Journal of Agricultural and Food Chemistry
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in vacuo, and the residue was subjected to column chromatography on
silica gel with petroleum ether and ethyl acetate as solvents to give
product (19a−n).
to that of 26 using 93% spermine as amine material, and the solid filtered
was washed with 1,2-dichloroethane to give pure product.
General Synthetic Procedure for 2-(3-Bromo-1-(3-chloropyr-
idin-2-yl)-1H-pyrazol-5-yl)-5-substituted-1,3,4-oxadiazole (28,
29a−c). A mixture of pyrazole carboxylic acid (5b, 1.5 mmmol) with
SOCl2 (10 mL) was refluxed for 4 h and condensed under reduced
pressure to give carbonyl chloride (17b), which was immediately
dissolved in dry toluene (7 mL) and added to a solution of 5-methyl-1H-
tetrazole or compound 10 (1.2 mmol) in dry pyridine (10 mL) with
stirring. The mixture was further stirred at 100−110 °C for 2 h and
cooled to room temperature, and water (50 mL) was added. The
mixture was then extracted with ethyl acetate (10 mL × 4), and the
extracts were dried with anhydrous sodium sulfate. The solvent was
removed in vacuo, and the residue was recrystallized with 95% EtOH to
give product.
Synthesis of 6-(3-Bromo-1-(3-chloropyridin-2-yl)-1H-pyra-
zol-5-yl)-3-methyl-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazole (30).
A mixture of pyrazole carboxylic acid (5b, 2 mmol) and 4-amino-5-
methyl-4H-1,2,4-triazole-3-thiol (2 mmol) in POCl3 (7 mL) was
refluxed for 5 h and condensed under reduced pressure. The residue was
poured into ice−water, and the mixture was adjusted to pH 10−11 with
30% sodium hydroxide solution. The solid was collected by filtration,
washed with water, and recrystallized with DMF−H2O to afford
compound 30 as pink crystals.
General Synthetic Procedure for N-(4-Halo-2-methyl-6-
(substituted-carbamoyl)phenylcarbamothioyl)-1-(3-chloropyr-
idin-2-yl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazole-5-carboxa-
mide (20a−g). To a mixture of 0.24 g (2.5 mmol) of KSCN in 15 mL of
dry acetonitrile were added two drops of PEG-400, and the mixture was
stirred at room temperature for 5 min to give a homogeneous solution;
then, the solution of crude pyrazole carbonyl chloride (17c) (1 mmol)
in 5 mL of dry acetonitrile was added. After stirring at room temperature
for 40 min, the reaction was filtered to give the acetonitrile solution of
pyrazole carbonyl isothiocyanate (18c), and then the amino compound
(14a−g) (0.85 mmol) was added; after stirring at room temperature for
another 3−4 h, the reaction mixture was evaporated in vacuo, and the
residue was subjected to column chromatography on silica gel with
petroleum ether and ethyl acetate as solvents to give product.
General Synthetic Procedure for 3-Substituted-N-(4-halo-2-
methyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl)-1-(3-chloro-
pyridin-2-yl)-1H-pyrazole-5-carboxamide (21a−c). To a mixture
of oxadiazole-containing substituted aniline (15a or 15b) (0.95 mmol)
and triethylamine (1 mmol) in dichloromethane (15 mL) was added the
solution of pyrazole carbonyl chloride (17b or 17c, 1 mmol) in dry
dichloromethane (7 mL) at 0−5 °C. The reaction mixture was then
stirred at room temperature for 3−4 h and washed with 5% NaHCO3
solution and water successively. The organic layer was dried over
anhydrous sodium sulfate. The solvent was removed in vacuo, and the
residue was subjected to column chromatography on silica gel with
petroleum ether and ethyl acetate as solvents to give product.
General Synthetic Procedure for N-(2-(5-(2-Azidopyridin-3-
yl)-1,3,4-oxadiazol-2-yl)-4-chloro-6-methylphenyl)-3-bromo-1-
(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (22). The
synthesis was similar to that of compounds 21a−c. Using oxadiazole-
containing aniline (15e) and pyrazole carbonyl chloride (17b) as
materials, compound 22 was obtained as a yellow solid.
Synthesis of 1-(2-Hydroxyethyl/hyroxypropyl)-3-(2,4,6-tri-
substituted-phenyl)thiourea (32a−d). According to the method
in the literature,24 to a solution of 1,3,5-trisubstituted-2-isothiocyana-
tobenzene (31a−c, 4 mmol) in diethyl ether (15 mL) was added 2-
aminoethanol or 1-amino-2-propanol (4.5 mmol), and the mixture was
refluxed for 1−2 h. The produced precipitate was filtered and washed
with diethyl ether to give compound 32 as a white solid, which was used
for following reaction without purification.
Synthesis of 5-Substituted-N-(2,4,6-trisubstituted-phenyl)-
4,5-dihydrothiazol-2-amine (33a−d). The intermediate thiourea
(32, 3 mmol) was mixed with concentrated HCl (8 mL) and refluxed for
2 h. The reaction solution was diluted with water (15 mL) and
decolorized by activated charcoal. After cooling to room temperature,
the mixture was adjusted to pH ∼10 with aqueous sodium hydroxide (6
mol/L), and the solid was collected by filtration, washed with water and
recrystallized with EtOH−H2O to afford compound 33.
General Synthetic Procedure for N′-(4-Chloro-2-methyl-6-(5-
methyl-1,3,4-oxadiazol-2-yl)phenyl)-N-(1-(3-chloro-2-pyridyl)-
3-bromo-1H-prazole-5-carbonyl)thiourea (23). The procedure
was similar to those of 19 and 20. Using 15a as substituted aniline
material, compound 23 was obtained as a yellow solid.
33a: white crystal; yield 40%; mp 117−119 °C (lit.,25 mp 118−119
°C).
General Synthetic Procedure for 3-Halo-N-(4-chloro-2-meth-
yl-6-(5-aryl-1,3,4-oxadiazol-2-yl)phenylcarbamothioyl)-1-(3-
chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (24a−c). The
synthesis was similar with those of 19 and 20. Using 15c or 15d as
substituted aniline material, compounds 24a−c were obtained.
Synthesis of 3-Substituted-1-(3-chloropyridin-2-yl)-1H-pyr-
azole-5-carboxamide (25a, 25b). To a suspension of pyrazole
carboxylic acid (5b or 5d) (8 mmol) in 50 mL of dichloromethane were
added successively oxalyl chloride (17 mmol) and two drops of DMF.
After stirring at room temperature for 3−4 h, the solution was
evaporated. The resulting carbonyl chloride was dissolved in 50 mL of
dry tetrahydrofuran (THF) and added to a mixture of aqueous ammonia
(25%) (40 mmol) and water (100 mL) at 0 °C. After stirring overnight, a
large amount of solid formed and was filtered, which was further purified
by a silica gel column eluted with petroleum ether and ethyl acetate to
give the pyrazole caboxamide. 25a: white solid; yield 84%; mp 200−202
°C. 25b: white solid; yield 77%; mp 183−185 °C.
General Synthetic Procedure for 3-Bromo-N-(4-chloro-2-
m e t h y l - 6 - ( 5 - s u b s t i t u t e d - 1 , 3 , 4 - o x a d i a z o l - 2 - y l ) -
phenylcarbamoyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-car-
boxamide (26a, 26b). A suspension of compound 25 (1 mmol) in 20
mL of 1,2-dichloroethane and oxalyl chloride (1.1 mmol) was heated to
reflux and kept for 2 h. After the mixture had cooled slightly, oxadiazole-
containing aniline (15a or 15d) was added, and the mixture was further
refluxed for 1−2 h. After cooling, the produced precipitate was filtered
and washed with 1,2-dichloroethane and ethyl acetate successively to
give product.
33b: white crystal; yield 46%; mp 124−126 °C (lit.,24 mp 124−125
°C).
33c: white crystal; yield 65%; mp 165−166 °C (lit.,24 mp 165.5−166
°C).
1
33d: white crystal; yield 42%; mp 122−123 °C; H NMR (CDCl3,
400 MHz) δ 1.44 (d, J = 6.8 Hz, 3H, CH3), 3.34 (dd, J1 = 10.0 Hz, J2 = 6.4
Hz, 1H, CH2), 3.78 (dd, J1 = 10.0 Hz, J2 = 6.4 Hz, 1H, CH2), 3.88 (m,
1H, CH), 6.80 (s, 1H, NH), 7.30 (s, 2H, Ph−H).
General Synthetic Procedure for 3-Substituted-1-(3-chlor-
opyridin-2-yl)-N-(5-substituted-4,5-dihydrothiazol-2-yl)-N-
(2,4,6-trisubstituted-phenyl)-1H-pyrazole-5-carboxamide
(34a−e). The synthesis was similar to the synthesis of compounds 21a−
c. Using thiazoline-containing aniline (33) and pyrazole carbonyl
chloride (compound 17b or 17c) as materials, compound 34 was
obtained.
Biological Assay. All bioassays were performed on representative
test organisms reared in the laboratory. The bioassay was repeated at 25
1 °C according to statistical requirements. Assessments were made on
a dead/alive basis, and mortality rates were corrected using Abbott’s
formula.26 Evaluations were based on a percentage scale of 0−100, in
which 0 = no activity and 100 = total kill. The standard deviations of the
tested biological values were 5%. LC50 and LC95 values were calculated
by probit analysis.27
Larvicidal Activity against Oriental Armyworm (Mythimna
separata Walker) and Corn Borer (Ostrinia nubilalis). The
larvicidal activity of the title compounds and contrast compounds
chlorantraniliprole and diflubenzuron against oriental armyworm and
corn borer was tested according to the leaf-dip method using the
reported procedure.28 Leaf disks (about 5 cm) were cut from fresh corn
General Synthetic Procedure for O,O-Dimethyl 3-Substi-
tuted-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carbonylcarba-
moylphosphoramidothioate (27a, 27b). The procedure was similar
D
dx.doi.org/10.1021/jf4012467 | J. Agric. Food Chem. XXXX, XXX, XXX−XXX