Synthesis and Insecticidal Activity of Novel Nitropyridyl-Based Dichloropropene Ethers

Article abstract of DOI:10.1021/acs.jafc.5b02279

Dihalopropene ether insecticides are known for good features such as no cross-resistance to other insecticide classes and safety for mammals. Pyridalyl is the only currently commercialized dichloropropene ether insecticide; however, it contains a trifluoromethyl group, the synthesis of which requires harsh reagents and reaction conditions. To search for novel dihalopropene ethers with unique biological activities but without trifluoromethyl groups, a series of nitropyridyl-based dichloropropene ether analogues were synthesized by reacting nitro-based halopyridine with 2,6-dichloro-4-(3,3-dichloroallyloxy)phenol or 2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-hydroxypropyl ether. Bioassay showed that the compounds exhibited potent insecticidal activities against various lepidopteran pests. Particularly, 2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-(5-nitro-2-pyridyloxy)propyl ether (8e) was active against major agricultural pests, and its insecticidal potency was comparable to that of Pyridalyl. Besides the trifluoromethyl group in Pyridalyl, a nitro group on the 5-position of the pyridyl ring is also viable for the development of optimal insecticidal activity.

Full text of DOI:10.1021/acs.jafc.5b02279

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Letter
Synthesis and Insecticidal Activity of Novel
Nitropyridyl-based Dichloropropene Ethers
Aiping Liu, Wanqi Yu, Minhua Liu, Jianjun Bai, Weidong Liu,
Xingping Liu, Hui Pei, Li Hu, Mingzhi Huang, and Xiaoguang Wang
J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.5b02279 • Publication Date (Web): 24 Jul 2015
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Journal of Agricultural and Food Chemistry
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Synthesis and Insecticidal Activity of Novel Nitropyridylꢀbased Dichloropropene Ethers
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Aiping Liu,†‡ Wanqi Yu,†§ Minhua Liu,† Jianjun Bai,† Weidong Liu,† Xingping Liu,† Hui Pei,†
Li Hu,† Mingzhi Huang,* †ǂ Xiaoguang Wang*†
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†National Engineering Research Center for Agrochemicals, Hunan Research Institute of Chemical Industry,
Changsha 410007, People’s Republic of China;
‡Hunan Province Key Laboratory for Agrochemicals, Changsha 410014, People’s Republic of China;
§Department of Chemistry, Carleton College, Northfield 55057, United States of America;
ǂHunan Haili Chemical Industry Co. Ltd., Changsha 410007, People’s Republic of China.
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KEYWORDS: nitropyridylꢀbased dichloropropene ethers; synthesis; insecticide;
structureꢀactivity relationship
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ABSTRACT: Dihalopropene ether insecticides are known for good features such as no crossꢀresistance to
other insecticide classes, safe for mammals, etc. Pyridalyl is the only currently commercialized
dichloropropene ether insecticide, however it contains a trifluoromethyl group whose synthesis requires
harsh reagents and reaction conditions. In order to search for novel dihalopropene ethers with unique
biological activities but without trifluoromethyl groups, a series of nitropyridylꢀbased dichloropropene ether
analogues
were
synthesized
by
reacting
nitroꢀbased
halopyridine
with
2,6ꢀdichloroꢀ4ꢀ(3,3ꢀdichloroallyloxy)phenol or 2,6ꢀdichloroꢀ4ꢀ(3,3ꢀdichloroallyloxy)phenyl 3ꢀhydroxypropyl
ether. Bioassay showed that the compounds exhibited potent insecticidal activities against various
lepidopteran pests. Particularly, 2,6ꢀdichloroꢀ4ꢀ(3,3ꢀdichloroallyloxy)phenyl 3ꢀ(5ꢀnitroꢀ2ꢀpyridyloxy)propyl
ether (8e) was active against major agricultural pests and its insecticidal potency was comparable to that of
Pyridalyl. Besides the trifluoromethyl group in Pyridalyl, a nitro group on the 5ꢀposition of the pyridyl ring
is also viable for the development of optimal insecticidal activity.
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66
ꢀ
67 ꢀ INTRODUCTION
94 especially honey bees and bumble bees. Thus,
95 Pyridalyl is expected to be a key component for
96 pest control in Integrated Pest Management
97 (IPM) and insecticide resistance management.
68 The insecticide market has been dominated by
69 organophosphates, carbamates, synthetic
70 pyrethroids and neonicotinoids since the 1970s,
71 and consequently insect resistance to these
72 insecticides has become a serious problem. The
73 development of resistance to current treatments,
74 along with newly evolving pest problems, the
75 changing regulatory landscape and market
76 environment, gives rise to an emerging demand
77 of new insecticides that are not only active to
78 resistance strains but also safe to humans and
79 the environment.
98
Sakamoto et al. pioneered in the research of
99 Pyridalyl analogues. He pointed out that a
100 trifluoromethyl group on the 5ꢀposition of the
101 pyridyl ring was required for the development
102 of optimal insecticidal activity. More
103 specifically, although both the nitro group and
104 the
trifluoromethyl
group
are
105 electronꢀwithdrawing, introducing different
106 group on the 5ꢀposition of the pyridyl ring
107 yields distinctively different results. For the
80
81 wide range of pests (1-4). However only one
82 member of this group,
Dihalopropene ethers are active against a
108 nitro
109 [2ꢀ(2,6ꢀdichloroꢀ4ꢀ((3,3ꢀdichloroallyl)oxy)phen
110 oxy)ꢀ5ꢀnitropyridine], insecticidal activity
product
1a
83 2,6ꢀdichloroꢀ4ꢀ(3,3ꢀdichloroallyoxy)phenyl
84 3ꢀ[5ꢀ(trifluoromethyl)ꢀ2ꢀpyridyloxy]propyl
85 ether (Sꢀ1812) (5-8), has been developed as an
86 agricultural insecticide under the trade name
87 'Pyridalyl' by Sumitomo Chemical Co Ltd.,
88 Japan (Figure 1). Although the mechanism of
89 Pyridalyl is yet unknown or undetermined, it
90 exhibits diverse characteristics, such as long
91 residual activity, excellent rain fastness, no
92 crossꢀresistance to other insecticide classes, and
93 great safety to nonꢀtarget beneficial organisms
111 against Spodoptera litura dropped considerably
112 to LC50 > 200 mg/L as opposed to that of the
113 trifluoromethyl
product
2a
114 [2ꢀ(2,6ꢀdichloroꢀ4ꢀ((3,3ꢀdichloroallyl)oxy)phen
115 oxy)ꢀ5ꢀ(trifluoromethyl)pyridine] with LC50
116 1.25ꢀ5.00 mg/L (Figure 1) (6). This also makes
117 sense theoretically because the trifluoromethyl
118 group confers increased metabolic stability and
119 lipophilicity in addition to its high
=
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120 electronegativity (9-10). However, the current
121 processes for trifluoromethyl compounds
122 require harsh reagents and reaction conditions,
149 8aꢀ2
was
synthesized
starting
from
150 2,6ꢀdichloroꢀ3ꢀnitropyridine, and 8a’ꢀ2, the
151 3ꢀNO2 compound, was obtained as a byꢀproduct
152 of 8aꢀ2, the 5ꢀNO2 compound. However, the
153 insecticidal activity against M. separate of
154 5ꢀNO2 compound (LC50 = 7.45 mg/L) was
155 relatively stronger than that of the 3ꢀNO2
156 compound (LC50 > 40 mg/L). In addition,
157 bioassay showed that biological activities of
158 8aꢀ2 against the larvae of some important pests
159 such as M. separate (LC50 = 7.45 mg/L) and
160 Plutella xylostella (LC50 = 7.07 mg/L) were
161 comparable to that of Pyridalyl (LC50 = 4.81
162 mg/L and 4.29 mg/L respectively). However,
163 8aꢀ2 (LC50 = 54.92 mg/L) was less active
164 against Prodenia litura compared to Pyridalyl
165 (LC50 = 10.07 mg/L).
123 and
the
degradation
products
of
is
124 trifluoromethylꢀsubstituted
compounds
125 usually environmental unfriendly. It is thus
126 meaningful to develop new dihalopropene ether
127 insecticides that have insecticidal activities
128 comparable to that of Pyridalyl but are more
129 readily
130 environmentally friendly.
131 In our previous work (3), we derived 3a
to
be
produced
and
more
132 [2,6ꢀdichloroꢀ4ꢀ(3,3ꢀdichloroallyloxy)phenyl
133 3ꢀ[6ꢀtrifluoromethylꢀ2ꢀethoxyꢀ4ꢀpyrimidyloxy]
134 propyl ether] from Pyridalyl and Fluacrypyrim,
135 a commercial acaricide, and 3a showed
136 remarkable
insecticidal activity against
166
In fact, we did not discover any compound
137 Mythimna separate (LC50 = 23.72 mg/L). In
138 order to obtain novel dihalopropene ethers
139 without trifluoromethyl groups, 3a was
140 optimized first by removing the trifluoromethyl
141 group. Because both the nitro group and the
142 nitrogen atom in the pyrimidyl ring are strongly
143 electronꢀwithdrawing, 3a was then optimized by
144 replacing the nitrogen atom next to the
145 trifluoromethyl group in the pyrimidyl ring with
167 whose insecticidal activity against P. litura was
168 comparable to that of Pyridalyl until we
169 replaced 6ꢀethoxy in 8aꢀ2 with hydrogen, which
170 led
to
our
final
product
8e
171 [2,6ꢀdichloroꢀ4ꢀ(3,3ꢀdichloroallyloxy)phenyl
172 3ꢀ[5ꢀnitroꢀ2ꢀpyridyloxy]propyl ether]. Although
173 Sakamoto et al. suggested that trifluoromethyl
174 group on the 5ꢀposition was required, our other
175 works on nitropyridylꢀbased compounds
176 indicated that hydrogen exhibited similar or
177 stronger insecticidal activities than 6ꢀalkoxy.
146 CꢀNO2.
This
led
to
8aꢀ2
147 [2,6ꢀdichloroꢀ4ꢀ(3,3ꢀdichloroallyloxy)phenyl
148 3ꢀ[5ꢀnitroꢀ6ꢀethoxyꢀ2ꢀpyridyloxy]propyl ether].
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178 Therefore, 8aꢀ2 was optimized by replacing the
182 as M. separate, P. xylostella, P. litura, and etc
183 at levels similar to that of Pyridalyl. The design
184 strategies of all compounds are shown in Figure
185 2.
179 ethoxy with hydrogen to give 8e. Bioassay
180 results indicated that 8e exhibited insecticidal
181 activities against major agricultural pests such
186
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216 combined ethyl acetate extracts were washed
187 ꢀ MATERIALS AND METHODS
217 with water and dried with anhydrous sodium
218 sulfate. Then the solvent was removed using
219 rotary evaporator. The residue was separated by
188 Unless otherwise noted, reagents and solvents
189 were used as received from commercial
190 suppliers. NMR spectra were obtained with a
220 silicaꢀgel
column
chromatography
with
191 Varian
INOVAꢀ300
spectrometer
using
221 petroleum ether and ethyl acetate (10:1 by
222 volume) as eluant to give 99.5% (GC)
223 4ꢀ((3,3ꢀdichloroallyl)oxy)phenol 26.2 g (63.0%).
224 Sulfuryl dichloride (35.0 g, 260 mmol) was
192 tetramethylsilane (TMS) as the internal standard
193 and deuteriochloroform (CDCl3) as the solvent.
194 LCꢀMS
were
recorded
with
an
195 Agilent 1260/6120 Series and GCꢀMS with an
196 Agilent 7890ꢀ5975C Series. Uncorrected
197 melting points were taken in a WRSꢀ1A digital
198 melting points apparatus. Elemental analyses
199 were obtained with a Vario EL III from
200 Elementar.
225 added dropwise
to
the
solution
of
226 4ꢀ((3,3ꢀdichloroallyl)oxy)phenol (26.2 g, 120
227 mmol) and triethylamine (0.70 g, 7.0 mmol) in
228 toluene (150 mL) at 90ꢀ100℃. The reaction was
229 stirred for 8ꢀ10 h. After the extra sulfuryl
230 dichloride was removed, the resulting solution
231 was poured into iceꢀwater (500 mL), washed
232 with saturated sodium hydrogencarbonate
233 solution and then water, and dried with
234 anhydrous sodium sulfate. The solvent was
235 removed to give 95.5% (GC) 4a 26.6 g (73.7%).
201
Synthesis. The general synthetic methods for
202 the target compounds 8 are shown in Figure 3.
203 Representative procedures are given below.
204 Yields were not optimized. All reactions were
205 carried out under a protective atmosphere of dry
206 nitrogen or utilizing a calcium chloride tube.
236
2,6-Dichloro-4-(3,3-dichloroallyloxy)phenyl
207
2,6-Dichloro-4-(3,3-dichloroallyloxy)phenol
237 3-hydroxypropyl ether (5a). 3ꢀBromopropanol
238 (2.02 g, 14.5 mmol) in DMF (20 mL) was added
239 dropwise to a solution of 4a (2.88 g, 10 mmol)
240 and potassium carbonate (2.00 g, 14.5 mmol) in
241 DMF (60 mL) at room temperature. The reaction
242 mixture was stirred for 26ꢀ28 h, after which the
243 reaction was poured into iceꢀwater (150 mL) and
244 extracted with ethyl acetate (2*100 mL). The
208 (4a). 1,1,3ꢀTrichloropropene (27.6 g, 190 mmol)
209 in N,Nꢀdimethyl formamide (DMF; 30 mL) was
210 added dropwise to a solution of hydroquinone
211 (23.1 g, 210 mmol) and potassium carbonate
212 (30.4 g, 220 mmol) in DMF (100 mL) at room
213 temperature. After stirred for 6ꢀ8 h, the reaction
214 was poured into iceꢀwater (500 mL) and
215 extracted with ethyl acetate (2*250 mL). The
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245 combined ethyl acetate extracts were washed
274 q, J=7.2 Hz, CH2), 7.01 (1H, d, J=8.1 Hz, Py H),
275 8.24 (1H, d, J=8.1 Hz, Py H).
246 with water and dried with anhydrous sodium
247 sulfate. Then the solvent was removed using
248 rotary evaporator. The residue was separated by
276
2-Chloro-6-ethoxy-3-nitropyridine
(6a’-2).
277 Sodium ethanolate (4.10 g, 60 mmol) in ethanol
278 (20 mL) was added dropwise to a solution of
279 2,6ꢀdichloroꢀ3ꢀnitropyridine (11.6 g, 60 mmol)
280 in ethanol (40 mL) at 0℃. After stirred for 4ꢀ5 h
249 silicaꢀgel
column
chromatography
with
250 petroleum ether and ethyl acetate (10:1 by
251 volume) as eluant to give 96.0% (GC) 5a 2.14 g
252 (59.4%).
281 at room temperature, the reaction was poured
282 into iceꢀwater (350 mL) and extracted with ethyl
283 acetate (2*100 mL). The combined ethyl acetate
284 extracts were washed with water and dried with
285 anhydrous sodium sulfate. Then the solvent was
286 removed using rotary evaporator to give a
253
6-Chloro-2-ethoxy-3-nitropyridine
(6a-2).
254 Ethanol (2.40 g, 52.0 mmol) in toluene (10 mL)
255 was added dropwise to a solution of 60% sodium
256 hydride (4.48 g, 112 mmol) in toluene (80 mL)
257 at 0 ℃
and stirred for 30ꢀ45 min.
258 2,6ꢀDichloroꢀ3ꢀnitropyridine (10.0 g, 52.0 mmol)
259 in toluene (40 mL) was added dropwise to the
260 reaction mixture. After stirred for 2ꢀ4 h at room
261 temperature, the reaction was poured into
262 iceꢀwater (250 mL) and extracted with toluene
263 (2*150 mL). The combined toluene extracts
264 were washed with water and dried with
265 anhydrous sodium sulfate. The solvent was
266 removed to give a residue 9.80 g. After
267 separated by silicaꢀgel column chromatography
268 with petroleum ether and ethyl acetate
269 (100:1~50:1 by volume) as eluant to give 95.2%
270 (GC) 6aꢀ2 7.92 g (71.7%); GCꢀMS (EI, 70Ev)
271 (m/z) 202 (50% M+), 174 (70% M+ꢀ28), 158
287 residue
which
was
then
288 recrystallized from petroleum ether and ethyl
289 acetate to give 97.0% (GC) 6a’ꢀ2 5.62 g (44.7%).
290 GCꢀMS (EI, 70Ev) (m/z) 202 (30% M+), 187
291 (100% M+ꢀ15), 174 (60% M+ꢀ28), 158 (60%
292 M+ꢀ44), 117 (30% M+ꢀ85); H NMR δ(CDCl3)
1
293 1.40 (3H, t, J=7.2 Hz, CH3), 4.44 (2H, q, J=7.2
294 Hz, CH2), 6.74 (1H, d, J=8.7 Hz, Py H), 8.24
295 (1H, d, J=8.7 Hz, Py H).
296
2-(3-Bromopropoxy)-6-ethoxy-3-nitropyridine
297 (7a’-2). 6a’ꢀ2 (2.02 g, 10 mmol) in
298 tetrahydrofuran (THF; 20 mL) was added
299 dropwise to a solution of 60% sodium hydride
300 (0.52 g, 13 mmol) in THF (30 mL) at 0℃ and
272 (100% M+ꢀ44), 117 (60% M+ꢀ85); H NMR
1
301 stirred for 15ꢀ30 min. 3ꢀBromopropanol (1.39 g,
273 δ(CDCl3) 1.45 (3H, t, J=7.2 Hz, CH3), 4.55 (2H,
302 10.0 mmol) in THF (15 mL) was then added
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303 dropwise. The reaction mixture was stirred at
332 100:1 by volume) as eluant to give 95.7%
333 (HPLC) 8aꢀ2 as an oil 0.38 g, yield 28.0%.
334 LCꢀMS (APCI, Pos)(m/z）511 (M++1); calc for
304 room temperature for 2ꢀ3 h, after which the
305 reaction was treated as described in the synthesis
306 of 5a. The residue was separated by silicaꢀgel
307 column chromatography with petroleum ether
308 and ethyl acetate (50:1 by volume) as eluant to
309 give 98.9% (GC) 7a’ꢀ2 2.00 g (64.9%). GCꢀMS
310 (EI, 70Ev) (m/z) 304 (60% M+), 289 (15%
311 M+ꢀ15), 169 (100% M+ꢀ135), 156 (75% M+ꢀ148),
312 140 (65% M+ꢀ164); 1H NMR δ(CDCl3) 1.40 (3H,
313 t, J=7.05 Hz, CH3), 2.36ꢀ2.42 (2H, m, CH2),
314 3.67 (2H, t, J=6.15 Hz, CH2), 4.43 (2H, q, J=7.1
315 Hz, CH2), 4.62 (2H, t, J=6.0 Hz, CH2), 6.35 (1H,
316 d, J=8.7 Hz, Py H), 8.32 (1H, d, J=8.7 Hz, Py
317 H).
335 C19H18Cl4N2O6: C 44.56, H 3.54, N 5.47; found:
1
336 C 44.65, H 3.59, N 5.42; H NMR (CDCl3, 300
337 MHz) δ: 1.45 (3H, t, J =7.1 Hz), 2.26～2.34 (2H,
338 m), 4.10 (2H, t, J=5.9 Hz), 4.54 (2H, q, J =7.1
339 Hz), 4.56 (2H, t, J=6.3 Hz), 4.57 (2H, d, J=6.6
340 Hz), 6.09 (1H, t, J=6.2 Hz), 6.34 (1H, d, J=8.7
341 Hz), 6.84 (2H, s), 8.31 (1H, d, J=9.0 Hz); 13C
342 NMR (CDCl3, 75 MHz) δ: 14.39, 29.34, 63.76,
343 64.15, 65.41, 69.66, 126.53, 115.19, 120.55,
344 124.43, 124.93, 129.58, 138.61, 145.53, 154.00,
345 157.03, 164.93.
346
2,6-Dichloro-4-(3,3-dichloroallyloxy)phenyl
318
2,6-Dichloro-4-(3,3-dichloroallyloxy)phenyl
347 3-[6-ethoxy-3-nitro-2-pyridyloxy]propyl ether
348 (8a’-2). 7a’ꢀ2 (1.62 g, 5.30 mmol) in THF (10
349 mL) was added dropwise to a solution of 60%
350 sodium hydride (0.26 g, 6.50 mmol) and 4a
351 (1.53 g, 5.30 mmol) in THF (20 mL) at 0℃. The
319 3-[6-ethoxy-5-nitro-2-pyridyloxy] propyl ether
320 (8a-2). 5a (0.88 g, 2.54 mmol) in THF (10 mL)
321 was added dropwise to a solution of 6aꢀ2 (0.52 g,
322 2.54 mmol) and 60% sodium hydride (0.12 g,
323 3.00 mmol) in THF (20 mL) at 0℃, then stirred
352 reaction mixture was stirred for 25ꢀ30 min at
324 for 8ꢀ10 h at 20ꢀ30℃. The reaction mixture was
353 0℃, then for 10ꢀ12 h at 20ꢀ30 ℃. The reaction
325 poured into iceꢀwater (120 mL) and extracted
326 with ethyl acetate (2*50 mL). The combined
327 ethyl acetate extracts were washed with water
328 and dried with anhydrous sodium sulfate. After
329 the solvent was removed, the crude product was
330 separated by silicaꢀgel column chromatography
331 using petroleum ether and ethyl acetate (200:1 to
354 was then treated as described in the synthesis of
355 8aꢀ2 to give 96.6% (HPLC) 8a’ꢀ2 as an oil 1.05
356 g, yield 37.6%. LCꢀMS (APCI, Pos)(m/z）511
357 (M++1); calc for C19H18Cl4N2O6: C 44.56, H
358 3.54, N 5.47; found: C 44.59, H 3.50, N 5.52; 1H
359 NMR (CDCl3, 300 MHz) δ: 1.39 (3H, t, J =7.1
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388 kept in a room for normal cultivation. Mortality
360 Hz), 2.31～2.39 (2H, m), 4.17 (2H, t, J=5.9 Hz),
389 was determined 72 h after treatment. A control
390 group was tested with the solvent only. Test was
391 run 3 times, and results were averaged. Data
392 were subjected to probit analysis and the
393 medium lethal concentration (LC50) value of
394 tested compounds were calculated (95% FL)
395 (15).
361 4.41 (2H, q, J =7.1 Hz), 4.56 (2H, d, J=6.3 Hz),
362 4.75 (2H, t, J=6.3 Hz), 6.09 (1H, t, J=6.2 Hz),
363 6.32 (1H, d, J=8.7 Hz), 6.82 (2H, s), 8.31 (1H, d,
364 J=8.7 Hz); 13C NMR (CDCl3, 75 MHz) δ: 14.36,
365 29.37, 63.45, 64.27, 65.44, 69.73, 102.56,
366 115.18, 124.50, 124.90, 126.26, 129.58, 138.54,
367 145.54, 154.00, 157.03, 165.05.
396
Activity against Plutella xylostella or
368
The synthesis of 8a’ꢀ1, 8aꢀ3 – 8aꢀ10, 8bꢀ1 –
397 Prodenia litura. Cabbage leaves were dipped
398 into test solutions for 10 s. After airꢀdrying, five
399 leaves were put into a Petri dish with ten
400 thirdꢀinstar of test insects, kept in a room for
401 normal cultivation. Mortality was assessed 72 h
402 after treatment. A control group was tested with
403 the solvent only. Test was run 4 times. Data were
404 treated as described in M. separate.
369 8bꢀ10, 8c’ꢀ1, 8cꢀ2 – 8cꢀ4, 8dꢀ1 – 8dꢀ4, 8e’ and
370 8e with ≥95.0% purity (HPLC) were similar to
371 that of 8aꢀ2 or 8a’ꢀ2 and their structures were
372 supported by spectroscopic data in Table 1 ꢀ
373 Table 2.
374
375
Biological assay (11-14)
Test insects. Stock colonies of test insects
376 were reared in a conditioned room maintained at
377 25(±1)℃, 60(±5)% relative humidity and 14:10
378 h / light:dark.
405
406 ꢀ RESULTS AND DISCUSSION
407
Chemistry. The synthesis scheme shown in
379
Test compounds. Stock solution of every test
408 Figure 3 provides moderate yields of the test
380 compound was prepared in DMF or acetone at a
381 concentration of 1.0 g litreꢀ1, and then diluted to
382 the required test concentrations (1～500 mg
409 compounds. The structures of all synthesized
1
410 compounds were analyzed and confirmed by H
411 NMR and MS. Due to the structural similarity of
412 compounds 8, only some representative
413 compounds, such as 8a’ꢀ1, 8aꢀ2, 8a’ꢀ2, 8bꢀ2, 8e
414 and 8e’, were analyzed and confirmed by 13C
415 NMR and 8aꢀ2, 8a’ꢀ2 and 8e by elemental
416 analysis. Table 1 summarizes the chemical
9
383 litreꢀ1) with water containing 0.2% Tween 80.
384
Activity against M. separate. Ten thirdꢀinstar
385 of M. separata and 5 pieces of corn fragments
386 were placed in a Petri dish, and sprayed with test
387 solutions using a potter sprayer. After airꢀdrying,
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417 structures, MS data and physical characteristics
446 1H NMR, the hydrogen on the ortho position of
447 chlorine on the pyridyl ring has lower chemical
448 shift value than the hydrogen on the ortho
449 position of alkoxy, alkylthio or alkylamino on
450 the pyridyl ring. For example, δH = 7.01 ppm for
451 6aꢀ2 and δH = 6.74 ppm for 6a’ꢀ2. In GCꢀMS,
452 when alkoxy locates between the nitro group and
453 the nitrogen atom in the pyridyl ring, the base
454 peak is usually M+ ꢀ alkoxy + 1 or M+ ꢀ alkyl + 1
455 because alkoxy or alkyl can be removed easily.
456 For example, the base peak of 6aꢀ2 is 158 (202 ꢀ
457 OCH2CH3 + 1), but the base peak of 6a’ꢀ2 is 187
458 (202 ꢀ CH3).
418 of compounds 8. NMR and elemental analysis
419 data are listed in Table 2.
420
Due to the presence of the nitro group on the
421 pyridyl ring, we expected to observe positional
422 isomers on compounds 8. Selective synthesis of
423 positional isomers of 6 can be achieved by
424 selecting different solvents. In aprotic solvent,
425 the reaction of 2,6ꢀdichloroꢀ3ꢀnitropyridine and
426 nucleophilic alcohol yields mostly 3ꢀNO2
427 product 6a’; in protic solvent, however, the same
428 reaction gives mainly 5ꢀNO2 product 6a. Also in
429 protic
solvent,
the
reaction
of
430 2,6ꢀdichloroꢀ3ꢀnitropyridine and nucleophilie
459
Insecticidal activity. All compounds prepared
431 amine or thiol gives 3ꢀNO2 product 6b’ or 6c’.
460 were evaluated for initial activity against M.
461 separate at 100 mg/L by typical assay above, and
462 LC50 was calculated through further assay in
463 which five to six different concentrations were
464 used and listed in Table 1. A few representative
465 compounds were evaluated against P. xylostella
466 and P. litura, and LC50 values of 8aꢀ2 and 8e
467 were listed in Table 3. The activities of Pyridalyl
468 were also shown in Table 1 and Table 3.
432
Positional isomers may be differentiated with
433 1H NMR data. Because NO2 is a strongly
434 electronꢀwithdrawing group, when NO2 is on the
435 ortho position of ꢀOCH2CH2CH2Oꢀ (defined as
436 3ꢀNO2), the maximum value of δH in
437 ꢀOCH2CH2CH2Oꢀ is usually ≥ 4.75 ppm;
438 however when NO2 is on the para position of
439 ꢀOCH2CH2CH2Oꢀ (defined as 5ꢀNO2), the
440 maximum value of δH in ꢀOCH2CH2CH2Oꢀ is
441 often < 4.75 ppm. For example, δH = 4.56 ppm
442 for 8aꢀ2 and δH = 4.75 ppm for 8a’ꢀ2.
469
As shown in Table 1, all compounds 8 except
470 8aꢀ9, 8aꢀ10, 8dꢀ2, 8dꢀ4 and 8’ exhibit 100%
471 insecticidal activity against M. separate at 100
472 mg/L, and some compounds have shown potent
473 insecticidal activities when compared with
474 commercial insecticides. For example, 8aꢀ2,
443
Another way to identify positional isomers of
444 compounds 8 is to study the 1H NMR or GCꢀMS
445 of their corresponding intermediate 6 and 7. In
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475 8aꢀ4, 8aꢀ5, 8bꢀ2, 8dꢀ1 and 8e have LC50 (mg Lꢀ1)
504 respectively; for R=H, the resulting compound
505 8e showed the highest activity among
506 compounds 8 and it possessed levels of
507 insecticidal activity comparable to that of
508 Pyridalyl. When the position of the nitro group
509 was changed from 5ꢀNO2 to 3ꢀNO2 and R was
510 kept constant, the insecticidal activity of the
476 values of 7.45, 5.58, 8.58, 7.13, 8.37 and 4.09
477 respectively. Particularly, LC50 value of 8e is at
478 the same level with that of Pyridalyl
.
479 Apparent Structureꢀactivity Relationship.
480 The general structure of compounds 8 (Figure 3)
481 was optimized through R moiety and the
482 position of the nitro group. Different choices of
483 R and position of NO2 can greatly affect
484 insecticidal activity (Table 1).
511 corresponding
compound
decreased
as
512 illustrated by the orders 8a’ꢀ2 << 8aꢀ2, and 8e’
513 << 8e.
485
When the nitro group was kept on the
514
515
516
In general, for compounds 8:
486 5ꢀposition, the insecticidal activity against M.
487 separata was influenced by the nature of the R
488 group. Changing the R group from 6ꢀalkoxy to
489 6ꢀalkylamino or 6ꢀalkylthio maintained or
490 slightly reduced the insecticidal activity. For
491 example, the insecticidal activities were
492 correlated as following: 8cꢀ2 < 8bꢀ2 ≈ 8aꢀ2,
493 8bꢀ3 < 8cꢀ3 < 8aꢀ3, 8cꢀ4 < 8bꢀ4 < 8aꢀ4. For
494 6ꢀsubstituted analogues, the results in Table 1
495 showed that a C2ꢀC3 saturated chain alkyl was
496 required for the development of optimal
497 insecticidal activity, and there was no obvious
498 relationship between activity and the number of
499 carbon atoms in alkyl; for 3ꢀsubstituted
500 analogues, the insecticidal activities of the
501 corresponding compounds increased. For
502 example, the insecticidal activities of 8dꢀ1 and
503 8dꢀ3 were stronger than that of 8dꢀ2 and 8dꢀ4
Activity order of NO2: 5ꢀNO2 >> 3ꢀNO2.
Activity order of R: H > 6ꢀOCH(CH3)2 >
517 6ꢀOCH2CH3, 6ꢀNHCH2CH3 > 6ꢀO(CH2)3CH3,
518 3ꢀCl
>
6ꢀO(CH2)2CH3, 6ꢀNHCH(CH3)2
6ꢀNHCH3, 6ꢀS(CH2)2CH3
,
519 6ꢀSCH2CH3
>
>
520 3ꢀNH2, 6ꢀNHCH2CH ≡CH, 6ꢀNH(CH2)2CH3,
521 6ꢀNHCH2CH=CH2, 6ꢀNHCH2C6H5.
522
The above results demonstrate that besides the
523 trifluoromethyl group in Pyridalyl (6), a nitro
524 group on the 5ꢀposition of the pyridyl ring is also
525 viable for the development of optimal insecticidal
526 activity when the chain between the phenyl ring
527 and the pyridyl ring is ꢀOCH2CH2CH2Oꢀ. Further
528 studies on the biological activity and
529 structureꢀactivity relationships of this series of
530 compounds are in progress.
531
532 ꢀ AUTHOR INFORMATION
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565 (6) Sakamoto, N.; Saito, S.; Hirose, T.; Suzuki, M.;
533 Corresponding Authors
566 Matsuo, S.; Izumi, K.; Nagatomi, T.; Ikegami, H.;
567 Umeda, K.; Tsushima, K.; Matsuo, N. The discovery of
568 Pyridalyl: a novel insecticidal agent for controlling
569 lepidopterous pests. Pest Manag. Sci. 2004, 60, 25ꢀ34.
570 (7) Sakamoto, N.; Suzuki, M.; Tsushima, K.; Umeda, K.
534 *Telephone:
86ꢀ731ꢀ85357883.
Eꢀmail:
Eꢀmail:
535 huangꢀmz@163.com (M Huang).
536 *Telephone:
86ꢀ731ꢀ85357859.
537 Wang5999@163.com (X Wang).
538 Funding
571 Preparation
of
substituted
phenylꢀcontaining
572 dihalopropene insecticides and acaricides. European
573 Patent Application EP 722430, 1996.
539 Financial support was provided by the National
540 Natural Science Foundation of China
574 (8) Sakamoto, N.; Suzuki, M.; Nagatomi, T.; Tsushima,
575 K.; Umeda, K. Preparation of dihalopropene aryl ethers
576 as insecticides and acaricides. European Patent
577 Application EP 648729, 1995.
541 (21272062).
542
543 ꢀ REFERENCES
578 (9) Welch, J. T.; Eswarakrishnan, S. Fluorine in
579 Bioorganic Chemistry (Version 1.0); New York, Wiley,
580 1991.
544 (1) Picardi, P.; Massardo, P.; Bettarini, F.; Longoni A.
545 New chlorinated juenile hormone analoguse and their
546 activity. Pestic Sci. 1980, 11,423ꢀ431.
581 (10) Banks, R. E.; Smart, B. E.; Tatlow, J. C.; editors.
582 Organofluorine Chemistry: Principles and Commercial
583 Applications (Version 1.0); New York, Plenum Press,
584 1994.
547 (2) Quistad, B. G.; Cerf, C. D.; Kramer, J. S.; Bergot, B.
548 J.; Schooley, A.D. Design of novel insect and juvenile
549 hormones: allylic alcohol derivatives. J. Agric. Food
550 Chem. 1985, 33, 47ꢀ50.
585 (11) Liu, A. P.; Ou, X. P.; Huang, M. Z.; Wang, X. G.;
586 Liu, X. P.; Wang, Y. J.; Chen, C.; Yao, J. R.; Synthesis
587 and insecticidal activities of novel oximeꢀether
588 pyrethroids. Pest Manag. Sci. 2005, 61, 166ꢀ170.
589 (12) Liu, A. P.; Wang, X. G.; Ou, X. M.; Huang, M. Z.;
590 Chen, C.; Liu, S. D.; Huang, L.; Liu, X. P.; Zhang, C. L.;
591 Zhen, Y. Q.; Ren, Y. G.; He, L.; Yao, J. R. Synthesis and
551 (3) Wei, T. L.; Xu, M. C.; Liu, X. P.; Pei, H.; Zuo, J. J.;
552 Yu, Y. Y.; Xiang, J.; Lin, X. M.; Liu A. P. Synthesis and
553 insecticidal activity of dichloroally ethers containing
554 pyrimidine group. Fine Chemical Intermediates 2012,
555 42(1), 14ꢀ17.
556 (4) Sakamoto, N.; Matsuo, S.; Suzuki, M.; Hirose, T.;
557 Tsushima, K.; Umeda, K. Prepartion of dihalopropene
558 insecticides and acaricides. European Patent Application
559 EP 785923, 1997.
592 Fungicidal
Activities
of
Novel
593 Bis(trifluoromethyl)phenylꢀbased Strobilurins. J. Agric.
594 Food Chem. 2008, 56, 6562–6566.
560 (5) Saito, S.; Isayama, S.; Sakamoto, N.; Umeda, K.;
561 Kasamatsu, K. Pyridalyl: A novel insecticidal agent for
562 controlling lepidopterous pests. Proc Brighton Crop Prot
563 Conf-Pests and Diseases, BCPC, Farnham, Surrey, UK,
564 2002, 33ꢀ38.
595 (13) Liu, A. P.; Wang, X. G.; Chen, C.; Pei, H.; Mao, C.
596 H.; Wang, Y. J.; Liu, X. P.; Hu, Z. B.; Huang, L.; He, H.
597 J.; Ou, X. M.; Huang, M. Z.; Yao, J. R. The discovery of
598 HNPCꢀA3066: a novel strobilurin acaricide. Pest Manag.
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Journal of Agricultural and Food Chemistry
599 Sci. 2009, 65, 229ꢀ234.
603 2011, 41(5), 1ꢀ6.
600 (14) Liu, A. P.; Wang, X. G.; Ou, X. M.; , Huang, M. Z.;
601 Pei, H.; Liu, X. P.; Liu, S. D. The discovery of
602 insecticide sufluoxime. Fine Chemical Intermediates
604 (15) Bliss, C. The calculation of the dosageꢀmortality
605 curve. Ann. Appl. Biol. 1935, 22, 134ꢀ167.
606
607
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608
609
Table 1. Chemical Structures, MS, Physical Characteristics, Insecticidal Activity against M. separate at 100 mg/L and LC50 (3d)
of compounds 8.
100
20
LC50
formula
MS
mp ( oC )
regression equation
r
mg/L
mg/L
mg/L
No.
NO2
R
8a’ꢀ1
8aꢀ2
8a’ꢀ2
8aꢀ3
8aꢀ4
8aꢀ5
8aꢀ6
8aꢀ7
8aꢀ8
8aꢀ9
3ꢀNO2
5ꢀNO2
3ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
6ꢀOCH3
C18H16Cl4N2O6
C19H18Cl4N2O6
C19H18Cl4N2O6
C20H20Cl4N2O6
C20H20Cl4N2O6
C21H22Cl4N2O6
C21H22Cl4N2O6
C21H22Cl4N2O6
C22H24Cl4N2O6
C22H22Cl4N2O6
C23H24Cl4N2O6
C18H17Cl4N3O5
C19H19Cl4N3O5
C20H21Cl4N3O5
C20H21Cl4N3O5
C21H23Cl4N3O5
C20H19Cl4N3O5
C20H17Cl4N3O5
C23H19Cl4N3O5
C24H21Cl4N3O5
C17H15Cl4N3O5
C18H16Cl4N2O5S
C19H18Cl4N2O5S
C20H20Cl4N2O5S
C20H20Cl4N2O5S
C17H13Cl5N2O5
C17H13Cl5N2O5
496
510
510
524
524
538
538
538
552
550
564
495
509
523
523
537
521
519
557
571
481
512
526
540
540
500
500
oil
0a
0
ꢀc
ꢀ
> 40
6ꢀOCH2CH3
6ꢀOCH2CH3
6ꢀOCH2CH2CH3
6ꢀOCH(CH3)2
6ꢀO(CH2)3CH3
6ꢀOCHCH3CH2CH3
6ꢀOC(CH3)3
6ꢀO(CH2)4CH3
oil
100
0a
100
0
Y=2.6262+2.77x
ꢀ
0.993
ꢀ
7.45
oil
> 40
oil
100
100
100
100
100
100
30
100
100
100
9 a
11
45
0
17b
100
100
27
100
30
43
53
0
Y=ꢀ0.9779+4.5542x 0.9439
9.78
oil
Y=0.1333+6.5171x
0.9528
0.9974
ꢀ
5.58
viscous solid
oil
Y=1.5059+3.7473x
8.58
ꢀ
> 20
viscous solid
viscous solid
oil
ꢀ
ꢀ
> 20
Y=1.4715+2.4428x
ꢀ
0.9988
ꢀ
27.83
> 100
> 20
8aꢀ10 5ꢀNO2
oil
80
ꢀ
ꢀ
8bꢀ1
8bꢀ2
8bꢀ3
8bꢀ4
8bꢀ5
8bꢀ6
8bꢀ7
8bꢀ8
8bꢀ9
5ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
6ꢀNHCH3
6ꢀNHCH2CH3
6ꢀNH(CH2)2CH3
6ꢀNHCH(CH3)2
6ꢀNH(CH2)3CH3
6ꢀNHCH2CH=CH2
6ꢀNHCH2C≡CH
6ꢀNHC6H5
6ꢀNHCH2C6H5
6ꢀNH2
81.7ꢀ83.2
36.0ꢀ36.9
63.2ꢀ64.5
62.4ꢀ66.1
61.6ꢀ64.1
52.6ꢀ55.0
76.4ꢀ97.4
74.9ꢀ76.2
oil
100
100
100
100
100
100
100
0a
Y=ꢀ0.0586+4.901x
Y=1.0031+4.6838x
Y=0.7600+3.4073x
Y=1.3962+3.7704x
0.9721
0.9629
1.0000
0.9270
10.77
7.13
17.48
9.03
Y=ꢀ2.8521+5.5649x 0.9738
Y=ꢀ2.5045+5.9926x 0.9534
Y=ꢀ1.9984+5.7114x 0.9699
25.76
17.88
16.80
> 40
ꢀ
ꢀ
100
100
20
37
< 50
0
Y=1.8561+2.5131x
0.9869
17.82
16.47
> 100
9.24
8bꢀ10 5ꢀNO2
yellow solid
89.9ꢀ91.1
viscous solid
viscous solid
oil
Y=ꢀ1.0132+4.3627x 0.9037
8c’ꢀ1
8cꢀ2
8cꢀ3
8cꢀ4
8dꢀ1
8dꢀ2
8dꢀ3
8dꢀ4
8e
3ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
5ꢀNO2
3ꢀNO2
6ꢀSCH3
ꢀ
ꢀ
6ꢀSCH2CH3
6ꢀS(CH2)2CH3
6ꢀSCH(CH3)2
3ꢀCl
100
100
100
100
0
87
73
3.3
100
0
Y=2.9291+2.144x
0.9081
0.9854
ꢀ
Y=2.2714+2.6178x
11.02
> 20
ꢀ
oil
Y=2.3223+2.9004x
0.9826
ꢀ
8.37
6ꢀCl
oil
ꢀ
> 100
26.41
> 500
4.09
3ꢀBr
C17H13BrCl4N2O5 544
C17H13BrCl4N2O5 544
viscous solid
oil
100
0
ꢀ
Y=0.9814+2.8266x
0.9586
6ꢀBr
0
H
C17H14Cl4N2O5
C17H14Cl4N2O5
466
466
oil
100
ꢀ
100
ꢀ
Y=3.2727+2.8259x
0.9888
8e’
H
oil
Y=ꢀ0.5573+2.7648x 0.9657
Y=2.8967+3.0826x 0.9948
102.3
4.81
Pyridalyl
100
100
610
611
a:40 mg/L; b:12.5 mg/L; c:no test;
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612
Table 2. 1H NMR data of the synthesized nitropyridylꢀbased dichloropropene ethers
No.
1H NMR (CDCl3, 300 MHz) and 13C NMR (CDCl3, 75 MHz) , δ ppm; elemental analysis
1H NMR: 2.34～2.40 (2H, m), 4.01 (3H, s), 4.12 (2H, t, J =6.0 Hz), 4.56 (2H, d, J =6.6 Hz), 4.79 (2H, t, J =6.0 Hz), 6.09 (1H, t, J =6.3 Hz),
6.35 (1H, d, J =9.0 Hz), 6.82 (2H, s), 8.32 (1H, d, J =9.0 Hz); 13C NMR: 29.40, 54.63, 64.35, 65.48, 69.74, 102.67, 115.25, 124.50, 124.90,
126.26, 129.69, 138.63, 145.69, 154.00, 157.05,165.35
8a’ꢀ1
1H NMR: 1.04 (3H, t, J =7.5 Hz), 1.84～1.91 (2H, m), 2.28～2.34 (2H, m), 4.12 (2H, t, J =6.15 Hz), 4.46 (2H, t, J =6.6 Hz), 4.58 (2H, d, J
=6.6 Hz), 4.67 (2H, t, J =6.3 Hz), 6.11 (1H, t, J =6.0 Hz), 6.34 (1H, d, J =9.0 Hz), 6.82 (2H, s), 8.33 (1H, d, J =8.7 Hz).
1H NMR: 1.44 (6H, d, J =6.3 Hz), 2.26～2.34 (2H, m), 4.11 (2H, t, J =5.85 Hz), 4.60 (2H, d, J =6.3 Hz), 4.65 (2H, t, J =4.2 Hz), 5.44～5.52
(1H, m), 6.11 (1H, t, J =6.3 Hz), 6.32 (1H, d, J =8.7 Hz), 6.81 (2H, s), 8.31 (1H, d, J =8.7 Hz).
1H NMR: 0.95 (3H, t, J =7.5Hz), 1.48～1.55 (2H, m), 1.80～1.85 (2H, m), 2.28～2.32 (2H, m), 4.12 (2H, t, J =6.0 Hz), 4.50 (2H, t, J =6.6 Hz),
4.58 (2H, d, J =6.3 Hz), 4.65 (2H, t, J =6.3 Hz), 6.11 (1H, t, J =6.3 Hz), 6.34 (1H, d, J =8.7 Hz), 6.84 (2H, s), 8.32 (1H, d, J =8.7 Hz).
1H NMR: 1.00 (3H, t, J =7.5 Hz), 1.40 (3H, d, J =6.6 Hz), 1.70～1.89 (2H, m), 2.26～2.34 (2H, m), 4.12 (2H, t, J =6.0 Hz),4.58 (2H, d, J =6.3
Hz), 4.65 (2H, t, J =6.3 Hz), 5.22～5.34 (1H, m), 6.11 (1H, t, J =6.3 Hz), 6.32 (1H, d, J =9.0 Hz), 6.84 (2H, s), 8.31 (1H, d, J =8.7 Hz).
8aꢀ3
8aꢀ4
8aꢀ5
8aꢀ6
1H NMR: 1.68 (9H, s), 2.30～2.32 (2H, m), 4.13 (2H, t, J =5.85 Hz), 4.57 (2H, d, J =6.3 Hz), 4.62 (2H, t, J =6.6 Hz), 6.11 (1H, t, J =6.3 Hz),
8aꢀ7
8aꢀ8
8aꢀ9
8aꢀ10
8bꢀ1
8bꢀ2
6.31 (1H, d, J =9.0 Hz), 6.84 (2H, s), 8.24 (1H, d, J =8.7 Hz).
1H NMR: 0.92 (3H, t, J =6.9 Hz), 1.39～1.59 (4H, m), 1.82～1.87 (2H, m), 2.28～2.32 (2H, m), 4.12 (2H, t, J =6.0 Hz), 4.49 (2H, t, J =6.6
Hz), 4.58 (2H, d, J =6.6 Hz), 4.67 (2H, t, J =6.3 Hz), 6.11 (1H, t, J =6.3 Hz), 6.34 (1H, d, J =8.7 Hz), 6.84 (2H, s), 8.32 (1H, d, J =8.7 Hz).
1H NMR: 1.60～2.05 (8H, m), 2.26～2.36 (2H, m), 4.12 (2H, t, J =5.85 Hz), 4.58 (2H, d, J =6.0 Hz), 4.67 (2H, t, J =6.45 Hz), 5.54～5.59 (1H,
m), 6.11 (1H, t, J =6.3 Hz), 6.31 (1H, d, J =8.7 Hz), 6.84 (2H, s), 8.29 (1H, d, J =9.0 Hz).
1H NMR:1.40～1.97 (10H, m), 2.25～2.33 (2H, m), 4.12 (2H, t, J =5.85 Hz), 4.58 (2H, d, J =5.7 Hz), 4.64 (2H, t, J =6.45 Hz), 5.26～5.28
(1H, m), 6.11 (2H, t, J =6.15 Hz), 6.31 (1H, d, J =9.0 Hz), 6.84 (2H, s), 8.30 (1H, d, J =8.7 Hz).
1H NMR: 2.22～2.34 (2H, m), 3.15(3H, d, J =5.1 Hz), 4.12 (2H, t, J =5.85 Hz), 4.58 (2H, d, J =6.3 Hz), 4.69 (2H, t, J =6.3 Hz), 6.05 (1H, t, J
=9.0 Hz), 6.12 (1H, t, J =6.0 Hz), 6.84 (2H, s), 8.30 (1H, d, J=9.0 Hz), 8.640 (1H, s).
1H NMR: 1.29 (3H, t, J =7.2 Hz), 2.25～2.33 (2H, m), 3.60～3.69 (2H, m), 4.10 (2H, t, J =6.0 Hz), 4.57 (2H, d, J =6.3 Hz), 4.64 (2H, t, J =6.3
Hz), 6.02 (1H, t, J =9.3 Hz), 6.09 (1H, t, J =6.3 Hz), 6.82 (2H, s), 8.27 (1H, d, J =9.3 Hz), 8.65 (1H, s); 13C NMR: 14.65, 36.14, 29.31, 63.75,
65.39, 69.82, 100.40, 115.14, 121.64, 124.44, 124.85, 129.59, 138.88, 153.93, 145.56, 153.16, 166.52; Anal. Calcd. for C19H19Cl4N3O5: C
44.64, H 3.75, N 8.22; found: C 44.64, H 3.82, N 8.16.
1H NMR: 1.00 (3H, t, J =7.5 Hz), 1.65～1.75 (2H, m), 2.25～2.33 (2H m), 3.55～3.61 (2H, m), 4.13 (2H, t, J =5.85 Hz), 4.57 (2H, d, J =6.3
8bꢀ3
8bꢀ4
8bꢀ5
Hz), 4.64 (2H, t, J =5.55 Hz), 6.03(1H, d, J =9.3 Hz), 6.11(1H, t, J =6.15 Hz), 6.84 (2H, s), 8.29 (1H, d, J =9.3 Hz) , 8.73 (1H, s).
1H NMR: 1.25 (6H, d), 2.25～2.34 (2H, m), 4.12 (2H, t, J =6.0 Hz), 4.43～4.48 (1H, m), 4.58 (2H, d, J =6.0 Hz), 4.66 (2H, t, J =6.0 Hz), 6.03
(1H, d, J =9.0 Hz), 6.12 (1H, t, J=6.3 Hz), 6.84 (2H, s), 8.29 (1H, d, J =9.3 Hz), 8.60 (1H, s).
1H NMR: 0.97 (3H, t, J =7.2 Hz), 1.37～1.49 (2H, m), 1.62～1.72 (2H, m), 2.25～2.36 (2H, m), 3.57～3.65 (2H, m), 4.10 (2H, t, J =6.0 Hz),
4.58 (2H, d, J =6.0 Hz), 4.68 (2H, t, J =6.0 Hz), 6.03 (1H, d, J =9.3 Hz), 6.11 (1H, t, J =6.15 Hz), 6.84 (2H, s), 8.29 (1H, d, J =9.3 Hz) , 8.72
(1H, s).
1H NMR: 2.26～2.32 (2H, m), 4.11 (2H, t, J =5.85 Hz), 4.23～4.28 (2H, m), 4.57 (2H, d, J=6.6 Hz), 4.65 (2H, t, J =6.3 Hz), 5.16～5.31 (2H,
m), 5.91～5.99 (1H, m), 6.06 (1H, d, J =9.0 Hz), 6.11 (1H, t, J =6.3 Hz), 6.84 (2H, s), 8.30 (1H, d, J=9.0 Hz) , 8.75 (1H, s).
1H NMR: 2.24 (1H, t, J =2.4 Hz), 2.29～2.38 (2H, m), 4.12 (2H, t, J =6.0 Hz), 4.38～4.40 (2H, m), 4.58 (2H, d, J =6.0 Hz), 4.71 (2H, t, J =6.3
Hz), 6.11 (1H, t, J =6.3 Hz)., 6.12 (1H, d, J =9.0 Hz), 6.84(2H, s), 8.32 (1H, d, J =9.0 Hz), 8.65 (1H, s).
8bꢀ6
8bꢀ7
8bꢀ8
1H NMR: 2.25～2.39 (2H, m), 4.09 (2H, t, J =5.85 Hz), 4.58 (2H, d, J =6.3 Hz), 4.63 (2H, t, J =6.45 Hz), 6.11 (1H, t, J =6.15 Hz), 6.22 (1H, d,
J =9.0 Hz), 6.83 (2H, s), 7.23～7.67 (5H, m), 8.42 (1H, d, J =9.0 Hz) , 10.64 (1H, s).
1H NMR: 2.18～2.26 (2H, m), 4.07 (2H, t, J =5.85 Hz), 4.57 (2H, t, J =6.0 Hz), 4.58 (2H, d, J =6.3 Hz), 4.81 (2H, d, J =5.7 Hz), 6.09 (1H, d, J
=9.0 Hz), 6.10 (1H, t, J =6.15 Hz), 6.84 (2H, s), 7.28～7.37 (5H, m), 8.30 (1H, d, J =9.0 Hz), 9.02(1H, s).
8bꢀ9
1H NMR: 2.25～2.33 (2H, m), 4.11 (2H, t, J =5.7 Hz), 4.58 (2H, d, J =6.6 Hz), 4.60 (2H, t, J =5.7 Hz), 6.12 (1H, t, J =6.6 Hz), 6.16 (1H, d, J
8bꢀ10
8c’ꢀ1
8cꢀ2
8cꢀ3
8cꢀ4
8dꢀ1
8dꢀ2
8dꢀ3
8dꢀ4
8e’
=9.3 Hz), 6.84 (2H, s), 8.30 (1H, d, J =9.3 Hz).
1H NMR: 2.34～2.38 (2H, m), 2.62 (3H, s), 4.19 (2H, t, J =5.85 Hz), 4.59 (2H, d, J =6.3 Hz), 4.85 (2H, t, J =6.3 Hz), 6.11(1H, t, J =6.3 Hz),
6.83 (2H, s), 6.88 (1H, d, J =8.7 Hz), 8.17(1H, d, J =8.7 Hz).
1H NMR: 1.38 (3H, t, J =7.2 Hz), 2.30～2.36 (2H, m), 3.22 (2H, q, J =7.2 Hz), 4.13 (2H, t, J =5.85 Hz), 4.59 (2H, d, J =6.3 Hz), 4.73 (2H, t, J
=6.3 Hz), 6.11 (1H, t, J =6.3 Hz), 6.54 (1H, d, J =9.0 Hz), 6.84 (2H, s,), 8.41 (1H, d, J =9.0 Hz).
1H NMR: 1.07 (3H, t, J =7.5 Hz), 1.72～1.85 (2H, m), 2.28～2.36 (2H, m), 3.18 (2H, t, J =7.2 Hz), 4.14 (2H, t, J =6.3 Hz), 4.58 (2H, d, J =6.0
Hz), 4.72 (2H, t, J =6.3 Hz), 6.11 (2H, t, J =6.3 Hz), 6.45 (1H, d, J =9.0 Hz), 6.84 (2H, s), 8.40 (1H, d, J =9.0 Hz).
1H NMR: 1.43 (6H, d, J =6.9 Hz), 2.28～2.36 (2H, m,), 4.07～4.17 (1H, m,), 4.13 (2H, t, J =5.7 Hz), 4.58 (2H, d, J =6.6 Hz,), 4.72 (2H, t, J
=6.45 Hz), 6.11 (2H, t, J =6.3 Hz), 6.50 (1H, d, J =9.0 Hz), 6.85 (2H, s), 8.40 (1H, d, J =9.0 Hz).
1H NMR: 2.36～2.41 (2H, m), 4.18 (2H, t, J =6.0 Hz), 4.68 (2H, d, J =6.3 Hz), 4.82 (2H, t, J =6.0 Hz), 6.17 (1H, t, J =6.3 Hz), 6.84 (2H, s),
8.45 (1H, d, J =2.7 Hz), 8.99 (1H, d, J =2.4 Hz).
1H NMR: 2.30～2.38 (2H, m), 4.18 (2H, t, J =6.0 Hz), 4.57 (2H, d, J =6.0 Hz), 4.80 (2H, t, J =6.3 Hz), 6.11 (1H, t, J =6.3Hz), 6.83 (2H, s),
7.02 (1H, d, J=8.1 Hz), 8.26 (1H, d, J =8.1 Hz).
1H NMR: 2.27～2.35 (2H, m), 4.13 (2H, t, J =6.0 Hz), 4.61 (2H, d, J =6.3 Hz), 4.69 (2H, t, J =6.3 Hz), 6.14 (1H, t, J =6.2 Hz), 6.82 (2H, s),
8.61 (1H, d, J =2.7 Hz), 8.99 (1H, d, J =2.7 Hz).
1H NMR: 2.30～2.40 (2H, m), 4.18 (2H, t, J=6.0 Hz), 4.57 (2H, d, J =6.3 Hz), 4.80 (2H, t, J =6.0 Hz), 6.11 (1H, t, J =6.0 Hz), 6.82 (2H, s),
7.22 (1H, d, J =8.4 Hz), 8.13 (1H, d, J =8.1 Hz).
1H NMR: 2.30ꢀ2.38 (2H, m), 4.18 (2H, t, J=6.0 Hz), 4.57 (2H, d, J=6.3 Hz), 4.81(2H, t, J=6.0 Hz), 6.09 (1H, t, J=6.3 Hz), 6.82 (2H, s),
7.01(1H, dd, J=8.1 Hz, 4.8 Hz), 8.25(1H, dd, J=8.1 Hz, 1.8 Hz), 8.39(1H, dd, J=4.8 Hz, 1.8 Hz); 13C NMR: 29.41, 64.15, 65.45, 69.74, 115.18,
116.34, 124.51, 124.89, 129.70, 133.95, 134.91, 145.74, 153.43, 153.93,156.28.
8e
1H NMR: 2.28ꢀ2.36 (2H, m), 4.12 (2H, t, J=6.0 Hz), 4.57 (2H, d, J=6.3 Hz), 4.70 (2H, t, J=6.3 Hz), 6.09 (1H, t, J=6.3 Hz), 6.82 (1H, d, J=9.0
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Hz), 6.83 (2H, s), 8.34 (1H, dd, J=9.0 Hz, 2.7 Hz), 9.09 (1H, d, J=2.7 Hz); 13C NMR: 29.39, 64.29, 65.40, 69.74, 111.22, 115.16, 124.43,
124.96, 129.66, 133.85, 139.30, 144.88, 145.62, 153.97,167.05; Anal. Calcd. for C17H14Cl4N2O5: C 43.62, H 3.01, N 5.98; found: C 43.64, H
3.00, N 6.00.
613
614
615
616
617
Table 3. LC50 against P. xylostella and P. litura of 8aꢀ2, 8e and Pyridalyl (3d)
No.
Y=a+bx
r
LC50(mg/L)
7.07
test insect
8aꢀ2
8e
Y=2.6262+2.77x
Y=4.0618+1.4006x
Y=3.9255+1.6996x
Y=ꢀ3.1505+4.6849x
Y=2.8096+2.0033x
Y=2.8738+2.1177x
0.993
0.9964
0.9880
0.9659
0.9734
0.9942
P. xylostella
4.68
Pyridyl
4.29
8aꢀ2
8e
54.92
11.66
10.07
P. litura
Pyridyl
618
619
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Journal of Agricultural and Food Chemistry
620
621
622
623
624
625
626
627
628
629
630
631
Figure captation
Figure 1: Pyridalyl and NO2, CF3 analogues quantitative structureꢀactivity profiles
Figure 2: Design strategies of the target compounds containing nitropyridyl
Figure 3: Synthetic pathways for the novel nitropyridylꢀbased dichloropropene ethers
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632
Figure 1
633
634
635
636
Figure 2
637
638
639
640
Figure 3
641
642
643
644
645
646
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Journal of Agricultural and Food Chemistry
647
648
TOC Graphic
649
650
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