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

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

Reference:

MOLSTR 127234

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. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier B.V.

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* a

College of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an/Xianyang, China b

Department of Medcine, Ankang Vocational and Technical College, Ankang, China

c

State 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: [email protected]. [email protected]

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) benzaldehyde, respectively. Their structures were confirmed by melting point, IR, 1H 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 on invia FT-Raman instrument by using 523 nm excitation; 1H NMR and 13C 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-(1Himidazol-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 N C H CH3

N

N

Id OH

CHO

S CH3COOH H2NHN C NHNH2 H3C

S

CHO

Br

N NH

HN N

O

S N NH2

N

N

Br

N N C H CH3 Ie

2

O

HO

CHO

S HN N

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) Yellow needle crystal, yield 67.3 %, m.p.>280 ˚C. 1H 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.: 203.5 205.1 ˚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.: 198.2 199.3 ˚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.: 262.0

263.0 ˚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.: 228.1 230.2 ˚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) Light yellow solid, yield 66.3 %, m.p.: 263.1

264.2 ˚C. 1H 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);

13

C 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

C13H12N6S

Formula weight /(g·mol-1)

284.35

Temperature /K

296(2)

Crystal system

Monoclinic

Space group

P21/n

a /Å

11.156(4)

b /Å

9.025(3)

c /Å

14.262(5)

α /(º)

90

β /(º)

105.475(6)

γ /(º)

90 3

Volume /Å

1383.8(9)

Z

4

Dcalc /Mg·m-3

1.365

Absorption coefficient /mm-1

0.233

F(000)

592

θ range /(º)

2.70 25.10

Limiting indices

-13<=h<=13, -10<=k<=10, -17<=l<=15

Reflections collected

6708

Reflections unique

2464 [R(int) = 0.0297]

Completeness to θ = 25.10

99.8 %

Refinement method

Full-matrix least-squares on F2

Goodness-of-fit on F2

1.074

Final R indices [l>2σ(l)]

R1 = 0.0405, wR2 = 0.1147

R indices (all data)

R1 = 0.0495, wR2 = 0.1203 -3

Largest diff. peak and hole /(e·Ǻ )

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

1b

1c

1d

1e

Pathogen

EC50/(g·L-1)

EC95/(g· L-1)

A B

0.21 0.05

30.03 707.07

C D

7.32 0.42

/ /

A B

0.14 0.04

40.25 50.12

C D

3.12 1.28

/ 36.54

A B C

0.12 0.05 1.23

25.56 43.23 45.21

D

0.78

6.98

A B

0.58 0.83

27.95 /

C D

2.48 0.75

/ 64.35

A B

0.35 0.56

29.36 8.98

C D

1.96 0.38

19.96 8.49

A

0.12

15.63

1f

Triadimefon

B

0.09

2.35

C D

0.24 0.08

12.1 6.3

A B

0.06 0.01

7.39 0.28

C

0.02

7.57

D 0.01 1.05 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)

d(H…A)

d(D…A)

< D-H…A

N(1)-H(1)…N(6)

0.86

1.96

2.8143

175

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

Bond angles

Bond

Exp.

Cal.

A .D .

Bond

Cal.

A .D .

S(1)-C(3)

1.6682

1.6727

0.0045

C(3)-N(1)-N(2)

114.5316

115.0212

0.4896

N(1)-C(3)

1.3302

1.3566

0.0264

C(2)-N(2)-N(1)

104.2815

104.4229

0.1414

N(1)-N(2)

1.3692

1.3687

0.0005

C(2)-N(3)-C(3)

108.4715

108.2170

0.2545

N(2)-C(2)

1.2963

1.2972

0.0009

C(2)-N(3)-N(4)

118.7216

118.4721

0.2495

N(3)-C(2)

1.3763

1.3944

0.0181

C(3)-N(3)-N(4)

132.7116

133.3106

0.5990

Exp.

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. References [1] R.Y. Jin, C.Y. Zeng, X.H. Liang, X.H. Sun, Y. F. Liu, Y.Y. Wang, S. Zhou. Design, synthesis, biological activities and DFT calculation of novel 1,2,4-triazole Schiff base derivatives, Bioorganic Chemistry, 80 (2018) 253-260. [2] J.Y. Zhang, S. Wang, Y.Y. Ba, Z. Xu. 1,2,4-Triazole-quinoline/quinolone hybrids as potential anti-bacterial agents, European Journal of Medicinal Chemistry, 174 (2019) 1-8. [3] S.A. Shahzad, M. Yar, Z.A. Khan, L. Shahzadi, S.A.R. Naqvi, A. Mahmood, S. Ullah, A.J. Shaikh, T.A. Sherazi, A.T. Bale, J. Kukułowicz, M. Bajda. Identification of 1,2,4-triazoles as new thymidine phosphorylase inhibitors: Future anti-tumor drugs, Bioorganic Chemistry, 85 (2019) 209-220. [4] A. Kaur, S. Mann, A. Kaura, N. Priyadarshi, B. Goyal, N.K. Singhal, D. Goyal. Multitarget-directed triazole derivatives as promising agents for the treatment of Alzheimer’s disease, Bioorganic Chemistry, 87 (2019) 572-584. [5] W. Yan, X. Wang, K. Li, T. X. Li, J.J. Wang, K. C. Yao, L.L. Cao, S.S. Zhao, Y. H. Ye. Design, synthesis, and antifungal activity of carboxamide derivatives possessing 1,2,3-triazole as potential succinate dehydrogenase inhibitors, Pesticide Biochemistry and Physiology,156 (2019) 160-169. [6] S. Zhang, Z. Xu, C. Gao, Q.C. Ren, L. Chang, Z.S. Lv, L.S. Feng. Triazole derivatives and

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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.