Pyrazole derivatives and their use as pesticides

Abstract

The present application relates to pyrazole derivatives and their use in pesticides, in particular their use in the prevention and treatment of plant diseases caused by fungi. The structure of the pyrazole derivatives is shown in (I): wherein R1 is at least one of fluorine atom, chlorine atom, bromine atom, methyl, methoxy, difluoromethyl, trifluoromethyl, trifluoromethoxy; R2 is difluoromethyl or trifluoromethyl; X is nitrogen atom or oxygen atom. The pyrazole derivatives disclosed in the present application have good inhibitory effect on plant pathogenic fungi and can be applied to the prevention and treatment of plant diseases caused by fungi.

Description

TECHNICAL FIELD

[0001] The present application relates to pyrazole derivatives and their use in pesticides, in particular their use in the control of plant diseases caused by fungi. BACKGROUND

[0002] As a class of innovative fungicides, succinate dehydrogenase inhibitors occupy a pivotal position in the field of pesticide research. These compounds mainly act on succinate dehydrogenase (SDH), a key enzyme involved in the respiratory chain electron transport, to inhibit its respiration, thereby blocking energy supply and leading to the death of the pathogenic fungi. Succinate dehydrogenase plays a role in oxidizing succinate to fumarate in fungi and some bacteria, which is crucial for maintaining the basic life activities of cells. Therefore, targeting and inhibiting the activity of this enzyme through chemical means opens up a new way for the development of new, efficient and low-toxicity pesticide products.

[0003] Currently, the succinate dehydrogenase inhibitors developed on the market, such as boscalid, ethaboxam, fenhexamid and fluazinam, all contain the amide group (-CONH-) as the core functional group in their chemical structures. This common feature not only reflects the key role of amide bond in the construction of such inhibitor molecules, but also embodies the in-depth understanding and application of researchers on the biological activity of amide compounds. These fungicides, due to their unique mechanism of action, have shown excellent performance in the prevention and control of various plant diseases caused by fungi, especially for diseases such as rice sheath blight, which seriously affect the yield and quality of crops, and have a significant control effect.

[0004] It is worth noting that the biggest advantage of succinate dehydrogenase inhibitor fungicides compared with 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 pathogenic fungi, and long-term use can easily lead to the development of drug resistance in pathogenic fungi. Succinate dehydrogenase inhibitors, by inhibiting a key enzyme that exists universally in many pathogenic fungi, reduce the possibility of pathogenic fungi developing resistance, thereby prolonging the service life of the fungicide. In addition, this class of fungicides has higher selectivity and less impact on plants, which is conducive to the protection of the ecological environment and conforms to the green and sustainable development concept of modern agriculture.

[0005] In terms of chemical synthesis, researchers are constantly exploring and optimizing the structure of succinate dehydrogenase inhibitors in order to obtain more active, broader-spectrum and safer fungicides. SUMMARY

[0006] The first object of the present application is to provide a class of pyrazole derivatives that can be used in the control of plant diseases caused by fungi.

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

[0008]

[0009] in,

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

[0011] R2 is difluoromethyl or trifluoromethyl;

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

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

[0014] Preferably, R1 is a chlorine atom.

[0015] Preferably, R2 is difluoromethyl.

[0016] Preferably, X is an oxygen atom.

[0017] A second object of the present invention is to provide applications of the above-mentioned pyrazole derivatives, including applications in the prevention and control of plant diseases caused by fungi.

[0018] Preferably, the fungus is at least one of rice sheath blight fungus, wheat sheath blight fungus, wheat scab fungus, corn leaf blight fungus, potato late blight fungus, tomato gray mold fungus, or rapeseed sclerotinia.

[0019] Preferably, the fungus is at least one of rice sheath blight fungus, wheat scab fungus, tomato gray mold fungus, or rapeseed sclerotinia.

[0020] Preferably, the fungus is *Sclerotinia sclerotiorum*, the causal agent of rapeseed disease.

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

[0022] The following detailed description of specific embodiments further illustrates the above-mentioned content of the present invention. However, this should not be construed as a limitation of the present invention. Detailed Implementation

[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 is described in the reference (Tahmineh Akbarzadeh, et al, Bioorganic & Medicinal Chemistry, 2003, Pages 769-773).

[0027] The synthesis method of aminopyrazole is described in the reference (Dongyan Yang, et al, Journal of Agricultural and Food Chemistry, 2019, 13185-13194)

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

[0029] Yield 80%; 1 H NMR (400 MHz, CDCl3) δ 8.20 (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] Preparation of compound 2 of example 2

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

[0032] Yield 85%; 1 H NMR (400 MHz, CDCl3) δ 8.20 (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 14 Cl2F2N3O2(M+H) + 412.0431, found 412.0489.

[0033] Example 3 Compound 3 Preparation

[0034] Compound 3 is prepared using the same method as 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] Compound 4 was prepared using the same method as 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] Compound 5 was prepared using the same method as 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] Compound 6 was prepared using the same method as 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 the fungicidal activity of pyrazole derivatives against plant pathogenic fungi

[0046] 1. Tested plant pathogenic fungi

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

[0048] 2. Experimental Methods

[0049] Determination of relative mycelial inhibition rate (%) using the toxic culture medium method:

[0050] Firstly, the pyrazole derivative is diluted with sterile water and then mixed with PDA medium, the final concentration of the pyrazole derivative is prepared by a series of uniform thickness containing drug plates using double dilution method, using sterile water as a blank control, and each treatment is repeated 3 times. After the medium is solidified, the plant pathogenic fungi test bacteria cake is inoculated on the solidified medium, and cultured at 27-28℃ for 3-5 days, the mycelial growth inhibition rate is calculated by measuring the colony diameter with a cross method.

[0051]

[0052] 3. Experimental results

[0053] The inhibition activity of the pyrazole derivative on the plant pathogenic fungi is shown in Table 1. As shown in Table 1, the pyrazole derivative has good inhibition effect on the 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 derivative of the present application has good broad-spectrum fungicidal activity, and can be developed into a new type of green pesticide with high efficiency, which has broad prospects.

Claims

1. A class of pyrazole derivatives, characterized in that, The structure of the pyrazole derivative is shown as (I): （I） wherein, R1 is a chlorine atom; R2 is difluoromethyl or trifluoromethyl; X is an oxygen atom.

2. A class of pyrazole derivatives according to claim 1, characterized by The R2 is difluoromethyl.

3. Use of a pyrazole derivative according to claim 1 or 2, characterized in that The application includes the use in the prevention and treatment of plant diseases caused by fungi, the fungi being Gibberella zeae.

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