Synthesis and insecticidal activity of anthranilic diamides with hydrazone substructure

Article abstract of DOI:10.1515/chempap-2015-0100

A series of anthranilic diamides with a hydrazone substructure was synthesised and characterised using ¹H NMR, ¹³C NMR, IR and elemental analyses. The in vitro insecticidal activity of all the compounds was tested against Plutella xylostella. The results showed the synthesised compounds to possess good insecticidal activity. The LC50 values of compounds VIIg, VIIl, VIIm, VIIn exhibited excellent insecticidal activities, with the LC₅₀ affording 7.92 mg L^-1, 12.01 mg L^-1, 0.62 mg L^-1 and 10.71 mg L^-1, respectively. These may prove to be useful as potential insecticidal agents.

Full text of DOI:10.1515/chempap-2015-0100

Chemical Papers 69 (7) 993–1003 (2015)
DOI: 10.1515/chempap-2015-0100
ORIGINAL PAPER
Synthesis and insecticidal activity of anthranilic diamides
with hydrazone substructure
a,b
a,b
c
c
c
‡
‡
Jian Wu* , Dan-Dan Xie , Wei-Li Shan, Yong-Hui Zhao, Wei Zhang,
a,bBaoan Song, a,bSong Yang, a,bJuan Ma
aState Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide
and Agricultural Bioengineering, Ministry of Education, bResearch and Development Centre for Fine Chemicals,
Guizhou University, Guiyang 550025, China
cInstitute for the Control of Agrochemicals, Ministry of Agriculture, Beijing 100125, China
Received 25 October 2014; Revised 24 December 2014; Accepted 5 January 2015
A series of anthranilic diamides with a hydrazone substructure was synthesised and characterised
using 1H NMR, 13C NMR, IR and elemental analyses. The in vitro insecticidal activity of all the
compounds was tested against Plutella xylostella. The results showed the synthesised compounds to
possess good insecticidal activity. The LC50 values of compounds VIIg, VIIl, VIIm, VIIn exhibited
excellent insecticidal activities, with the LC50 affording 7.92 mg L−1, 12.01 mg L−1, 0.62 mg L−1
and 10.71 mg L−1, respectively. These may prove to be useful as potential insecticidal agents.
c
ꢀ 2015 Institute of Chemistry, Slovak Academy of Sciences
Keywords: anthranilic diamides, hydrazone, insecticidal activity, synthesis
Introduction
diamides represent a new class of insecticides that
binds to the ryanodine receptor, resulting in the un-
controlled release of calcium stores from the sar-
coendoplasmic reticulum (Lahm et al., 2009, 2007).
The anthranilic diamide insecticides have exhibited a
high efficacy against various pests including the di-
amondback moth. In recent years, the phthalic di-
amides insecticides have become the focus for the de-
velopment of novel insecticidal molecules, the skele-
tons of the commercial phthalic diamides insecticides
were selected as lead structures, and a large num-
ber of phthalic diamides with high insecticidal activ-
ity have been reported (Chen et al., 2013; Clark et
al., 2008; Feng et al., 2010, 2011; Selby et al., 2013;
Koyanagi et al., 2006; Lahm et al., 2006; Ikegami
et al., 2007, 2008a, 2008b; Zhao et al., 2012; Yack-
man & Sanemitsu, 2007; Yasuyuki et al., 2005; Zhang
et al., 2012, 2014; Zhou et al., 2014), such as com-
pounds A–F in Fig. 1 (Clark et al., 2008; Ikegami
et al., 2007, 2008a; Selby et al., 2013; Zhang et al.,
2014; Zhou et al., 2014); some of the highly active
In recent years, pests in crops have become in-
creasingly difficult to control; more and more resis-
tant pests have been developed due to the continued
and widespread application of traditional pesticides,
thereby leading to enormous losses in worldwide crop
production each year (Oerke, 2006). The diamondback
moth (Plutella xylostella L.) can serve as an example:
it is a serious pest in many parts of the world (Hasan-
shahi et al., 2013), and significant losses to crucifers
and oilseed crops have become more common (Fur-
long et al., 2013). Hence, the development of new in-
secticidal molecules against the insects has attracted
increased attention.
In recent decades, several insecticides with a struc-
ture containing phthalic diamides (such as fluobendi-
amide, chlorantraniliprole and cyantraniliprole; Fig. 1)
have been developed and commercialised (Lahm et
al., 2006, 2007, 2009; Selby et al., 2013; Seo et al.,
2007; Tohnishi et al., 2000, 2005). These anthranilic
*Corresponding author, e-mail: wujian2691@126.com
‡
The first and the second authors contributed equally to this work.
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J. Wu et al./Chemical Papers 69 (7) 993–1003 (2015)
Fig. 1. Structures of phthalic diamides with insecticidal activity.
compounds are at the stage of industrial produc-
tion.
lent activity against Plutella xylostella (Linnaeus), He-
licoverpa armigera (Hu¨bner), Culex pipiens pallens,
Laphygma exigua (Hu¨bner), Spodoptera litura (Fabri-
cius), Nilaparvata lugens (St˚al) and Rhopalosiphum
maidis (Fitch). In particular, compound N (Fig. 2) ex-
hibits excellent activity (IC50 = 0.71 mg L−1) against
Plutella xylostella (Wu et al., 2012). Accordingly, an
attempt was made to carry out some modifications
via changed substituent groups on the benzene ring,
as well as in the hydrazone substructure, which may
result in new phthalic diamides with better insecti-
cidal activity than that of the compounds previously
reported (Wu et al., 2012). In addition, this modi-
fication may enhance information on the structure-
activity relationship (SAR) to this type of substruc-
ture. In the present work, a series of new anthranilic
diamides with a hydrazone substructure was synthe-
sised (Fig. 3). Biological assays revealed that some of
the synthesised compounds exhibited good insectici-
dal activity against Plutella xylostella (Linnaeus).
The hydrazone substructure has been widely used
in pesticide design. Many compounds (such as com-
pounds G–J; Fig. 2) with hydrazone and a wide spec-
trum of activities have been reported as insecticidal
agents (B¨oger et al., 2001; Hollingshaus, 1987; Li et
al., 2014; Liu et al., 2010a, 2010b; Tabanca et al.,
2013; Wang et al., 2006), including the metaflumizone
(Fig. 2), which was developed by BASF (Germany)
(Takagi et al., 1992; Klein, 2005). More recently, a se-
ries of nalidixic acid derivatives containing hydrazone
(K; Fig. 2) was reported as possessing excellent insec-
ticidal activity against Spodoptera litura (Fabricius)
(Aggarwal et al., 2010). Liu et al. (2010a) disclosed a
series of hydrazone derivatives (L; Fig. 2) with good
insecticidal activity by using fluobendiamide as a lead
structure. In a previous work, a series of novel insec-
ticidal molecules was developed containing a hydra-
zone substructure (M; Fig. 2), which exhibited excel-
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J. Wu et al./Chemical Papers 69 (7) 993–1003 (2015)
995
Fig. 2. Insecticidal molecules containing hydrazone group.
Fig. 3. Synthesis of compounds VIIa–VIIs.
Experimental
Bangcheng chemical (China) and Nuotai chemical
(China). All anhydrous solvents were dried and pu-
rified in accordance with the standard techniques im-
mediately prior to use. Melting points were left un-
Unless stated otherwise, all reagents were of ana-
lytical grade or chemically pure and purchased from
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J. Wu et al./Chemical Papers 69 (7) 993–1003 (2015)
Table 1. Physical properties and analytical data for newly synthesised compounds
wi(calc.)/%
wi(found)/%
Yield
M.p.
Compound
Formula
Appearance
Mr
C
H
N
%
91
85
83
81
85
80
80
78
85
94
96
96
90
90
92
79
88
79
96
◦C
VIIa
VIIb
VIIc
VIId
VIIe
VIIf
VIIg
VIIh
VIIi
VIIj
VIIk
VIIl
C19H16BrCl2N7O2
C21H13BrCl2N6O3
C19H15BrCl2N6O2
C19H15BrCl2N6O2
C22H19BrCl2N6O2
yellow solid 525.19
white solid 548.18
43.45
43.43
3.07
3.18
18.67
18.82
227–230
169–173
126–131
220–224
213–216
243–247
162–164
238–240
220–223
126–128
126–128
223–224
220–224
235–237
190–192
> 250
46.01
46.12
2.39
2.43
15.33
15.27
yellow solid 510.17
yellow solid 510.17
yellow solid 550.24
44.73
44.56
2.96
3.02
16.47
16.51
44.73
44.66
2.96
2.89
16.47
16.38
48.02
48.23
3.48
3.53
15.27
15.31
C24H14BrCl2F3N6O2 yellow solid 626.21
21H12BrCl3N6O3 yellow solid 582.62
46.03
45.98
2.25
2.31
13.42
13.51
C
43.29
43.28
2.08
2.14
14.42
14.36
C23H12BrCl5N6O2
C22H15BrCl4N8O2
C22H18BrCl3N6O2
C23H21BrCl2N6O2
C20H12BrCl3N8O2
C19H15BrCl3N7O2
C24H16BrCl3N6O3
C22H16BrClN6O3
C24H16BrCl2FN6O2
C24H16BrClFN6O2
C25H19BrCl2N6O3
C25H20BrClN6O3
white solid
white solid
white solid
white solid
white solid
white solid
white solid
white solid
white solid
white solid
white solid
white solid
661.55
645.12
584.68
564.26
582.62
559.63
622.69
527.76
590.23
555.79
590.23
567.82
41.76
41.85
1.83
1.92
12.70
12.75
40.96
41.03
2.34
2.52
17.37
17.54
45.19
45.24
3.10
3.34
14.37
14.43
48.96
29.03
3.75
3.68
14.89
14.83
49.19
48.98
2.48
2.53
11.47
11.23
VIIm
VIIn
VIIo
VIIp
VIIq
VIIr
VIIs
40.78
40.82
2.70
2.71
17.52
17.39
46.29
46.44
2.59
2.48
13.50
13.56
50.07
50.21
3.06
3.11
15.92
15.88
48.84
48.89
2.73
2.72
14.24
14.17
51.86
51.83
3.08
3.12
15.12
15.09
153–155
150–152
210–211
48.84
48.89
2.73
2.72
14.24
14.17
52.88
52.76
3.55
3.54
14.80
14.78
corrected and determined on a XT-4 binocular mi-
croscope (Beijing Tech Instrument, China). The 1H
NMR and 13C NMR spectra were recorded on a JEOL
ECX 500 NMR spectrometer (Japan) at ambient tem-
perature operating at 500 MHz for 1H NMR and
125 MHz for 13C NMR by using CDCl3 or DMSO
as solvents and TMS as an internal standard. Chem-
ical shifts are given in δ relative to TMS. Infrared
spectra were recorded using KBr technique on an IR
Pristige-21 spectrometer (Shimadzu, Japan) elemen-
tal analysis was performed on an Elemental Vario-III
CHN analyser (Elementar, German). The course of
the reactions was monitored by TLC; analytical TLC
was performed on silica gel GF 254 (Merck, Germany).
The key intermediate pyrazole-5-carboxylic acid (IV)
was obtained in five steps by following the recognised
procedure using 2,3-dichloropyridine and hydrazine as
starting materials with good yields (Lahm et al., 2006,
2007).
General procedure for synthesis of substituted-
4H-benzo[d][1,3]oxazin-4-one (V)
To a solution of acid (IV; 0.6 g, 2 mmol) in ace-
tonitrile (10 mL) methanesulphonyl chloride (0.27 mL,
3.6 mmol) and pyridine (0.6 g) were added, the result-
ing mixture was then stirred at ambient temperature
for 10 min. Next, the substituted 2-amino-benzoic acid
(3 mmol) was added, followed by pyridine (0.4 mL,
5 mmol), and the mixture was stirred at ambient tem-
perature for a further 20 min. Methanesulphonyl chlo-
ride (0.4 mL, 5.2 mmol) was then added, the mixture
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Table 2. Spectral data of newly prepared compounds
997
Compounds
Spectral data
IR, ν˜/cm−1: 3232.7, 3124.6 (NH), 3064.8 (ArH), 2954.0, 2910.5 (CH3), 1687.7, 1645.2 (C O), 1585.4, 1517.9,
—
—
VIIa
1506.4, 1465.9 (skeleton vibration of aromatic ring)
1H-NMR (DMSO-d6), δ: 12.58 (s, 1H, -CONHAr), 11.09 (s, 1H, -ArCONH), 8.51 (dd, 4J = 4.6 Hz, 3J = 1.2 Hz,
1H, pyridine-H), 8.21–8.18 (m, 2H, -CH N + Ph-H), 7.88–7.83 (m, 2H, Ph-H), 7.64 (dd, 4J = 8.1 Hz, 3J = 5.2 Hz,
—
—
1H, pyridine-H), 7.48 (dd, 4J = 7.5 Hz, 3J = 1.2 Hz, 1H, pyridine-H), 7.15 (s, 1H, 4-pyrazole-H), 2.84 (s, 6H,
CH3—N—CH3)
13C NMR (DMSO-d6), δ: 162.1, 156.2, 155.1, 153.7, 149.7,148.6, 147.8, 140.0, 137.4, 131.8, 128.4, 127.9, 127.7, 127.4,
122.8, 119.4, 110.3, 33.7
—
VIIb
IR, ν˜/cm−1: 3250.0, 3178.6 (NH), 3064.8, 2951.0 (ArH), 1689.6, 1645.2 (C O), 1622.1, 1595.1, 1577.7, 1506.4
—
(skeleton vibration of aromatic ring)
1H-NMR (DMSO-d6), δ: 12.04 (s, 1H, -CONHAr), 11.67 (s, 1H, -ArCONH), 8.48 (d, J = 4.6 Hz, 1H, pyridine-H),
8.25 (s, 1H, -CH N), 8.17 (d, J = 8.0 Hz, 1H, Ph-H), 8.04 (dd, 3J = 7.5 Hz, 4J = 1.2 Hz, 1H, pyridine-H), 7.91
(s, 1H, Ph-H), 7.87 (s, 1H, furan-H), 7.61 (dd, 4J = 4.6 Hz, 3J = 7.5 Hz, 1H), 7.57 (d, 4J = 8.6 Hz, Ph-H), 7.23 (s,
1H, pyrazole-H), 6.98 (s, 1H, furan-H), 6.64 (t, 3J = 1.7 Hz, 1H, furan-H)
13C NMR (DMSO-d6), δ: 163.4, 162.8, 156.2, 155.3, 149.6, 148.6, 147.8, 146.2, 140.0, 139.9, 139.3, 136.7, 132.5,
128.7, 128.3, 127.7, 127.3, 124.5, 124.5, 124.4, 115.0, 112.9, 110.8
—
—
IR, ν˜/cm−1: 3298.3, 3232.6 (NH), 3087.8, 3012.0 (ArH), 2934.2, 2889.5 (CH2CH3), 1700.6, 1678.2 (C O), 1632.4,
—
VIIc
—
1600.4, 1578.7, 1536.4 (skeleton vibration of aromatic ring)
1H-NMR (DMSO-d6), δ: 11.78 (s, 1H, -CONHAr), 11.74 (s, 1H, -ArCONH), 8.53 (dd, J = 4.6 Hz, J = 2.3 Hz,1H,
pyridine-H), 7.68–7.55 (m, 2H, Ph-H), 7.44 (dd, 4J = 8.1 Hz, 3J = 5.2 Hz, 1H, pyridine-H), 7.35 (dd, 4J = 7.5 Hz,
3J = 1.2 Hz, 1H, pyridine-H), 7.23 (s, 1H, 4-pyrazole-H), 2.31 (q, J = 5.5 Hz, 2H, -CH2-), 1.09 (t, J = 5.5 Hz, 2H,
-CH3)
13C NMR (DMSO-d6), δ: 162.4, 155.2, 153.4, 149.3, 148.4, 146.8, 140.2, 137.4, 133.2, 128.6, 126.7, 127.4, 121.8,
120.4, 110.3, 20.5, 17.7
—
VIId
VIIe
VIIf
VIIg
IR, ν˜/cm−1: 3275.3, 3244.2 (NH), 3138.1, 3126.6 (ArH), 2968.4 (CH3), 1685.7, 1660.7 (C O), 1595.1, 1577.7,
—
1521.8, 1506.4 (skeleton vibration of aromatic ring)
1
H-NMR (DMSO-d6), δ: 11.69 (s, 1H, -CONHAr), 10.82 (s, 1H, -ArCONH), 8.50 (s, 1H, -CH N), 8.19 (d, 3J =
—
—
8.1 Hz, 1H, Ph-H), 8.01 (d, 3J = 5.8 Hz, 1H, pyridine-H), 7.81 (s, 1H, Ar-H), 7.45–7.64 (m, 3H, Ar-H), 7.20 (s, 1H,
pyrazole-H), 2.00 (s, 3H, CH3), 1.91 (s, 3H, CH3)
13C NMR (DMSO-d6), δ: 163.5, 163.3, 155.4, 148.6, 147.8, 140.0, 139.9, 136.5, 132.1, 129.1, 128.6, 128.4, 127.7,
127.4, 124.8, 124.0, 110.6, 25.6, 18.9
IR, ν˜/cm−1: 3267.4 (NH), 3122.7 (ArH), 2935.6, 2845.0 (-CH2-), 1670.3, 1660.7 (C O), 1595.1, 1575.8, 1519.1,
—
—
1469.7 (skeleton vibration of aromatic ring)
1H-NMR (DMSO-d6), δ: 11.72 (s, 1H, -CONHAr), 11.00 (s, 1H, -ArCONH), 8.54 (d, 3J = 4.6 Hz, 1H, pyridine-H),
8.20 (d, 3J = 8.0 Hz, 1H, Ph-H), 8.02 (d,3J = 8.6 Hz, 1H, Ar-H), 7.63–7.51 (m, 3H, Ar-H), 7.19 (s, 1H, pyrazole-H),
2.35–2.29 (m, 4H, hexamethylene-H), 1.70–1.38 (m, 6H, hexamethylene-H)
13C NMR (DMSO-d6), δ: 168.6, 163.6, 160.4, 155.4, 148.6, 147.8, 140.0, 136.5, 132.1, 129.0, 128.5, 127.7, 127.4,
124.7, 124.0, 110.7, 35.5, 28.8, 27.4, 26.3, 25.5, 19.1
IR, ν˜/cm−1: 3323.3, 3209.5 (NH), 3197.9, 3170.9 (ArH), 1695.4, 1683.8 (C O), 1585.4, 1558.4, 1521.8, 1506.4,
—
—
1490.9 (skeleton vibration of aromatic ring), 1295.4 (—C—N)
1H-NMR (DMSO-d6), δ: 11.60 (s, 1H, -CONHAr), 9.98 (s, 1H, -ArCONH), 8.52 (dd, 4J = 1.2 Hz, 3J = 4.6 Hz, 1H,
Pyridine-H), 8.48 (s, 1H, CH), 8.10 (dd, 4J = 1.7 Hz, 3J = 8.0 Hz, 1H, pyridine-H), 7.75 (dd, 4J = 1.2 Hz, 3J =
4.6 Hz, 1H, pyridine-H), 7.56 (d, J = 8.1 Hz, 2H, Ph-H), 7.25–7.48 (m, 3H, Ph-H), 7.23 (d, J = 8.06 Hz, 2H, Ph-H)
13C NMR (DMSO-d6), δ: 165.3, 162.5, 160.4, 158.2, 155.6, 149.2, 148.2, 147.3, 144.4, 142.0, 138.4, 137.6, 136.3,
132.5, 128.7, 128.4, 122.7, 126.4, 124.1, 121.4, 115.2, 111.9
IR, ν˜/cm−1: 3242.3, 3134.3 (N-H), 3064.9 (Ar-H), 1670.4, 1660.7 (C O), 1622.1, 1573.9, 1539.2, 1463.9 (skeleton
—
—
—
—
vibration of aromatic ring)
1H-NMR (DMSO-d6), δ: 11.77 (br, 1H, NH), 10.59 (br, 1H, NH), 8.40 (dd, 1H, 4J = 1.8 Hz, 3J = 4.6 Hz, pyridine-
H), 8.06 (s, 1H, C NH), 8.04 (dd, 1H, 4J = 1.7 Hz, 3J = 8.0 Hz, pyridine-H), 7.88 (d, 1H, 3J = 4.6 Hz, furan-H),
—
—
7.83 (s, 1H, Ph-H), 7.63 (s, 1H, Ph-H), 7.50 (dd, 4J = 5.2 Hz, 3J = 8.0 Hz, 1H, pyridine-H), 7.37 (d, 3J = 1.7 Hz,
1H, furan-H ), 6.92 (s, 1H, pyrazole-H), 6.61 (t, 3J = 1.7 Hz, 1H, furan-H)
13C NMR (DMSO-d6), δ: 161.6, 157.2, 148.9, 148.9, 148.7, 147.2, 143.3, 138.6, 138.2, 136.6, 135.5, 134.3, 133.3,
132.6, 132.1, 131.3, 131.2, 129.9, 128.4, 128.2, 127.7, 127.3, 111.3
IR, ν˜/cm−1: 3223.0, 3187.8 (N—H), 3001.2 (Ar—H), 1672.0, 1651.0 (C O), 1618.2, 1587.0, 1570.0, 1463.0 (skeleton
—
—
VIIh
vibration of aromatic ring)
1
—
H-NMR (DMSO-d6), δ: 12.09 (br, 1H, NH), 10.62 (br, 1H, NH), 8.51 (s, 1H, C NH), 8.44 (d, 1H, J = 3.4 Hz,
—
pyridine-H), 8.00–7.82 (m, 3H, J = 4.6 Hz, pyridine-H + 2Ph-H), 7.71 (d, 1H, J = 9.8 Hz, pyridine-H), 7.54–7.49
(m, 2H, 2Ph-H), 7.39 (s, 1H, pyrazole-H), 7.29–7.20 (m, 1H, Ph-H)
13C NMR (DMSO-d6), δ: 161.6, 157.2, 148.9, 148.9, 148.7, 147.2, 143.3, 138.6, 138.2, 136.6, 135.5, 134.3, 133.3,
132.6, 132.1, 131.3, 131.2, 129.9, 128.4, 128.2, 127.7, 127.3, 111.3
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Table 2. (continued)
Compounds
Spectral data
—
VIIi
VIIj
VIIk
VIIl
IR, ν˜/cm−1: 3277.0, 3226.9 (N—H), 3049.4 (Ar—H), 2933.2, 2905.5 (CH3), 1697.4, 1683.9 (C O), 1616.3, 1573.9,
1525.6, 1479.4 (skeleton vibration of aromatic ring)
—
1H-NMR (DMSO-d6), δ: 11.63 (br, 1H, NH), 10.59 (br, 1H, NH), 8.44 (dd, 1H, 4J = 1.7 Hz, 3J = 4.6 Hz, pyridine-
H), 8.13 (s, 1H, C NH), 8.06 (dd, 1H, 4J = 4.6 Hz, 3J = 8.6 Hz, pyridine-H), 7.90 (d, 1H,4 J = 2.3 Hz, Ph-H),
—
—
7.68 (d, 1H, 4J = 1.7 Hz, Ph-H), 7.56 (dd, 1H, 4J = 4.6 Hz, 3J = 8.0 Hz, pyridine-H), 7.44 (s, 1H, pyrazole-H),
3.77 (s, 3H, -CH3), 2.35 (s, 3H, -CH3)
13C NMR (DMSO-d6), δ: 160.6, 156.2, 148.8, 147.5, 147.0, 141.3, 139.6, 137.4, 136.6, 134.3, 132.8, 132.2, 131.5,
131.2, 129.9, 18.4, 128.2, 127.7, 127.3, 111.3, 36.4, 19.0
IR, ν˜/cm−1: 3275.3 (N—H), 3003.0 (ArH), 2935.4, 2861.0 (-CH3 or -CH2-), 1689.8, 1678.3 (C O), 1637.6, 1575.8,
—
—
1485.0 (skeleton vibration of aromatic ring).
1H-NMR (DMSO-d6), δ: 10.73 (br, 1H, NH), 10.27 (br, 1H, NH), 8.49 (dd, 1H, 4J = 1.2 Hz, 3J = 4.6 Hz, pyridine-
H), 8.14 (dd, 1H, 4J = 1.7 Hz, 3J = 8.0 Hz, pyridine-H), 7.59 (dd, 1H, 4J = 4.6 Hz, 3J = 8.0 Hz, pyridine-H), 7.50
(d, 1H, 4J = 2.3 Hz, Ph-H), 7.38 (d, 1H, 4J = 2.3 Hz, Ph-H), 7.36 (s, 1H, pyrazole-H), 2.24–2.28 (m, 4H, 2CH2),
1.64–1.49 (m, 6H, 3CH2)
13C NMR (DMSO-d6), δ: 167.3, 162.5, 159.3, 154.2, 147.5, 146.6, 138.9, 135.4, 130.9, 127.9, 127.4, 126.5, 126.2,
123.6, 122.8, 109.5, 34.3, 27.2, 26.3, 25.2, 24.4, 17.9
IR, ν˜/cm−1: 3228.7 (N—H), 3000.0 (ArH), 2937.5, 2860.0 (-CH3 or -CH2-), 1702.8, 1675.6 (C O), 1575.8, 1489.0
—
—
(skeleton vibration of aromatic ring)
1H-NMR (DMSO-d6), δ: 10.47 (br, 1H, NH), 10.24 (br, 1H, NH), 8.46 (dd, 1H, 4J = 1.2 Hz, 3J = 4.6 Hz, pyridine-
H), 8.13 (dd, 1H, 4J = 1.7 Hz, 3J = 8.0 Hz, pyridine-H), 7.58 (dd, 1H, 4J = 4.6 Hz, 3J = 8.0 Hz, pyridine-H), 7.47
(d, 1H, 4J = 2.3 Hz, Ph-H), 7.36 (d, 1H, 4J = 2.3 Hz, Ph-H), 7.33 (s, 1H, pyrazole-H), 2.21–2.27 (m, 4H, 2CH2),
2.14 (s, 3H, -CH3), 1.62–1.41 (m, 6H, 3CH2)
13C NMR (125 MHz), δ: 161.4, 156.2, 149.7, 148.8, 147.5, 146.0, 139.2, 138.2, 137.3, 134.4, 132.8, 131.5, 127.6, 127.3,
114.5, 111.4, 29.1, 28.1, 26.2, 25.3, 20.2
IR, ν˜/cm−1: 3224.7 (N—H), 3000.0 (ArH), 2937.5, 2860.0 (-CH3 or -CH2-), 1683.8, 1667.8 (C O), 1635.6, 1575.8,
—
—
1489.0 (skeleton vibration of aromatic ring)
1H-NMR (DMSO-d6), δ: 12.82 (br, 1H, NH), 11.89 (br, 1H, NH), 10.65 (br, 1H, NH), 8.39 (d, 1H, 3J = 2.9 Hz,
pyridine-H), 8.10 (s, 1H, -CH N), 8.03 (d, 1H, 3J = 8.0 Hz, pyridine-H), 7.89 (s, 1H, Ph-H), 7.68 (s, 1H, Ph-H),
—
—
7.49 (dd, 1H, 4J = 4.6 Hz, 3J = 8.0 Hz, pyridine-H), 7.39 (d, 1H, imidazole-H), 7.10–7.26 (m, 2H, pyrazole-H +
imidazole-H)
13C NMR (DMSO-d6), δ: 161.1, 156.3, 148.8, 147.6, 142.7, 140.4, 139.6, 139.2, 137.3, 134.4, 132.9, 131.9, 131.5,
131.3, 18.4, 127.6, 127.3, 127.0, 111.4
—
VIIm
VIIn
IR, ν˜/cm−1: 3232.7 (NH), 3124.5, 3068.8 (ArH), 2954.0, 2910.5 (CH3), 1688.7, 1685.2 (C O), 1575.4, 1517.9,
1506.4, 1465.5 (skeleton vibration of aromatic ring)
—
1H-NMR (DMSO-d6), δ: 11.93 (s, 1H, -CONHAr), 10.92 (s, 1H, -ArCONH), 8.31 (d, 3J = 4.1 Hz, 1H, pyridine-H),
3
—
—
8.16 (d, 1H, J = 8.1 Hz, pyridine-H), 7.98 (s, 1H, -CH N), 7.93 (s, 1H, Ph-H), 7.70 (s, 1H, Ph-H), 7.50 (dd, 3H,
3J = 8.0 Hz, 4J = 4.6 Hz, Ar-H), 7.18 (s, 1H, pyrazole-H), 2.91 (s, 3H, CH3), 2.89 (s, 3H, CH3)
13C NMR (DMSO-d6), δ: 163.8, 158.4, 148.6, 147.4, 145.4, 141.1, 140.7, 138.8, 132.6, 131.7, 130.0, 126.4, 124.9,
123.5, 111.5, 34.7
IR, ν˜/cm−1: 3288.6, 3122.7 (N—H), 3061.0 (ArH), 2810 (-CH3), 1687.7, 1670.3 (C O), 1647.2, 1573.9, 1554.63,
—
—
1485.1 (skeleton vibration of aromatic ring)
1H-NMR (DMSO-d6), δ: 11.87 (br, 1H, NH), 10.61 (br, 1H, NH), 8.39 (dd, 1H, J = 4.0 Hz, pyridine-H), 8.16 (s, 1H,
C
NH), 8.06 (d, 1H, J = 8.0 Hz, pyridine-H), 7.89 (d, 1H, Ph-H), 7.65 (s, 1H, Ph-H), 7.51 (dd, 1H, 4J = 4.6 Hz, 3J
—
—
= 7.5 Hz, pyridine-H), 7.40 (s, 1H, Ph-H), 7.36 (t, 1H, J = 7.5 Hz, Ph-H), 7.18–7.24 (m, 2H, Ph-H + pyrazole-H)),
7.00 (d, J = 8.0 Hz, 1H, Ph-H), 3.77 (s, 3H, -CH3)
13C NMR (DMSO-d6), δ: 161.2, 160.0, 159.7, 156.2, 148.8, 148.5, 147.5, 139.6, 139.4, 139.1, 137.2, 136.0, 134.3, 13.8,
131.3, 130.5, 128.4, 127.8, 127.3, 127.0, 120.7, 117.0, 111.6, 55.7
IR, ν˜/cm−1: 3242.3 (NH), 3067.2, 3025.2 (ArH), 2889.3 (CH3), 1689.6, 1667.0 (C O), 1558.5, 1541.1, 1464.0, 1458.2
—
—
VIIo
(skeleton vibration of aromatic ring)
1
—
—
—
H-NMR (DMSO-d6), δ: 11.07 (bs, 1H, –CONHAr), 10.05 (bs, 1H, –CONHN ), 8.41 (s, 1H, CH), 8.33 (dd, 1H,
—
4JHH = 1.2 Hz, JHH = 4.6 Hz, 6-pyridine-H), 8.05 (dd, 1H, JHH = 1.2 Hz, JHH = 8.1 Hz, 4-pyridine-H), 7.88
3
4
3
3
3
(s, 1H, 5-Ph-H), 7.56 (dd, 1H, JHH = 4.6 Hz, JHH = 8.1 Hz, 1H, 5-pyridine-H), 7.37 (s, 1H, 3-Ph-H), 6.54–7.72
(m, 4H, pyrazole-H + 3 furan-H), 2.18 (s, 3H, CH3)
13C NMR (DMSO-d6), δ: 162.5, 161.9, 157.1, 154.3, 148.6, 147.2, 147.3, 144.1, 142.0, 138.9, 138.3, 136.7, 132.8,
128.7, 128.1, 122.7, 126.3, 123.5, 124.1, 121.4, 115.2, 111.9, 110.8, 18.9
VIIp
IR, ν˜/cm−1: 3402.4, 3383.1 (NH), 3007.2, 2998.2 (ArH), 2889.3(CH3), 1687.6, 1662.0 (C=O), 1648.3, 1627.8, 1558.5,
1458.2 (skeleton vibration of aromatic ring)
1H-NMR (DMSO-d6), δ: 11.92 (br, 1H, NH),10.37 (br, 1H, NH), 8.49 (s, 1H,
CH), 8.43 (dd, 4J = 1.7 Hz, 3J
—
—
= 4.6 Hz, 1H, pyridine-H), 8.07 (dd, 4J = 1.7 Hz, 3J = 8.0 Hz, 1H, pyridine-H), 7.92 (t, J = 6.3 Hz, 1H, Ph-H),
7.46–7.51 (m, 5H, Ar-H), 7.39 (s, 1H, pyrazole-H), 7.29–7.33 (m, 2H, Ph-H), 2.20 (s, 3H, Ph-CH3)
13C NMR (DMSO-d6), δ: 161.5, 160.5, 159.5, 156.1, 148.9, 148.6, 146.5, 139.8, 139.3, 139.1, 135.8, 135.2, 134.3,
132.8, 131.2, 130.6, 128.2, 127.5, 127.1, 128.8, 120.7, 117.0, 111.4, 19.2
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Table 2. (continued)
Compounds
Spectral data
—
VIIq
VIIr
VIIs
IR, ν˜/cm−1: 3363.9, 3205.7 (NH), 3086.4 (ArH), 2949.3(CH3), 1705.1, 1668.1 (C O), 1527.6, 1489.1, 1458.2 (skele-
—
ton vibration of aromatic ring)
1
H-NMR (DMSO-d6), δ: 11.83, (br, 1H, NH)Lꢀ 10.29, (br, 1H, NH), 8.47 (s, 1H, CH), 8.39 (dd, 1H, 4J = 1.2 Hz,
—
—
3J = 3.5 Hz, pyridine-H), 8.02 (dd, 1H, 4J = 1.7 Hz, 3J = 8.0 Hz, pyridine-H), 7.89 (t, 1H, J = 7.5 Hz, Ph-H), 7.51
(dd, 1H, 4J = 4.6 Hz, 3J = 8.0 Hz, pyridine-H), 7.25–7.46 (m, 7H, Ar-H + pyrazole-H ), 7.29–7.33 (m, 2H, Ph-H),
2.16 (s, 3H, Ph-CH3)
13C NMR (DMSO-d6), δ: 162.7, 161.8, 159.6, 157.3, 149.2, 148.7, 147.4, 139.8, 139.2, 139.1, 135.2, 133.1, 132.3,
131.5, 130.2, 129.7, 128.2, 127.4, 127.1, 128.3, 120.2, 117.4, 110.4, 18.4
IR, ν˜/cm−1: 3385.1, 3242.3 (NH), 3132.4, 3066.8 (Ar-H), 2966.5, 2833.4 (CH3), 1689.2, 1658.8 (C O), 1579.7,
—
—
1541.1, 1489.1, 1460.1 (skeleton vibration of aromatic ring)
1H-NMR (DMSO-d6), δ: 10.15 (1H, NH), 9.66 (1H, NH), 8.34 (dd, 1H, 4J = 1.2 Hz, 3J = 4.6 Hz, pyridine-H),
7.93(s, 1H, CH), 7.72 (dd, 1H, 4J = 1.7 Hz, 3J = 8.0 Hz, pyridine-H), 7.23–7.26 (m, 4H, Ar-H), 7.18 (d, J =
—
—
7.4 Hz, Ph-H), 7.14 (s, 1H, pyrazole-H), 7.05 (s, 1H, Ph-H), 7.02 (s, 1H, Ph-H), 6.93 (dd, 1H, 4J = 1.2 Hz, 3J =
4.6 Hz, pyridine-H), 3.80 (s, 3H, Ph-OCH3), 2.07 (s, 3H, Ph-CH3)
13C NMR (DMSO-d6), δ: 163.1, 162.3, 160.7, 158.3, 149.1, 147.4, 146.5, 139.6, 139.2, 139.1, 137.4, 136.3, 134.1,
132.8, 131.3, 130.1, 129.1, 128.3, 127.5, 128.1, 121.8, 118.2, 111.6, 55.7, 21.2
IR, ν˜/cm−1: 3377.4, 3219.2 (NH), 3136.3, 3064.9 (ArH), 2960.7, 2922.2 (CH3), 1689.3, 1654.9 (C O), 1608.3,
—
—
1587.5, 1554.6, 1464.0 (skeleton vibration of aromatic ring)
1H-NMR (DMSO-d6), δ: 11.74 (br, 1H, NH), 10.30 (br, 1H, NH), 8.43 (dd, 1H, 4J = 1.7 Hz, 3J = 4.6 Hz, pyridine-
H), 8.22 (s,1H, CH), 8.05 (dd, 1H, 4J = 1.2 Hz, 3J = 8.0 Hz, pyridine-H), 7.55 (dd, 1H, 4J = 5.2 Hz, 3J = 8.0 Hz,
—
—
pyridine-H), 7.24–7.43 (m, 8H, Ar-H), 7.01 (dd, 1H, 4J = 2.3 Hz, 3J = 8.0 Hz, pyridine-H), 3.80 (s, 3H, Ph-OCH3),
2.19 (s, 3H, Ph-CH3)
13C NMR (DMSO-d6), δ: 162.8, 162.4, 159.9, 158.4, 149.3, 147.2, 145.5, 138.6, 138.2, 138.1, 137.1, 136.6, 132.1,
131.5, 131.2, 129.5, 129.1, 127.2, 127.1, 126.8, 121.5, 117.3, 110.2, 58.4, 20.6
was stirred at ambient temperature and the reaction
monitored by TLC. After completion of the reaction,
water (5 mL) was added to the mixture to afford a
crystalline solid which was filtered and recrystallised
from ethanol.
Insecticidal bioassays
Previously reported procedures (Wu et al., 2014,
2012) were used to evaluate the insecticidal activity
of the synthesised compounds VIIa to VIIq against P.
xylostella. Fresh cabbage discs (diameter 2 cm) were
dipped into the prepared solutions containing com-
pounds VIIa to VIIq for 10 s, dried in air and placed
in a Petri dish (diameter 9 cm) lined with filter paper.
Ten larvae of second-instar P. xylostella were care-
fully transferred to the Petri dish. Chlorpyrifos, Chlo-
rantraniliprole and compound N (Wu et al., 2012)
were used as reference; three replicates were performed
for each experiment. Mortalities were determined af-
ter 72 h. Evaluations were based on a percentage scale
(0 = no activity and 100 = complete eradication), at
intervals of 5 %. The results are summarised in Ta-
ble 3.
General procedure for preparation of hydrazine
(VI)
A suspension of V (1 mmol) in tetrahydrofuran
(THF; 4 mL) was added to a mixture of hydrazine
hydrate (80 %, 0.15 mL, 2.5 mmol) and THF (2 mL)
under vigorous stirring, after the addition of V, and
the mixture was stirred at ambient temperature for
a further 40 min. The precipitated solid was filtered,
washed with ethanol (3 mL) and dried to afford the
intermediate VI.
General procedure for preparation of title com-
pounds (VIIa–VIIs)
Results and discussion
To a well-stirred solution of hydrazine (VI; 2 mmol)
in ethanol (5 mL), ketones (or aldehydes and hemiac-
etals) (2 mmol) were added over 10 min. The result-
ing mixtures were stirred at ambient temperature to
afford a solid; after completion of the reaction, the
solids were filtered and recrystallised from a mixture
of ethanol and N,N-dimethylformamide (DMF; ϕr =
1 : 1). The properties and analytical data for the syn-
thesised compounds are listed in Table 1, and the spec-
tral data are shown in Table 2.
Synthesis
The synthetic protocol of the anthranilic di-
amides with a hydrazone group is depicted in Fig. 3.
First, 3-chloro-2-hydrazinylpyridine (II ) was synthe-
sised with a good yield (up to 90 %) by the re-
action of 2,3-dichloropyridine (I ) with 80 % hy-
drazine hydrate, then compound II was allowed
to further react with diethyl maleate under re-
flux in the presence of sodium ethoxide to af-
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J. Wu et al./Chemical Papers 69 (7) 993–1003 (2015)
Table 3. Insecticidal activity of compounds VIIa to VIIs, chlorantraniliprole, compound N and chlorpyrifos against P. xylostella
Insecticidal activity at different concentrations/(mg L−1
)
Compound
300
200
100
50
%
25
10
5
VIIa
VIIb
20
55
–
–
–
–
–
–
–
–
–
–
–
–
VIIc
VIId
60
45
30
–
–
–
–
–
–
–
–
–
–
–
VIIe
55
–
–
–
–
–
–
VIIf
15
–
–
–
–
–
–
VIIg
VIIh
VIIi
VIIj
VIIk
VIIl
VIIm
VIIn
100
100
80
90
87
100
100
100
30
100
93
73
73
70
100
100
100
–
100
73
50
56
53
100
100
100
–
93
50
23
33
30
95
100
90
–
80
33
–
20
10
73
100
67
–
60
17
–
–
–
33
100
50
–
43
–
–
–
–
23
100
30
–
VIIo
VIIp
VIIq
100
10
100
–
97
–
63
–
43
–
20
–
–
–
VIIr
VIIs
100
20
100
–
90
–
50
–
20
–
–
–
–
–
chlorpyrifos
chlorantraniliprole
compound N
blank control
100
100
100
0
100
100
100
0
100
100
100
0
90
100
100
0
83.3
100
100
0
60
100
100
0
40
100
100
0
1
ford ethyl 2-(3-chloropyridin-2-yl)-5-oxopyrazolidine-
3-carboxylate (III ) with a 50 % yield (Lahm et
al., 2006, 2007). 3-Bromo-1-(3-chloropyridin-2-yl)-1H-
pyrazole-5-carboxylic acid (IV ) was then obtained
from III via bromination, oxydehydrogenation and
acidolysis with good yields (Lahm et al., 2006, 2007).
Next, substituted-4H-benzo[d][1,3]oxazin-4-one (V )
was carried out in a single step by the treatment of IV
with substituted-2-aminobenzoic acid in the presence
of methanesulphonyl chloride and pyridine in acetoni-
trile at ambient temperature (Lahm et al., 2006, 2007).
Subsequently, 3-bromo-1-(3-chloropyridin-2-yl)-N-(2-
(hydrazinecarbonyl) substituted phenyl)-1H-pyrazole-
5-carboxamide (VI ) was readily obtained with an ex-
cellent yield (> 93 %) by the treatment of Vwith
80 % hydrazine hydrate in THF. Finally, the title
compounds (VIIa–VIIq) were readily obtained with
excellent yields by the treatment of intermediates VI
with the corresponding different ketones, aldehydes or
hemiacetals in ethanol at ambient temperature (Wu et
al., 2012).
1660–1710 cm−1, respectively. In the H-NMR spec-
tra, taking compound VIIa as an example, two differ-
ent N—H protons appeared as a broad singlet near δ
12.58 and 11.09, respectively. The proton at position
5 of pyridine appeared as a doublet of doublets at δ
8.51 due to the coupling coefficients from the protons
at positions 3 and 4 of the pyridine ring; the coupling
constants were 4.6 and 1.15 Hz (4J = 4.6 Hz, 3J =
1.2 Hz), respectively. 4-Pyrazole-H exhibited a singlet
near δ 7.15. The six protons (-N(CH3)2) appeared as
1
a singlet near δ 2.84; The properties, H NMR, 13C
NMR, IR and the elemental analysis data of the title
compounds VIIa toVIIs are listed in more detail in
the Experimental section.
Insecticidal activity
The insecticidal activities of the synthesised com-
pounds against P. xylostella were evaluated using pro-
cedures reported previously (Wu et al., 2012, 2014).
Commercial chlorantraniliprole, chlorpyrifos and the
active compound N were used as positive controls. The
results listed in Table 3 indicate that some of the syn-
thesised compounds VIIa–VIIs exhibited good insecti-
cidal activities against P. xylostella at the test concen-
tration. It can be seen that all the compounds VIIg,
VIIl, VIIm, VIIn, VIIp and VIIr displayed 100 % ac-
tivities against P. xylostella at 200 mg L−1. When the
concentration was 100 mg L−1, the activities of com-
The structures of the synthesised compounds
(VIIa–VIIs) were established on the basis of the spec-
troscopic data. The IR (KBr) spectra indicated ab-
sorption bands around 3050 cm−1 for the Ar—H
stretching vibrations. The absorption bands at 1445–
1610 cm−1 were the skeletal vibration of the aromatic
ring; all the compounds exhibited the charac−te1ristic
—
N—H and C O absorptions at 3150–3430 cm and
—
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1001
Table 4. LC50 values of parts of synthesised compounds, chlorantraniliprole, chlorpyrifos and compound N against Plutella xy-
lostella
Compound
y = a + bx
LC50/(mg L−1
)
r
95 % Confidence interval
VIIg
VIIh
VIIi
VIIj
VIIk
VIIl
VIIm
VIIn
VIIp
y = 3.31 + 1.87x
y = 2.03 + 1.85x
y = 0.49 + 2.20x
y = 1.42 + 1.89x
y = 0.83 + 2.10x
y = 2.16 + 2.63x
y = 5.32 + 1.60x
y = 3.22 + 1.73x
y = 1.72 + 2.36x
y = 1.26 + 2.32x
y = 3.56 +1.65x
y = 6.20 + 0.93x
y = 5.28 + 1.88x
7.92
39.93
110.76
77.72
96.23
12.01
0.62
10.71
24.41
40.58
7.39
0.99
0.98
0.99
0.98
0.99
0.97
0.96
0.98
0.96
0.97
0.99
0.95
0.95
5.88–10.65
30.01–53.14
80.90–141.19
58.97–102.43
75.20–123.12
9.62–14.99
0.42–0.92
7.95–14.43
19.25–30.97
29.89–55.09
5.28–10.33
0.024–0.11
0.52–0.97
VIIr
chlorpyrifos
chlorantraniliprole
compound N
0.05
0.71
pounds VIIg, VIIl, VIIm and VIIn attained 100 %, and
their activities were over 90 % at 50 mg L−1. In par-
ticular, compound VIIm exhibited excellent activity;
Conclusions
In conclusion, nineteen new anthranilic diamides
the activity of VIIm still achieved 100 % at 5 mg L−1
,
with a hydrazone group (VIIa–VIIs) were synthesised,
1
which was the same as for chlorantraniliprole and com-
pound N. The LC50 values for some of the synthe-
sised compounds, chlorantraniliprole and compound
N were tested; the results are listed in Table 4. The
table shows that the LC50 values of compounds VIIg,
VIIl, VIIm, VIIn exhibited excellent insecticidal ac-
characterised and confirmed by H NMR, 13C NMR,
IR and elemental analyses. The preliminary insectici-
dal activities of the synthesised compounds were eval-
uated. The results indicated that some of the com-
pounds exhibited a high efficiency against Plutella xy-
lostella; in particular, compounds VIIg, VIIl, VIIm
and VIIn exhibited excellent insecticidal activities,
tivities, with the LC50 of 7.92 mg L−1, 12.01 mg L−1
,
0.62 mg L−1 and 10.71 mg L−1, respectively. In par-
ticular, VIIm exhibited a much higher activity than
that of chlorpyrifos (LC50 was 7.39 mg L−1) and bet-
ter than the compounds previously reported (Wu et
al., 2012).
with the LC50 being 7.92 mg L−1, 12.01 mg L−1
,
0.62 mg L−1 and 10.71 mg L−1, respectively. In partic-
ular, compound VIIm exhibited a much higher activity
than that of chlorpyrifos (LC50 was 7.39 mg L−1) as
well as higher than that of compound N (an active
compound reported on previously). It may be con-
cluded that the substituent groups on benzene at both
the 2 and 4-positions could increase the activities of
this type of compound. In addition, the substituent
groups on the functional moiety of “N = R3 R4” were
also a crucial factor that governing the activities; the
activity was found to decrease when a bulky group was
introduced. Further studies are currently underway to
optimise the structure to obtain a better insecticidal
activity in these new anthranilic diamides with a hy-
drazone group based on these findings.
A previous study found that only compounds with
a methyl group at the 2-position of benzene exhibited
weak activity (Wu et al., 2012); similar results were
also found in this work (such as VIIo, VIIq and VIIs).
It was also found that compounds with only chorine at
the 4-position (VIIa–VIIf ) of benzene exhibited weak
(or no) activities against P. xylostella. However, those
compounds with both 2-methyl and 4-chorine on ben-
zene (such as VIIk, VIIp) or 2,4-di-chorines on ben-
zene (VIIg, VIIh, VIIi, VIIj, VIIl, VIIm and VIIn)
exhibited excellent activities After combining these re-
sults with those reported previously (Wu et al., 2012),
it may be concluded that the substituent at both the 2-
and 4-positions of benzene can increase the activities
of this type of compounds. It was also found that the
activity could be enhanced by exchanging the methyl
group (at 2-position of benzene) for chorine and de-
creased in the following order (VIIm, N, VIIj, VIIk,
VIIn, VIIr). In addition, the substituent groups on
the functional moiety of “N = R3, R4” were also a
crucial factor that governed the activities; the activity
was found to decrease when a bulky group was intro-
duced (Wu et al., 2012), so that the activities of VIIh,
VIIi and VIIk were much lower than that of VIIg.
Acknowledgements. This work was financially supported
by the National Natural Science Foundation of China (nos.
21162004, 21302025), and the Science & Technology Founda-
tion of Guizhou Province (J[2014]2056#).
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