WO2019128871A1 - N-alkyl-n-cyanoalkylbenzamide compound and use thereof - Google Patents

N-alkyl-n-cyanoalkylbenzamide compound and use thereof Download PDF

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WO2019128871A1
WO2019128871A1 PCT/CN2018/122721 CN2018122721W WO2019128871A1 WO 2019128871 A1 WO2019128871 A1 WO 2019128871A1 CN 2018122721 W CN2018122721 W CN 2018122721W WO 2019128871 A1 WO2019128871 A1 WO 2019128871A1
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compound
alkyl
formula
halogen
methyl
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PCT/CN2018/122721
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French (fr)
Chinese (zh)
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冯美丽
李宏举
石欣欣
王林波
姚凯诚
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江苏中旗科技股份有限公司
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Priority claimed from CN201811502023.7A external-priority patent/CN109988150B/en
Application filed by 江苏中旗科技股份有限公司 filed Critical 江苏中旗科技股份有限公司
Priority to BR112020013303-5A priority Critical patent/BR112020013303B1/en
Priority to US16/958,711 priority patent/US11390602B2/en
Priority to EP18897562.7A priority patent/EP3733660B1/en
Publication of WO2019128871A1 publication Critical patent/WO2019128871A1/en

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    • A—HUMAN NECESSITIES
    • 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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/50—1,3-Diazoles; Hydrogenated 1,3-diazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the invention relates to the field of insecticides, in particular to an N-alkyl-N-cyanoalkylbenzamide compound having insecticidal activity and application thereof.
  • the problem of pest resistance has always been a problem for plant protection workers. To solve this problem, it is necessary to constantly seek new types of pesticides.
  • the benzamides developed by DuPont are a new class of compounds targeting the nitinin receptor, representing the compound chlorantraniliprole (RynaxypyrTM), which exhibits excellent insecticidal activity and field Evaluation results, such as low toxicity to mammals and good environmental compatibility.
  • N-cyanoalkyl anthranilamide compound is reported in the patent WO 2008134969, in which the compound 1.14 (KC1) has good insecticidal activity.
  • N-alkyl-N-cyanoalkylbenzamides as shown in the present invention are not disclosed.
  • the invention provides a novel N-alkyl-N-cyanoalkylbenzamide compound with higher insecticidal effect, which can be applied to the control of pests.
  • R 1 is selected from halogen or C 1 -C 3 alkyl
  • R 2 is selected from halogen or CN
  • R 3 is selected from halogen or C 1 -C 3 haloalkyl
  • R 4 is selected from halogen
  • R 5 is selected from H or halogen.
  • R 6 is selected from C 1 -C 3 alkyl, C1-C3 haloalkyl or C 1 -C 5 alkoxyalkyl
  • R 7 is selected from C 1 -C 5 alkyl
  • R 8 is selected from hydrogen or C 1 - C 5 alkyl.
  • Preferred compounds of the invention are those of formula I:
  • R 1 is selected from chlorine, bromine or methyl
  • R 2 is selected from chlorine, bromine, fluorine or CN
  • R 3 is selected from chlorine, bromine or trifluoromethyl
  • R 4 is selected from chlorine
  • R 5 is selected from H or chlorine
  • R 6 is selected from the group consisting of C 1 -C 3 alkyl, CH 2 OCH 3 , CH 2 O CH 2 CH 3 , CH 2 CH 2 OCH 3 , CF 3 , CH 2 CH 2 F, CH 2 CHF 2 , CH 2 CF 3 , CF 2 CF 3 or CF(CF 3 ) 2
  • R 7 is selected from methyl
  • R 8 is selected from hydrogen or methyl.
  • R 1 is selected from chlorine, bromine or methyl
  • R 2 is selected from chlorine, bromine, fluorine or CN
  • R 3 is selected from chlorine or bromine
  • R 4 is selected from chlorine
  • R 5 It is selected from H
  • R 6 is selected from a methyl group
  • R 7 is selected from a methyl group
  • R 8 is selected from a methyl group.
  • the invention also includes intermediates useful directly in the preparation of compounds of formula I, the structure of which is shown in Formula II:
  • R 1 is selected from halogen or C 1 -C 3 alkyl
  • R 2 is selected from halogen or CN
  • R 6 is selected from C 1 -C 3 alkyl, C 1 -C 3 haloalkyl or C 1 -C 5 alkoxylated
  • R 7 is selected from C 1 -C 5 alkyl
  • R 8 is selected from hydrogen or C 1 -C 5 alkyl.
  • Alkyl means a saturated aliphatic hydrocarbon group, including both straight chain and branched forms, such as methyl, ethyl, propyl, isopropyl, and the like.
  • Haloalkyl means a group wherein the alkyl group is substituted by one or more halogen atoms, such as chloroethyl, trifluoromethyl and the like.
  • Alkoxy means a group having an oxygen atom bonded to the terminal of the alkyl group, such as methoxy, ethoxy, and the like.
  • the compound of the formula I can be prepared by the reaction formula 1, wherein the substituent is as defined above unless otherwise specified.
  • the process of Scheme 1 comprises reacting a compound of formula II with a compound of formula III in the presence or absence of a base to provide a compound of formula I.
  • a base substance is advantageous for the reaction, wherein the organic base is as follows: pyridine, triethylamine, potassium t-butoxide, 4-dimethylaminopyridine or N-methylmorpholine, and inorganic bases: sodium hydride, hydrogencarbonate Sodium, sodium carbonate, potassium carbonate, sodium hydroxide, and the like.
  • the reaction is suitably carried out in an inert solvent such as tetrahydrofuran, acetonitrile, toluene, dichloromethane or the like.
  • reaction mixture containing the desired product is subjected to separation treatment according to an ordinary method, and if necessary, purification by recrystallization, column chromatography or the like, whereby the intended product can be obtained.
  • the compound of the formula II can be prepared from the reaction formula 2, wherein the substituent is as defined above unless otherwise specified.
  • the compound represented by the general formula V is produced by a known method (for example, Organic Syntheses, 9, 32 (1929).), and a compound of the formula V is obtained by a commercially available acid chloride reagent such as thionyl chloride, oxalyl chloride or the like.
  • the compounds represented by the formula IV or IV' are partially commercially available and partly prepared by a known general method, for example, J. Am. Chem. Soc., 75, 4841-4842 (1953), Chemical Communications, 48 (50), 6253. -6255 (2012) and so on.
  • the compound of the formula VI can be obtained by reacting a compound of the formula V with a compound of the formula IV, which can be prepared by known methods, for example, J. Am. Chem. Soc., 135 (12), 4628-4631 (2013) and the like.
  • Typical methods include hydrogenation reduction in the presence of a metal catalyst such as Pd/C, platinum oxide or Ni in a hydroxyl solvent such as ethanol, methanol, isopropanol (eg Chinese Journal of Chemical Engineering, 24(9), 1195- 1200 (2016)). It can also be prepared by reduction of a metal such as zinc powder or iron powder under the catalysis of an acid.
  • a metal catalyst such as Pd/C, platinum oxide or Ni
  • a hydroxyl solvent such as ethanol, methanol, isopropanol
  • the fat solubility of the molecule can be improved.
  • the introduction of the methyl group in the present invention causes the molecular to change in the spatial arrangement.
  • the fat solubility of molecules is closely related to the grooming of molecules in plants, insects and other organisms; the changes in molecular space structure also have an impact on the ability of molecules to bind to targets. These two points play an important role in the efficacy of drugs.
  • the effects of molecular fat solubility and spatial structure on the bioactive molecular grooming properties and binding ability to the target are unpredictable and require a lot of creative labor to know.
  • the compounds of the formula I according to the invention have an unexpectedly high insecticidal activity compared to the known benzamidoacetonitriles, and therefore the invention also includes compounds of the formula I for use in the control. The use of pests.
  • the present invention also encompasses pesticidal compositions having a compound of formula I as an active ingredient.
  • the active ingredient in the pesticidal composition is present in an amount between 1 and 99% by weight.
  • Also included in the pesticidal composition are agricultural, forestry, and hygienic acceptable carriers.
  • compositions of the invention may be administered in the form of a formulation.
  • the compound of the formula I is dissolved or dispersed in the carrier as an active ingredient or formulated into a formulation for easier dispersion when used as an insecticide.
  • these chemicals can be formulated as wettable powders or emulsifiable concentrates.
  • at least one liquid or solid carrier is added, and a suitable surfactant may be added as needed.
  • the technical solution of the present invention also includes a method of controlling pests by applying the pesticidal composition of the present invention to the pest or the growth medium thereof.
  • a more suitable effective amount is usually selected from 10 grams to 1000 grams per hectare.
  • one or more other fungicides, insecticides, herbicides, plant growth regulators or fertilizers, etc. may be added to the pesticidal composition of the invention, thereby producing additional The advantages and effects.
  • An advantage of the present invention is that the present invention discloses two compounds, the compound of the formula I has a higher activity at a lower concentration than the compound of the prior art, especially at a concentration of less than 1 ppm.
  • the compound of the invention has more than 60% insecticidal activity, greatly reduces the amount of the compound used in the farmland, reduces the residue of the compound in the farmland, and protects the environment.
  • the compound of the formula II is an intermediate for the synthesis of the compound of the formula I, and the compound of the formula I and the formula II synthesized by the method of the invention has a short process route and a high yield; the invention provides a formula
  • the new synthetic route of the compound of I solves the problem of inconvenient synthesis of similar compounds in the prior art, greatly reduces the production cost of the compound of the formula I, makes it more suitable for industrial applications, and reduces the production cost of the enterprise.
  • Figure 1 is a diagram showing the physical properties of a part of the compound of the formula I of the present invention.
  • Figure 2 is a diagram showing the physical properties of a compound of the formula II in the present invention.
  • Figure 3 is a schematic diagram showing the results of a nuclear magnetic resonance spectrum test of a compound of the formula I in the present invention: 1 H NMR: DMSO-d 6 , 300 MHz.
  • reaction solution was poured into 50 ml of water and extracted with dichloromethane (3 ⁇ 20 ml).
  • the reaction was continued at 40 to 45 ° C for 4 h, cooled to room temperature, and poured into a cold aqueous solution of glacial acetic acid with stirring, and 650-700 mL of ethanol was distilled off under reduced pressure, cooled to room temperature, allowed to stand, and filtered, and the filter cake was 65 mL ⁇ 2
  • the mixture was washed with ethanol, and the cake was collected and dried to obtain 120 g of a finished product.
  • the filtrate and the washing liquid were combined, and almost all the ethanol was concentrated under reduced pressure to obtain a large amount of dark green solution with a black solid.
  • the solution was extracted with chloroform (200 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness. After cooling to room temperature, the refrigerator was frozen overnight, filtered, washed with 15 mL of toluene, and dried to obtain 9 g of dark green solid recovered, the total yield was 57.2%.
  • reaction solution was poured into 50 ml of water, and extracted with dichloromethane 3*20 ml.
  • test agents were all dissolved in a 1000 mg/L solution using a mixture of acetone: N ⁇ N'-dimethylformamide.
  • 1% Tween-80 was added as an emulsifier to each of the drug solutions. These solutions were then diluted to the desired concentration of test solution with 1% Tween-20 aqueous solution. An aqueous solution containing 1% Tween-20 was used as a control.
  • Example 4 Insecticidal effect on beet armyworm
  • amaranth leaves were punched into a 1cm diameter leaf disc with a puncher and sprayed with Airbrush. A certain concentration of the test compound was sprayed on the front and back of each leaf disc, and the amount of liquid sprayed was 0.5 ml. After the dry operation, 10 shots per treatment were applied. Insects (3rd instar larvae) were treated three times per treatment. After treatment, they were placed at 25 ° C, relative humidity of 60% to 70%, and cultured in the absence of light. After 120 hours, the number of surviving insects was investigated and the mortality was calculated.
  • Example 5 Insecticidal effect on Spodoptera litura
  • the leaves of the leek that have not been exposed to the insecticide are made of scissors and about 40mm square leaves. These leaves are immersed in the solution of each compound for 30s, the leaves are placed on the absorbent paper, and air-dried to the leaves. Obvious water stains. Place the leaf dish after the dipping in a Petri dish (7 cm) and place 3 leaf discs per dish.
  • the 3rd instar larvae of Spodoptera litura which were raised from the indoor amaranth seedlings, were gently picked up on a leaf dish placed on a petri dish with a writing brush, and 10 to 15 worms were placed in each dish. The larvae were covered with a petri dish cover and placed in a larvae room at 25 ° C. The light was exposed for 16 h/dark for 8 h. After 120 h, the number of viable worms was investigated and the mortality was calculated.
  • the prepared fresh amaranth leaf disc is immersed in a certain concentration of the test compound liquid solution for 10 seconds, and taken out and naturally dried.
  • a 24-well plate was used, and one tablet was placed in each well.
  • a third-instar cotton bollworm larva was inserted and moisturized. After 120 hours, the number of surviving insects was investigated and the mortality was calculated.
  • Example 7 Insecticidal effect on rice leaf roller
  • the roots of the rice seedlings that have not been exposed to the insecticide are pulled out, the roots are washed, and the stems and leaves of the seedlings are immersed in the liquid of different concentration of the drug after the leaves have no obvious water stains (the liquid is contained in the test tube, the stem The leaves are immersed in it); after 30s of immersion, they are taken out and placed on absorbent paper to dry to the leaves without water stains. Filter the paper in a Petri dish (7 cm), moisten with water and invert the Petri dish until no water droplets flow out; cut the seedlings of the infiltrated leaves into leaves of the same diameter as the Petri dish, and lay the leaf sections on the Petri dish On the filter paper, place 15 to 20 leaf segments per petri dish.
  • Example 8 Insecticidal effect on Plutella xylostella
  • Plutella xylostella larvae Three-year-old Plutella xylostella larvae were selected Select amaranth, wash and dry, use a puncher to make a leaf dish, dip in the liquid for 10 seconds, and then dry it naturally and put it into the dish. 10 dishes of 3rd instar larvae of Plutella xylostella were added to each dish and repeated 3 times. The number of dead insects in 3 days was investigated and the mortality was counted.
  • the comparative compound KC1 (compound 1.14 in WO 2008134969) and KC2 (compound 1.18 in WO 2008134969) which are structurally closest to the compound of the present invention are selected for parallel determination of Plutella xylostella, and the experimental results are obtained. As shown in the table below.
  • KC2 The structural formula of KC2 is as follows:

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Abstract

Disclosed are an N-alkyl-N-cyanoalkylbenzamide compound: general formula (I), and an intermediate with general formula (II) used for preparing the compound, wherein: R1 is selected from halogen or C1-C3alkyl; R2 is selected from halogen or CN; R3 is selected from halogen and C1-C3haloalkyl; R4 is selected from halogen; R5 is selected from H or halogen; R6 is selected from C1-C3alkyl, C1-C3haloalkyl or C1-C5alkoxyalkyl; R7 is selected from C1-C5alkyl; and R8 is selected from hydrogen or C1-C5alkyl. Compared with compounds in the prior art, the compound of the general formula I of the present invention has a higher activity at low concentrations, particularly at concentrations below 1 ppm. The compound of the present invention has an insecticidal activity of more than 60%, greatly reducing the amount of compounds used in farmland and reducing the residue of compounds in farmland, which is conducive to protecting the environment.

Description

N-烷基-N-氰基烷基苯甲酰胺类化合物及其应用N-alkyl-N-cyanoalkylbenzamides and their applications 技术领域Technical field
本发明涉及杀虫剂领域，尤其涉及一种具有杀虫活性的N-烷基-N-氰基烷基苯甲酰胺类化合物及其应用。The invention relates to the field of insecticides, in particular to an N-alkyl-N-cyanoalkylbenzamide compound having insecticidal activity and application thereof.
背景技术Background technique
害虫的抗药性问题一直是困惑植物保护工作者的问题，要解决这一问题需要不断寻求新型的杀虫剂。由杜邦公司研发的苯甲酰胺类化合物就是一类新型的以鱼尼丁受体为作用靶标的化合物，代表化合物氯虫苯甲酰胺(chlorantraniliprole，RynaxypyrTM)表现出了综合优异的杀虫活性和田间效果、对哺乳动物毒性低及环境相容性良好等评价结果。The problem of pest resistance has always been a problem for plant protection workers. To solve this problem, it is necessary to constantly seek new types of pesticides. The benzamides developed by DuPont are a new class of compounds targeting the nitinin receptor, representing the compound chlorantraniliprole (RynaxypyrTM), which exhibits excellent insecticidal activity and field Evaluation results, such as low toxicity to mammals and good environmental compatibility.
专利WO 2008134969中报道了一种N-氰基烷基邻氨基苯甲酰胺类化合物，其中化合物1.14(KC1)具有较好的杀虫活性。An N-cyanoalkyl anthranilamide compound is reported in the patent WO 2008134969, in which the compound 1.14 (KC1) has good insecticidal activity.
Figure PCTCN2018122721-appb-000001
Figure PCTCN2018122721-appb-000001
在现有技术中，如本发明所示的N-烷基-N-氰基烷基苯甲酰胺类化合物未见公开。In the prior art, N-alkyl-N-cyanoalkylbenzamides as shown in the present invention are not disclosed.
发明内容Summary of the invention
本发明提供了一种结构新颖的、具有更高杀虫效果的N-烷基-N- 氰基烷基苯甲酰胺类化合物，它可应用于虫害的防治。The invention provides a novel N-alkyl-N-cyanoalkylbenzamide compound with higher insecticidal effect, which can be applied to the control of pests.
本发明采用的技术方案如下：一种通式I的N-烷基-N-氰基烷基苯甲酰胺的化合物，The technical scheme adopted by the present invention is as follows: a compound of the formula I N-alkyl-N-cyanoalkylbenzamide,
Figure PCTCN2018122721-appb-000002
Figure PCTCN2018122721-appb-000002
通式I中：In formula I:
R 1选自卤素或C 1-C 3烷基；R 2选自卤素或CN；R 3选自卤素或C 1-C 3卤烷基；R 4选自卤素；R 5选自H或卤素；R 6选自C 1-C 3烷基，C1-C3卤代烷基或C 1-C 5烷氧烷基；R 7选自C 1-C 5烷基；R 8选自氢或C 1-C 5烷基。其中部分通式I化合物的物理性能如图1所示；部分通式I化合物的进行核磁共振氢谱测试： 1HNMR：DMSO-d 6、300MHz所得的结果如图3所示。 R 1 is selected from halogen or C 1 -C 3 alkyl; R 2 is selected from halogen or CN; R 3 is selected from halogen or C 1 -C 3 haloalkyl; R 4 is selected from halogen; and R 5 is selected from H or halogen. ; R 6 is selected from C 1 -C 3 alkyl, C1-C3 haloalkyl or C 1 -C 5 alkoxyalkyl; R 7 is selected from C 1 -C 5 alkyl; R 8 is selected from hydrogen or C 1 - C 5 alkyl. The physical properties of some of the compounds of the general formula I are shown in Figure 1; some of the compounds of the general formula I were subjected to nuclear magnetic resonance spectroscopy: 1 H NMR: DMSO-d 6 , 300 MHz The results obtained are shown in FIG.
本发明优选的化合物为，通式I中：Preferred compounds of the invention are those of formula I:
R 1选自氯、溴或甲基；R 2选自氯、溴、氟或CN；R 3选自氯、溴或三氟甲基；R 4选自氯；R 5选自H或氯；R 6选自C 1-C 3烷基、CH 2OCH 3、CH 2O CH 2CH 3、CH 2CH 2OCH 3、CF 3、CH 2CH 2F、CH 2CHF 2、CH 2CF 3、CF 2CF 3或CF(CF 3) 2；R 7选自甲基；R 8选自氢或甲基。 R 1 is selected from chlorine, bromine or methyl; R 2 is selected from chlorine, bromine, fluorine or CN; R 3 is selected from chlorine, bromine or trifluoromethyl; R 4 is selected from chlorine; and R 5 is selected from H or chlorine; R 6 is selected from the group consisting of C 1 -C 3 alkyl, CH 2 OCH 3 , CH 2 O CH 2 CH 3 , CH 2 CH 2 OCH 3 , CF 3 , CH 2 CH 2 F, CH 2 CHF 2 , CH 2 CF 3 , CF 2 CF 3 or CF(CF 3 ) 2 ; R 7 is selected from methyl; R 8 is selected from hydrogen or methyl.
更优选的化合物为，通式I中：R 1选自氯、溴或甲基；R 2选自氯、溴、氟或CN；R 3选自氯或溴；R 4选自氯；R 5选自H；R 6选自甲基；R 7 选自甲基；R 8选自甲基。 More preferred compounds are, in formula I: R 1 is selected from chlorine, bromine or methyl; R 2 is selected from chlorine, bromine, fluorine or CN; R 3 is selected from chlorine or bromine; R 4 is selected from chlorine; R 5 It is selected from H; R 6 is selected from a methyl group; R 7 is selected from a methyl group; and R 8 is selected from a methyl group.
本发明还包括直接用于制备通式I化合物的中间体，结构如通式II所示：The invention also includes intermediates useful directly in the preparation of compounds of formula I, the structure of which is shown in Formula II:
Figure PCTCN2018122721-appb-000003
Figure PCTCN2018122721-appb-000003
通式II中：In Formula II:
R 1选自卤素或C 1-C 3烷基；R 2选自卤素或CN；R 6选自C 1-C 3烷基，C 1-C 3卤代烷基或C 1-C 5烷氧烷基；R 7选自C 1-C 5烷基；R 8选自氢或C 1-C 5烷基。其中部分通式II化合物的物理性能如图2所示。 R 1 is selected from halogen or C 1 -C 3 alkyl; R 2 is selected from halogen or CN; R 6 is selected from C 1 -C 3 alkyl, C 1 -C 3 haloalkyl or C 1 -C 5 alkoxylated R 7 is selected from C 1 -C 5 alkyl; R 8 is selected from hydrogen or C 1 -C 5 alkyl. The physical properties of some of the compounds of formula II are shown in Figure 2.
除非另外说明，在说明书和权利要求中使用的以下术语具有下面讨论的含义：Unless otherwise stated, the following terms used in the specification and claims have the meanings discussed below:
“烷基”表示饱和的脂烃基，包括直链和支链形式，例如甲基、乙基、丙基、异丙基等。“卤烷基”表示烷基被一个或多个卤原子取代的基团，如氯乙基、三氟甲基等。“烷氧基”表示烷基末端连有氧原子的基团，例如甲氧基、乙氧基等。"Alkyl" means a saturated aliphatic hydrocarbon group, including both straight chain and branched forms, such as methyl, ethyl, propyl, isopropyl, and the like. "Haloalkyl" means a group wherein the alkyl group is substituted by one or more halogen atoms, such as chloroethyl, trifluoromethyl and the like. "Alkoxy" means a group having an oxygen atom bonded to the terminal of the alkyl group, such as methoxy, ethoxy, and the like.
本发明的典型制备方法如下，但是它决不在于以任何方式限制本发明的范围。The typical preparation of the present invention is as follows, but it is in no way intended to limit the scope of the invention in any way.
通式化合物I可以通过反应式1制备，其中取代基除特别指明外均如前所限定。The compound of the formula I can be prepared by the reaction formula 1, wherein the substituent is as defined above unless otherwise specified.
反应式1：Reaction formula 1:
Figure PCTCN2018122721-appb-000004
Figure PCTCN2018122721-appb-000004
反应式1的方法包括在有碱或无碱的情况下，通式II化合物与通式III反应得到通式I化合物。The process of Scheme 1 comprises reacting a compound of formula II with a compound of formula III in the presence or absence of a base to provide a compound of formula I.
加入适量的碱类物质对反应有利，其中有机碱如下：吡啶、三乙胺、叔丁醇钾、4-二甲氨基吡啶或N-甲基吗啉等，以及无机碱：氢化钠、碳酸氢钠、碳酸钠、碳酸钾、氢氧化钠等。该反应适合在惰性溶剂中进行，惰性溶剂如下：四氢呋喃、乙腈、甲苯、二氯甲烷等。Adding an appropriate amount of a base substance is advantageous for the reaction, wherein the organic base is as follows: pyridine, triethylamine, potassium t-butoxide, 4-dimethylaminopyridine or N-methylmorpholine, and inorganic bases: sodium hydride, hydrogencarbonate Sodium, sodium carbonate, potassium carbonate, sodium hydroxide, and the like. The reaction is suitably carried out in an inert solvent such as tetrahydrofuran, acetonitrile, toluene, dichloromethane or the like.
反应完全后，按照普通方法将含有预期产物的反应混合物进行分离处理，必要时通过重结晶、柱色谱等进行纯化，由此可以得到预期产物。这些方法在文献中有较多的记载，例如J.Org.Chem.32,3069(1967)等。After completion of the reaction, the reaction mixture containing the desired product is subjected to separation treatment according to an ordinary method, and if necessary, purification by recrystallization, column chromatography or the like, whereby the intended product can be obtained. These methods are well documented in the literature, for example, J. Org. Chem. 32, 3069 (1967) and the like.
通式II化合物可以由反应式2来制备，其中取代基除特别指明外均如前所限定。The compound of the formula II can be prepared from the reaction formula 2, wherein the substituent is as defined above unless otherwise specified.
反应式2：Reaction 2:
Figure PCTCN2018122721-appb-000005
Figure PCTCN2018122721-appb-000005
通式V代表的化合物采用已知通用的方法制备(例如Organic Syntheses,9,32(1929).)，通过市售的酰氯化试剂如氯化亚砜、草酰氯等，得到通式V化合物。The compound represented by the general formula V is produced by a known method (for example, Organic Syntheses, 9, 32 (1929).), and a compound of the formula V is obtained by a commercially available acid chloride reagent such as thionyl chloride, oxalyl chloride or the like.
通式IV或IV’代表的化合物部分市售，部分采用已知通用的方法制备，例如J.Am.Chem.Soc.,75,4841-4842(1953)、Chemical Communications,48(50),6253-6255(2012)等。The compounds represented by the formula IV or IV' are partially commercially available and partly prepared by a known general method, for example, J. Am. Chem. Soc., 75, 4841-4842 (1953), Chemical Communications, 48 (50), 6253. -6255 (2012) and so on.
(1)通式V→通式VI(1) Formula V → Formula VI
由通式V化合物和通式IV化合物反应获得通式VI化合物，可以采用已知方法加以制备，例如J.Am.Chem.Soc.,135(12),4628-4631(2013)等。The compound of the formula VI can be obtained by reacting a compound of the formula V with a compound of the formula IV, which can be prepared by known methods, for example, J. Am. Chem. Soc., 135 (12), 4628-4631 (2013) and the like.
(2)通式VI→通式II(2) Formula VI → Formula II
典型的方法包括在金属催化剂如Pd/C、氧化铂或Ni的存在下，在羟基溶剂如乙醇、甲醇、异丙醇中加氢还原(例如Chinese Journal of Chemical Engineering,24(9),1195-1200(2016))。也可以用金属如锌粉、铁粉，在酸的催化下来还原制备，这些方法在文献中有较多的记载，例如WO 2010042699、染料工业,37(4):16-18(2000)等。Typical methods include hydrogenation reduction in the presence of a metal catalyst such as Pd/C, platinum oxide or Ni in a hydroxyl solvent such as ethanol, methanol, isopropanol (eg Chinese Journal of Chemical Engineering, 24(9), 1195- 1200 (2016)). It can also be prepared by reduction of a metal such as zinc powder or iron powder under the catalysis of an acid. These methods are described in the literature, for example, WO 2010042699, Dye Industry, 37(4): 16-18 (2000) and the like.
在有机分子中，用甲基或其它烷基取代氢原子后，可以提高分子的脂溶性，通过核磁数据分析可知，本发明中由于甲基的引入，导致了分子在空间排布上发生了变化。分子的脂溶性与分子在植物、昆虫等生物体内的疏导性密切相关；分子空间结构的变化对分子与靶标的结合能力也会产生影响，这两点对药效的发挥起着重要的作用。分子 脂溶性和空间结构的变化对生物活性分子疏导性能以及与靶标结合能力的影响是不可预知的，需要大量的创造性劳动才能获知。In the organic molecule, after the hydrogen atom is replaced by a methyl group or other alkyl group, the fat solubility of the molecule can be improved. According to the analysis of the nuclear magnetic data, the introduction of the methyl group in the present invention causes the molecular to change in the spatial arrangement. . The fat solubility of molecules is closely related to the grooming of molecules in plants, insects and other organisms; the changes in molecular space structure also have an impact on the ability of molecules to bind to targets. These two points play an important role in the efficacy of drugs. The effects of molecular fat solubility and spatial structure on the bioactive molecular grooming properties and binding ability to the target are unpredictable and require a lot of creative labor to know.
现已发现，同已知的苯甲酰胺基乙腈类化合物相比，本发明通式I所示的化合物具有意想不到的高杀虫活性，因此，本发明还包括了通式I化合物用于控制虫害的用途。It has now been found that the compounds of the formula I according to the invention have an unexpectedly high insecticidal activity compared to the known benzamidoacetonitriles, and therefore the invention also includes compounds of the formula I for use in the control. The use of pests.
本发明还包括以通式I化合物作为活性组分的杀虫组合物。该杀虫组合物中活性组分的重量百分含量在1-99％之间。该杀虫组合物中还包括农业、林业、卫生上可接受的载体。The present invention also encompasses pesticidal compositions having a compound of formula I as an active ingredient. The active ingredient in the pesticidal composition is present in an amount between 1 and 99% by weight. Also included in the pesticidal composition are agricultural, forestry, and hygienic acceptable carriers.
本发明的组合物可以制剂的形式施用。通式I化合物作为活性组分溶解或分散于载体中或配制成制剂以便作为杀虫剂使用时更易于分散。例如：这些化学制剂可被制成可湿性粉剂或乳油。在这些组合物中，至少加入一种液体或固体载体，并且当需要时可以加入适当的表面活性剂。The compositions of the invention may be administered in the form of a formulation. The compound of the formula I is dissolved or dispersed in the carrier as an active ingredient or formulated into a formulation for easier dispersion when used as an insecticide. For example, these chemicals can be formulated as wettable powders or emulsifiable concentrates. In these compositions, at least one liquid or solid carrier is added, and a suitable surfactant may be added as needed.
本发明的技术方案还包括防治虫害的方法：将本发明的杀虫组合物施于所述的害虫或其生长介质上。通常选择的较为适宜有效量为每公顷10克到1000克。The technical solution of the present invention also includes a method of controlling pests by applying the pesticidal composition of the present invention to the pest or the growth medium thereof. A more suitable effective amount is usually selected from 10 grams to 1000 grams per hectare.
对于某些应用，例如在农业上可在本发明的杀虫组合物中加入一种或多种其它的杀菌剂、杀虫剂、除草剂、植物生长调节剂或肥料等，由此可产生附加的优点和效果。For certain applications, for example, in agriculture, one or more other fungicides, insecticides, herbicides, plant growth regulators or fertilizers, etc. may be added to the pesticidal composition of the invention, thereby producing additional The advantages and effects.
本发明的优点在于：本发明公开了两种化合物，通式I的化合物相比于现有技术中的化合物，在低浓度下具有更高的活性，特别是在低于1ppm的浓度下，本发明的化合物任具有60％以上的杀虫活性， 大大缩减了化合物在农田中的使用量，减少了化合物在农田中的残留，保护环境。An advantage of the present invention is that the present invention discloses two compounds, the compound of the formula I has a higher activity at a lower concentration than the compound of the prior art, especially at a concentration of less than 1 ppm. The compound of the invention has more than 60% insecticidal activity, greatly reduces the amount of the compound used in the farmland, reduces the residue of the compound in the farmland, and protects the environment.
通式II的化合物是合成通式I化合物的中间体，采用本发明的方法合成的通式I和通式II的化合物，其工艺路线短，收率高；本发明提供了一种针对通式I的化合物的新的合成路线，解决了现有技术中类似化合物合成不方便的问题，大大缩减了通式I的化合物的生产成本，使其更加适用于工业上应用，缩减企业的生产成本。The compound of the formula II is an intermediate for the synthesis of the compound of the formula I, and the compound of the formula I and the formula II synthesized by the method of the invention has a short process route and a high yield; the invention provides a formula The new synthetic route of the compound of I solves the problem of inconvenient synthesis of similar compounds in the prior art, greatly reduces the production cost of the compound of the formula I, makes it more suitable for industrial applications, and reduces the production cost of the enterprise.
附图说明DRAWINGS
图1为本发明的中部分通式I化合物的物理性能图；Figure 1 is a diagram showing the physical properties of a part of the compound of the formula I of the present invention;
图2为本发明中部分通式II化合物的物理性能图；Figure 2 is a diagram showing the physical properties of a compound of the formula II in the present invention;
图3为本发明中部分通式I化合物的进行核磁共振氢谱测试： 1HNMR：DMSO-d 6、300MHz所得的结果示意图。 Figure 3 is a schematic diagram showing the results of a nuclear magnetic resonance spectrum test of a compound of the formula I in the present invention: 1 H NMR: DMSO-d 6 , 300 MHz.
具体实施方式Detailed ways
下面结合具体实施方式对本发明作进一步详细的描述，但不意味着限制本发明。The invention is further described in detail below with reference to specific embodiments, but is not intended to limit the invention.
实施例1Example 1
化合物1.15：N-(6-N-((2-氰基丙基-2-基)-N-甲基胺甲酰基)-2,4-二氯苯基)-1-(3-氯吡啶-2-基)-3-溴-1H-吡唑-5-甲酰胺的合成Compound 1.15: N-(6-N-((2-cyanopropyl-2-yl)-N-methylcarbamoyl)-2,4-dichlorophenyl)-1-(3-chloropyridine Synthesis of 2-yl)-3-bromo-1H-pyrazole-5-carboxamide
(1)2-甲基-2-(甲胺基)丙腈的合成(1) Synthesis of 2-methyl-2-(methylamino)propionitrile
Figure PCTCN2018122721-appb-000006
Figure PCTCN2018122721-appb-000006
将8.5g(0.1mol)的丙酮氰醇加入至50ml的四口烧瓶中， 室温下缓慢通入3.1g(0.1mol)的甲胺气体，通毕后，继续在室温下搅拌反应5h后，用10ml×3二氯甲烷萃取，合并有机相，无水硫酸钠干燥，减压脱溶，得6.18g无色透明液体，收率63.0％。8.5 g (0.1 mol) of acetone cyanohydrin was added to a 50 ml four-necked flask, and 3.1 g (0.1 mol) of methylamine gas was slowly introduced at room temperature. After completion, the reaction was further stirred at room temperature for 5 hours. The organic phase was extracted with 10 ml of EtOAc (3 mL), dried over anhydrous sodium sulfate, and evaporated.
(2)2-硝基苯甲酰氯的合成(2) Synthesis of 2-nitrobenzoyl chloride
Figure PCTCN2018122721-appb-000007
Figure PCTCN2018122721-appb-000007
将8.4g(0.05mol)的2-硝基苯甲酸、100ml的二氯乙烷、17.8g(0.15mol)的氯化亚砜和1滴DMF依次加入至250ml的单口烧瓶中，升温至回流反应，反应3h后，减压脱溶，得8.9g黄色液体，收率95.9％。不做进一步后处理，直接用于下一步。8.4 g (0.05 mol) of 2-nitrobenzoic acid, 100 ml of dichloroethane, 17.8 g (0.15 mol) of thionyl chloride and 1 drop of DMF were sequentially added to a 250 ml single-mouth flask, and the temperature was raised to reflux. After reacting for 3 hours, it was desolvated under reduced pressure to obtain 8.9 g of a yellow liquid, yield 95.9%. Without further post-processing, use it directly in the next step.
(3)2-硝基-N-甲基-N-(2-氰基丙-2-基)苯甲酰胺的合成(3) Synthesis of 2-nitro-N-methyl-N-(2-cyanopropan-2-yl)benzamide
Figure PCTCN2018122721-appb-000008
Figure PCTCN2018122721-appb-000008
将4.9g(0.05mol)的2-甲基-2-(甲胺基)丙腈、20ml的二氯甲烷和5.1g(0.05mol)三乙胺依次加入至250ml的四口烧瓶中，0℃下滴加含8.9g(0.048mol)2-硝基苯甲酰氯的20ml二氯甲烷溶液，滴毕后，继续在0℃下搅拌反应2h。向反应液中加入50ml水后，用20ml×3的二氯甲烷萃取，合并有机相，有机相依次用饱和氯化钠水溶液洗涤，无水硫酸钠干燥，减压脱溶，得9.1g黄色固体，收率76.6％。4.9 g (0.05 mol) of 2-methyl-2-(methylamino)propionitrile, 20 ml of dichloromethane and 5.1 g (0.05 mol) of triethylamine were sequentially added to a 250 ml four-necked flask at 0 ° C. A solution of 8.9 g (0.048 mol) of 2-nitrobenzoyl chloride in 20 ml of dichloromethane was added dropwise, and after completion of the dropwise addition, the reaction was further stirred at 0 ° C for 2 h. After adding 50 ml of water to the reaction mixture, the mixture was extracted with EtOAc (EtOAc m. The yield was 76.6%.
(4)2-氨基-N-甲基-N-(2-氰基丙-2-基)苯甲酰胺的合成Synthesis of (4) 2-Amino-N-methyl-N-(2-cyanopropan-2-yl)benzamide
Figure PCTCN2018122721-appb-000009
Figure PCTCN2018122721-appb-000009
依次将20ml水、2.2g(0.04mol)的还原Fe粉和1ml的30％盐酸加入至100ml的四口烧瓶中，缓慢加热至80℃，再在80℃下搅拌30min后，分批分次加入2.5g(0.01mol)的2-硝基-N-甲基-N-(2-氰基丙-2-基)苯甲酰胺，温度一直保持不超过80℃，加毕后，继续在80℃下搅拌反应，HPLC追踪至反应结束。反应液降至室温后，加入1.6g的氢氧化钠后，抽滤，滤饼用热水洗涤，收集的滤液用2×100ml的乙酸乙酯萃取，有机相经水、饱和碳酸钠溶液和饱和食盐水洗涤后，用无水硫酸钠干燥，减压脱溶，得1.37g棕色液体，收率63.3％。20 ml of water, 2.2 g (0.04 mol) of reduced Fe powder and 1 ml of 30% hydrochloric acid were successively added to a 100 ml four-necked flask, slowly heated to 80 ° C, and further stirred at 80 ° C for 30 min, and then added in portions. 2.5 g (0.01 mol) of 2-nitro-N-methyl-N-(2-cyanopropan-2-yl)benzamide, the temperature is kept at not more than 80 ° C, after the addition, continue at 80 ° C The reaction was stirred and the HPLC was traced to completion. After the reaction solution was cooled to room temperature, 1.6 g of sodium hydroxide was added, followed by suction filtration, and the filter cake was washed with hot water. The collected filtrate was extracted with 2×100 ml of ethyl acetate. The organic phase was saturated with water, saturated sodium carbonate and saturated. After washing with brine, it was dried over anhydrous sodium sulfate and evaporated, and evaporated,
(5)N-(1-氰基异丙基)-N-甲基-2-氨基-3,-5-二氯苯甲酰胺的合成(5) Synthesis of N-(1-cyanoisopropyl)-N-methyl-2-amino-3,-5-dichlorobenzamide
Figure PCTCN2018122721-appb-000010
Figure PCTCN2018122721-appb-000010
依次将1.1g(5mmol)的2-氨基-N-甲基-N-(2-氰基丙-2-基)苯甲酰胺、2.2g(12.5mmol)N-氯代丁二酰亚胺和20ml的DMF加入至100ml的四口烧瓶中，室温下搅拌反应，HPLC追踪至反应结束。将反应液倒入100ml水中，用20ml×3的乙酸乙酯萃取，合并有机相，有机相依次用饱和氯化钠水溶液洗涤，无水硫酸钠干燥，减压脱溶，得1.1g淡黄色色固体，收率78.6％。1.1 g (5 mmol) of 2-amino-N-methyl-N-(2-cyanopropan-2-yl)benzamide, 2.2 g (12.5 mmol) of N-chlorosuccinimide and 20 ml of DMF was added to a 100 ml four-necked flask, and the reaction was stirred at room temperature, and the HPLC was traced to completion. The reaction mixture was poured into 100 ml of water, and extracted with 20 ml of ethyl acetate. The organic phase was combined, and the organic phase was washed sequentially with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate Solid, yield 78.6%.
(6)N-(6-N-((2-氰基丙基-2-基)-N-甲基胺甲酰基)-2,4-二氯苯基)-1-(3-氯吡啶-2-基)-3-溴-1H-吡唑-5-甲酰胺的合成(6) N-(6-N-((2-Cyanopropyl-2-yl)-N-methylcarbamoyl)-2,4-dichlorophenyl)-1-(3-chloropyridine Synthesis of 2-yl)-3-bromo-1H-pyrazole-5-carboxamide
Figure PCTCN2018122721-appb-000011
Figure PCTCN2018122721-appb-000011
将1g(0.00376mol)的2-氨基-3,5-二氯-N-甲基-N-(2-氰基丙-2-基)苯甲酰胺、10ml的四氢呋喃和0.3g(0.00376mol)的吡啶依次加入至50ml的四口烧瓶中，冰浴下，缓慢滴加含1.2g(0.00376mol)2-(3-氯-吡啶-2-基)-5-溴-2H-吡唑-3-碳酰氯(按照WO 02/070483方法制得)的10ml的四氢呋喃溶液，滴毕后，再在冰浴下搅拌反应过夜，HPLC追踪反应进程。将反应液倒入50ml水中，二氯甲烷3×20ml萃取，有机相依次用饱和碳酸钠、饱和氯化钠水溶液和水洗涤，无水硫酸钠干燥，减压脱溶，粗产品通过柱色谱提纯(洗脱剂：乙酸乙酯：石油醚＝3:1)，得0.85g白色固体，收率41.9％。1 g (0.00376 mol) of 2-amino-3,5-dichloro-N-methyl-N-(2-cyanopropan-2-yl)benzamide, 10 ml of tetrahydrofuran and 0.3 g (0.00376 mol) The pyridine was sequentially added to a 50 ml four-necked flask, and 1.2 g (0.00376 mol) of 2-(3-chloro-pyridin-2-yl)-5-bromo-2H-pyrazole-3 was slowly added dropwise under ice cooling. - 10 ml of a tetrahydrofuran solution of carbonyl chloride (prepared according to the method of WO 02/070483), after completion of the dropwise addition, the reaction was stirred overnight under an ice bath, and the progress of the reaction was followed by HPLC. The reaction solution was poured into 50 ml of water and extracted with dichloromethane (3×20 ml). The organic phase was washed successively with saturated sodium carbonate, saturated aqueous sodium chloride and water, dried over anhydrous sodium sulfate (eluent: ethyl acetate: petroleum ether = 3:1) gave 0.85 g of white solid.
实施例2Example 2
化合物1.1：N-(2-N-((2-氰基丙基-2-基)-N-甲基胺甲酰基)-4-氯-6-甲基苯基)-1-(3-氯吡啶-2-基)-3-溴-1H-吡唑-5-甲酰胺的合成Compound 1.1: N-(2-N-((2-cyanopropyl-2-yl)-N-methylcarbamoyl)-4-chloro-6-methylphenyl)-1-(3- Synthesis of chloropyridin-2-yl)-3-bromo-1H-pyrazole-5-carboxamide
(1)、2-硝基-3-甲基苯甲酰氯的合成(1) Synthesis of 2-nitro-3-methylbenzoyl chloride
Figure PCTCN2018122721-appb-000012
Figure PCTCN2018122721-appb-000012
将5.4g(0.03mol)的2-硝基-3-甲基苯甲酸、100ml的二氯乙烷、23.8g(0.2mol)的氯化亚砜和1滴DMF依次加入至250ml的单口烧瓶中，升温至回流反应，反应3h后，加压脱溶，得5.7g棕色液体，收率95.2％。不做进一步后处理，直接用于下一步。5.4 g (0.03 mol) of 2-nitro-3-methylbenzoic acid, 100 ml of dichloroethane, 23.8 g (0.2 mol) of thionyl chloride and 1 drop of DMF were sequentially added to a 250 ml single-mouth flask. The temperature was raised to reflux reaction, and after 3 hours of reaction, the solution was decomposed by pressure to obtain 5.7 g of a brown liquid in a yield of 95.2%. Without further post-processing, use it directly in the next step.
(2)、N-(1-氰基异丙基)-N-甲基-3-甲基-2-硝基苯甲酰胺的合成Synthesis of (2), N-(1-Cyanoisopropyl)-N-methyl-3-methyl-2-nitrobenzamide
Figure PCTCN2018122721-appb-000013
Figure PCTCN2018122721-appb-000013
将4.0g(0.03mol)的2-甲基-2-(甲胺基)丙腈盐酸盐、10ml的四氢呋喃、10ml水和5.1g(0.06mol)NaHCO 3依次加入至250ml的四口烧瓶中，-10℃下滴加含5.7g 2-硝基-3-甲基苯甲酰氯的20ml四氢呋喃溶液，滴毕后，继续在-10℃下搅拌反应2h。向反应液中加入50ml水后，用20ml×3的乙酸乙酯萃取，合并有机相，有机相依次用饱和氯化钠水溶液洗涤，无水硫酸钠干燥，减压脱溶，得4.4g棕色固体，收率56.5％。 4.0 g (0.03 mol) of 2-methyl-2-(methylamino)propionitrile hydrochloride, 10 ml of tetrahydrofuran, 10 ml of water and 5.1 g (0.06 mol) of NaHCO 3 were sequentially added to a 250 ml four-necked flask. A solution of 5.7 g of 2-nitro-3-methylbenzoyl chloride in 20 ml of tetrahydrofuran was added dropwise at -10 ° C, and after completion of the dropwise addition, the reaction was further stirred at -10 ° C for 2 h. After adding 50 ml of water to the reaction mixture, the mixture was extracted with EtOAc (EtOAc m. The yield was 56.5%.
(3)、N-(1-氰基异丙基)-N-甲基-3-甲基-2-氨基苯甲酰胺的合成Synthesis of (3), N-(1-Cyanoisopropyl)-N-methyl-3-methyl-2-aminobenzamide
Figure PCTCN2018122721-appb-000014
Figure PCTCN2018122721-appb-000014
依次将20ml水、2.2g(0.04mol)的还原Fe粉和1ml的30％盐酸加入至100ml的四口烧瓶中，缓慢加热至80℃，再在80℃下搅拌30min 后，分批分次加入2.6g(0.01mol)的N-(1-氰基异丙基)-N-甲基-3-甲基-2-硝基苯甲酰胺，温度一直保持不超过80℃，加毕后，继续在80℃下搅拌反应，HPLC追踪至反应结束。反应液降至室温后，加入1.6g的氢氧化钠后，抽滤，滤饼用热水洗涤，收集的滤液用2×100ml的乙酸乙酯萃取，有机相经水、饱和碳酸钠溶液和饱和食盐水洗涤后，用无水硫酸钠干燥，减压脱溶，得1.68g棕色固体，收率71.3％。20 ml of water, 2.2 g (0.04 mol) of reduced Fe powder and 1 ml of 30% hydrochloric acid were successively added to a 100 ml four-necked flask, slowly heated to 80 ° C, and stirred at 80 ° C for 30 min, and then added in portions. 2.6g (0.01mol) of N-(1-cyanoisopropyl)-N-methyl-3-methyl-2-nitrobenzamide, the temperature is kept at not more than 80 ° C, after the addition, continue The reaction was stirred at 80 ° C and the HPLC was traced to completion. After the reaction solution was cooled to room temperature, 1.6 g of sodium hydroxide was added, followed by suction filtration, and the filter cake was washed with hot water. The collected filtrate was extracted with 2×100 ml of ethyl acetate. The organic phase was saturated with water, saturated sodium carbonate and saturated. After washing with brine, it was dried over anhydrous sodium sulfate and evaporated to dryness.
(4)、N-(1-氰基异丙基)-N-甲基-2-氨基-3-甲基-5-氯苯甲酰胺的合成Synthesis of (4), N-(1-Cyanoisopropyl)-N-methyl-2-amino-3-methyl-5-chlorobenzamide
Figure PCTCN2018122721-appb-000015
Figure PCTCN2018122721-appb-000015
依次将1.6g(6.9mmol)的N-(1-氰基异丙基)-N-甲基-3-甲基-2-氨基苯甲酰胺、1.4g(10.3mmol)N-氯代丁二酰亚胺和20ml的DMF加入至100ml的四口烧瓶中，室温下搅拌反应，HPLC追踪至反应结束。将反应液倒入100ml水中，用20ml×3的乙酸乙酯萃取，合并有机相，有机相依次用饱和氯化钠水溶液、水洗涤，无水硫酸钠干燥，减压脱溶，得1.52g淡黄色色固体，收率83.1％。1.6 g (6.9 mmol) of N-(1-cyanoisopropyl)-N-methyl-3-methyl-2-aminobenzamide, 1.4 g (10.3 mmol) of N-chlorobutane The imide and 20 ml of DMF were placed in a 100 ml four-necked flask, and the reaction was stirred at room temperature, and the HPLC was traced to completion. The reaction mixture was poured into 100 ml of water, and extracted with 20 ml of EtOAc (3 mL). Yellow solid, yield 83.1%.
(5)、N-(2-N-((2-氰基丙基-2-基)-N-甲基胺甲酰基)-4-氯-6-甲基苯基)-1-(3-氯吡啶-2-基)-3-溴-1H-吡唑-5-甲酰胺的合成(5), N-(2-N-((2-cyanopropyl-2-yl)-N-methylcarbamoyl)-4-chloro-6-methylphenyl)-1-(3) Synthesis of -chloropyridin-2-yl)-3-bromo-1H-pyrazole-5-carboxamide
Figure PCTCN2018122721-appb-000016
Figure PCTCN2018122721-appb-000016
将0.3g(1mmol)的N-(1-氰基异丙基)-N-甲基-2-氨基-3-甲基-5-氯苯甲酰胺、10ml的二氯甲烷、0.1g(1mmol)的三乙胺和0.32g(1mmol)2-(3-氯-吡啶-2-基)-5-溴-2H-吡唑-3-碳酰氯(按照WO02/070483方法制得)依次加入至50ml的单口烧瓶中，室温搅拌，HPLC追踪至反应结束。将反应液倒入50ml水中，二氯甲烷3×20ml萃取，有机相依次用饱和碳酸钠、饱和氯化钠水溶液和水洗涤，无水硫酸钠干燥，减压脱溶，粗产品通过柱色谱提纯(洗脱剂：乙酸乙酯：石油醚＝3:1)，得0.20g白色固体，收率36.1％。0.3 g (1 mmol) of N-(1-cyanoisopropyl)-N-methyl-2-amino-3-methyl-5-chlorobenzamide, 10 ml of dichloromethane, 0.1 g (1 mmol) Triethylamine and 0.32 g (1 mmol) of 2-(3-chloro-pyridin-2-yl)-5-bromo-2H-pyrazole-3-carbonyl chloride (prepared according to the method of WO 02/070483) are sequentially added to The mixture was stirred at room temperature in a 50 ml single-necked flask and traced to completion by HPLC. The reaction solution was poured into 50 ml of water and extracted with dichloromethane (3×20 ml). The organic phase was washed successively with saturated sodium carbonate, saturated aqueous sodium chloride and water, dried over anhydrous sodium sulfate (eluent: ethyl acetate: petroleum ether = 3:1) afforded 0.20 g of white solid.
实施例3Example 3
化合物1.6：N-(2-N-((2-氰基丙基-2-基)-N-甲基胺甲酰基)-4-氰基-6-甲基苯基)-1-(3-氯吡啶-2-基)-3-氯-1H-吡唑-5-甲酰胺的合成Compound 1.6: N-(2-N-((2-cyanopropyl-2-yl)-N-methylcarbamoyl)-4-cyano-6-methylphenyl)-1-(3) Synthesis of -chloropyridin-2-yl)-3-chloro-1H-pyrazole-5-carboxamide
(1)、2-氨基-3-甲基-5-碘-N-(1-氰基异丙基)-N-甲基苯甲酰胺(1) 2-Amino-3-methyl-5-iodo-N-(1-cyanoisopropyl)-N-methylbenzamide
Figure PCTCN2018122721-appb-000017
Figure PCTCN2018122721-appb-000017
依次将76.3g(0.33mol)的N-(1-氰基异丙基)-N-甲基-3-甲基-2-氨基苯甲酰胺和250ml的DMF依次加入至500ml的四口烧瓶中，室温搅拌下，缓慢加入78.2g(0.35mol)的N-碘代丁二酰亚胺，加毕 后，升温至75℃反应，HPLC追踪至反应结束。将反应液倾入500ml的水中，析出大量固体，抽滤，烘干的淡紫色粉末固体69.1g，收率58.6％。76.3 g (0.33 mol) of N-(1-cyanoisopropyl)-N-methyl-3-methyl-2-aminobenzamide and 250 ml of DMF were sequentially added to a 500 ml four-necked flask. 78.2 g (0.35 mol) of N-iodosuccinimide was slowly added under stirring at room temperature. After the addition, the reaction was heated to 75 ° C, and the HPLC was traced to completion. The reaction solution was poured into 500 ml of water to precipitate a large amount of solid, and suction-dried, dried lavender powder solid 69.1 g, yield 58.6%.
(2)、2-氨基-3-甲基-5-氰基苯甲酸的合成(2) Synthesis of 2-amino-3-methyl-5-cyanobenzoic acid
Figure PCTCN2018122721-appb-000018
Figure PCTCN2018122721-appb-000018
依次将60g(0.17mol)的2-氨基-3-甲基-5-碘-N-(1-氰基异丙基)-N-甲基苯甲酰胺、33g(0.37mol)的CuCN和300ml的DMF依次加入至500ml的四口烧瓶中，升温至145℃反应，HPLC追踪至反应结束。脱溶出去大部分溶剂后，再加入720ml的水和15.8g的乙二胺，抽滤除去不溶物后，向滤液中缓慢加入64g的30％盐酸，将pH值调至弱酸性，有大量的白色固体析出，抽滤，滤饼烘干得18.8g白色固体，收率43.2％。60 g (0.17 mol) of 2-amino-3-methyl-5-iodo-N-(1-cyanoisopropyl)-N-methylbenzamide, 33 g (0.37 mol) of CuCN and 300 ml were successively The DMF was sequentially added to a 500 ml four-necked flask, and the temperature was raised to 145 ° C for reaction, and the HPLC was traced to completion. After most of the solvent was desolvated, 720 ml of water and 15.8 g of ethylenediamine were added, and after insoluble matter was removed by suction filtration, 64 g of 30% hydrochloric acid was slowly added to the filtrate to adjust the pH to a weak acidity, and a large amount of The white solid precipitated, suction filtered, and the cake was dried to yield 18.8 g of a white solid.
(3)、3-氯-2-吡啶肼的合成(3) Synthesis of 3-chloro-2-pyridinium
Figure PCTCN2018122721-appb-000019
Figure PCTCN2018122721-appb-000019
将185g(1.25mol)2,3-二氯吡啶加入800mL正丁醇中，随后加入315g水合肼，升温至回流反应35～40h，冷却至室温，过滤，干燥得白色晶体120g，收率66.9％。185 g (1.25 mol) of 2,3-dichloropyridine was added to 800 mL of n-butanol, followed by the addition of 315 g of hydrazine hydrate, and the temperature was raised to reflux for 35-40 h, cooled to room temperature, filtered, and dried to give white crystals, 120 g, yield 66.9%. .
(4)、2-(3-氯-2-吡啶基)-5-羰基吡唑啉酮-3-甲酸乙酯的合成Synthesis of (4), 2-(3-Chloro-2-pyridyl)-5-carbonylpyrazolone-3-carboxylic acid ethyl ester
Figure PCTCN2018122721-appb-000020
Figure PCTCN2018122721-appb-000020
将24g(1.04mol)碎钠块分次加入920g无水乙醇中，自然升温至回流。待钠全溶后，冷却至40℃以下，一次加入120g 3-氯-2-吡啶肼(0.836mol)，保持40～45℃，滴加210g(1.22mol)马来酸二乙酯，1h滴完。保持40～45℃继续反应4h，冷却至室温，搅拌下分数次倾入冰醋酸的冷水溶液中，减压蒸出乙醇650～700mL，冷却至室温，静置，过滤，滤饼以65mL×2乙醇洗涤，收集滤饼，干燥得成品120g。合并滤液和洗涤液，减压浓缩出几乎全部乙醇，得大量墨绿色溶液伴有黑色固体，氯仿200mL萃取上述溶液，无水硫酸镁干燥，过滤，浓缩至干，加入甲苯50mL，加热得均一溶液，冷至室温后，置冰箱冷冻过夜，过滤，甲苯15mL洗涤，干燥得墨绿色固体回收物9g，总收率57.2％。24 g (1.04 mol) of crushed sodium was added to 920 g of absolute ethanol in portions, and the temperature was naturally raised to reflux. After the sodium is completely dissolved, it is cooled to below 40 ° C, 120 g of 3-chloro-2-pyridinium (0.836 mol) is added in one portion, and the temperature is maintained at 40 to 45 ° C, and 210 g (1.22 mol) of diethyl maleate is added dropwise, 1 hour. Finish. The reaction was continued at 40 to 45 ° C for 4 h, cooled to room temperature, and poured into a cold aqueous solution of glacial acetic acid with stirring, and 650-700 mL of ethanol was distilled off under reduced pressure, cooled to room temperature, allowed to stand, and filtered, and the filter cake was 65 mL × 2 The mixture was washed with ethanol, and the cake was collected and dried to obtain 120 g of a finished product. The filtrate and the washing liquid were combined, and almost all the ethanol was concentrated under reduced pressure to obtain a large amount of dark green solution with a black solid. The solution was extracted with chloroform (200 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness. After cooling to room temperature, the refrigerator was frozen overnight, filtered, washed with 15 mL of toluene, and dried to obtain 9 g of dark green solid recovered, the total yield was 57.2%.
(5)、3-氯-1-(3-氯-2-吡啶基)-4,5-二氢吡唑-5-甲酸乙酯的合成Synthesis of (5), 3-Chloro-1-(3-chloro-2-pyridyl)-4,5-dihydropyrazole-5-carboxylic acid ethyl ester
Figure PCTCN2018122721-appb-000021
Figure PCTCN2018122721-appb-000021
将109.8g(0.716mol)三氯氧磷加入430g乙腈中，随后加入134.5g(0.499mol)的2-(3-氯-2-吡啶基)-5-羰基吡唑啉酮-3-甲酸乙酯，升温至回流反应4～5h后将反应液倾入1200g冰水中，用400mL 氯仿萃取两次后以300mL 10％碳酸氢钠水溶液洗涤一次，分出有机相，无水硫酸钠干燥5h，过滤，减压浓缩至近干。加入无水乙醇200mL，加热至60℃搅拌均匀，乘热移出，-18℃冷冻过夜，过滤，无水乙醇洗涤，干燥得浅紫色结晶113.7g，收率79.1％。109.8 g (0.716 mol) of phosphorus oxychloride was added to 430 g of acetonitrile, followed by the addition of 134.5 g (0.499 mol) of 2-(3-chloro-2-pyridyl)-5-carbonylpyrazolone-3-carboxylic acid The ester was heated to a refluxing reaction for 4 to 5 hours. The reaction solution was poured into 1200 g of ice water, extracted twice with 400 mL of chloroform, and then washed once with 300 mL of 10% aqueous sodium hydrogencarbonate. The organic phase was separated and dried over anhydrous sodium sulfate for 5h. Concentrate under reduced pressure to near dryness. Add 200 mL of absolute ethanol, heat to 60 ° C, stir well, remove by heat, freeze at -18 ° C overnight, filter, wash with absolute ethanol, and dry to obtain 113.7 g of light purple crystal, the yield is 79.1%.
(6)、3-氯-1-(3-氯-2-吡啶基)-吡唑-5-甲酸乙酯的合成Synthesis of (6), 3-Chloro-1-(3-chloro-2-pyridyl)-pyrazole-5-carboxylic acid ethyl ester
Figure PCTCN2018122721-appb-000022
Figure PCTCN2018122721-appb-000022
将110.1g(0.382mol)的3-氯-1-(3-氯-2-吡啶基)-4,5-二氢吡唑-5-甲酸乙酯加入910mL乙腈中，搅拌至溶，加入浓硫酸65.1g(0.664mol)，随后加入181g过硫酸钾(0.67mol)升温至回流，搅拌回流反应15h，冷却后倾入1500g冰水中，500mL氯仿萃取两次，100mL10％碳酸氢钠洗涤，无水硫酸镁干燥，过滤，减压浓缩至干，得浅黄色固体85.8g，收率76.5％。110.1 g (0.382 mol) of ethyl 3-chloro-1-(3-chloro-2-pyridyl)-4,5-dihydropyrazole-5-carboxylate was added to 910 mL of acetonitrile, stirred until dissolved, and added to a thick 65.1 g (0.664 mol) of sulfuric acid, followed by adding 181 g of potassium persulfate (0.67 mol) to reflux, stirring and refluxing for 15 h, cooling, pouring into 1500 g of ice water, extracting twice with 500 mL of chloroform, washing with 100 mL of 10% sodium hydrogencarbonate, anhydrous The residue was dried (MgSO4), filtered
(7)、3-氯-1-(3-氯-2-吡啶基)-吡唑-5-甲酸的合成Synthesis of (7), 3-Chloro-1-(3-chloro-2-pyridyl)-pyrazole-5-carboxylic acid
Figure PCTCN2018122721-appb-000023
Figure PCTCN2018122721-appb-000023
将57.2g(0.2mol)悬浮于850g乙醇中，升温至50℃，开始滴加28.6g(0.511mol)氢氧化钾的250mL水溶液，30min加完。保持50～55℃反应5h，减压浓缩出全部乙醇，补入300mL水，冷却至室温，乙酸乙酯100mL萃取，水相减压蒸出残留乙酸乙酯，冷却至室 温，搅拌下缓慢滴加15％盐酸至溶液pH＝2，继续搅拌2h，过滤，水洗，干燥得浅黄色固体46.1g，收率89.3％。57.2 g (0.2 mol) was suspended in 850 g of ethanol, and the temperature was raised to 50 ° C, and a solution of 28.6 g (0.511 mol) of potassium hydroxide in 250 mL of water was added dropwise thereto, and the addition was completed for 30 minutes. The reaction was kept at 50-55 ° C for 5 h, all ethanol was concentrated under reduced pressure, 300 mL of water was added, the mixture was cooled to room temperature, ethyl acetate (100 mL) was extracted, and the aqueous phase was evaporated under reduced pressure to dryness ethyl ether, cooled to room temperature, and slowly added dropwise with stirring. 15% hydrochloric acid to the solution pH=2, stirring was continued for 2 h, filtered, washed with water and dried to give 46.1 g of pale yellow solid.
(10)、3-溴-1-(3-氯-2-吡啶基)-吡唑-5-甲酰氯的合成Synthesis of (10), 3-bromo-1-(3-chloro-2-pyridyl)-pyrazole-5-carbonyl chloride
Figure PCTCN2018122721-appb-000024
Figure PCTCN2018122721-appb-000024
将30g(0.33mol)的3-氯-1-(3-氯-2-吡啶基)-吡唑-5-甲酸悬浮于1500mL二氯甲烷中,加入1mLDMF，4h左右将63g(0.496mol)草酰氯滴加入上述悬浮液，搅拌反应过夜，得澄清溶液，减压浓缩至干，得半固体，密封备用。30 g (0.33 mol) of 3-chloro-1-(3-chloro-2-pyridyl)-pyrazole-5-carboxylic acid was suspended in 1500 mL of dichloromethane, and 1 mL of DMF was added, and 63 g (0.496 mol) of grass was added in about 4 h. The acid chloride was added dropwise to the above suspension, and the reaction was stirred overnight to obtain a clear solution, which was concentrated to dryness under reduced pressure to give a semi solid.
(11)、N-(2-N-((2-氰基丙基-2-基)-N-甲基胺甲酰基)-4-氰基-6-甲基苯基)-1-(3-氯吡啶-2-基)-3-氯-1H-吡唑-5-甲酰胺的合成(11), N-(2-N-((2-Cyanopropyl-2-yl)-N-methylcarbamoyl)-4-cyano-6-methylphenyl)-1-( Synthesis of 3-chloropyridin-2-yl)-3-chloro-1H-pyrazole-5-carboxamide
Figure PCTCN2018122721-appb-000025
Figure PCTCN2018122721-appb-000025
将0.26g(1mmol)的N-(1-氰基异丙基)-N-甲基-3-甲基-2-氨基-5-氰基苯甲酰胺、10ml的乙腈和0.1g(1mmol)的三乙胺依次加入至50ml的单口烧瓶中，加热至回流，在回流温度下，一次性加入含0.28g(1mmol)2-(3-氯-吡啶-2-基)-5-氯-2H-吡唑-3-碳酰氯的2ml的乙腈溶液，继续在回流温度下搅拌反应，HPLC追踪至反应结束。 将反应液倒入50ml水中，二氯甲烷3*20ml萃取，有机相依次用饱和碳酸钠、饱和氯化钠水溶液和水洗涤，无水硫酸钠干燥，减压脱溶，粗产品通过柱色谱提纯(洗脱剂：乙酸乙酯：石油醚＝3:1)，得0.28g白色固体，收率56.7％。0.26 g (1 mmol) of N-(1-cyanoisopropyl)-N-methyl-3-methyl-2-amino-5-cyanobenzamide, 10 ml of acetonitrile and 0.1 g (1 mmol) The triethylamine was sequentially added to a 50 ml single-necked flask, heated to reflux, and 0.28 g (1 mmol) of 2-(3-chloro-pyridin-2-yl)-5-chloro-2H was added in one portion at reflux temperature. 2-pyridine solution of pyrazole-3-carbonyl chloride in 2 ml of acetonitrile, the reaction was stirred at reflux temperature and the HPLC was followed until the end of the reaction. The reaction solution was poured into 50 ml of water, and extracted with dichloromethane 3*20 ml. The organic phase was washed successively with saturated sodium carbonate, saturated aqueous sodium chloride and water, dried over anhydrous sodium sulfate (eluent: ethyl acetate: petroleum ether = 3:1) gave 0.28 g of white solid.
生物活性测定Biological activity assay
供试药剂均用丙酮∶N`N`—二甲基甲酰胺等比混合液溶解成1000mg/L的溶液。在各药剂溶液中加入1％的吐温-80作乳化剂。然后将这些溶液用1％吐温-20水溶液稀释成所需浓度试验溶液。以含1％吐温-20的水溶液作对照处理。The test agents were all dissolved in a 1000 mg/L solution using a mixture of acetone: N`N'-dimethylformamide. 1% Tween-80 was added as an emulsifier to each of the drug solutions. These solutions were then diluted to the desired concentration of test solution with 1% Tween-20 aqueous solution. An aqueous solution containing 1% Tween-20 was used as a control.
实施例4：对甜菜夜蛾的杀虫效果Example 4: Insecticidal effect on beet armyworm
将苞菜叶片用打孔器打成直径1cm的叶碟，用Airbrush喷雾处理，一定浓度的测试化合物在每叶碟正反面喷雾，喷液量为0.5ml，阴干后每处理接入10头试虫(3龄幼虫)，每处理3次重复，处理后放入25℃、相对湿度60％～70％，无光照的室内培养，120小时后调查存活虫数，计算死亡率。The amaranth leaves were punched into a 1cm diameter leaf disc with a puncher and sprayed with Airbrush. A certain concentration of the test compound was sprayed on the front and back of each leaf disc, and the amount of liquid sprayed was 0.5 ml. After the dry operation, 10 shots per treatment were applied. Insects (3rd instar larvae) were treated three times per treatment. After treatment, they were placed at 25 ° C, relative humidity of 60% to 70%, and cultured in the absence of light. After 120 hours, the number of surviving insects was investigated and the mortality was calculated.
药液浓度为10ppm时，部分化合物如1.1、1.15、1.23、1.32和1.33对甜菜夜蛾的防治效果较好，达到80％以上。When the concentration of the chemical solution is 10 ppm, some compounds such as 1.1, 1.15, 1.23, 1.32 and 1.33 have better control effects on beet armyworm, reaching 80% or more.
实施例5：对斜纹夜蛾的杀虫效果Example 5: Insecticidal effect on Spodoptera litura
采自于未接触过杀虫剂的苞菜叶片用剪刀制成40mm左右见方的叶碟，这些叶碟在各化合物溶液中浸渍30s，将叶碟置于吸水纸上，风干至叶碟上无明显水渍。将浸药后的叶碟置于培养皿中(7cm)，每培养皿放3个叶碟。从室内苞菜苗上饲养的3龄斜纹夜蛾幼虫用毛笔轻 轻挑取置于培养皿的叶碟上，每培养皿接虫10～15头。接虫后盖培养皿盖，放于25℃养虫室内，光照16h/黑暗8h，120h后调查存活虫数，计算死亡率。The leaves of the leek that have not been exposed to the insecticide are made of scissors and about 40mm square leaves. These leaves are immersed in the solution of each compound for 30s, the leaves are placed on the absorbent paper, and air-dried to the leaves. Obvious water stains. Place the leaf dish after the dipping in a Petri dish (7 cm) and place 3 leaf discs per dish. The 3rd instar larvae of Spodoptera litura, which were raised from the indoor amaranth seedlings, were gently picked up on a leaf dish placed on a petri dish with a writing brush, and 10 to 15 worms were placed in each dish. The larvae were covered with a petri dish cover and placed in a larvae room at 25 ° C. The light was exposed for 16 h/dark for 8 h. After 120 h, the number of viable worms was investigated and the mortality was calculated.
部分测试结果如下：Some test results are as follows:
药液浓度为4ppm时，部分化合物如1.1、1.9、1.15、1.23、1.32和1.33对3龄斜纹夜蛾幼虫的死亡率在80％以上。When the concentration of the drug solution was 4 ppm, some compounds such as 1.1, 1.9, 1.15, 1.23, 1.32 and 1.33 had a mortality rate of more than 80% against the 3rd instar larvae of Spodoptera litura.
药液浓度为1ppm时，部分化合物如1.1、1.9、1.15和1.23对3龄斜纹夜蛾幼虫的死亡率在80％以上。When the concentration of the drug solution was 1 ppm, some compounds such as 1.1, 1.9, 1.15 and 1.23 had a mortality rate of more than 80% against the 3rd instar larvae of Spodoptera litura.
实施例6：对棉铃虫的杀虫效果Example 6: Insecticidal effect on cotton bollworm
将做好的新鲜苞菜叶碟在一定浓度的测试化合物药液中浸渍10秒，取出自然晾干。采用24孔板，每孔内放置一片药碟，同时接入1头三龄棉铃虫幼虫，并保湿，120h后调查存活虫数，计算死亡率。The prepared fresh amaranth leaf disc is immersed in a certain concentration of the test compound liquid solution for 10 seconds, and taken out and naturally dried. A 24-well plate was used, and one tablet was placed in each well. At the same time, a third-instar cotton bollworm larva was inserted and moisturized. After 120 hours, the number of surviving insects was investigated and the mortality was calculated.
部分测试结果如下：Some test results are as follows:
药液浓度为4ppm时，部分化合物如1.1、1.15、1.32和1.33对3龄棉铃虫幼虫的死亡率在80％以上。When the concentration of the chemical solution is 4 ppm, some compounds such as 1.1, 1.15, 1.32 and 1.33 have a mortality rate of more than 80% for the 3rd instar cotton bollworm larvae.
药液浓度为1ppm时，部分化合物如1.1、1.5、1.15和1.33对3龄棉铃虫幼虫的死亡率在80％以上。When the concentration of the drug solution is 1 ppm, some compounds such as 1.1, 1.5, 1.15 and 1.33 have a mortality rate of more than 80% for the 3rd instar cotton bollworm larvae.
实施例7：对稻纵卷叶螟的杀虫效果Example 7: Insecticidal effect on rice leaf roller
未接触过杀虫剂的水稻秧苗连根拔出后，洗净根部泥土，待叶片上无明显水渍后将秧苗的茎叶部浸于不同药剂浓度的药液中(药液装于试管中，茎叶向下浸于其中)；浸渍30s后取出放在吸水纸上风干至叶片无水渍。培养皿中(7cm)垫上滤纸，用清水湿润并倒置培养 皿至无水滴流出；将浸药的的秧苗剪取其叶片与培养皿直径约等长的叶段，将叶段平铺于培养皿的滤纸上，每培养皿药放置15～20张叶段。After the roots of the rice seedlings that have not been exposed to the insecticide are pulled out, the roots are washed, and the stems and leaves of the seedlings are immersed in the liquid of different concentration of the drug after the leaves have no obvious water stains (the liquid is contained in the test tube, the stem The leaves are immersed in it); after 30s of immersion, they are taken out and placed on absorbent paper to dry to the leaves without water stains. Filter the paper in a Petri dish (7 cm), moisten with water and invert the Petri dish until no water droplets flow out; cut the seedlings of the infiltrated leaves into leaves of the same diameter as the Petri dish, and lay the leaf sections on the Petri dish On the filter paper, place 15 to 20 leaf segments per petri dish.
从室内小麦苗上饲养的3～4龄稻纵卷叶螟幼虫用毛笔轻轻挑取置于培养皿的叶段上，每培养皿接虫10头。接虫后盖培养皿盖，放于25℃养虫温箱内，光照16h/黑暗8h。接虫后72h调查稻纵卷叶螟死亡情况。Three to four-year-old rice leaf roller larvae raised from indoor wheat seedlings were gently picked up on the leaf sections of the petri dish with a writing brush, and 10 dishes were received per dish. The cover of the petri dish was placed on the back of the incubator and placed in a temperature incubator at 25 ° C for 16 h / dark for 8 h. The death of Cnaphalocrocis medinalis was investigated 72h after inoculation.
部分测试结果如下：Some test results are as follows:
药液浓度为20ppm时，部分化合物如1.1、1.9、1.15、1.23、1.32和1.33对3～4龄稻纵卷叶螟的死亡率在80％以上。When the concentration of the chemical solution is 20 ppm, some compounds such as 1.1, 1.9, 1.15, 1.23, 1.32 and 1.33 have a mortality rate of more than 80% for 3 to 4 years old rice leaf roller.
药液浓度为10ppm时，部分化合物如1.1、1.15和1.32对3～4龄稻纵卷叶螟的死亡率在80％以上。When the concentration of the chemical solution is 10 ppm, some compounds such as 1.1, 1.15 and 1.32 have a mortality rate of more than 80% for 3 to 4 years old rice leaf roller.
实施例8：对小菜蛾的杀虫效果Example 8: Insecticidal effect on Plutella xylostella
选择3龄小菜蛾幼虫。选取苞菜，清洗并晾干，用打孔器做成叶碟，在药液中浸10秒钟取出，待自然晾干后装入培养皿内。每皿接入小菜蛾3龄幼虫10头，重复3次，调查3天的死亡虫数，统计死亡率。Three-year-old Plutella xylostella larvae were selected Select amaranth, wash and dry, use a puncher to make a leaf dish, dip in the liquid for 10 seconds, and then dry it naturally and put it into the dish. 10 dishes of 3rd instar larvae of Plutella xylostella were added to each dish and repeated 3 times. The number of dead insects in 3 days was investigated and the mortality was counted.
部分测试结果如下：Some test results are as follows:
药液浓度为1ppm时，部分化合物如1.1、1.9、1.15、1.23、1.24、1.28～1.30、1.32和1.33对小菜蛾的死亡率在90％以上。When the concentration of the drug solution is 1 ppm, some compounds such as 1.1, 1.9, 1.15, 1.23, 1.24, 1.28 to 1.30, 1.32 and 1.33 have a mortality rate of more than 90% against Plutella xylostella.
按照以上方法，选取现有技术中结构上与本发明化合物最为接近的对比化合物KC1(WO 2008134969中的化合物1.14)和KC2(WO 2008134969中的化合物1.18)，进行杀小菜蛾的平行测定，实验结果如下表所示。According to the above method, the comparative compound KC1 (compound 1.14 in WO 2008134969) and KC2 (compound 1.18 in WO 2008134969) which are structurally closest to the compound of the present invention are selected for parallel determination of Plutella xylostella, and the experimental results are obtained. As shown in the table below.
本发明化合物1.15与已知化合物KC1和KC2杀小菜蛾活性的平行比较(死亡率％)Parallel comparison of the activity of the compound 1.15 of the present invention with the known compounds KC1 and KC2 against Plutella xylostella (% mortality)
Figure PCTCN2018122721-appb-000026
Figure PCTCN2018122721-appb-000026
从上表可知：现有技术中公开的化合物KC1和化合物KC2在应用于小菜蛾的杀灭过程中，在低于1ppm的浓度下，本发明的化合物任然具有更高的活性，对比KC1和KC2的测试结果，本化合物的应用量更小，但是其活性更高。It can be seen from the above table that the compound KC1 and the compound KC2 disclosed in the prior art have a higher activity in the killing process of Plutella xylostella at a concentration of less than 1 ppm, compared with KC1 and The KC2 test results show that the compound is applied in a smaller amount, but its activity is higher.
其中KC2的结构式如下：The structural formula of KC2 is as follows:
Figure PCTCN2018122721-appb-000027
Figure PCTCN2018122721-appb-000027

Claims (8)

  1. 一种通式Ⅰ的N-烷基-N-氰基烷基苯甲酰胺类化合物，An N-alkyl-N-cyanoalkylbenzamide compound of the formula I,
    Figure PCTCN2018122721-appb-100001
    Figure PCTCN2018122721-appb-100001
    其中：among them:
    R 1选自卤素或C 1-C 3烷基； R 1 is selected from halogen or C 1 -C 3 alkyl;
    R 2选自卤素或CN； R 2 is selected from halogen or CN;
    R 3选自卤素、C 1-C 3卤烷基； R 3 is selected from the group consisting of halogen, C 1 -C 3 haloalkyl;
    R 4选自卤素； R 4 is selected from halogen;
    R 5选自H或卤素； R 5 is selected from H or halogen;
    R 6选自C 1-C 3烷基、C 1-C 3卤代烷基或C 1-C 5烷氧烷基； R 6 is selected from C 1 -C 3 alkyl, C 1 -C 3 haloalkyl or C 1 -C 5 alkoxyalkyl;
    R 7选自C 1-C 5烷基； R 7 is selected from C 1 -C 5 alkyl;
    R 8选自氢或C 1-C 5烷基。 R 8 is selected from hydrogen or C 1 -C 5 alkyl.
  2. 根据权利要求1所述的N-烷基-N-氰基烷基苯甲酰胺类化合物，其特征在于，优选的通式I的化合物：The N-alkyl-N-cyanoalkylbenzamide compound according to claim 1, wherein a preferred compound of the formula I:
    R 1选自氯、溴或甲基； R 1 is selected from chlorine, bromine or methyl;
    R 2选自氯、溴、氟或CN； R 2 is selected from the group consisting of chlorine, bromine, fluorine or CN;
    R 3选自氯、溴或三氟甲基； R 3 is selected from chlorine, bromine or trifluoromethyl;
    R 4选自氯； R 4 is selected from chlorine;
    R 5选自H或氯； R 5 is selected from H or chlorine;
    R 6选自C 1-C 3烷基、CH 2OCH 3、CH 2OCH 2CH 3、CH 2CH 2OCH 3、CF 3、CH 2CH 2F、CH 2CHF 2、CH 2CF 3、CF 2CF 3或CF(CF 3) 2； R 6 is selected from the group consisting of C 1 -C 3 alkyl, CH 2 OCH 3 , CH 2 OCH 2 CH 3 , CH 2 CH 2 OCH 3 , CF 3 , CH 2 CH 2 F, CH 2 CHF 2 , CH 2 CF 3 , CF 2 CF 3 or CF(CF 3 ) 2 ;
    R 7选自甲基； R 7 is selected from a methyl group;
    R 8选自氢或甲基。 R 8 is selected from hydrogen or methyl.
  3. 根据权利要求1所述的N-烷基-N-氰基烷基苯甲酰胺类化合物，其特征在于，优选的通式I的化合物：The N-alkyl-N-cyanoalkylbenzamide compound according to claim 1, wherein a preferred compound of the formula I:
    R 1选自氯、溴或甲基； R 1 is selected from chlorine, bromine or methyl;
    R 2选自氯、溴、氟或CN； R 2 is selected from the group consisting of chlorine, bromine, fluorine or CN;
    R 3选自氯或溴； R 3 is selected from chlorine or bromine;
    R 4选自氯； R 4 is selected from chlorine;
    R 5选自H； R 5 is selected from H;
    R 6选自甲基； R 6 is selected from a methyl group;
    R 7选自甲基； R 7 is selected from a methyl group;
    R 8选自甲基。 R 8 is selected from a methyl group.
  4. 一种用于制备权利要求1所述的N-烷基-N-氰基烷基苯甲酰胺类化合物的中间体，其特征在于，所述的中间体化合物如通式II所示：An intermediate for the preparation of the N-alkyl-N-cyanoalkylbenzamide compound of claim 1, wherein the intermediate compound is as shown in Formula II:
    Figure PCTCN2018122721-appb-100002
    Figure PCTCN2018122721-appb-100002
    式中：R 1选自卤素或C 1-C 3烷基； Wherein R 1 is selected from halogen or C 1 -C 3 alkyl;
    R 2选自卤素或CN； R 2 is selected from halogen or CN;
    R 6选自C 1-C 3烷基、C 1-C 3卤代烷基或C 1-C 5烷氧烷基；； R 6 is selected from C 1 -C 3 alkyl, C 1 -C 3 haloalkyl or C 1 -C 5 alkoxyalkyl;
    R 7选自C 1-C 5烷基； R 7 is selected from C 1 -C 5 alkyl;
    R 8选自氢或C 1-C 5烷基。 R 8 is selected from hydrogen or C 1 -C 5 alkyl.
  5. 一种如权利要求4所述的通式II的化合物用于制备通式I化合物的方法，其特征在于，所述的方法如下：A method of preparing a compound of formula I according to claim 4, wherein the method is as follows:
    将通式II的化合物与通式Ⅲ的化合物反应得到通式I化合物，反应式如下：The compound of the formula II is reacted with a compound of the formula III to give a compound of the formula I, the reaction formula being as follows:
    Figure PCTCN2018122721-appb-100003
    Figure PCTCN2018122721-appb-100003
    其中：among them:
    R 3选自卤素、C 1-C 3卤烷基； R 3 is selected from the group consisting of halogen, C 1 -C 3 haloalkyl;
    R 4选自卤素； R 4 is selected from halogen;
    R 5选自H或卤素。 R 5 is selected from H or halogen.
  6. 根据权利要求1或2或3所述的通式I的化合物用于制备杀虫剂控制虫害的应用。Use of a compound of formula I according to claim 1 or 2 or 3 for the preparation of insecticides for controlling pests.
  7. 一种杀虫组合物，含有权利要求1所述的通式I化合物和农业、林业、卫生上可接受的载体，组合物中活性组分的重量百分含量为0.1～99.5％。A pesticidal composition comprising a compound of formula I according to claim 1 and an agricultural, forestry, hygienic acceptable carrier, wherein the active ingredient is present in the composition in an amount of from 0.1 to 99.5% by weight.
  8. 一种控制虫害的方法，其特征在于：将权利要求7所述的杀虫组合物以10g/hm 2～1000g/hm 2的有效剂量施放于害虫或者害虫的生长介质上。 A method for controlling pests, characterized in that the pesticidal composition according to claim 7 is applied to a growth medium of pests or pests at an effective dose of 10 g/hm 2 to 1000 g/hm 2 .
PCT/CN2018/122721 2017-12-29 2018-12-21 N-alkyl-n-cyanoalkylbenzamide compound and use thereof WO2019128871A1 (en)

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