Design, synthesis, biological activity, crystal structure and theoretical calculations of novel 1,2,4-triazole derivatives

Article abstract of DOI:10.1016/j.molstruc.2019.127234

Series of 1,2,4-triazole Schiff base (Ia-f) were designed and synthesized. Their in-vitro antifungal activity to pythium solani, gibberlla nicotiancola, fusarium oxysporium fs.p. niveum and gibberlla saubinetii were evaluated. The results showed compound If exhibited good activity with tested fungi, which indicated that 1,2,4-triazole scaffold with introduction of imidazole phenyl could keep the antifungal activity. In order to further research the compound If, the crystal structure was detected by X-ray diffraction. Meanwhile, the FT-IR, FT-Raman, natural bond orbital (NBO), HOMO-LUMO and MEP were calculated at B3LYP/6-311G+(d,p) level. All the results will be helpful for further drug design in 1,2,4-triazole analogues.

Full text of DOI:10.1016/j.molstruc.2019.127234

Journal Pre-proof
Design, synthesis, biological activity, crystal structure and theoretical calculations of
novel 1,2,4-triazole derivatives
Ruyi Jin, Yanyan Wang, Hui Guo, Xu Long, Jiajia Li, Shijun Yue, Shuan Zhang,
Guanghui Zhang, Qinghua Meng, Chuan Wang, Hao Yan, Yuping Tang, Sha Zhou
PII:
S0022-2860(19)31343-2
DOI:
https://doi.org/10.1016/j.molstruc.2019.127234
MOLSTR 127234
Reference:
To appear in: Journal of Molecular Structure
Received Date: 21 May 2019
Revised Date: 22 September 2019
Accepted Date: 14 October 2019
Please cite this article as: R. Jin, Y. Wang, H. Guo, X. Long, J. Li, S. Yue, S. Zhang, G. Zhang, Q.
Meng, C. Wang, H. Yan, Y. Tang, S. Zhou, Design, synthesis, biological activity, crystal structure and
theoretical calculations of novel 1,2,4-triazole derivatives, Journal of Molecular Structure (2019), doi:
https://doi.org/10.1016/j.molstruc.2019.127234.
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Design, synthesis, crystal structure, biological activity
and theoretical calculations of novel 1,2,4-triazole
derivatives
Ruyi Jina, Yanyan Wangb, Hui Guoa, Xu Longa, Jiajia Lia, Shijun Yuea, Shuan Zhanga, Guanghui Zhanga, Qinghua
Menga, Chuan Wanga, Hao Yana, Yuping Tanga*, Sha Zhouc*
Series of 1,2,4-triazole derivatives (Ia-f) were designed and synthesized. Their in-vitro
antifungal activity against pythium solani, gibberlla nicotiancola, fusarium oxysporium fs.p.
niveum and gibberlla saubinetii were evaluated. The results showed compound If exhibited good
activity with tested fungi, which indicated imidazole phenyl introduced in 1,2,4- triazole scaffold
could keep the antifungal activity. In order to further research the compound If, the crystal
structure was detected by X-ray diffraction. Meanwhile, the FT-IR, FT-Raman, natural bond
orbital (NBO), HOMO-LUMO and MEP were calculated at B3LYP/6-311G+(d,p) level. All the
results will be helpful for further drug design of 1,2,4-triazole derivatives.

Design, synthesis, biological activity, crystal structure
and theoretical calculations of novel 1,2,4-triazole
derivatives
Ruyi Jina, Yanyan Wangb, Hui Guoa, Xu Longa, Jiajia Lia, Shijun Yuea, Shuan Zhanga, Guanghui Zhanga, Qinghua
Menga, Chuan Wanga, Hao Yana, Yuping Tanga*, Sha Zhouc*
aCollege of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an/Xianyang, China
bDepartment of Medcine, Ankang Vocational and Technical College, Ankang, China
cState Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Collaborative
Innovation Center of Chemical Science and Engineering (Tianjin), College of Chemistry, Nankai University,
Tianjin, China
Abstract: Series of 1,2,4-triazole Schiff base (Ia-f) were designed and synthesized. Their in-vitro
antifungal activity to pythium solani, gibberlla nicotiancola, fusarium oxysporium fs.p. niveum
and gibberlla saubinetii were evaluated. The results showed compound If exhibited good activity
with tested fungi, which indicated that 1,2,4-triazole scaffold with introduction of imidazole
phenyl could keep the antifungal activity. In order to further research the compound If, the crystal
structure was detected by X-ray diffraction. Meanwhile, the FT-IR, FT-Raman, natural bond
orbital (NBO), HOMO-LUMO and MEP were calculated at B3LYP/6-311G+(d,p) level. All the
results will be helpful for further drug design in 1,2,4-triazole analogues.
Keywords: Synthesis; 1,2,4-Triazole; Antifungal activities; DFT.
1. Introduction
Triazole derivatives have been found with broad-spectrum bioactivity in antifungal[1],
antibacterial[2], antitumor[3], anti-alzheimer[4], pesticide[5] and anti-tubercular[6]. Triazole
derivatives have been widely used as antifungal agents, especially, many known triazole agents
presently play a leading role in the treatment of agricultural fungal infections, for instance,
including epoxiconazole, epoxiconazole, tebuconazole and triadimefon, et al. What’s more,
triazole agents have a big market share in the field of pesticide because of strong systematic and
unique mechanism property. However, with more and more side effects and drug resistance, it is a
great challenge to innovate novel antifungal agents with high-efficiency, unique mode of action,
environmentally friendly and safe to mammals.
1,2,4-Triazole Schiff bases also exhibited potential bioactivity[7-10]. In our previous research,
large amount of Schiff bases were synthesized and evaluated for antifungal activity. The bioassay
showed parts of the compounds exhibited excellent antifungal activity and could be the potential
antifungal agent candidates[11], compounds A reached same antifungal level compared with
triadimefon (Fig.1), this result stimulate us to introduce different substituents at position Q and P,
which might bring us some unknown biological properties.
Corresponding author. E-mail: yupingtang@sntcm.edu.cn. zhousha@nankai.edu.cn

Fig. 1 Schematic diagram depicting for the design of the target compounds
Based on the above viewpoints, series of 4-amino-5-substituent-1,2,4-triazole-3-thione Schiff
bases were synthesized via compounds 1 and 2 with 2-Chlorine-6-fluorine-benzaldehyde,
4-Pyridine benzaldehyde, 3-Bromo-6-hydroxy-2-methoxybenzaldehyde and 4-(1H-imidazol-1-yl)
1
benzaldehyde, respectively. Their structures were confirmed by melting point, IR, H NMR,13C
NMR, HRMS. The crystal structure of compound If was obtained by X-ray diffraction, the CCDC
number is 1919697. Their antifungal activities against pythium solani, gibberlla nicotiancola,
fusarium oxysporium f.sp. niveum, and gibberlla saubinetii were evaluated. Meanwhile, the IR,
Raman, natural bond orbital (NBO), HOMO-LUMO and ESP were calculated at B3LYP
/6-311G+(d,p) level by DFT of Gaussian 09.
2. Experimental and theoretical methods
2.1 Chemistry
IR (KBr) spectra was recorded on an IR-400 spectrophotomete; Raman spectra was recorded
1
13
on invia FT-Raman instrument by using 523 nm excitation; H NMR and C NMR spectra were
measured with a Varian unity INOVA-400 nuclear magnetic resonance using CDCl3 and DMSO-d6
as the solvent; mass spectra was obtained from micrOTOF-Q II mass spectrometer; the X-ray
diffraction data was collected on a Bruker SMART-APEX II CCD diffractometer.
2.2 Synthesis
The synthetic routs of Ia-c and Id-e were presented in Scheme 1 and Schemem 2, respectively.
The compounds 1 and 2 were prepared in our previous research[1]. The target compounds Ia-e
were synthesized by dehydration reaction using compounds 1 and 2 with 4-Pyridine benzaldehyde,
3-Bromo-6-hydroxy-2-methoxybenzaldehyde, 2-Chlorine-6-fluorine-benzaldehyde and 4-(1H-
imidazol-1-yl) benzaldehyde, respectively, the reaction was monitored by TLC until raw material
disappeared, the crude products were purified by column chromatography (ethyl acetate/petroleum
ether).

Scheme 1 The synthetic route of compounds Ia-c
S
HN
N
N C
H
N
N
CH3
Id
OH
N
CHO
S
O
Br
CHO
Br
N
NH
S
C
HN
N
O
CH3COOH
N
N C
H2NHN
NHNH2
H3C
S
H
N
NH2
HO
CH3
Ie
2
N
CHO
N
S
N
HN
N
N C
H
N
N
CH3
If
Scheme 2 The synthetic route of compounds Id-f
4-(2-Chloro-6-fluorobenzylideneamino)-5-(pyridin-4-yl)-1,2,4-triazole-3-thione (Ia)
1
Yellow needle crystal, yield 67.3 %, m.p.>280 ˚C. H NMR (400 MHz, CDCl3) 10.47 (1H,
s)ꢀ7.87 (4H, m), 7.60 (3H, m), 2.55 (3H, s); IR (KBr) v/cm-1: 3136, 2996, 1610, 1491, 1225, 928,
821, 634, 587; ESI/MS (m/z): 347.8099[M+1].
4-(2-Chloro-6-fluorobenzylideneamino)-5-p-tolyl-1,2,4-triazole-3-thione (Ib)
White solid, yield 66.3 %, m.p.: 203.5ꢁ205.1 ˚C. 1H NMR (400 MHz, CDCl3) δ 10.47 (1H,
s), 7.87 (4H, m), 7.60 (3H, m), 2.55 (3H, s); IR (KBr) v/cm-1: 3136, 2996, 1610, 1491, 1225, 928,
821, 634, 587; ESI/MS (m/z): 347.8099[M+1].
4-(2-Chloro-6-fluorobenzylideneamino)-5-(2-methoxyphenyl)-1,2,4-triazole-3-thione (Ic)
White solid, yield 69.9 %, m.p.: 198.2ꢁ199.3 ˚C. 1H NMR (400 MHz, CDCl3) δ 10.04 (1H,

s), 7.28 (4H, m), 6.85 (3H, m), 3.04 (3H, s); IR (KBr) v/cm-1: 3103, 2909, 1587, 1489, 1267, 924,
835, 638, 582; ESI/MS (m/z): 363.8095[M+1].
4-((Pyridin-4-yl)methyleneamino)-5-methyl-1,2,4-triazole-3-thione (Id)
Yellow solid, yield 77.2 %, m.p.: 262.0ꢁ263.0 ˚C. 1H NMR (400 MHz, CDCl3) δ 10.86 (1H,
s), 10.35 (1H, s), 7.72 (3H, d, J = 5.2 Hz), 7.52 (1H, m), 2.41 (3H, s); IR (KBr) v/cm-1: 3061, 2892,
1590, 1490, 1251, 956, 850, 685, 561; ESI/MS (m/z): 220.2662[M+1].
4-(2,6-Dihydroxy-3-brominebenzylideneamino)-5-methyl-1,2,4-triazole-3-thione (Ie)
Light brown powder, yield 71.3 %, m.p.: 228.1ꢁ230.2 ˚C. 1H NMR (400 MHz, DMSO-d6) δ
10.51 (1H, s), 10.26 (1H, s), 7.72 (1H, t, J = 7.6 Hz), 7.45 (1H, t, J = 7.4 Hz), 4.03 (3H, s), 2.92
(2H, q), 1.36 (3H, t, J = 7.2 Hz); IR (KBr) ν (cm-1): 3424, 3139, 2998, 1618, 1569, 1439, 1226,
1128, 897, 656; ESI/MS(m/z): 280.7 321[M+1].
4-(4-(1H-imidazol-1-yl)benzylideneamino)-5-methyl-1,2,4-triazole-3-thione (If)
1
Light yellow solid, yield 66.3 %, m.p.: 263.1ꢁ264.2 ˚C. H NMR (400 MHz, DMSO-d6) δ
14.09 (1H, s), 9.62 (1H, s), 9.01 (1H, s), 8.84 (2H, d, J = 7.6 Hz), 7.80 (1H, t, J = 7.2 Hz), 2.94
(1H, s), 2.78 (1H, s), 3.86 (1H, s); 13C NMR (400 MHz, DMSO-d6); 162.60, 161.60, 148.93,
140.23, 136.16, 130.69, 120.81, 118.25, 11.24. IR (KBr) v/cm-1: 3156, 2978, 1587, 1458, 1267,
1030, 867, 643; ESI/MS (m/z): 285.3399[M+1].
2.3 X-ray crystal structure determination
A light yellow single crystal of the compound If with dimensions of 0.39 mm × 0.31 mm ×
0.25 mm was selected for X-ray diffraction analysis. The structure was solved by direct method
with SHELXS-97[12], and refined using the full-matrix least squares method on F2 with anisotropic
thermal parameters for all non-hydrogen atoms using SHELXL-97. All hydrogen atoms were
located theoretically and refined with riding model position parameters and fixed isotropic thermal
parameters. Details of the data collection conditions and the parameters of refinement process are
given in Table 1.
Table 1 Crystal data and structure refinement of compound If.
Empirical formula
Formula weight /(g·mol-1)
Temperature /K
Crystal system
Space group
C13H12N6S
284.35
296(2)
Monoclinic
P21/n
a /Å
11.156(4)

b /Å
c /Å
9.025(3)
14.262(5)
α /(º)
90
β /(º)
105.475(6)
γ /(º)
90
Volume /Å3
1383.8(9)
Z
4
Dcalc /Mg·m-3
1.365
Absorption coefficient /mm-1
F(000)
0.233
592
θ range /(º)
2.70ꢁ25.10
Limiting indices
Reflections collected
Reflections unique
Completeness to θ = 25.10
Refinement method
Goodness-of-fit on F2
Final R indices [l>2σ(l)]
R indices (all data)
Largest diff. peak and hole /(e·Ǻ -3
-13<=h<=13, -10<=k<=10, -17<=l<=15
6708
2464 [R(int) = 0.0297]
99.8 %
Full-matrix least-squares on F2
1.074
R1 = 0.0405, wR2 = 0.1147
R1 = 0.0495, wR2 = 0.1203
0.194 and -0.215
)
2.4 Antifungal activities
The antifungal activities of target compounds were evaluated for pythium solani, gibberlla
nicotiancola, fusarium oxysporium f.s.p. niveum and gibberlla saubinetii, triadimefon and solvent
(DMSO) are the positive and blank control. The plants pathogenic fungi were purchased from
Microbiology Institute of Shaanxi, the details was published in previous research work[13]
.
2.5 Computational details
The density functional theoretical computations of compound If was performed at
DFT/B3LYP/6-311G+(d,p) level to derive the complete geometry optimization. The vibrational
frequencies were calculated at same level, and the obtained frequencies were scaled by 0.9613[14]
.
In addition, natural bond orbitals (NBO), HOMO-LUMO and ESP were also investigated by
B3LYP/6-311G+(d,p). All calculations were carried out by Gaussian 09 program[15]
.
3. Results and discussion
3.1 Synthesis and characterization
The general synthetic routes of 1,2,4-triazole Schiff base derivatives were outlined in the
Schemes. The compounds 1 and 2 , which were versatile intermediates for the preparation of
1,2,4-triazole derivatives, could be prepared in different methods from carboxylic acid. For solid

carboxylic acid with a high boiling point, method was shown in Scheme 2, otherwise used the
method in scheme 1. Finally, the target compounds were prepared from
4-amino-5-substituent-1,2,4-triazole with substituted benzaldehyde. Their structure was confirmed
on the basis of spectral data and elemental analysis. All spectral and analytical data were
consistent with the assigned structures.
3.2 Antifungal activities
The antifungal activities of target compounds and triadimefon against gibberlla nicotiancola
(A), pythium solani (B), gibberlla saubinetii (C), and fusarium oxysporium f. sp. niveum (D) were
listed in Table 1, and the bar chart of antifungal activity (EC50) of target compounds was also
showed in Fig.2. As shown in Table 2, all the target compounds showed moderate to good
antifungal activity, unfortunately, all are weaker than the positive control. At previous research, we
found methyl at position Q can increase the antifungal activity, hence we compared the activity of
compound A with Id-e, although position Q of this four compounds is the same methyl group,
their antifungal activities are quite difference. The activity order is A > Ie > If > Id, and compound
A showed a remarkable antifungal activity. This means the antifungal activity of this analogous
were affected by substituent at position Q and P simultaneously. As for Ia-f, compound If showed
best antifungal activity, which indicated methyl at position Q and 4-imidazol-benzyl at position P
can keep the antifungal activity.
Table 2 The antifungal activity results of title compounds against four vegetable pathogens
Compounds
1a
Pathogen
EC50/(g·L-1)
EC95/(g· L-1)
A
B
C
D
A
B
C
D
A
B
C
D
A
B
C
D
A
B
C
D
A
0.21
0.05
7.32
0.42
0.14
0.04
3.12
1.28
0.12
0.05
1.23
0.78
0.58
0.83
2.48
0.75
0.35
0.56
1.96
0.38
0.12
30.03
707.07
/
/
40.25
50.12
/
1b
1c
1d
1e
36.54
25.56
43.23
45.21
6.98
27.95
/
/
64.35
29.36
8.98
19.96
8.49
15.63

1f
B
C
D
A
B
C
D
0.09
0.24
0.08
0.06
0.01
0.02
0.01
2.35
12.1
6.3
7.39
0.28
7.57
1.05
Triadimefon
Symbols: EC50 = 50% effective concentration; EC95 = 95% effective concentration; A = gibberlla nicotiancola;
B = pythium solani; C = gibberlla saubinetii; D = fusarium oxysporium f. sp. niveum; (/) = EC50, EC95>1000 g/L.
～
Fig. 2 The bar chart of antifungal activity of target compounds (EC50 / g•L-1)
3.3 Crystallography and optimized structure
The molecular structure and optimized structure at B3LYP/6-311+G(d,p) level of compound
If were presented in Fig.3 and Fig.4, hydrogen bonds were exhibited at Fig.5 and the distance
between donor and acceptor was listed at Table 3. Meanwhile, the crystal packing of this
compound was presented in Fig. 6. Some selected bond lengths and bond angles for compound 1f
determined by X-ray diffraction and DFT calculation were shown in Table 4. Compound 1f is
linked through intermolecular hydrogen bonds N(1)-H•••N(6) and the distance between the donor
and acceptor atoms is 2.8143 Å (Fig.3 and Table 2). Besides, there is a intramolecular hydrogen
bonds C(4)-H(4)•••S(1) in the compound 1f and the distance between the donor and acceptor
atoms is 3.2223 Å. The calculated results showed that the computed bond lengths, bond angles are
in general agreement with experimental data, the A.D. of the bond lengths and Bond angles are
less than 0.02 and 0.6, respectively.
Table 3 Relevant H-bonding metrical parameters of compound 1f
D-H…A
d(D-H)
0.86
d(H…A)
1.96
d(D…A)
2.8143
< D-H…A
175
N(1)-H(1)…N(6)
C(4)-H(4)…S(1)
0.93
2.49
3.2223
136
Table 4 The selected bond lengths (A˚) and bond angles(°) for compound 1f determined by X-ray diffraction
and B3LYP/6-311G+(d,p) calculation

Bond lengths
Exp.
Bond angles
Exp.
A.D.
A.D.
Bond
Cal.
Bond
Cal.
S(1)-C(3)
N(1)-C(3)
N(1)-N(2)
N(2)-C(2)
N(3)-C(2)
1.6682
1.6727
1.3566
0.0045
0.0264
0.0005
0.0009
0.0181
C(3)-N(1)-N(2)
C(2)-N(2)-N(1)
C(2)-N(3)-C(3)
C(2)-N(3)-N(4)
C(3)-N(3)-N(4)
114.5316
104.2815
108.4715
118.7216
132.7116
115.0212
104.4229
108.2170
118.4721
133.3106
0.4896
0.1414
0.2545
0.2495
0.5990
1.3302
1.3692
1.2963
1.3763
1.3687
1.2972
1.3944
Fig. 3. The ORTEP diagram of compound 1f
～
Fig. 4. The optimized structure at B3LYP/6-311+G(d,p) level of compound If
Fig. 5. Hydrogen bonds of compound If

Fig. 6. Packing of the crystal lattice of compound If (b axis)
3.4 Vibrational frequencies
Based on optimized geometries, the vibrational frequencies are calculated by the B3LYP
functional with the 6-311G+(d,p) basis set[16], the observed and calculated data of the vibrational
frequencies are given in Table S1, the comparison of stimulated and observed FT-IR and
FT-Raman spectrum of compound 1f were presented in Fig.7. The appearance of broad band near
3480 cm-1 is due to symmetric stretching vibrations of the N-H group, while the calculated one is
found at 3658 cm-1[17]. The typical aromatic C-H stretching bands are near 3100 cm-1, the
calculated frequency for C-H stretching mode by B3LYP/6-311+G(d,p) method is also near 3100
cm-1, showing excellent agreement with recorded spectrum as well as literature data[18]. The bands
due to C-H in-plane bending vibrations are observed around 1100 cm-1[19]. For this compound, the
C-H in-plane bending vibrations were observed at 1033 and 1233 cm-1 in FT-IR, and this mode
was calculated at 1024 and 1241 cm-1. The C-H out-of-plane bending vibration generally lie in the
range of 900-650 cm-1[24], the band appeared at 698 cm-1 in FT-IR is assigned as C-H in-plane
bending vibrations, the calculational value is 733 cm-1. The N=C stretching mode is observed at
1600 cm-1 in FT-IR spectrum and 1608 cm-1 in FT-Raman spectrum, which is the strongest
absorption peak in FT-IR and Raman, and this theoretical frequency is calculated at 1642 cm-1.
From the experiment Raman spectrum, only the strongest N=C stretching mode peak can be
exhibited, because this compound is a conjugate system, the ultraviolet absorption affects the
Raman signal.

～
～
Fig. 7. Experimental and calculated Infrared and Raman spectra of compound If
3.5. NBO calculation
Natural atomic charges were calculated by B3LYP/6-311+G(d,p) method and the results were
listed at Table S2. All of the nitrogen atoms in the molecule are negative, especially the N7 and N8,
which are in the imidazol ring. Compared with all other atoms in this molecular, C9 atom is
having the maximum negative charge with the value of -0.61817. The magnitudes of the hydrogen
atomic charges are found to be positive at the basis sets ranging from 0.19724 to 0.42268.
Natural Bound Orbital (NBO) analysis give strong insight in the intra and inner molecular
bonding and interaction among bonds, and also provide a convenient basis for investigation of
charge transfer or conjugative interactions in molecular system[20]. Large E(2) value shows the
greater conjugation of the whole system. The selected second-order perturbation theory analysis of
compound 1f in NBO basis were presented in Table S3. The interaction LP(1) N2→BD*(2)
S1-C14 has the highest E(2) value around 74.14 kcal/mol, hence gives the strongest conjugation to
the molecular. In a similar way, the interactions CR(1) C31→BD*(1) C31-H32, LP(1)
N5→BD*(2) S1-C14, BD*(2) C18-C20→BD*(2) C17- C25 are giving stabilization to the
structure with higher E(2) values. Lone pair electrons of N atoms make a good contribution to the
molecular stabilization.
3.6. Frontier molecular orbitals and molecular electrostatic potential
Frontier molecular orbital theory manifested HOMO and LUMO are the most important
factors effected bioactivity. HOMO provide electrons first, while LUMO accepts electrons in the
first place[21-23]. The energy of the HOMO-LUMO has been calculated and the maps of the
compound 1f was given in Fig.8. The calculations indicated compound 1f has 74 occupied
molecular orbitals, the HOMO orbital is mainly delocalized on Schiff base double bond (C=N),
1,2,4-triazole ring and S atom, especially later, while the LUMO orbital is mainly delocalized on
benzene ring, Schiff base double bond (C=N), S atom and 1,2,4-triazole ring. Both HOMO and

LUMO of compound 1f mainly located on 1,2,4-triazole ring, Schiff base double bond (C=N) and
S atoms, it was concluded that the 1,2,4-triazole ring, S atom and Schiff base double bond (C=N)
might make a main contribution to the activity. The value of the energy separation between the
HOMO and LUMO is 0.08467 a.u.
HOMO (-0.00585)
LUMO (-0.09052)
Fig. 8. LUMO and HOMO maps for compound If from B3LYP/6-311G+(d,p) calculation. The green parts
represent positive molecular orbital, and the red parts represent negative molecular orbital.
3.7. MEP calculation
The MEP map of compound 1f is shown in Fig.9, whereas electrophilic attack is presented by
red (negative) regions, nucleophilic reactivity is shown by the blue (positive) regions of MEP.
From Fig.9, the negative region is mainly localized on the N (8), S (1) and N (4), whereas the
positive region is mainly localized on the surface of the H atom bound to N(2). This results
indicated the N (8), S (1), N (4) and N(2) atoms are easy to interact with receptor through
dipole-dipole interaction.
～
Fig.9. Electrostatic potential map of compound If. (Red color for negative and blue color for positive)
4 Conclusions
In conclusion, series of novel 1,2,4-triazole derivatives with different substituted groups have
been synthesized, and their antifungal activities were evaluated for several pathogenic fungi.
Compound If showed good antifungal activities. The crystal of compound If was obtained by
X-ray, meanwhile, the geometric parameters of compound If have been calculated using DFT
(B3LYP) method with 6-311G+(d,p) basis set. Compared with the experimental findings, FT-IR

and Raman spectra of compound If have been presented by experiment and DFT calculation, the
calculated values are generally agreement with the experimental data. From NBO study, Lone pair
electrons of N atoms make a good contribution to the molecular stabilization. The HOMO-LUMO
and ESP have been calculated by DFT, the value of the energy separation between the HOMO and
LUMO is 0.08467 a.u.
Acknowledgments
The authors are grateful to the Natural Science Basic Research Program of
Shaanxi Provincial Education Department (19JK0235), Subject Innovation Team of Shaanxi
University of Chinese Medicine (2019-PY02), National Natural Science Foundation of China (No.
81800401),Young Talent fund of University Association for Science and Technology in Shaanxi,
(20170406) and Natural Science Foundation of Shaanxi Province (2019JQ-874) for their financial
support of this paper.
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1. A novel series of 1,2,4-triazole derivatives were first synthesized and
evaluated against four plants pathogenic fungi.
2. The calculated and experimental data on geometric parameters, FT-IR
and FT-Raman spectra of the molecule If were studied.
3. The HOMO-LUMO, ESP and NBO of the compound If were first
being presented.