Design, Synthesis, Acaricidal Activities, and Structure-Activity Relationship Studies of Novel Oxazolines Containing Sulfonate Moieties

Article abstract of DOI:10.1021/acs.jafc.9b05547

With the ultimate goal of addressing pest-related constraints on global agricultural production, we used combination principles to design and synthesize 2,4-diphenyl-1,3-oxazolines containing a sulfonate moiety at the para-position of the 4-phenyl group. The target compounds, which have strong affinity for lipids and can be expected to traverse cell membranes, were characterized by ¹H and ¹³C NMR spectroscopy and high-resolution mass spectrometry. Their activities against the larvae and eggs of carmine spider mites (Tetranychus cinnabarinus) were determined by a leaf-dipping method and compared with the activity of the commercial acaricide etoxazole. Most of the test compounds displayed good ovicidal and larvicidal activities. In particular, a tert-butylphenyl-substituent compound possessed better larvicidal activity (LC₅₀ = 0.022 ± 0.009 mg/L) and ovicidal activity (0.044 ± 0.020 mg/L) than etoxazole (0.091 ± 0.051 and 0.095 ± 0.059 mg/L, respectively). Given its outstanding bioactivities, this compound deserves further attention as a pesticide candidate.

Full text of DOI:10.1021/acs.jafc.9b05547

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Agricultural and Environmental Chemistry
Design, Synthesis, Acaricidal Activities, and Structure–Activity
Relationship Studies of Novel Oxazolines Containing Sulfonate Moieties
Qingmin Wang, Shilin Chen, Yu Zhang, and Yuxiu Liu
J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.9b05547 • Publication Date (Web): 14 Nov 2019
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Design, Synthesis, Acaricidal Activities, and Structure–Activity
Relationship Studies of Novel Oxazolines Containing Sulfonate Moieties
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*,†
*,†,‡
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Shilin Chen, Yu Zhang, Yuxiu Liu, Qingmin Wang
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†State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic
Chemistry, College of Chemistry, Nankai University, Tianjin 300071, People’s Republic of China.
‡Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071,
People’s Republic of China
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ABSTRACT
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With the ultimate goal of addressing pest-related constraints on global
agricultural production, we used combination principles to design and
synthesize 2,4-diphenyl-1,3-oxazolines containing a sulfonate moiety at
the para-position of the 4-phenyl group. The target compounds, which
have strong affinity for lipids and can be expected to traverse cell
1
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membranes, were characterized by H and C NMR spectroscopy and
high-resolution mass spectrometry. Their activities against the larvae and
eggs of carmine spider mites (Tetranychus cinnabarinus) were
determined by a leaf-dipping method and compared with the activity of
the commercial acaricide etoxazole. Most of the test compounds
displayed good ovicidal and larvicidal activities. In particular, a
tert-butylphenyl-substituent compound possessed better larvicidal activity
(LC50 = 0.022 ± 0.009 mg/L) and ovicidal activity (0.044 ± 0.020 mg/L)
than etoxazole (0.091 ± 0.051 and 0.095 ± 0.059 mg/L, respectively).
Given its outstanding bioactivities, this compound deserves further
attention as a pesticide candidate.
KEYWORDS: 2,4-diphenyl-1,3-oxazolines; etoxazole; acaricidal
activity; sulfonate; structure–activity relationship
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INTRODUCTION
Mites transmit human diseases and reduce the yields of agricultural
crops.1 For example, Tetranychus cinnabarinus (carmine spider mite),
which is one of the most widely distributed polyphagous pests in
agricultural areas around the world, feeds on more than 800 species of
host plants, including fruit trees, potatoes, wheat, vegetables, corn, and
cotton.2 Mites generally feed directly on the cytosol, which results in the
formation of punctate necrotic tissue, reduced photosynthetic activity, and
leaf abscission in severe infestations.3,4 Because mites have high
reproductive potential and a short life cycle, mite infestations are a
serious threat to agriculture; however, owing to the long-term use and
abuse of existing traditional acaricides, mite infestations are hard to
control.5–7 Nevertheless, because chemical control by means of pesticides
remains the most effective pest management method, new, highly
effective acaricides with low toxicity are in great demand.
Etoxazole, a 2,4-diphenyl-1,3-oxazoline analogue, is widely used for
control of pests, including mite species, because of its unique mode of
action and low toxicities to mammals, birds, and aquatic organisms.8–11
Research on the mechanism of action of etoxazole has been underway
since the compound was discovered in 1994. Although there is some
dispute about whether the target site of etoxazole is the sulfonylurea
receptor12–14 or chitin synthase,15–22 it is generally accepted that etoxazole
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inhibits chitin synthesis.15 In 2006, Nauen and Smagghe used an isotopic
tracer method to study etoxazole and the benzoylurea insecticide
diflubenzuron and found that both compounds inhibit the synthesis of
chitin from N-acetylglucosamine.11 Nearly 20 benzoylurea insecticides
are commercially available, but only one acaricide with a
2,4-diphenyl-1,3-oxazoline skeleton has entered the market to date;
therefore, work on the development of new etoxazole analogues still
generates considerable interest.
In 2016, our group designed and synthesized dozens of oxazoline
derivatives containing sulfone or sulfoxide groups (I and II in Figure 1)23
to target a sulfonylurea receptor protein, which has been reported13,14 to
be a binding site for chitin synthesis inhibitors. Most of the synthesized
compounds showed excellent acaricidal activities against larvae and eggs.
In addition, Takeda Chemical Industries synthesized a series of
sulfonyl-group-containing compounds based on the commercially
available insecticidal diflubenzuron (III in Figure 1) and found that they
showed high activity against lepidopteran pests.24
In 2013, our group found that a diflubenzuron derivative in which the
Cl atom has been replaced with a sulfonate moiety (IV in Figure 1)
exhibits bioactivity similar to that of a commercial insecticide.25 Many of
the early commercial pesticides contained a sulfonate moiety (Fenson,
Genite, and chlorfenson)26,27 or a thiosulfonate moiety (Bensultap).28
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Owing to their physicochemical properties, sulfonate-bearing compounds
have strong affinity for lipid phases and can cross the cuticle membrane
easily to bind to target sites. Therefore, in this study, with the goal of
developing new chitin synthesis inhibitors, we used combination
principles to design a series of 2,4-diphenyl-1,3-oxazolines containing a
sulfonate moiety at the para-position of the 4-phenyl substituent on the
oxazoline ring, and we synthesized the compounds and evaluated their
acaricidal activities.
MATERIALS AND METHODS
Chemicals: All regular reagents and solvents were purchased from
Tianjin Chemical Reagents Supply and Marketing Company without any
extra treatment unless otherwise noted. All required anhydrous solvents
were treated according to standard techniques just before use.
Compounds 2,6-difluorobenzamide (Beijing Ouhe Technology Co., Ltd),
dimethylchloroacetal (Shanghai Macklin Biochemical Technology Co.,
Ltd), anisole (Tianjin Chemical Reagents Supply and Marketing
Company), AlCl3 (Tianjin Chemical Reagents Supply and Marketing
Company), BBr3 (Beijing Innochem Technology Co., Ltd), different
substituted sulfonyl chloride (Tiajin Heowns Biochemical Technology
Co., Ltd; Beijing Innochem Technology Co., Ltd; Beijing J&K
Technology Co., Ltd; Shanghai Bidepharm Technology Co., Ltd;
Shanghai Boka-chemical Technology Co., Ltd; or SAEN Chemical
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Technology (Shanghai) Co., Ltd) and trifluoromethanesulfonic anhydride
(Beijing Innochem Technology Co., Ltd) were purchased separately from
different commercial sources listed above.
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Instruments: Reaction progress was monitored by thin-layer
chromatography on silica gel GF254 with ultraviolet (UV) detection.
Melting points were obtained using an X-4 binocular microscope melting
point (mp) apparatus and are uncorrected. Yields were not optimized.
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1H-NMR spectra and C-NMR spectra were recorded utilizing a Bruker
AV400 spectrometer with CDCl3 or DMSO-d6 as solvent and
tetramethylsilane as internal standard. High-resolution mass spectra
(HRMS) data were obtained with a Fourier Transform Ion Cyclotron
Resonance Mass Spectrometry (FTICR-MS) spectrometer (ionspec,
7.0T).
Procedures for the Synthesis of Compounds in Scheme 1.
Synthesis of N-(2-chloro-1-methoxyethyl)-2,6-difluorobenzamide (2).
Compound 2 (21.7 g, yield 87%) was synthesized by the reaction of
2,6-difluorobenzamide (15.7 g，100 mmol) and dimethylchloroacetal (44
mL，300 mmol) catalyzed with concentrated sulfuric acid (6.5 mL，120
mmol) according to the method reported in our previous study.29 The
physical data are included in Supporting Information.
Synthesis
of
N-(2-chloro-1-(4-methoxyphenyl)ethyl)-2,6-difluorobenzamide (3).
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A mixture of 2 (5.0 g, 20 mmol) and anisole (2.6 mL, 24 mmol) in 30
mL of dry CH2Cl2 was cooled to below 0 °C. The anhydrous AlCl3 (5.34
g, 40 mmol) was slowly added to the mixture under stirring, and the
reaction was carried out at room temperature subsequently until the
reaction was complete as indicated by TLC. The mixture was poured into
ice water to quench AlCl3. After separation of the organic phase, the
aqueous phase was extracted with dichloromethane three times. The
combined organic phase was washed with saturated brine, dried with
anhydrous sodium sulfate, filtered, and evaporated to give 3 (with a small
amount of 2-methoxyphenyl isomer) (5.86 g, yield 90%).
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Synthesis
of
N-(2-chloro-1-(4-hydroxyphenyl)ethyl)-2,6-difluorobenzamide (4).
To the solution of crude 3 (10 mmol, 3.26 g) in 20 mL of dry CH2Cl2
was added dropwise BBr3 (2.4 mL, 24 mmol) at -10 °C under the argon
protection, followed by stirring at room temperature for 4 h. After the
reaction was complete, the reaction solution was poured into ice-water
slowly to quench BBr3, and then the mixture was stirred until the
precipitates disappeared. The organic phase was collected and the
aqueous phase was extracted with dichloromethane three times. After the
combined organic phase was washed with saturated brine, dried with
anhydrous sodium sulfate, filtered and evaporated, compound 4 (with a
small amount of 2-hydroxyphenyl isomer) (2.84 g, yield 91%) was
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obtained.
Synthesis of 4-(2-(2,6-difluorophenyl)-4,5-dihydrooxazol-4-yl)phenol
(5).
Crude 4 (1.87 g, 6 mmol) was dissolved in 10 mL of methanol. The
solution was stirred for 1 h after the addition of NaOH (0.48 g, 12 mmol).
After most of the methanol was removed under reduced pressure, the
aqueous phase was extracted with ethyl acetate three times. The
combined organic phase was washed, dried, filtrated, concentrated in
vacuo, and further purified by flash chromatography on silica gel using
petroleum ether and ethyl acetate (v/v = 5:1) to give the target compound
5 (0.84 g, yield 51%).
Synthesis of 4-(2-(2,6-difluorophenyl)-4,5-dihydrooxazol-4-yl)phenyl
methanesulfonate (6a)
To a solution of 5 (0.55 g, 2 mmol) and triethylamine (0.57 mL, 4
mmol) in 10 mL of dry THF was added slowly the solution of
methanesulfonyl chloride (0.19 mL, 2.4 mmol) in 10 mL of dry THF at
room temperature under stirring, the mixture was then continuously
stirred until the reaction was complete as indicated by TLC. After THF
was removed under reduced pressure, ethyl acetate and water were added
to separate the organic phase, and the aqueous phase was extracted with
ethyl acetate three times. The combined organic phase was washed, dried,
concentrated in vacuo, and further purified by flash chromatography on
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silica gel using petroleum ether and ethyl acetate (v/v = 6:1) to give the
target compound 6a (1.16 g, yield 71%).
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Compounds 6b-w were synthesized according to the similar procedure
used for compound 6a. The physical data are in datail in the Supporting
Information.
Synthesis of 4-(2-(2,6-difluorophenyl)-4,5-dihydrooxazol-4-yl)phenyl
trifluoromethanesulfonate (6x)
To a solution of 5 (0.55 g, 2 mmol) and NaOH (0.10 g, 2.4 mmol) in
10 mL of solvent (H2O/CCl4 = 1/1) was slowly added a solution of
trifluoromethanesulfonic anhydride (0.19 mL, 2.4 mmol) in 5 mL of CCl4
at 0 °C under stirring, and the mixture was continuously stirred for 3 h
until the reaction was complete as indicated by TLC. Dichloromethane
and water were added to separate the organic phase, and the aqueous
phase was extract with dichloromethane three times. The combined
organic phase was washed, dried, concentrated in vacuo, and further
purified by flash chromatography on silica gel using petroleum ether and
ethyl acetate (v/v = 5:1) to give the target compound 6x (0.58 g, yield
71%).
Biological Assays
Biological assays of the activities of the test compounds against mites and
various insects were conducted according to literature procedures29–32 at
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25 ± 1 °C in a greenhouse. The assay details are provided in Supporting
Information.
Acaricidal Activity against Eggs and Larvae of T. cinnabarinus. Each test
compound was dissolved in acetone, and the acetone solution was diluted
with distilled water to the desired concentration (200–0.05 mg/L). Fresh
sieva bean leaves infested with mite eggs or larvae (60–100 eggs or
larvae per leaf) were dipped into the test solution and swirled around for 3
s and then placed in a tube (10 cm inner diameter) lined with a piece of
filter paper. The bioactivities were evaluated 4 days after treatment and
are reported as mortality percentages, where 0% indicates no activity and
100% indicates total kill.
Larvicidal Activities against Cotton Bollworm (Helicoverpa armigera),
Corn Borer (Ostrinia nubilalis), and Oriental Armyworm (Mythimna
separata). Disks (diameter approximately 5 cm) were cut from fresh corn
leaves and then dipped into the prepared test solution and swirled around
for 3–5 s. After air-drying, each treated leaf disk was placed in a glass
vessel (7 cm diameter), and 10 third-instar larvae were added to the vessel
and lined with a piece of filter paper. Percentage mortality was evaluated
4 days after treatment. Leaves treated with acetone were used as controls.
Larvicidal Activity against Mosquito (Culex pipiens pallens). Twenty
fourth-instar mosquito larvae were placed in 10 mL of the test solution,
and after 8 days, the number of dead larvae were counted. Results are
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expressed as mortality percentages.
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Statistical Analysis
Each treatment was carried out three times. The mortality data given in
Tables 1–4 are means ± SDs for the three replicates. Linear regression
equations and correlation coefficients were obtained with four or five sets
of data in Tables 2 and 3 by means of the DPS Data Processing System
software. LC50 values were auto-calculated and are reported with 95%
confidence intervals.
RESULT AND DISCUSSION
Chemistry
The route used to synthesize the test compounds is outlined in Scheme 1.
Briefly, key intermediate 5 was prepared from 2,6-difluorobenzamide (1)
via a sequence involving condensation with dimethylchloroacetal, a
Friedel–Crafts reaction with anisole, demethylation with BBr3, and
oxazoline ring formation. Because a mixture of para- and
ortho-methoxy-substituted isomers was obtained from the Friedel–Crafts
reaction and the isomers had similar polarities, they were not separated
prior to the demethylation reaction. After the methyl group had been
removed, the reaction mixture was allowed to stir long enough to ensure
that phenol 4 was completely dissolved in the solvent, so that it could be
separated by filtration from the precipitate (H3BO3) that formed when the
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BBr3 was quenched.33 Under alkaline conditions, 4 cyclized to give
oxazoline 5. Analysis of structure–activity relationships has indicated that
para-substitution on the 4-phenyl group is beneficial for bioactivity,9,10 so
para-hydroxyphenyl compound 5 was purified from other isomers by
means of column chromatography. Note that in an attempt to avoid the
formation of ortho-isomers in the Friedel–Crafts reaction, we explored
the use of various phenyl ethers, but only t-butoxybenzene worked.
However, owing to the difficulty of synthesizing t-butoxybenzene and the
high cost of obtaining it from commercial suppliers, we chose anisole.
Isoxazole 5 reacted with various sulfonyl chlorides and sulfonyl
anhydride to afford target compounds 6a–x (60–96%) in moderate to high
yields, except in the cases of 6r and 6s (22 and 44%, respectively).
Biological Activities and Structure–Activity Relationships
Activities against T. cinnabarinus Larvae and Eggs. The acaricidal
activities of compounds 6a–x and etoxazole (as a control) against larvae
and eggs of mites were tested (Table 1). Most of the sulfonate-
-containing compounds displayed good to excellent larvicidal and
ovicidal activities. Among the alkanesulfonates (6a–e), 6c (which has a
medium-length n-propyl group) had much higher activities than 6a
(methyl), 6b (ethyl), and 6d (n-butyl). Benzenesulfonates with a
straight-chain alkane substituent (6a–d) showed similar or better
larvicidal activities than cyclohexane-substituted compound 6e. For
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benzenesulfonates 6g to 6j, the phenyl group of which has a para-halogen
atom, the activities against both larvae and eggs increased as the
electronegativity of the halogen atom decreased, except in the case of
I-substituted compound 6j. There were no obvious differences between
the activities of para-F-, ortho-F-, and meta-F-substituted compounds 6g,
6k, and 6l. The activities of 6n and 6o (which have two and three F atoms,
respectively) were higher than the activities of the mono-F-substituted
compounds (6g, 6k, and 6l). Compared with compounds bearing a
strongly electron-withdrawing group, such as 6m and 6w, compound 6q,
which has an electron-donating t-butyl group, possessed higher larvicidal
and ovicidal activities. Finally, vinyl-substituted compound 6f and
trifluoromethyl-substituted compound 6x showed only moderate
acaricidal activities.
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Because 6c, 6i, and 6q showed the best bioactivities against both larvae
and eggs, their activities were assayed at lower concentrations, and LC50
values were calculated for both larvae and eggs (Tables 2 and 3).
Compounds 6c and 6i (LC50 = 0.066 ± 0.021 and 0.073 ± 0.021 mg/L,
respectively) showed larvicidal activities comparable to that of etoxazole
(0.091 ± 0.051 mg/L). Remarkably, however, t-butylphenyl-substituted
compound 6q exhibited a lower LC50 (0.022 ± 0.009 mg/L) against larvae
than that of etoxazole. In addition, the ovicidal activities of 6c and 6q
(0.043 ± 0.031 and 0.044 ± 0.020 mg/L) were lower than that of
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etoxazole (0.095 ± 0.059 mg/L). Taken together, these results suggest that
benzenesulfonate 6q deserves to be further studied.
Activity against Mosquito Larvae and Lepidopteran Pests. We also
evaluated the activities of 6a–x and etoxazole against mosquito larvae
(Table 4). Most of the compounds showed 100% mortality at 10 mg/L,
whereas treatment with etoxazole resulted in only 70% mortality. Notably,
the mortalities of 6d, 6g, 6h, and 6k were 60% or more at 2 mg/L.
Compound 6h showed 100% mortality at 2 mg/L, exhibiting the best
insecticidal activity against mosquito larvae of all the tested compounds.
In contrast, the activities of 6a–x against lepidopteran pests (cotton
bollworm, corn borer, and oriental armyworm) (see Supporting
information) were not as high as those against mosquito: most of the test
compounds showed mortalities lower than 60% even at a concentration of
600 mg/L.
In summary, we designed and synthesized a series of novel sulfonate-
containing 2,4-diphenyl-1,3-oxazoline derivatives and assayed their
acaricidal activity. All of the test compounds exhibited good larvicidal
and ovicidal activity against spider mites, and one compound in
particular—4-t-butylphenyl-substituted compound 6q—showed higher
activities than etoxazole. Our results indicate that oxazoline derivatives
containing a sulfonate group are worthy of further study.
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ASSOCIATED CONTENT
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Supporting Information. The physical data and spectra of all target
compounds. This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
*Phone: +86-(0)22-23503952. Fax: +86-(0)22-23503952. E-mail:
wangqm@nankai.edu.cn, liuyuxiu@nankai.edu.cn
Notes
The authors declare no competing financial interest.
Funding Sources
This work was supported by the National Key Research and Development
Program of China (2016YFD0300708) and the National Natural Science
Foundation of China (21772102).
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Synthesis
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acaricidal/insecticidal
2,4-diphenyl-1,3-oxazolines. J. Pestic. Sci. 2002, 27, 1–8.
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segregant mapping uncovers resistance mutations and the mode of action of a chitin
synthesis inhibitor in arthropods. Proc. Natl. Acad. Sci. U. S. A., 2012, 109(12),
4407-4412.
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Regulation of chitin synthesis in the larval midgut of Manduca sexta. Insect Biochem.
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Leeuwen, T.; Nauen, R.; Vontas, J. Resistance mutation conserved between insects
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1989-06-27.
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insecticidal evaluation of new benzoylureas containing amide and sulfonate groups
based on the sulfonylurea receptor protein binding site for diflubenzuron and
glibenclamide. J. Agric. Food Chem., 2013, 61(3), 517-522.
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group. J. Agric. Food Chem. 2011, 59, 4851-4859.
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1-(substituented)thioalkylpyrroles. U.S. Patent 5302383, 1993.
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Faraday Soc., 1955, 51, 19-22.
410
411
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413
Figure Captions
414
415
416
417
Figure 1. Inspirations for the Design of Sulfonate-Containing Oxazolines 6a–x.
Scheme 1. Synthesis and Chemical Structures of Sulfonate-Containing Oxazolines
6a–x.
418
419
420
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422
423
Figure 1
F
F
O
Cl
O
OEt
O
O
N
S
O
N
F
O
F
O
S
I
R1
Fenson
Etoxazole
Cl
F
F
O
O
O
O
N
S
Cl
F
F
O
S
Genite
O
N
R2
II
Cl
O
S
O
O
O
S
R5
O
O
F
Cl
X
O
O
C
O
S
Chlorfenson
H
N
H
C
N
R3
F
O
C
O
C
O
N
H
H
III
O
F
F
N
N
Cl
S
S
O
O
S
F
O
C
O
C
O
S
S
H
N
H
N
O
R4
O
Diflubenzuron
O
IV
Bensultap
F
424
425
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427
Scheme 1
F
Cl
O
F
F
HN
OMe
H
N
AlCl3
CH2Cl2
0C-rt
H2SO4
NH2
Cl
O
Cl
MeO
F
F
O
OMe
F
O
O
1
2
3
F
F
F
F
F
F
Cl
O
O
N
HN
BBr3
dry CH2Cl2
RSO2X/base
OH
NaOH
N
MeOH
O
O
O
S
O
R
OH
6a-x
Br
5
4
R =
F
I
Cl
6d
6f
6g
6j
6a
6b
6c
6e
6h
6q
6i
NH
O
F
F
CF3
F
F
F
O
F
6l
F
6o
O
6k
6t
6m
6n
6p
6r
6s
CF3
6x
CN
NO2
6v
6w
6u
428
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431
Table 1. Mortalities of Oxazolines 6a–x and Etoxazole against Carmine Spider Mite
Larvae and Eggsa
Mortality (%) against larvae
Mortality (%) against eggs
Comp
200
mg/
L
200
mg/
L
100
ound
10 mg/L
100
1 mg/L
80 ± 5
0.1 mg/L
50 ± 0
100 mg/L
93.3 ± 2.9
10 mg/L
80 ± 0
1 mg/L
70 ± 0
0.1 mg/L
mg/L
6a
100
100
100
—
6b
6c
6d
100
100
100
100
100
100
90 ± 0
100
60 ± 0
100
100
100
100
93.3 ± 2.9
100
80 ± 0
100
50 ± 0
90 ± 0
60 ± 0
—
—
50 ± 0
—
80 ± 0
60 ± 0
100
90 ± 0
93.3 ± 2.9
85 ± 5
6e
6f
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
80 ± 0
100
90 ± 0
80 ± 0
90 ± 0
95 ± 0
100
60 ± 0
60 ± 0
50 ± 0
86.6 ± 5.8
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
80 ± 0
100
90 ± 0
60 ± 0
90 ± 0
90 ± 0
90 ± 0
70 ± 0
—
—
—
—
—
6g
6h
6i
58.3 ± 5.8
70±0
—
—
100
60 ± 0
70 ± 0
—
95 ± 0
100
—
100
73.3 ± 5.8
30 ± 0
—
6j
100
86.7 ± 5.8 63.3 ± 5.8
100
86.7 ± 5.8 58.3 ± 5.8
6k
6l
100
90±0
90±0
80 ± 0
50 ± 0
50 ± 0
—
93.3 ± 2.9
100
80 ± 0
90 ± 0
50 ± 0
56.7 ± 5.8
70 ± 0
—
100
—
6m
6n
6o
6p
6q
6r
100
95±0
80 ± 0
58.3 ± 5.8
58.3 ± 5.8
58.3 ± 5.8
—
100
90 ± 0
—
100
95±0
80 ± 0
90 ± 0
100
86.7 ± 5.8
50 ± 0
—
100
100
90 ± 0
93.3 ± 5.8 66.7 ± 5.8
—
100
86.7 ± 5.8
100
70 ± 0
91.7 ± 2.9
100
70 ± 0
96.7 ± 2.9
50 ± 0
50 ± 0
90 ± 0
—
—
100
96.7 ± 2.8
50 ± 0
85
46.7 ± 5.8
—
90 ± 0
70 ± 0
70 ± 0
—
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Journal of Agricultural and Food Chemistry
6s
6t
100
100
100
100
100
100
100
100
93.3 ± 2.8
80 ± 0
100
70 ± 0
53.3 ± 5.8
95 ± 0
40 ± 0
—
100
100
100
100
90
95 ± 0
80 ± 0
95 ± 0
93.3 ± 2.9
80 ± 0
90 ± 0
100
90 ± 0
70 ± 0
90 ± 0
70 ± 0
40 ± 0
70 ± 0
95 ± 0
60 ± 0
30 ± 10
63.3 ± 5.8
46.7 ± 5.8
—
—
—
—
—
90 ± 0
100
6u
6v
6w
6x
63.3 ± 5.8
—
—
95 ± 0
70 ± 0
70 ± 0
30 ± 10
—
—
—
90 ± 5 73.3 ± 5.8
60 ± 0
90 ± 0
100
100
56.7 ± 5.8
80 ± 0
—
—
Etoxa
zole
100
100
63.3 ± 5.8
30 ± 0
432
aValues are means ± SDs (n = 3).
433
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436
Table 2. Mortalities and LC50 Values for Oxazolines 6c, 6i, and 6q and Etoxazole
against Carmine Spider Mite Larvae
Mortality (%)a against larvae and LC50 values
Compound
10
1
0.5
0.05
0.01
mg/L
—
Formula (y =
ax + b)
Correlation
coefficient
b
0.1 mg/L
80 ± 0
LC50
mg/L mg/L
mg/L
mg/L
y = 3.39x +
9.01
6c
100a
100
100
95 ± 5
90 ± 0
40 ± 0
40 ± 0
0.066 ± 0.021
0.90
—
y = 3.38x +
8.83
6i
100
100
70 ± 0
0.073 ± 0.021
0.87
0.94
6q
95 ± 5 90 ± 0
86.7 ±
5.8
50 ± 0 36.7 ± 5.8
y = 1.67x +
7.45
0.022 ± 0.009
63.3 ±
5.8
—
y = 1.24x +
6.29
Etoxazole
100
90 ± 0 80 ± 0
30 ± 0
0.091 ± 0.051
0.96
437
438
aMortality percentages are means ± SDs (n = 3). bValues are given with 95% confidence intervals.
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440
Table 3. Mortalities and LC50 Values for Oxazolines 6c, 6i, and 6q and Etoxazole
441
against Carmine Spider Mite Eggs
Mortality (%)a against eggs and LC50 values
Compound
0.5
0.05
0.01
mg/L
20 ± 0
Formula (y = ax
+ b)
Correlation
coefficient
0.99
b
1 mg/L
0.1 mg/L
LC50
mg/L
90 ± 5
75 ± 5
mg/L
6c
6i
100
76.7 ± 5.8
60 ± 0
50 ± 0
30 ± 0
45 ± 5
30 ± 0
y = 1.28x + 6.75
y = 1.21x + 6.21
y = 1.33x + 6.81
y = 1.48x + 6.52
0.043 ± 0.031
0.101 ± 0.058
0.044 ± 0.020
0.095 ± 0.059
90 ± 0
0.96
6q
96.7 ± 2.9 90 ± 5
95 ± 5 80 ± 0
78.3 ± 2.9
60 ± 0
0.96
Etoxazole
0.97
442
443
444
aMortality percentages are means ± SDs (n = 3). bValues are given with 95% confidence intervals.
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Table 4. Mortalities of Oxazolines 6a–x and Etoxazole against Mosquito Larvae
Mortality (%)a against mosquito larvae
Compound
10 mg/L
5 mg/L
20 ± 10
60 ± 5
31.3 ± 2.9
100
2 mg/L
1 mg/L
—
6a
6b
100
—
—
100
—
6c
100
—
—
6d
100
68.3 ± 2.9
—
—
6e
100
50 ± 5
—
—
6f
61.7 ± 2.9
100
—
—
6g
100
60 ± 5
100
—
—
6h
100
100
20 ± 5
—
6i
68.3 ± 5.8
100
—
6j
63.3 ± 5.8
100
—
—
6k
100
78.3 ± 2.9
—
—
6l
100
50 ± 0
30 ± 5
30 ± 10
50 ± 5
51.7 ± 2.9
—
—
6m
6n
100
—
—
100
—
—
6o
100
—
—
6p
100
—
—
6q
71.7 ± 2.9
100
—
—
6r
53.3 ± 5.8
—
—
—
6s
60 ± 5
60 ± 0
40 ± 10
100
—
—
6t
—
—
—
6u
—
—
—
6v
40 ± 0
—
—
—
6w
6x
61.7 ± 2.9
68.3 ± 2.9
70 ± 5
—
—
—
—
—
Etoxazole
—
—
—
447
448
aMortality percentages are means ± SDs (n = 3).
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Journal of Agricultural and Food Chemistry
Graphical Abstract
Agricultural and Environmental Chemistry
F
O
Cl
F
O
O
N
O
N
S
OEt
O
O
O
F
S
I
R1
Fenson
F
F
O
Cl
O
O
O
Etoxazole
S
N
O
S
F
Cl
R2
F
F
II
Genite
O
N
Cl
O
S
O
O
O
S
O
R5
O
F
F
X
Cl
O
O
O
S
H
H
Chlorfenson
C
N
C
N
R3
with excellent acaricidal activities
O
N
III
F
O
S
O
H
O
C
S
H
O
C
N
N
Cl
O
S
S
F
O
F
O
O
C
O
H
H
N
C
N
S
O R4
Diflubenzuron
Bensultap
O
IV
F
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