Synthesis of novel 1,2,3-triazole-containing pyridinepyrazole amide derivatives based on one-pot click reaction and their evaluation for potent nematicidal activity against Meloidogyne incognita

Article abstract of DOI:10.1007/s11164-015-2381-y

In order to find a novel, leading nematicide compound, a series of pyridinepyrazole amide derivatives containing 1,2,3-triazoles were synthesized via click chemistry in a one-pot reaction. Their structures were characterized by proton nuclear magnetic res

Full text of DOI:10.1007/s11164-015-2381-y

Res Chem Intermed
DOI 10.1007/s11164-015-2381-y
Synthesis of novel 1,2,3-triazole-containing pyridine–
pyrazole amide derivatives based on one-pot click
reaction and their evaluation for potent nematicidal
activity against Meloidogyne incognita
Xiulei Chen1 Youxin Xiao1 Gaolei Wang1
•
•
•
Zhong Li1,2 Xiaoyong Xu1,2
•
Received: 29 June 2015 / Accepted: 25 November 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract In order to find a novel, leading nematicide compound, a series of
pyridine–pyrazole amide derivatives containing 1,2,3-triazoles were synthesized via
click chemistry in a one-pot reaction. Their structures were characterized by proton
1
nuclear magnetic resonance ( H NMR), 13C NMR, 19F NMR and high-resolution
mass spectrometry (HRMS). Preliminary bioassays showed that most of the syn-
thesized compounds exhibited good inhibitory activity in vivo against Meloidogyne
incognita at 25 mg L-1. Among the tested compounds, 3a, 3e, 3f, 3g, 3j, 3m, 3q,
3s, 3t, 3v and 3w exhibited 100 % inhibition rates. Moreover, 3k displayed a
92.4 % inhibitory activity at 10 mg L-1. This investigation suggested that this
pyridine–pyrazole amide containing a 1,2,3-triazole scaffold could be further
optimized to explore novel, high-bioactivity nematicidal leads.
Keywords Pyridine–pyrazole amide Á 1,2,3-Triazole Á Nematicide Á Click
chemistry
Introduction
Root-knot nematodes (RKNs) are soil worms belonging to the plant-parasitic
nematodes [1] that feed on the roots of different crops such as tomato, pepper,
watermelons and onions, resulting in an annual crop loss of about 100 billion US
dollars around the world. RKNs have become one of the most difficult pests to
control [2, 3]. Currently, nematode control is mainly achieved by two groups of
&
Xiaoyong Xu
xyxu@ecust.edu.cn
1
2
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of
Science and Technology, 130 Meilong Road, Shanghai 200237, China
Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong
Road, Shanghai 200237, China
123

X. Chen et al.
chemical nematicides. One is the synthetic fumigant nematicides like methyl
bromide; however, methyl bromide has now been withdrawn from the market in
many countries due to the degradation of the ozone layer [4–6]. Another group is
non-fumigant nematicides, including carbamates such as carbofuran and aldicarb,
and organophosphates such as fenamiphos and fosthiazate [7]. Recently, newly
developed nematicides fluensulfonne [8–10] and tioxazafen [11] were released to
the market in 2011 and 2014, respectively. However, with the development of
resistance and environment problems caused by carbamates and organophosphates
[12, 13], the nematicides available are still limited; as such, it is urgent to develop
efficacious alternatives.
Substituted pyridine–pyrazole amide is an important functional group which has
been used to act on insecticide targets in ryanodine receptors [14], such as in
chlorantraniliprole [15] and cyantraniliprole [16]. What’s more, BASF crop science
reported in 2007 that the pyridine–pyrazole amide derivative 1–1 can be used as a
nematicide [17]. In our group’s previous study, Li et al. [18] reported that pyridine–
pyrazole amide derivative 1–2 containing a diphenylacetylene scaffold exhibited
100 and 93.9 % inhibition rates against Meloidogyne incognita at 25 and
10 mg L-1, respectively. In this study, we tried to use this significant core structure
to develop novel nematicides, and the 1,2,3-triazole structure was introduced to the
target compound to derive structural diversity (Fig. 1).
In the last 10 years, an exciting development in the synthesis of 1,2,3-triazoles
has been click chemistry, discovered by Sharpless [19, 20]. Enlightened by all of the
intriguing reasons above, a series of novel 1,2,3-triazole-containing pyridine–
pyrazole amide derivatives were designed and synthesized by click reactions
(Scheme 1). Their nematicidal activities against M. incognita in vivo were
evaluated.
Results and discussion
Synthesis
The synthesis of target compounds 3 was illustrated in Scheme 2. In the click
reaction, the starting material sodium azide is hazardous and explosive. Recently,
click-based, one-pot synthesis of 1,2,3-triazoles without isolation of aryl azides was
Fig. 1 Some insecticides and nematicides containing pyridine–pyrazole amide structures
123

Synthesis of novel 1,2,3-triazole-containing pyridine–pyrazole…
Scheme 1 Synthesis of novel pyridine–pyrazole amide derivatives containing 1,2,3-triazoles via click
reactions
Scheme 2 General synthetic route for the target compound 3
reported [21]. Aryl azides were synthesized from their corresponding amines using
stable and non-explosive reagents: tertbutyl nitrite (t-BuONO) and azidotrimethyl-
silane (TMSN3). This provides a mild and safe option for the straightforward
preparation of 1,2,3-triazoles in a one-pot reaction. Therefore, we chose this
convenient approach to initiate our synthesis.
Compound 1 was synthesized according to the literature [22]. First, compound 1
was treated with oxalyl chloride to give corresponding acyl chloride, then the
corresponding acyl chloride was dissolved in anhydrous dichloromethane (DCM)
and added dropwise to a solution of propargylamine in DCM to obtained compound
2 in 75 % yield. Then, a wide range of anilines were dissolved in acetonitrile and
reacted in the presence of t-BuONO and TMSN3 at 0 °C, with warming to room
temperature. After complete consumption of the starting material, catalytic amounts
of CuI (0.2 eq), Et3N (1.2 eq) and compound 2 (1.0 eq) were added directly at room
temperature under Argon gas. The target compounds 3 were obtained in moderate to
high yields.
Nematicidal activity
The nematicidal activities of 3a–3w against M. incognita are listed in Table 1. The
preliminary bioassays indicated that most of the target compounds had good
inhibitory activity against M. incognita at 25 mg L-1. Among the tested
123

X. Chen et al.
Table 1 Nematicidal activities of compounds 3a–3w against M. incognita
No.
Compound
R
Inhibition rate
25 mg L-1
10 mg L-1
1
3a
R=H
100.0 %
88.5 %
78.1 %
78.1 %
100.0 %
100.0 %
100.0 %
96.7 %
p.t.
16.1 %
n.t.
2
3b
R=3-F
3
3c
R=3-Cl
n.t.
4
3d
R=4-Cl
n.t.
5
3e
R=2-Br
0.0 %
60.1 %
72.2 %
38.9 %
75.9 %
66.4 %
92.4 %
n.t.
6
3f
R=3-Br
7
3g
R=4-Br
8
3h
R=2-CH3
R=3-CH3
R=4-CH3
R=2-OCH3
R=3-OCH3
R=4-OCH3
R=4-NO2
R=4-CN
R=3-CF3
R=2-F,6-F
R=2-F,4-F
R=3-CN,4-F
R=2-F,4-Cl
R=2-Br,3-F
R=2-Br,6-F
R=3-F,4-OCH3
–
9
3i
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
3j
100.0 %
p.t.
3k
3l
72.2 %
100.0 %
89.1 %
78.1 %
72.7 %
100.0 %
95.5 %
100.0 %
100.0 %
90.3 %
100.0 %
100.0 %
–
3m
60.8 %
n.t.
3n
3o
n.t.
3p
n.t.
3q
43.8 %
n.t.
3r
3s
23.9 %
n.t.
3t
3u
n.t.
3v
27.2 %
60.3 %
100.0 %a
100.0 %a
0.0 %
0.0 %
3w
Fenamiphos
Avermectin
DMF (1.0 %)b
CK
–
–
–
0.0 %
–
–
p.t. plant toxic, n.t. not tested
Inhibitory activity at 1 mg L-1
a
b
CK with DMF (1.0 %)
123

Synthesis of novel 1,2,3-triazole-containing pyridine–pyrazole…
compounds, 3a, 3e, 3f, 3g, 3j, 3m, 3q, 3s, 3t, 3v and 3w exhibited 100 % inhibition
rates; 3i and 3k were toxic to the plants and resulted in the death of plants because
of their high concentration. Consequently, the compounds with high nematicidal
potency or toxicity to plants were investigated further at lower concentrations. The
plant toxicity of 3i and 3k did not exist when treated at 10 mg L-1, and some of the
tested compounds still showed moderate nematicidal activity. Especially, compound
3k displayed more than a 90 % inhibition rate against M. incognita at 10 mg L-1
.
When bromine was introduced into the three or four position of the benzene ring,
compounds 3f and 3g exhibited higher inhibitory activity than other compound
bearing halogen-substituted or no substituents in the benzene ring (entries 1–7),
which indicated that the bromine group played a positive role in promoting the
nematicidal activity of the target compounds. Also, the compounds containing
electron-withdrawing ability in the benzene ring caused a large drop in inhibitory
activity compared with counterparts when R were electron-donating groups (entries
8–15). Meanwhile, the compound 3w with the existence of 3-F,4-OCH3 group
showed better inhibitory activity than other double position-substituted target
compounds (entries 16–22), which confirmed that this electron-donating substituent
was the key factor for the maintenance of higher nematicidal activity.
Experimental
Instrumentation and chemicals
Melting points (Mps) of compounds were recorded on a Bu¨chi B540 apparatus
(Bu¨chi Labortechnik, Flawil, Switzerland) and are uncorrected. Nuclear magnetic
resonance (NMR) spectra were recorded on Bruker AM-400 spectrometer with
deuterated chloroform (CDCl3 ) or deuterated dimethyl sulfoxide (DMSO-d6 ) as
solvents and tetramethylsilane (TMS) as an internal standard. Two-dimensional
(2D) NMR for compound 3d spectra were recorded on Bruker AM-500 spectrom-
eter with DMSO-d6 as the solvent and TMS as the internal standard.
Chemical shifts are reported in d (parts per million). High-resolution electron
mass spectra [electrospray ionization time-of-flight (ESI-TOF) or electron ioniza-
tion TOF (EI-TOF)] were performed on a micromass liquid chromatography (LC)-
TOF spectrometer. Unless otherwise noted, reagents and solvents were used as
received from commercial suppliers.
Biological assay [23, 24]
In vivo All compounds were dissolved with dimethylformamide (DMF) and
diluted with distilled water to obtain concentrations of 25.0 and 10.0 mg L-1 for
bioassays. The final concentration of DMF in each treatment never exceeded 1 %
v/v. The 1-week-old cucumber seedlings were replanted in sterilized sand in test
tubes (one seedling per test tube, tube size: 20 9 250 mm), and the roots of each
seedling were treated with 3 mL of test solution. Then, approximately 2000 living
J2 nematodes were inoculated into the rhizosphere sand of each host plant.
123

X. Chen et al.
Fenamiphos and avermectin (B1) at concentrations of 5.0 and 1.0 mg L-1
,
respectively, served as positive control, and the negative control group was prepared
in the same way but lacked the tested compound. Distilled water without nematodes
served as blank control. Each treatment was replicated four times and the
experiment was repeated three times. All the above test tubes were incubated at 20–
25 °C for 20 days, with 10 h in the daylight and 14 h in the dark per day. The
number of root knots in each test tube was counted and a score recorded. The
inhibition rate on J2 of M. incognita was calculated by comparison with the negative
control group:
Inhibition rate ð%Þ ¼ ½ðscore of negative control À score of treatmentÞ=
ðscore of negative controlފ  100 %:
Scoring criteria: 0: 0–5 knots; 5: 6–10 knots; 10: 11–20 knots; 20: more than 20
knots.
Synthesis of compound 1
Compound 1 was synthesized according to the literature [22].
1
Data for compound 1: yellow solid; Mp: 198.6–199.8 °C; H NMR (400 MHz,
DMSO-d6) d 13.99 (s, 1H), 8.57 (s, 1H), 8.26 (d, J = 7.2 Hz, 1H), 7.69 (s, 1H), 7.26
(s, 1H) ppm. 13C NMR (100 MHz, DMSO-d6) d 158.47, 148.14, 147.32, 139.45,
137.40, 128.04, 127.19, 127.00, 113.36 ppm. HRMS (EI?): m/z [M]? calcd. for
?
C9H355Cl79BrN3O2?, 300.9254, found: 300.9256; calcd. for C9H357Cl79BrN3O2
,
302.9224, found: 302.9227; calcd. for C9H355Cl81BrN3O2?, 302.9233, found:
302.9277; calcd. for C9H537Cl81BrN3O2?, 304.9204, found: 304.9207.
Synthesis of compound 2
A mixture of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (1,
1.0 mmol), an excess of oxalyl chloride (3 mL) was stirred at room temperature for
10 min, then one drop DMF was added. The reaction mixture was stirred at room
temperature for another 3 h and concentrated in vacuo to give corresponding acyl
chloride. The corresponding acyl chloride was dissolved in 2 mL of anhydrous
dichloromethane (DCM), then added dropwise to a solution of propargylamine
(1.0 mmol), N,N-diisopropylethylamine (DIPEA, 1.2 mmol) in 15 mL of anhy-
drous DCM in an ice bath. The reaction mixture was then stirred at room
temperature and monitored by thin layer chromatography (TLC); after completion,
the solvent was evaporated under reduced pressure. The residual solid was purified
by column chromatography on silica gel with ethyl acetate/petroleum ether as eluent
1
to afford compound 2 in 75 % yield, white solid. H NMR (400 MHz, CDCl3) d
8.51 (d, J = 4.8 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.44 (dd, J = 8.0, 4.4 Hz, 1H),
6.85 (s, 1H), 6.77 (s, 1H), 4.08 (dd, J = 5.2, 2.0 Hz, 2H), 2.17 (t, J = 2.0 Hz, 1H)
ppm. 13C NMR (100 MHz, CDCl3) d 157.1, 148.8, 146.7, 139.4, 138.6, 129.3,
128.0, 126.0, 110.2, 78.4, 72.4, 29.3 ppm. HRMS (ESI): m/z [M ? Na]? calcd. for
C12H385Cl79BrN4ONa?, 360.9468, found: 360.9463; calcd. for C12H835Cl81BrN4ONa?,
123

Synthesis of novel 1,2,3-triazole-containing pyridine–pyrazole…
found: 362.9433; calcd. for C12H837Cl81BrN4ONa?, 364.9418, found: 364.9403; calcd.
for C12H387Cl79BrN4ONa?, 362.9438, found: 362.9438.
General procedure for the synthesis of target compounds 3
Different aniline (0.75 mmol) was dissolved in CH3CN (10 mL) in a 25-mL round-
bottomed flask and cooled to 0 °C in an ice bath. To this stirred mixture was added
t-BuONO (1.125 mmol) followed by TMSN3 (0.9 mmol) dropwise. The resulting
solution was stirred at room temperature for 2 h. Compound 2 (0.5 mmol), CuI
(0.1 mmol) and Et3N (0.6 mmol) were then added and the reaction was stirred at
room temperature. The progress of the reaction was monitored by TLC. After the
completion of reaction, the solvent was removed under reduced pressure, and the
residue was purified by silica gel column chromatography using petroleum ether/
ethyl acetate as eluting solution to afford the target compounds 3 [25–29]. The data
of 3a–3w are shown as follows. We selected one compound, 3d, as a representative
compound and signal positions of carbon protons were assigned.
Data for 3a: Yield 55 %; yellow solid; Mp: 204.2–204.5 °C; 1H NMR
(400 MHz, DMSO-d6) d 9.37 (t, J = 5.6 Hz, 1H), 8.65 (s, 1H), 8.50 (d,
J = 4.4 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H), 7.88 (d, J = 8.0 Hz, 2H), 7.66–7.57
(m, 3H), 7.49 (t, J = 7.2 Hz, 1H), 7.29 (s, 1H), 4.49 (d, J = 5.6 Hz, 2H) ppm. 13
C
NMR (100 MHz, DMSO-d6) d 157.2, 149.1, 147.5, 145.6, 139.8, 139.7, 137.1,
130.4, 129.1, 128.5, 127.1, 127.1, 121.7, 120.4, 110.6, 34.8 ppm. HRMS (ESI):
m/z [M - H]? calcd. for C18H Cl79BrN7O?, 455.9975, found: 455.9976; calcd. for
35
12
C18H Cl81BrN7O?, 457.9955, found: 457.9955; calcd. for C18H Cl79BrN7O?,
457.9946, found: 457.9955; calcd. for C18H Cl81BrN7O?, 459.9925, found:
35
12
37
12
37
12
459.9931.
Data for 3b: Yield 68 %; yellow solid; Mp: 173.6–174.1 °C; 1H NMR
(400 MHz, DMSO-d6) d 9.41 (t, J = 5.6 Hz, 1H), 8.74 (s, 1H), 8.50 (dd,
J = 4.8, 1.2 Hz, 1H), 8.20 (dd, J = 8.0, 1.2 Hz, 1H), 7.85 (dt, J = 10.0, 2.0 Hz,
1H), 7.80 (dd, J = 8.0, 1.2 Hz, 1H), 7.68–7.61 (m, 2H), 7.35 (td, J = 8.8, 2.4 Hz,
1H), 7.30 (s, 1H), 4.49 (d, J = 5.6 Hz, 2H) ppm. 13C NMR (100 MHz, DMSO-d6) d
162.9 (J = 243.6 Hz), 157.2, 149.1, 147.5, 145.9, 139.8, 139.7, 138.3
(J = 10.7 Hz), 132.3 (J = 9.1 Hz), 128.5, 127.1, 127.1, 121.9, 116.30
(J = 3.0 Hz), 115.8 (J = 20.9 Hz), 110.6, 107.9 (J = 25.6 Hz), 34.69 ppm. 19F
NMR (376 MHz, DMSO-d6) d -110.5 (m) ppm. HRMS (ESI): m/z [M - H]?
calcd. for C18H11F35Cl79BrN7O?, 473.9881, found: 473.9880; calcd. for C18H11-
F35Cl81BrN7O?, 475.9861, found: 475.9859; calcd. for C18H11F37Cl79BrN7O?,
475.9852, found: 475.9859; calcd. for C18H11F37Cl81BrN7O?, 477.9831, found:
477.9838.
Data for 3c: Yield 76 %; yellow solid; Mp: 169.6–170.0 °C; 1H NMR (400 MHz,
DMSO-d6) d 9.40 (t, J = 5.6 Hz, 1H), 8.76 (s, 1H), 8.50 (d, J = 3.6 Hz, 1H), 8.20
(d, J = 8.0 Hz, 1H), 8.04 (s, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.66–7.54 (m, 3H), 7.30
(s, 1H), 4.49 (d, J = 5.6 Hz, 2H) ppm. 13C NMR (100 MHz, DMSO-d6) d 157.2,
149.1, 147.5, 145.9, 139.8, 139.7, 138.1, 134.7, 132.1, 128.9, 128.5, 127.1, 127.1,
121.9, 120.2, 119.0, 110.6, 34.7 ppm. HRMS (ESI): m/z [M - H]? calcd. for
C18H Cl729BrN7O?, 489.9586, found: 489.9590; calcd. for C18H Cl37Cl79BrN7O?,
35
11
35
11
123

X. Chen et al.
491.9556, found: 491.9566; calcd. for C18H Cl821BrN7O?, 491.9565, found:
35
11
491.9566; calcd. for C18H Cl729BrN7O?, 493.9527, found: 493.9539; calcd. for
C18H Cl37Cl81BrN7O?, 493.9536, found: 493.9539; calcd. for C18H Cl281BrN7O?,
37
11
35
11
37
11
495.9505, found: 495.9510.
Data for 3d: Yield 66 %; yellow solid; Mp: 210.0–210.6 °C; 1H NMR
(500 MHz, DMSO-d6) d 9.39 (t, J = 5.5 Hz, 1H, NH), 8.69 (s, 1H, NCH=C),
8.50 (dd, J = 5.0, 1.5 Hz, 1H, ArCH), 8.19 (dd, J = 8.0, 1.5 Hz, 1H, ArCH),
7.97–7.90 (m, 2H, ArCH), 7.64–7.72 (m, 3H, ArCH), 7.29 (s, 1H, COC=CH=C),
4.49 (d, J = 5.5 Hz, 2H, CH2) ppm. 13C NMR (126 MHz, DMSO-d6) d 157.10
(C=O), 149.04 (ArCH), 147.41 (ArCH), 145.76 (CH=C-CH2), 139.70 (COC=CH),
139.60 (ArCH), 135.75 (ArCH), 133.26 (ArCH), 130.22 (ArCH), 128.36 (ArCH),
127.02 (C-Br), 126.95 (ArCH), 121.99 (ArCH), 121.75 (N-CH=C-CH2), 110.49
35-
11
(C=CH-CBr), 34.64 (CH2) ppm. HRMS (ESI): m/z [M - H]? calcd. for C18H
Cl729BrN7O?, 489.9586, found: 489.9574; calcd. for C18H Cl37Cl79BrN7O?,
35
11
491.9556, found: 491.9555; calcd. for C18H Cl821BrN7O?, 491.9565, found:
35
11
491.9555; calcd. for C18H Cl729BrN7O?, 493.9527, found: 493.9530; calcd. for
37
11
C18H Cl37Cl81BrN7O?, 493.9536, found: 493.9530; calcd. for C18H Cl281BrN7O?,
35
11
37
11
495.9505, found: 495.9502.
Data for 3e: Yield 62 %; yellow solid; Mp: 212.5–212.9 °C; 1H NMR (400 MHz,
DMSO-d6) d 9.41 (t, J = 5.6 Hz, 1H), 8.50 (d, J = 4.8 Hz, 1H), 8.35 (s, 1H), 8.19
(d, J = 8.0 Hz, 1H), 7.91 (d, J = 7.6 Hz, 1H), 7.66–7.53 (m, 4H), 7.29 (s, 1H), 4.51
(d, J = 5.6 Hz, 2H) ppm. 13C NMR (100 MHz, DMSO-d6) d 157.2 149.1, 147.5,
144.6 139.8, 139.7, 136.7 134.1, 132.4 129.4, 129.1 128.5 127.1, 127.1 125.7 119.2
110.6 34.6 ppm. HRMS (ESI): m/z [M - H]? calcd. for C18H Cl79Br2N7O?,
35
11
533.9080, found: 533.9075; calcd. for C18H Cl79Br81BrN7O?, 535.9060, found:
35
11
535.9056; calcd. for C18H Cl79Br2N7O?, 535.9051, found: 535.9056; calcd. for
37
11
35
11
37
11
C18H Cl81Br2N7O?, 537.9039, found: 537.9039; calcd. for C18H Cl79Br81BrN7-
37
11
O?, 537.9030, found: 537.9039; calcd. for C18H Cl81Br2N7O?, 539.9010, found:
539.9016.
Data for 3f: Yield 63 %; yellow solid; Mp: 166.0–166.4 °C; 1H NMR (400 MHz,
DMSO-d6) d 9.36 (t, J = 5.2 Hz, 1H), 8.74 (s, 1H), 8.50 (dd, J = 4.8 Hz, 1.2 Hz,
1H), 8.19(d, 8.0 Hz, 1H), 8.15 (s, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 8.0 Hz,
1H), 7.63 (dd, J = 8.0, 4.8 Hz, 1H), 7.55 (t, J = 8.0 Hz, 1H), 7.29 (s, 1H), 4.49 (d,
J = 5.2 Hz, 2H) ppm. 13C NMR (100 MHz, DMSO-d6) d 156.7, 148.6, 147.0, 145.4,
139.3, 139.2, 137.7, 131.8, 131.3, 128.0, 126.6, 126.6, 122.4, 122.3, 121.4, 118.9,
35
11
110.1, 34.2 ppm. HRMS (ESI): m/z [M - H]? calcd. for C18H Cl79Br2N7O?,
35
11
533.9080, found: 533.9084; calcd. for C18H Cl79Br81BrN7O?, 535.9060, found:
535.9061; calcd. for C18H Cl79Br2 N7O?, 535.9051, found: 535.9061; calcd. for
37
11
C18H Cl81Br2N7O?, 537.9039, found: 537.9039; calcd. for C18H Cl79Br81BrN7O?,
35
11
37
11
537.9030, found: 537.9039; calcd. for C18H Cl81Br2N7O?, 539.9010, found:
37
11
539.9019.
Data for 3g: Yield 58 %; yellow solid; Mp: 216.6–217.2 °C; 1H NMR
(400 MHz, DMSO-d6) d 9.36 (t, J = 5.6 Hz, 1H), 8.68 (s, 1H), 8.50 (dd,
J = 4.8, 1.2 Hz, 1H), 8.19 (dd, J = 8.0, 1.2 Hz, 1H), 7.87 (d, J = 8.8 Hz, 2H), 7.79
(d, J = 8.8 Hz, 2H), 7.63 (dd, J = 8.0, 4.8 Hz, 1H), 7.28 (s, 1H), 4.49 (d,
J = 5.6 Hz, 2H) ppm. 13C NMR (100 MHz, DMSO-d6) d 156.7, 148.6, 147.0,
123

Synthesis of novel 1,2,3-triazole-containing pyridine–pyrazole…
145.4, 139.3, 139.2, 135.8, 132.8, 128.0, 126.6, 126.6, 121.9, 121.3, 121.2, 110.1,
34.3 ppm. HRMS (ESI): m/z [M - H]? calcd. for C18H Cl79Br2N7O?, 533.9080,
35
11
35
11
found: 533.9080; calcd. for C18H Cl79Br81BrN7O?, 535.9060, found: 535.9060;
37
11
35-
11
calcd. for C18H Cl79Br2N7O?, 535.9051, found: 535.9060; calcd. for C18H
37
11
Cl81Br2N7O?, 537.9039, found: 537.9041; calcd. for C18H Cl79Br81BrN7O?,
537.9030, found: 537.9041; calcd. for C18H Cl81Br2N7O?, 539.9010, found:
37
11
539.9001.
Data for 3h: Yield 49 %; yellow solid; Mp: 184.7–185.1 °C; 1H NMR
(400 MHz, DMSO-d6) d 9.66 (t, J = 5.2 Hz, 1H), 8.49 (d, J = 3.6 Hz, 1H), 8.32
(s, 1H), 8.19 (d, J = 8.0 Hz, 1H), 7.64 (dd, J = 8.0, 4.8 Hz, 1H), 7.51–7.46 (m,
3H), 7.43–7.37 (m, 2H), 4.48 (d, J = 5.6 Hz, 2H), 2.13 (s, 3H) ppm. 13C NMR
(100 MHz, DMSO-d6) d 156.7, 148.7, 147.0, 144.2, 139.4, 139.2, 136.2, 132.9,
131.3, 129.7, 128.0, 126.9, 126.6, 126.6, 125.9, 124.8, 110.3, 34.2, 17.4 ppm.
HRMS (ESI): m/z [M - H]? calcd. for C19H Cl79BrN7O?, 470.0132, found:
35
14
470.0128; calcd. for C19H Cl81BrN7O?, 472.0111, found: 472.0110; calcd. for
35
14
C19H Cl79BrN7O?, 472.0102, found: 472.0110; calcd. for C19H Cl81BrN7O?,
37
14
37
14
474.0082, found: 474.0089.
Data for 3i: Yield 56 %; yellow solid; Mp: 170.2–170.5 °C; 1H NMR (400 MHz,
DMSO-d6) d 9.36 (t, J = 5.6 Hz, 1H), 8.61 (s, 1H), 8.50 (dd, J = 4.8, 1.2 Hz, 1H),
8.19 (dd, J = 8.0, 1.2 Hz, 1H), 7.72 (s, 1H), 7.68–7.61 (m, 2H), 7.46 (t, J = 8.0 Hz,
1H), 7.30–7.28 (m, 2H), 4.49 (d, J = 5.6 Hz, 2H), 2.41 (s, 3H) ppm. 13C NMR
(100 MHz, DMSO-d6) d 156.7, 148.7, 147.0, 145.07, 139.6, 139.3, 139.2, 136.6,
129.6, 129.2, 128.0, 126.6, 126.6, 121.2, 120.3, 117.0, 110.1, 34.3, 20.9 ppm.
HRMS (ESI): m/z [M - H]? calcd. for C19H Cl79BrN7O?, 470.0132, found:
35
14
470.0131; calcd. for C19H Cl81BrN7O?, 472.0111, found: 472.0110; calcd. for
35
14
C19H Cl79BrN7O?, 472.0102, found: 472.0110; calcd. for C19H Cl81BrN7O?,
37
14
37
14
474.0082, found: 474.0085.
Data for 3j: Yield 25 %; yellow solid; Mp: 172.3–173.0 °C; 1H NMR (400 MHz,
DMSO-d6) d 9.37 (t, J = 5.6 Hz, 1H), 8.60 (s, 1H), 8.50 (dd, J = 4.4, 1.6 Hz, 1H),
8.19 (dd, J = 8.0, 1.6 Hz, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.64 (dd, J = 8.0, 4.8 Hz,
2H), 7.39 (d, J = 8.4 Hz, 2H), 7.29 (s, 1H), 4.48 (d, J = 5.6 Hz, 2H), 2.38 (s, 3H)
ppm. 13C NMR (100 MHz, DMSO-d6) d 157.1, 149.1, 147.5, 145.5, 139.8, 139.7,
138.7, 134.8, 130.7, 128.4, 127.1, 127.1, 121.6, 120.3, 110.6, 34.8, 21.0 ppm.
HRMS (ESI): m/z [M - H]? calcd. for C19H Cl79BrN7O?, 470.0132, found:
35
14
35
14
470.0140; calcd. for C19H Cl81BrN7O?, 472.0111, found: 472.0108; calcd. for
37
14
37
14
C19H Cl79BrN7O?, 472.0102, found: 472.0108; calcd. for C19H Cl81BrN7O?,
474.0082, found: 474.0076.
Data for 3k: Yield 52 %; yellow solid; Mp: 195.6–196.2 °C; 1H NMR
(400 MHz, DMSO-d6) d 9.35 (t, J = 5.2 Hz, 1H), 8.49 (d, J = 4.4 Hz, 1H), 8.25
(s, 1H), 8.19 (d, J = 8.0 Hz, 1H), 7.63 (dd, J = 8.0, 4.8 Hz, 1H), 7.59 (d,
J = 8.0 Hz, 1H), 7.52 (t, J = 8.0 Hz, 1H), 7.31 (d, J = 8.4 Hz, 1H), 7.28 (s, 1H),
7.14 (t, J = 7.6 Hz, 1H), 4.49 (d, J = 5.6 Hz, 2H), 3.84 (s, 3H) ppm. 13C NMR
(100 MHz, DMSO-d6) d 156.7, 151.5, 148.7, 147.0, 143.8, 139.4, 139.2, 130.6,
128.0, 126.6, 126.5, 125.7, 125.6, 124.9, 120.9, 113.1, 110.0, 56.1, 34.2 ppm.
HRMS (ESI): m/z [M - H]? calcd. for C19H Cl79BrN7O2?, 486.0085, found:
35
14
486.0082; calcd. for C19H Cl81BrN7O2?, 488.0060, found: 488.0060; calcd. for
35
14
123

X. Chen et al.
C19H Cl79BrN7O2?, 488.0051, found: 488.0060; calcd. for C19H Cl79BrN7O2
,
37
14
37
14
?
490.0031, found: 490.0039.
Data for 3l: Yield 42 %; white solid; Mp: 175.4–175.6 °C; 1H NMR (400 MHz,
DMSO-d6) d 9.38 (t, J = 5.6 Hz, 1H), 8.69 (s, 1H), 8.50 (dd, J = 4.8, 1.6 Hz, 1H),
8.19 (dd, J = 8.0, 1.6 Hz, 1H), 7.64 (dd, J = 8.0, 4.8 Hz, 1H), 7.55–7.45 (m, 3H),
7.29 (s, 1H), 7.07–7.03 (m, 1H), 4.48 (d, J = 5.6 Hz, 2H), 3.85 (s, 3H) ppm. 13C
NMR (100 MHz, DMSO-d6) d 160.7, 157.2, 149.2, 147.5, 145.6, 139.8, 139.7,
138.1, 131.3, 128.5, 127.1, 127.1, 121.9, 114.8, 112.4, 110.6, 106.0, 56.1, 34.7 ppm.
HRMS (ESI): m/z [M - H]? calcd. for C19H Cl79BrN7O2?, 488.0237, found:
35
16
488.0238; calcd. for C19H Cl81BrN7O2?, 490.0217, found: 490.0218; calcd. for
35
16
C19H Cl79BrN7O2?, 492.0187, found: 492.0193.
37
16
Data for 3m: Yield 59 %; yellow solid; Mp: 187.3–187.5 °C; 1H NMR
(400 MHz, DMSO-d6) d 9.33 (t, J = 5.6 Hz, 1H), 8.52 (s, 1H), 8.50 (dd, J = 4.8,
1.2 Hz, 1H), 8.18 (dd, J = 8.0, 1.2 Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.63 (dd,
J = 8.0, 4.8 Hz, 1H), 7.29 (s, 1H), 7.12 (d, J = 8.8 Hz, 2H), 4.47 (d, J = 5.6 Hz,
2H), 3.83 (s, 3H) ppm. 13C NMR (100 MHz, DMSO-d6) d 159.2, 156.7, 148.7,
147.0, 144.9, 139.4, 139.2, 130.0, 128.0, 126.6, 126.5, 121.6, 121.2, 114.9, 110.1,
55.5, 34.3 ppm. HRMS (ESI): m/z [M - H]? calcd. for C19H Cl79BrN7O2
,
35
14
?
486.0081, found: 486.0082; calcd. for C19H Cl81BrN7O2?, 488.0060, found:
488.0061; calcd. for C19H Cl79BrN7O2?, 488.0051, found: 488.0061; calcd. for
35
14
37
14
C19H Cl79BrN7O2?, 490.0031, found: 490.0039.
37
14
Data for 3n: Yield 62 %; yellow solid; Mp: 254.6–255.1 °C; 1H NMR
(400 MHz, DMSO-d6) d 9.43 (t, J = 5.6 Hz, 1H), 8.89 (s, 1H), 8.50 (dd,
J = 4.8, 1.6 Hz, 1H), 8.45 (d, J = 8.8 Hz, 2H), 8.24–8.18 (m, 3H), 7.64 (dd,
J = 8.0, 4.8 Hz, 1H), 7.30 (s, 1H), 4.51 (d, J = 5.6 Hz, 2H) ppm. 13C NMR
(100 MHz, DMSO-d6) d 157.2, 149.1, 147.6, 147.1, 146.4, 141.3, 139.7, 128.5,
127.1, 127.1, 126.1, 122.2, 120.9, 110.6, 34.7 ppm. HRMS (ESI): m/z [M - H]?
35
11
35-
11
?
calcd. for C18H Cl79BrN8O3?, 500.9826, found: 500.9827; calcd. for C18H
?
37
11
Cl81BrN8O3
,
502.9806, found: 502.9806; calcd. for C18H Cl79BrN8O3
502.9797, found: 502.9806; calcd. for C18H Cl81BrN8O3?, 504.9776, found:
,
37
11
504.9782.
Data for 3o: Yield 69 %; yellow solid; Mp: 245.4–246.1 °C; 1H NMR
(400 MHz, DMSO-d6) d 9.42 (t, J = 5.6 Hz, 1H), 8.84 (s, 1H), 8.50 (dd,
J = 4.8, 1.6 Hz, 1H), 8.19 (dd, J = 8.0, 1.6 Hz, 1H), 8.15 (d, J = 8.8 Hz, 2H), 8.09
(d, J = 8.8 Hz, 2H), 7.63 (dd, J = 8.0, 4.8 Hz, 1H), 7.29 (s, 1H), 4.51 (d,
J = 5.6 Hz, 2H) ppm. 13C NMR (100 MHz, DMSO-d6) d 157.2, 149.1, 147.5,
146.2, 139.9, 139.7, 139.7, 134.8, 128.4, 127.1, 127.1, 122.0, 120.8, 118.6, 111.5,
110.6, 34.7 ppm. HRMS (ESI): m/z [M - H]? calcd. for C19H Cl79BrN8O?,
35
11
480.9928, found: 480.9926; calcd. for C19H Cl81BrN8O?, 482.9907, found:
35
11
482.9905; calcd. for C19H Cl79BrN8O?, 482.9898, found: 482.9905; calcd. for
37
11
C19H Cl81BrN8O?, 484.9878, found: 484.9881.
37
11
Data for 3p: Yield 74 %; yellow solid; Mp: 182.1–182.5 °C; 1H NMR
(400 MHz, DMSO-d6) d 9.42 (t, J = 5.6 Hz, 1H), 8.87 (s, 1H), 8.50 (dd,
J = 4.8, 1.2 Hz, 1H), 8.31–8.22 (m, 2H), 8.19 (dd, J = 8.0, 1.6 Hz, 1H), 7.93–7.76
(m, 2H), 7.63 (dd, J = 8.0, 4.8 Hz, 1H), 7.30 (s, 1H), 4.51 (d, J = 5.6 Hz, 2H) ppm.
13C NMR (100 MHz, DMSO-d6) d 157.2, 149.1, 147.5, 146.0, 139.7, 139.6, 137.5,
123

Synthesis of novel 1,2,3-triazole-containing pyridine–pyrazole…
131.0 (q, J = 32.3 Hz), 130.5, 128.5, 127.1, 127.1, 125.6 (q, J = 4.1 Hz), 124.3,
124.0 (q, J = 271.0 Hz), 122.1, 117.0 (q, J = 3.8 Hz) 110.6, 34.7 ppm. 19F NMR
(376 MHz, DMSO-d6) d -61.22(s) ppm. HRMS (ESI): m/z [M - H]? calcd. for
C19H11F335Cl79BrN7O?, 523.9849, found: 523.9847; calcd. for C19H11F335Cl81BrN7-
O?, 525.9829, found: 525.9829; calcd. for C19H11F337Cl79BrN7O?, 425.9820, found:
425.9829; calcd. for C19H11F337Cl81BrN7O?, 527.9799, found: 527.9806.
Data for 3q: Yield 42 %; yellow solid; Mp: 184.5–184.8 °C; 1H NMR
(400 MHz, DMSO-d6) d 9.42 (t, J = 5.2 Hz, 1H), 8.50 (dd, J = 4.4, 1.2 Hz,
1H), 8.44 (s, 1H), 8.19 (d, J = 8.0 Hz, 1.2 Hz, 1H), 7.77–7.69 (m, 1H), 7.64 (dd,
J = 8.0, 4.4 Hz, 1H), 7.46 (t, J = 8.8 Hz, 2H), 7.29 (s, 1H), 4.53 (d, J = 5.2 Hz,
2H) ppm. 19F NMR (376 MHz, DMSO-d6) d -120.51 to -120.55 (m) ppm. HRMS
(ESI): m/z [M - H]? calcd. for C18H10F235Cl79BrN7O?, 491.9787, found: 491.9792;
calcd. for C18H10F325Cl81BrN7O?, 493.9766, found: 493.9772; calcd. for C18H10F327-
Cl79BrN7O?, 493.9757, found: 493.9772; calcd. for C18H10F237Cl81BrN7O?,
495.9735, found: 495.9736.
Data for 3r: Yield 54 %; yellow solid; Mp: 190.1–190.4 °C; 1H NMR (400 MHz,
DMSO-d6) d 9.39 (t, J = 5.6 Hz, 1H), 8.50 (dd, J = 4.8, 1.6 Hz, 1H), 8.40 (d,
J = 2.0 Hz, 1H), 8.19 (dd, J = 8.0, 1.6 Hz, 1H), 7.87 (td, J = 8.8, 6.0 Hz, 1H),
7.71–7.64 (m, 1H), 7.64 (dd, J = 8.0, 4.8 Hz, 1H), 7.38–7.32 (m, 1H), 7.28 (s, 1H),
4.50 (d, J = 5.6 Hz, 2H) ppm. 19F NMR (376 MHz, DMSO-d6) d -107.53 to
-108.61 (m), -118.94 to -119.03 (m) ppm. HRMS (ESI): m/z [M - H]? calcd.
for C18H10F235Cl79BrN7O?, 491.9787, found: 491.9790; calcd. for C18H10F325-
Cl81BrN7O?, 493.9766, found: 493.9772; calcd. for C18H10F237Cl79BrN7O?,
493.9757, found: 493.9772; calcd. for C18H10F327Cl81BrN7O?, 495.9735, found:
495.9750.
Data for 3s: Yield 59 %; yellow solid; Mp: 226.4–226.9 °C; 1H NMR (400 MHz,
DMSO-d6) d 9.43 (t, J = 5.6 Hz, 1H), 8.73 (s, 1H), 8.54 (dd, J = 5.6, 2.8 Hz, 1H),
8.50 (dd, J = 4.2, 1.6 Hz, 1H), 8.34 (ddd, J = 9.2, 4.4, 2.8 Hz, 1H), 8.19 (dd,
J = 8.0, 1.6 Hz, 1H), 7.78 (t, J = 9.2 Hz, 1H), 7.64 (dd, J = 8.0, 4.8 Hz, 1H), 7.29
(s, 1H), 4.50 (d, J = 5.6 Hz, 2H) ppm. 19F NMR (376 MHz, DMSO-d6) d -108.73
to -108.91 (m) ppm. HRMS (ESI): m/z [M - H]? calcd. for C19H10F35Cl79BrN8-
O?, 498.9834, found: 498.9837; calcd. for C19H10F35Cl81BrN8O?, 500.9813, found:
500.9814; calcd. for C19H10F37Cl79BrN8O?, 500.9804, found: 500.9814; calcd. for
C19H10F37Cl81BrN8O?, 502.9784, found: 502.9793
Data for 3t: Yield 50 %; yellow solid; Mp: 137.6–138.2 °C; 1H NMR (400 MHz,
DMSO-d6) d 9.41 (t, J = 5.6 Hz, 1H), 8.50 (dd, J = 4.8, 1.6 Hz, 1H), 8.45 (d,
J = 1.6 Hz, 1H), 8.19 (dd, J = 8.0, 1.6 Hz, 1H), 7.96 (dd, J = 6.4, 2.4 Hz, 1H),
7.71–7.61 (m, 3H), 7.28 (s, 1H), 4.51 (d, J = 5.6 Hz, 2H) ppm. 19F NMR
(376 MHz, DMSO) d -125.08 to -125.15 (m) ppm. HRMS (ESI): m/z [M - H]?
calcd. for C18H10F35Cl279BrN7O?, 507.9491, found: 507.9490; calcd. for C18H10-
F35Cl37Cl79BrN7O?, 509.9471, found: 509.9469; calcd. for C18H10F35Cl281BrN7O?,
509.9462, found: 509.9469; calcd. for C18H10F37Cl279BrN7O?, 511.9441, found:
511.9446; calcd. for C18H10F35Cl37Cl81BrN7O?, 511.9432, found: 511.9446; calcd.
for C18H10F37Cl281BrN7O?, 513.9412, found: 513.9427.
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X. Chen et al.
Data for 3u: Yield 64 %; yellow solid; Mp: 142.1–142.5 °C; 1H NMR
(400 MHz, DMSO-d6) d 9.42 (t, J = 5.6 Hz, 1H), 8.50 (dd, J = 4.8, 1.6 Hz,
1H), 8.40 (s, 1H), 8.20 (dd, J = 8.0, 1.6 Hz, 1H), 7.68–7.62 (m, 3H), 7.50–7.47 (m,
1H), 7.29 (s, 1H), 4.52 (d, J = 5.6 Hz, 2H) ppm. 19F NMR (376 MHz, DMSO-d6) d
-103.71 to -103.75 (m) ppm. HRMS (ESI): m/z [M - H]? calcd. for C18H10F35-
Cl79Br2N7O?, 551.8996, found: 551.8990; calcd. for C18H10F35Cl79Br81BrN7O?,
553.8966, found: 553.8968; calcd. for C18H10F37Cl79Br2N7O?, 553.8957, found:
553.8968; calcd. for C18H10F35Cl81Br2N7O?, 555.8945, found: 555.8940; calcd. for
C18H10F37Cl79Br81BrN7O?, 555.8936, found: 555.8940; calcd. for C18H10F37Cl81-
Br2N7O?, 557.8916, found: 557.8926.
Data for 3v: Yield 35 %; yellow solid; Mp: 206.2–206.7 °C; 1H NMR
(400 MHz, DMSO-d6) d 9.44 (t, J = 5.6 Hz, 1H), 8.50 (dd, J = 4.8, 1.6 Hz,
1H), 8.39 (s, 1H), 8.19 (dd, J = 8.0, 1.6 Hz, 1H), 7.77 (d, J = 7.6 Hz, 1H),
7.68–7.58 (m, 3H), 7.29 (s, 1H), 4.52 (d, J = 5.6 Hz, 2H) ppm. 19F NMR
(376 MHz, DMSO-d6) d -117.98 to -118.23 (m) ppm. HRMS (ESI): m/z
[M - H]? calcd. for C18H10F35Cl79Br2N7O?, 551.8996, found: 551.8996; calcd. for
C18H10F35Cl79Br81BrN7O?, 553.8966, found: 553.8970; calcd. for C18H10F37Cl79-
Br2N7O?, 553.8957, found: 553.8970; calcd. for C18H10F35Cl81Br2N7O?, 555.8945,
found: 555.8945; calcd. for C18H10F37Cl79Br81BrN7O?, 555.8936, found: 555.8945;
calcd. for C18H10F37Cl81Br2N7O?, 557.8916, found: 557.8920.
1
Data for 3w: Yield 68 %; white solid; Mp: 216.5–217.0 °C; H NMR (400 MHz,
DMSO-d6) d 9.37 (t, J = 5.6 Hz, 1H), 8.61 (s, 1H), 8.50 (dd, J = 4.8, 1.2 Hz, 1H),
8.19 (dd, J = 8.0, 1.2 Hz, 1H), 7.85 (dd, J = 12.0, 2.4 Hz, 1H), 7.70 (d, J = 8.8 Hz,
1H), 7.64 (dd, J = 8.0, 4.8 Hz, 1H), 7.37 (t, J = 9.2 Hz, 1H), 7.29 (s, 1H), 4.47
(d, J = 5.6 Hz, 2H) ppm. 19F NMR (376 MHz, DMSO-d6) d -126.19 to -137.40
(m) ppm. HRMS (ESI): m/z [M - H]? calcd. for C19H13F35Cl79BrN7O2?, 503.9987,
found: 503.9990; calcd. for C19H13F35Cl81BrN7O2?, 505.9966, found: 505.9969; calcd.
for C19H13F37Cl79BrN7O2?, 505.9957, found: 505.9969; calcd. for C19H13F37Cl81-
BrN7O2?, 507.9937, found: 507.9946.
Conclusions
In conclusion, 22 novel pyridine–pyrazole amide derivatives containing 1,2,3-
triazoles were synthesized via click chemistry in a one-pot reaction and their
nematicidal activities against M. incognita in vivo were evaluated. Some of the
tested compounds showed good nematicidal activity against M. incognita at
25 mg L-1. Among them, compound 3k displayed a 92.4 % inhibition rate at
10 mg L-1, which might be developed as a potential lead compound for further
optimization.
Acknowledgments This work was financially supported by the National High Technology Research
and Development Program of China (863 Program, 2013AA065202). This work was also partly supported
by National Natural Science Foundation of China (21272071) and the Fundamental Research Funds for
the Central Universities.
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Synthesis of novel 1,2,3-triazole-containing pyridine–pyrazole…
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