Synthesis and pesticidal activities of novel anthranilic diamides containing pyridylpyrazole and iminodithiocarbamate or thiosemicarbazone motifs

Article abstract of DOI:10.1080/10426507.2018.1487433

A series of novel anthranilic diamide derivatives containing pyridylpyrazole and iminodithiocarbamate or thiosemicarbazone motifs were synthesized via multi-step reactions. The structures of seven title compounds (methyl 2-(2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamido)-5-chloro-3- methylbenzylidene)hydrazinecarbodithioate 7 and 3-bromo-N-(2-((2-substitutedcarbamothioylhydrazono)methyl)-4-chloro-6-methylphenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide 8a-8f) were confirmed by melting points, IR, ¹H NMR, ¹³C NMR, and HRMS. The bioassays showed that some of the compounds exhibited modest insecticidal activities against oriental armyworm (Mythimna separata Walker), particularly, compound 8b (3-bromo-N-(4-chloro-2-methyl-6-((2-(methylcarbamothioyl)hydrazono)methyl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide) held 100% and 30% larvicidal activity at the concentration of 25 mg/L and 10 mg/L, respectively. In addition, several compounds displayed favorable fungicidal activities against Alternaria solani Sorauer and Physalospora piricola at 50 μg/mL, and were comparable with the controls Chlorothalonil and Triadimefon. The results in this paper will provide important information for further research and development of sulfur-containing heterocyclic agrochemicals.

Full text of DOI:10.1080/10426507.2018.1487433

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Synthesis and pesticidal activities of novel
anthranilic diamides containing pyridylpyrazole
and iminodithiocarbamate or thiosemicarbazone
motifs
Qiao-Xia Liu, Bao-Lei Wang, Ming-Zhen Mao, Li-Xia Xiong & Zheng-Ming Li
To cite this article: Qiao-Xia Liu, Bao-Lei Wang, Ming-Zhen Mao, Li-Xia Xiong & Zheng-Ming Li
(2018): Synthesis and pesticidal activities of novel anthranilic diamides containing pyridylpyrazole
and iminodithiocarbamate or thiosemicarbazone motifs, Phosphorus, Sulfur, and Silicon and the
Related Elements, DOI: 10.1080/10426507.2018.1487433
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PHOSPHORUS, SULFUR, AND SILICON
https://doi.org/10.1080/10426507.2018.1487433
Synthesis and pesticidal activities of novel anthranilic diamides containing
pyridylpyrazole and iminodithiocarbamate or thiosemicarbazone motifs
ꢀ
Qiao-Xia Liu, Bao-Lei Wang , Ming-Zhen Mao, Li-Xia Xiong, and Zheng-Ming Li
State Key Laboratory of Elemento-Organic Chemistry Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College
of Chemistry, Nankai University, Tianjin, China
ABSTRACT
ARTICLE HISTORY
Received 22 January 2018
Accepted 7 June 2018
A series of novel anthranilic diamide derivatives containing pyridylpyrazole and iminodithiocarbamate
or thiosemicarbazone motifs were synthesized via multi-step reactions. The structures of seven title
compounds (methyl 2-(2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamido)-5-chloro-3-
methylbenzylidene)hydrazinecarbodithioate 7 and 3-bromo-N-(2-((2-substitutedcarbamothioylhydrazo-
no)methyl)-4-chloro-6-methylphenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide 8a-8f) were
KEYWORDS
Anthranilic diamides;
pyridylpyrazole; thiosemicar-
bazone; pesticidal activities
1
confirmed by melting points, IR, H NMR, 13C NMR, and HRMS. The bioassays showed that some of
the compounds exhibited modest insecticidal activities against oriental armyworm (Mythimna sepa-
rata Walker), particularly, compound 8b (3-bromo-N-(4-chloro-2-methyl-6-((2-(methylcarbamothioyl)
hydrazono)methyl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide) held 100% and 30%
larvicidal activity at the concentration of 25 mg/L and 10 mg/L, respectively. In addition, several com-
pounds displayed favorable fungicidal activities against Alternaria solani Sorauer and Physalospora
piricola at 50 lg/mL, and were comparable with the controls Chlorothalonil and Triadimefon. The
results in this paper will provide important information for further research and development of sul-
fur-containing heterocyclic agrochemicals.
GRAPHICAL ABSTRACT
Introduction
DuPont’s two new insecticides that target at insect ryanodine
receptor are anthranic diamide compounds both containing
a N-pyridylpyrazole moiety.[11,12] In addition, an amide
bridge modification strategy based on such N-((alkylcarba-
moyl)aryl)-pyridylpyrazole carboxamide structure has been
proven to be an efficient way to yield remarkable larvicidal
acylthiourea derivatives against oriental armyworm, beet
armyworm and diamondback moth in our previous
reports.[9,10] Besides the excellent insecticidal properties of
this kind of compounds, some N-pyridylpyrazole derivatives
were also found have promising fungicidal activities towards
a variety of crop fungal diseases.[13,14] At present, the follow
up research based on such pyridylpyrazole-containing
agrochemicals has become a hot topic in the pesticide
It is known that thiocarbonyl (>C¼S) -containing
compounds such as iminodithiocarbamate and their
thiosemicarbazone derivatives play very important roles
because of their versatile and useful properties, and many of
them were reported to be used as antibacterial, antioxidant,
anticancer, fungicidal and insecticidal agents, and also
friction modifier.[1–10] They are significant components of
various functional sulfur-containing organic compounds.
Furthermore, as one kind of nitrogen-containing bihetero-
cylic compounds, N-pyridylpyrazole derivatives have drawn
considerable attention in recent years owing to their
outstanding biological activities in pesticide chemistry.[11,12]
For instance, chlorantraniliprole and cyantraniliprole, chemistry area.[15]
CONTACT Bao-Lei Wang
wangbaolei@126.com
State Key Laboratory of Elemento-Organic Chemistry Collaborative Innovation Center of Chemical Science
and Engineering (Tianjin), College of Chemistry, Nankai University, Tianjin 300071, China.
Supplemental data for this article can be accessed at https://doi.org/10.1080/10426507.2018.1487433.
ß 2018 Taylor & Francis Group, LLC

2
Q.-X. LIU ET AL.
Figure 1. The design of the title compounds.
Taking into account all those information mentioned nucleophilic reagent with large steric hindrance group con-
above, in this paper a series of novel anthranilic diamide necting the NH2 group, can even hardly undergo this reaction.
In addition, some other attempts by reacting 7 with some
high steric hindrance amines e.g. 2,4,6-trimethylaniline, 4,6-
dimethyl-2-(piperazine-1-yl)pyrimidine in ethanol under reflux
were also unsuccessful. These results proved that the steric
hindrance factor of the nucleophilic reagent – substituted
amine makes great influence on this nucleophilic reaction.
The title compounds 7 and 8a-8f were identified by
melting point, IR, 1 H NMR, 13C NMR and HRMS. Take
compound 8d as an example: in 1 H NMR of 8d, the active
proton signals of -CONH- and -C(¼S)NH- in amide and
thiourea moieties were observed at d 10.46 and d 11.52, d
8.20, respectively. These results were consistent with those of
in literatures.[9,18] The imine -N¼CH- proton and the proton
in pyrazole ring appeared at d 8.11 and d 7.43 as a singlet,
respectively. The resonance signal of CH3 protons neighbor-
ing to the benzene ring were observed at d 2.14, in accord
with the corresponding data in literatures.[9,18] The resonance
signals of CH3 and CH protons in isopropyl group
(CH(CH3)2) showed up at d 1.22 and d 4.51–4.56, as doublet
and multiplet, respectively. Moreover, the proton signals in
pyridine and benzene rings appeared at d 8.51, d 8.24, d 8.17,
d 7.62 and d 7.42. In the 13C NMR spectrum of 8d, the typ-
ical carbon resonances at d 176.2 and d 156.6 were indicative
of thiocarbonyl group (C¼S) and carbonyl group (C¼O),
respectively. The carbon signal in -N¼CH- group appeared at
d 139.8. The carbon signals for aromatic rings (benzene, pyri-
dine and pyrazole) were observed at d 111.3-148.7. The iso-
propyl signals appeared at d 46.3 and d 22.3 for CH carbon
and CH3 carbon, respectively. The carbon signal of CH3 in
benzene ring showed up at d 17.9. In IR spectrum of 8d, it
showed absorption bands at 3351.36cmꢁ1 and 3140.73cmꢁ1
assigned to N-H stretching. The strong absorption band at
1686.12cmꢁ1 can be ascribed to the C¼O stretching. The
stretching vibration ꢀ(C¼N) showed up at 1528.37 cmꢁ1. The
absorption band at 1464.76cmꢁ1 is due to the vibration of
aromatic ring skeleton. In addition, the characteristic stretch-
derivatives containing pyridylpyrazole and iminodithiocarba-
mate or thiosemicarbazone motifs as shown in Figure 1 were
designed and synthesized. The pesticidal activities of the
target compounds against oriental armyworm (Mythimna
separata Walker) and some crop fungi were investigated.
Results and discussion
Synthesis and structural characterization
As shown in Scheme 1, referring to the procedure
reported by Klayman et al.,[16] the key intermediate methyl
hydrazinecarbodithioate 1 was prepared from carbon disul-
fide as starting material via hydrazinolysis and iodomethane
nucleophilic substitution successively.
Following the literature method,[17] the intermediate
2-amino-5-chloro-3-methylbenzaldehyde 4 (Scheme 2) was
synthesized from LiAlH4-reduction of 2-amino-5-chloro-3-
methylbenzoic acid 2 and MnO2-oxidation of the generated
alcohol product. As shown in Scheme 3, the intermediate
aldehyde (4) was treated with pyridylpyrazole acid chloride
that was derived from the corresponding acid 5[11] to give
the formyl-containing pyridylpyrazole amide compound 6 in
good yield. Compound 6 and thiosemicarbazide underwent
an addition-condensation in boiling ethanol giving rise to
the title compound 8a in high yield (80.6%); treating
compound 6 with methyl hydrazinecarbodithioate 1 under
similar conditions yielded title compound 7 successfully.
When refluxing 7 with various nucleophilic reagents –
primary amines in ethanol, the MeS- group in compound 7
can be smoothly substituted to give the corresponding title
compounds 8b-8f with >40% yield. It was found that the
yields for generating 8e and 8f that have n-Pr and n-Bu
groups respectively were higher than those for 8c and 8d that
contain c-Pr and i-Pr groups respectively. This indicates the
steric hindrance around the N atom in amine with branched
chain structure (i. e. cyclopropyl or isopropyl) will be an
unfavorable factor for the substitution of MeS group to RNH
group (Scheme 3), probably owing to the relatively unsmooth
attacking of the amine N atom to thiocarbonyl (>C¼S) under
ing vibration ꢀ(C¼S) appeared at 1239–1397cmꢁ1
.
Pesticidal activities
branched chain group influence. Furthermore, this situation As shown in Table S1 (Supplemental Materials), in a prelim-
can be well reflected by the fact that tert-butylamine, as a inary bioassay at the test concentration of 200 mg/L, all the

PHOSPHORUS, SULFUR, AND SILICON
3
CS
Scheme 1. Synthetic route to intermediate 1.
Scheme 2. Synthetic route to intermediate 4.
Br
N
Br
N
CHO
H
N
DMF,
,
(1) (COCl)2
HOOC
r.t.
1
CH2Cl2
,
N
N
Cl
Cl
5 h
EtOH, reflux
4
,
(2) Pyridine,
CH2Cl2
O
N
Cl
Me
N
0 oC to
r.t.
5
6
S
S
Br
NH
S
2NHCNH2
Br
N
EtOH, reflux
S
NH
N
HN NH
N
O
8a
Cl
N
O
Me
N
R
R-NH2
EtOH, reflux
N
Cl
NH
Me
:
=
=
=
=
=
8a
R
R
R
R
R
H;
NH
Me
N
:
8b
Me;
N
c
:
8c
-Pr;
:
8d
i-Pr;
Cl
Cl
n
:
8e
-Pr;
n
:
=
8f
R
-Bu
7
8b-8f
Scheme 3. Synthetic route of compounds 7 and 8a-8f.
title compounds 7 and 8a-8f, like the insecticide control better fungicidal activity than that of Chlorothalonil and
Chlorantraniliprole, exhibited 100% larvicidal activities
against oriental armyworm (Mythimna separata Walker). At
lower concentration, e. g. 50 mg/L, the lethality rates of 8b,
8c, 8d, 8e and 8f against oriental armyworm were 100%,
60%, 100%, 60% and 100%, respectively. In particular, 8b
and 8d possessed 30% and 10% larvicidal activities even at
the concentration of 10 mg/L. In analyzing the structure-
activity relationship (SAR) of this series of compounds, it
was found that iminothiourea-containing compounds 8
showed better insecticidal activity than hydrazinecarbodi-
thioate 7, and the electron-donating group beared at thiourea
moiety of 8 is favorable for the insectividal activity towards
oriental armyworm. For the substituent R, it showed insecti-
cidal activity trend of Me > i-Pr > n-Bu > n-Pr, c-Pr > H. It
is worthy of note that all the title compounds, hydrazinecar-
bodithioate 7 and iminothiourea-containing compounds 8,
exhibited higher insecticidal activities against oriental
armyworm than that of their precusor – intermediate 6
(Table S1), which indicates the introduction of these sulfur-
containg groups to the formyl-containing pyridylpyrazole
amide precusor let to a promotion of the insecticidal activity.
In addition, several compounds also exhibited good in
vitro fungicidal activities against Alternaria solani Sorauer
and Physalospora piricola at the test concentration of
50 lg/mL (Table S2). For instance, compound 8c displayed
an inhibitory rate of 63% against Alternaria solani
Sorauer, which is higher than that of fungicide controls
Triadimefon.
Experimental
Materials and instruments
The melting points were determined on an X-4 binocular
microscope melting point apparatus (Beijing Tech
Instruments Co., Beijing, China) and were uncorrected.
Infrared spectra were recorded on a Nicolet MAGNA-560
spectrophotometer as KBr tablets. NMR spectra were
recorded at 300 MHz using a Bruker AC-P300 spectrometer
or 400 MHz using a Bruker AV 400 spectrometer (Bruker
Co., Switzerland) in DMSO-d6 or (CD3)2CO solution with
tetramethylsilane as the internal standard, and chemical shift
values (d) were given in ppm. High-resolution mass
spectrometry (HRMS) data were obtained on a Varian QFT-
ESI instrument. Reagents were all analytically or chemically
pure. All solvents and liquid reagents dried by standard
methods in advance and distilled before use. The
Supplemental Materials provides sample 1 H and 13C NMR
spectra of the products 8.
General procedure
The intermediate methyl hydrazinecarbodithioate
1
(Scheme 1) was synthesized according to procedure reported
Chlorothalonil and Triadimefon; compound 8d whose inhib- by Klayman et al.[16] The intermediate 2-amino-5-chloro-3-
ition rate towards Physalospora piricola was 72%, showed methylbenzaldehyde 4 (Scheme 2) was synthesized from

4
Q.-X. LIU ET AL.
2-amino-5-chloro-3-methylbenzoic acid
2
according to (101 MHz, DMSO-d6) d 199.5 (C¼S), 156.6 (C¼O), 148.6
procedure reported by Mao et al.[17] The synthetic route for (Pyridyl-C), 147.7 (Pyridyl-C), 142.2 (CH¼N), 139.9
the title compounds 7 and 8a-8f is shown in Scheme 3.
(Pyrazole-C), 139.9 (Ph-C), 139.4 (Pyridyl-C), 133.9 (Ph-C),
132.9 (Ph-C), 132.7 (Ph-C), 132.3 (Ph-C), 128.1 (Pyridyl-C),
127.4 (Pyrazole-C), 127.2 (Ph-C), 122.5 (Pyridyl-C), 111.4
(Pyrazole-C), 17.9 (SCH3), 17.3 (Ar-CH3); HRMS calcd for
C19H15BrCl2N6OS2 556.9387 found 556.9362 ([M þ H]þ).
3-Bromo-N-(4-chloro-2-formyl-6-methylphenyl)-1-(3-
chloropyridin-2-yl)-1H-pyrazole-5-carboxamide 6
To a suspension of 3-bromo-1-(3-chloropyridin-2-yl)-1H-
pyrazole-5-carboxylic acid 5 (1 mmol) in dichloromethane
(CH2Cl2, 25 mL), oxalyl chloride (2 mmol) and two drops of
DMF were added successively under vigorous stirring. After
being stirred at room temperature for 5 h, the mixture was
3-Bromo-N-(2-((2-carbamothioylhydrazono)methyl)-4-
chloro-6-methylphenyl)-1-(3-chloropyridin-2-yl)-1H-
pyrazole-5-carboxamide 8a
evaporated to dryness in vacuo to afford the crude pyridyl- To a solution of intermediate 6 (1 mmol) in 15 mL of
pyrazole acid chloride as a yellow powder, which was used ethanol, thiosemicarbazide (1.1 mmol) was added at room
to the next step directly without further purification.
temperature. The reaction mixture was refluxed for 6 h and
The crude acid chloride was dissolved in CH2Cl2 (15 mL) cooled down. The solvent was evaporated under reduced
and the solution was added dropwise to a stirred mixture of pressure and the residue was subjected to column chroma-
intermediate 4 (1 mmol), pyridine (1 mmol) and CH2Cl2 tography on silica gel with petroleum-ethyl acetate (V/V,
(20 mL) at 0 ꢂC. After completion of addition, the reaction 6/1) as solvents to afford compound 8a as a pale yellow
mixture was warmed to room temperature and further solid. Yield 80.6%, mp 236-238 ꢂC; IR, ꢀ/cmꢁ1: 3386.76
stirred for 6 h, then washed with 1 mol/L hydrochloric acid, (N-H), 3170.63 (N-H), 1699.94 (C¼O), 1525.27 (C¼N),
saturated sodium bicarbonate solution and brine succes- 1464.17 (C¼C), 1286.36 (C¼S); 1 H NMR (300 MHz,
sively. The organic layer separated was dried over anhydrous Acetone-d6) d 10.51 (s, 1 H, CSNH), 9.56 (s, 1 H, CONH),
MgSO4, the solvent was removed under reduced pressure 8.39 (d, J ¼ 4.5 Hz, 1 H, Pyridyl-H) , 8.22 (s, 1 H, Ar-H),
and the residue was subjected to column chromatography 7.96 (d, J ¼ 8.1 Hz, 1 H, Pyridyl-H), 7.90 (s, 1 H, CH¼N),
on silica gel with petroleum-ethyl acetate (v/v, 6/1) as the 7.46 (dd, J ¼ 7.7, 5.0 Hz, 1 H, Pyridyl-H), 7.25 (s, 1 H, Ar-H),
solvents to afford compound 6 as a white solid. Yield 70.1%, 7.22 (s, 1 H, Pyrazole-H), 2.14 (s, 3 H, Ar-CH3); 13C NMR
mp 158-160 ꢂC; 1 H NMR (400 MHz, DMSO-d6) d 10.75 (s, (101 MHz, DMSO-d6) d 178.5 (C¼S), 156.6 (C¼O), 148.7
1H,CONH), 9.97 (s, 1 H, CHO), 8.47-8.54 (m, 1 H, Pyridine- (Pyridyl-C), 147.6 (Pyridyl-C), 139.8 (CH¼N), 139.5
H), 8.21 (d, J ¼ 8.1 Hz, 1 H, Pyridine-H), 7.75 (d, J ¼ 2.1 Hz, (Pyrazole-C), 139.3 (Ph-C), 138.1 (Pyridyl-C), 133.8 (Ph-C),
1H,Ar-H), 7.62-7.65 (m, 2 H, Ar-H, Pyridine-H), 7.49 133.2 (Ph-C), 132.8 (Ph-C), 131.3 (Ph-C), 128.1 (Pyridyl-C),
(s, 1 H, Pyrazole-H), 2.26 (s, 3 H, Ar-CH3); 13C NMR 127.3 (Pyrazole-C), 127.1 (Ph-C), 123.4 (Pyridyl-C), 111.3
(101 MHz, DMSO-d6) d 189.4 (HC¼O), 156.7 (NHC¼O), (Pyrazole-C), 17.9 (Ar-CH3); HRMS calcd for C18H14BrCl2
148.0 (Pyridyl-C), 147.2 (Pyridyl-C), 139.5 (Pyrazole-C), N7OS 525.9619 found 525.9603 ([M þ H]þ).
139.2 (Ph-C), 139.1 (Pyridyl-C), 135.4 (Ph-C), 135.2 (Ph-C),
133.2 (Ph-C), 132.1 (Ph-C), 126.9 (Pyridyl-C), 126.7
(Pyrazole-C), 126.6 (Ph-C), 125.1 (Pyridyl-C), 111.2
(Pyrazole-C), 17.1 (Ar-CH3).
3-Bromo-N-(4-chloro-2-methyl-6-((2-
(methylcarbamothioyl)hydrazono)methyl)phenyl)-1-(3-
chloropyridin-2-yl)-1H-pyrazole-5-carboxamide 8b
A mixture of intermediate 7 (1 mmol), methylamine (40%
Methyl 2-(2-(3-bromo-1-(3-chloropyridin-2-yl)-1H-
aqueous solution, 2 mmol) and ethanol (15 mL) was refluxed
pyrazole-5-carboxamido)-5-chloro-3-
for 12 h with TLC monitoring. After cooling to room tem-
methylbenzylidene)hydrazinecarbodithioate 7
perature, the solvent was evaporated under reduced pressure
A mixture of intermediate 6 (0.5 mmol), methyl hydrazine- and the residue was subjected to column chromatography
carbodithioate 1 (0.5 mmol) and ethanol (15 mL) was on silica gel with petroleum-ethyl acetate (V/V, 5/1) as sol-
refluxed for 5 h. After cooling to room temperature, the solv- vents to give compound 8 b as a pale yellow solid. Yield
ent was evaporated under reduced pressure and the residue 40.2%, mp 258-260 ꢂC; IR, ꢀ/cmꢁ1: 3366.49 (N-H), 3158.52
was subjected to column chromatography on silica gel with (N-H), 1680.55 (C¼O), 1526.80 (C¼N), 1459.76 (C¼C),
petroleum-ethyl acetate (V/V, 6/1) as solvents to give com- 1248.61 (C¼S); 1 H NMR (300 MHz, DMSO-d6) d 11.58 (s,
pound 7 as a pale yellow solid. Yield 53.6%, mp 204-206 ꢂC; 1 H, CSNH), 10.47 (s, 1 H, CONH), 8.65 (d, J ¼ 4.6 Hz, 1 H,
IR, ꢀ/cmꢁ1: 3214.74 (N-H), 3133.24 (N-H), 1654.25 (C¼O), Pyridyl-H), 8.46-8.55 (m, 1 H, Pyridyl-H), 8.16 (3 H, Ar-H,
1533.84 (C¼N), 1462.25 (C¼C), 1292.79 (C¼S); 1 H NMR Ar-H,CSNH), 7.60 (dd, J ¼ 8.1, 4.7 Hz, 1 H, Pyridyl-H) , 7.41
(400 MHz, DMSO-d6) d 13.38 (s, 1 H, CSNH), 10.54 (s, 1 H, (s, 1 H, N¼CH), 7.39 (s, 1 H, Pyrazole-H) , 3.00 (d,
CONH), 8.51 (d, J ¼ 4.6 Hz, 1 H, Pyridyl-H), 8.32 (s, 1 H, J ¼ 4.4 Hz, 3 H, N-CH3), 2.13 (s, 3 H, Ar-CH3); 13C NMR
N ¼ CH), 8.19 (d, J ¼ 8.1 Hz, 1 H, Pyridyl-H), 7.69 (d, (101 MHz, DMSO-d6) d 178.2 (C¼S), 156.6 (C¼O), 148.7
J ¼ 2.1 Hz, 1 H, Ar-H), 7.62 (dd, J ¼ 8.1, 4.7 Hz, 1 H, Pyridyl- (Pyridyl-C), 147.6 (Pyridyl-C), 139.8 (CH¼N), 139.6
H), 7.51 (d, J ¼ 2.0 Hz, 1 H, Ar-H), 7.43 (s, 1 H, Pyrazole-H), (Pyrazole-C), 139.5 (Ph-C), 137.6 (Pyridyl-C), 133.9 (Ph-C),
2.52 (s, 3 H, SCH3), 2.17 (s, 3 H, Ar-CH3); 13C NMR 133.1 (Ph-C), 132.7 (Ph-C), 131.2 (Ph-C), 128.1 (Pyridyl-C),

PHOSPHORUS, SULFUR, AND SILICON
5
127.3 (Pyrazole-C), 127.1 (Ph-C), 123.2 (Pyridyl-C), 111.3 8.73 (d, J ¼ 5.7 Hz, 1 H, Pyridyl-H), 8.51 (d, J ¼ 3.5 Hz, 1 H,
(Pyrazole-C), 31.3 (NHCH3), 17.9 (Ar-CH3); HRMS calcd Pyridyl-H), 8.15-8.19 (m, 3 H, CH¼N, Ar-H, CSNH), 7.61
for C19H16BrCl2N7OS 539.9776 found 539.9755 ([M þ H]þ).
(dd, J ¼ 7.9, 4.8 Hz, 1 H, Pyridyl-H), 7.42 (s, 1 H, Ar-H), 7.40
The synthetic procedure for compounds 8c-8f was similar (s, 1 H, Pyrazole-H), 3.47-3.51 (m, 2 H, CH2CH2CH3), 2.14(s,
with that for compound 8 b using corresponding 3 H, Ar-CH3), 1.56-1.60 (m, 2 H, CH2CH2CH3), 0.87 (t,
amine material.
J ¼ 7.4 Hz, 3 H, CH2CH2CH3); 13C NMR (101 MHz, DMSO-
d6) d 177.4 (C¼S), 156.6 (C¼O), 148.7 (Pyridyl-C), 147.6
(Pyridyl-C), 139.8 (CH¼N), 139.6 (Pyrazole-C), 139.4 (Ph-
C), 137.8 (Pyridyl-C), 133.8 (Ph-C), 133.1 (Ph-C), 132.7 (Ph-
C), 131.2 (Ph-C), 128.1 (Pyridyl-C), 127.3 (Pyrazole-C),
127.1 (Ph-C), 123.3 (Pyridyl-C), 111.3 (Pyrazole-C), 45.7
(CH2CH2CH3), 22.6 (CH2CH2CH3), 17.9 (Ar-CH3), 11.7
((CH2)2CH3); HRMS calcd for C21H20Br Cl2N7OS 568.0089
found 568.0013 ([M þ H]þ).
3-Bromo-N-(4-chloro-2-((2-(cyclopropylcarbamothioyl)
hydrazono)methyl)-6-methylphenyl)-1-(3-chloropyridin-
2-yl)-1H-pyrazole-5-carboxamide 8c
Pale yellow solid, yield 41.3%, mp 245-247 ꢂC; IR, ꢀ/cmꢁ1
:
3334.34 (N-H), 3134.31 (N-H), 1685.20 (C¼O), 1527.20
(C¼N), 1468.48 (C¼C), 1239.11 (C¼S); 1 H NMR
(300 MHz, DMSO-d6) d 11.62 (s, 1 H, CSNH), 10.45 (s, 1 H,
CONH), 8.50 (bs, 2 H, Pyridyl-H), 8.13-8.21 (m, 3 H, Ar-H,
CSNH, N¼CH), 7.61 (dd, J ¼ 8.0, 4.6 Hz, 1 H, Pyridyl-H),
7.41 (2 H, Pyrazole-H, Ar-H), 2.13 (s, 3 H, Ar-CH3), 1.99
(bs, 1 H, Cyclopropyl-H), 1.14-1.24 (m, 4 H, Cyclopropyl-H);
3-Bromo-N-(2-((2-(butylcarbamothioyl)hydrazono)
methyl)-4-chloro-6-methylphenyl)-1-(3-chloropyridin-2-
yl)-1H-pyrazole-5-carboxamide 8f
13C NMR (101 MHz, DMSO-d6) d 179.0 (C¼S), 156.6 Pale yellow solid, yield 45.6%, mp 236-237 ꢂC; IR, ꢀ/cmꢁ1
:
(C¼O), 148.7 (Pyridyl-C), 147.6 (Pyridyl-C), 139.8 (CH¼N), 3292.71 (N-H), 3155.67 (N-H), 1677.40 (C¼O), 1533.15
1
139.6 (Pyrazole-C), 139.4 (Ph-C), 138.2 (Pyridyl-C), 133.7 (C¼N), 1460.09 (C¼C), 1271.80 (C¼S); H NMR (400 MHz,
(Ph-C), 133.1 (Ph-C), 132.7 (Ph-C), 131.2 (Ph-C), 128.1 DMSO-d6) d 11.53 (s, 1 H, CSNH), 10.46 (s, 1 H, CONH),
(Pyridyl-C), 127.3 (Pyrazole-C), 127.1 (Ph-C), 123.6 8.71 (t, J ¼ 5.9 Hz, Pyridyl-H), 8.51 (d, J ¼ 3.9 Hz, 1 H,
(Pyridyl-C), 111.3 (Pyrazole-C), 27.6 (Cyclopropyl-CH), 17.9 Pyridyl-H), 8.14-8.16 (m, 3 H, CH ¼ N, Ar-H, CSNH), 7.62
(Ar-CH3), 7.1 (Cyclopropyl-(CH2)2); HRMS calcd for (dd, J ¼ 8.0, 4.7 Hz, 1 H, Pyridyl-H), 7.42 (s, 1 H, Ar-H), 7.40
C21H18BrCl2N7OS 565.9936 found 565.9914 ([M þ H]þ).
(s, 1 H, Pyrazole-H), 3.54 (dd, J ¼ 13.8, 6.6 Hz, 2 H,
CH2CH2CH2CH3), 2.14 (s, 3 H, Ar-CH3), 1.52-1.60 (m, 2 H,
CH2CH2CH2CH3), 1.28-1.34 (m, 2 H, CH2CH2CH2CH3),
0.91 (t, J ¼ 7.3 Hz, 3 H, CH2CH2CH2CH3); 13C NMR
(100 MHz, DMSO-d6) d 177.4 (C¼S), 156.6 (C¼O), 148.7
(Pyridyl-C), 147.6 (Pyridyl-C), 139.8 (CH ¼ N), 139.6
(Pyrazole-C), 139.4 (Ph-C), 137.8 (Pyridyl-C), 133.9 (Ph-C),
133.1 (Ph-C), 132.7 (Ph-C), 131.2 (Ph-C), 128.1 (Pyridyl-C),
127.3 (Pyrazole-C), 127.1 (Ph-C), 123.3 (Pyridyl-C), 111.3
(Pyrazole-C), 43.7 (CH2CH2CH2CH3), 31.5 (CH2CH2CH2
CH3), 20.1 (CH2CH2CH2CH3), 17.9 (Ar-CH3), 14.3 ((CH2)3
CH3); HRMS calcd for C22H22BrCl2N7OS 582.0245 found
582.0231 ([M þ H]þ).
3-Bromo-N-(4-chloro-2-((2-(isopropylcarbamothioyl)
hydrazono)methyl)-6-methylphenyl)-1-(3-chloropyridin-2-
yl)-1H-pyrazole-5-carboxamide 8d
Pale yellow solid, yield 40.9%, mp 253-255 ꢂC; IR, ꢀ/cm ꢁ1:
3351.36 (N-H), 3140.73 (N-H), 1686.12 (C¼O), 1528.37
(C¼N), 1464.76 (C¼C), 1297.28 (C¼S); 1 H NMR
(400 MHz, DMSO-d6) d 11.52 (s, 1 H, CSNH), 10.46 (s, 1 H,
CONH), 8.51 (d, J ¼ 4.5 Hz, 1 H, Pyridyl-H)
, 8.24
(d, J ¼ 8.6 Hz, 1 H, Pyridyl-H), 8.20 (s, 1 H, CSNH), 8.17 (s,
1 H, Ar-H), 8.11 (s, 1 H, C¼NH), 7.62 (dd, J ¼ 8.0, 4.7 Hz,
1 H, Pyridyl-H), 7.42-7.43 (m, 2 H, Ar-H, Pyrazole-H), 4.51-
4.56 (m, 1 H, CH), 2.14 (s, 3 H, Ar-CH3), 1.22 (d, J ¼ 6.7 Hz,
6 H, 2CH3); 13C NMR (101 MHz, DMSO-d6) d 176.2
Insecticidal activity assay
(C¼S), 156.6 (C¼O), 148.7 (Pyridyl-C), 147.6 (Pyridyl-C), The larvicidal activities of the intermediate 6, the title
139.8 (CH ¼ N), 139.6 (Pyrazole-C), 139.4 (Ph-C), 138.3 compounds 7, 8a-8f and the insecticide control
(Pyridyl-C), 133.7 (Ph-C), 133.1 (Ph-C), 132.6 (Ph-C), 131.3 Chlorantraniliprole against oriental armyworm (Mythimna
(Ph-C), 128.1 (Pyridyl-C), 127.3 (Pyrazole-C), 127.1 (Ph-C), separata Walker) were tested according to the leaf-dip
123.5 (Pyridyl-C), 111.3 (Pyrazole-C), 46.3 (CH(CH3)2), method using the reported procedure.[9,13] Assessments were
22.3 (CH(CH3)2), 17.9 (Ar-CH3); HRMS calcd for made on a dead/alive basis, and mortality rates were cor-
C21H20BrCl2N7OS 568.0089 found 567.9983 ([M þ H]þ).
rected using Abbott’s formula.[19] The insecticidal bioassay
result is summarized in Table S1.
3-Bromo-N-(4-chloro-2-methyl-6-((2-
(propylcarbamothioyl)hydrazono)methyl)phenyl)-1-(3-
chloropyridin-2-yl)-1H-pyrazole-5-carboxamide 8e
Fungicidal activity assay
The in vitro fungicidal activities of the title compounds 7
and 8a-8f against Alternaria solani Sorauer, Gibberella
Pale yellow solid, yield 42.1%, mp 235-237 ꢂC; IR, ꢀ/cmꢁ1
:
3339.48 (N-H), 3139.39 (N-H), 1681.41 (C¼O), 1529.76 sanbinetti, Cercospora arachidicola and Physalospora piricola
1
(C¼N), 1464.13 (C¼C), 1289.33 (C¼S); H NMR (400 MHz, were evaluated using the mycelium growth rate test.[20–22]
DMSO-d6) d 11.54 (s, 1 H, CSNH), 10.46 (s, 1 H, CONH), The method for testing these biological activities was

6
Q.-X. LIU ET AL.
Appl. Organomet. Chem. 2011, 25, 643–652. DOI: 10.1002/
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Piston Ring Coatings with Molybdenum Dithiocarbomate
Friction Modifier. J. Mater. Sci. 2006, 41, 1911–1915. DOI:
10.1007/s10853-006-4485-7.
performed in an isolated culture. The commercial fungicides
Chlorothalonil, Carbendazim and Triadimefon were used as
controls. The fungicidal bioassay result is summarized in
Table S2.
[7] Lukmantara, A. Y.; Kalinowski, D. S.; Kumar, N.; Richardson,
D. R. Synthesis and Biological Evaluation of Substituted 2-
Benzoylpyridine Thiosemicarbazones: Novel Structure-Activity
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Conclusion
In summary, a series of novel anthranilic diamide derivatives
containing pyridylpyrazole and iminodithiocarbamate or
thiosemicarbazone motifs were designed and synthesized.
The bioassays showed that some of the compounds exhib-
ited modest insecticidal activities against oriental armyworm
(Mythimna separata Walker), especially, compound 8b held
100% and 30% larvicidal activity at the concentration of
25 mg/L and 10 mg/L, respectively. Moreover, several com-
pounds showed favorable fungicidal activities against some
agricultural plant fungi. This research will provide useful
information for further study and exploration on the synthe-
sis and various biological activities of heterocyclic com-
pounds with sulfur-containing groups.
[10] Wang, B.; Ma, Y.; Xiong, L.; Li, Z. Synthesis and Insecticidal
Activity of Novel N-Pyridylpyrazole Carbonyl Thioureas. Chin.
J. Chem. 2012, 30, 815–821. DOI: 10.1002/cjoc.201100386.
[11] Lahm, G. P.; Stevenson, T. M.; Selby, T. P.; Freudenberger,
J. H.; Cordova, D.; Flexner, L.; Bellin, C. A.; Dubas, C. M.;
Smith, B. K.; Hughes, K. A.; et al. Rynaxypyr (TM): a New
Insecticidal Anthranilic Diamide That Acts as a Potent and
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[12] Hughes, K. A.; Lahm, G. P.; Selby, T. P.; Stevenson, T. M. New
Cyano Anthranilamide Having Insecticidal Activity, Useful for
Controlling Pests e.g. Cockroach, Ant or Termite.
WO2004067528 2004.
Acknowledgment
We thank Ms. Xiao Zhang and Shu-Jing Yu of the Biological Assay
Center, Nankai University, for fungicidal test of compounds.
Disclosure statement
No potential conflict of interest was reported by the author(s).
[13] Wang, B.-L.; Zhu, H.-W.; Li, Z.-M.; Wang, L.-Z.; Zhang, X.;
Xiong, L.-X.; Song, H.-B. Synthesis, Biological Evaluation and
SAR Analysis of Novel Poly-Heterocyclic Compounds
Containing Pyridylpyrazole Group. Pest Manag. Sci. 2018, 74,
726–736. DOI: 10.1002/ps.4770.
[14] Yan, T.; Yu, S.; Liu, P.; Liu, Z.; Wang, B.; Xiong, L.; Li, Z.
Design, Synthesis and Biological Activities of Novel Benzoyl
Hydrazines Containing Pyrazole. Chin. J. Chem. 2012, 30,
919–923. DOI: 10.1002/cjoc.201100347.
Funding
This work was supported by grants from the National Key Research
and Development Program of China (No. 2017YFD0200505), the
National Natural Science Foundation of China (No. 21772103) and
Tianjin Natural Science Foundation (No. 17JCYBJC19900).
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