A pyrazole amide compound and its application

Abstract

This invention relates to the field of pesticide insecticide technology, specifically disclosing a pyrazole amide compound and its applications. The pyrazole amide compound with a specific structure provided by this invention exhibits excellent insecticidal activity. Indoor insecticidal tests have verified that the pyrazole amide compound has high insecticidal activity and is highly effective in killing lepidopteran insects. Using the pyrazole amide compound provided by this invention for the control of agricultural pests and diseases can solve the problem of high resistance to existing insecticides. Furthermore, pyrazole amide compounds can be combined with insecticides with different mechanisms of action, which not only improves the comprehensive function of pesticide formulations and effectively controls crop pests and diseases, but also further mitigates the resistance of harmful insects, giving it high market competitiveness.

Description

Technical Field

[0001] This invention relates to the field of pesticide and insecticide technology, and in particular to a pyrazole amide compound and its application. Background Technology

[0002] Tolfenpyrad is a novel pyrazole heterocyclic insecticide and acaricide with the chemical formula C. 21 H 22 ClN3O2, with the structural formula shown in Formula 1, primarily works by inhibiting oxidative phosphorylation in insects. It also possesses ovicidal, feeding-inhibiting, oviposition-inhibiting, and bactericidal effects. This pesticide has a broad insecticidal spectrum, exhibiting high control efficacy against various Lepidoptera, Hemiptera, Beetles, Hymenoptera, Diptera, and mites. It is particularly effective against diamondback moth, thrips, and tea green leafhoppers, as well as adult, larval, and egg-borne urticaria spider mites. It primarily acts through contact and has no systemic activity; peak insect mortality occurs 48 hours after application. Dimpropyridaz is a pyrazole carboxamide insecticide with the chemical formula C0.05. 16 H 23 N5O, with the structural formula shown in Formula 2, inhibits the function of the stringing organ by blocking signal transduction upstream of the vanillic acid transient receptor (TRPV) channel. This interferes with the hearing, balance, sense of direction, gravity perception, and locomotion of pests, causing them to lose coordination, become unable to feed, and ultimately die. This pesticide exhibits good activity against Lepidoptera, Coleoptera, Diptera (flies, mosquitoes, vegetable leafminers, etc.), Hemiptera, and Thysanoptera, and is particularly effective against piercing-sucking pests such as aphids, whiteflies, and psyllids.

[0003]

[0004] Formula 1.

[0005]

[0006] Formula 2.

[0007] However, with the widespread use of these pesticides, the problem of pesticide resistance in pests has become increasingly prominent. Therefore, the search for novel pesticides that are highly effective, low in toxicity, and have entirely new structures has become an urgent need. Summary of the Invention

[0008] To address the problem of high resistance in existing insecticides, this invention provides a pyrazole amide compound and its applications.

[0009] To achieve the above-mentioned objectives, the present invention adopts the following technical solution:

[0010] In a first aspect, the present invention provides a pyrazolamide compound having the structural formula shown in Formula I:

[0011]

[0012] Formula I.

[0013] Compared to existing technologies, the pyrazole amide compounds provided by this invention exhibit excellent insecticidal activity. Indoor insecticidal tests have verified that pyrazole amide compounds possess high insecticidal activity and are highly effective in killing lepidopteran insects. Using the pyrazole amide compounds provided by this invention for the control of agricultural pests and diseases can solve the problem of high resistance in existing insecticides, giving it high market competitiveness.

[0014] Secondly, the present invention provides a method for synthesizing pyrazole amide compounds, comprising the following steps:

[0015] 4-(4-methylphenoxy)benzylamine, an acid binder, and 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxyl chloride were added to a first solvent to carry out a substitution reaction, yielding pyrazole amide compounds.

[0016] The reaction equation is shown in Equation 3:

[0017]

[0018] Formula 3.

[0019] The present invention provides a method for synthesizing pyrazole amide compounds by using active functional group splicing and screening to synthesize a novel, highly active insecticide.

[0020] Preferably, the acid-binding agent is a 35wt%~45wt% aqueous solution of sodium hydroxide.

[0021] Preferably, the first solvent is toluene.

[0022] 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-carboxyl chloride, and the first solvent is 1:(0.8~1.2):(0.9~1.2):(2~3.5), more preferably 1:(0.9~1.1):(0.9~1.1):(2~3).

[0023] Preferably, the temperature of the substitution reaction is 5℃~40℃, and the reaction time is 1.5h~3h.

[0024] Preferably, after the substitution reaction is completed, the process further includes:

[0025] Water was added to the resulting reaction system to separate the phases. The organic phase was washed with water and concentrated to obtain the pyrazole amide compound.

[0026] Preferably, the method for synthesizing 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-formyl chloride includes the following steps:

[0027] 5-Methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxylic acid and thionyl chloride were added to a second solvent and refluxed to obtain 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxyl chloride.

[0028] The reaction equation is shown in Equation 4:

[0029]

[0030] Formula 4.

[0031] More preferably, the second solvent is dichloroethane.

[0032] More preferably, the mass ratio of the 5-methyl-1-(3-methylbutane-2-yl)-1H-pyrazole-4-carboxylic acid, the thionyl chloride, and the second solvent is 1:(0.6~1):(2.5~4.5), and more preferably 1:(0.6~0.9):(3~4).

[0033] More preferably, the reflux reaction time is 3h to 5h.

[0034] For example, after the reflux reaction is complete, the reaction system is further subjected to vacuum distillation to remove the second solvent and unreacted thionyl chloride.

[0035] Thirdly, the present invention provides a pharmaceutical composition whose active component includes the aforementioned pyrazole amide compounds.

[0036] Preferably, the active ingredient further includes at least one of chlorantraniliprole, chlorfenapyr, abamectin, indoxacarb, brofenoxam, or fipronil.

[0037] When the pyrazole amide compounds provided by this invention are used to control pests and diseases, the active components, in addition to pyrazole amide compounds, can also be used in combination with insecticidal substances with different mechanisms of action. This can not only improve the comprehensive function of pesticide formulations, but also further slow down the development of pesticide resistance in harmful insects.

[0038] Fourthly, the present invention provides a pesticide formulation whose active component includes the pyrazole amide compound or the pharmaceutical composition described above.

[0039] Preferably, the pesticide formulation further includes pharmaceutically acceptable excipients.

[0040] More preferably, the mass content of the active component is 0.2% to 80%, and more preferably 2% to 50%.

[0041] More preferably, the excipient is selected from at least one of silicates, diatomaceous earth, or silica.

[0042] Fifthly, the present invention provides an application of the pyrazole amide compound described above in the control of crop pests.

[0043] Preferably, the crop pests are lepidopteran insects.

[0044] More preferably, the lepidopteran insect is the diamondback moth.

[0045] The pyrazole amide compounds provided by this invention have excellent insecticidal effects and can effectively prevent and control crop diseases and pests. Attached Figure Description

[0046] Figure 1 This indicates that the pyrazole amide compound in Embodiment 1 of the present invention 1 H NMR spectrum. Detailed Implementation

[0047] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0048] Example 1

[0049] This embodiment provides a pyrazole amide compound as shown in Formula I, which 1 See the H NMR spectrum. Figure 1 .

[0050] The synthetic method of the above-mentioned pyrazole amide compounds (the reaction equations are shown in Equation 5) includes the following steps:

[0051] S1, 30.0 g (0.153 mol) of 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxylic acid and 100 g of dichloroethane were added to a 250 mL reaction flask and mixed thoroughly. Then, 21.9 g (0.184 mol) of thionyl chloride was added dropwise, and the mixture was slowly heated to reflux. After reacting for 4 h, the dichloroethane and excess thionyl chloride were removed by vacuum distillation to obtain 32.82 g of a brownish-red oily substance (the main component of which was 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxyl chloride). This substance was used directly for the next step of synthesis without further processing.

[0052] S2, 60 g of toluene, 25.38 g (0.119 mol) of 4-(4-methylphenoxy)benzylamine and 25.4 g of 40 wt% sodium hydroxide aqueous solution were added to a 250 mL reaction flask and mixed thoroughly. Then, 25.55 g of the above brownish-red oily substance was added dropwise and the mixture was stirred at room temperature to carry out the substitution reaction. After 2 h, the reaction was completed. A water phase was added, and the organic layer was washed with water and concentrated to obtain 41.9 g (0.107 mol) of pyrazole amide compounds, with a yield of 89.9%.

[0053]

[0054] Formula 5.

[0055] 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).

[0056] Example 2

[0057] This embodiment provides a method for synthesizing pyrazole amide compounds as shown in Formula I (the reaction equation is given in Formula 5), ​​comprising the following steps:

[0058] S1, 30.0 g (0.153 mol) of 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxylic acid and 90 g of dichloroethane were added to a 250 mL reaction flask and mixed thoroughly. 18.2 g (0.153 mol) of thionyl chloride was added dropwise, and the mixture was slowly heated to reflux. After reacting for 5 h, the dichloroethane and excess thionyl chloride were removed by vacuum distillation to obtain 31.45 g of a brownish-red oily substance (the main component of which was 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxyl chloride). This substance was used directly for the next step of synthesis without further processing.

[0059] S2, 50 g toluene, 24.53 g (0.115 mol) 4-(4-methylphenoxy)benzylamine and 20.0 g 45 wt% sodium hydroxide aqueous solution were added to a 250 mL reaction flask and mixed thoroughly. 22.3 g of the above brownish-red oily substance was added dropwise, and the reaction was carried out by stirring at room temperature. After 3 h, the reaction was completed. Water was added to the phase phase, the organic layer was washed with water, and concentrated to obtain 35.6 g (0.091 mol) of pyrazole amide compounds, with a yield of 79.1%.

[0060] The hydrogen spectrum identification results are the same as in Example 1.

[0061] Example 3

[0062] This embodiment provides a method for synthesizing pyrazole amide compounds as shown in Formula I (the reaction equation is given in Formula 5), ​​comprising the following steps:

[0063] S1, 30.0 g (0.153 mol) of 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxylic acid and 120 g of dichloroethane were added to a 250 mL reaction flask and mixed thoroughly. Then, 30.0 g (0.252 mol) of thionyl chloride was added dropwise, and the mixture was slowly heated to reflux. After reacting for 3 h, the dichloroethane and excess thionyl chloride were removed by vacuum distillation to obtain 32.80 g of a brownish-red oily substance (the main component of which was 5-methyl-1-(3-methylbutan-2-yl)-1H-pyrazole-4-carboxyl chloride). This substance was used directly for the next step of synthesis without further processing.

[0064] S2, 85g toluene, 24.74g (0.116mol) 4-(4-methylphenoxy)benzylamine and 29.6g 35wt% sodium hydroxide aqueous solution were added to a 250mL reaction flask and mixed thoroughly. Then, 29.9g of the above brownish-red oily substance was added dropwise and the mixture was stirred at room temperature to carry out the substitution reaction. After 1.5h, the reaction was completed. Aqueous phase was added, and the organic layer was washed with water and concentrated to obtain 42.3g (0.108mol) of pyrazole amide compounds, with a yield of 93.1%.

[0065] The hydrogen spectrum identification results are the same as in Example 1.

[0066] Application Example 1

[0067] This application example provides an insecticidal activity test of different insecticides against diamondback moth.

[0068] Leaf soaking feeding method:

[0069] Accurately weigh the pyrazolamide compounds, fenpropathrin, and fenpropathrin provided in Examples 1-3 into weighing bottles, dissolve them in methanol to prepare a 1 wt% stock solution, and then dilute the sample to the required concentration with an aqueous solution containing 0.5 wt% Tween 80 to prepare the test solution. Select similar leaves, immerse the leaves in the solution for 10 seconds with tweezers, remove them, air dry them, and place them in petri dishes. First, treat the blank control (except for the absence of the main drug, the content of methanol and Tween 80 is the same as the test solution, and the remaining amount is made up with water). Then, repeat the above operation from low to high solution concentration, one tablet each time, for a total of three tablets per sample, and treat them sequentially according to the sample marking order. Next, prepare for insect inoculation. Select uniform second-instar diamondback moth larvae, inoculate 30 diamondback moth larvae into each petri dish, place all petri dishes on a white disk, and cover them with two layers of damp gauze to maintain moisture. Place the treated test insects in a standard treatment room, check the results after 72 hours, and calculate the mortality rate (the insect is considered dead if it does not move when gently touched with a needle). The experiment was repeated three times, and the average value was taken. The mortality results are shown in Table 1.

[0070] Table 1. Insecticidal activity test results of different insecticides against diamondback moth.

[0071]

[0072] As can be seen from Table 1, the pyrazole amide compounds provided by this invention are significantly more effective against diamondback moth than the comparative compounds acetamiprid and fenproxetil (fenproxetil at ≥500 ppm is effective against lepidopterans). 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.

[0073] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

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

2. A pharmaceutical composition, characterized in that, Its active components include the pyrazole amide compounds as described in claim 1.

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

4. A pesticide formulation, characterized in that, Its active components include the pyrazole amide compounds of claim 1 or the pharmaceutical compositions of claim 2 or 3.

5. The pesticide formulation as described in claim 4, characterized in that, The pesticide formulation also includes pharmaceutically acceptable excipients.

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

7. The pesticide formulation as described in claim 5, characterized in that, The auxiliary material is selected from at least one of silicates, diatomaceous earth, or silica.

8. The application of the pyrazole amide compound according to claim 1 in the control of crop pests, characterized in that, The crop pests mentioned are lepidopteran insects.

9. The application of the pyrazole amide compound as described in claim 8 in the control of crop pests, characterized in that, The lepidopteran insect in question is the diamondback moth.

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