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CN113773312A - Novel isoxazoline derivative and preparation method and application thereof - Google Patents

Novel isoxazoline derivative and preparation method and application thereof Download PDF

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CN113773312A
CN113773312A CN202111049132.XA CN202111049132A CN113773312A CN 113773312 A CN113773312 A CN 113773312A CN 202111049132 A CN202111049132 A CN 202111049132A CN 113773312 A CN113773312 A CN 113773312A
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isoxazoline derivative
novel isoxazoline
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曲书昊
朱丽飞
王瑞宁
王小莉
李利红
樊克锋
李艳玲
匡秀华
郭永刚
李宇伟
赵玉丛
李慧娟
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Henan University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
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Abstract

本发明公开了一种新型异噁唑啉类衍生物及其制备方法和用途，所述新型异噁唑啉类衍生物的架构式如I所示：

Figure DDA0003252219600000011
其中，R为：
Figure DDA0003252219600000012
Figure DDA0003252219600000013
的一种。与现有技术相比，本发明首次合成了一系列新型异噁唑啉类衍生物，合成步骤简单，总产率较高，本发明制备的新型异噁唑啉类衍生物I1对二斑叶螨毒力表现出较好活性，因此本发明制得的新型异噁唑啉类衍生物I1可用于制备二斑叶螨杀虫剂，为吡唑类杀虫剂的制备提供了新的可能。

Figure 202111049132

The invention discloses a novel isoxazoline derivative, a preparation method and application thereof, and the structural formula of the novel isoxazoline derivative is shown in I:

Figure DDA0003252219600000011
where R is:
Figure DDA0003252219600000012
Figure DDA0003252219600000013
a kind of. Compared with the prior art, the present invention has synthesized a series of novel isoxazoline derivatives for the first time, the synthesis steps are simple, and the total yield is high. The virulence of spider mites shows good activity, so the novel isoxazoline derivative I 1 prepared by the present invention can be used to prepare spider mite insecticides, which provides a new method for the preparation of pyrazole insecticides. possible.

Figure 202111049132

Description

Novel isoxazoline derivative and preparation method and application thereof
Technical Field
The invention relates to the field of isoxazolines, in particular to a novel isoxazoline derivative and a preparation method and application thereof.
Background
Heterocyclic compounds are important intermediates or chemical entities in the synthesis and development of pesticides. Isoxazoles are valuable five-membered heterocyclic compounds with unique chemical structures and biological activities, and many derivatives thereof are developed into agricultural chemical products. The aryl isoxazoline compounds not only occupy a relatively important position in the field of organic synthesis, but also have good application values in the aspects of inflammation diminishing, cancer resistance, sterilization, virus resistance, weeding and the like, and in addition, the aryl isoxazoline derivatives containing heterocyclic compounds have unique insecticidal activity in the aspects of modern crop and animal protection, such as flurarana which is a commercially available veterinary drug and fluxaflutolide which is an insecticide.
Tetranychus urticae is a worldwide important pest mite, and damages hundreds of plants, especially vegetables, flowers and fruit trees, causing serious economic loss. The aryl isoxazole derivative containing heterocyclic compounds has unique insecticidal activity in the aspects of modern crop and animal protection, such as marketed veterinary drug fluranide and insecticide fluxaflutolamide. The pyrazole pesticide is an important heterocyclic compound and is widely applied to a plurality of fields of insect killing, mite killing, sterilization, weeding and the like. Among them, N-alkylpyrazole-5-carboxamide pesticides are attracting attention because of their advantages such as unique action mechanism, safety, high efficiency, no cross resistance, small effective dosage, and the like, and representative varieties thereof are tebufenpyrad and tolfenpyrad.
The present invention considers that the design strategy that the aryl isoxazoline can be structurally combined with the pesticide N-alkyl pyrazole-5-formamide derivatives is an effective way to discover new bioactive molecules. Therefore, the research work for searching novel isoxazoline insecticides is of great significance.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provides a novel isoxazoline derivative and a preparation method and application thereof.
In order to achieve the purpose, the invention is implemented according to the following technical scheme:
the first object of the present invention is to provide a novel isoxazoline derivative, wherein the structural formula of the novel isoxazoline derivative is shown as formula I:
Figure BDA0003252219580000021
wherein R is:
Figure BDA0003252219580000022
Figure BDA0003252219580000023
one of (1) and (b).
The second object of the present invention is to provide a method for preparing a novel isoxazoline derivative, which comprises the following steps:
s1, dissolving 1-methyl-3-aldehyde-5-pyrazole ethyl formate, hydroxylamine hydrochloride and sodium acetate in ethanol to obtain a compound II:
Figure BDA0003252219580000024
s2, dissolving a compound II, NCS, 1, 3-dichloro-5- (3,3, 3-trifluoroprop-1-en-2-yl) benzene and triethylamine in N, N-dimethylformamide, extracting an obtained reaction system by water and ethyl acetate, combining organic phases, drying the organic phases, filtering and concentrating to obtain a reaction crude product, and performing column chromatography separation and gradient elution on the reaction crude product to obtain a compound III:
Figure BDA0003252219580000031
s3, dissolving the compound III and NaOH in tetrahydrofuran THF and water, and heating and refluxing to obtain a compound IV:
Figure BDA0003252219580000032
s4, compound IV, EDCI, HOBt, corresponding amine derivatives, Et3Dissolving N in dichloromethane, extracting the obtained reaction system by 1M HCl, ethyl acetate and saturated sodium bicarbonate aqueous solution, combining organic phases, drying the organic phases, filtering and concentrating to obtain a reaction crude product, separating the reaction crude product by column chromatography, and performing gradient elution to obtain a compound shown as a general formula I:
Figure BDA0003252219580000033
wherein R is:
Figure BDA0003252219580000034
Figure BDA0003252219580000035
one of (1) and (b).
The third purpose of the invention is to provide the application of the novel isoxazoline derivative in the preparation of the tetranychus urticae insecticide.
Compared with the prior art, the invention synthesizes a series of novel isoxazoline derivatives for the first time, the synthesis steps are simple, the total yield is higher, and the novel isoxazoline derivatives I prepared by the invention1The isoxazoline derivative I has good activity on the virulence of tetranychus urticae koch, so that the novel isoxazoline derivative I prepared by the invention1Can be used for preparing tetranychus urticae insecticide, and provides a new possibility for preparing pyrazole insecticide.
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FIG. 1 is a flow chart of the preparation of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. The specific embodiments described herein are merely illustrative of the invention and do not limit the invention.
Example 1
Referring to FIG. 1, 3- [5- (3, 5-dichlorophenyl) -4, 5-dihydro-5- (trifluoromethyl) -3-isoxazolyl]-1-methyl-N- [ 2-oxo-2- [ (2,2, 2-trifluoro-2-ethyl) amino]Ethyl radical]-1H-pyrazole-5-carboxamide (I)1)：
Under the protection of nitrogen, 1-methyl-3-aldehyde-5-pyrazole ethyl formate (3.64g, 20.00mmol) is dissolved in ethanol (100mL), hydroxylamine hydrochloride (2.57g, 37.00mmol) and sodium acetate (2.13g, 26.00mmol) are added continuously, the reaction is stirred at room temperature for 14 hours, the mixture is poured into water, white solid is separated out, and after suction filtration, 3.5g of white solid compound II is obtained, wherein the yield is 89%.
Compound II (3.2g, 16.23mmol) was dissolved in DMF (40mL) under nitrogen and NCS (2.75g, 20) was added.61mmol), the mixture was stirred at room temperature for 4 hours, and 1, 3-dichloro-5- (3,3, 3-trifluoroprop-1-en-2-yl) benzene (3.82mL, 21.75mmol) and Et were added to the above solution3N (3.02mL, 21.75mmol), the mixture was allowed to react at room temperature for an additional 4 hours, the mixture was extracted with water and ethyl acetate, the organics were combined, MgSO4Drying, suction filtering and concentrating the filtrate under rotary evaporation. The crude product was purified by silica gel chromatography eluting with 80% petroleum ether in ethyl acetate to give 4.3g of white solid III in 61% yield:1H NMR(CD3OD,400MHz)δ7.61(d,J＝1.6Hz,2H),7.57(t,J＝2.0Hz,1H),7.23(s,1H),4.37(q,J＝7.2Hz,2H),4.23(d,J＝18.4Hz,1H),4.18(d,J＝7.2Hz,3H),3.93(d,J＝18.4Hz,1H),1.40-1.36(m,3H)；13C NMR(CD3OD,100MHz)δ160.5,153.7,140.8,140.6,136.8,136.0,130.8,126.8,125.4(q,J＝277.9Hz),110.6,88.1(q,J＝30.8Hz),62.7,44.8,40.5,14.6；19F NMR(CD3OD,376MHz)δ-81.4；HRMS(ESI)found 438.0434[calc for C17H15Cl2F3N3O3(M+H)+438.0434].
compound III (3.93g, 9.01mmol) and NaOH (0.72g, 18.02mmol) were dissolved in THF (20mL) and H2O (20mL) was refluxed at 66 ℃ for 3 hours, THF was evaporated after completion of the reaction, the pH of the mixed solution was adjusted to 4 with 1M HCl, a white solid was precipitated, and the compound IV (3.3g) was obtained by suction filtration in a yield of 90%.
Compound IV (1.0g, 2.45mmol), EDCI (0.70g,3.68mmol) and HOBt (0.50g, 3.68mmol) were dissolved in dichloromethane (20mL) under nitrogen, reacted at room temperature for 30 minutes, and then 2-amino-N- (2,2, 2-trifluoroethyl) acetamide (460mg, 2.94mmol) and Et were added3N (0.68mL, 4.90mmol), the mixture was stirred at room temperature for 15 h, then washed with 1M HCl, saturated sodium bicarbonate and saturated NaCl, respectively, and the organics were combined, MgSO4Drying, suction filtering and concentrating the filtrate under rotary evaporation. Purifying the crude product by silica gel column chromatography, eluting with 95% petroleum ether in ethyl acetate to obtain white solid I1250mg, yield 19%.1H NMR(CD3OD,400MHz)δ7.61(d,J＝1.6Hz,2H),7.58-7.57(m,1H),7.23(s,1H),4.23(d,J＝18.4Hz,1H),4.15(s,3H),4.04(s,2H),3.97-3.94(m,2H),3.92-3.90(m,1H)；13C NMR(CD3OD,100MHz)δ172.1,161.8,153.8,140.8,140.5,138.4,136.8,130.8,126.8,125.9(q,J＝277.9Hz),125.4(q,J＝283.8Hz),107.3,88.1(q,J＝30.4Hz),44.8,43.3,41.4(q,J＝34.7Hz),40.2；19F NMR(CD3OD,376MHz)δ-74.0(t,J＝7.5Hz),-81.4；HRMS(ESI)found548.0537[calc for C19H16Cl2F6N5O3(M+H)+548.0537].
Example 2
Referring to FIG. 1, 3- [5- (3, 5-dichlorophenyl) -4, 5-dihydro-5- (trifluoromethyl) -3-isoxazolyl]-1-methyl-N- (2-ethyl-3-oxo-4-iso puff oxazolidinyl) -1H-pyrazole-5-carboxamide (I)2)：
Compound IV (500mg, 1.23mmol), EDCI (0.35g, 1.85mmol) and HOBt (0.25g, 1.85mmol) were dissolved in dichloromethane (10mL) under nitrogen, reacted at room temperature for 30 minutes, and then 4-amino-2-ethylisoxazolin-3-one hydrochloride (244.9mg, 1.47mmol) and Et were added3N (0.68mL, 4.92mmol), the mixture was stirred at room temperature for 15 h, then washed with 1M HCl, saturated sodium bicarbonate and saturated NaCl, respectively, and the organics were combined, MgSO4Drying, suction filtering and concentrating the filtrate under rotary evaporation. Purifying the crude product by silica gel column chromatography, eluting with 96% petroleum ether in ethyl acetate to obtain white solid I2140mg, yield 22%.1H NMR(CD3OD,400MHz)δ7.60(d,J＝1.6Hz,2H),7.58-7.57(m,1H),7.23(s,1H),4.23(d,J＝18.3Hz,1H),4.15(s,3H),4.11-4.02(m,2H),3.92(d,J＝18.3Hz,1H),3.73-3.66(m,2H),3.65-3.59(m,1H),1.26(t,J＝6.9Hz,3H)；13C NMR(CD3OD,100MHz)δ170.1,161.8,153.8,140.8,140.5,138.4,136.8,130.8,126.8,125.4(q,J＝283.8Hz),107.3,88.1(q,J＝30.4Hz),60.5,57.5,46.7,44.8,40.2,12.1；19F NMR(CD3OD,376MHz)δ-81.3；HRMS(ESI)found 521.0913[calc for C20H19Cl2F3N5O4(M+H)+521.0913].
Example 3
Referring to FIG. 1, 3- [5- (3, 5-dichlorophenyl) -4, 5-dihydro-5- (trifluoromethyl) -3-isoxazolyl]-1-methyl-N- [4- (1,1, 1-trifluoroisopropoxy) -1-benzyl]-1H-pyrazole-5-carboxamide (I)3)：
Compound IV (500mg, 1.23mmol), EDCI (0.35g, 1.85mmol) and HOBt (0.25g, 1.85mmol) were dissolved in dichloromethane (10mL) under nitrogen, reacted at room temperature for 30 minutes, and 4- (1,1, 1-trifluoroisopropoxy) benzylamine (322.2mg, 1.47mmol) and Et were added3N (0.34mL, 2.46mmol), the mixture was stirred at room temperature for 15 h, then washed with 1M HCl, saturated sodium bicarbonate and saturated NaCl, respectively, and the organics were combined, MgSO4Drying, suction filtering and concentrating the filtrate under rotary evaporation. Purifying the crude product by silica gel column chromatography, eluting with 95% petroleum ether in ethyl acetate to obtain white solid I3112mg, 15% yield.1H NMR(CD3OD,400MHz)δ7.59(d,J＝1.6Hz,2H),7.57-7.56(m,1H),7.25-7.23(m,2H),7.16(s,1H),6.87-6.85(m,2H),5.90-5.88(m,1H),4.44(s,2H),4.21(d,J＝18.4Hz,1H),4.14(s,3H),3.91(d,J＝18.4Hz,1H),1.40(t,J＝7.0Hz,3H)；13C NMR(CD3OD,100MHz)δ161.2,159.9,153.8,140.8,140.4,138.9,136.8,131.7,130.8,130.1,126.8,125.4(q,J＝283.6Hz),125.0(q,J＝277.9Hz),115.6,106.9,88.0(q,J＝30.3Hz),86.6,64.6,44.8,40.2,6.3；19F NMR(CD3OD,376MHz)δ-76.0(d,J＝9.4Hz),-81.3；HRMS(ESI)found610.1712[calc for C25H21Cl2F6N4O3(M+H)+610.1712].
Example 4
Referring to FIG. 1, N-4-tert-butylbenzyl-3- [5- (3, 5-dichlorophenyl) -4, 5-dihydro-5- (trifluoromethyl) -3-isoxazolyl is prepared]-1-methyl-1H-pyrazole-5-carboxamide (I)4)：
Compound IV (500mg, 1.23mmol), EDCI (0.35g, 1.85mmol) and HOBt (0.25g, 1.85mmol) were dissolved in dichloromethane (10mL) under nitrogen, reacted at room temperature for 30 minutes, and 4-tert-butylbenzylamine (240.0mg, 1.47mmol) and Et were added3N (0.34mL, 2.46mmol), the mixture was stirred at room temperatureStirring for 15 hours, then adding 1M HCl, saturated sodium bicarbonate and saturated NaCl, washing respectively, combining the organic matters and MgSO 24Drying, suction filtering and concentrating the filtrate under rotary evaporation. Purifying the crude product by silica gel column chromatography, eluting with 96% petroleum ether in ethyl acetate to obtain white solid I490mg, yield 13%.1H NMR(CD3OD,400MHz)δ7.60(d,J＝2.0Hz,2H),7.58-7.57(m,1H),7.39-7.36(m,2H),7.26(d,J＝8.4Hz,2H),7.19(s,1H),4.49(s,2H),4.22(d,J＝18.4Hz,1H),4.15(s,3H),3.92(d,J＝18.4Hz,1H),1.30(s,9H)；13C NMR(CD3OD,100MHz)δ161.2,159.9,153.8,140.8,140.5,138.9,136.8,131.7,130.8,130.1,126.8,125.4(q,J＝283.7Hz),115.6,106.9,88.0(q,J＝30.4Hz),64.6,44.8,43.7,40.2,15.3；19F NMR(CD3OD,376MHz)δ-81.3；HRMS(ESI)found 555.1380[calc for C26H26Cl2F3N4O2(M+H)+555.1380].
Example 5
Referring to FIG. 1, 3- [5- (3, 5-dichlorophenyl) -4, 5-dihydro-5- (trifluoromethyl) -3-isoxazolyl]-1-methyl-N- (4-ethoxybenzyl) -1H-pyrazole-5-carboxamide (I)5)：
Compound IV (500mg, 1.23mmol), EDCI (0.35g, 1.85mmol) and HOBt (0.25g, 1.85mmol) were dissolved in dichloromethane (10mL) under nitrogen, reacted at room temperature for 30 minutes, and 4-ethoxybenzylamine (222.3mg, 1.47mmol) and Et were added3N (0.34mL, 2.46mmol), the mixture was stirred at room temperature for 15 h, then washed with 1M HCl, saturated sodium bicarbonate and saturated NaCl, respectively, and the organics were combined, MgSO4Drying, suction filtering and concentrating the filtrate under rotary evaporation. The crude product was purified by silica gel column chromatography eluting with 94% petroleum ether in ethyl acetate to give white solid I5120mg, yield 18%.1H NMR(CD3OD,400MHz)δ7.59(d,J＝1.6Hz,2H),7.56-7.55(m,1H),7.25-7.23(m,2H),7.16(s,1H),6.87-6.85(m,2H),4.44(s,2H),4.21(d,J＝18.4Hz,1H),4.14(s,3H),4.00(q,J＝6.8Hz,2H),3.91(d,J＝18.4Hz,1H),1.36(t,J＝7.0Hz,3H)；13C NMR(CD3OD,100MHz)δ161.2,159.9,153.8,140.8,140.4,138.9,136.8,131.7,130.8,130.1,126.8,125.4(q,J＝283.7Hz),115.6,106.9,88.0(q,J＝30.3Hz),64.6,44.8,43.7,40.2,15.3；19F NMR(CD3OD,376MHz)δ-81.3；HRMS(ESI)found 543.0996[calc for C24H22Cl2F3N4O3(M+H)+543.0996].
Example 6
Referring to FIG. 1, 3- [5- (3, 5-dichlorophenyl) -4, 5-dihydro-5- (trifluoromethyl) -3-isoxazolyl]-1-methyl-N- [4- (4-methylphenoxy) benzyl]-1H-pyrazole-5-carboxamide (I)6)：
Compound IV (500mg, 1.23mmol), EDCI (0.35g, 1.85mmol) and HOBt (0.25g, 1.85mmol) were dissolved in dichloromethane (10mL) under nitrogen, reacted at room temperature for 30 minutes, and 4- (4-methylphenoxy) benzylamine hydrochloride (0.37g, 1.47mmol) and Et were added3N (0.68mL, 4.92mmol), the mixture was stirred at room temperature for 15 h, then washed with 1M HCl, saturated sodium bicarbonate and saturated NaCl, respectively, and the organics were combined, MgSO4Drying, suction filtering and concentrating the filtrate under rotary evaporation. The crude product was purified by silica gel column chromatography eluting with 94% petroleum ether in ethyl acetate to give white solid I6150mg, yield 20%.1H NMR(CD3OD,400MHz)δ7.59(d,J＝1.6Hz,2H),7.56(t,J＝2.0Hz,1H),7.32-7.29(m,2H),7.18(s,1H),7.15-7.13(m,2H),6.92-6.89(m,2H),6.86-6.84(m,2H),4.48(s,2H),4.22(d,J＝18.4Hz,1H),4.15(s,3H),3.91(d,J＝18.4Hz,1H),2.30(s,3H)；13C NMR(CD3OD,100MHz)δ161.2,158.7,156.3,153.8,140.8,140.5,138.8,136.8,134.4,134.3,131.4.130.8,130.3,126.8,125.4(q,J＝283.6Hz),120.1,119.5,107.0,88.0(q,J＝30.4Hz),44.8,43.6,40.2,20.8；19F NMR(CD3OD,376MHz)δ-81.3；HRMS(ESI)found 605.1141[calc for C29H24Cl2F3N4O3(M+H)+605.1141].
Example 7
The novel isoxazoline derivative prepared by the invention is used for researching the toxicity of the novel isoxazoline derivative on two-spotted spider mites, and in order to verify the toxicity effect of the novel isoxazoline derivative on the two-spotted spider mites, the following experiments are carried out:
biological targets to be assayed: tetranychus urticae (Koch) is a sensitive population raised in laboratories for long periods. The breeding method comprises the following steps: placing potted cowpea seedlings growing to 4-6 leaf stages in an insect breeding cage (40cm is multiplied by 40cm, and a 200-mesh spun yarn is sealed), connecting tetranychus urticae to cowpea leaves, breeding, and placing the insect breeding cage in an insect breeding room; feeding conditions are as follows: 24. + -. 1 ℃ and 60. + -. 5% humidity, photoperiod 16: 8 (L: D). Adult mites are selected as test insects.
Novel isoxazoline derivative I synthesized in the above example1-I6For example, virulence effects on Tetranychus urticae:
the bioassay method refers to the NY/T3539 and 2020 tetranychus resistance monitoring technical specification and adopts a method of soaking leaves with insects. The specific method comprises the following steps: soaking sponge (5 multiplied by 4 multiplied by 1cm) (length multiplied by width multiplied by height) is arranged in a culture dish (diameter 9cm), fresh cowpea leaves without insects are cut into sponge size by using an aseptic scalpel, then the cowpea leaves are placed on the sponge surface in the culture dish, and a layer of filter paper with the same size is laid between the sponge and the leaves to form a three-layer sandwich structure of the cowpea leaves-filter paper-sponge. Carefully picking 30 female adult mites on the cowpea leaves by using a No. 0 wiring brush pen under a stereoscopic microscope, observing under the stereoscopic microscope after 3 hours, removing injured and dead individuals and supplementing healthy individuals.
The mother liquors were prepared in acetone and diluted as necessary (with 0.1% Triton X-100 aqueous solution) to a range of working concentrations. And (3) immersing the cowpea leaves with the female adult mites into the solution of the medicament to be detected, taking out after 5s, and quickly sucking the redundant liquid medicament of the mite bodies by using absorbent paper. Drying in the shade and placing the back face upward on the surface of the soaking sponge stuck with the filter paper. Each concentration was set to 3 replicates, each replicate 30 spider mites. Control was made by treatment with 0.1% aqueous Triton X-100. After 24h, the result was checked, and the mites were touched with a fine hair brush, and the mites were considered dead.
Analysis of Experimental data
The virulence regression line parameters were analyzed by POLO-plus 2.0 software to calculate LC50。
Results of the experiment
Isoxazoline derivatives I1-I6Toxic effect on two-spotted spider mite
Isoxazoline derivative I is determined by taking indoor sensitive population tetranychus urticae as test insects and adopting a method of carrying insects to soak leaves1-I6The results for its virulence level were as follows (table 1): isoxazoline derivatives I1LC of (2)50A value of 6.352 mg/L; isoxazoline derivatives I2LC of (2)5010.423 mg/L; isoxazoline derivatives I3LC of (2)5070.402 mg/L; isoxazoline derivatives I4LC of (2)5063.385 mg/L; isoxazoline derivatives I5The toxicity to the two-spotted spider mites is low, the mortality rate to the two-spotted spider mites after 24 hours of 500ppm treatment is 45.99%, and the mortality rate after 24 hours of 1000ppm treatment is 100%. Estimating LC50Between 500 and 1000 ppm; isoxazoline derivatives I6Low toxicity to Tetranychus urticae and LC50The value was 469.63 mg/L.
TABLE 1
Figure BDA0003252219580000111
As is clear from Table 1, the novel isoxazoline derivative I produced by the present invention1The isoxazoline derivative I has good activity on the virulence of tetranychus urticae koch, so that the novel isoxazoline derivative I prepared by the invention1Can be used for preparing tetranychus urticae insecticide, and provides a new possibility for preparing pyrazole insecticide.
The technical solution of the present invention is not limited to the limitations of the above specific embodiments, and all technical modifications made according to the technical solution of the present invention fall within the protection scope of the present invention.

Claims (3)

1. A novel isoxazoline derivative is characterized in that the framework formula of the novel isoxazoline derivative is shown as I:
Figure FDA0003252219570000011
wherein R is:
Figure FDA0003252219570000012
Figure FDA0003252219570000013
one of (1) and (b).
2. A method for producing a novel isoxazoline derivative according to claim 1, which comprises the steps of:
s1, dissolving 1-methyl-3-aldehyde-5-pyrazole ethyl formate, hydroxylamine hydrochloride and sodium acetate in ethanol to obtain a compound II:
Figure FDA0003252219570000014
s2, dissolving a compound II, NCS, 1, 3-dichloro-5- (3,3, 3-trifluoroprop-1-en-2-yl) benzene and triethylamine in N, N-dimethylformamide, extracting an obtained reaction system by water and ethyl acetate, combining organic phases, drying the organic phases, filtering and concentrating to obtain a reaction crude product, and performing column chromatography separation and gradient elution on the reaction crude product to obtain a compound III:
Figure FDA0003252219570000015
s3, dissolving the compound III and NaOH in tetrahydrofuran THF and water, and heating and refluxing to obtain a compound IV:
Figure FDA0003252219570000021
s4, compound IV, EDCI, HOBt, corresponding amine derivatives, Et3N in dichloromethane, the reaction system was saturated with 1M HCl and ethyl acetateExtracting with sodium bicarbonate water solution, combining organic phases, drying the organic phases, filtering, concentrating to obtain a reaction crude product, separating the reaction crude product by column chromatography, and performing gradient elution to obtain a compound shown as a general formula I:
Figure FDA0003252219570000022
wherein R is:
Figure FDA0003252219570000023
Figure FDA0003252219570000024
one of (1) and (b).
3. Use of the novel isoxazoline derivative according to claim 1 in the preparation of a tetranychus urticae insecticide.
CN202111049132.XA 2021-09-08 2021-09-08 Novel isoxazoline derivative and preparation method and application thereof Pending CN113773312A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114853748A (en) * 2022-05-06 2022-08-05 武汉工程大学 Trifluoromethyl-containing isoxazoline derivative, and preparation method and application thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114853748A (en) * 2022-05-06 2022-08-05 武汉工程大学 Trifluoromethyl-containing isoxazoline derivative, and preparation method and application thereof

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