Synthesis and Insecticidal Evaluation of Novel N-pyridylpyrazole Derivatives Containing Diacylhydrazine/1,3,4-Oxadiazole Moieties

Article abstract of DOI:10.1002/jhet.3505

Two series of novel N-pyridylpyrazole derivatives containing diacylhydrazine/1,3,4-oxadiazole moieties were designed and synthesized based on the structure of chlorantraniliprole and characterized via ¹H-NMR, ¹³C-NMR, IR, MS, and elemental analysis. The preliminary bioassay indicated that some of the title compounds I and II exhibited larvicidal activities against Mythimna separata with 90–100% death rates at 500?mg/L. The further test showed that these compounds had weak insecticidal activity against Mythimna separata and Plutella xylostella at 200?mg/L and might be not suitable as insecticide lead compound for further optimization.

Full text of DOI:10.1002/jhet.3505

Month 2019
Synthesis and Insecticidal Evaluation of Novel N-pyridylpyrazole
Derivatives Containing Diacylhydrazine/1,3,4-Oxadiazole Moieties
*
*
Xiao-Rui Zheng, Xiao-Ying Huang, Ming-Zhen Mao, Kang-Yun Liu, Chao Xue, Lie-Ping Wang, and
Wei Wang,
*
Bin-Ke Ning
State Key Laboratory of Fluorine & Nitrogen Chemicals, Xi’an Modern Chemistry Research Institute, Xi’an, Shaanxi,
People’s Republic of China
*E-mail: wangwei204@aliyun.com; wlpcxm@qq.com; bkning@126.com
Received May 17, 2018
DOI 10.1002/jhet.3505
Published online 00 Month 2019 in Wiley Online Library (wileyonlinelibrary.com).
NH
O
Br
H
N
N
N
Cl
O
Cl
N
X
Br
Br
R
O
X
R
Y
O
NHNH
O
N
N
N
N
O
N
N
O
Cl
Y
Cl
N
N
R= Me or H
R= Me or H
Two series of novel N-pyridylpyrazole derivatives containing diacylhydrazine/1,3,4-oxadiazole moieties
were designed and synthesized based on the structure of chlorantraniliprole and characterized via 1H-
NMR, 13C-NMR, IR, MS, and elemental analysis. The preliminary bioassay indicated that some of the title
compounds I and II exhibited larvicidal activities against Mythimna separata with 90–100% death rates at
500 mg/L. The further test showed that these compounds had weak insecticidal activity against Mythimna
separata and Plutella xylostella at 200 mg/L and might be not suitable as insecticide lead compound for fur-
ther optimization.
J. Heterocyclic Chem., 00, 00 (2019).
INTRODUCTION
other hand, among various biologically scaffolds,
diacylhydrazine [13–19] and 1,3,4-oxadiazole [20–22]
moieties have occupied important positions in pesticide
chemistry and are often introduced in the design of
bioactive compounds. On the basis of the aforementioned
As the main pests control tool, insecticides play a very
important role in modern agriculture [1,2]. Because
agricultural pests can develop resistance rapidly all over
the world, it is necessary to develop efficient insecticides
with novel structures and modes of action [2–6]. As a
selective activator of the insect ryanodine receptor,
chlorantraniliprole (A, Scheme 1) which has attracted
considerable attention for decades because of its
exceptional insecticidal activity on a broad spectrum and
low mammalian toxicity [2–7]. Recently, Li and Song
et al. have designed and synthesized series of novel N-
pyridylpyrazole derivatives on the basis of the structure
of chlorantraniliprole [2–11]. Their results demonstrated
observations,
a
series of novel N-pyridylpyrazole
derivatives containing diacylhydrazine moiety (I-1–12)
and their corresponding 1,3,4-oxadiazole derivatives (II-
1–4) (Figure 1) were designed and synthesized as part of
our ongoing work amied at searching for new insecticidal
compounds. Herein, we report the synthesis and
insecticidal activity of the N-pyridylpyrazole derivatives I
and II.
that
the
modifications
in
the
structure
of
RESULTS AND DISCUSSION
chlorantraniliprole are still attractive.
In our previous work, some series of novel N-
pyridylpyrazole derivatives were designed and
synthesized, and the ensuing bioassay results exhibited
excellent larvicidal activity against Mythimna separata
and Plutella xylostella in some cases [5–7,12]. On the
The title compounds I-1–12 were prepared by
condensation of intermediate 7 with the pyrazole-5-
carbonyl chloride 5 in the presence of K2CO3 as a base
in tetrahydrofuran (THF) (Scheme 1). The 2-(substituted
phenoxy)acetate carbonyl hydrazines 7 were prepared
© 2019 Wiley Periodicals, Inc.

W. Wang, X.-R. Zheng, X.-Y. Huang, M.-Z. Mao, K.-Y. Liu, C. Xue, L.-P. Wang, and B.-K. Ning Vol 000
Scheme 1. Synthetic route of compounds I-1–I-12. Reagents and conditions: (a) diethyl maleate, NaOEt, EtOH, reflux; (b) POBr3, MeCN, 80°C; (c)
K2S2O8, H2SO4, MeCN, reflux; (d) (i) aqueous NaOH, MeOH and (ii) aqueous HCl; (e) SOCl2, reflux; (f) Hydrazine hydrate, reflux; (g) K2CO3,
THF, H2O.
H2N
N
N
N
N
N
N
NH
CO2Et
Cl
N
N
CO2Et
Cl
COCl
Cl
N
3
a
CO2H
Cl
N
2
d
N
b
N
4
e
c
Cl
N
1
5
X
Br
R
O
Y
R
OEt
O
R
O
NHNH2
O
X
O
X
NHNH
5
g
N
f
N
O
O
Y
Y
Cl
N
NH
O
Br
H
N
N
N
Cl
O
Cl
N
X
Br
Br
R
X
R
Y
O
NHNH
O
N
N
N
N
O
O
N
N
O
Cl
Y
Cl
N
N
R= Me or H
R= Me or H
Figure 1. Chemical modification of lead structure A (chlorantraniliprole). [Color figure can be viewed at wileyonlinelibrary.com]
according to the reported methods [23]. The ethyl
2-(substituted phenoxy)acetate 6 could be synthesized
from the corresponding substituted phenols and ethyl 2-
bromoacetate in good yields [24]. According to the
literature [2,4], the pyrazole carboxylic acid 4 was
synthesized from 3-chloro-2-hydrazinylpyridine 1 which
was used directly as obtained commercially. In addition,
the pyrazole-5-carbonyl chloride 5 could be prepared by
the reaction of pyrazole carboxylic acid 4 with thionyl
chloride in reflux for 5–6 h. The synthetic route of the
title compound II is shown in Scheme 2. The title
compounds II-1–4 could be obtained by the reaction of
diacylhydrazines I with POCl3 under the condition of
refluxing [2,23].
The structures of the title compounds I and II were
characterized by 1H-NMR, 13C-NMR, IR, MS, and
Scheme 2. Synthetic route of compounds II-1–II-4.
Br
Br
R
O
X
R
Y
POCl3
reflux
O
O
NHNH
N
N
N
O
N
N
N
Cl
Y
O
Cl
N
N
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
Synthesis and Insecticidal Evaluation of Novel Pyridylpyrazole Derivatives
Table 1
Structure and insecticidal activity of compound I.
Chemical structure
X,Y
MS
PX
Compd
R
500 mg/L
200 mg/L
500 mg/L
200 mg/L
I-1
I-2
I-3
I-4
I-5
I-6
I-7
I-8
I-9
I-10
I-11
I-12
H
CH3
H
CH3
H
CH3
H
CH3
H
4-Cl
4-Cl
2,4-diCl
2,4-diCl
3-Cl
3-Cl
2-Cl
2-Cl
4-CH3
4-CH3
2-CH3
2-CH3
73
100
75
80
65
98
20
25
50
55
55
95
100
NT
10
NT
NT
NT
10
NT
NT
NT
NT
NT
0
58
85
68
70
53
70
13
15
35
35
35
68
100
NT
5
NT
NT
NT
0
NT
NT
NT
NT
NT
0
CH3
H
CH3
Chlorantraniliprol
100
100
NT, not test; MS, Mythimna separata; PX, Plutella xylostella.
Table 2
Structure and insecticidal activity of compound II.
Chemical structure
X,Y
MS
PX
Compd
R
500 mg/L
200 mg/L
500 mg/L
200 mg/L
II-1
II-2
II-3
II-4
H
CH3
H
2-Cl
2-Cl
4-Cl
90
10
33
30
100
0
65
5
28
20
100
0
NT
NT
NT
100
NT
NT
NT
100
H
2,4-diCl
Chlorantraniliprol
NT, not test; MS, Mythimna separata; PX, Plutella xylostella.
elemental analysis. In the 1H-NMR spectra of the title
compounds I-1–12, the proton signal corresponding to –
CONHNHCO– appears as two singlets at δ 10.20–10.85.
IR spectra of the title compounds I-1–12 showed normal
stretching absorption bands, indicating the existence of
C=O (~1718 cmꢀ1). The typical carbon resonance at δc
155–171 in the 13C-NMR spectra of I-2–12 also confirms
the presence of two carbon–oxygen double bonds. The
ESI mass spectra of the title compounds I and II revealed
the existence of the molecular ion peaks, which were in
good accordance with the given structures of title
compounds. The elemental analysis of all target
compounds is in good agreement with the theoretical data.
concentration. For example, the larvicidal activities of
compounds I-1, I-6, I-12, and II-1 against M. separata at
500 mg/L were 90–100%. Especially, compounds I-1
exhibited 100% larvicidal activities against M. separata.
Then, some of compounds were selected for further test
against M. separata and P. xylostella at 200 mg/L. The
subsequent results showed that compounds I-2, I-6, I-12,
and II-1 had weak insecticidal activity against
M. separata and P. xylostella with 0–10% death rates.
Comparing insecticidal activities among the title
compounds in Table 1, it was found that the R group and
the substituents X,Y have an impact on the insecticidal
activity. For example, when the kind and positions of
substituents X,Y were kept constant, compound I with R
as CH3 showed better activity than that of compounds
with R as H. Comparing insecticidal activities among the
title compound II in Table 2, it is noteworthy that
compound with X, Y as 2-Cl and R as H showed higher
insecticidal activities against M. separata and
P. xylostella at 500 mg/L compared to those compounds
containing X,Y as 2-Cl and R as CH3 or X,Y as 4-Cl,
2,4-Cl2, and R as H. However, further exploring of
Insecticidal activity.
The preliminary insecticidal
activity of I and II was evaluated against M. separata
and P. xylostella at 500 mg/L using the known procedure
[12] and chlorantraniliprol as a positive control. As
shown in Tables 1, 2, compounds I and II exhibited 10–
100% and 5–85% larvicidal activities against M. separata
and P. xylostella at 500 mg/L, respectively. Bioassay
results indicated that some compounds had excellent
larvicidal activities against M. separata at the tested
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

W. Wang, X.-R. Zheng, X.-Y. Huang, M.-Z. Mao, K.-Y. Liu, C. Xue, L.-P. Wang, and B.-K. Ning Vol 000
structure–activity relationship about compound II could
not be successfully ascertained due to lack of structural
diversity.
temperature. After evaporation under reduced pressure,
the residue was washed with 30 mL of petroleum ether
and then filtered to give compound 7 with yield of
80–95%.
General procedure for the synthesis of I-1–I-12.
A
CONCLUSION
mixture of intermediate 7 (2 mmol) and K2CO3 (1 mmol)
in THF/H2O 10 mL (1:1, v/v) was stirred, and
intermediate 5 (2 mmol) in THF (5 mL) was added. After
stirring for 3–4 h at room temperature, the reaction
mixture was evaporated off under reduced pressure,
poured into water, and then filtered and recrystallized
from ethanol to afford compounds I-1–I-12.
In conclusion, two series of novel N-pyridylpyrazole
derivatives I and II were designed and synthesized based
on the structure of chlorantraniliprole. The insecticidal
activities of the new compounds against M. separata and
P. xylostella were evaluated. Some of the N-
pyridylpyrazole derivatives (compounds I-2, 6, 12, and
II-1) exhibited larvicidal activities against M. separata
with 90–100% death rates at 500 mg/L. The results of
further test showed that these compounds had weak
insecticidal activity against M. separata and P. xylostella
with 0–10% death rates at 200 mg/L. Generally speaking,
these types of compounds might be not suitable as
insecticide lead compound for further optimization.
N0-(2-(4-Chlorophenoxy)acetyl)-3-bromo-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carbohydrazide (I-1).
White solid;
yield, 89%; mp, 158–160°C; 1H-NMR (500 MHz,
DMSO-d6): δ 4.61 (s, 2H, -CH2-), 6.97–7.01 (m, 2H,
4
2,6H-Ar), 7.30 (s, 1H, H-pyrazole), 7.31–7.34 (m, 2H,
3,5H-Ar), 7.64–7.67 (dd, J = 5 Hz, J = 8 Hz, 1H, H-
5
4
pyridine), 8.20–8.22 (m, 1H, H-pyridine), 8.50–8.52 (m,
6
1H, H-pyridine), 10.31 (s, 1H, CONH), 10.77 (s, 1H,
CONH); IR (KBr)/cmꢀ1: 3389, 3296, 3120, 3072, 3001,
1717, 1692, 1599, 1582, 1519, 1504, 1466, 1418, 1360,
1245, 1206, 1120, 1094, 1052, 965, 884, 919, 830, 799,
753; ESI-MS m/z: 482.95 (M+); Anal. Calcd for
C17H12BrCl2N5O3: C, 42.09; H, 2.49; N, 14.44; Found:
C, 42.12; H, 2.44; N, 14.39.
EXPERIMENTAL
Chemicals and reagents were obtained from commercial
sources, and all of the solvents were dried and purified by
standard techniques prior to use. Column chromatography
was carried out with Merck silica gel (200–300 mesh).
Melting points (mp) were measured on a Buchi B-545
melting point apparatus and were uncorrected. IR spectra
were recorded as KBr pellets on a Perkin-Elmer Fourier
transform infrared spectrophotometer. 1H-NMR were
recorded on Varian XL-500 spectrometer at 500 MHz
using tetramethylsilane as internal standard (solvent
CDCl3). Chemical shifts (δ) are given in ppm, coupling
constants (J) are in Hz, and multiplicities are implicated
by s (singlet), d (doublet), t (triplet), q (quartet), and m
(multiplet). MS spectra were analyzed on a Finnigen
TRACE spectrometer and API2000LC/MS. Elemental
analyses were performed by a Vario EL III elemental
analyzer.
N0-(2-(4-Chlorophenoxy)propanoyl)-3-bromo-1-(3-
chloropyridin-2-yl)-1H-pyrazole-5-carbohydrazide (I-2). White
1
solid; yield, 90%; mp, 165–167°C; H-NMR (500 MHz,
DMSO-d6): δ 1.43 (d, 3H, J = 6.5 Hz, CH-CH3),4.82 (q,
1H, J = 6.0 Hz, CH-CH3), 6.94 (s, 1H), 6.96 (s, 1H), 7.26
(s, 1H, 4H-pyrazole), 7.29–8.51 (m, 4H), 10.34 (s, 1H,
CONH), 10.78 (s, 1H, CONH); IR (KBr)/cmꢀ1: 3391,
3270, 3078, 2854, 1706, 1673, 1579, 1539, 1506, 1465,
1415, 1355, 1235, 1213, 1200, 1100, 1080, 1046, 979, 961,
809, 778, 762; 13C-NMR (125 MHz, DMSO-d6): 19.0,
73.3, 110.7, 117.6, 125.5, 127.3, 129.1, 129.7, 130.1,
133.2, 139.8, 147.6, 148.9, 156.3, 156.4, 170.4; ESI-MS m/
z: 496.97 (M+); Anal. Calcd for C18H14BrCl2N5O3: C,
43.31; H, 2.83; N, 14.03; Found: C, 43.26; H, 2.87; N, 14.08.
N0-(2-(2,4-Dichlorophenoxy)acetyl)-3-bromo-1-(3-
General procedure for the synthesis of 5.
The
chloropyridin-2-yl)-1H-pyrazole-5-carbohydrazide (I-3). White
1
intermediate compound 4 was synthesized according to
the literature [2,4]. A mixture containing the intermediate
compound 4 (3.5 mmol) and thionyl chloride (3 mL) was
added into a 25 mL of flask and refluxed for 5–6 h.
Excess thionyl chloride was evaporated off under reduced
pressure, and a light yellow oil 5 was obtained with a
yield of 94%.
solid; yield, 92%; mp, 199–201°C; H-NMR (500 MHz,
DMSO-d6): δ 4.74 (s, 2H, CH2), 7.02 (d, 1H, J = 9.0 Hz,
6H-Ar), 7.29 (s, 1H, 4H-pyrazole), 7.32–8.51 (m, 5H,
4,5,6H-Py, 3,5H-Ar), 10.34 (s, 1H, CONH), 10.85 (s, 1H,
CONH); IR (KBr)/cmꢀ1: 3460, 3371, 3188, 2953, 1701,
1630, 1574, 1519, 1479, 1456, 1292, 1267, 1071, 1033,
999, 960, 819, 763; 13C-NMR (125 MHz, DMSO-d6):
67.2, 110.8, 115.9, 123.1, 125.7, 127.3, 127.4, 128.4,
129.9, 130.1, 133.2, 139.8, 147.6, 148.9, 152.9, 156.3,
166.7; ESI-MS m/z: 516.91 (M+); Anal. Calcd for
C17H11BrCl3N5O3: C, 39.30; H, 2.13; N, 13.48; Found: C,
39.34; H, 2.14; N, 13.46.
General procedure for the synthesis of 7.
The
intermediate compound 6 was synthesized according to
the literature [24]. A mixture of 6 (4 mmol) and
hydrazine hydrate (4.4 mmol) was refluxed for 5–8 h.
The mixture was then stirred over night at room
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
Synthesis and Insecticidal Evaluation of Novel Pyridylpyrazole Derivatives
N0-(2-(2,4-Dichlorophenoxy)propanoyl)-3-bromo-1-(3-
DMSO-d6): 66.6, 110.5, 114.3, 121.7, 122.5, 126.9,
128.3, 128.7, 129.7, 130.2, 137.4, 139.5, 147.3, 148.5,
153.4, 155.9, 166.6; ESI-MS m/z: 482.95 (M+); Anal.
Calcd for C17H12BrCl2N5O3: C, 42.09; H, 2.49; N,
chloropyridin-2-yl)-1H-pyrazole-5-carbohydrazide (I-4). White
1
solid; yield, 88%; mp, 102–104°C; H-NMR (500 MHz,
DMSO-d6): δ 1.48 (d, 3H, J = 6.5 Hz, CH-CH3), 4.87 (q,
6
1H, J = 6.5 Hz, CH-CH3), 7.03 (d, 1H, J = 8.5 Hz, H-
14.44; Found: C, 42.11; H, 2.46; N, 14.49.
4
Ar), 7.26–8.52 (m, 6H, H-pyrazole, 4,5,6H-Py, 3,5H-Ar),
N0-(2-(2-Chlorophenoxy)propanoyl)-3-bromo-1-(3-
chloropyridin-2-yl)-1H-pyrazole-5-carbohydrazide (I-8). White
10.39 (s, 1H, CONH), 10.84 (s, 1H, CONH); IR (KBr)/
cmꢀ1: 3389, 3209, 2988, 2872, 1714, 1682, 1645, 1576,
1524, 1476, 1416, 1358, 1285, 1244, 1105, 1060, 1046,
1027, 961, 872, 803, 763; 13C-NMR (125 MHz,
DMSO-d6): 19.1, 74.3, 110.8, 116.8, 123.8, 125.9, 127.3,
127.3, 128.4, 129.1, 129.9, 130.1, 133.2, 139.8, 147.6,
152.3, 156.3, 169.8; ESI-MS m/z: 530.93 (M+); Anal.
Calcd for C18H13BrCl3N5O3: C, 40.52; H, 2.46; N, 13.12;
1
solid; yield, 90%; mp, 144–146°C; H-NMR (500 MHz,
DMSO-d6): δ 1.49 (d, 3H, J = 6.5 Hz, CH-CH3), 4.85 (q,
1H, J = 6.5 Hz, CH-CH3), 6.95–8.52 (m, 8H, 4H-
pyrazole, 4,5,6H-Py, 3,4,5,6H-Ar), 10.38 (s, 1H, CONH),
10.83 (s, 1H, CONH); IR (KBr)/cmꢀ1: 3428, 3273, 3124,
3030, 2996, 2938, 1714, 1688, 1658, 1583, 1521, 1479,
1470, 1389, 1278, 1243, 1147, 1093, 1059, 965, 916,
883, 797, 759; 13C-NMR (125 MHz, DMSO-d6): 18.8,
73.6, 110.4, 115.3, 122.3, 122.5, 126.9, 126.9, 128.2,
128.7, 129.7, 130.2, 139.5, 147.3, 148.5, 152.8, 155.9,
169.9; ESI-MS m/z: 496.97 (M+); Anal. Calcd for
C18H14BrCl2N5O3: C, 43.31; H, 2.83; N, 14.03; Found:
Found: C, 40.48; H, 2.50; N, 13.09.
N0-(2-(3-Chlorophenoxy)acetyl)-3-bromo-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carbohydrazide (I-5).
White solid;
yield, 91%; mp, 191–193°C; 1H-NMR (500 MHz,
DMSO-d6): δ 4.65 (s, 2H, -CH2-), 6.95 (d, 1H,
J = 8.0 Hz, 6H-Ar), 7.02–8.52 (m, 7H, 4H-pyrazole,
4,5,6H-Py, 2,4,5H-Ar), 10.33 (s, 1H, CONH), 10.79 (s, 1H,
CONH); IR (KBr)/cmꢀ1: 3607, 3298, 3179, 3136, 3072,
3026, 2979, 1708, 1677, 1596, 1581, 1544, 1512, 1467,
1439, 1359, 1282, 1225, 1076, 1060, 962, 898, 814, 774,
760; 13C-NMR (125 MHz, DMSO-d6): 66.7, 110.7,
114.3, 115.4, 121.8, 127.3, 127.3, 129.1, 130.1, 131.3,
134.1, 139.8, 147.6, 148.9, 156.4, 158.9, 167.1; ESI-MS
m/z: 482.95 (M+); Anal. Calcd for C17H12BrCl2N5O3: C,
42.09; H, 2.49; N, 14.44; Found: C, 42.13; H, 2.46; N,
C, 43.35; H, 2.84; N, 13.99.
N0-(2-(4-Methylphenoxy)acetyl)-3-bromo-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carbohydrazide (I-9).
White solid;
yield, 79%; mp, 128–130°C; 1H-NMR (500 MHz,
DMSO-d6): δ 2.2 (s, 3H, Ar-CH3), 4.54 (s, 2H, -CH2-),
6.84–8.52 (m, 8H, 4H-pyrazole, 4,5,6H-Py, 3,4,5,6H-Ar),
10.27 (s, 1H, CONH), 10.77 (s, 1H, CONH); IR (KBr)/
cmꢀ1: 3438, 3241, 3131, 3055, 2990, 1699, 1676, 1616,
1579, 1545, 1511, 1462, 1417, 1359, 1275, 1230, 1171,
1098, 1055, 1030, 968, 889, 812, 760; 13C-NMR
(125 MHz, DMSO-d6): 20.1, 66.2, 110.3, 114.6, 125.4,
126.9, 126.9, 128.2, 128.3, 129.8, 132.8, 139.4, 147.2,
155.6, 155.9, 167.1; ESI-MS m/z: 463.00 (M+); Anal.
Calcd for C18H15BrClN5O3: C, 46.52; H, 3.25; N, 15.07;
14.41.
N0-(2-(3-Chlorophenoxy)propanoyl)-3-bromo-1-(3-
chloropyridin-2-yl)-1H-pyrazole-5-carbohydrazide (I-6). White
1
solid; yield, 89%; mp, 148–150°C; H-NMR (500 MHz,
DMSO-d6): δ 1.45 (d, 3H, J = 6.5 Hz, CH-CH3), 4.87
(q, 1H, J = 6.5 Hz, CH-CH3), 6.92 (d, 1H, J = 7.5 Hz,
Found: C, 46.50; H, 3.28; N, 15.11.
N0-(2-(4-Methylphenoxy)propanoyl)-3-bromo-1-(3-
chloropyridin-2-yl)-1H-pyrazole-5-carbohydrazide (I-10).
4
6H-Ar), 6.99–8.52 (m, 7H, H-pyrazole, 4,5,6H-Py, 2,4,5H-
White solid; yield, 79%; mp, 185–187°C; 1H-NMR
(500 MHz, DMSO-d6): δ 1.42 (d, 3H, J = 6.5 Hz, CH-
CH3), 2.21 (s, 3H, Ar-CH3), 4.75 (q, 1H, J = 6.5 Hz,
CH-CH3), 6.81–8.52 (m, 8H, 4H-pyrazole, 4,5,6H-Py,
2,3,5,6H-Ar), 10.29 (s, 1H, CONH), 10.73 (s, 1H, CONH);
IR (KBr)/cmꢀ1: 3418, 3249, 3137, 3060, 2986, 1697,
1660, 1613, 1582, 1537, 1509, 1467, 1417, 1359, 1285,
1227, 1177, 1124, 1097, 1050, 1030, 962, 886, 812, 764;
13C-NMR (125 MHz, DMSO-d6):18.7, 20.1, 72.6, 110.4,
115.3, 126.9, 126.9, 128.2, 128.6, 129.8, 137.4, 139.4,
147.2, 148.5, 155.0, 155.9, 170.6; ESI-MS m/z: 477.02
Ar), 10.35 (s, 1H, CONH), 10.78 (s, 1H, CONH); IR
(KBr)/cmꢀ1: 3607, 3288, 3270, 3179, 3078, 3026, 2979,
1706, 1673, 1579, 1539, 1506, 1465, 1439, 1415, 1355,
1288, 1213, 1080, 1046, 961, 869, 809, 778, 762; 13C-
NMR (125 MHz, DMSO-d6): 18.6, 72.8, 110.3, 114.3,
115.5, 121.3, 126.9, 126.9, 128.6, 129.7, 130.9, 133.7,
139.4, 147.2, 148.5, 155.9, 158.0, 170.0; ESI-MS m/z:
496.97 (M+); Anal. Calcd for C18H14BrCl2N5O3: C,
43.31; H, 2.83; N, 14.03; Found: C, 43.29; H, 2.85; N,
14.07.
N0-(2-(2-Chlorophenoxy)acetyl)-3-bromo-1-(3-chloropyridin-
(M+); Anal. Calcd for C19H17BrClN5O3: C, 47.67; H,
3.58; N, 14.63; Found: C, 47.64; H, 3.58; N, 14.66.
N0-(2-(2-Methylphenoxy)acetyl)-3-bromo-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carbohydrazide (I-7).
White solid;
yield, 91%; mp, 127–129°C; 1H-NMR (500 MHz,
4
DMSO-d6): δ 4.72 (s, 2H, -CH2-), 6.96–8.52 (m, 8H, H-
pyrazole, 4,5,6H-Py, 3,4,5,6H-Ar), 10.32 (s, 1H, CONH),
10.84 (s, 1H, CONH); IR (KBr)/cmꢀ1: 3428, 3296, 3072,
3030, 3001, 2996, 1717, 1692, 1599, 1582, 1519, 1504,
1479, 1466, 1389, 1360, 1278, 1245, 1206, 1147, 1094,
1052, 965, 919, 884, 799, 753; 13C-NMR (125 MHz,
2-yl)-1H-pyrazole-5-carbohydrazide (I-11).
White solid;
yield, 85%; mp, 171–173°C; 1H-NMR (500 MHz,
DMSO-d6): δ 2.20 (s, 3H, Ar-CH3), 4.60 (s, 2H,-CH2-),
6.83–8.52 (m, 8H, 4H-pyrazole, 4,5,6H-Py, 3,4,5,6H-Ar),
10.20 (s, 1H, CONH), 10.78 (s, 1H, CONH); IR (KBr)/
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

W. Wang, X.-R. Zheng, X.-Y. Huang, M.-Z. Mao, K.-Y. Liu, C. Xue, L.-P. Wang, and B.-K. Ning Vol 000
cmꢀ1: 3401, 3223, 3099, 2998, 2917, 1709, 1679, 1669,
1583, 1499, 1470, 1351, 1313, 1227, 1193, 1139, 1139,
1058, 964, 919, 883, 809, 759; 13C-NMR (125 MHz,
DMSO-d6):16.1, 66.3, 110.3, 111.6, 121.1, 126.3, 126.9,
128.2, 128.6, 129.6, 130.6, 132.7, 137.4, 139.4, 147.2,
148.5, 155.9, 167.1; ESI-MS m/z: 463.00 (M+); Anal.
Calcd for C18H15BrClN5O3: C, 46.52; H, 3.25; N, 15.07;
Found: C, 46.51; H, 3.27; N, 15.06.
2-(5-(5-((4-Chlorophenoxy)methyl)-1,3,4-oxadiazol-2-yl)-3-
bromo-1H-pyrazol-1-yl)-3-chloropyridine (II-3).
solid; yield, 57%; mp, 130–132°C; H-NMR (500 MHz,
White
1
CDCl3): δ 5.20 (s, 2H, -CH2-), 6.88 (d, 2H, J = 9.0 Hz,
2,6H-Ar), 7.12 (s, 1H, 4H-pyrazole), 7.25 (d, 2H,
J = 9.0 Hz, 3,5H-Ar),7.42–8.45 (m, 3H, 4,5,6H-Py); IR
(KBr)/cmꢀ1: 3129, 2929, 2856, 1699, 1625, 1580,
1509, 1461, 1426, 1377, 1273, 1225, 1131, 1060, 1041,
1016, 959, 879, 851, 801, 748; 13C-NMR (125 MHz,
CDCl3): δ 59.9, 112.5, 116.2, 126.6, 127.5, 128.9,
129.4, 129.7, 129.9, 130.9, 139.6, 147.8, 155.9, 156.5,
162.1; ESI-MS m/z: 464.94 (M+); Anal. Calcd for
C17H10BrCl2N5O2: C, 43.71; H, 2.16; N, 14.99; Found:
C, 43.73; H, 2.14; N, 14.97.
N0-(2-(2-Methylphenoxy)propanoyl)-3-bromo-1-(3-
chloropyridin-2-yl)-1H-pyrazole-5-carbohydrazide (I-12).
White solid; yield, 77%; mp, 175–177°C; 1H-NMR
(500 MHz, DMSO-d6): δ 1.45 (d, 3H, J = 6.5 Hz, CH-
CH3), 2.18 (s, 3H, Ar-CH3), 4.76 (q, 1H, J = 6.5 Hz,
CH-CH3), 6.81–8.52 (m, 8H, 4H-pyrazole, 4,5,6H-Py,
2,3,5,6H-Ar), 10.25 (s, 1H, CONH), 10.74 (s, 1H,
CONH); IR (KBr)/cmꢀ1: 3427, 3278, 3124, 3025, 2990,
2937, 1715, 1689, 1675, 1583, 1521, 1493, 1464, 1358,
1303, 1238, 1193, 1147, 1131, 1052, 964, 917, 883,
800, 756; 13C-NMR (125 MHz, DMSO-d6):16.2, 18.9,
72.8, 110.4, 112.5, 121.0, 126.8, 126.9, 128.6, 129.6,
130.6, 132.7, 137.4, 139.4, 147.2, 148.5, 155.4, 155.9,
170.6; ESI-MS m/z: 477.02 (M+); Anal. Calcd for
C19H17BrClN5O3: C, 47.67; H, 3.58; N, 14.63; Found:
C, 47.71; H, 3.57; N, 14.66.
2-(5-(5-((2,4-Dichlorophenoxy)methyl)-1,3,4-oxadiazol-2-yl)-
3-bromo-1H-pyrazol-1-yl)-3-chloropyridine (II-4).
White
1
solid; yield, 71%; mp, 126–128°C; H-NMR (500 MHz,
CDCl3): δ 5.28 (s, 2H, -CH2-), 6.96 (d, 1H, J = 4.5 Hz,
6H-Ar), 7.14 (s, 1H, 4H-pyrazole), 7.16–7.46 (m, 5H,
3,5H-Ar, 4,5,6H-Py); IR (KBr)/cmꢀ1: 3131, 2930, 2925,
2854, 1701, 1621, 1577, 1489, 1463, 1421, 1379, 1352,
1277, 1129, 1128, 1063, 1042, 1019, 957, 879, 850,
800, 749; 13C-NMR (125 MHz, CDCl3): δ 61.0, 112.6,
115.7, 124.7, 126.6, 127.9, 128.2, 128.9, 129.3, 129.8,
130.6, 139.6, 147.2, 147.8, 151.8, 156.7, 161.6; ESI-MS
m/z: 498.90 (M+); Anal. Calcd for C17H9BrCl3N5O2: C,
40.71; H, 1.81; N, 13.96; Found: C, 40.72; H, 1.80;
N, 13.99.
General procedure for the synthesis of II-1–II-4.
A
mixture of compound I (3 mmol) and POCl3 (4 mL) was
heated at 120°C for 6 h. Ice water (40 mL) was added,
and then, the mixture was neutralized with concentrated
Insecticidal activity testing.
ammonia
and
extracted
with
dichloromethane
Larvicidal activity against Mythimna separata.
The
(3 × 15 mL). After drying with anhydrous Na2SO4, the
solvent was evaporated off under reduced pressure to
give crude products. These compounds were purified by
column chrimatography with silica gel using ethyl
accetate/petroleum ether (3:1, v/v) as an eluent.
larvicidal activities of compounds I, II, and
chlorantraniliprol were determined according the
reference methods [12]. The insecticial activity against
M. separata was tested by foliar application; individual
corn (Tangyu10, Zea mays L.) leaves were placed on
moistened pieces of filter paper in Petri dishes. The
leaves were then sprayed with the test solution and
allowed to dry. The dishes were infested with 10 third-
instar oriental aymyworm larvae. Percentage mortalities
were evaluated 2 days after treatment. Each treatment
was replicated three times.
2-(5-(5-((2-Chlorophenoxy)methyl)-1,3,4-oxadiazol-2-yl)-3-
bromo-1H-pyrazol-1-yl)-3-chloropyridine (II-1).
solid; yield, 65%; mp, 126–128°C; H-NMR (500 MHz,
CDCl3): δ 5.29 (s, 2H, -CH2-), 6.86–8.44 (m, 8H, H-
White
1
4
pyrazole, 4,5,6H-Py, 3,4,5,6H-Ar); IR (KBr)/cmꢀ1: 3138,
2925, 2854, 1699, 1621, 1575, 1483, 1461, 1426, 1352,
1277, 1229, 1128, 1063, 1042, 1019, 959, 879, 801, 748;
ESI-MS m/z: 464.94 (M+); Anal. Calcd for
C17H10BrCl2N5O2: C, 43.71; H, 2.16; N, 14.99; Found:
C, 43.68; H, 2.15; N, 14.98.
Larvicidal activity against Plutella xylostella.
The
larvicidal activity of compounds I, II, and
chlorantraniliprol were tested by the leaf-dip method
[12]. At first, a solution of each test sample in
dimethylformamide at a concentration of 500 mg/L was
prepared. Leafs disks (6 × 2 cm) were cut from fresh
cabbage leaves and then sprayed with the test solution
for 3 s and allowed to dry. The resulting leaf disks
were placed individually into glass tubes. Each disk
was infested with 30 s of instar diamondback moth
larvae. Percentage mortalities were evaluated 2 days
after treatment. Each treatment was performed three
times.
2-(5-(5-(1-(2-Chlorophenoxy)ethyl)-1,3,4-oxadiazol-2-yl)-3-
bromo-1H-pyrazol-1-yl)-3-chloropyridine (II-2).
White
1
solid; yield, 62%; mp, 115–117°C; H-NMR (500 MHz,
CDCl3): δ 1.77 (d, 3H, J = 6.5 Hz, CH-CH3), 5.53 (q, 1H,
4
J = 6.5 Hz, CH-CH3), 6.94–8.43 (m, 8H, H-pyrazole,
4,5,6H-Py, 3,4,5,6H-Ar); IR (KBr)/cmꢀ1: 3140, 2928, 2854,
1700, 1626, 1580, 1483, 1464, 1379, 1287, 1232, 1130,
1061, 1042, 1021, 958, 851, 803, 748; ESI-MS m/z:
478.96 (M+); Anal. Calcd for C18H12BrCl2N5O2: C, 44.93;
H, 2.51; N, 14.56; Found: C, 44.94; H, 2.54; N, 14.52.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2019
Synthesis and Insecticidal Evaluation of Novel Pyridylpyrazole Derivatives
[13] Mao, C. H.; Wang, Q. M.; Huang, R. Q.; Bi, F. C.; Chen, L.;
Liu, Y. X.; Shang, J. J Agric Food Chem 2004, 52, 6737.
[14] Zhao, Q. Q.; Shang, J.; Liu, Y. X.; Wang, K. Y.; Bi, F. C.;
Huang, R. Q.; Wang, Q. M. J Agric Food Chem 2007, 55, 9614.
[15] Zhao, Q. Q.; Shang, J.; Huang, Z. Q.; Wang, K. Y.; Bi, F. C.;
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Acknowledgment. The present work was supported by Science
and Technology Entire Innovation Project Plan Foundation of
Shaanxi Province (2016KTCL01-09).
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SUPPORTING INFORMATION
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Additional supporting information may be found online
in the Supporting Information section at the end of the
article.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet