Synthesis and fungicidal activity of novel 1,2,4-triazole derivatives containing a pyrimidine moiety

Article abstract of DOI:10.1080/10426507.2019.1633321

A series of novel 1,2,4-triazole derivatives containing a pyrimidine moiety were synthesized and their fungicidal activities were evaluated. The preliminary biological test indicated that some of the target compounds exhibited moderate to good fungicidal activities against the tested plant pathogenic fungi compared with the commercial agent. Among them, compounds 9n and 9o exhibited excellent antifungal activity against Phompsis sp., with the half-maximal effective concentration (EC₅₀) values of 25.4 and 31.6 μg/mL, which were even better than the commercial agent of Pyrimethanil (32.1 μg/mL). Meanwhile, compound 9o showed better fungicidal activities against B. dothidea and B. cinerea with 40.1 and 55.1 μg/mL, respectively, in comparison with that of commercial Pyrimethanil (57.6 and 62.8 μg/mL).

Full text of DOI:10.1080/10426507.2019.1633321

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: https://www.tandfonline.com/loi/gpss20
Synthesis and fungicidal activity of novel 1,2,4-
triazole derivatives containing a pyrimidine moiety
Wen-Neng Wu, Yang-Ming Jiang, Qiang- Fei & Hai-Tang Du
To cite this article: Wen-Neng Wu, Yang-Ming Jiang, Qiang- Fei & Hai-Tang Du (2019):
Synthesis and fungicidal activity of novel 1,2,4-triazole derivatives containing a pyrimidine moiety,
Phosphorus, Sulfur, and Silicon and the Related Elements, DOI: 10.1080/10426507.2019.1633321
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PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2019.1633321
Synthesis and fungicidal activity of novel 1,2,4-triazole derivatives containing
a pyrimidine moiety
Wen-Neng Wua† , Yang-Ming Jiangb†, Qiang-Feia, and Hai-Tang Dua
b
aFood and pharmaceutical Engineering Institute, Guiyang University, Guiyang, PR China; State Key Laboratory of Functions and Applications
of Medicinal Plants, Guizhou Medical University, Guiyang, PR China
ABSTRACT
ARTICLE HISTORY
Received 2 March 2019
Accepted 14 June 2019
A series of novel 1,2,4-triazole derivatives containing a pyrimidine moiety were synthesized and
their fungicidal activities were evaluated. The preliminary biological test indicated that some of
the target compounds exhibited moderate to good fungicidal activities against the tested plant
pathogenic fungi compared with the commercial agent. Among them, compounds 9n and 9o
exhibited excellent antifungal activity against Phompsis sp., with the half-maximal effective concen-
tration (EC50) values of 25.4 and 31.6 lg/mL, which were even better than the commercial agent
of Pyrimethanil (32.1 lg/mL). Meanwhile, compound 9o showed better fungicidal activities against
B. dothidea and B. cinerea with 40.1 and 55.1 lg/mL, respectively, in comparison with that of com-
mercial Pyrimethanil (57.6 and 62.8 lg/mL).
KEYWORDS
Synthesis; 1,2,4-triazole
derivatives; pyrimidine;
fungicidal activity
GRAPHICAL ABSTRACT
1. Introduction
molecules contain the pyrimidine moiety, such as the fungi-
cides for pyrimethanil and azixystrobin (Figure 1).
Substituted 1,2,4-triazoles are an important class of hetero-
cyclic compounds, which play a significant role in medicinal
chemistry because of their remarkable biological and
pharmacological properties. Recently, differently substituted
1,2,4-Triazoles have been reported for their wide biological
properties, such as antibacterial,[1,2] antifungal,[3,4] anti-
viral,[5] inflammatory,[6] antitubercular,[7] antitumoral,[8]
antimicrobial,[9] and herbicidal[10] activities. Some of them
had been developed to commercial pesticides, such as pro-
thioconazole and amicarbazone (Figure 1).
Meanwhile, one of the strategies in modern medicinal
chemistry to explore novel and highly active molecules is the
combination of different pharmacophores into a single hybrid
molecule.[19,20] To develop effective fungicidal agents, we
designed and synthesized a series novel 1,2,4-triazoles deriva-
tives with a pyrimidine moiety base on this strategy (Figure 2).
Hence, a series of novel 1,2,4-triazole derivatives containing a
pyrimidine moiety was synthesized and investigated their in
vitro fungicidal activities against three plant pathogenic fungi
including Botryosohaeria dothidea (B. dothidea), Phompsis sp.
and Botrytis cinerea (B. cinerea) of kiwifruit soft rot disease in
vitro using method of the poison plate technique.
Additionally, the pyrimidine derivatives play an import-
ant since several of its derivatives have been found to have a
wide range of pharmacological application. Literature survey
revealed that synthetic studies of pyrimidine derivatives have
been reported as a result of their structural diversities, owing
to its broad spectrum of biological activity including insecti-
cidal,[11] fungicidal,[12,13] herbicidal,[14,15] antiviral,[16,17] and
2. Results and discussion
2.1. Chemistry
The synthetic procedures to obtain the title compounds
anticancer activities.[18] Some commercial pesticide 9a–9o were summarized in Scheme 1.
CONTACT Wen-Neng Wu
wuwenneng123@126.com
Food and pharmaceutical Engineering Institute, Guiyang University, Guiyang, 550003, PR China.
†The authors contributed equally to this work.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/gpss.
Supplemental data for this article is available online at https://doi.org/10.1080/10426507.2019.1633321.
ß 2019 Taylor & Francis Group, LLC

2
W.-N. WU ET AL.
Figure 1. Chemical structures of bioactive molecules.
tested plant pathogenic fungi compared with the commercial
agent. Among of them 9n and 9o showed good fungicidal
activity against B. dothidea, Phompsis sp. and B. cinerea,
which were better than that of the commercial pyrimethanil.
Figure 2. Design strategy for target compounds 6a–6o.
3. Experimental
Intermediate 2 was obtained from readily available cya-
noacetamide, DMF, and POCl3 at ꢀ10 ꢁC.[21] Secondly,
intermediate 3 was synthesized via condensation and cycliza-
tion from intermediate 2 and acetimidamide hydrochloride
in methanol at room stirring.[22] Thirdly, compound 8 was
synthesized from intermediate 3 through sequential reac-
tions including hydrolyzation, esterification, hydrazidation,
condensation, and cyclization by the published proce-
dures.[23–24] Finally, the target compounds (9a–9o) were
obtained by the reaction of equimolar quantities of com-
pound 8 with various halohydrocarbon in water with NaOH
as catalyst at room temperature.[25] The title compounds
were purified by recrystallized with ethanol and DMF.
3.1. General
The melting points of the products were determined on a
XT-4 binocular microscope (Beijing Tech Instrument Co.,
China) and were not corrected. H and 13C NMR (solvent
1
DMSO-d6) spectra were recorded on a JEOL-ECX 500 NMR
spectrometer at room temperature using TMS as an internal
standard. Elemental analysis was performed on an
Elementar Vario-III CHN analyzer. Mass spectral studies
were conducted on an Agilent 5973 organic mass spectrom-
eter. All anhydrous solvents were dried and purified accord-
ing to standard techniques before use. Unless otherwise
noted, all common reagents and solvents were used as
obtained from commercial supplies without further purifica-
tions. The intermediates 2–7 were prepared according to the
literature procedure.[26,27] The Supplemental Materials con-
tains sample 1H and 13C NMR spectra of 9a-9o
(Figures S1–S30).
The structures of the synthesized compounds were con-
firmed by 1H NMR, 13C NMR, mass spectrometry, and
elemental analysis data. In the 1H NMR spectra of 8 and
9a–9o, one singlet at d 2.37–2.42 ppm was attributed to the
signal of the CH3 protons of the pyrimidine-CH3. The two
NH2 protons of the pyrimidine-NH2 and triazole-NH2 frag-
ment appeared at d 7.36–7.74 ppm and d 6.09–6.22 ppm as
a singlet. The CH proton of the pyrimidine ring was
3.2. Preparation of 5-(4-amino-2-methylpyrimidin-5-yl)-
1,2,4-triazole-2-thiol 8
1
appeared at d 8.40–8.97 ppm as one singlet. The H NMR
spectrum of 9b in DMSO-d6 displayed a triplet at d
1.37 ppm and a singlet at d 4.14 ppm that corresponds to S-
CH2CH3 functionality, a singlet at d 2.38 ppm integrating
for three protons was assigned to methyl protons of pyrimi-
dine-CH3. Two singlet that appeared at d 8.94 and 6.15 ppm
The intermediate 7 (20 mmol), ethanol (80 mL) and 80%
hydrazine were added in 250 mL three-necked flask
equipped, and stirred until the solution became homogen-
ous. The mixture was refluxed for 6 h. The mixture was
poured in water (200 mL) and the yellow solid was filtered,
were observed because of the protons of pyrimidine-NH2 washed with water and recrystallized from DMF to obtain
and 1,2,4-triazole-NH2 group. It was noteworthy that the
compound 8.
pyrimidine proton appeared singlet (d 8.94 ppm) in DMSO-
4-amino-5-(4-amino-2-methylpyrimidin-5-yl)-4H-1,2,4-
d6 solvent. All the target compounds were confirmed using triazole-3-thiol (8): yellow solid; yield 67.0%; m.p. 215-
ESI-MS, which displayed the existence of [M þ H]þ peaks.
218ꢁ‘; 1H NMR (500 MHz, DMSO-d6) d 8.79 (s, 1H,
Pyrimidine-H), 7.68 (s, 2H, NH2), 6.16 (s, 2H, NH2), 5.68
(s, 1H, SH), 2.39 (s, 3H, CH3) 13;C NMR (125 MHz, DMSO-
d6) d 167.98, 167.13, 160.57, 156.29, 146.74, 100.62, 25.81；
MS (ESI) m/z: 224. ([M þ H]þ); Anal. Calcd. for C7H9N7S:
C 37.66, H 4.06, N 43.92; found: C 37.68, H 4.05, N 43.90.
2.2. Fungicidal activity in vitro
The title compounds 8 and 9a 2 9o were tested for fungi-
cidal activities in vitro against B. dothidea, Phompsis sp. and
B. cinerea of kiwifruit soft rot disease via the poison plate
technique.[23–25] The commercial pyrimethanil was used as
positive control. The results of the fungicidal activities are
discussed in the Supplemental Materials and presented in
3.3. Preparation of 5-(4-amino-5-(substitutedthio)-4H-
1,2,4-triazol-3-yl)-2-methyl-pyrimidin-4-amine 9a–9o
Tables S1–S4. The results indicated most of compounds To a solution of 4-amino-5-(4-amino-2-methylpyrimidin-5-
exhibited moderate to good fungicidal activities against the yl)-4H-1,2,4-triazole-3-thiol (3 mmol) and sodium
8

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
Scheme 1. Synthesis of 5-(4-amino-2-methylpyrimidin-5-yl)-4H-1,2,4-triazole-2-thiol derivatives.
hydroxide (3.3 mmol) in water (20 mL), which was stirred at
5-(4-amino-5-(benzylthio)-4H-1,2,4-triazol-3-yl)-2-meth-
room temperature for 15 min, and then the approximate hal- ylpyrimidin-4-amine (9d): White crystals; yield 68.3%; m.p.
1
ide (3.3 mmol) was added to the reaction mixture and 224-226ꢁ‘; H NMR (500 MHz, DMSO-d6) d 8.95 (s, 1H,
stirred at room temperature for 8 h.[28] The mixture was fil- Pyrimidine-H), 7.46-7.40 (m, 3H, Ph-H, NH2), 7.34-7.26 (m,
tered and the solid obtained and recrystallized from DMF 4H, Ph-H), 6.15 (s, 2H, NH2), 4.44 (s, 2H, CH2), 2.38 (s,
and ethanol to give the title compounds.
3H, CH3); 13C NMR (125 MHz, DMSO-d6) d 167.38, 160.48,
5-(4-amino-5-(methylthio)-4H-1,2,4-triazol-3-yl)-2-methyl- 154.69, 153.93, 151.03, 137.82, 129.50, 128.89, 127.85,
pyrimidin-4-amine (9a): yellow solid; yield 81.6%; m.p. 189- 100.04, 35.26, 25.96; MS (ESI) m/z: 314.1 ([M þ H]þ); Anal.
192ꢁ‘; 1H NMR (500 MHz, DMSO-d6) d 8.97 (s, 1H, Calcd. For C14H15N7S: C 53.66, H 4.82, N 31.29; found: C
Pyrimidine-H), 7.67 (s, 2H, NH2), 6.17 (s, 2H, NH2), 2.81 53.69, H 4.80, N 31.31.
(s, 3H, CH3), 2.41 (s, 3H, CH3); 13C NMR (125 MHz,
5-(4-amino-5-((2-methylbenzyl)thio)-4H-1,2,4-triazol-3-
DMSO-d6) d 163.08, 160.66, 154.71, 153.78, 151.07, 100.64, yl)-2-methylpyrimidin-4-amine (9e): White crystals; yield
34.37, 25.95; MS (ESI) m/z: 238.1 ([M þ H]þ); Anal. Calcd. 63.5%; m.p. 201-203ꢁ‘; 1H NMR (500 MHz, DMSO-d6) d
For C7H9N7S: C 40.49, H 4.67, N 41.32; found: C 40.52, H 8.56 (s, 1H, Pyrimidine-H), 7.67-7.59 (m, 4H, Ph-H, NH2),
4.65, N 41.29.
7.28-7.21 (m, 2H, Ph-H), 6.09 (s, 2H, NH2), 4.43 (s, 2H,
5-(4-amino-5-(ethylthio)-4H-1,2,4-triazol-3-yl)-2-meth- CH2), 2.37 (s, 3H, CH3), 2.21 (s, 3H, CH3); 13C NMR
ylpyrimidin-4-amine (9b): yellow solid; yield 72.2%; m.p. (125 MHz, DMSO-d6) d 164.05, 151.60, 141.66, 139.83,
1
204-205ꢁ‘; H NMR (DMSO-d6, 500 MHz) d: 8.94 (s, 1H, 136.88, 134.67, 130.84, 126.48, 123.62, 121.25, 112.74,
Pyrimidine-H), 7.64 (s, 2H, NH2), 6.15 (s, 2H, NH2), 4.14 102.83, 34.72, 25.55, 20.67; MS (ESI) m/z: 328.1 ([M þ H]þ);
(q, J ¼ 6.50 Hz, 2H), 2.38 (s, 3H), 1.37 (t, 3H, J ¼ 7.45 Hz); Anal. Calcd. For C15H17N7S: C 55.03, H 5.23, N 29.95;
13C NMR (DMSO-d6, 125 MHz) d: 167.65, 160.57, 154.29, found: C 55.00, H 5.21, N 29.97.
145.70, 100.05, 34.36, 30.61, 25.96; MS (ESI) m/z: 252.1
5-(4-amino-5-((3-methylbenzyl)thio)-4H-1,2,4-triazol-3-
([M þ H]þ); Anal. Calcd. For C9H13N7S: C 43.01, H 5.21, N yl)-2-methylpyrimidin-4-amine (9f): White crystals; yield
39.01; found: C 43.03, H 5.20, N 39.00.
67.2%; m.p. 211-212ꢁ‘; 1H NMR (500 MHz, DMSO-d6) d
5-(5-(allylthio)-4-amino-4H-1,2,4-triazol-3-yl)-2-methyl- 8.61 (s, 1H, Pyrimidine-H), 7.68 (s, 1H, NH2), 7.27-7.18 (m,
pyrimidin-4-amine (9c): white solid; yield 63.2%; m.p. 184- 3H, Ph-H), 7.09 (d, J ¼ 7.3 Hz, 1H, Ph-H), 6.13 (s, 1H,
186ꢁ‘; 1H NMR (500 MHz, DMSO-d6) d 8.97 (s, 1H, NH2), 4.52 (s, 2H, CH2), 2.42 (s, 3H, CH3), 2.26 (s, 3H,
Pyrimidine-H), 7.68 (s, 2H, NH2), 6.16 (s, 2H, NH2), 5.31- CH3); 13C NMR (125 MHz, DMSO-d6) d 169.57, 163.20,
5.27 (m, 1H, CH), 5.13-5.06 (m, 2H, CH ¼ CH2), 3.84 (d, 162.92, 159.47, 155.45, 138.18, 136.83, 130.05, 128.91,
J ¼ 6.9 Hz, 2H, CH2), 2.38 (s, 3H, CH3); 13C NMR 126.57, 97.43, 36.29, 26.16, 21.36; MS (ESI) m/z: 328.1
(125 MHz, DMSO-d6) d 167.34, 160.51, 154.67, 153.60, ([M þ H]þ); Anal. Calcd. For C15H17N7S: C 55.03, H 5.23,
150.99, 133.93, 118.99, 100.68, 34.23, 25.95; MS (ESI) m/z: N 29.95; found: C 55.04, H 5.25, N 30.00.
264.1 ([M þ H]þ); Anal. Calcd. For C10H13N7S: C 45.61, H
5-(4-amino-5-((4-methylbenzyl)thio)-4H-1,2,4-triazol-3-
yl)-2-methylpyrimidin-4-amine (9g): White crystals; yield
4.98, N 37.23; found: C 45.60, H 4.99, N 37.20.

4
W.-N. WU ET AL.
1
69.4%; m.p. 237-239ꢁ‘; H NMR (DMSO-d6, 500 MHz) d:
8.94 (s, 1H, Pyrimidine-H), 7.68 (s, 2H, NH2), 7.37-7.31 (m,
2H, Ph-H), 7.14-7.11 (m, 2H, Ph-H), 6.13 (s, 2H, NH2), 4.39
(s, 2H, CH2), 2.38 (s, 3H, CH3), 2.26 (s, 3H, CH3); 13C
NMR (DMSO-d6, 125 MHz) d: 166.91, 160.04, 154.24,
153.50, 150.54, 136.63, 134.20, 129.12, 128.99, 128.98,
100.21, 34.69, 25.52, 20.64; MS (ESI) m/z: 328.1 ([M þ H]þ);
Anal. Calcd. For C15H17N7S: C 55.03, H 5.23, N 29.95;
found: C 55.02, H 5.26, N 29.92.
5-(4-amino-5-((2,3-dichlorobenzyl)thio)-4H-1,2,4-triazol-
3-yl)-2-methylpyrimidin-4-amine (9m): White crystals; yield
1
59.3%; m.p. 241-244ꢁ‘; H NMR (500 MHz, DMSO-d6) d:
8.94 (s, 1H, Pyrimidine-H), 7.64 (s, 2H, NH2), 7.60 (d, 2H,
J ¼ 8.0 Hz, Ph-H) , 7.35 (t, 1H, J ¼ 7.6 Hz, Ph-H), 7.13 (t,
2H, J ¼ 8.0 Hz, Ph-H), 6.18 (s, 2H, NH2), 4.58 (s, 2H, CH2),
2.39 (s, 3H, CH3); 13C NMR (125 MHz, DMSO-d6) d:
167.48, 160.53, 154.81, 153.27, 151.32, 138.04, 132.44,
131.83, 130.50, 130.31, 128.58, 100.62, 34.00, 25.99; MS (ESI)
m/z: 382.1 ([M þ H]þ); Anal. Calcd. For C14H13Cl2N7S: C
43.99, H 3.43, N 25.65; found: C 43.50, H 3.45, N 25.63.
5-(4-amino-5-((2,4-dichlorobenzyl)thio)-4H-1,2,4-triazol-
3-yl)-2-methylpyrimidin-4-amine (9n): White crystals; yield
5-(4-amino-5-((2-fluorobenzyl)thio)-4H-1,2,4-triazol-3-yl)-
2-methylpyrimidin-4-amine (9h): White crystals； yield
72.8%；m.p.220-222 ꢁC; 1H NMR (DMSO-d6, 500 MHz) d: 8.95
(s, 1H, Pyrimidine-H), 7.67 (s, 2H, NH2), 7.55 (t, 1H, J¼ 9.0 Hz,
Ph-H) , 7.34 (m, 1H, Ph-H), 7.20 (m, 2H, Ph-H), 6.18 (s, 2H,
NH2), 4.47 (s, 2H, CH2), 2.38 (s, 3H, CH3); 13C NMR (DMSO-
d6, 125 MHz) d: 172.17, 165.25, 164.41, 158.25, 155.93, 136.66,
135.02, 134.94, 129.62, 120.67, 120.46, 105.37, 33.60, 30.71; MS
(ESI) m/z: 332.2 ([M þ H]þ); Anal. Calcd. For C14H14FN7S: C
50.74, H 4.26, N 29.59; found: C 50.75, H 4.24, N 29.60.
1
51.6%; m.p. 267-268 ꢁC; H NMR (DMSO-d6, 500 MHz) d:
8.94 (s, 1H, Pyrimidine-H), 7.66-7.62 (m, 4H, Ph-H, NH2),
7.42-7.39 (m, 1H, Ph-H) , 6.18 (s, 2H, NH2), 4.50 (s, 2H,
CH2), 2.39 (s, 3H, CH3); 13C NMR (DMSO-d6, 125 MHz) d:
167.49, 160.54, 154.81, 151.31, 134.75, 134.59, 133.56,
133.19, 129.40, 127.90, 100.64, 32.72, 26.00; MS (ESI) m/z:
382.1 ([M þ H]þ); Anal. Calcd. For C14H13Cl2N7S: C 43.99,
H 3.43, N 25.65; found: C 43.52, H 3.42, N 25.66.
5-(4-amino-5-((4-fluorobenzyl)thio)-4H-1,2,4-triazol-3-yl)-
2-methylpyrimidin-4-amine (9i): White crystals； yield
1
75.9%；m.p.231-232 ꢁC; H NMR (DMSO-d6, 500 MHz) d:
5-(4-amino-5-((3,4-dichlorobenzyl)thio)-4H-1,2,4-triazol-
3-yl)-2-methylpyrimidin-4-amine(9o): White crystals; yield
8.66 (s, 1H, Pyrimidine-H), 7.67 (s, 2H, NH2), 7.63 (m, 2H,
Ph-H) , 7.18 (m, 2H, Ph-H), 6.17 (s, 2H, NH2), 4.45 (s, 2H,
CH2), 2.40 (s, 3H, CH3); 13C NMR (DMSO-d6, 125 MHz) d:
167.40, 160.51, 154.74, 153.71, 151.12, 137.25, 132.42,
131.40, 128.80, 100.05, 34.39, 25.99; MS (ESI) m/z: 332.2
([M þ H]þ); Anal. Calcd. For C14H14FN7S: C 50.74, H 4.26,
N 29.59; found: C 50.75, H 4.24, N 29.60.
1
72.8%; m.p. 244-246ꢁ‘; H NMR (500 MHz, DMSO-d6) d:
8.94 (s, 1H, Pyrimidine-H), 7.73 (d, 1H, J ¼ 2.4 Hz, Ph-H),
7.65 (s, 2H, NH2), 7.58 (d, 1H, J ¼ 8.4 Hz, Ph-H), 7.46 (dd,
1H, J1 ¼ 2.4 Hz, J2 ¼ 8.4 Hz, Ph-H), 6.18 (s, 2H, NH2), 4.52
(s, 2H, CH2), 2.39 (s, 3H); 13C NMR (126 MHz, DMSO-d6)
d 166.98, 160.03, 154.28, 153.11, 150.75, 139.23, 130.96,
130.75, 130.47, 129.88, 129.43, 100.14, 33.25, 25.52; MS (ESI)
m/z: 382.1 ([M þ H]þ); Anal. Calcd. For C14H13Cl2N7S: C
43.99, H 3.43, N 25.65; found: C 43.51, H 3.40, N 25.62.
5-(4-amino-5-((3-chlorobenzyl)thio)-4H-1,2,4-triazol-3-yl)-
2-methylpyrimidin-4-amine (9j)： White crystals； yield
1
46.6%； m.p. 253-254 ꢁC; H NMR (500 MHz, DMSO-d6) d
8.95 (s, 1H, Pyrimidine-H), 7.66 (s, 2H, NH2), 7.39 (s, 1H, Ph-
H), 7.30-7.28 (m, 2H, Ph-H), 6.16 (s, 2H, NH2), 4.44 (s, 2H,
CH2-), 2.39 (s, 3H, CH3-); 13C NMR (125 MHz, DMSO-d6) d
167.67, 160.53, 154.76, 153.74, 151.15, 137.26, 132.44,; MS
(ESI) m/z: 348.1 ([M þ H]þ); Anal. Calcd. For C14H14ClN7S:
C 48.34, H 4.06, N 28.19; found: C 48.35, H 4.07, N 28.18.
5-(4-amino-5-((4-chlorobenzyl)thio)-4H-1,2,4-triazol-3-yl)-
2-methylpyrimidin-4-amine (9k): White crystals； yield
4. Conclusions
A series of novel 1,2,4-triazole derivatives containing a pyrimi-
dine moiety were synthesized by an eight step reaction and
investigated for their fungicidal activities against B. dothidea,
Phompsis sp. And B. cinerea. The preliminary biological test
indicated that some of the target compounds exhibited moder-
ate to good fungicidal activities against the tested plant patho-
genic fungi compared with the commercial agent. Among
them, compounds 9n and 9o exhibited good fungicidal activ-
ities against B. dothidea, Phompsis sp. And B. cinerea which
were superior to those of Pyrimethanil. To the best of our
knowledge, this is the first report on the antifungal activity of
this series of 1,2,4-triazol derivatives bearing a pyrimidine moi-
ety as potential fungicidal agent in agricultural applications.
1
54.3%；m.p. 264-265 ꢁC; H NMR (DMSO-d6, 500 MHz) d:
8.96 (s, 1H, Pyrimidine-H), 7.66 (s, 2H, NH2), 7.42 (m, 2H,
Ph-H) , 7.40 (m, 2H, Ph-H) , 6.16 (s, 2H, NH2), 4.44 (s, 2H,
CH2), 2.40 (s, 3H, CH3); 13C NMR (DMSO-d6, 125 MHz) d:
167.40, 160.51, 154.73, 153.71, 151.12, 137.26, 132.44 131.40,
128.83, 100.67, 34.40, 26.00; MS (ESI) m/z: 348.1
([M þ H]þ); Anal. Calcd. For C14H14ClN7S: C 48.34, H 4.06,
N 28.19; found: C 48.37, H 4.05, N 28.22.
5-(4-amino-5-((4-nitrobenzyl)thio)-4H-1,2,4-triazol-3-yl)-
2-methylpyrimidin-4-amine (9l): Yellow crystals; yield
68.4%; m.p. 255-256ꢁ‘; 1H NMR (500 MHz, DMSO-d6) d
8.99 (s, 1H, Pyrimidine-H), 8.10-8.07 (m, 2H, Ph-H), 7.68-
7.64 (m, 4H, Ph-H, NH2), 6.22 (s, 2H, NH2), 4.51 (s, 2H,
CH2), 2.41 (s, 3H, CH3); 13C NMR (126 MHz, DMSO-d6) d
167.48, 160.53, 154.81, 153.27, 151.32, 138.04, 132.44,
131.83, 130.50, 130.31, 128.58, 100.62, 34.00, 25.99; MS (ESI)
m/z: 359.1 ([M þ H]þ); Anal. Calcd. For C14H14N8O2S: C
46.92, H 3.94, N 31.27; found: C 46.90, H 3.96, N 31.28.
Funding
This work was supported by the Natural Science Foundation of the
Department of Education of Guizhou Province (NO.: qian jiao he KY
word [2016]091), the Guizhou Science and Technology Fund Project
(NO.: [2016]1006), National Natural Science Foundation of China (No.
31701821 and 21462010), Guiyang Science and Technology Bureau and
Guiyang University Special Project (NO.: GYU-KYZ[2018]01-09) and
China Postdoctoral Science Foundation (NO.: 2017M623070).

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
5
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2018, 66, 3773–3782. DOI: 10.1021/acs.jafc.8b00665.
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ORCID
Wen-Neng Wu
http://orcid.org/0000-0001-8704-226X
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