Pyrazole derivative and application thereof in pesticide

Abstract

The invention relates to a pyrazole derivative and application thereof in pesticides, in particular to application of the pyrazole derivative in prevention and treatment of plant diseases caused by fungi. The structure of the pyrazole derivative is as shown in (I), wherein R1 is at least one of fluorine atoms, chlorine atoms, bromine atoms, methyl, methoxyl, difluoromethyl, trifluoromethyl and trifluoromethoxyl; r2 is a difluoromethyl group or a trifluoromethyl group; x is a nitrogen atom or an oxygen atom. The pyrazole derivative disclosed by the invention has a relatively good inhibition effect on plant pathogenic fungi and can be applied to prevention and treatment of plant diseases caused by fungi. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to pyrazole derivatives and their application in pesticides, in particular to their application in preventing and controlling plant diseases caused by fungi. Background Art

[0002] As an innovative fungicide, succinate dehydrogenase inhibitors have played an important role in the field of pesticide research. This type of compound mainly inhibits the respiration of pathogens by acting on succinate dehydrogenase (SDH), a key enzyme involved in the electron transfer of the respiratory chain, thereby blocking the energy supply and causing the death of pathogens. Succinate dehydrogenase plays a role in oxidizing succinic acid to fumaric acid in fungi and some bacteria, a step that is essential for maintaining the basic life activities of cells. Therefore, targeting and inhibiting the activity of this enzyme by chemical means has opened up a new path for the development of new, efficient and low-toxic pesticide products.

[0003] At present, the succinate dehydrogenase inhibitor fungicides developed on the market, such as boscalid, thiopyrad, furazolidone and fluopyram, all contain the core functional group of amide (-CONH-) in their chemical structure. This common feature not only reflects the key role of amide bonds in the construction of such inhibitor molecules, but also reflects the researchers' in-depth understanding and application of amide compounds in biological activity. Due to their unique mechanism of action, these fungicides have performed well in preventing and controlling a variety of plant diseases caused by fungi, especially for diseases such as rice sheath blight that seriously affect crop yield and quality, and have significant prevention and control effects.

[0004] It is worth noting that the biggest advantage of succinate dehydrogenase inhibitor fungicides compared to other traditional fungicides on the market is their novel mechanism of action and lower risk of cross-resistance. Traditional fungicides often target a specific physiological process of pathogens, and long-term use can easily lead to drug resistance in pathogens. Succinate dehydrogenase inhibitors, by inhibiting a key enzyme that is commonly found in a variety of pathogens, reduce the possibility of pathogens developing resistance, thereby extending the service life of fungicides. In addition, this type of fungicide has a high selectivity and less impact on the plant itself, which is conducive to protecting the ecological environment and is in line with the green and sustainable development concept of modern agriculture.

[0005] In terms of chemical synthesis, researchers continue to explore and optimize the structure of succinate dehydrogenase inhibitors in order to obtain more active, broader-spectrum, and safer fungicides. Summary of the invention

[0006] The first object of the present invention is to provide a class of pyrazole derivatives which can be used for preventing and controlling plant diseases caused by fungi.

[0007] To achieve the purpose of the present invention, the structure of the pyrazole derivative is as shown in (I):

[0008]

[0009] in,

[0010] R1 is at least one of a fluorine atom, a chlorine atom, a bromine atom, a methyl group, a methoxy group, a difluoromethyl group, a trifluoromethyl group, and a trifluoromethoxy group;

[0011] R2 is difluoromethyl or trifluoromethyl;

[0012] X is a nitrogen atom or an oxygen atom.

[0013] Preferably, R1 is at least one of a fluorine atom, a chlorine atom and a bromine atom.

[0014] Preferably, the R1 is a chlorine atom.

[0015] Preferably, R2 is difluoromethyl.

[0016] Preferably, X is an oxygen atom.

[0017] The second object of the present invention is to provide the use of the pyrazole derivatives, including use in preventing and controlling plant diseases caused by fungi.

[0018] Preferably, the fungus is at least one of Rhizoctonia solani, Rhizoctonia solani, Gibberella fusca, Blight solani, Phytophthora infestans, Botrytis cinerea, or Sclerotinia sclerotiorum.

[0019] Preferably, the fungus is at least one of Rhizoctonia solani, Gibberella fusca, Botrytis cinerea, or Sclerotinia sclerotiorum.

[0020] Preferably, the fungus is Sclerotinia sclerotiorum.

[0021] The pyrazole derivative of the invention is easy to synthesize, has low cost, has good inhibitory effect on plant fungi, and has a novel structure, and has not been reported in the currently known compounds with good inhibitory effect on plant fungi.

[0022] The above contents of the present invention are further described in detail below through specific implementation modes, but this should not be construed as limiting the present invention. DETAILED DESCRIPTION

[0023] The pyrazole derivatives in the following examples were all from Sichuan University, and the tested plant pathogens were from Sichuan University and Sichuan Agricultural University.

[0024] Example 1 Compound 1 Preparation

[0025]

[0026] The synthesis method of diphenyl ether chloride can be found in reference (Tahmineh Akbarzadeh, et al, Bioorganic & Medicinal Chemistry, 2003, Pages 769-773).

[0027] The synthesis method of aminopyrazoles can be found in references (Dongyan Yang, et al, Journal of Agricultural and Food Chemistry, 2019, 13185-13194)

[0028] 20 mmol of aminopyrazole was placed in a three-necked flask, and then 25 mL of anhydrous dichloromethane and 5 mL of triethylamine were added thereto respectively. The mixture was stirred in an ice bath. Then 20 mmol of diphenyl ether chloride was transferred to a constant pressure funnel and slowly added dropwise to the three-necked flask. The mixture was allowed to drip for 30 minutes. The mixture was then naturally warmed to room temperature. The reaction was completed in 3 hours. The generated salt was removed by filtration. The organic phases were combined and then washed with saturated NaHCO3 solution for 3 times and with clean water for 3 times respectively. The phases were separated, dried over anhydrous Na2SO4, and the solvent was removed by rotary evaporation to obtain a crude product. The crude product was passed through a normal pressure silica gel column (eluent: petroleum ether: ethyl acetate = 50:1 (V / V)) to obtain compound 1.

[0029] Yield 80%; 1 H NMR(400MHz, CDCl3)δ8.20(s,1H),7.76(1H),7.52(2H),7.40-7.28(6H),6.52(1H),3.85(3H).HRMS(ESI)m / z calcd for C 18 H 15 ClF2N3O2(M+H) + 378.0821, found 378.0898.

[0030] Example 2 Compound 2 Preparation

[0031] The preparation method of compound 2 is the same as the synthesis method of compound 1.

[0032] Yield 85%; 1 HNMR(400MHz, CDCl3)δ8.20(1H),7.78(1H),7.61-7.46(3H),7.46(1H),7.41-7.34(2H),7.22(1H),6.55(1H),3.88(3H).HRMS(ESI)m / z calcd forC18 H 14 Cl2F2N3O2(M+H) + 412.0431, found 412.0489.

[0033] Example 3 Compound 3 Preparation

[0034] The preparation method of compound 3 is the same as the synthesis method of compound 1.

[0035] Yield 81%; 1 HNMR(400MHz, CDCl3)δ8.20(s,1H),7.76(1H),7.60-7.50(3H),7.46(1H),7.42-7.36(2H),7.24(1H),6.56(1H),3.88(3H).HRMS(ESI)m / z calcd forC 18 H 14 Cl2F2N3O2(M+H) + 412.0431, found 412.0431.

[0036] Example 4 Compound 4 Preparation

[0037] The preparation method of compound 4 is the same as the synthesis method of compound 1.

[0038] Yield 78%; 1 HNMR(400MHz, CDCl3)δ8.25(1H),7.77(1H),7.65-7.37(5H),7.28-7.14(2H),3.93(3H).HRMS(ESI)m / z calcd for C 18 H 13 Cl2F3N3O2(M+H) + 430.0337, found 430.0387.

[0039] Example 5 Compound 5 Preparation

[0040] The preparation method of compound 5 is the same as the synthesis method of compound 1.

[0041] Yield 85%; 1HNMR(400MHz, CDCl3)δ9.50(1H),8.19(1H),7.78(1H),7.52(2H),7.42-7.30(6H),6.52(1H),3.86(3H).HRMS(ESI)m / z calcd for C 18 H16ClF2N4O(M+H) + 377.0981, found 377.1002.

[0042] Example 6 Compound 5 Preparation

[0043] The preparation method of compound 6 is the same as the synthesis method of compound 1.

[0044] Yield 86%; 1 HNMR(400MHz, CDCl3)δ9.50(1H),8.22(s,1H),7.75(1H),7.60-7.52(3H),7.45(1H),7.42-7.34(2H),7.22(1H),6.55(1H),3.88(3H).HRMS(ESI)m / z calcd forC 18 H 15 Cl2F2N4O(M+H)+411.0591,found 411.0621.

[0045] Example 7 Determination of fungicidal activity of pyrazole derivatives against plant pathogenic fungi

[0046] 1. Plant pathogenic fungi

[0047] Rice sheath blight (Rhizoctonia solani), wheat fusarium (Fusarium graminearum), corn leaf blight (Bipolaris maydis), potato late blight (Phytophthora infestans), tomato gray mold (Botrytis cirerea), rapeseed sclerotinia (Sclerotinia sclerotiorum).

[0048] 2. Experimental Methods

[0049] Determination of relative inhibition rate of mycelium by toxic medium method (%):

[0050] First, dilute the pyrazole derivative with sterile water and mix it with PDA medium. The final concentration of the pyrazole derivative is made by double dilution method to prepare a series of drug-containing plates with uniform thickness. Sterile water is used as a blank control, and each treatment is repeated 3 times. After the culture medium solidifies, the plant pathogenic fungus test cake is connected to the solidified culture medium and cultured at 27-28℃ for 3-5 days. The diameter of the cake is 0.4cm. The colony diameter is measured by the cross method to calculate the mycelium growth inhibition rate.

[0051]

[0052] 3. Experimental results

[0053] The results of the inhibitory activity of pyrazole derivatives on plant pathogenic fungi are shown in Table 1. As shown in Table 1, pyrazole derivatives also have good inhibitory effects on plant pathogenic fungi.

[0054] Table 1 Relative inhibition rate of compounds 1-6 at 20 mg / L on plant pathogenic fungi (%)

[0055]

[0056]

[0057] In summary, the pyrazole derivatives of the present invention have good broad-spectrum fungicidal activity against plant pathogenic fungi, and developing them into new green pesticides with high efficiency has broad prospects.

Claims

1. A pyrazole derivative, characterized in that: The structure of the pyrazole derivative is shown in (I): in, R1 is at least one of a fluorine atom, a chlorine atom, a bromine atom, a methyl group, a methoxy group, a difluoromethyl group, a trifluoromethyl group, and a trifluoromethoxy group; R2 is difluoromethyl or trifluoromethyl; X is a nitrogen atom or an oxygen atom.

2. A pyrazole derivative according to claim 1, characterized in that: The R1 is at least one of a fluorine atom, a chlorine atom, and a bromine atom.

3. A pyrazole derivative according to claim 1, characterized in that: The R1 is a chlorine atom.

4. A pyrazole derivative according to claim 1 or 2, characterized in that: The R2 is difluoromethyl.

5. A pyrazole derivative according to claim 1 or 2, characterized in that: The X is an oxygen atom.

6. The use of the pyrazole derivative according to any one of claims 1 to 5, characterized in that: The application includes application in preventing and controlling plant diseases caused by fungi.

7. The use according to claim 6, characterized in that: The fungus is at least one of rice sheath blight, wheat sheath blight, wheat fusarium rust, corn leaf blight, potato infestation, tomato gray mold or rapeseed sclerotinia.

8. The use according to claim 7, characterized in that: The fungus is at least one of rice sheath blight, wheat fusarium rust, tomato gray mold or rapeseed sclerotinia.

9. The use according to claim 7, characterized in that: The fungus is Sclerotinia sclerotiorum of rapeseed.

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