Novel anthranilic diamide insecticides: Design, synthesis, and insecticidal evaluation

Article abstract of DOI:10.1071/CH13701

Three series of new anthranilic diamide derivatives containing sulfide, N-cyanomethylsulfilimine, and N-cyanomethylsulfoximine groups were designed and synthesized by coupling the active substructures of anthranilic diamides and sulfoxaflor. The structures of the synthesized compounds were confirmed by infrared spectroscopy, 1H and 13C NMR, and elemental analysis. Several unique structural characteristics were revealed via the crystal structure analysis of compound N-(2-(2-methyl-2-(methylthio)propylcarbamoyl)-4-chloro-6-methylphenyl)-3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide 16e. Bioassay results indicated that most of the synthesized compounds showed superior insecticidal activities against Mythimna separata and Plutella xylostella when compared with the positive control cyantraniliprole. In particular, N-(2-(2-methyl-2-(N-cyanomethylsulfideimino)propylcarbamoyl)-4-chloro-6-methylphenyl)-3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide 17e showed excellent insecticidal activity against Mythimna separata, with a mortality rate of 100% at a concentration of 1μgmL-1. These results indicated that sulfide, N-cyanomethylsulfilimine, and N-cyanomethylsulfoximine moieties, as important active substructures, could improve or maintain the activity of the anthranilic diamide and promote novel pesticide development.

Full text of DOI:10.1071/CH13701

CSIRO PUBLISHING
Aust. J. Chem. 2014, 67, 1491–1503
Full Paper
http://dx.doi.org/10.1071/CH13701
Novel Anthranilic Diamide Insecticides: Design,
Synthesis, and Insecticidal Evaluation
A B
,
B C
,
A B E
, ,
A B
,
Xuewen Hua,
Fengyun Li,
Like Zhou,
Wutao Mao,
Guangning Zong,
Zhijin Fan,
Xiaotian Ji,
A B
,
A B
,
A
A B
,
Haibin Song, Juanjuan Li,
A B
,
D
D
D
Lifeng Zhou, Xiaowen Liang, Genhao Wang,
D
and Xiaoyan Chen
A
State Key Laboratory of Elemento-Organic Chemistry, Nankai University,
No. 94, Weijin Road, Nankai District, Tianjin 300071, P. R. China.
B
Collaborative Innovation Center of Chemical Science and Engineering (Tianjin),
Tianjin 300071, P. R. China.
C
College of Chemistry and Pharmacy Engineering, Nanyang Normal University,
Henan 473061, P. R. China.
D
Jiangxi Tianren Ecological Co. Ltd, No. 181 Junshan Dadao, Jian, Jiangxi 343100,
P. R. China.
E
Corresponding author. Email: fanzj@nankai.edu.cn
Three series of new anthranilic diamide derivatives containing sulfide, N-cyanomethylsulfilimine, and N-cyanomethyl-
sulfoximine groups were designed and synthesized by coupling the active substructures of anthranilic diamides and
sulfoxaflor. The structures of the synthesized compounds were confirmed by infrared spectroscopy, 1H and 13C NMR, and
elemental analysis. Several unique structural characteristics were revealed via the crystal structure analysis of compound
N-(2-(2-methyl-2-(methylthio)propylcarbamoyl)-4-chloro-6-methylphenyl)-3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-
5-carboxamide 16e. Bioassay results indicated that most of the synthesized compounds showed superior insecticidal
activities against Mythimna separata and Plutella xylostella when compared with the positive control cyantraniliprole. In
particular, N-(2-(2-methyl-2-(N-cyanomethylsulfideimino)propylcarbamoyl)-4-chloro-6-methylphenyl)-3-bromo-1-(3-
chloropyridin-2-yl)-1H-pyrazole-5-carboxamide 17e showed excellent insecticidal activity against Mythimna separata,
witha mortalityrate of 100 % ataconcentration of 1mg mLꢀ1. Theseresultsindicatedthat sulfide, N-cyanomethylsulfilimine,
and N-cyanomethylsulfoximine moieties, as important active substructures, could improve or maintain the activity of the
anthranilic diamide and promote novel pesticide development.
Manuscript received: 23 October 2013.
Manuscript accepted: 22 February 2014.
Published online: 10 April 2014.
Introduction
receptors, leading to uncontrolled calcium release originally
stored in the muscle, thus preventing further muscle contrac-
tion, and ultimately leading to death.[6,11–13] The exceptional
levels of mammalian safety are attributed to a strong selec-
tivity for insects over mammalian receptors.[6]
Ryanodine receptors (RyRs) comprise a class of intracellular
calcium release channels in various excitable tissues and cells
such as muscles and neurons.[1,2] These receptors are the
major cellular mediators of calcium ion release from the sar-
coplasmic and endoplasmic reticulum,[2,3] an essential step in
muscle excitation–contraction coupling (ECC).[2–5] Diamide
insecticides have emerged as one of the most promising new
compound classes in insecticide chemistry owing to their
excellent insecticidal efficacy and high levels of mammalian
safety.[6] Cyantraniliprole,[7] chlorantraniliprole,[8] and flu-
bendiamide,[9] the first three insecticides developed from
this class, demonstrate exceptional broad-spectrum activity
against Lepidoptera.[6,10] Flubendiamide is a phthalic diamide,
whereas chlorantraniliprole and cyantraniliprole (Fig. 1)
belong to the anthranilic diamide structural class. Although
structurally distinct, both classes of compounds exhibit
insecticidal properties via activation of the ryanodine
Sulfoxaflor (Fig. 1) is the first product from a novel class of
insect control agents based on the sulfoximine scaffold[14,15]
developed by Dow AgroSciences. It exhibits broad-spectrum
control of many sap-feeding insect pests including aphids,
whiteflies, hoppers, and insects of the genus Lygus.[14] Further-
more, sulfoxaflor is notable for its efficacy against sap-feeding
insect pests that are resistant to currently available insecti-
cides.[16,17] The insecticidal mechanism of sulfoxaflor is reliant
on the agonistic action towards the insect nicotinic acetylcholine
receptor (nAChR).[18–21] The effects of sulfoxaflor on the
insects include excitatory symptoms, such as tremors, followed
by paralysis and mortality, thereby suggesting that the molecule
acts on the insect nervous system.[19]
Journal compilation Ó CSIRO 2014
www.publish.csiro.au/journals/ajc

1492
X. Hua et al.
HN
HN
O
O
O
S
O
O
Br
Br
O
S
N
Cl
NC
NH
O
NH
O
CF3
F
CF3
NH
HN
I
N
N
N
N
N
F3C
CN
N
N
O
Cl
Cl
Chlorantraniliprole
Cyantraniliprole
Sulfoxaflor
Flubendiamide
Fig. 1. Structures of diamide insecticides and sulfoxaflor.
X
NC
N
O
S
N
N
N
S
Cl
O
O
HN
HN
F3C
N
CN
N
O
Sulfoxaflor
Y
HN
O
O
X
NC
S
O
N
O
Br
N
N
NC
NH
CF3
S
I
NH
HN
Cl
O
O
F
N
N
O
HN
HN
CF3
N
O
N
O
Cl
Y
Cyantraniliprole
Flubendiamide
XϭCl, Br; YϭCl, Br, CN
Scheme 1. Design strategy of target molecules.
Recent studies have reported that the sulfoximine structure
can improve the insecticidal activities of anthranilic diamides.
The consistently high activity of sulfoximines is thought to be
due to their high water solubility and relatively low logP, leading
to systemicity (or compound uptake) in the plant and good
distribution in the soil.[22] In this study, active substructures
consisting of sulfide, N-cyanomethylsulfilimine, and N-cyano-
methylsulfoximine groups were introduced into the anthranilic
diamide to obtain highly active compounds with improved
absorption profiles (Scheme 1). A convenient, effective, and
rapid synthetic route towards the synthesis of intermediates 8a–f
and target compounds 16a–e, 17a–e, 18a–e, 19a–f, 20a–f, and
21a–e was designed and carried out according to the schemes in
Tables 1 and 2, respectively.
potassium persulfate in concentrated sulfuric acid (volume
fraction 98%). 1-(3-Chloropyridin-2-yl)-3-halo-1H-pyrazole-5-
carboxylic acids (6a and 6b) were synthesized by hydrolysis of
the corresponding esters 5a and 5b with sodium hydroxide in
methanol. Intermediates 2-amino-5-chloro (or bromo)-3-methyl-
benzoic acids (7a and 7b) were obtained by reaction between
2-amino-3-methylbenzoic acid and N-chlorosuccinimide (or
N-bromosuccinimide) in N,N-dimethylformamide (DMF);
2-amino-5-iodo-3-methylbenzoic acid was prepared in the same
manner. 2-Amino-5-cyano-3-methylbenzoic acid (7c) was syn-
thesized by heating 2-amino-5-iodo-3-methylbenzoic acid and
copper(I) cyanide to 1408C in N,N-dimethylformamide (DMF).
The pyrazine intermediates 8a–f were synthesized according to
the reported literature.[7] First, to a solution of methanesulfonyl
chloride in acetonitrile was added dropwise a mixture of com-
pounds 6a and 6b and pyridine in acetonitrile at 0–58C. Then,
substituted benzoic acid 7a–c and pyridine, followed by metha-
nesulfonyl chloride were added. The two types of substituted
amines (11 and 15) were prepared according to the reactions in
Scheme 2. 2-Methyl-1-(methylthio)propan-2-amine (11) was
synthesized from the raw material 2-amino-2-methylpropan-1-ol
(9) as reported in literature.[23] First, compound 9 was converted
into the corresponding sulfonic acid ammonium salt 10 by
refluxing with 98% H2SO4 in toluene/water (v/v 60 : 1). Then,
amine 11 was synthesized by heating compound 10 with 10%
NaOH solution, 20% NaSCH3 solution at 808C in toluene.
2-(Methylthio)ethanamine hydrochloride (15) was obtained
through the reactions of protection of amino group with (Boc)2O,
substitution of chloro with methylthio group, and deprotection
of amino group with HCl gas from the starting material
2-chloroethanamine (12), as reported in literature.[24] Amine 12
was converted into compound 13 by protecting its amino group
Results and Discussion
Chemistry
The corresponding substituted pyrazine intermediates 8a–f
were synthesized from the starting materials 2,3-dichloropyridine
and diethyl maleate. (3-Chloropyridin-2-yl)hydrazine (2) was
synthesized by refluxing 2,3-dichloropyridine (1) and 80%
hydrazine hydrate in ethanol. 1-(3-Chloropyridin-2-yl)-3-
pyrazolidinone-5-carboxylate (3) was prepared by reaction
between compound 2 and diethyl maleate in the presence of an
appropriate amount of sodium ethoxide. Intermediate 3 was
converted into the corresponding ethyl 1-(3-chloropyridin-2-yl)-
3-halo-4,5-dihydro-1H-pyrazole-5-carboxylates (4a and 4b) by
refluxing with phosphorus oxychloride or phosphorus oxy-
bromide in acetonitrile. Compounds 4a and 4b were converted
into the corresponding ethyl 1-(3-chloropyridin-2-yl)-3-halo-
1H-pyrazole-5-carboxylates (5a and 5b) by oxidation with

Design and Activity of Anthranilic Diamides
1493
Table 1. Synthesis of intermediates 8a f
]
Reagents and conditions: (a) 80 % NH2NH2ꢁH2O, C2H5OH, reflux, 24 h, yield 94 %; (b) (i) diethylmaleate, Na/C2H5OH, reflux, 30 min, (ii) acetic acid, 408C,
yield 46 %; (c) POCl3 or POBr3, CH3CN, reflux, 3 h; (d) K2S2O8, 98 % H2SO4, CH3CN, reflux, 6 h; (e) NaOH, CH3OH, room temperature (RT), 12 h;
(f) CH3SO2Cl, pyridine, CH3CN, RT, 6 h
O
X
X
Cl
NHNH2
Cl
C2H5O
C2H5O
C2H5O
NH
N
N
Cl
N
N
N
c
a
d
b
N
N
O
O
O
Cl
Cl
Cl
N
N
N
CH3
NH2
COOH
1
2
5a, 5b
3
4a, 4b
X
Y
Y
HO
N
N
e
7a–c
N
N
Cl
O
f
Cl
N
N
O
O
N
a YϭCl
b YϭBr
c YϭCN
X
6a, 6b
8a–f
Intermediates
X
Y
Yield [%]
Intermediates
X
Y
Yield [%]
4a
5a
6a
4b
5b
6b
Cl
Cl
Cl
Br
Br
Br
–
–
–
–
–
–
98
72
74
95
74
81
8a
8b
8c
8d
8e
8f
Cl
Cl
Cl
Br
Br
Br
Cl
Br
85
77
67
84
92
70
CN
Br
Cl
CN
Table 2. Synthesis of target compounds 16a e, 17a e, 18a e, 19a f, 20a f, and 21a e
]
]
]
]
]
]
Reagents and conditions: (a) tetrahydrofuran (THF), 608C, 8 h; (b) NCNH2, (diacetoxyiodo)benzene (PhI(AcO)2), THF, 08C, 10 h; (c) 3-chloroperoxybenzoic
acid (mCPBA), K2CO3, CH3OH/H2O, 08C, 8 h; (d) triethylamine (Et3N), THF, RT, 6 h
X
X
X
NC
NC
N
N
N
N
N
N
N
N
S
S
S
Cl
Cl
Cl
O
O
O
O
b
c
HN
HN
HN
HN
HN
S
HN
NH2
N
N
N
O
O
O
11
a
Y
Y
Y
Y
18a–e
16a–e
17a–e
N
N
Cl
N
O
O
N
X
X
X
X
NC
NC
8a–f
N
N
d
N
N
N
N
N
N
S
S
S
Cl
Cl
Cl
S
O
O
O
O
NH2·HCl
c
b
HN
HN
HN
HN
HN
HN
15
N
N
N
O
O
O
Y
Y
Y
19a–f
20a–f
21a–e
Products
X
Y
Yield [%]
Products
X
Y
Yield [%]
Products
X
Y
Yield [%]
16a
16b
16d
16e
17a
17b
17c
17d
17e
18a
Cl
Cl
Br
Br
Cl
Cl
Cl
Br
Br
Cl
Cl
Br
Br
Cl
Cl
Br
CN
Br
Cl
Cl
56
42
50
46
92
77
63
69
62
51
18b
18c
18d
18e
19a
19b
19c
19d
19e
19f
Cl
Cl
Br
Br
Cl
Cl
Cl
Br
Br
Br
Br
CN
Br
83
71
56
57
91
81
51
57
65
55
20a
20b
20c
20e
20f
Cl
Cl
Cl
Br
Br
Cl
Cl
Cl
Br
Br
Cl
Br
90
59
89
45
49
68
60
52
47
55
CN
Cl
Cl
Cl
CN
Cl
Br
21a
21b
21c
21d
21e
CN
Br
Br
CN
Br
Cl
CN
Cl

1494
X. Hua et al.
O
S
Ϫ
a
b
O
O
OH
Cl
S
H3N
H2N
H2N
H2N
ϩ
O
9
10
11
Cl
c
d
S
S
e
N
H
Boc
Boc
N
H
NH2·HCl
12
13
14
15
Scheme 2. Synthesis of amine intermediates 11 and 15. Reagents and conditions: (a) 98 % H2SO4, toluene/water
(v/v 60 : 1), reflux, 20 h, yield 89 %; (b) 10 % NaOH solution, 20 % NaSCH3 solution, toluene, 808C, 8 h, yield 78 %;
(c) (Boc)2O, Et3N, CH2Cl2, RT, 24 h, yield 92 %; (d) KI (catalytic amount), tetrabutylammonium bromide (catalytic
amount), 20 % NaSCH3 solution, CH3CN, reflux, 24 h, yield 86 %; (e) HCl (gas), ethyl ether, 4 h, 08C, yield 85 %.
(a)
with (Boc)2O in dichloromethane. Then, compound 14 was
obtained via substitution of the chloride atom with methylthio
group in the presence of catalytic amounts of potassium iodide
and tetrabutylammonium bromide in acetonitrile. Intermediate 15
was synthesized by Boc-deprotection of compound 14 with HCl
gas in ethyl ether. The synthetic route towards the target com-
pounds is summarised in Table 2. Subsequently, a total of 30
target molecules were smoothly synthesized by reaction between
substituted pyrazine intermediates 8a–f and two types of substi-
tuted amines (11 and 15). Products 16a–e and 19a–f were
obtained by nucleophilic reactions between amine 11 or 15 and
pyrazine compounds 8a–f in tetrahydrofuran. Owing to the
stronger nucleophilic activity of amine 15, the reactions were
carried out at room temperature for amine 15, and under reflux
for amine 11. Molecules 17a–e and 20a–f were prepared
through oxidation reactions of compounds 16a–e and 19a–f
with (diacetoxyiodo)benzene, cyanamide in tetradydrofuran.
Compounds 17a–e and 20a–f were converted into target products
18a–e and 21a–e by oxidation with 3-chloroperoxybenzoic acid,
potassium carbonate in methanol/water. All target compounds
were purified by chromatography on silica gel using petroleum
ether/ethyl acetate as eluent. The synthesized compounds were
identified and characterised by infrared spectroscopy (IR),
1H NMR, 13C NMR, elemental analysis (EA), and (for select
compounds) high-resolution mass spectrometry (HRMS).
C19
C21
C22
C7
C18
C20
N5
O2
C17
C15
Br1
S1
N4
C9
C14
C6
N3
C10
C13
Cl2
C8
N1
N2
C5
O1
C12
C11
C16
Cl1
C1
C4
C3
C2
(b)
Crystal Structure Analysis
Several molecular characteristics were revealed upon crystal
structure analysis of compound 16e (Fig. 2; CCDC no. 965590).
The torsion angles of N(3)–N(2)–C(5)–C(4) and C(8)–N(2)–
C(5)–N(1) were ꢀ98.2(3)8 and ꢀ109.9(3)8, respectively, indi-
cating that the pyridine and pyrazole rings were non-planar,
adopting an approximately perpendicular conformation. The
torsion angles of N(2)–C(8)–C(9)–O(1) and C(10)–C(15)–
C(17)–O(2) were 13.8(4)8 and 46.8(4)8, respectively, indicating
that the pyrazole ring and amide group, as well as the benzene
ring and the other amide group, were non-planar. The torsion
angles of C(7)–C(8)–C(9)–N(4) and C(9)–N(4)–C(10)–C(15)
were 18.4(5)8 and 105.5(3)8, respectively, indicating that the
pyrazole and benzene rings were non-planar. The angles of
C(6)–C(7)–H(7), C(8)–C(7)–H(7), and C(8)–C(7)–C(6) were
128.28, 128.28, and 103.5(3)8, respectively, and the sum of these
angles was 3608, indicating the sp2 hybridisation state of the
C(7) atom. As expected, the C–N amide bonds possessed some
double bond character.[25] The bond lengths of C(9)–N(4) and
Fig. 2. Single crystal structure of compound 16e: (a) molecular structure
and (b) crystal packing.
C(10)–N(4)–H(4) angles was 359.38, indicating the sp2 hybri-
disation state of the N(4) atom. Similarly, the N(5) atom also
adopted an sp2 hybridisation state. As noted, one intermolecular
hydrogen bond, N(4)–H(4)ꢁꢁꢁO(2), and two intermolecular weak
interactions at C(7)–H(7)ꢁꢁꢁO(2) and N(5)–H(5)ꢁꢁꢁO(1) linked
the adjacent molecules to form a one-dimensional chain struc-
ture (Fig. 2). These chains intersected into a two-dimensional
framework by the intermolecular weak interactions at Cl(1)ꢁꢁꢁ
Br(1) and C(3)–H(3)ꢁꢁꢁN(1). Additionally, weak p–p inter-
actions occurred among the benzene, pyridine, and pyrazole
˚
˚
C(17)–N(5) were 1.351(4) A and 1.344(4) A, respectively, and
were much shorter than the normal C–N bond length
(1.47 A), but slightly greater than C¼N (1.33 A).[25,26] From
[26]
˚
˚
the data, the sum of C(9)–N(4)–C(10), C(9)–N(4)–H(4), and

Design and Activity of Anthranilic Diamides
1495
Table 3. Insecticidal activities of the target compounds
–: not detected (activities for 19c, 19f, 20a–c, and 21c were not detected at concentrations of 1 and 0.1 mg mLꢀ1
)
Compound
Substituent groups
Mortality [%]
M. separata
X
Y
P. xylostella
10 mg mLꢀ1
5 mg mLꢀ1
1 mg mLꢀ1
0.1 mg mLꢀ1
16a
16b
16d
16e
Cl
Cl
Br
Br
Cl
Cl
Cl
Br
Br
Br
Cl
Cl
Cl
Br
Br
Cl
Cl
Cl
Br
Br
Cl
Cl
Cl
Br
Br
Cl
Cl
Cl
Br
Br
–
Cl
Br
Br
Cl
100
100
100
100
100
100
40
20
50
0
0
0
0
0
0
0
–
0
0
–
0
0
0
0
0
–
–
–
0
0
0
0
0
0
0
0
0
–
0
0
0
100
86
86
70
20
0
100
100
100
86
19a
19b
19c
Cl
Br
CN
Br
Cl
–
19d
19e
100
100
20
0
100
100
100
86
50
–
19f
CN
Cl
17a
17b
17c
100
100
100
100
100
40
0
Br
CN
Br
Cl
0
86
70
40
100
–
100
100
86
17d
17e
20a
20b
20c
Cl
100
100
100
86
Br
CN
Cl
60
–
60
–
20e
100
100
100
100
80
0
20f
CN
Cl
0
100
71
18a
18b
18c
0
Br
CN
Br
Cl
0
57
0
100
86
18d
18e
100
100
70
0
0
71
21a
21b
21c
Cl
0
100
71
Br
CN
Br
Cl
100
20
20
–
100
86
21d
21e
100
100
100
0
0
86
cyantraniliprole
–
100
100
rings of the adjacent molecules, and strengthened the stability of
the 2D networks.
Furthermore, 17e showed an excellent insecticidal activity
against M. separata at 1 mg mLꢀ1, with a mortality of 100 %.
The synthetic compounds also demonstrated good insecticidal
activity against P. xylostella at 10 mg mLꢀ1, with mortality
rates over 80 % (Table 3). From the data, the insecticidal activity
of compounds containing sulfide and N-cyanosulfilimine
moieties was higher than that of compounds containing
N-cyanosulfoximine. This result is probably due to the greater
polarity of N-cyanosulfoximine, thereby exhibiting greater
insect repulsion when compared with the other two kinds of
compounds studied. Moreover, in a given category, compounds
with a cyano group instead of a chloride or bromide group in the
anthraniloyl moiety commonly had very low insecticidal
activities. For example, the mortality against M. separata at a
concentration of 5 mg mLꢀ1 was 100 % for compounds 18a, 18b,
18d, 18e, 19a, 19b, 19d, 19e, 21b, 21d, and 21e, but the cor-
responding insecticidal activities of 18c, 19c, 19f, and 21c were
80, 40, 20, and 20 % respectively. This result is significant for
pesticide development. Furthermore, the insecticidal activities
of compounds containing the 2-methylpropylcarbamoyl group
in the anthraniloyl moiety were higher than those containing
the ethylcarbamoyl group. For example, in a given category,
the mortality rates against M. separata at a concentration of
1 mg mLꢀ1 of compounds 16a, 16b, 16e, 17c, 17d, and 17e
were 20, 50, 70, 70, 40, and 100 %, respectively, but the
Biological Activities Against Mythimna separata
and Plutella xylostella
The insecticidal activities of the target compounds, with cyan-
traniliprole as a positive control, against Mythimna separata
(M. separata) at 5 mg mLꢀ1 and Plutella xylostella (P. xylostella)
at 10 mg mLꢀ1 are shown in Table 3. The literature reports that
P. xylostella is more sensitive to anthranilic diamides than
M. separata.[27] Our experimental studies revealed that the
amount of food taken by P. xylostella is less than that of
M. separata, hence, the insecticidal activity against M. separata
at 5 mg mLꢀ1 was chosen for subsequent experiments for com-
parison with compounds that display good results against
P. xylostella at 10 mg mLꢀ1. The compounds displaying insec-
ticidal activities against M. separata over 70 % were further
tested at concentrations of 1 mg mLꢀ1 and 0.1 mg mLꢀ1 for a fair
comparison of the activity of the target compounds with that of
cyantraniliprole. The results of gradient concentration screening
are shown in Table 3. As can be seen from the table, compounds
16a, 16b, 16d–e, 19a, 19b, 19d, 19e, 17a–e, 20e, 20f, 18a, 18b,
18d–e, 21b, 21d, and 21e displayed good insecticidal activity
against M. separata at 5 mg mLꢀ1, with a mortality rate of 100 %.

1496
X. Hua et al.
corresponding insecticidal activities of compounds 19a, 19b,
19d, 19e, 20e, and 20f were only 20, 0, 0, 50, 0, and 0 %,
respectively. From the above results, it is concluded that either a
chloride or a bromide group, a sulfide or N-cyanosulfilimine,
and a 2-methylpropylcarbamoyl group in the anthraniloyl
moiety will enhance the insecticidal activity. However, the
mortality rate against M. separata at 0.1 mg mLꢀ1 of all target
compounds and positive control cyantraniliprole was 0 %. This
result indicates that a concentration of 0.1 mg mLꢀ1 is below the
required minimum effective concentration of target compounds
against M. separata.
mixture was concentrated using a rotary evaporator to remove
methanol. The residue was dissolved in water (60 mL) and then
washed with diethyl ether (3 ꢂ 30 mL). The water layer was
acidified to pH 2. The resulting precipitate was filtered off,
washed with water, and dried to give 6a as a pale yellow solid
(10.13 g, 81 %). Compound 6b was synthesized in a similar
manner.
General Procedure for the Synthesis of Substituted
Benzoic Acids 7a–c
2-Amino-5-chloro-3-methylbenzoic acid 7a was synthesized
according to a literature procedure.[29] To a solution of 2-amino-
3-methylbenzoic acid (4.00 g, 26.5 mmol) in N,N-dimethyl-
formamide (30 mL) was added N-chlorosuccinimide (3.72 g,
27.8 mmol), and the reaction mixture was heated at 758C (oil
bath temperature) overnight, and reaction progress was moni-
tored by TLC. After reaction completion, the reaction mixture
was cooled to room temperature and slowly poured into ice
water (100 mL) to precipitate a light grey solid. The solid was
filtered, washed with water, and dried to give 7a (4.47 g, 91 %).
Compounds 7b and 2-amino-5-iodo-3-methylbenzoic acid were
synthesized in the same manner.
2-Amino-5-cyano-3-methylbenzoic acid 7c was prepared
according to a literature procedure.[29] A mixture of 2-amino-
5-iodo-3-methylbenzoic acid (15.00g, 54.1mmol) and copper(I)
cyanide (7.27 g, 81.2 mmol) was heated to 140–1458C in
N,N-dimethylformamide (150 mL) for 20 h, and reaction prog-
ress was monitored by TLC. After completion, the reaction
mixture was cooled to room temperature, and most of the N,N-
dimethylformamide was removed by concentration on a rotary
evaporator. The residue was poured into ice water (150 mL),
followed by immersion in ethylenediamine (20 mL). The mix-
ture was stirred vigorously to dissolve most of the solid, and the
residual solid was recovered by filtration. Then, concentrated
hydrochloric acid was added to the filtrate to adjust the pH to 4 to
precipitate a light grey solid. The solid was filtered, washed with
water, dried, and purified by chromatography on silica gel using
petroleum ether/ethyl acetate (v/v 3 : 1) as eluent to give 7c
(4.48 g, 47 %).
Conclusion
In conclusion, three important anthranilic diamide structural
classes were designed and synthesized via incorporation of
sulfide, N-cyanomethylsulfilimine, or N-cyanomethylsul-
foximine moiety into the lead structure. The structures of the
1
novel synthesized compounds were confirmed by IR, H and
13C NMR, and EA, and the insecticidal activities of the com-
pounds against Mythimna separata and Plutella xylostella were
tested. Bioassay results indicated that most of the synthesized
compounds possessed good insecticidal activities against
M. separata at 5 mg mLꢀ1 and P. xylostella at 10 mg mLꢀ1 when
compared with the positive control cyantraniliprole. However,
no compounds exhibited higher activities than that of cyan-
traniliprole against M. separata when concentrations were
reduced to 1 mg mLꢀ1, with the exception of compound 17e,
which showed an excellent insecticidal activity against
M. separata, with a mortality rate of 100 %. Furthermore, none
of the compounds tested (including the control) exhibited
insecticidal activity against M. separata on further concentra-
tion reduction to 0.1 mg mLꢀ1
.
Experimental
General
Melting points of all compounds were determined on an X-4
binocular microscope (Gongyi Tech. Instrument Co., Henan,
China), and the temperatures were not corrected. 1H and
13C nuclear magnetic resonance (NMR) spectra were obtained at
400 MHz using a Bruker AV-400 spectrometer; chemical-shift
values (d) were reported as parts per million (ppm) with tetra-
methylsilane as the internal standard. Elemental analyses were
determined on a Yanaca CHN Corder MT-3 recorder. Infrared
(IR) spectra were recorded on a Bruker Vector 22 Fourier
transform infrared (FTIR) spectrometer using KBr pellets. Mass
spectra were recorded using a high-resolution mass spectro-
meter (HRMS) (Varian 7.0T FTMS). All solvents and liquid
reagents were of analytical grade and were dried and distilled
before use. Column chromatography purification was carried
out using silica gel (200–300 mesh).
2-Amino-5-chloro-3-methylbenzoic Acid 7a
Light grey solid (91 % yield), mp 198–1998C. dH (400 MHz,
[D6]DMSO) 7.55 (s, 1H, Ph-H), 7.22 (s, 1H, Ph-H), 2.10 (s,
3H, CH3).
2-Amino-5-bromo-3-methylbenzoic Acid 7b
Light grey solid (88 % yield), mp 215–2178C (lit.[30] 218–
2208C). dH (400 MHz, [D6]DMSO) 7.68 (s, 1H, Ph-H), 7.30 (s,
1H, Ph-H), 2.08 (s, 3H, CH3).
2-Amino-5-cyano-3-methylbenzoic Acid 7c
General Procedure for the Synthesis of Acids 6a and 6b
Light grey solid (47 % yield), mp 184–1868C. dH (400 MHz,
[D6]DMSO) 7.96 (s, 1H, Ph-H), 7.49 (s, 1H, Ph-H), 7.40 (br,
1H), 2.12 (s, 3H, CH3).
Compound 2 was synthesized by heating 2,3-dichloropyridine 1
and 80 % hydrazine hydrate to reflux in ethanol. Intermediates 3,
4a, and 4b, and esters 5a and 5b were designed and prepared as
previously reported.[28] Acid 6a was also synthesized as previ-
ously reported.[28] To a 250-mL flask containing compound 5a
(15.07 g, 0.05 mol) and methanol (90 mL) was added dropwise a
mixture of sodium hydroxide (2.53 g, 0.06 mol) in methanol
(30 mL). The reaction was stirred for 6 h at room temperature,
and reaction progress was monitored by thin layer chromato-
graphy (TLC). Following completion of the reaction, the reaction
General Procedure for the Synthesis of Intermediates 8a–f
6-Chloro-2-(3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-
8-methyl-4H-benzo[d][1,3]oxazin-4-one 8a was synthesized
according to a literature procedure.[7] To a solution of methane-
sulfonyl chloride (3.50 g, 30.5 mmol) in acetonitrile (20 mL)
was added dropwise a mixture of 1-(3-chloropyridin-2-yl)-3-
chloro-1H-pyrazole-5-carboxylic acid (5.25 g, 20.3 mmol) and

Design and Activity of Anthranilic Diamides
1497
pyridine (3.21 g, 40.6 mmol) in acetonitrile (20 mL) at 0–58C.
The reaction temperature was maintained at ,08C throughout
the addition. After stirring for 15 min, 2-amino-5-chloro-3-
methylbenzoic acid (3.78 g, 20.3 mmol) was added and stirring
was continued for an additional 10 min. A solution of pyridine
(4.82 g, 61.0 mmol) in acetonitrile (20 mL) was then added
dropwise, and the reaction mixture was stirred for 30 min, fol-
lowed by the addition of methanesulfonyl chloride (4.66 g,
40.7 mmol). The reaction mixture was stirred for 15 min at 08C
and then warmed to room temperature and stirred overnight, and
reaction progress was monitored by TLC. After reaction com-
pletion, water (,100 mL) was added, and extraction followed
with ethyl acetate (3 ꢂ 50 mL). The combined organic phases
were washed with water (1 ꢂ 20 mL), followed by brine
(1 ꢂ 20 mL), dried over anhydrous sodium sulfate, filtered, and
concentrated. The crude product was purified by chromatogra-
phy on silica gel using petroleum ether/ethyl acetate (v/v 3 : 1)
as eluent to give 8a (7.02 g, 85 %). Compounds 8b–f were
synthesized using the same procedure.
(dd, J1 8.1, J2 1.2, 1H, pyridine-H), 7.88 (d, J 2.0, 1H, Ar-H),
7.74–7.79 (m, 2H, pyridine-H, Ar-H), 7.52 (s, 1H, pyrazole-H),
1.71 (s, 3H, CH3).
6-Cyano-2-(3-bromo-1-(3-chloropyridin-2-yl)-
1H-pyrazol-5-yl)-8-methyl-4H-benzo[d][1,3]
oxazin-4-one 8f
Yellow solid (70 % yield), mp 233–2358C. dH (400 MHz,
[D6]DMSO) 8.63 (d, J 4.8, 1H, pyridine-H), 8.36–8.37 (m, 2H,
pyridine-H, Ar-H), 8.08 (s, 1H, Ar-H), 7.76 (dd, J1 8.0, J2 4.8,
1H, pyridine-H), 7.55 (s, 1H, pyrazole-H), 1.70 (s, 3H, CH3).
General Procedure for the Synthesis of Target
Compounds 16a–e
N-(2-(2-Methyl-2-(methylthio)propylcarbamoyl)-4-chloro-6-
methylphenyl)-3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-
5-carboxamide 16a was synthesized according to a literature
procedure.[7] To a 250-mL flask was added a solution of com-
pound 8a (7.02 g, 17.2mmol) and 2-methyl-1-(methylthio)pro-
pan-2-amine (6.16 g, 51.6 mmol) in tetrahydrofuran (70 mL).
The mixture was heated to 608C and stirred for 8 h, and reaction
progress was monitored by TLC. After completion, the solvent
was removed and the residue was purified by chromatography
on silica gel using petroleum ether/ethyl acetate (v/v 3 : 1) as
eluent to give 16a (5.08 g, 56 %). Compounds 16b–e were
synthesized in the same manner.
6-Chloro-2-(3-chloro-1-(3-chloropyridin-2-yl)-
1H-pyrazol-5-yl)-8-methyl-4H-benzo[d][1,3]
oxazin-4-one 8a
Yellow solid (85 % yield), mp 189–1918C. dH (400 MHz,
[D6]DMSO) 8.63 (dd, J1 4.8, J2 1.2, 1H, pyridine-H), 8.35 (dd,
J1 8.0, J2 1.2, 1H, pyridine-H), 7.85 (d, J 1.6, 1H, Ar-H), 7.77
(dd, J1 8.0, J2 4.8, 1H, pyridine-H), 7.74 (d, J 1.6, 1H, Ar-H),
7.47 (s, 1H, pyrazole-H), 1.70 (s, 3H, CH3).
N-(2-(2-Methyl-2-(methylthio)propylcarbamoyl)-
4-chloro-6-methylphenyl)-3-chloro-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 16a
6-Bromo-2-(3-chloro-1-(3-chloropyridin-2-yl)-1H-
pyrazol-5-yl)-8-methyl-4H-benzo[d][1,3]oxazin-
4-one 8b
Transparent granules (56 % yield), mp 187–1898C.
max(KBr)/cmꢀ1 3262, 3064, 2976, 2908, 2358, 1641, 1541,
Yellow solid (77 % yield), mp 194–1968C. dH (400 MHz,
CDCl3) 8.55 (dd, J1 4.4, J2 1.2, 1H, pyridine-H), 8.11 (d, J 2.0,
1H, Ar-H), 7.97 (dd, J1 8.0, J2 1.2, 1H, pyridine-H), 7.64 (d, J
1.6, 1H, Ar-H), 7.50 (dd, J1 8.0, J2 4.8, 1H, pyridine-H), 7.16 (s,
1H, pyrazole-H), 1.79 (s, 3H, CH3).
n
1462, 1368, 1312, 1247, 1198, 1135, 1030, 971, 877, 809, 758,
658. dH (400 MHz, [D6]DMSO) 10.20 (s, 1H, NH), 8.49 (dd, J1
4.4, J2 1.2, 1H, pyridine-H), 8.18 (dd, J1 8.0, J2 1.2, 1H,
pyridine-H), 7.84 (s, 1H, NH), 7.62 (dd, J1 8.0, J2 4.4, 1H,
pyridine-H), 7.46 (d, J 2.0, 1H, Ar-H), 7.35 (d, J 0.8, 1H, Ar-H),
7.28 (s, 1H, pyrazole-H), 2.93 (s, 2H, CH2), 2.16 (s, 3H,
Ar-CH3), 2.03 (s, 3H, SCH3), 1.27 (s, 6H, CH3). dC (400 MHz,
[D6]DMSO) 166.7, 156.8, 149.6, 148.2, 140.7, 140.4, 140.2,
139.9, 138.4, 132.2, 132.0, 129.1, 127.8, 126.8, 108.4, 55.7,
44.8, 27.2, 18.8, 18.1. Anal. Calc. for C22H22Cl3N5O2S:
C 50.15, H 4.21, N 13.29. Found: C 50.06, H 4.33, N 13.02.
6-Cyano-2-(3-chloro-1-(3-chloropyridin-2-yl)-1H-
pyrazol-5-yl)-8-methyl-4H-benzo[d][1,3]oxazin-
4-one 8c
Yellow solid (67 % yield), mp 222–2248C. dH (400 MHz,
[D6]DMSO) 8.63 (d, J 4.8, 1H, pyridine-H), 8.35–8.36 (m, 2H,
pyridine-H, Ar-H), 8.08 (s, 1H, Ar-H), 7.77 (dd, J1 8.0, J2 4.8,
1H, pyridine-H), 7.55 (s, 1H, pyrazole-H), 1.71 (s, 3H, CH3).
N-(2-(2-Methyl-2-(methylthio)propylcarbamoyl)-
4-bromo-6-methylphenyl)-3-chloro-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 16b
6-Bromo-2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-
pyrazol-5-yl)-8-methyl-4H-benzo[d][1,3]oxazin-
4-one 8d
White granules (42 % yield), mp 195–1978C. nmax(KBr)/
cmꢀ1 3366, 3143, 3066, 2979, 2922, 2358, 1645, 1540, 1460,
1370, 1304, 1197, 1149, 1026, 974, 866, 807, 759, 661. dH
(400 MHz, CDCl3) 10.15 (s, 1H, NH), 8.44 (dd, J1 4.8, J2 1.6,
1H, pyridine-H), 7.84 (dd, J1 8.0, J2 1.2, 1H, pyridine-H), 7.37
(dd, J1 8.0, J2 4.8, 1H, pyridine-H), 7.36 (s, 1H, Ar-H), 7.24 (s,
2H, Ar-H, pyrazole-H), 6.24 (s, 1H, NH), 2.95 (s, 2H, CH2), 2.11
(s, 3H, Ar-CH3), 2.09 (s, 3H, SCH3), 1.40 (s, 6H, CH3). dC
(400 MHz, CDCl3) 167.7, 157.2, 149.3, 146.8, 141.6, 139.1,
138.8, 138.3, 135.9, 135.0, 130.7, 129.2, 127.2, 125.7,
120.8, 107.9, 55.7, 45.1, 26.4, 18.3, 17.6. Anal. Calc. for
C22H22BrCl2N5O2S: C 46.25, H 3.88, N 12.26. Found:
C 46.43, H 3.98, N 12.18.
Yellow solid (84 % yield), mp 204–2058C. dH (400 MHz,
CDCl3) 8.56 (dd, J1 4.8, J2 1.2, 1H, pyridine-H), 8.13 (d, J 2.0,
1H, Ar-H), 7.97 (dd, J1 8.0, J2 1.6, 1H, pyridine-H), 7.65 (d,
J 1.6, 1H, Ar-H), 7.50 (dd, J1 8.0, J2 4.8, 1H, pyridine-H), 7.25
(s, 1H, pyrazole-H), 1.80 (s, 3H, CH3).
6-Chloro-2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-
pyrazol-5-yl)-8-methyl-4H-benzo[d][1,3]oxazin-
4-one 8e
Yellow solid (92 % yield), mp 192–1938C. dH (400 MHz,
[D6]DMSO) 8.63 (dd, J1 4.5, J2 1.2, 1H, pyridine-H), 8.35

1498
X. Hua et al.
N-(2-(2-Methyl-2-(methylthio)propylcarbamoyl)-4-
bromo-6-methylphenyl)-3-bromo-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 16d
130.8, 127.9, 126.6, 125.4, 107.3, 38.3, 32.4, 17.6, 14.5. Anal.
Calc. for C20H18Cl3N5O2S: C 48.16, H 3.64, N 14.04. Found:
C 48.06, H 3.92, N 13.86.
White granules (50 % yield), mp 213–2158C. nmax(KBr)/
cmꢀ1 3258, 3062, 2975, 2906, 2357, 1641, 1541, 1461, 1353,
1246, 1193, 1132, 1031, 959, 866, 811, 763, 655. dH (400 MHz,
[D6]DMSO) 10.19 (s, 1H, NH), 8.50 (d, J 4.4, 1H, pyridine-H),
8.18 (d, J 8.0, 1H, pyridine-H), 7.87 (br, 1H, NH), 7.62 (dd, J1
8.0, J2 4.8, 1H, pyridine-H), 7.60 (s, 1H, Ar-H), 7.42 (s, 2H,
Ar-H, pyrazole-H), 2.94 (s, 2H, CH2), 2.17 (s, 3H, Ar-CH3), 2.04
(s, 3H, SCH3), 1.28 (s, 6H, CH3). dC (400 MHz, [D6]DMSO)
165.4, 155.4, 148.4, 147.0, 139.2, 139.1, 139.0, 137.4, 133.8,
131.4, 128.4, 127.9, 126.7, 126.6, 119.4, 110.6, 54.5, 43.6, 26.0,
17.5, 16.9. Anal. Calc. for C22H22Br2ClN5O2S: C 42.91, H 3.60,
N 11.37. Found: C 42.68, H 3.85, N 11.08.
N-(2-(2-(Methylthio)ethylcarbamoyl)-4-bromo-6-
methylphenyl)-3-chloro-1-(3-chloropyridin-2-yl)-
1H-pyrazole-5-carboxamide 19b
White powder (81 % yield), mp 107–1088C. nmax(KBr)/cmꢀ1
3249, 3066, 2978, 2918, 2358, 1656, 1533, 1462, 1365, 1301,
1190, 1137, 1032, 973, 863, 803, 757, 659. dH (400 MHz,
CDCl3) 10.07 (s, 1H, NH), 8.44 (dd, J1 4.4, J2 1.2, 1H,
pyridine-H), 7.84 (dd, J1 8.0, J2 1.2, 1H, pyridine-H), 7.36
(dd, J1 8.0, J2 4.8, 1H, pyridine-H), 7.29 (s, 1H, Ar-H), 7.28 (s,
1H, Ar-H), 7.13 (s, 1H, pyrazole-H), 6.76 (s, 1H, NH), 3.54 (q, J
6.4, 2H, CH2), 2.64 (t, J 6.4, 2H, CH2), 2.11 (s, 3H, Ar-CH3),
2.09 (s, 3H, SCH3). dC (400 MHz, CDCl3) 168.0, 156.7, 149.2,
146.8, 141.7, 138.9, 138.5, 138.4, 135.6, 133.3, 131.6, 129.0,
127.5, 125.7, 120.2, 107.8, 38.2, 33.3, 18.5, 15.0. Anal. Calc. for
C20H18BrCl2N5O2S: C 44.22, H 3.34, N 12.89. Found: C 44.57,
H 3.52, N 12.74.
N-(2-(2-Methyl-2-(methylthio)propylcarbamoyl)-4-
chloro-6-methylphenyl)-3-bromo-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 16e
Pale yellow solid (46 % yield), mp 185–1868C. nmax(KBr)/
cmꢀ1 3127, 3066, 2972, 2921, 2356, 1669, 1536, 1466, 1365,
1299, 1137, 1032, 957, 873, 808, 750. dH (400 MHz, CDCl3)
10.16 (s, 1H, NH), 8.43 (dd, J1 4.8, J2 1.6, 1H, pyridine-H), 7.82
(dd, J1 8.0, J2 1.6, 1H, pyridine-H), 7.47 (s, 1H, NH), 7.35 (dd, J1
8.0, J2 4.4, 1H, pyridine-H), 7.06 (d, J 2.0, 1H, Ar-H), 7.02 (d, J
2.0, 1H, Ar-H), 6.26 (s, 1H, pyrazole-H), 2.93 (s, 2H, CH2), 2.09
(s, 3H, Ar-CH3), 2.05 (s, 3H, SCH3), 1.38 (s, 6H, CH3). dC
(400 MHz, CDCl3) 168.0, 157.3, 149.3, 146.8, 138.9, 138.8,
138.4, 136.1, 132.8, 131.9, 129.9, 129.1, 128.1, 125.7, 124.4,
111.4, 55.7, 45.1, 26.4, 18.2, 17.6. Anal. Calc. for
C22H22BrCl2N5O2S: C 46.25, H 3.88, N 12.26. Found:
C 46.13, H 3.95, N 12.17.
N-(2-(2-(Methylthio)ethylcarbamoyl)-4-cyano-6-
methylphenyl)-3-chloro-1-(3-chloropyridin-2-yl)-
1H-pyrazole-5-carboxamide 19c
White granules (51 % yield), mp 200–2028C. nmax(KBr)/
cmꢀ1 3376, 3272, 3049, 2983, 2928, 2358, 2228, 1643, 1524,
1459, 1364, 1304, 1146, 1041, 972, 893, 808, 762. dH (400 MHz,
[D6]DMSO) 10.52 (s, 1H, NH), 8.56 (s, 1H, NH), 8.50 (dd, J1
4.4, J2 0.8, 1H, pyridine-H), 8.18 (dd, J1 8.0, J2 1.2, 1H,
pyridine-H), 7.90 (s, 1H, Ar-H), 7.77 (s, 1H, Ar-H), 7.62 (dd,
J1 8.0, J2 4.8, 1H, pyridine-H), 7.39 (s, 1H, pyrazole-H), 3.33 (q,
J 6.8, 2H, CH2), 2.52 (t, J 6.8, 2H, CH2), 2.24 (s, 3H, Ar-CH3),
2.06 (s, 3H, SCH3). dC (400 MHz, [D6]DMSO) 165.4, 155.4,
148.3, 147.1, 139.6, 139.2, 138.8, 137.7, 137.1, 135.3, 134.8,
129.6, 127.9, 126.7, 118.0, 109.2, 107.6, 38.4, 32.3, 17.7, 14.5.
Anal. Calc. for C21H18Cl2N6O2S: C 51.54, H 3.71, N 17.17.
Found: C 51.33, H 3.91, N 17.07.
General Procedure for the Synthesis of Target
Compounds 19a–f
N-(2-(2-(Methylthio)ethylcarbamoyl)-4-chloro-6-methylphenyl)-
3-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide
19a was synthesized according to a literature procedure.[7] To a
solution of compound 8a (4.89 g, 12.0mmol) in tetrahydrofuran
(40 mL) was added 2-(methylthio)ethanamine hydrochloride
(3.06 g, 24.0mmol). The mixture was stirred for 10min at 0–58C,
followed by dropwise addition of triethylamine (3.64 g,
36.0 mmol). The reaction was then warmed to room temperature
and stirred for 6 h, and reaction progress was monitored by TLC.
After completion, the mixture was filtered and the filtrate was
concentrated. The crude material was purifiedbychromatography
on silica gel using petroleum ether/ethyl acetate (v/v 3 : 1) as
eluent to give 19a (5.45 g, 91%). Compounds 19b–f were syn-
thesized similarly.
N-(2-(2-(Methylthio)ethylcarbamoyl)-4-bromo-6-
methylphenyl)-3-bromo-1-(3-chloropyridin-2-yl)-
1H-pyrazole-5-carboxamide 19d
Pale yellow solid (57 % yield), mp 216–2188C. nmax(KBr)/
cmꢀ1 3222, 3066, 2969, 2922, 2358, 1664, 1533, 1459, 1354,
1300, 1131, 1034, 959, 865, 805, 753. dH (400 MHz,CDCl3)
10.06 (s, 1H, NH), 8.43 (dd, J1 4.8, J2 1.2, 1H, pyridine-H), 7.82
(d, J 8.0, 1H, pyridine-H), 7.34 (dd, J1 8.0, J2 4.8, 1H, pyridine-
H), 7.26 (s, 1H, Ar-H), 7.22 (s, 2H, Ar-H, pyrazole-H), 6.94 (s,
1H, NH), 3.52 (q, J 6.4, 2H, CH2), 2.62 (t, J 6.4, 2H, CH2), 2.10
(s, 3H, Ar-CH3), 2.04 (s, 3H, SCH3). dC (400 MHz, CDCl3)
167.0, 155.6, 148.1, 145.8, 137.8, 137.5, 137.3, 134.3, 132.7,
130.3, 127.9, 127.2, 126.6, 124.7, 119.2, 110.2, 37.3, 32.2, 17.3,
14.0. Anal. Calc. for C20H18Br2ClN5O2S: C 40.87, H 3.09,
N 11.92. Found: C 40.65, H 3.49, N 11.79.
N-(2-(2-(Methylthio)ethylcarbamoyl)-4-chloro-6-
methylphenyl)-3-chloro-1-(3-chloropyridin-2-yl)-
1H-pyrazole-5-carboxamide 19a
White granules (91 % yield), mp 147–1498C. nmax(KBr)/
cmꢀ1 3263, 3068, 2980, 2920, 2359, 1650, 1534, 1465, 1367,
1303, 1196, 1138, 1032, 974, 877, 806, 757. dH (400 MHz, [D6]
DMSO) 10.22 (s, 1H, NH), 8.49 (s, 2H, pyridine-H, NH), 8.17
(d, J 8.0, 1H, pyridine-H), 7.62 (dd, J1 8.0, J2 4.0, 1H, pyridine-
H), 7.49 (s, 1H, Ar-H), 7.35 (s, 2H, Ar-H, pyrazole-H), 3.32 (q,
J 6.4, 2H, CH2), 2.52 (t, J 6.0, 2H, CH2), 2.18 (s, 3H, Ar-CH3),
2.06 (s, 3H, SCH3). dC (400 MHz, [D6]DMSO) 165.7, 155.6,
148.4, 147.0, 139.6, 139.2, 138.7, 135.8, 131.6, 131.6, 131.2,
N-(2-(2-(Methylthio)ethylcarbamoyl)-4-chloro-6-
methylphenyl)-3-bromo-1-(3-chloropyridin-2-yl)-
1H-pyrazole-5-carboxamide 19e
Pale yellow solid (65 % yield), mp 160–1628C. nmax(KBr)/
cmꢀ1 3253, 3064, 2977, 2917, 2357, 1655, 1533, 1462, 1353,
1301, 1193, 1132, 1031, 960, 875, 805, 756. dH (400 MHz,
CDCl3) 10.08 (s, 1H, NH), 8.47 (dd, J1 4.8, J2 1.2, 1H, pyridine-H),
7.86 (dd, J1 8.0, J2 1.2, 1H, pyridine-H), 7.38 (dd, J1 8.0, J2 4.8,

Design and Activity of Anthranilic Diamides
1499
1H, pyridine-H), 7.22 (s, 2H, Ar-H, pyrazole-H), 7.16 (s, 1H, Ar-
H), 6.62 (s, 1H, NH), 3.59 (q, J 6.4, 2H, CH2), 2.68 (t, J 6.4, 2H,
CH2), 2.16 (s, 3H, Ar-CH3), 2.12 (s, 3H, SCH3). dC (400 MHz,
CDCl3) 167.9, 156.3, 149.0, 146.9, 138.9, 138.8, 138.5, 133.0,
132.2, 131.6, 129.0, 128.2, 125.7, 124.5, 111.0, 38.1, 33.4, 18.8,
15.0. Anal. Calc. for C20H18BrCl2N5O2S: C 44.22, H 3.34,
N 12.89. Found: C 44.13, H 3.59, N 12.75.
1247, 10742, 1030, 977, 864, 810, 760, 673. dH (400 MHz, [D6]
DMSO) 10.21 (s, 1H, NH), 8.52 (d, J 4.0, 1H, pyridine-H), 8.40
(s, 1H, NH), 8.18 (d, J 8.0, 1H, pyridine-H), 7.61–7.65 (m, 2H,
pyridine-H, Ar-H), 7.50 (s, 1H, Ar-H), 7.36 (s, 1H, pyrazole-H),
3.67 (d, J 13.6, 1H, HA-CH2), 3.50 (d, J 13.6, 1H, HB-CH2), 2.76
(s, 3H, n ¼ SCH3), 2.19 (s, 3H, Ar-CH3), 1.41 (s, 3H, CH3), 1.36
(s, 3H, CH3). dC (400 MHz, [D6]DMSO) 166.0, 155.5, 148.4,
147.1, 139.6, 139.2, 139.0, 138.9, 136.6, 134.0, 131.5, 128.6,
127.9, 126.6, 120.4, 119.4, 107.2, 57.7, 52.2, 33.3, 26.9, 26.6,
17.5. Anal. Calc. for C23H22BrCl2N7O2S: C 45.19, H 3.63,
N 16.04. Found: C 45.31, H 3.84, N 15.69.
N-(2-(2-(Methylthio)ethylcarbamoyl)-4-cyano-6-
methylphenyl)-3-bromo-1-(3-chloropyridin-2-yl)-
1H-pyrazole-5-carboxamide 19f
Pale yellow solid (55 % yield), mp 216–2188C. nmax(KBr)/
cmꢀ1 3380, 3277, 3049, 2980, 2925, 2358, 2228, 1684, 1640,
1524, 1458, 1349, 1302, 1144, 1041, 959, 893, 808, 762. dH
(400 MHz, CDCl3) 10.52 (s, 1H, NH), 8.46 (dd, J1 6.0, J2 2.0,
1H, pyridine-H), 7.87 (dd, J1 10.4, J2 2.0, 1H, pyridine-H), 7.63
(s, 1H, Ar-H), 7.61 (s, 1H, Ar-H), 7.40 (dd, J1 10.8, J2 6.4, 1H,
pyridine-H), 7.04 (s, 1H, pyrazole-H), 6.63 (s, 1H, NH), 3.64 (q,
J 8.0, 2H, CH2), 2.74 (t, J 8.0, 2H, CH2), 2.25 (s, 3H, Ar-CH3),
2.13 (s, 3H, SCH3). Anal. Calc. for C21H18BrClN6O2S: C 47.25,
H 3.40, N 15.74. Found: C 47.54, H 3.79, N 15.53.
N-(2-(2-Methyl-2-(N-cyanomethylsulfideimino)
propylcarbamoyl)-4-cyano-6-methylphenyl)-3-
chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-
carboxamide 17c
White granules (63 % yield), mp 237–2398C. nmax(KBr)/
cmꢀ1 3247, 3127, 3060, 2979, 2915, 2357, 2226, 2154, 1682,
1535, 1464, 1374, 1305, 1218, 1155, 1030, 972, 888, 819, 762,
668. dH (400 MHz, [D6]DMSO) 10.44 (s, 1H, NH), 8.52 (d, J
4.8, 1H, pyridine-H), 8.48 (s, 1H, NH), 8.19 (d, J 8.0, 1H,
pyridine-H), 7.91 (s, 1H, Ar-H), 7.82 (s, 1H, Ar-H), 7.63 (dd, J1
8.0, J2 4.8, 1H, pyridine-H), 7.38 (s, 1H, pyrazole-H), 3.64 (d, J
13.6, 1H, HA-CH2), 3.52 (d, J 13.6, 1H, HB-CH2), 2.77 (s, 3H,
n ¼ SCH3), 2.25 (s, 3H, Ar-CH3), 1.41 (s, 3H, CH3), 1.36 (s, 3H,
CH3). dC (400 MHz, [D6]DMSO) 165.8, 155.4, 148.3, 147.2,
139.6, 139.3, 138.8, 137.6, 136.8, 135.2, 135.1, 130.2, 127.9,
126.7, 120.5, 118.0, 109.2, 107.5, 57.7, 52.2, 33.4, 26.9, 26.6,
17.6. Anal. Calc. for C24H22Cl2N8O2S: C 51.71, H 3.98,
N 20.10. Found: C 51.77, H 4.16, N 19.98.
General Procedure for the Synthesis of Target
Compounds 17a–e and 20a–f
N-(2-(2-Methyl-2-(N-cyanomethylsulfideimino)propylcarbamyl)-
4-chloro-6-methylphenyl)-3-chloro-1-(3-chloropyridin-2-yl)-
1H-pyrazole-5-carboxamide 17a was synthesized as previously
described.[31] A solution of compound 16a (3.71 g, 7.04 mmol)
and cyanamide (0.59 g, 14.1 mmol) in tetrahydrofuran (30 mL)
was stirred for 10 min at 0–58C, followed by addition of (diace-
toxyiodo)benzene (2.49 g, 7.74 mmol). Stirring was continued at
0–58C and the reaction progress was monitored by TLC. After
completion, the solvent was removed and the residue was purified
by chromatography on silica gel using petroleum ether/ethyl
acetate (v/v 1 :1) as eluent to give 17a (3.09 g, 92 %). Compounds
17b–e and 20a–f were synthesized similarly.
N-(2-(2-Methyl-2-(N-cyanomethylsulfideimino)
propylcarbamoyl)-4-bromo-6-methylphenyl)-3-
bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-
carboxamide 17d
White granules (69 % yield), mp 175–1768C. nmax(KBr)/
cmꢀ1 3276, 3210, 2976, 2865, 2358, 2147, 1672, 1529, 1464,
1353, 1301, 1255, 1159, 1063, 962, 864, 814, 767, 672. dH
(400 MHz, [D6]DMSO) 10.10 (s, 1H, NH), 8.51 (dd, J1 4.8, J2
1.2, 1H, pyridine-H), 8.42 (s, 1H, NH), 8.17 (dd, J1 8.0, J2 1.2,
1H, pyridine-H), 7.60–7.63 (m, 2H, pyridine-H, Ar-H), 7.49 (s,
1H, Ar-H), 7.41 (s, 1H, pyrazole-H), 3.66 (d, J 13.6, 1H, HA-
CH2), 3.49 (d, J 13.6, 1H, HB-CH2), 2.75 (s, 3H, n ¼ SCH3), 2.18
(s, 3H, Ar-CH3), 1.37 (s, 3H, CH3), 1.35 (s, 1H, CH3). dC
(400 MHz, [D6]DMSO) 166.0, 155.4, 148.4, 147.1, 139.2,
139.2, 138.8, 136.6, 134.0, 131.6, 128.6, 127.9, 126.8, 126.6,
120.4, 119.3, 110.6, 57.8, 52.2, 33.3, 27.0, 26.6, 17.5. Anal.
Calc. for C23H22Br2ClN7O2S: C 42.12, H 3.38, N 14.95. Found:
C 42.05, H 3.58, N 14.85.
N-(2-(2-Methyl-2-(N-cyanomethylsulfideimino)
propylcarbamoyl)-4-chloro-6-methylphenyl)-3-
chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-
carboxamide 17a
Whitegranules(92 % yield), mp111–1128C. nmax(KBr)/cmꢀ1
3261, 3058, 2982, 2926, 2358, 2147, 1671, 1537, 1463, 1370,
1308, 1248, 1158, 1033, 972, 881, 811, 764. dH (400 MHz, [D6]
DMSO) 10.20 (s, 1H, NH), 8.51 (dd, J1 4.8, J2 1.6, 1H, pyridine-
H), 8.40(s,1H, NH), 8.18(dd,J1 8.0,J2 1.2,1H, pyridine-H), 7.62
(dd, J1 8.0, J2 4.4, 1H, pyridine-H), 7.48 (d, J 2.0, 1H, Ar-H), 7.38
(d, J 2.0, 1H, Ar-H), 7.35 (s, 1H, pyrazole-H), 3.66 (d, J 13.6, 1H,
HA-CH2), 3.49 (d, J 13.6, 1H, HB-CH2), 2.75 (s, 3H, n ¼ SCH3),
2.18 (s, 3H, Ar-CH3), 1.40 (s, 3H, CH3), 1.35 (s, 3H, CH3). dC
(400 MHz, [d6]DMSO) 166.1, 155.6, 148.5, 147.1, 139.6, 139.2,
139.0, 138.6, 136.3, 131.1, 130.8, 127.9, 126.6, 125.8, 120.4,
107.2, 57.8, 52.2, 33.3, 26.9, 26.6, 17.6. HRMS (MALDI)
588.0519, 589.0556, 590.0488, 591.0525, 592.0458, 593.0493
([M þ Na]þ). Anal. Calc. for C23H22Cl3N7O2S: C 48.73, H 3.91,
N 17.30. Found: C 48.60, H 4.25, N 17.22.
N-(2-(2-Methyl-2-(N-cyanomethylsulfideimino)
propylcarbamoyl)-4-chloro-6-methylphenyl)-3-
bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-
carboxamide 17e
White solid (62 % yield), mp 128–1308C. nmax(KBr)/cmꢀ1
3251, 3058, 2980, 2924, 2358, 2147, 1674, 1536.27, 1462, 1355,
1304, 1246, 1153, 1029, 960, 879, 809, 761. dH (400 MHz, [D6]
DMSO) 10.20 (s, 1H, NH), 8.51 (dd, J1 4.8, J2 1.2, 1H, pyridine-
H), 8.40 (s, 1H, NH), 8.18 (dd, J1 8.4, J2 1.2, 1H, pyridine-H),
7.62 (dd, J1 8.0, J2 4.4, 1H, pyridine-H), 7.48 (d, J 2.0, 1H, Ar-
H), 7.41 (s, 1H, pyrazole-H), 7.38 (d, J 2.4, 1H, Ar-H), 3.65 (d, J
13.6, 1H, HA-CH2), 3.49 (d, J 13.6, 1H, HB-CH2), 2.75 (s, 3H,
N-(2-(2-Methyl-2-(N-cyanomethylsulfideimino)
propylcarbamoyl)-4-bromo-6-methylphenyl)-3-chloro-
1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide
17b
White powder (77 % yield), mp 193–1958C. nmax(KBr)/cmꢀ1
3248, 2999, 2921, 2356, 2138, 1669, 1533, 1464, 1371, 1301,

1500
X. Hua et al.
n ¼ SCH3), 2.18 (s, 3H, Ar-CH3), 1.40 (s, 3H, CH3), 1.34 (s, 3H,
CH3). dC (400 MHz, [D6]DMSO) 166.2, 155.5, 148.4, 147.1,
139.2, 139.1, 138.6, 136.4, 131.1, 130.9, 127.9, 126.8, 126.6,
125.8, 120.4, 110.6, 57.7, 52.2, 33.3, 27.0, 26.6, 17.6. Anal.
Calc. for C23H22BrCl2N7O2S: C 45.19, H 3.63, N 16.04. Found:
C 44.97, H 3.81, N 15.88.
10.27 (s, 1H, NH), 8.75–8.78 (m, 1H, NH), 8.52 (d, J 4.0, 1H,
pyridine-H), 8.18 (d, J 7.6, 1H, pyridine-H), 7.62 (dd, J1 8.0, J2
4.8, 1H, pyridine-H), 7.50 (s, 1H, Ar-H), 7.39–7.41 (m, 2H, Ar-
H, pyrazole-H), 3.45–3.60 (m, 2H, CH2), 3.18–3.28 (m, 2H,
CH2), 2.81 (s, 3H, n ¼ SCH3), 2.18 (s, 3H, Ar-CH3). Anal. Calc.
for C21H18BrCl2N7O2S: C 43.24, H 3.11, N 16.81. Found:
C 43.01, H 3.49, N 16.71.
N-(2-(2-(N-Cyanomethylsulfideimino)ethylcarbamoyl)-
4-chloro-6-methylphenyl)-3-chloro-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 20a
N-(2-(2-(N-Cyanomethylsulfideimino)ethylcarbamoyl)-
4-cyano-6-methylphenyl)-3-bromo-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 20f
White granules (90 % yield), mp 198–2008C. nmax(KBr)/
cmꢀ1 3217, 3067, 2986, 2357, 2151, 1647, 1539, 1465, 1370,
1308, 1162, 1038, 972, 880, 808, 763, 690. dH (400 MHz, [D6]
DMSO) 10.32 (s, 1H, NH), 8.78 (s, 1H, NH), 8.53 (d, J 4.0, 1H,
pyridine-H), 8.19 (d, J 7.6, 1H, pyridine-H), 7.62 (dd, J1 7.2, J2
4.4, 1H, pyridine-H), 7.52 (s, 1H, Ar-H), 7.42 (s, 1H, Ar-H), 7.36
(s, 1H, pyrazole-H), 3.51–3.57 (m, 2H, CH2), 3.19–3.32 (m, 2H,
CH2), 2.82 (s, 3H, n ¼ SCH3), 2.19 (s, 3H, Ar-CH3). dC
(400 MHz, [D6]DMSO) 166.1, 155.7, 148.4, 147.1, 139.7,
139.3, 139.1, 138.8, 135.3, 131.5, 131.3, 131.0, 127.9, 126.6,
125.5, 120.4, 107.4, 48.8, 33.3, 32.3, 17.6. Anal. Calc. for
C21H18Cl3N7O2S: C 46.81, H 3.37, N 18.20. Found: C 46.71,
H 3.45, N 18.12.
White solid (49 % yield), mp 245–2478C. nmax(KBr)/cmꢀ1
3224, 3074, 2976, 2359, 2229 2152, 1681, 1533, 1466, 1353,
1301, 1161, 1036, 962, 895, 811, 768. dH (400 MHz, [D6]
DMSO) 9.07 (s, 1H, NH), 8.52 (d, J 3.6, 1H, pyridine-H), 8.18
(d, J 6.8, 1H, pyridine-H), 7.88 (s, 1H, Ar-H), 7.83 (s, 1H, Ar-H),
7.62 (dd, J1 4.8, J2 8.0, 1H, pyridine-H), 7.39 (s, 1H, pyrazole-H),
3.50–3.59 (m, 2H, CH2), 3.17–3.26 (m, 2H, CH2), 2.81 (s, 3H,
n ¼ SCH3), 2.22 (s, 3H, Ar-CH3). HRMS (MALDI) 595.0035,
596.0082, 597.0010, 598.0055, 599.0004, 600.0049 ([M þ
Na]þ). Anal. Calc. for C22H18BrClN8O2S: C 46.05, H 3.16,
N 19.53. Found: C 45.79, H 3.69, N 19.31.
General Procedure for the Synthesis of Target
Compounds 18a–e and 21c–e
N-(2-(2-(N-Cyanomethylsulfideimino)ethylcarbamoyl)-
4-bromo-6-methylphenyl)-3-chloro-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 20b
N-(2-(2-Methyl-2-(N-cyanomethylsulfoximino)propylcarbamoyl)-
4-chloro-6-methylphenyl)-3-chloro-1-(3-chloropyridin-2-yl)-
1H-pyrazole-5-carboxamide 18a was synthesized according to a
literature procedure.[31] To a solution of 3-chloroperoxybenzoic
acid (1.78 g, 10.3 mmol) in methanol (20 mL) was added dropwise
a mixture of potassium carbonate (2.14 g, 15.5 mmol) and water
(20 mL) at 08C. The reaction was stirred for 20 min at 08C, fol-
lowed by addition of a solution of compound 17a (2.92 g,
5.15 mmol) in methanol (20 mL). The reaction mixture was stirred
at 08C, and the progress was monitored by TLC. After completion,
the methanol was removed and the residue was extracted with ethyl
acetate (3 ꢂ 50 mL). The combined organic phases were washed
with water (1 ꢂ 20 mL), followed by brine (1 ꢂ 20 mL), dried over
anhydrous sodium sulfate, filtered, and concentrated. The crude
material was purified by chromatography on silica gel using
petroleum ether/ethyl acetate (v/v 1 : 1) as eluent to give 18a
(1.53 g, 51 %). Compounds 18b–eand 21b–ewere synthesized in a
similar manner.
White granules (59% yield), mp 184–1868C. nmax(KBr)/cmꢀ1
3201, 3067, 2992, 2358, 2153, 1671, 1532, 1464, 1367, 1304,
1186, 1140, 1036, 866, 807, 754. dH (400 MHz, [D6]DMSO)
10.28 (s, 1H, NH), 8.62 (s, 1H, NH), 8.51 (d, J 4.0, 1H, pyridine-
H), 8.18 (d, J 7.6, 1H, pyridine-H), 7.63 (s, 2H, pyridine-H, Ar-H),
7.49 (s, 1H, Ar-H), 7.36 (s, 1H, pyrazole-H), 3.45–3.55 (m, 2H,
CH2), 2.78–2.99 (m, 2H, CH2), 2.54 (s, 3H, n ¼ SCH3), 2.18 (s,
3H, Ar-CH3). dC (400 MHz, [D6]DMSO) 165.7, 155.6, 148.4,
147.1, 139.5, 139.2, 139.1, 139.0, 135.9, 134.2, 132.8, 131.8,
128.2, 127.9, 126.6, 119.3, 107.3, 52.6, 38.0, 33.1, 17.5. Anal.
Calc. for C21H18BrCl2N7O2S: C 43.24, H 3.11, N 16.81. Found:
C 43.37, H 3.45, N 16.72.
N-(2-(2-(N-Cyanomethylsulfideimino)ethylcarbamoyl)-
4-cyano-6-methylphenyl)-3-chloro-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 20c
Yellow powder (89 % yield), mp 202–2038C. nmax(KBr)/
cmꢀ1 3148, 3074, 2974, 2358, 2230, 2151, 1671, 1536, 1467,
1369, 1307, 1161, 1035, 972, 895, 811, 765. dH (400 MHz, [D6]
DMSO) 10.57 (s, 1H, NH), 8.92 (s, 1H, NH), 8.52 (s, 1H,
pyridine-H), 8.18 (s, 1H, pyridine-H), 7.84–7.90 (m, 2H, pyri-
dine-H, Ar-H), 7.62 (s, 1H, Ar-H), 7.34 (s, 1H, pyrazole-H),
3.50–3.57 (m, 2H, CH2), 3.20–3.25 (m, 2H, CH2), 2.82 (s, 3H,
n ¼ SCH3), 2.23 (s, 3H, Ar-CH3). dC (400 MHz, [D6]DMSO)
165.8, 155.6, 148.4, 147.1, 147.1, 139.6, 139.3, 139.2, 137.6,
135.4, 129.8, 129.7, 127.9, 126.7, 120.4, 118.1, 107.5, 48.8,
33.4, 32.2, 17.7. Anal. Calc. for C22H18Cl2N8O2S: C 49.91,
H 3.43, N 21.17. Found: C 49.76, H 3.59, N 21.12.
N-(2-(2-Methyl-2-(N-cyanomethylsulfoximino)
propylcarbamoyl)-4-chloro-6-methylphenyl)-3-
chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-
carboxamide 18a
White powder (51 % yield), mp 142–1448C. nmax(KBr)/cmꢀ1
3279, 3065, 2986, 2924, 2359, 2195, 1675, 1536, 1463, 1366,
1308, 1246, 1194, 1035, 974, 879, 814, 762. dH (400 MHz, [D6]
DMSO) 10.20 (s, 1H, NH), 8.49 (dd, J1 4.8, J2 1.2, 1H, pyridine-
H), 8.29 (s, 1H, NH), 8.17 (dd, J1 8.0, J2 1.2, 1H, pyridine-H),
7.62 (dd, J1 8.0, J2 4.8, 1H, pyridine-H), 7.48 (d, J 1.6, 1H,
Ar-H), 7.36 (d, J 2.0, 1H, Ar-H), 7.33 (s, 1H, pyrazole-H), 4.20
(s, 2H, CH2), 3.45 (s, 3H, N(O)¼SCH3), 2.18 (s, 3H, Ar-CH3),
1.42 (s, 6H, CH3). dC (400 MHz, [D6]DMSO) 166.0, 155.5,
148.4, 147.0, 139.6, 139.2, 138.9, 138.6, 136.5, 131.1, 131.0,
130.9, 127.9, 126.6, 125.8, 112.4, 107.2, 58.9, 52.3, 42.7, 26.9,
26.8, 17.5. HRMS (MALDI) 604.0460, 605.0500, 606.0435,
607.0467, 608.0423, 609.0453, 610.0395, 611.0432
([M þ Na]þ).
N-(2-(2-(N-Cyanomethylsulfideimino)ethylcarbamoyl)-
4-chloro-6-methylphenyl)-3-bromo-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 20e
White solid (45 % yield), mp 206–2088C. nmax(KBr)/cmꢀ1
3224, 3065, 2992, 2358, 2150, 1671, 1536, 1464, 1355, 1304,
1164, 1034, 962, 878, 806, 763. dH (400 MHz, [D6]DMSO)

Design and Activity of Anthranilic Diamides
1501
N-(2-(2-Methyl-2-(N-cyanomethylsulfoximino)
propylcarbamoyl)-4-bromo-6-methylphenyl)-3-
chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-
carboxamide 18b
8.37 (s, 1H, NH), 8.19 (d, J 8.0, 1H, pyridine-H), 7.62 (dd, J1 8.0,
J2 4.0, 1H, pyridine-H), 7.48 (s, 1H, Ar-H), 7.39 (s, 2H, Ar-H,
pyrazole-H), 4.22 (s, 2H, CH2), 3.47 (s, 3H, N(O)¼SCH3), 2.19
(s, 3H, Ar-CH3), 1.44 (s, 6H, CH3). dC (400 MHz, [D6]DMSO)
166.1, 162.4, 155.5, 148.5, 147.0, 139.2, 138.4, 131.0, 127.9,
126.8, 126.6, 125.8, 112.4, 110.5, 58.9, 52.2, 42.6, 26.9, 26.8,
17.6. HRMS (MALDI) 647.9930, 649.0066, 649.9937,
651.0013, 651.9921, 653.0014 ([M þ Na]þ). Anal. Calc. for
C23H22BrCl2N7O3S: C 44.03, H 3.53, N 15.63. Found: C 43.88,
H 3.69, N 15.58.
White granules (83% yield), mp 125–1278C. nmax(KBr)/cmꢀ1
3277, 3063, 2988, 2924, 2358, 2196, 1672, 1533, 1466, 1371,
1305, 1249, 1197, 1030, 976, 868, 813, 759. dH (400 MHz, [D6]
DMSO) 10.20 (s, 1H, NH), 8.50 (d, J 4.4, 1H, pyridine-H), 8.31
(s, 1H, NH), 8.18 (d, J 8.0, 1H, pyridine-H), 7.62–7.64 (m, 2H,
pyridine-H, Ar-H), 7.50 (s, 1H, Ar-H), 7.34 (s, 1H, pyrazole-H),
4.22 (s, 2H, CH2), 3.47 (s, 3H, N(O)¼SCH3), 2.19 (s, 3H,
Ar-CH3), 1.44 (s, 6H, CH3). dC (400 MHz, [D6]DMSO) 166.4,
156.1, 149.0, 147.6, 140.1, 139.7, 139.5, 139.3, 137.2, 134.5,
132.0, 129.1, 128.4, 127.2, 119.8, 112.9, 107.7, 59.4, 52.8, 43.2,
27.4, 27.3, 18.0. Anal. Calc. for C23H22BrCl2N7O3S: C 44.03,
H 3.53, N 15.63. Found: C 43.88, H 3.87, N 15.56.
N-(2-(2-(N-Cyanomethylsulfoximino)ethylcarbamoyl)-
4-chloro-6-methylphenyl)-3-chloro-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 21a
White granules (68 % yield), mp 112–1148C. nmax(KBr)/
cmꢀ1 3272, 3068, 3006, 2925, 2363, 2197, 1670, 1534, 1466,
1370, 1304, 1252, 1198, 1134, 1032, 974, 878, 812, 758. dH
(400 MHz, [D6]DMSO) 10.29 (s, 1H, NH), 8.75 (s, 1H, NH),
8.51 (d, J 4.4, 1H, pyridine-H), 8.18 (d, J 8.0, 1H, pyridine-H),
7.62 (dd, J1 8.0, J2 4.8, 1H, pyridine-H), 7.53 (s, 1H, Ar-H), 7.43
(s, 1H, Ar-H), 7.36 (s, 1H, pyrazole-H), 3.72–3.80 (m, 2H, CH2),
3.63–3.64 (m, 2H, CH2), 3.49 and 3.00 (s, 3H, N(O)¼SCH3),
2.20 (s, 3H, Ar-CH3). dC (400 MHz, [D6]DMSO) 166.1, 155.7,
148.4, 147.1, 139.6, 139.3, 139.1, 138.6, 135.1, 131.6, 131.4,
130.8, 127.9, 126.6, 125.5, 112.4, 107.3, 52.9, 40.6, 33.0,
17.6. HRMS (MALDI) 576.0149, 577.0191, 578.0119,
579.0157, 580.0088, 581.0127 ([M þ Na]þ). Anal. Calc. for
C21H18Cl3N7O3S: C 45.46, H 3.27, N 17.67. Found: C 45.28,
H 3.52, N 17.52.
N-(2-(2-Methyl-2-(N-cyanomethylsulfoximino)
propylcarbamoyl)-4-cyano-6-methylphenyl)-3-
chloro-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-
carboxamide 18c
Colourless granules (71 % yield), mp 135–1378C. nmax(KBr)/
cmꢀ1 3284, 3064, 2994, 2890, 2354, 2194, 2056, 1996, 1686,
1534, 1468, 1370, 1253, 1150, 1035, 978, 884, 813, 758. dH
(400 MHz, [D6]DMSO) 10.44 (s, 1H, NH), 8.51 (d, J 4.4, 1H,
pyridine-H), 8.42 (s, 1H, NH), 8.19 (d, J 8.0, 1H, pyridine-H),
7.91 (s, 1H, Ar-H), 7.78 (s, 1H, Ar-H), 7.63 (dd, J1 8.0, J2 4.8,
1H, pyridine-H), 7.38 (s, 1H, pyrazole-H), 4.22 (s, 2H, CH2),
3.48 (s, 3H, N(O)¼SCH3), 2.26 (s, 3H, Ar-CH3), 1.44 (s, 6H,
CH3). dC (400 MHz, [D6]DMSO) 166.9, 156.6, 149.5, 148.3,
140.8, 140.5, 139.9, 138.8, 138.0, 136.5, 136.3, 131.3, 129.1,
127.9, 119.3, 113.6, 110.4, 108.7, 60.2, 53.5, 43.9, 28.1, 28.0,
18.8. HRMS (MALDI) 595.0804, 596.0848, 597.0783,
598.0828, 599.0790, 600.0830 ([M þ Na]þ). Anal. Calc. for
C24H22Cl2N8O3S: C 50.27, H 3.87, N 19.54. Found: C 50.13,
H 4.02, N 19.44.
N-(2-(2-(N-Cyanomethylsulfoximino)ethylcarbamoyl)-
4-bromo-6-methylphenyl)-3-chloro-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 21b
White powder (60 % yield), mp 123–1258C. nmax(KBr)/cmꢀ1
3276, 3068, 3007, 2927, 2358, 2197, 1674, 1533, 1466, 1369,
1303, 1253, 1196, 1133, 1032, 972, 864, 810, 759. dH (400 MHz,
[D6]DMSO) 10.30 (s, 1H, NH), 8.76 (br, 1H, NH), 8.52 (s, 1H,
pyridine-H), 8.18 (d, J 8.0, 1H, pyridine-H), 7.65 (s, 2H,
pyridine-H, Ar-H), 7.55 (s, 1H, Ar-H), 7.36 (s, 1H, pyrazole-
H), 3.76–3.77 (m, 1H, HA-CH2), 3.64–3.65 (m, 1H, HB-CH2),
3.55–3.56 (m, 1H, HC-CH2), 3.50 and 3.00 (s, 3H, N(O)¼
SCH3), 3.24–3.26 (m, 1H, HD-CH2), 2.20 (s, 3H, Ar-CH3). dC
(400 MHz, [D6]DMSO) 166.2, 156.1, 149.0, 147.6, 140.1,
139.8, 139.6, 139.3, 135.0, 134.9, 132.4, 128.8, 128.4, 127.1,
119.7, 112.9, 107.8, 53.4, 53.3, 41.1, 33.7, 33.5, 18.0. Anal.
Calc. for C21H18BrCl2N7O3S: C 42.09, H 3.03, N 16.36. Found:
C 41.97, H 3.28, N 16.28.
N-(2-(2-Methyl-2-(N-cyanomethylsulfoximino)
propylcarbamoyl)-4-bromo-6-methylphenyl)-3-
bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-
carboxamide 18d
White powder (56 % yield), mp 136–1388C. nmax(KBr)/cmꢀ1
3272, 3063, 2989, 2923, 2365, 2196, 1669, 1533, 1465, 1353,
1302, 1248, 1196, 1029, 966, 867, 813, 758. dH (400 MHz, [D6]
DMSO) 10.18 (s, 1H, NH), 8.50 (d, J 4.4, 1H, pyridine-H), 8.31
(s, 1H, NH), 8.18 (d, J 8.0, 1H, pyridine-H), 7.62–7.64 (m, 2H,
pyridine-H, Ar-H), 7.50 (s, 1H, Ar-H), 7.40 (s, 1H, pyrazole-H),
4.22 (s, 2H, CH2), 3.47 (s, 3H, N(O)¼SCH3), 2.19 (s, 3H, Ar-
CH3), 1.43 (s, 6H, CH3). dC (400 MHz, [D6]DMSO) 166.0,
155.4, 148.4, 147.1, 139.2, 139.1, 138.8, 136.7, 134.0, 131.5,
128.6, 127.9, 126.8, 126.6, 119.3, 112.4, 110.6, 58.9, 52.3, 42.7,
26.9, 26.8, 17.5. Anal. Calc. for C23H22Br2ClN7O3S: C 41.12,
H 3.30, N 14.59. Found: C 40.94, H 3.62, N 14.29.
N-(2-(2-(N-Cyanomethylsulfoximino)ethylcarbamoyl)-
4-cyano-6-methylphenyl)-3-chloro-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 21c
White granules (52 % yield), mp 200–2028C. nmax(KBr)/
cmꢀ1 3273, 3072, 2987, 2930, 2358, 2199, 1648, 1535, 1465,
1368, 1304, 1263, 1136, 1076, 1034, 970, 894, 811, 760. dH
(400 MHz, [D6]DMSO) 10.53 (s, 1H, NH), 8.79 (br, 1H, NH),
8.51 (d, J 4.0, 1H, pyridine-H), 8.18 (d, J 8.0, 1H, pyridine-H),
7.93 (s, 1H, Ar-H), 7.82 (s, 1H, Ar-H), 7.62 (dd, J1 7.6, J2 4.8,
1H, pyridine-H), 7.38 (s, 1H, pyrazole-H), 3.73–3.80 (m, 1H,
HA-CH2), 3.62–3.65 (m, 1H, HB-CH2), 3.53–3.56 (m, 1H,
HC-CH2), 3.48 and 2.99 (s, 3H, N(O)¼SCH3), 3.23–3.26 (m,
1H, HD-CH2), 2.26 (s, 3H, Ar-CH3). dC (400 MHz, [D6]DMSO)
165.8, 155.6, 148.3, 147.2, 139.7, 139.3, 138.8, 137.6, 137.0,
N-(2-(2-Methyl-2-(N-cyanomethylsulfoximino)
propylcarbamoyl)-4-chloro-6-methylphenyl)-3-
bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-
carboxamide 18e
White solid (57 % yield), mp 131–1328C. nmax(KBr)/cmꢀ1
3283, 3065, 2987, 2926, 2358, 2196, 1673, 1534, 1464, 1353,
1303, 1249, 1197, 1135, 1029, 965, 878, 812, 757. dH (400 MHz,
[D6]DMSO) 10.29 (s, 1H, NH), 8.50 (d, J 4.0, 1H, pyridine-H),

1502
X. Hua et al.
135.6, 135.5, 129.8, 127.9, 126.7, 118.0, 112.4, 109.2,
107.6, 52.9, 52.8, 40.6, 33.3, 33.0, 17.6. HRMS (MALDI)
567.0493, 568.0533, 569.0464, 570.0505, 571.0436, 572.0461
([M þ Na]þ). Anal. Calc. for C22H18Cl2N8O3S: C 48.45, H 3.33,
N 20.55. Found: C 48.19, H 3.52, N 20.37.
least-squares to give the final r ¼ 0.0558 and wR ¼ 0.1287,
w ¼ 1/(s2(F02) þ (0.0653P)2 þ 0.0000P), where P ¼ (F02 þ 2F2c)/3
with (D/s)max ¼ 0.999 and S ¼ 1.067 using the SHELXL
program. The hydrogen atoms were located from a difference
Fourier map and refined isotropically. The corrections for
absorption is multi-scan, Tmin ¼ 0.6944, Tmax ¼ 0.7982.
N-(2-(2-(N-Cyanomethylsulfoximino)ethylcarbamoyl)-
4-bromo-6-methylphenyl)-3-bromo-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 21d
Insecticidal Activity Screening
Mythimna separata Screening
White solid (47 % yield), mp 206–2088C. nmax(KBr)/cmꢀ1
3226, 3068, 3008, 2925, 2355, 1660, 1540, 1461, 1300, 1195,
1133, 1035, 961, 865, 800, 757. dH (400 MHz, [D6]DMSO)
10.50 (s, 1H, NH), 8.84 (dd, J1 4.4, J2 2.4, 1H, pyridine-H), 8.51
(s, 1H, NH), 8.18 (d, J 7.2, 1H, pyridine-H), 7.93 (d, J 0.8, 1H,
Ar-H), 7.81 (d, J 0.8, 1H, Ar-H), 7.62 (dd, J1 6.4, J2 4.8, 1H,
pyridine-H), 7.42 (s, 1H, pyrazole-H), 3.74–3.77 (m, 1H,
HA-CH2), 3.62–3.64 (m, 1H, HB-CH2), 3.53–3.54 (m, 1H,
HC-CH2), 3.48 and 2.98 (s, 3H, N(O)¼SCH3), 3.23–3.25 (m,
1H, HD-CH2), 2.25 (s, 3H, Ar-CH3). dC (400 MHz, [D6]DMSO)
165.8, 155.5, 148.4, 147.1, 139.2, 138.9, 135.6, 134.4, 131.8,
128.3, 127.8, 126.8, 126.6, 119.3, 110.6, 52.7, 40.5, 33.2, 17.5.
Anal. Calc. for C21H18Br2ClN7O3S: C 39.18, H 2.82, N 15.23.
Found: C 38.99, H 3.11, N 15.15.
The activity of the target compounds against M. separata was
tested using the leaf-disk method.[33,34] Fresh corn leaves were
dipped for 10 s in the test acetone solution (5 mg mLꢀ1), which
was diluted with 200 mg mLꢀ1 of mother solution containing
3.0 mg of target compound and 15 mL acetone. After air-drying
to evaporate the acetone and water, the treated leaves were cut
into small pieces and placed in petri dishes with a 10-cm
diameter. Thirty individual M. separata were transferred to
each petri dish. The petri dishes were finally secured with rubber
bands and placed in a standard cultivation room at 258C for 72 h
with 80 % humidity. The percentage mortality was evaluated
according to the corresponding blank controls, whereby cyan-
traniliprole was used as a positive control and water as a
negative control. Each experiment was performed in triplicate.
Target compound concentrations of 1 mg mLꢀ1 and 0.1 mg mLꢀ1
were tested in the same manner. The insects displaying no
reaction when touched by a brush pen were regarded as dead.
N-(2-(2-(N-Cyanomethylsulfoximino)ethylcarbamoyl)-
4-chloro-6-methylphenyl)-3-bromo-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 21e
White solid (55 % yield), mp 142–1448C. nmax(KBr)/cmꢀ1
3267, 3068, 3007, 2924, 2357, 2197, 1672, 1533, 1466, 1354,
1302, 1251, 1197, 1132, 1033, 965, 877, 811, 757. dH (400 MHz,
CDCl3) 9.61 (s, 1H, NH), 8.45 (dd, J1 4.8, J2 1.6, 1H, pyridine-
H), 7.88 (dd, J1 8.0, J2 1.2, 1H, pyridine-H), 7.40 (dd, J1 8.0, J2
4.8, 1H, pyridine-H), 7.31 (s, 1H, Ar-H), 7.22 (s, 1H, Ar-H), 7.09
(s, 1H, pyrazole-H), 3.89–3.93 (m, 2H, CH2), 3.60–3.64 (m, 2H,
CH2), 3.28 (s, 3H, N(O)¼SCH3), 2.19 (s, 3H, Ar-CH3). HRMS
(MALDI) 619.9640, 620.9679, 621.9609, 622.9645, 623.9592,
624.9626, 625.9574, 626.9619 ([M þ Na]þ). Anal. Calc. for
C21H18BrCl2N7O3S: C 42.09, H 3.03, N 16.36. Found: C 41.91,
H 3.41, N 16.26.
Plutella xylostella Screening
The insecticidal activity of the synthesized compounds
against P. xylostella was tested using the leaf-dip method.[35–38]
Fresh cabbage discsꢀ(71 cm ꢂ 2 cm) were dipped in the test water
solutions (10 mg mL ) for 10 s. The test water solutions were
diluted with 200 mg mLꢀ1 of mother solution containing target
compounds (2.0 mg), DMF (0.5 mL), and water with 9.5 mL
Tween 80 (0.2 %). After drying in air, the discs were placed
individually in glass tubes (length 10 cm). Ten larvae of second-
instar P. xylostella were carefully transferred to the glass tubes,
which were then kept in a chamber at 20 ꢃ 18C and relative
humidity of 60 %. Cyantraniliprole was used as a positive
control, and each experiment was performed in triplicate.
Mortality levels were determined after 72 h. Leaves treated with
water served as a negative control. The insects displaying no
reaction when touched by a brush pen were regarded as dead.
X-ray Diffraction Analysis
A crystal of the target compound 16e was extracted in ethyl
acetate and petroleum ether. A colourless crystal of 16e with
dimensions of 0.20 ꢂ 0.18 ꢂ 0.12 mm was selected and moun-
ted on a glass fibre for X-ray diffraction analysis. All measure-
ments were made on a Rigaku Saturn 724 CCD diffractometre
Supplementary Material
The Supplementary Material contains crystal data for compound
16e and characterisation data of all target compounds, including
IR, 1H and 13C NMR, and HRMS. It is available on the Journal’s
website.
´
˚
MoKa radiation (l ¼ 0.71073 A). The data were collected at a
temperature of 113(2) K to a maximum y value of 27.888. The
molecular formula is C22H22BrCl2N5O2S and the formula
weight is 571.32. The crystal is a monoclinic system, space
˚
group P2(1)/c, with unit cell parameters: a ¼ 9.498(2) A, b ¼
Acknowledgement
´
˚
3
˚
˚
11.107(2) A, c ¼ 23.921(5) A, V ¼ 2504.9(9) A , Z ¼ 4, density
(calculated) ¼ 1.515 g cmꢀ3, and linear absorption coeffi-
cient 1.967 mmꢀ1. In total, 25834 integrated reflections were
collected, reducing to a dataset of 5981 unique with
Rint ¼ 0.0566, and completeness of data (to y ¼ 27.888) of
99.9 %. Data were collected and processed using CrystalClear
(Rigaku). An empirical absorption correction was applied using
CrystalClear (Rigaku). The structure was resolved by direct
methods with the SHELXL-97 program.[32] Refinements were
done by the full-matrix least-squares on F2 with SHELXL-97.
All the non-H atoms were refined anisotropically by full-matrix
This work was supported, in part, by the National Natural Science Foun-
dation of China (21372132).
References
[1] M. Fill, J. A. Copello, Physiol. Rev. 2002, 82, 893.
[2] L. Zhu, X. W. Zhong, S. R. Wayne Chen, N. Banavali, Z. Liu, J. Biol.
Chem. 2013, 288, 903. doi:10.1074/JBC.M112.429670
[3] S. L. Hamilton, Cell Calcium 2005, 38, 253. doi:10.1016/J.CECA.
2005.06.037
[4] L. Kimlicka, F. Petegem, Sci. China C Life Sci. 2011, 54, 712.
doi:10.1007/S11427-011-4198-2

Design and Activity of Anthranilic Diamides
1503
[5] A. F. Dulhunty, Clin. Exp. Pharmacol. Physiol. 2006, 33, 763.
doi:10.1111/J.1440-1681.2006.04441.X
[6] G. P. Lahm, D. Cordova, J. D. Barry, Bioorg. Med. Chem. 2009, 17,
4127. doi:10.1016/J.BMC.2009.01.018
[7] K. A. Hughes, G. P. Lahm, T. P. Selby, T. M. Stevenson, W. O. Patent
2004067528 A1 2004.
[20] T. C. Sparks, G. B. Watson, M. R. Michael, C. X. Geng, J. M. Babcock,
J. D. Thomas, Pestic. Biochem. Physiol. 2013, 107, 1. doi:10.1016/
J.PESTBP.2013.05.014
[21] P. Cutler, R. Slater, A. J. F. Edmunds, P. Maienfisch, R. G. Hall, F. G.
P. Earley, T. Pitterna, S. Pal, V. L. Paul, J. Goodchild, Pest Manag. Sci.
2013, 69, 607. doi:10.1002/PS.3413
[8] G. P. Lahm, T. P. Selby, T. M. Stevenson, W. O. Patent 2003015519
A1 2003.
[22] C. Gnamm, A. Jeanguenat, A. C. Dutton, C. Grimm, D. P. Kloer, A. J.
Crossthwaite, Bioorg. Med. Chem. Lett. 2012, 22, 3800. doi:10.1016/
J.BMCL.2012.03.106
[23] H. Blaschke, S. Pazenok, W. O. Patent 2007022901 A1 2007.
[24] J. H. Choi, M. H. Kim, S. H. Kim, C. H. Park, B. Y. Joe, K. Chun, B. K.
Oh, D. Ryu, R. Won, J. S. Park, K. H. Kim, H. C. Lee, W. O. Patent
2009061131 A2 2009.
[9] M. S. Tohnishi, H. K. Nakao, E. H. Kohno, T. T. Nishida, T. I. Furuya,
T. K. Shimizu, A. H. Seo, K. K. Sakata, S. K. Fujioka, H. I. Kanno,
E. P. Patent 1006107 2010.
[10] B. S. Chai, X. M. He, J. F. Wang, Z. N. Li, C. L. Liu, Agrochemicals
2010, 49, 167. [In Chinese]
[11] S. Tiwari, L. L. Stelinski, Pest Manag. Sci. 2013, 69, 1066.
doi:10.1002/PS.3468
[25] Z. J. Ye, L. N. Shi, X. S. Shao, X. Y. Xu, Z. P. Xu, Z. Li, J. Agric. Food
Chem. 2013, 61, 312. doi:10.1021/JF3044132
[12] L. A. Teixeira, J. T. Andaloro, Pestic. Biochem. Physiol. 2013, 106, 76.
doi:10.1016/J.PESTBP.2013.01.010
[26] F. F. Jian, H. L. Xiao, P. S. Zhao, Chinese J. Struct. Chem. 2004,
23, 486.
[13] D. B. Sattelle, D. Cordova, T. R. Cheek, Invert. Neurosci. 2008, 8, 107.
doi:10.1007/S10158-008-0076-4
[27] J. F. Zhang, J. Y. Xu, B. L. Wang, Y. X. Li, L. X. Xiong, Y. Q. Li,
Y. Ma, Z. M. Li, J. Agric. Food Chem. 2012, 60, 7565. doi:10.1021/
JF302446C
[28] K. A. Hughes, G. P. Lahm, T. P. Selby, W. O. Patent 2004046129 A2
2004.
[14] Y. M. Zhu, X. P. Huang, R. Rogers, M. R. Loso, G. Whiteker, J.
Daeuble, B. Nugent, In Proceedings of the 242nd ACS National
Meeting & Exposition, Denver, CO, USA, 28 August–1 September
2011. 2011; ORGN-326 (American Chemical Society, Washington,
D. C.).
[29] G. P. Lahm, T. P. Selby, W. O. Patent 2005118552 A2 2005.
[30] P. J. Montoya-Pelaez, Y.-S. Uh, C. Lata, M. P. Thompson, R. P.
Lemieux, C. M. Crudden, J. Org. Chem. 2006, 71, 5921. doi:10.1021/
JO060553D
[31] M. R. Loso, B. M. Nugent, R. B. Rogers, Y. M. Zhu, J. M. Renga, V. B.
Hegde, J. J. Demark, W. O. Patent 2007095229 A2 2007.
[32] SHELXTL ver. 5.0 (Ed G. M. Sheldrick) 2001 (University of Go¨ttingen:
Go¨ttingen, Germany).
[15] C. Longhurst, J. M. Babcock, I. Denholm, K. Gorman, J. D. Thomas,
T. C. Sparks, Pest Manag. Sci. 2013, 69, 809. doi:10.1002/PS.3439
[16] T. C. Sparks, M. R. Loso, G. B. Watson, J. M. Babcock, V. J. Kramer,
Y. M. Zhu, B. M. Nugent, J. D. Thomas, in Modern Crop Protection
Compounds, 2nd edn (Eds W. Kraemer, U. Schirmer, P. Jeschke) 2012,
Vol. 3, pp. 1226–1237 (VCH Verlagsgesellschaft: Weinheim).
[17] J. M. Babcock, C. B. Gerwick, J. X. Huang, M. R. Loso, G. Nakamura,
S. P. Nolting, R. B. Rogers, T. C. Sparks, J. Thomas, G. B. Watson,
Pest Manag. Sci. 2011, 67, 328. doi:10.1002/PS.2069
[18] R. J. Rasoulpour, J. Reza, R. G. Ellis-Hutchings, C. Terry, N. S. Millar,
C. L. Zablotny, A. Gibb, V. Marshall, T. Collins, E. W. Carney,
R. Billington, Toxicol. Sci. 2012, 127, 522. doi:10.1093/TOXSCI/
KFS118
[33] H. Xu, J. L. Zhang, Bioorg. Med. Chem. Lett. 2011, 21, 5177.
doi:10.1016/J.BMCL.2011.07.075
[34] J. Cui, M. L. Li, M. S. Yuan, J. Pestic. Sci. 2012, 37, 95. doi:10.1584/
JPESTICS.G11-47
[35] G. Goudar, A. R. Alagawadi, J. Biopestic. 2012, 5, 208.
[36] Q. Feng, Z. L. Liu, L. X. Xiong, M. Z. Wang, Y. Q. Li, Z. M. Li,
J. Agric. Food Chem. 2010, 58, 12327. doi:10.1021/JF102842R.
[37] J. Wu, B. A. Song, D. Y. Hu, M. Yue, S. Yang, Pest Manag. Sci. 2012,
68, 801. doi:10.1002/PS.2329
[19] Y. M. Zhu, M. R. Loso, G. B. Watson, T. C. Sparks, R. B. Rogers, J. X.
Huang, B. C. Gerwick, J. M. Babcock, D. Kelley, V. B. Hegde, B. M.
Nugent, J. M. Renga, J. Agric. Food Chem. 2011, 59, 2950.
doi:10.1021/JF102765X
[38] C. P. Moraes, L. A. Foerster, Cienc. Rural 2012, 42, 1335. doi:10.1590/
S0103-84782012000800001