Preparation method and use of pyridine aryl ether derivatives with substituted pyrazole bipyridine units

Abstract

The present invention relates to a preparation method and use of pyridine aryl ether derivatives having a substituted pyrazole-linked pyridine unit. It is obtained by the reaction of pyrazole acid and pyridine aryl ether methylamine. The pyridine aryl ether derivatives having a substituted pyrazole-linked pyridine unit have excellent control effects on harmful insects, and the compound can be used to prepare insecticides in the fields of agriculture, horticulture, etc.

Description

Technical Field

[0001] The present invention relates to the field of chemical pesticides, and specifically to a preparation method and use of pyridine aryl ether derivatives with a substituted pyrazole-linked pyridine unit. Background Art

[0002] In recent years, pesticides have played an important role in the field of plant protection. However, with the long-term use of traditional pesticides, pests have gradually developed resistance, and even cross-resistance, to traditional pesticides. In addition, with the continuous emergence of new pests, the continuous research and development of new pesticides have become an inevitable choice.

[0003] Pyridine aryl ether derivatives are an important class of heterocyclic pesticide molecules and have extensive applications in agricultural production and other aspects. Pyridine and pyrazole are important heterocyclic fragments, and compounds containing pyridine and pyrazole groups often exhibit good insecticidal effects.

[0004] Therefore, in order to find new compounds with excellent insecticidal effects from pyridine aryl ether derivatives and connect pyridine, pyrazole heterocycles and pyridine aryl ether structures, the present invention discloses a class of pyridine aryl ether derivatives with a substituted pyrazole-linked pyridine unit having agricultural insecticidal application value. Summary of the Invention

[0005] The object of the present invention is to provide pyridine aryl ether derivatives with a substituted pyrazole-linked pyridine unit that exhibit insecticidal effects against pests such as Plutella xylostella and Mythimna separata to meet the demand for highly efficient insecticides in crop protection.

[0006] Another object of the present invention is to provide the use of the above compounds in the preparation of insecticides.

[0007] Another object of the present invention is to provide a preparation method of the above compounds.

[0008] To solve the above technical problems, the first aspect of the present invention provides pyridine aryl ether derivatives with a substituted pyrazole-linked pyridine unit, having the following structure:

[0009]

[0010]

[0011] The second aspect of the present invention provides a preparation method of the above pyridine aryl ether derivatives with a substituted pyrazole-linked pyridine unit, which includes the following steps:

[0012]

[0013]

[0014] Among them, the pyrazole acid and pyridine aryl ether methylamine intermediates are prepared by conventional methods and formed.

[0015] The compounds of the present invention show insecticidal activity against pests such as Plutella xylostella and Mythimna separata, so the compounds of the present invention can be used to prepare insecticides to protect plants in agriculture, horticulture, etc.

[0016] When the compounds of the present invention are used as insecticides in the fields of agriculture, horticulture, etc., they can be used alone or in the form of insecticidal compositions. For example, taking the compound as the active ingredient and adding common pesticide adjuvants in the art to process into emulsion in water, suspension concentrate, water dispersible granules, emulsifiable concentrate, etc.

[0017] Common pesticide adjuvants include: liquid carriers such as water; organic solvents such as toluene, xylene, cyclohexanol, methanol, butanol, ethylene glycol, acetone, dimethylformamide, acetic acid, dimethyl sulfoxide, animal and vegetable oils and fatty acids; common surfactants such as emulsifiers and dispersants, including anionic surfactants, cationic surfactants, nonionic surfactants and amphoteric surfactants; other adjuvants such as wetting agents, thickeners, etc.

[0018] When the compounds of the present invention are used as the active ingredient in insecticides, their content in the insecticides is selected within the range of 0.1% to 99.5%, and the appropriate content of the active ingredient can be determined according to the formulation form and application method. Generally, the emulsion in water contains 5% to 50% (weight percentage, the same below) of the active ingredient, and preferably its content is 10% to 40%; the suspension concentrate contains 5% to 50% of the active ingredient, and preferably its content is 5% to 40%.

[0019] For the use of the insecticides of the present invention, common application methods can be selected, such as foliar spraying, surface application, soil treatment and seed treatment, etc. For example, when foliar spraying is adopted, the available concentration range of the compound represented by general formula I as the active ingredient is 1 to 1000 μg / mL of emulsion in water, suspension concentrate, water dispersible granules, emulsifiable concentrate, and preferably its concentration is 1 to 500 μg / mL.

[0020] The pyridine aryl ether derivatives with substituted pyrazole-linked pyridine units disclosed in the present invention have insecticidal activity against pests such as Plutella xylostella and Mythimna separata, and can be used to prepare insecticides for the fields of agriculture, horticulture, etc. Detailed implementation mode

[0021] The above scheme is further described below in conjunction with specific embodiments. It should be understood that these embodiments are for illustrating the present invention and not for limiting the scope of the present invention. The implementation conditions adopted in the embodiments can be further adjusted according to the conditions of specific manufacturers, and the implementation conditions not specified are usually the conditions in conventional experiments.

[0022] Example 1:

[0023]

[0024] Dissolve 3 mmol of intermediate Ⅱa, 3 mmol of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI), and 4 mmol of 1-hydroxybenzotriazole (HOBt) in 35 mL of DMF. Add 4 mmol of intermediate Ⅲa at room temperature. After addition, heat the reaction solution to 35 °C and react for 12 hours. After removing the solvent, the obtained crude product is separated by silica gel column chromatography to obtain the target product Ia; 1 H NMR(400MHz,DMSO-d 6 )δ:9.41(t,J=6.00Hz,1H),8.51~8.53(m,2H),8.46(s,1H),8.19~8.22(m,1H),7.62~7.65(m,1H),7.25(s,1H),7.19(d,J=8.40Hz,1H),7.08(s,1H),6.91(d,J=8.00Hz,Ar-H),4.41(d,J=5.60Hz,2H),3.67(s,3H).HRMS calcd forC 23 H 15 Cl 3 F 3 N 5 O 3 Na[M+Na] + 594.0090,found 594.0084.

[0025] Example 2:

[0026]

[0027] Dissolve 2 mmol of intermediate Ⅱa and 2 mmol of benzotriazole-N,N,N’,N’-tetramethyluronium hexafluorophosphate (HBTU) in 30 mL of DMF. Add 9 mmol of triethylamine and 2.1 mmol of intermediate Ⅲb thereto under stirring at room temperature. After addition, continue to stir the reaction solution at room temperature for 9 hours. After removing the solvent, the obtained crude product is separated by silica gel column chromatography to obtain the target product Ib; 1 H NMR(400MHz,DMSO-d 6)δ: 9.39 (t, J=6.00 Hz, 1H), 8.51~8.52 (m, 1H), 8.29 (d, J=2.40 Hz, 1H), 8.20~8.22 (m, 1H), 8.08 (d, J=2.40 Hz, 1H), 7.63~7.66 (m, 1H), 7.24 (s, 1H), 7.14 (d, J=8.00 Hz, 1H), 7.04 (s, 1H), 6.88 (d, J=8.00 Hz, 1H), 4.38 (d, J=6.00 Hz, 2H), 3.66 (s, 3H). HRMS calcd for C 22 H 15 Cl 4 N 5 O 3 Na[M+Na] + 559.9827, found 559.9823.

[0028] Example 3:

[0029]

[0030] Dissolve 3 mmol of intermediate Ⅱb and 3 mmol of benzotriazole-N,N,N’,N’-tetramethyluronium hexafluorophosphate (HBTU) in 25 mL of DMSO. Add 10 mmol of triethylamine and 3.6 mmol of intermediate Ⅲc thereto under stirring at room temperature. After addition, heat the reaction solution to 45 °C and react for 10 hours. After removing the solvent, the obtained crude product is separated by silica gel column chromatography to obtain the target product Ic; 1 H NMR (400 MHz, DMSO-d 6 )δ: 9.29 (t, J=6.00 Hz, 1H), 8.49 (d, J=4.80 Hz, 1H), 8.34 (d, J=2.40 Hz, 1H), 8.13~8.17 (m, 2H), 7.57~7.61 (m, 1H), 7.31 (d, J=8.40 Hz, 2H), 7.14 (d, J=8.40 Hz, 2H), 6.73 (s, 1H), 4.85~4.92 (m, 2H), 4.37 (d, J=5.60 Hz, 2H). HRMS calcd for C 23 H 15 Cl 3 F 3 N 5 O 3 Na[M+Na] + 594.0090, found 594.0094.

[0031] Example 4:

[0032] Determination of the Insecticidal Activity of Compounds against Plutella xylostella

[0033] Using the leaf-dipping method proposed by the Insecticide Resistance Action Committee (IRAC): Select Plutella xylostella as the test object. That is, soak an appropriate amount of corn leaves in the prepared liquid medicine, air-dry them naturally, place them in a petri dish lined with filter paper, inoculate the 2nd instar larvae of Plutella xylostella, and culture them in an observation room at 25°C. After 48 hours, investigate the results. Touch the insect body with a writing brush, and those with no response are regarded as dead insects. The test concentration is 500 μg / mL (the liquid medicines of other concentrations are obtained by diluting the 500 μg / mL liquid medicine).

[0034] Example 5:

[0035] Determination of the Insecticidal Activity of Compounds against Mythimna separata

[0036] Using the leaf-dipping method proposed by the Insecticide Resistance Action Committee (IRAC): Select Mythimna separata as the test object. That is, soak an appropriate amount of corn leaves in the prepared liquid medicine, air-dry them naturally, place them in a petri dish lined with filter paper, inoculate the mid-3rd instar larvae of Mythimna separata, and culture them in an observation room at 25°C. After 48 hours, investigate the results. Touch the insect body with a writing brush, and those with no response are regarded as dead insects. The test concentration is 500 μg / mL (the liquid medicines of other concentrations are obtained by diluting the 500 μg / mL liquid medicine).

[0037] As can be seen from Table 1, at a test concentration of 500 μg / mL, the mortality rates of compounds Ia - Ic against Plutella xylostella are all 100%. At 100 μg / mL, the mortality rates of compounds Ia and Ib against Plutella xylostella are 90% and 70% respectively. At 20 μg / mL, compound Ia still shows a 60% mortality rate against Plutella xylostella. In addition, at 500 μg / mL, the mortality rate of compound Ic against Mythimna separata reaches 100%. At 100 μg / mL and 20 μg / mL, the mortality rates of compound Ic against Mythimna separata are 90% and 50% respectively.

[0038] Table 1. Preliminary Insecticidal Activity Data of Ia - Ic

[0039]

[0040] "-": Indicates not determined

[0041] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above examples. The above examples and the descriptions in the specification only illustrate the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention will have various changes and improvements, and these changes and improvements all fall within the scope of the present invention claimed. The scope of protection claimed by the present invention is defined by the appended claims and their equivalents.

Claims

1. A pyridine aryl ether derivative I having a substituted pyrazole bipyridine unit, characterized in that The structure is:

2. The method for preparing the pyridine aryl ether derivative I having a substituted pyrazole bipyridine unit according to claim 1, characterized in that Here’s how:

3. Use of the pyridine aryl ether derivative I having a substituted pyrazole bipyridine unit as claimed in claim 1 in the preparation of an insecticide.

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