Synthesis and structures of 1,2,4-triazoles derivatives

Article abstract of DOI:10.1134/S1070363215030330

Abstract A series of novel 1,2,4-triazole derivatives were synthesized, and their structures were characterized by IR, UV-Vis, FL, NMR, ESI-MS, and elemental analysis. In the meanwhile, the single crystal structures of 3,4-diethyl-5-(4-pyridyl)-1,2,4-triazole and 3,4-dimethyl-5-(o-hydroxyphenyl)-1,2,4-triazole were determined by X-ray diffraction.

Full text of DOI:10.1134/S1070363215030330

ISSN 1070-3632, Russian Journal of General Chemistry, 2015, Vol. 85, No. 3, pp. 746–751. © Pleiades Publishing, Ltd., 2015.
1
Synthesis and Structures of 1,2,4-Triazoles Derivatives
Ning Wang, Jun-feng Sheng, Fei Song, Yu-zhu Tong, and Zuo-xiang Wang
College of Chemistry and Chemical Engineering, Southeast University,
Nanjing, 210096 People’s Republic of China
e-mail: wangzx0908@aliyun.com
Received October 17, 2014
Abstract—A series of novel 1,2,4-triazole derivatives were synthesized, and their structures were characterized
by IR, UV-Vis, FL, NMR, ESI-MS, and elemental analysis. In the meanwhile, the single crystal structures of
3
,4-diethyl-5-(4-pyridyl)-1,2,4-triazole and 3,4-dimethyl-5-(o-hydroxyphenyl)-1,2,4-triazole were determined
by X-ray diffraction.
Keywords: 1,2,4-triazole derivatives, 3,4-diethyl-5-(4-pyridyl)-1,2,4-triazole, 3,4-dimethyl-5-(o-hydroxyphenyl)-
1
,2,4-triazole, X-ray diffraction
DOI: 10.1134/S1070363215030330
INTRODUCTION
triazoles derivatives were designed and synthesized as
the target compounds [17].
In the last few years, considerable attention had
been paid to the synthesis of 1,2,4-triazoles and their
derivatives due to their significant pharmacological
activities and specific magnetic properties [1–3], and
wide application as antitumor drugs, pesticide,
weedicide, fungicide and so on [4, 5]. 1,2,4-Triazole
and their derivatives are important five-membered
heterocyclic structures [6], which have a lower toxicity
than imidazole as pharmacophores. Moreover, 1,2,4-
triazoles and their derivatives have a large conjugate
planarity and exhibited good electronic transmission
performance, which can be used extensively as
electron transport materials, such as small organic
molecule electron transport materials [7–9]. However,
more details about the crystal design and crystal
engineering, prediction and computation of molecular
crystal structures through inter molecular interactions
also had an aroused attention [10–12]. There are
various methods for the preparation of 1,2,4-triazoles
and their derivatives. A generally used method for the
preparation of substituted 1,2,4-triazoles is by the
cyclization reaction of hydrazide with hydrazine
derivatives, hydrazide or amide derivatives [13–16].
In addition, the compounds were characterized by
IR, UV-Vis, FL, NMR, ESI-MS, and elemental
analysis. The single crystal of VIIc and VIId had been
obtained, and their structures were characterized by X-
ray diffraction analyses.
RESULTS AND DISCUSSION
The carboxylic acids I were easily converted into
the hydrazides III following the known procedure.
Then the N-substitued acetamide IV reacted with
oxalylchloride to form imide chloride V, and sub-
sequently cyclized to form 1,2,4-triazole compounds
VII. The general procedure for the synthesis is given
in Experimental. The synthesis of the targets is
described in the Scheme 1.
In order to determine the spatial structure of the
synthesized compound, we performed the X-ray
diffraction analysis of 3,4-dimethyl-5-(4-pyridyl)-
1,2,4-triazole and 3,4-dimethyl-5-(o-hydroxyphenyl)-
1,2,4-triazole. The spatial structure of VIIc and VIId
are shown in the figures.
The data of VIIc obtained show that both of the
triazole ring and pyridine ring have planar structures,
while they are not coplanar. The molecular structure of
VIIc was shown in Fig. 1. There are a dihedral angle
between them, such as a dihedral angle of 37.29(7)°
Herein, we described the procedure of the reaction
of N-substituted acetamide and oxalylchloride to form
imide chloride derivatives, which can easily react with
hydrazides. After the cyclization, a series of 1,2,4-
2
1
2
3
3
between the triazole ring (C , N , N , C , and N ) and
4
5
6
4
7
8
pyridine ring (C , C , C , N , C , and C ). The selected
bond lengths and angles were listed in Table 1.
1
The text was submitted by the authors in English.
7
46

SYNTHESIS AND STRUCTURES OF 1,2,4-TRIAZOLES DERIVATIVES
747
Scheme 1.
C H OH
.
4
9
NH NH2 H O
2
2
R−COOH
R−COOC H
R−CONHNH2
4
9
I
II
III
O
NH2
CH3
N
Oxalyl chloride
,6-lutidine
R
N
H
O
2
O
Cl
H
N CH
NaHCO (sat)
3
3
CH3
R
CH3
CH3
R
N
o
H C
3
N
H
Refulx 100 C, 3 h
H C
N
N
3
N N
VII
H
CH3
IV
V
VI
R = 2-pyridyl (VIIa), 3-pyridyl (VIIb), 4-pyridyl (VIIc), o-hydroxyphenyl (VIId).
The crystal water molecules involve several
hydrogen bond interactions in VIIc (Table 2). There
are five edge-to-face C–H···π interactions and four
face-to-face π···π interactions that exist between the
triazole rings and pyridine rings. The compound VIIc
is stabilized through all these interactions and forms a
three-dimensional network (Fig. 2).
EXPERIMENTAL
Reagents and all solvents were analytically pure
grade and used without further purification. Melting
points were determined using
a
X-4 digital
microscopic melting point apparatus and uncorrected.
UV-Vis were recorded on a UV–6000PC spectro-
photometer. Fluorescence spectra were recorded on a
F-2700 FL fluorescence spectrophotometer. IR spectra
were recorded on a prestige-21 infrared spectrometer
The data of VIId obtained show that the triazole
and phenyl rings were not in the same plane, and the
dihedral angle between them was 50.15(6)°.The
molecular structure of VIId was shown in Fig. 3. The
selected bond lengths and angles were listed (Table 3).
1
13
using KBr pellets. H and C NMR spectra were
recorded on a Bruker AV300 magnetic resonance
spectrometer in CDCl solution. MS were determined
3
There are one intramolecule hydrogen bond
on a thermofisher Finnigan LCQ Advantage Max.
Elemental analysis was performed by the Perkin-Elmer
24 elemental analyzer.
4
4C
1
(
(
C –H ···O ) and two inter– molecule hydrogen bonds
1
1
1
9
9
2
O –H ···N and C –H ···N ) in VIId (Table 4). In
addition, there are several C–H···π interactions. All
these interactions link the compound VIId into a
network structure (Fig. 4).
X-Ray diffraction analysis of compound VIIc.
The crystal data were collected at 296(2) K on a
Fig. 1. The molecular structure of VIIc.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 3 2015

7
48
NING WANG et al.
Table 1. Selected bond lengths (d, Å) and bond angles (ω,
deg) of crystal VIIc
Bruker Smart APEX II CCD diffractometer by using
graphite-monochromated MoKα (λ = 0.71073 Å)
–
radiation. VIIc crystallized in triclinic system P1.
Absorption corrections were applied using SADABS
program [18]. The structure was solved by direct
method and refined by full-matrix least-squares
techniques using the SHELXL-97 program [19]. All
nonhydrogen atoms were refined anisotropically. All
hydrogens were generated geometrically and allowed
to ride on their parent atoms. The water hydrogens in
VIIc were found from the Fourier map, but not refined
anisotropically. The coordinates of the atoms are
deposited at the Cambridge Crystallographic Data
Center (CCDC 1017676).
Bond
d, Å
Bond angle
ω, deg
1
2
1
2
3
N –C
1.315(3)
1.380(2)
1.313(3)
1.363(3)
1.461(3)
1.379(3)
1.333(3)
1.338(3)
1.391(3)
1.372(3)
N –C –N
110.22(16)
107.51(16)
122.96(16)
104.77(15)
119.32(19)
126.89(15)
118.57(17)
117.58(16)
123.82(19)
107.26(15)
1
2
2
1
2
N –N
N –N –C
2
3
2
9
2
3
4
N –C
N –C –C
3
2
3
3
N –C
C –N –C
3
4
8
7
N –C
C –C –C
5
6
2
3
9
C –C
C –N –C
4
6
3
4
8
8
8
N –C
C –C –C
4
7
5
4
N –C
C –C –C
4
8
4
7
X-Ray diffraction analysis of compound VIId.
According to the same procedures, the structure of
VIId was solved. VIId crystallized in monoclinic
C –C
N –C –C
7
8
1
2
3
C –C
N –N –C
Table 2. The hydrogen bond, C–H···π, and π···π interactions of VIIc
D–H···A
D–H, Å
0.865(9)
0.861(10)
0.842(9)
0.848(9)
0.857(10)
0.860(10)
0.9600
H···A, Å
2.066(17)
1.948(17)
2.00(2)
2.13(2)
2.08(3)
2.04(2)
2.5880
D···A, Å
2.925(3)
2.800(4)
2.841(4)
2.909(3)
2.819(4)
2.874(3)
3.424(3)
3.357(3)
3.468(3)
3.468(3)
3.967(3)
3.466(3)
∠DHA, deg
171.9(18)
168(2)
1
w
1wA
5
O –H ···N
1w
1wB
3w a
1w a
8 b
O –H ···O
2w
2wA
O –H ···O
175(2)
153(2)
145(3)
164.2(19)
145.73
84.08
2w
2wB
O –H ···N
3w
3wB
2w c
4 d
O –H ···O
3w
3wA
O –H ···N
18
18C
1e
C –H ···N
5
5
g2 f
C –H ···C
0.9300
3.3230
9
9B
g4 g
C –H ···C
0.9600
3.0376
108.82
91.72
9
9C
g4 g
C –H ···C
0.9600
3.3042
10
10A
g3 h
C –H ···C
0.9600
3.3892
120.76
93.06
15
15
g1 i
C –H ···C
0.9300
3.2899
g1
g4 g
g4 f
g3 h
g3 i
C ···C
4.080(3)
3.707(3)
3.842(3)
9.67
g1
C ···C
9.67
g2
C ···C
10.79
g2
C ···C
3.776(3)
10.79
a
b
c
d
e
f
g
h
Symmetry codes: 1 – x, 1 – y, 1– z; 1 – x, –y, –z; –1 + x, y, z; 1 – x,1 – y,2 – z; 1 – x, –y,1 – z; 1 + x, y, 1 + z; x, y, 1 + z; –1 + x, y,
i
–
1 + z; x, y, –1 + z.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 3 2015

SYNTHESIS AND STRUCTURES OF 1,2,4-TRIAZOLES DERIVATIVES
749
Fig. 2. The 3D network of VIIc showing hydrogen bond, C–H···π, and π···π interactions.
system P2(1)/c. The coordinates of the atoms are
deposited at the Cambridge Crystallographic Data
Center (CCDC 1017677).
The obtained compounds II was dissolved with
ethanol (90 mL) and hydrazine hydrate (85%, 30 mL),
then the mixture was heated to reflux for 6 h. After the
reaction was completed, ethanol and the excess of
hydrazine hydrate were distilled out under a reduced
pressure, and a white product was left. The crude
product was recrystallized from ethanol to afford white
crystals III.
Synthesis of compound III (general procedure).
To the solution of n-butyl alcohol (110 mL) and
benzene (30 mL) which contained compounds of I
(
0.2 mol), concentrated sulfuric acid (98%, d = 1.84)
was added and stirred. The mixture was heated to
reflux with a water separator and stirred for 8 hours,
then the excess n-butyl alcohol and benzene was
distillated out, the residuum was pour into ice water
Synthesis of 3,4-dimethyl-5-(2-pyridyl)-1,2,4-tri-
azole (VIIa). To dichloromethane solution (300 mL)
which contained N-methylacetamide (4.38 g, 0.06 mol)
and 2,6-lutidine (14.0 mL, 0.1 mol), oxalyl chloride
(5.2 mL, 0.06 mol) was added, and the mixture was
stirred for 40 min at 0°C. Then to the solution 2-
(
150 mL) and neutralized to pH = 7–8 with saturated
sodium carbonate solution. The water solution was
extracted with isopropyl ether (3 × 100 mL). The
combined extract solution was dried overnight by
anhydrous magnesium sulfate and filtered. The filtrate
was distillated out first the isopropyl ether then
distillated out the ester of II under vacuum.
Table 3. Selected bond lengths (d, Å) and torsion angles (ω,
deg) of crystal VIId
Bond
d, Å
Bond angle
ω, deg
3
2
2
3
3
N –C
1.3586(17)
1.3907(17)
1.3109(17)
1.3692(17)
1.4586(19)
1.398(2)
N –C –N
109.83(11)
118.22(12)
106.93(11)
119.28(13)
122.44(12)
109.71(12)
117.56(12)
126.00(13)
128.26(12)
107.86(11)
1
2
1
10
5
N –N
O –C –C
2
3
1
2
3
N –C
N –N –C
3
3
5
10
9
9
N –C
C –C –C
3
5
1
10
C –C
O –C –C
5
6
1
2
3
C –C
N –C –N
6
7
3
5
6
C –C
1.377(2)
C –C –C
7
8
1
2
1
4
2
C –C
1.378(2)
N –C –C
8
9
3
3
C –C
1.380(2)
C –N –C
9
10
2
1
Fig. 3. The molecular structure of VIId.
C –C
1.393(2)
N –N –C
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 3 2015

7
50
NING WANG et al.
Fig. 4. The hydrogen bonding and C–H···π interactions of VIId.
picolinyl hydrazide (8.22 g, 0.06 mol) was added and
the mixture was stirred for 5 h at room temperature.
After the reaction was completed, the solvent was
removed under a reduced pressure and a residue was
left. To the residue, a saturated sodium bicarbonate
solution (300 mL) was added and the mixture was
refluxed for 3 h at 100°C, then cooled to the room
temperature, extracted with chloroform (3 × 100 mL).
The extract was dried overnight by anhydrous
magnesium sulfate. After the filtration chloroform was
distilled out and a yellowish solid was separated. The
crude product was recrystallized from ethyl acetate to
afford white crystals (2.7 g). Yield 25.6 %, mp 113–
spectrum, δ , ppm: 10.986, 32.418, 123.494, 123.757,
136.930, 148.174, 148.609, 152.320, 153.665. UV-Vis
С
(CH Cl ), λ , nm: 233, 269. FL (CH CO C H ), nm:
2
2
max
3
2
2
5
+
λex = 308, λem = 344. MS (ESI): m/z 175.2 [M + 1] .
Found, %: C 62.17; H 5.74; N 32.19. C H N .
9
10
4
Calculated, %: C 62.05; H 5.79; N 32.16.
Compound VIIb, VIIc, and VIId were obtained
similarly.
3,4-Dimethyl-5-(3-pyridyl)-1,2,4-triazole (VIIb)
–
1
Yield 27.1 %, mp 106–107°C. IR spectrum, ν, cm :
1437, 1488, 1599 (C–C), 2972 (CH ), 3050 (C–H, 2-
pyridyl). H NMR spectrum (CDCl ), δ, ppm: 2.51
(3H, CCH ), 3.62 (3H, NCH ), 7.42–8.85 (4H, 2-
, ppm: 11.065, 31.314,
123.764, 123.864, 136.311, 148.945, 150.930, 152.154,
3
1
3
–
1
1
2
14°C. IR spectrum, ν, cm : 1437, 1491, 1588 (C–C),
3
3
1
13
975 (CH ), 3054 (C–H, 2-pyridyl). H NMR spectrum
pyridyl). C NMR spectrum, δ
С
3
(
CDCl ), δ, ppm: 2.457 (3H, CCH ), 3.941 (3H,
3
3
1
3
NCH ), 7.250–8.581 (4H, 2-pyridyl). C NMR
153.034. UV-Vis (CH
2
Cl
2
), λmax, nm: 233, 270. FL
3
Table 4. The hydrogen bond and C–H···π interactions for VIId
D–H···A
D–H, Å
0.82
H···A, Å
1.9784
2.5620
2.4986
2.7492
3.0843
2.9948
3.3958
D···A, Å
2.7546
3.0377
3.3707
3.5425
3.4555
3.4555
3.7451
3.7338
∠DHA, deg
1
1
1 a
O –H ···N
157.68
4
4C
1
C –H ···O
0.9600
0.9300
0.9600
0.9600
0.9600
0.9300
110.75
156.25
140.44
104.73
110.88
104.95
104.45
9
9
2a
C –H ···N
1
1B
g1 b
C –H ···C
4
4A
g2 c
C –H ···C
4
4B
g2 c
C –H ···C
6
6
g1 d
C –H ···C
7
7
g1 d
C –H ···C
0.9300
3.3915
a
b
c
d
Symmetry codes: –1 + x, y, z; 1 – x, –y, –z; x, 1/2 – y, –1/2 + z; 1 – x, 1– y, –z.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 3 2015

SYNTHESIS AND STRUCTURES OF 1,2,4-TRIAZOLES DERIVATIVES
Table 5. Synthesis of compounds II and III
ACKNOWLEDGMENTS
751
Yield,
%
bp, °C
(16 mmHg)
Yield,
%
Product
Product
mp, °C
This work was financially supported by the
development project 8507040052.
IIa
IIb
IIc
IId
82
80
76
90
141–142
141–142
141–142
145–147
IIIa
IIIb
IIIc
IIId
80.5 100–102
78.7 161–163
74.1 170–171
74.4 147–149
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2
3
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(
CH CO C H ), nm: λ = 301, λ = 334. MS (ESI):
3 2 2 5 ex em
+
m/z 175.2 [M + 1] . Found, %: C 62.16; H 5.90; N
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10
4
ARKIVOC, 2013, no. 3, p. 413.
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,4-Dimethyl-5-(4-pyridyl)-1,2,4-triazole (VIIc).
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5. Li, Y., Wang, Z.X., Zhang, C.G., Liu, Q., and Liu, L.,
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1
Yield 49.8 %, mp 148–149°C. IR spectrum, ν, cm :
485, 1536, 1610 (C–C), 2971 (CH ), 3048 (C–H, 2-
pyridyl). H NMR spectrum (CDCl ), δ, ppm: 2.498
3H, CCH ), 3.649 (3H, NCH ), 7.550–8.744 (4H, 2-
pyridyl). C NMR spectrum, δ , ppm: 11.038, 31.443,
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1
Inorg. Chem. Commun., 2013, no. 38, p. 58. DOI:
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1
0.1016/j.inoche.2013.09.074.
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(
3 3
13
6
7
С
2
1
(
2
%
22.443, 135.066, 150.488, 152.412, 153.456. UV-Vis
CH Cl ), λ , nm: 247. FL (CH CO C H ), nm: λ =
2
2
max
3
2
2
5
ex
+
89, λ = 334. MS (ESI): m/z 175.2 [M + 1] . Found,
em
: C 61.89; H 5.77; N 32.01. C H N . Calculated, %:
C 62.05; H 5.79; N 32.16.
1
0.1007/b13531.
9 10 4
8
. Zhu, D., Xu, Y., Yu, Z.; Guo, Z., Sang, H., Liu, T., and
You, X., Chem. Mater., 2002, no. 14, p. 838. DOI:
10.1021/cm010688u.
3
,4-Dimethyl-5-(o-hydroxyphenyl)-1,2,4-triazole
(
VIId). Yield 48.5 %, mp 228–229°C. IR spectrum, ν,
9
. Kitchen, J.A. and Brooker, S., Coord. Chem. Rev.,
2008, no. 252, p. 2072. DOI: 10.1016/j.ccr.2007.11.010.
–
1
cm : 1225 (C–O), 1456, 1490, 1609 (C–C), 2926
(
spectrum (CDCl ), δ, ppm: 2.518 (3H, CCH ), 3.768
(
OH). C NMR spectrum, δ , ppm: 11.034, 32.544,
1
1
1
CH ), 3034 (C–H, 2-pyridyl), 3460 (OH). H NMR
3
10. McKinnon, J.J., Jayatilaka, D., and Spackman, M.A.,
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3
3
3H, NCH ), 6.918–7.497 (4H, 2-pyridyl), 7.381 (1H,
3
1
3
С
11.219, 118.077, 119.043, 125.983, 131.598,
52.117, 152.861, 157.530. UV-Vis (CH Cl ), λmax,
2
2
nm: 220, 280. FL (CH CO C H ), nm: λ = 286, λ =
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3
2
2
5
ex
em
+
no. 36, p. 697. DOI: http://dx.doi.org/10.3184/
1
3
6
6
25. MS (ESI): m/z 190.2 [M + 1] . Found, %: C
74751912X13503977364032.
3. Busch, M. and Schneider, C., J. für Praktische Chemie,
914, no. 89, p. 310.
3.57; H 5.85; N 21.99. C H N O. Calculated, %: C
1
0
11
3
1
1
1
3.48; H 5.86; N 22.21.
1
4. Curtius, T., J. für Praktische Chemie, 1914, no. 89,
CONCLUSIONS
p. 508.
5. Herbst, R.M. and Garrison, J.A., J. Org. Chem., 1953,
To summarize, a series of new 1,2,4-triazoles
no. 18, p. 872.
derivatives were synthesized and their structures were
experimentally characterized by NMR, UV-Vis, FL,
IR, ESI-MS, and elemental analysis. The single crystal
structures for compound VIIc and VIId have been
determined by X-ray diffraction. The crystal structures
showed that the two aromatic rings of VIIc and VIId
were not in a common plane.
1
1
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