Pyrazole amide compound and application thereof

Abstract

The invention relates to the technical field of pesticides, and particularly discloses a pyrazole amide compound and application thereof. The pyrazole amide compound with a specific structure provided by the invention has excellent insecticidal activity. An indoor insecticidal test proves that the pyrazole amide compound is relatively high in insecticidal activity and has an efficient killing effect on lepidoptera insects. When the pyrazole amide compound provided by the invention is used for preventing and treating agricultural diseases and insect pests, the problem that the existing insecticide is relatively high in insecticide resistance can be solved; besides, pyrazole amide compounds can be combined with insecticidal substances with different action mechanisms for use, so that the comprehensive function of a pesticide preparation is improved, plant diseases and insect pests of crops are effectively prevented and treated, the drug resistance of harmful insects is further relieved, and the insecticidal composition has high market competitiveness.

Description

Technical Field

[0001] The present invention relates to the technical field of pesticides and insecticides, and in particular to a pyrazole amide compound and application thereof. Background Art

[0002] Tolfenpyrad is a new type of pyrazole heterocyclic insecticide and acaricide with the chemical formula C 21 H 22 ClN3O2, with a structural formula as shown in Formula 1, has a main mechanism of action of preventing oxidative phosphorylation of insects. It also has ovicidal, feeding inhibition, oviposition inhibition and bactericidal effects. The drug has a wide insecticide spectrum and has a high control effect on various Lepidoptera, Hemiptera, Beetles, Hymenoptera, Diptera pests and mites, especially on Plutella xylostella, thrips and tea green leafhoppers, as well as adults, larvae and eggs of urticaria spider mites. It mainly kills by contact and has no systemic absorption. The peak of dead insects occurs 48 hours after application. Dimpropyridaz is a pyrazole carboxamide insecticide with a chemical formula of C 16 H 23 N5O, with a structural formula as shown in Formula 2, inhibits the action of the chord organ by blocking the signal transduction upstream of the transient vanilloid receptor (TRPV) channel, interfering with the hearing, balance, sense of direction, gravity perception, and movement ability of the pests, causing the poisoned pests to lose coordination, be unable to feed, and eventually die. The drug has good activity against Lepidoptera, Coleoptera, Diptera (flies, mosquitoes, vegetable leafminers, etc.), Hemiptera, and Thysanoptera, especially against aphids, whiteflies, psyllids, and other piercing-sucking mouthparts pests.

[0003]

[0004] Formula 1.

[0005]

[0006] Formula 2.

[0007] However, with the widespread use of such pesticides, the problem of pest resistance has become increasingly prominent. Therefore, it has become an urgent need to find new pesticides with high efficiency, low toxicity and a completely new structure. Summary of the invention

[0008] In view of the problems of high resistance of existing insecticides, the present invention provides a pyrazole amide compound and application thereof.

[0009] In order to achieve the above-mentioned object of the invention, the present invention adopts the following technical solutions: In a first aspect, the present invention provides a pyrazole amide compound, the structural formula of which is shown in Formula I:

[0010] Formula I.

[0011] Compared with the prior art, the pyrazole amide compounds provided by the present invention have excellent insecticidal activity. According to indoor insecticidal test results, the insecticidal activity of pyrazole amide compounds is relatively high, and they have a highly effective killing effect on lepidopteran insects. The pyrazole amide compounds provided by the present invention are used for the prevention and treatment of agricultural pests and diseases, which can solve the problem of drug resistance of existing pesticides and have high market competitiveness.

[0012] In a second aspect, the present invention provides a method for synthesizing a pyrazole amide compound, comprising the following steps: 4-(4-methylphenoxy)benzylamine, an acid-binding agent and 5-methyl-1-(3-methylbutane-2-yl)-1H-pyrazole-4-carbonyl chloride are added to the first solvent to carry out a substitution reaction to obtain a pyrazole amide compound.

[0013] The reaction equation is shown in Formula 3:

[0014] Formula 3.

[0015] The method for synthesizing pyrazole amide compounds provided by the invention adopts active functional group splicing screening to synthesize a novel insecticide with high activity.

[0016] Preferably, the acid binding agent is a 35wt% to 45wt% aqueous sodium hydroxide solution.

[0017] Preferably, the first solvent is toluene.

[0018] Preferably, the mass ratio of the 4-(4-methylphenoxy)benzylamine, the acid binding agent, the 5-methyl-1-(3-methylbutane-2-yl)-1H-pyrazole-4-carbonyl chloride and the first solvent is 1:(0.8~1.2):(0.9~1.2):(2~3.5), and more preferably 1:(0.9~1.1):(0.9~1.1):(2~3).

[0019] Preferably, the temperature of the substitution reaction is 5°C to 40°C, and the reaction time is 1.5h to 3h.

[0020] Preferably, after the substitution reaction is completed, the method further comprises: Water is added to the obtained reaction system for phase separation, and the organic phase is washed with water and concentrated to obtain the pyrazole amide compound.

[0021] Preferably, the synthesis method of 5-methyl-1-(3-methylbutane-2-yl)-1H-pyrazole-4-carbonyl chloride comprises the following steps: 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxylic acid and thionyl chloride are added to the second solvent for reflux reaction to obtain the 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxylic acid chloride.

[0022] The reaction equation is shown in Formula 4:

[0023] Formula 4.

[0024] More preferably, the second solvent is ethylene dichloride.

[0025] Further preferably, the mass ratio of the 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxylic acid, the thionyl chloride and the second solvent is 1:(0.6~1):(2.5~4.5), more preferably 1:(0.6~0.9):(3~4).

[0026] Further preferably, the reflux reaction time is 3h~5h.

[0027] For example, after the reflux reaction is completed, the method further includes: subjecting the reaction system to reduced pressure distillation to remove the second solvent and unreacted thionyl chloride.

[0028] In a third aspect, the present invention provides a pharmaceutical composition, the active ingredient of which includes the pyrazole amide compound.

[0029] Preferably, the active ingredient further comprises at least one of chlorantraniliprole, chlorfenapyr, avermectin, indoxacarb, bromofenac or fipronil.

[0030] When the pyrazole amide compounds provided by the present invention are used to control pests and diseases, the active components, in addition to the pyrazole amide compounds, can also be used in combination with insecticides with different mechanisms of action, which can not only improve the comprehensive function of the pesticide preparation, but also further reduce the drug resistance of harmful insects.

[0031] In a fourth aspect, the present invention provides a pesticide preparation, the active component of which includes the pyrazole amide compound or the pharmaceutical composition.

[0032] Preferably, the pesticide preparation further comprises pharmaceutically acceptable excipients.

[0033] Further preferably, the mass content of the active component is 0.2% to 80%, more preferably 2% to 50%.

[0034] Further preferably, the auxiliary material is selected from at least one of silicate, diatomaceous earth or white carbon black.

[0035] In a fifth aspect, the present invention provides a use of the pyrazole amide compound in preventing and controlling crop pests.

[0036] Preferably, the crop pests are Lepidoptera insects.

[0037] Further preferably, the Lepidoptera insect is Plutella xylostella.

[0038] The pyrazole amide compounds provided by the present invention have excellent insecticidal effects and can effectively prevent and control diseases and insect pests of crops. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 In the embodiment of the present invention, the pyrazole amide compound 1 H NMR spectrum. DETAILED DESCRIPTION

[0040] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0041] Example 1 This embodiment provides a pyrazole amide compound as shown in Formula I, 1 H NMR spectra are shown in Figure 1 .

[0042] The synthesis method of the above pyrazole amide compound (the reaction equation thereof is shown in Formula 5) comprises the following steps: S1, add 30.0g (0.153mol) of 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxylic acid and 100g of dichloroethane into a 250mL reaction bottle, mix well, drop 21.9g (0.184mol) of thionyl chloride, slowly raise the temperature to reflux, react for 4h, remove dichloroethane and excess thionyl chloride by vacuum distillation, and obtain 32.82g of brown-red oil (the main component is 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carbonyl chloride), which is directly used for the next step of synthesis without further treatment.

[0043] S2, add 60g toluene, 25.38g (0.119mol) 4-(4-methylphenoxy)benzylamine and 25.4g 40wt% sodium hydroxide aqueous solution into a 250mL reaction bottle, mix well, add 25.55g of the above brown-red oil dropwise, stir at room temperature for substitution reaction, the reaction is completed after 2h, add water to phase, take the organic layer, wash with water, and concentrate to obtain 41.9g (0.107mol) pyrazole amide compound, the yield is 89.9%.

[0044]

[0045] Formula 5.

[0046] 1 H NMR (400 MHz, DMSO) δ 8.49 (t, J = 5.9 Hz, 1H), 7.97 (s, 1H), 7.30(d, J = 8.5 Hz, 2H), 7.17 (d, J = 8.3 Hz, 2H), 6.91 (dd, J = 19.6, 8.5 Hz, 4H),4.38 (d, J = 5.9 Hz, 2H), 4.05 -3.91 (m, 1H), 2.51 (s, 3H), 2.28 (s, 3H), 2.13-1.95 (m, 1H), 1.35 (d, J = 6.6 Hz, 3H), 0.95 (d, J = 6.7 Hz, 3H), 0.60 (d, J = 6.6Hz, 3H). Example 2 This embodiment provides a method for synthesizing a pyrazole amide compound as shown in Formula I (the reaction equation thereof is shown in Formula 5), ​​comprising the following steps: S1, add 30.0g (0.153mol) of 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxylic acid and 90g of dichloroethane into a 250mL reaction bottle, mix well, drop 18.2g (0.153mol) of thionyl chloride, slowly raise the temperature to reflux, react for 5h, remove dichloroethane and excess thionyl chloride by vacuum distillation, and obtain 31.45g of brown-red oil (the main component is 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carbonyl chloride), which is directly used for the next step of synthesis without further treatment.

[0047] S2, add 50g toluene, 24.53g (0.115mol) 4-(4-methylphenoxy)benzylamine and 20.0g 45wt% sodium hydroxide aqueous solution into a 250mL reaction bottle, mix well, add 22.3g of the above brown-red oil dropwise, stir at room temperature for substitution reaction, the reaction is completed after 3h, add water to phase, take the organic layer, wash with water, and concentrate to obtain 35.6g (0.091mol) pyrazole amide compound, the yield is 79.1%.

[0048] The results of hydrogen spectrum identification are the same as those in Example 1.

[0049] Example 3 This embodiment provides a method for synthesizing a pyrazole amide compound as shown in Formula I (the reaction equation thereof is shown in Formula 5), ​​comprising the following steps: S1, add 30.0g (0.153mol) of 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxylic acid and 120g of dichloroethane into a 250mL reaction bottle, mix well, drop 30.0g (0.252mol) of thionyl chloride, slowly raise the temperature to reflux, react for 3h, remove dichloroethane and excess thionyl chloride by vacuum distillation, and obtain 32.80g of brown-red oil (the main component is 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carbonyl chloride), which is directly used for the next step of synthesis without further treatment.

[0050] S2, add 85g toluene, 24.74g (0.116mol) 4-(4-methylphenoxy)benzylamine and 29.6g 35wt% sodium hydroxide aqueous solution into a 250mL reaction bottle, mix well, add 29.9g of the above brown-red oil dropwise, stir at room temperature for substitution reaction, the reaction is completed after 1.5h, add water to phase, wash the organic layer with water, and concentrate to obtain 42.3g (0.108mol) pyrazole amide compound, the yield is 93.1%.

[0051] The results of hydrogen spectrum identification are the same as those in Example 1.

[0052] Application Example 1 This application example provides an insecticidal activity test of different insecticides against Plutella xylostella.

[0053] Using leaf dipping method: Accurately weigh the pyrazole amide compounds, thiamethoxam and thiamethoxam provided in Examples 1 to 3 in a weighing bottle, dissolve them in methanol to prepare a 1wt% mother liquor, and then dilute the sample to the required concentration with an aqueous solution containing 0.5wt% of Tween 80 to form a test solution. Select similar leaves, immerse the leaves in the solution for 10s with tweezers, take them out and dry them in the shade, and put them in a culture dish. First treat the blank control (except for the absence of the main drug, the content of the remaining methanol and Tween 80 is the same as the test solution, and the remaining part is filled with water), and then repeat the above operation from low to high according to the concentration of the solution, 1 piece each time, 3 pieces for each sample, and process them in the order of sample marking. After that, prepare to pick up the worm, select the neat and consistent 2-year-old diamondback moth larvae, inoculate 30 diamondback moth larvae in each culture dish, put all the culture dishes in a white disk, and cover them with two layers of wet gauze to keep them moist. The treated test worms are placed in a standard treatment room, and the results are checked for 72h, and the mortality rate is calculated (the needle is pulled out and the insect body is touched lightly, and the unmoved ones are dead). The experiment was repeated three times and the average value was taken. The mortality results are shown in Table 1.

[0054] Table 1 Test results of insecticidal activity of different insecticides against Plutella xylostella

[0055] As can be seen from Table 1, the efficacy of the pyrazole amide compounds provided by the present invention on diamondback moth is significantly better than that of the comparative compounds tolfenpyrad and methoprene (metaprene at ≥500ppm has an insecticidal effect on Lepidoptera), and the insecticidal activity against the tested target pest (diamondback moth) has been significantly improved. Under the same efficacy, the amount of insecticide used can be greatly reduced, and it has the potential to be developed into a highly efficient, green and environmentally friendly insecticide.

[0056] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modification, equivalent substitution or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A pyrazole amide compound, characterized in that: Its structural formula is shown in Formula I: Formula I.

2. A pharmaceutical composition, characterized in that The active component thereof comprises the pyrazole amide compound described in claim 1.

3. The pharmaceutical composition according to claim 2, characterized in that The active component also includes at least one of chlorantraniliprole, chlorfenapyr, avermectin, indoxacarb, bromofenac or fipronil.

4. A pesticide preparation, characterized in that: The active component thereof comprises the pyrazole amide compound according to claim 1 or the pharmaceutical composition according to claim 2 or 3.

5. The pesticide formulation according to claim 4, characterized in that The pesticide preparation also includes pharmaceutically acceptable excipients.

6. The pesticide formulation according to claim 4 or 5, characterized in that: The mass content of the active component is 0.2% to 80%.

7. The pesticide formulation according to claim 5, characterized in that The auxiliary material is selected from at least one of silicate, diatomaceous earth or white carbon black.

8. Use of the pyrazole amide compound according to claim 1 in preventing and controlling crop pests.

9. Use of the pyrazole amide compound in controlling crop pests as claimed in claim 8, characterized in that: The crop pests are lepidoptera insects.

10. Use of the pyrazole amide compound in controlling crop pests according to claim 9, characterized in that: The lepidopteran insect is Plutella xylostella.

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