Synthesis and insecticidal activity of novel N-pyridylpyrazole carbonyl thioureas

Article abstract of DOI:10.1002/cjoc.201100386

A series of novel N-pyridylpyrazole carbonyl thioureas were designed and synthesized. Their structures were characterized by melting points, ¹H NMR, IR and elemental analysis or HRMS. The bioassay tests indicated that some of these compounds exhibited moderate insecticidal activity against Mythimna separata Walker and Culex pipiens pallens. Among 17 compounds, 5n and 5p showed 100% larvicidal activity against Mythimna separata Walker at the test concentration of 100 mg/L. A series of novel N-pyridylpyrazole carbonyl thioureas were synthesized and their structures were characterized by melting points, ¹H NMR, IR and elemental analysis or HRMS. Their insecticidal activity were also investigated. Copyright

Full text of DOI:10.1002/cjoc.201100386

FULL PAPER
DOI: 10.1002/cjoc.201100386
Synthesis and Insecticidal Activity of Novel N-Pyridylpyrazole
Carbonyl Thioureas
Wang, Baolei(王宝雷)
Ma, Yi(马翼)
Xiong, Lixia(熊丽霞)
Li, Zhengming*(李正名)
State-Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry,
Nankai University, Tianjin 300071, China
A series of novel N-pyridylpyrazole carbonyl thioureas were designed and synthesized. Their structures were
1
characterized by melting points, H NMR, IR and elemental analysis or HRMS. The bioassay tests indicated that
some of these compounds exhibited moderate insecticidal activity against Mythimna separata Walker and Culex
pipiens pallens. Among 17 compounds, 5n and 5p showed 100% larvicidal activity against Mythimna separata
Walker at the test concentration of 100 mg/L.
Keywords carbonyl thiourea, insecticidal activity, N-pyridylpyrazole
Introduction
series of novel carbonyl thiourea title compounds con-
taining N-pyridylpyrazole heterocycles were designed
through a variation of the amide bridge of such general
structure of anthranilic diamides to the carbonyl thio-
urea bridge (Figure 1) and synthesized as shown in
Scheme 1. The bioactivity against Mythimna separata
Walker and Culex pipiens pallens was tested accord-
ingly. The preliminary structure-activity relationships
were also discussed using a conformation analysis
method.
The use of synthetic pesticides is an essential ele-
ment for fighting serious crop damage from harmful
pests in both guarantee of food supply and prevention of
disease transmission. However, over time, some pests
become pesticide-resistant due to annual applications. In
addition, due to environmental concerns associated with
the accumulation of pesticides in food products and wa-
ter supplies, there is a great demand for environmentally
friendly products that act on new biochemical targets. A
new class of insecticides has been discovered, the an-
thranilic diamides, that provide exceptional control
through action on a novel target, the ryanodine receptor.
Chlorantraniliprole (RynaxypyrTM) (Dupont’s) is the
first new insecticide from the anthranilic diamides,
characterized by its high levels of insecticidal activity
and low toxicity to mammals attributed to a high selec-
tivity for insect over mammalian ryanodine receptors.[1]
Owing to their prominent insecticidal activity, unique
modes of action and good environmental profiles, an-
thranilic diamides and their chemical synthesis have
recently attracted considerable attention in the field of
novel agricultural insecticides.[2-5]
R1
Br
H
H
CONHCH3
Cl
H
N
N
N
R2
N
N
N
N
O
S
Cl
O
N
Cl
CH3
N
R1 = Cl, Br
chlorantraniliprole
R2 = substituted aryl, substituted benzyl
title compounds (5)
Figure 1 Design of the title compounds.
Experimental
Materials and instruments
There were lots of literatures reported for the modi-
fication of the anthranilic diamides,[6-9] but the modifi-
cations on the amide bridge that links two aryl rings
were relatively seldom reported,[10,11] which encouraged
us to synthesize some other novel compounds with such
bridge-modified structure. In order to find more potent
insecticidal compounds and continue our work, in this
paper, according to the structure of chlorantraniliprole, a
The melting points were determined on an X-4 bin-
ocular microscope melting point apparatus (Beijing
Tech Instruments Co., Beijing, China) and were uncor-
rected. Infrared spectra were recorded on a Nicolet
1
MAGNA-560 spectrophotometer as KBr tablets. H
NMR spectra were recorded at 300 MHz or 400 MHz
using a Bruker AC-P 300 or AV 400 spectrometer in
CDCl3 solution with tetramethylsilane as the internal
*
E-mail: nkzml@vip.163.com; Tel.: 0086-022-23503732; Fax: 0086-022-23505948
Received September 23, 2011; accepted November 20, 2011; published online March 7, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201100386 or from the author.
Chin. J. Chem. 2012, 30, 815—821
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815

Wang et al.
FULL PAPER
Scheme 1 General synthetic route for title compounds 5a—5q
O
H
H
CO2C2H5
CO2C2H5
HN
Cl
CO2C2H5
Cl
Cl
N
POR1
NH2NH2 H2O
3
Cl
N
CH3CN
N
NHNH2
N
C2H5ONa, C2H5OH
R1
N
R1
N
R1
N
N
CO2C2H5
CO2H
N
CO2C2H5
N
N
(COCl)2, DMF
CH2Cl2
(1) NaOH
(2) HCl
K2S2O8
Cl
Cl
Cl
N
H2SO4, CH3CN
N
2
1
R1
N
R1
N
R1
N
H
N
H
R2
N
NH2
CH3CN
KSCN, PEG-400
CH3CN
COCl
CONCS
R2
N
N
N
Cl
Cl
Cl
O
N
S
N
N
5
3
4
standard. Elemental analyses were performed on a Vario
EL elemental analyzer. High-resolution mass spectro-
metry (HRMS) data were obtained on a Varian
QFT-ESI instrument. Reagents were all analytically or
chemically pure. Substituted anilines and 3,5-bis(tri-
fluoromethyl)benzylamine were purchased from Alfa
Aesar and Aladdin-Reagent. All solvents were dried by
standard methods in advance and distilled before use.
Chlorantraniliprole was synthesized according to the
literature[12] and used as the control.
solid, yield 89%, m.p. 198—200 ℃ (Lit.[14] 197—200
℃).
3-Substituted-1-(3-chloro-2-pyridyl)-1H-pyrazole-
5-carbonyl chloride (3) Compound 2 (1.0 mmol) was
suspended in 25 mL of dichloromethane. Under vigor-
ous stirring, oxalyl chloride (4 mmol) and two drops of
DMF were added successively. After stirring at room
temperature for 3—4 h, the mixture was evaporated to
dryness in vacuo, the residue, that is, the crude pyra-
zolecarbonyl chloride was obtained as a yellow powder
(100%), which was used directly in the next step with-
out further purification.
General procedure
Ethyl 2-amino-5-ethyl-thiophene-5-carboxylate was
synthesized by the method reported by literature.[13] The
intermediates ethyl 3-chloro-1-(3-chloro-2-pyridyl)-1H-
pyrazole-5-carboxylate (1a) and ethyl 3-bromo-1-(3-
chloro-2-pyridyl)-1H-pyrazole-5-carboxylate (1b) were
synthesized according to our previous work.[14] The title
compounds were prepared as shown in Scheme 1.
3-Chloro-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-
carboxylic acid (2a) To a solution of ester 1a (5.42 g,
19 mmol) in 30 mL of methanol and 15 mL of water, 3
mL of aq. sodium hydroxide (w＝50%) was added, and
the mixture was stirred at room temperature for 3 h,
then concentrated. The concentrated mixture was di-
luted with 30 mL water, and washed with 20 mL of
ethyl acetate to remove organic impurities. The aqueous
phase was acidified to pH 2 using concentrated hydro-
chloric acid to give 4.6 g of acid 2a: white solid, yield
94%, m.p. 199—201 ℃ (Lit.[14] 200—201 ℃).
N'-Substituted-N-(3-substitued-1-(3-chloro-2-
pyridyl)-1H-pyrazole-5-carbonyl)thiourea (5) To a
mixture of 0.24 g (2.5 mmol) of KSCN in 15 mL of dry
acetonitrile, two drops of PEG-400 were added, and the
mixture was stirred at room temperature for 5 min to
give a homogeneous solution, then, the solution of crude
pyrazole carbonyl chloride 3 (1 mmol) in 5 mL of dry
acetonitrile was added. After stirring at room tempera-
ture for 40 min, the mixture was filtrated to give the
acetonitrile solution of pyrazole carbonyl isothiocyanate
(4), and then the substituted amine (0.85 mmol) was
added, after stirring at room temperature for another 3—
4 h, the mixture was evaporated in vacuo and the resi-
due was subjected to column chromatography on silica
gel with petroleum ether and ethyl acetate as solvents to
give the title compounds.
N'-(2-Trifluoromethylphenyl)-N-[1-(3-chloro-2-
pyridyl)-3-chloro-1H-prazole-5-carbonyl] thiourea
(5a) Yield 61%; light yellow solid, m.p. 183—185 ℃;
1H NMR (400 MHz, CDCl3) δ: 7.02 (s, 1H, Pyrazol-H),
7.40—7.50 (m, 2H, Ph-H), 7.61 (t, J＝8.0 Hz, 1H,
With the same procedure using ester 1b as material,
3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-car-
boxylic acid (2b) could also be prepared: light yellow
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Chin. J. Chem. 2012, 30, 815—821

Synthesis and Insecticidal Activity of Novel N-Pyridylpyrazole Carbonyl Thioureas
Ph-H), 7.69 (d, J＝8.0 Hz, 1H, Ph-H), 7.84 (d, J＝8.0
Hz, 1H, Py-H), 7.99 (d, J＝8.0 Hz, 1H, Py-H), 8.56 (d,
J＝4.4 Hz, 1H, Py-H), 10.03 (s, 1H, NH), 11.81 (s, 1H,
NH). HRMS calcd for C17H10Cl2F3N5OS 481.9833,
found 481.9829 [M＋Na]＋.
MHz, CDCl3) δ: 7.12 (s, 1H, Pyrazol-H), 7.38—7.69 (m,
3H, Ph-H), 7.99 (d, J＝10.8 Hz, 1H, Py-H), 8.10 (dd,
J1＝11.2 Hz, J2＝1.6 Hz, 1H, Py-H), 8.36 (d, J＝10.8
Hz, 1H, Py-H), 8.57 (d, J＝4.4 Hz, 1H, Ph-H), 10.42 (s,
1H, NH), 12.34 (s, 1H, NH). HRMS calcd for C16H10Br-
ClN6O3S 502.9305, found 502.9303[M＋Na]＋.
N'-[3-Ethoxycarbonyl-5-ethyl-2-thienyl]-N-[1-(3-
chloro-2-pyridyl)-3-bromo-1H-prazole-5-carbonyl]-
thiourea (5h) Yield 81%; yellow solid, m.p. 216—
N'-[3,5-Bis(trifluoromethyl)phenyl]-N-[1-(3-
chloro-2-pyridyl)-3-chloro-1H-prazole-5-carbonyl]-
thiourea (5b) Yield 67%; light yellow solid, m.p.
1
177—179 ℃; H NMR (400 MHz, CDCl3) δ: 6.98 (s,
1H, Pyrazol-H), 7.54 (dd, J1＝8.0 Hz, J2＝4.8 Hz, 1H,
Py-H), 7.70 (s, 1H, Ph-H), 8.03 (d, J＝8.4 Hz, 1H,
Py-H), 8.14 (s, 2H, Ph-H), 8.67 (d, J＝4.0 Hz, 1H,
Py-H), 10.20 (s, 1H, NH), 12.22 (s, 1H, NH). Anal.
calcd for C18H9Cl2F6N5OS: C 40.93, H 1.72, N 13.26;
found C 40.95, H 2.14, N 13.21.
218 ℃; IR (KBr) v: 3399, 3140 (N—H), 1712, 1682
－
1
1
(C＝O, C＝N), 1279 (C＝S), 1177 (C—N) cm ; H
NMR (CDCl3, 300 MHz) δ: 1.29 (t, J＝7.2 Hz, 3H,
CH3), 1.30 (t, J＝7.5 Hz, 3H, CH3), 2.74 (q, J＝7.5 Hz,
2H, CH2), 4.33 (q, J＝7.2 Hz, 2H, CH2), 7.02 (s, 1H,
Pyrazol-H), 7.17 (s, 1H, Thiophene-H), 7.49 (dd, J1＝
8.1 Hz, J2＝4.8 Hz, 1H, Py-H), 8.00 (dd, J1＝8.1 Hz,
J2＝1.5 Hz, 1H, Py-H), 8.61 (dd, J1＝4.8 Hz, J2＝1.5
Hz, 1H, Py-H), 10.57 (s, 1H, NH), 14.19 (s, 1H, NH).
Anal. calcd for C19H17BrClN5O3S2: C 42.04, H 3.16, N
12.90; found C 41.76, H 3.19, N 12.68.
N'-(4-Fluoro-3-nitrophenyl)-N-[1-(3-chloro-2-
pyridyl)-3-chloro-1H-prazole-5-carbonyl] thiourea
1
(5c) Yield 56%; yellow solid, m.p. 139—141 ℃; H
NMR (400 MHz, CDCl3) δ: 7.02 (s, 1H, Pyrazol-H),
7.26—7.32 (m, 1H, Ph-H), 7.53 (dd, J1＝7.2 Hz, J2＝
5.2 Hz, 1H, Py-H), 7.90—7.92 (m, 1H, Ph-H), 8.01 (d,
J＝8.0 Hz, 1H, Py-H), 8.41 (d, J＝5.2 Hz, 1H, Ph-H),
8.61 (d, J＝4.0 Hz, 1H, Py-H), 10.07 (s, 1H, NH), 12.04
(s, 1H, NH). Anal. calcd for C16H9Cl2FN6O3S: C 42.21,
H 1.99, N 18.46; found C 41.93, H 2.32, N 18.62.
N'-[3,5-Bis(trifluoromethyl)phenyl]-N-[1-(3-
chloro-2-pyridyl)-3-bromo-1H-prazole-5-carbonyl]-
thiourea (5i) Yield 56%; light yellow solid, m.p.
182—184 ℃; IR (KBr) v: 3315, 3164 (N—H), 1678,
－
1
1644 (C＝O, C＝N), 1277 (C＝S), 1162 (C—N) cm ;
1H NMR (400 MHz, CDCl3) δ: 7.07 (s, 1H, Pyrazol-H),
7.54 (dd, J1＝7.6 Hz, J2＝4.8 Hz, 1H, Py-H), 7.71 (s,
1H, Ph-H), 8.02 (d, J＝8.4 Hz, 1H, Py-H), 8.14 (s, 2H,
Ph-H), 8.66 (d, J＝4.8 Hz, 1H, Py-H), 10.14 (s, 1H,
NH), 12.21 (s, 1H, NH). Anal. calcd for C18H9BrCl-
F6N5OS: C 37.75, H 1.58, N 12.23; found C37.99, H
2.15, N 12.34.
N'-(2-Methylphenyl)-N-[1-(3-chloro-2-pyridyl)-3-
bromo-1H-prazole-5-carbonyl] thiourea (5d) Yield
1
65%; light yellow solid, m.p. 179—181 ℃; H NMR
(400 MHz, CDCl3) δ: 2.25 (s, 3H, CH3), 7.09 (s, 1H,
Pyrazol-H), 7.22—7.26 (m, 3H, Ph-H), 7.46—7.50 (m,
1H, Ph-H), 7.57 (d, J＝4.8 Hz, 1H, Py-H), 7.97 (dd,
J1＝10.4 Hz, J2＝2.0 Hz, 1H, Py-H), 8.56 (d, J＝2.0 Hz,
1H, Py-H), 9.85 (s, 1H, NH), 11.51 (s, 1H, NH). Anal.
calcd for C17H13BrClN5OS: C 45.30, H 2.91, N 15.54;
found C 45.11, H 2.84, N 15.59.
N'-[3,5-Bis(trifluoromethyl)benzyl]-N-[1-(3-
chloro-2-pyridyl)-3-bromo-1H-prazole-5-carbonyl]-
thiourea (5j) Yield 59%; white solid, m.p. 171—173
1
N'-(2-Trifluoromethylphenyl)-N-[1-(3-chloro-2-
pyridyl)-3-bromo-1H-prazole-5-carbonyl] thiourea
℃; H NMR (400 MHz, CDCl3) δ: 4.95 (d, J＝5.6 Hz,
2H, CH2), 7.04 (s, 1H, Pyrazol-H), 7.48 (dd, J1＝7.6 Hz,
J2＝5.6 Hz, 1H, Py-H), 7.75—7.81 (m, 3H, Ph-H), 7.97
(d, J＝8.0 Hz, 1H, Py-H), 8.55 (d, J＝4.4 Hz, 1H,
Py-H), 9.76 (s, 1H, NH), 10.54 (br s, 1H, NH). Anal.
calcd for C19H11BrClF6N5OS: C 38.89, H 1.89, N 11.94;
found C 39.08, H 2.14, N 12.43.
1
(5e) Yield 50%; white solid, m.p. 181—183 ℃; H
NMR (400 MHz, CDCl3) δ: 7.11 (s, 1H, Pyrazol-H),
7.40—7.50 (m, 2H, Ph-H), 7.58—7.71 (m, 2H, Ph-H),
7.84 (d, J＝10.0 Hz, 1H, Py-H), 7.98 (d, J＝10.4 Hz,
1H, Py-H), 8.56 (d, J＝4.4 Hz, 1H, Py-H), 10.03 (s, 1H,
NH), 11.81 (s, 1H, NH). Anal. calcd for C17H10BrCl-
F3N5OS: C 40.46, H 2.00, N 13.88; found C 40.18, H
1.69, N 13.92.
N'-(4-Fluoro-3-nitrophenyl)-N-[1-(3-chloro-2-
pyridyl)-3-bromo-1H-prazole-5-carbonyl] thiourea
1
(5k) Yield 51%; yellow solid, m.p. 136—138 ℃; H
N'-(2-Chlorophenyl)-N-[1-(3-chloro-2-pyridyl)-3-
bromo-1H-prazole-5-carbonyl] thiourea (5f) Yield
73%; white solid, m.p. 188—189 ℃; H NMR (400
MHz, CDCl3) δ: 7.11 (s, 1H, Pyrazol-H), 7.19—7.34 (m,
2H, Ph-H), 7.42—7.51 (m, 2H, Ph-H), 7.98 (dd, J1＝
10.8 Hz, J2＝2.0 Hz, 1H, Py-H), 8.21 (d, J＝10.8 Hz,
1H, Py-H), 8.57 (dd, J1＝6.4 Hz, J2＝2.0 Hz, 1H, Py-H),
10.00 (s, 1H, NH), 11.97 (s, 1H, NH). Anal. calcd for
C16H10BrCl2N5OS: C 40.79, H 2.14, N 14.86; found C
40.35, H 1.89, N 14.87.
NMR (400 MHz, CDCl3) δ: 7.10 (s, 1H, Pyrazol-H),
7.26—7.32 (m, 1H, Ph-H), 7.53 (t, J＝5.6 Hz, 1H,
Py-H), 7.91 (d, J＝6.8 Hz, 1H, Ph-H), 8.01 (d, J＝8.4
Hz, 1H, Py-H), 8.41 (d, J＝6.0 Hz, 1H, Ph-H), 8.60 (d,
J＝4.0 Hz, 1H, Py-H), 10.04 (s, 1H, NH), 12.04 (s, 1H,
NH). Anal. calcd for C16H9BrClFN6O3S: C 38.46, H
1.82, N 16.82; found C 38.55, H 2.16, N 16.74.
N'-(4-Trifluoromethoxylphenyl)-N-[1-(3-chloro-2-
pyridyl)-3-bromo-1H-prazole-5-carbonyl] thiourea
(5l) Yield 86%; light yellow solid, m.p. 158—160 ℃;
1H NMR (400 MHz, CDCl3) δ: 7.07 (s, 1H, Pyrazol-H),
7.21 (d, J＝8.4 Hz, 2H, Ph-H), 7.50 (dd, J1＝8.0 Hz,
J2＝4.8 Hz, 1H, Py-H), 7.65 (d, J＝8.4 Hz, 2H, Ph-H),
1
N'-(2-Nitrophenyl)-N-[1-(3-chloro-2-pyridyl)-3-
bromo-1H-prazole-5-carbonyl] thiourea (5g) Yield
1
51%; yellow solid, m.p. 190—191 ℃; H NMR (400
Chin. J. Chem. 2012, 30, 815—821
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7.99 (d, J＝8.0 Hz, 1H, Py-H), 8.60 (d, J＝3.2 Hz, 1H,
Py-H), 9.81 (s, 1H, NH), 11.90 (s, 1H, NH). Anal. calcd
for C17H10BrClF3N5O2S: C 39.21, H 1.94, N 13.45;
found C 39.06, H 2.19, N 13.14.
greenhouse.[15] The bioassay was operated at (25±1) ℃
according to statistical requirements. The compounds
were dissolved in acetone to test at varying concentra-
tions. For each fourth-instar larva of oriental armyworm,
0.306 μL of tested solution was applied to the thoracic
tergite with a platinum loop. After treatment, the insects
were then transferred to their standard rearing condi-
tions. Mortalities were calculated 72 h after treatment.
Each treatment was performed three times.
Insecticidal activity was examined against mosquito
(Culex pipiens pallens).[15] One milliliter of differently
concentrated solution of each compound was added to
99 mL of water to get different concentrations of tested
solutions. Then, 20 fourth-instar mosquito larva were
put into 10 mL of the test solution and raised for 2 d,
and the results were expressed by death percentage.
N'-(2,3,4-Trifluorophenyl)-N-[1-(3-chloro-2-pyridyl)-
3-bromo-1H-prazole-5-carbonyl]
thiourea
(5m)
1
Yield 62%; yellow solid, m.p. 183—185 ℃; H NMR
(400 MHz, CDCl3) δ: 6.96—7.03 (m, 1H, Ph-H), 7.11 (s,
1H, Pyrazol-H), 7.50 (dd, J1＝8.0 Hz, J2＝4.4 Hz, 1H,
Py-H), 7.76—7.81 (m, 1H, Ph-H), 8.00 (dd, J1＝8.0 Hz,
J2＝1.2 Hz, 1H, Py-H), 8.58 (dd, J1＝4.4 Hz, J2＝1.2
Hz, 1H, Py-H), 10.06 (s, 1H, NH), 11.76 (s, 1H, NH).
HRMS calcd for C16H8BrClF3N5OS: 489.9352, found
489.9348 [M＋H]＋.
N'-(2,6-Dimethylphenyl)-N-[1-(3-chloro-2-pyridyl)-
3-bromo-1H-prazole-5-carbonyl]
thiourea
(5n)
1
Yield 71%; white solid, m.p. 202—204 ℃; H NMR
(400 MHz, CDCl3) δ: 2.23 (s, 6H, CH3), 7.09 (d, J＝7.6
Hz, 2H, Ph-H), 7.10 (s, 1H, Pyrazol-H), 7.18 (t, J＝7.6
Hz, 1H, Ph-H), 7.49 (dd, J1＝8.0 Hz, J2＝4.4 Hz, 1H,
Py-H), 7.98 (d, J＝8.0 Hz, 1H, Py-H), 8.57 (d, J＝4.4
Hz, 1H, Py-H), 9.75 (s, 1H, NH), 11.16 (s, 1H, NH).
Anal. calcd for C18H15BrClN5OS: C 46.52, H 3.25, N
15.07; found C 46.09, H 3.37, N 14.86.
Conformation analysis
Molecular modeling was performed using the Sybyl
6.91 software of Tripos running on an SGI (Silicon
Graphics, Inc.) workstation and the conformation opti-
mization for the lowest energy has been done according
to our previous works.[6,17] The control chloran-
traniliprole, owing to its excellent larvicidal activity,
was used as a template to build the molecular structures
of compounds 5f and 5p which represent the weakest
and the best active molecules in this series, respectively.
Each structure was fully geometry optimized using a
conjugate gradient procedure based on the TRIPOS
force field and Gasteiger and Hückel charges. Because
these compounds share some common skeleton,
non-hydrogen atoms of N-pyridylpyrazole and CONH
groups were used for superposition with the corre-
sponding atoms of the template structure to analyze the
optimized conformation differences between compound
5f or 5p and chlorantraniliprole.
N'-(4-Phenoxylphenyl)-N-[1-(3-chloro-2-pyridyl)-
3-bromo-1H-prazole-5-carbonyl]
thiourea
(5o)
1
Yield 52%; yellow solid, m.p. 164—166 ℃; H NMR
(400 MHz, CDCl3) δ: 7.07 (s, 1H, Pyrazol-H), 6.97—
7.54 (m, 10H, Ph-H＋Py-H), 7.98 (d, J＝8.0 Hz, 1H,
Py-H), 8.58 (d, J＝4.4 Hz, 1H, Py-H), 9.69 (s, 1H, NH),
11.77 (s, 1H, NH). Anal. calcd for C22H15BrClN5O2S: C
49.97, H 2.86, N 13.24; found C 49.61, H 2.39, N 13.52.
N'-(2-Methyl-4-nitrophenyl)-N-[1-(3-chloro-2-
pyridyl)-3-bromo-1H-prazole-5-carbonyl] thiourea
(5p) Yield 60%; yellow solid, m.p. 193—194 ℃; IR
(KBr) v: 3419, 3180 (N—H), 1687, 1616 (C＝O, C＝N),
－
1
1
1273 (C＝S), 1141 (C—N) cm ; H NMR (400 MHz,
CDCl3) δ: 2.35 (s, 3H, CH3), 7.13 (s, 1H, Pyrazol-H),
7.51 (dd, J1＝8.0 Hz, J2＝4.8 Hz, 1H, Py-H), 8.01 (d,
J＝8.0 Hz, 1H, Py-H), 8.10 (d, J＝8.8 Hz, 1H, Ph-H),
8.13 (s, 1H, Ph-H), 8.22 (d, J＝8.8 Hz, 1H, Ph-H), 8.59
(d, J＝4.0 Hz, 1H, Py-H), 10.20 (s, 1H, NH), 11.93 (s,
1H, NH). Anal. calcd for C17H12BrClN6O3S: C 41.19, H
2.44, N 16.95; found C 41.18, H 2.78, N 16.94.
Results and Discussion
Synthesis and structure characterization
The synthetic route of title compounds is illustrated
in Scheme 1. Pyrazole carbonyl chloride (3) was pre-
pared from the reaction of pyrazole acid with oxalyl
chloride, and it was treated with potassium thiocyanate
under the condition of solid-liquid phase transfer cataly-
sis using a small amount of polyethylene glycol-400
(PEG-400) as the catalyst to give pyrazole carbonyl
isothiocyanate (4). This compound does not need to be
isolated and it was treated immediately with amines to
obtain the title compounds (5) in good yields. The novel
structures of these compounds synthesized have been
N'-(2,4-Dichlorophenyl)-N-[1-(3-chloro-2-pyridyl)-
3-bromo-1H-prazole-5-carbonyl]
thiourea
(5q)
1
Yield 48%; white solid, m.p. 198—200 ℃; H NMR
(400 MHz, CDCl3) δ: 7.11 (s, 1H, Pyrazol-H), 7.29—
7.30 (m, 1H, Ph-H), 7.44—7.51 (m, 2H, Ph-H), 7.99 (dd,
J1＝10.4 Hz, J2＝1.6 Hz, 1H, Py-H), 8.23 (d, J＝12.0
Hz, 1H, Py-H), 8.57 (dd, J1＝6.0 Hz, J2＝1.6 Hz, 1H,
Py-H), 10.09 (s, 1H, NH), 11.99 (s, 1H, NH). HRMS
calcd for C16H9BrCl3N5OS: 503.8855, found 503.8852
[M＋H]＋.
1
characterized by melting points, H NMR, IR and ele-
mental analysis or HRMS.
1
In the H NMR spectra of 5, the two active proton
signals of NHCO and NHCS on carbonyl thiourea
bridge in most cases were observed at δ 9.69—10.42
and δ 10.54—12.34, respectively. Whereas in the situa-
tion of compound 5h, they were observed at δ 10.57 and
Biological activity
Insecticidal activities against oriental armyworm
(Mythimna separate Walker) were performed in the
818
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 815—821

Synthesis and Insecticidal Activity of Novel N-Pyridylpyrazole Carbonyl Thioureas
14.19, respectively. The latter has a very high chemical
shift value, which may be produced by a SH group, that
is, the compound 5h may be more stable in chloro-
form-d6 solution as a carbonyl isothiourea derivative.
However, the IR spectrum demonstrated the carbonyl
thiourea structure of 5h. In addition, the aromatic proton
of pyrazole ring appeared at δ 6.98—7.12 as a singlet.
Compounds 5i and 5p were selected to further investi-
gate the IR spectrum characterization of this kind of
compounds. The infrared spectrum of the compounds
ing vibrations ν(C＝S) and ν(C—N) appear at 1273—
－
1277 and 1141—1162 cm , respectively.
1
Insecticidal activity
Biological evaluation results of the title compounds
were listed in Table 1. Some of them exhibited certain
insecticidal activity against Mythimna separata Walker.
The larvicidal activity of 5q was 80% and 30% at the
concentration of 200 and 100 mg/L, respectively. While
the larvicidal activity of 5n and 5p were 100%, 100%,
40% and 100%, 100%, 60% at 200, 100 and 50 mg/L
separately. In addition, in the same table we can see that
some of the compounds had weak insecticidal activity
(10%—30%) against Culex pipiens pallens at 2 mg/L.
showed absorption bands at 3164—3419 cm－ for N—
1
H stretching. The strong peaks at 1616—1687 cm－ are
1
ascribed to the C＝O group and C＝N group of hetero-
cyclic ring skeleton as well. The characteristic stretch-
Table 1 Insecticidal activity data of title compounds (% mortality)
R1
N
H
H
N
N
R2
N
O
S
Cl
N
Mythimna separata Walker
Culex pipiens pallens
Compd.
R1
Cl
R2
200 mg/L
100 mg/L
50 mg/L
2 mg/L
50
ntb
nt
0
5a
CF3
F3C
Cl
Cl
10
20
nt
nt
nt
nt
nt
5b
5c
CF3
nt
F
NO2
Br
Br
Br
Br
0
10
0
nt
nt
nt
nt
nt
nt
nt
nt
nt
0
5d
5e
5f
CH3
CF3
30
30
Cl
10
5g
NO2
Chin. J. Chem. 2012, 30, 815—821
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
819

Wang et al.
FULL PAPER
Continued
Mythimna separata Walker
Culex pipiens pallens
Compd.
R1
Br
R2
200 mg/L
100 mg/L
50 mg/L
2 mg/L
CO2C2H5
30
nt
nt
0
5h
S
C2H5
F3C
Br
Br
Br
20
nt
nt
nt
nt
Nt
Nt
Nt
5i
5j
CF3
F3C
CH2
10
10
nt
nt
CF3
5k
F
NO2
Br
Br
10
20
nt
nt
nt
nt
Nt
Nt
5l
CF3O
F
F
F
5m
CH3
Br
100
100
40
10
5n
CH3
Br
Br
O
10
nt
nt
Nt
20
5o
5p
100
100
60
CH3
O2N
Br
80
30
nt
30
5q
Cl
Cl
Controla
100
100
100
100
a Chlorantraniliprole; b nt＝not tested.
To further explore the structure-activity relationship
on the basis of the data against Mythimna separata
Walker, a conformation analysis method was performed.
Compounds 5f and 5p which represent the weakest and
the best active molecules in this series, respectively,
were selected to compare the optimized conformation
with that of chlorantraniliprole. From Figure 2, we can
see that the sulfur atom and oxygen atom on the car-
bonyl thiourea bridge of this series compounds are on
the opposite positions. Meanwhile, owing to the better
flexibility of carbonyl thiourea bridge than the amide
bridge, the substituted phenyl parts of two kinds of
compounds showed apparent difference in space after
conformation optimization and superposition. The chlo-
rine atom on benzene ring of compound 5f is far away
from the CH3NHCO group of chlorantraniliprole, while
820
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 815—821

Synthesis and Insecticidal Activity of Novel N-Pyridylpyrazole Carbonyl Thioureas
vicidal activity against Mythimna separata Walker at
the test concentration of 100 mg/L. Though the most
active 5p showed less effect against Mythimna separata
Walker than the control chlorantraniliprole, its novel
structure and favorable larvicidal activity make it a
promising compound for further studies.
Acknowledgement
This work was supported by the National Basic Re-
search Program of China (No. 2010CB126106), the
Fundamental Research Funds for the Central Universi-
ties, the Tianjin Natural Science Foundation (No.
11JCYBJC04500) and the National Key Technologies
R&D Program (No. 2011BAE06B05).
(a)
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In summary, a series of novel N-pyridylpyrazole
carbonyl thioureas were synthesized and bioassayed.
Among 17 compounds, 5n and 5p showed 100% lar-
(Pan, B.; Qin, X.)
Chin. J. Chem. 2012, 30, 815—821
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
821