na)+]: 410; Anal. Calcd for
C20H16F3N4O2: C 62.01, H 4.16, N 10.85%. Found: C 61.88,
H 4.19, N 10.89%.
3-Ethyl-5-phenyl-7-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine
1
(6c). IR (KBr, cmꢀ1): 1649 (C═N) 1169, 1135 (C-F); H NMR
(CDCl3, 300MHz): d 1.40(t, 3H,-CH3), 2.32(q, 2H,-CH2-), 6.79
(s, 1H, Ar-H), 7.42–7.48(m, 2H, Ar-H), 7.53–7.60(m, 3H, Ar-H),
8.04 (s, 1H, Ar-H); MS (ESI): m/z [(M + H)+]: 292; Anal. Calcd
for C15H12F3N3: C 61.85, H 4.15, N 14.43%. Found: C 61.56, H
4.21, N 14.39%.
3-(4-Methoxyphenyl)-5-phenyl-7-(trifluoromethyl)-[1,2,4]
triazolo[4,3-a]pyridine (6g).
IR (KBr, cmꢀ1): 1647 (C═N)
1
2,2,2-Trifluoro-N’-(6-phenyl-4-(trifluoromethyl)pyridin-2-
1164, 1139 (C-F); H NMR (CDCl3, 300MHz): d 3.89(s, 3H,-
OCH3), 7.12–7.21(m, 2H, Ar-H), 7.35–7.55(m, 4H, Ar-H),
7.65–7.78(m, 4H, Ar-H), 7.99(s, 1H, Ar-H); MS (ESI):
m/z [(M + H)+]: 370, [(M + Na)+]: 392; Anal. Calcd for
C20H14F3N3O: C 65.04, H 3.82, N 11.38%. Found: C
64.85, H 3.78, N 11.28%.
yl)acetohydrazide (5d).
IR (KBr, cmꢀ1): 3422 (-CONH-),
1660 (-CONH-), 1170, 1123 (C-F); 1H NMR (CDCl3,
300 MHz): d 6.80(s, 1H, Ar-H), 7.02(br, 1H,-NH-), 7.42
(s, 1H, Ar-H), 7.48–7.51(m, 3H, Ar-H), 7.61(br, 1H,-NH-),
7.89–7.96(m, 2H, Ar-H); MS (ESI): m/z [(M + H)+]: 350,
[(M + Na)+]: 372; Anal. Calcd for C14H9F6N3O: C 48.15, H
2.60, N 12.03%. Found: C 47.88, H 2.53, N 12.01%.
3-Methoxy-N’-(6-phenyl-4-(trifluoromethyl)pyridin-2-yl)
benzohydrazide (5h).
IR (KBr, cmꢀ1): 3422 (-CONH-),
3,5-Diphenyl-7-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine
(6e). IR (KBr, cmꢀ1): 1618 (C═N) 1159, 1123 (C-F); 1H NMR
(CDCl3, 300MHz): d 6.97(s, 1H, Ar-H), 7.05–7.11(m, 8H, Ar-H),
1668 (-CONH-), 1174, 1138 (C-F); 1H NMR (CDCl3,
300 MHz): d 3.90(s, 3H,-OCH3), 6.90(s, 1H, Ar-H), 7.12
(br, 1H,-NH-), 7.31–7.49(m, 7H, Ar-H), 7.51–7.52(m, 3H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

G. Santhosh Kumar, C. Kurumurthy, P. Sambasiva Rao, B. Veeraswamy,
P. Shanthan Rao, and B. Narsaiah
Vol 000
Ar-H), 8.41(br, 1H,-NH-); MS (ESI): m/z [(M + H)+]: 388,
[(M + Na)+]: 410; Anal. Calcd for C20H16F3N4O2: C 62.01,
H 4.16, N 10.85%. Found: C 62.32, H 4.09, N 10.98%.
3-(3-Methoxyphenyl)-5-phenyl-7-(trifluoromethyl)-[1,2,4]
3-(3-Chlorophenyl)-5-phenyl-7-(trifluoromethyl)-[1,2,4]
triazolo[4,3-a]pyridine (6l).
IR (KBr, cmꢀ1): 1649 (C═N)
1170, 1138 (C-F); H NMR (CDCl3, 300 MHz): d 6.96(s, 1H,
Ar-H), 7.01–7.12(m, 6H, Ar-H), 7.12–7.18(m, 2H, Ar-H), 7.33
(m, 1H, Ar-H) 8.21(s, 1H, Ar-H); MS (ESI): m/z [(M + H)+]:
374, [(M + Na)+]: 396; Anal. Calcd for C19H11ClF3N3: C 61.06,
H 2.97, N 11.24%. Found: C 61.23, H 2.89, N 11.36%.
1
triazolo[4,3-a]pyridine (6h).
IR (KBr, cmꢀ1): 1653 (C═N)
1
1169, 1122 (C-F); H NMR (CDCl3, 300MHz): d 3.90(s, 3H,-
OCH3), 7.11–7.21(m, 2H, Ar-H), 7.35–7.76(m, 8H, Ar-H), 8.01
(s, 1H, Ar-H); MS (ESI): m/z [(M+ H)+]: 370, [(M + Na)+]:
392; Anal. Calcd for C20H14F3N3O: C 65.04, H 3.82, N 11.38%.
Found: C 64.73, H 3.79, N 11.46%.
3-Bromo-N’-(6-phenyl-4-(trifluoromethyl)pyridin-2-yl)
benzohydrazide (5m).
IR (KBr, cmꢀ1): 3400 (-CONH-),
1659 (-CONH-), 1171, 1135 (C-F); 1H NMR (DMSO-d6,
300 MHz): d 6.90(s, 1H, Ar-H), 7.35–7.25(m, 5H, Ar-H), 7.70
(s, 1H, Ar-H), 7.94–8.07(m, 4H, Ar-H), 8.58(br, 1H,-NH-), 10.60
(br, 1H,-NH-); MS (ESI): m/z [(M +H)+]: 436; Anal. Calcd
for C19H13BrF3N3O: C 52.31, H 3.00, N 9.63%. Found: C 52.19,
H 3.12, N 9.49%.
4-Fluoro-N’-(6-phenyl-4-(trifluoromethyl)pyridin-2-yl)
benzohydrazide (5i). IR (KBr, cmꢀ1): 3413 (-CONH-), 1662
(-CONH-), 1170, 1138 (C-F); 1H NMR (DMSO-d6, 300MHz):
d 6.92(s, 1H, Ar-H), 7.36–7.50(m, 5H, Ar-H), 7.72(s, 1H, Ar-H),
7.94–8.06(m, 4H, Ar-H), 8.51(br, 1H,-NH-), 10.58(br, 1H,-NH-);
MS (ESI): m/z [(M + H)+]: 376, [(M + Na)+]: 398; Anal. Calcd
for C19H13F4N3O: C 60.80, H 3.49, N 11.20%. Found: C 60.62,
H 3.52, N 11.15%.
3-(3-Bromophenyl)-5-phenyl-7-(trifluoromethyl)-[1,2,4]
triazolo[4,3-a]pyridine (6m). IR (KBr, cmꢀ1): 1637 (C═N)
1169, 1128 (C-F); 1H NMR (CDCl3, 300 MHz): d 6.98–7.00
(m, 2H, Ar-H), 7.05–7.22(m, 6H, Ar-H), 7.30–7.39(m, 2H, Ar-H),
8.21(s, 1H, Ar-H); MS (ESI): m/z [(M + H)+]: 418; Anal. Calcd
for C19H11BrF3N3: C 54.57, H 2.65, N 10.05%. Found: C 54.31,
H 2.58, N 10.09%.
3-(4-Fluorophenyl)-5-phenyl-7-(trifluoromethyl)-[1,2,4]
triazolo[4,3-a]pyridine (6i). IR (KBr, cmꢀ1): 1638 (C═N)
1172, 1138 (C-F); 1H NMR (CDCl3, 300 MHz): d 6.72–6.79
(m, 2H, Ar-H), 6.93(s, 1H, Ar-H), 7.05–7.19(m, 6H, Ar-H),
7.31(m, 1H, Ar-H) 8.19(s, 1H, Ar-H); MS (ESI): m/z
[(M + H)+]: 358, [(M + Na)+]: 380; Anal. Calcd for C19H11F4N3:
C 63.87, H 3.10, N 11.76%. Found: C 63.99, H 3.19, N 11.80%.
3-Fluoro-N’-(6-phenyl-4-(trifluoromethyl)pyridin-2-yl)
benzohydrazide (5j). IR (KBr, cmꢀ1): 3413 (-CONH-), 1661
3-Cyano-N’-(6-phenyl-4-(trifluoromethyl)pyridin-2-yl)
benzohydrazide (5n). IR (KBr, cmꢀ1): 3338 (-CONH-), 1663
1
(-CONH-), 1170, 1136 (C-F); H NMR (DMSO-d6, 300 MHz):
d 6.91(s, 1H, Ar-H), 7.35–7.26(m, 5H, Ar-H), 7.70(s, 1H,
Ar-H), 7.95–8.06(m, 4H, Ar-H), 8.59(br, 1H,-NH-), 10.61
(br, 1H,-NH-); MS (ESI): m/z [(M + H)+]: 383; Anal. Calcd
for C20H13F3N4O: C 62.83, H 3.43, N 14.65%. Found: C
62.72, H 3.35, N 14.76%.
1
(-CONH-), 1168, 1128 (C-F); H NMR (DMSO-d6, 300 MHz): d
6.92(s, 1H, Ar-H), 7.36–7.50(m, 5H, Ar-H), 7.72(s, 1H, Ar-H),
7.94–8.06(m, 4H, Ar-H), 8.51(br, 1H,-NH-), 10.58(br, 1H,-NH-);
MS (ESI): m/z [(M + H)+]: 376, [(M + Na)+]: 398; Anal. Calcd for
C19H13F4N3O: C 60.80, H 3.49, N 11.20%. Found: C 60.92, H
3.38, N 11.32%.
3-(3-Cyanophenyl)-5-phenyl-7-(trifluoromethyl)-[1,2,4]triazolo
[4,3-a]pyridine (6n). IR (KBr, cmꢀ1): 1649 (C═N) 1172, 1123
1
(C-F); H NMR (CDCl3, 300 MHz): d 6.95(s, 1H, Ar-H), 7.00–
3-(3-Fluorophenyl)-5-phenyl-7-(trifluoromethyl)-[1,2,4]
7.10(m, 6H, Ar-H), 7.12–7.18(m, 2H, Ar-H), 7.32(m, 1H, Ar-H)
8.20(s, 1H, Ar-H); MS (ESI): m/z [(M + H)+]: 365; Anal. Calcd
for C20H11F3N4: C 65.93, H 3.04, N 15.38%. Found: C 65.71, H
3.12, N 15.49%.
triazolo[4,3-a]pyridine (6j).
IR (KBr, cmꢀ1): 1649 (C═N)
1165, 1125 (C-F); 1H NMR (CDCl3, 300 MHz): d 6.73–6.79
(m, 2H, Ar-H), 6.96(s, 1H, Ar-H), 7.05–7.20(m, 6H, Ar-H), 7.35
(m, 1H, Ar-H) 8.20(s, 1H, Ar-H); MS (ESI): m/z [(M + H)+]: 358,
[(M + Na)+]: 380; Anal. Calcd for C19H11F4N3: C 63.87, H 3.10,
N 11.76%. Found: C 63.66, H 3.06, N 11.89%.
N’-(6-Phenyl-4-(trifluoromethyl)pyridin-2-yl)nicotinohydrazide
(5o).
IR (KBr, cmꢀ1): 3382 (-CONH-), 1660 (-CONH-), 1172,
1
1136 (C-F); H NMR (CDCl3, 300MHz): d 7.42–7.58(m, 7H, Ar-
H), 7.99–8.03(m, 2H, Ar-H), 8.20–8.25(d, 1H, Ar-H), 8.68(br,
1H,-NH-) 8.99 (s, 1H, Ar-H), 9.22(br, 1H,-NH-); MS (ESI): m/z
[(M + H)+]: 359, [(M + Na)+]: 381; Anal. Calcd for C18H13F3N4O:
4-Chloro-N’-(6-phenyl-4-(trifluoromethyl)pyridin-2-yl)
benzohydrazide (5k). IR (KBr, cmꢀ1): 3422 (-CONH-), 1662
1
(-CONH-), 1169, 1133 (C-F); H NMR (DMSO-d6, 300 MHz): d
6.82(s, 1H, Ar-H), 7.36–7.50(m, 5H, Ar-H), 7.72(s, 1H, Ar-H),
7.94–8.06(m, 4H, Ar-H), 8.78(br, 1H,-NH-), 10.49(br, 1H,-NH-);
MS (ESI): m/z [(M + H)+]: 392, [(M + Na)+]: 414; Anal. Calcd for
C19H13ClF3N3O: C 58.25, H 3.34, N 10.73%. Found: C 58.56, H
3.41, N 10.68%.
C 60.34, H 3.66, N 15.64%. Found: C 60.10, H 3.52, N 15.75%.
5-Phenyl-3-(pyridin-3-yl)-7-(trifluoromethyl)-[1,2,4]triazolo
[4,3-a]pyridine (6o).
IR (KBr, cmꢀ1): 1653 (C═N) 1172,
1
1135 (C-F); H NMR (CDCl3, 300 MHz): d 6.98(s, 1H, Ar-H),
7.36–7.55(m, 4H, Ar-H), 7.66–7.76(m, 5H, Ar-H), 8.19(s, 1H,
Ar-H); MS (ESI): m/z [(M + H)+]: 341; Anal. Calcd for
C18H11F3N4: C 63.53, H 3.26, N 16.46 %. Found: C 63.31, H
3-(4-Chlorophenyl)-5-phenyl-7-(trifluoromethyl)-[1,2,4]
triazolo[4,3-a]pyridine (6k).
IR (KBr, cmꢀ1): 1656 (C═N)
1172, 1128 (C-F); 1H NMR (CDCl3, 300MHz): d 6.96(s, 1H,
Ar-H), 7.00–7.10(m, 6H, Ar-H), 7.12–7.18(m, 2H, Ar-H), 7.32
(m, 1H, Ar-H) 8.20(s, 1H, Ar-H); MS (ESI): m/z [(M + H)+]:
374, [(M + Na)+]: 396; Anal. Calcd for C19H11ClF3N3: C 61.06,
H 2.97, N 11.24%. Found: C 61.23, H 2.88, N 11.35%.
3.31, N 16.38 %.
N’-(6-Phenyl-4-(trifluoromethyl)pyridin-2-yl)furan-2-
carbohydrazide (5p).
IR (KBr, cmꢀ1): 3183(-CONH-),
1659 (-CONH-), 1170, 1136 (C-F); 1H NMR (DMSO-d6,
300 MHz): d 6.82(s, 1H, Ar-H), 7.12–7.21(m, 3H, Ar-H),
7.38–7.45(m, 2H, Ar-H), 7.99–8.03(m, 2H, Ar-H), 8.20–8.25
(d, 1H, Ar-H), 8.88(br, 1H,-NH-) 8.99 (s, 1H, Ar-H), 10.21(br,
1H,-NH-); MS (ESI): m/z [(M + H)+]: 348; Anal. Calcd for
C17H12F3N3O2: C 58.79, H 3.48, N 12.10%. Found: C 58.61,
H 3.29, N 12.08%.
3-Chloro-N’-(6-phenyl-4-(trifluoromethyl)pyridin-2-yl)
benzohydrazide (5l). IR (KBr, cmꢀ1): 3423 (-CONH-), 1660
(-CONH-), 1169, 1139 (C-F); 1H NMR (DMSO-d6, 300 MHz): d 6.92
(s, 1H, Ar-H), 7.36–7.50(m, 5H, Ar-H), 7.72(s, 1H, Ar-H), 7.94–8.06
(m, 4H, Ar-H), 8.51(br, 1H,-NH-), 10.58(br, 1H,-NH-); MS (ESI): m/z
[(M + H)+]: 392, [(M + Na)+]: 414; Anal. Calcd for C19H13ClF3N3O:
C 58.25, H 3.34, N 10.73%. Found: C 58.42, H 3.48, N 10.82%.
3-(Furan-2-yl)-5-phenyl-7-(trifluoromethyl)-[1,2,4]triazolo
[4,3-a]pyridine (6p). IR (KBr, cmꢀ1): 1651 (C═N) 1170, 1138
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
A Facile Approach for the Synthesis of Novel 1,2,4-Triazolo[4,3-a]
Pyridine Derivatives in Single Step
(C-F); 1H NMR (CDCl3, 300 MHz): d 6.96(s, 1H, Ar-H), 7.36–7.55
(m, 4H, Ar-H), 7.66–7.78(m, 4H, Ar-H), 8.19(s, 1H, Ar-H); MS
(ESI): m/z [(M + H)+]: 330; Anal. Calcd for C17H10F3N4O: C
62.01, H 3.06, N 12.76%. Found: C 62.28, H 3.11, N 12.89%.
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Acknowledgments. Authors are grateful to Dr. J. S. Yadav,
Director, Indian Institute of Chemical Technology (IICT), for his
constant encouragement, and G. S. Kumar, C. K. Murthy, P. S.
Rao, and B. V. Swamy are thankful to the Council of Scientific
and Industrial Research (CSIR), India, for the financial support in
the form of Senior Research Fellowship (SRF).
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet