Phenoxazinamide compounds and their use in pesticides

Abstract

The present application relates to phenazine amide compounds and its application in pesticides, especially its application in preventing and treating plant diseases caused by fungi. The structure of the phenazine amide compound of the present application is shown in formula (I): wherein, X is a nitrogen atom or an oxygen atom; R 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. The phenazine amide compound disclosed in the present application has a 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] This invention relates to phenazine amide compounds and their application in pesticides, particularly their application in controlling plant diseases caused by fungi. Background Technology

[0002] In recent years, with global population growth and the development of intensive agriculture, crop disease control has become a crucial aspect of agricultural production. Pesticide companies have made significant progress in the development of novel structural fungicides, especially those with novel mechanisms of action. These new fungicides have played a vital role in improving crop yield and quality, but they have also brought about resistance problems. In particular, fungicides that act on mitochondrial cytochrome complexes, although once among the top sellers, have seen increasingly serious resistance issues due to their widespread use.

[0003] Against this backdrop, succinate dehydrogenase inhibitors (SDHIs) have attracted attention due to their unique mechanism of action. These fungicides effectively control diseases by acting on the succinate dehydrogenase of pathogens, inhibiting their respiration. Currently available SDHIs fungicides all contain an amide group (-CONH-) in their chemical structure, such as boscalid, thifluzamide, furazolidone, and fluopyram. These fungicides exhibit good control efficacy against plant diseases caused by fungi such as rice sheath blight, and due to their novel mechanism of action, they do not exhibit cross-resistance with most fungicides on the market.

[0004] SDHIs (Syntoviral Activated Hydroxide) fungicides target complex II in the mitochondrial respiratory electron transport chain, which consists of four subunits: flavoprotein (Fp, SdhA), iron-sulfur protein (Ip, SdhB), and two other membrane-embedded proteins (SdhC and SdhD). Studies have found that pathogen resistance to SDHIs primarily arises from amino acid mutations in target complex II, leading to reduced affinity for the fungicide and loss of its bactericidal effect. This resistance challenge jeopardizes the long-term effectiveness of SDHIs. To address this challenge, pesticide companies and research institutions are actively developing new compounds and formulations to delay the development and progression of resistance.

[0005] Globally, the market for SDHI-based fungicides continues to grow. This growth reflects the urgent market demand for novel fungicides and highlights the importance of resistance management. As more SDHI-based fungicides' patents expire, market competition will intensify, while also providing opportunities for the development of new compounds and formulations. Summary of the Invention

[0006] The first objective of this invention is to provide a phenazine amide compound that can be used to control plant diseases caused by fungi.

[0007] The structures of the phenazine amide compounds of the present invention are shown in formula (I):

[0008]

[0009] in,

[0010] X is a nitrogen atom or an oxygen atom;

[0011] R is at least one of fluorine, chlorine, bromine, methyl, methoxy, difluoromethyl, trifluoromethyl, and trifluoromethoxy.

[0012] Preferably, X is an oxygen atom.

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

[0014] Preferably, R is a chlorine atom.

[0015] Preferably, the number of chlorine atoms is 2.

[0016] A second object of the present invention is to provide applications of the above-mentioned phenazine amide compounds, including applications in the prevention and control of plant diseases caused by fungi.

[0017] 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.

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

[0019] Preferably, the fungus is at least one of *Botrytis cinerea* or *Sclerotinia sclerotiorum*.

[0020] The phenazine amide compounds of this invention are easy to synthesize, low in cost, and have good inhibitory effects on plant fungi. Moreover, they have novel structures and have not been reported among the currently known compounds with good inhibitory effects on plant fungi.

[0021] 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

[0022] The phenazine amide compounds in the following examples were all obtained from Sichuan University, and the tested plant pathogens were obtained from Sichuan University and Sichuan Agricultural University.

[0023] Example 1 Compound 1 Preparation

[0024]

[0025] The synthesis method of phenazine acyl chloride can be found in the reference (Long Ye, et al., Novel Bioorganic & Medicinal Chemistry Letters, 2010, 7369-7371).

[0026] The synthetic method for amino diphenyl ethers can be found in the reference (Fang Wen, et al., European Journal of Medicinal Chemistry, 2016, 244-251).

[0027] 20 mmol of aminodiphenyl ether was placed in a three-necked flask, and then 25 mL of anhydrous dichloromethane and 5 mL of triethylamine were added. The mixture was stirred in an ice bath. Then, 20 mmol of phenazinyl chloride was transferred to a constant pressure funnel and slowly added dropwise to the three-necked flask. The addition was completed in 30 min, and the mixture was then allowed to rise naturally to room temperature. The reaction was completed in 3 h. The generated salt was removed by filtration, and the organic phases were combined. The mixture was then washed three times with saturated NaHCO3 solution and three times with distilled water. The mixture was separated, dried over anhydrous Na2SO4, and the solvent was removed by rotary evaporation to obtain the crude product. The crude product was then passed through a silica gel column under normal pressure (eluent: petroleum ether: ethyl acetate = 50:1 (V / V)) to obtain compound 1.

[0028] 1 H NMR (400MHz, CDCl3): δ9.46 (1H), 8.21-8.33 (2H), 7.76-7.96 (4H), 7.26-7.36 (4H), 7.11-7.20 (4H). HRMS (ESI) m / z calcd for C 25 H 16 FN3O2(M+H) + 409.1227, found 409.1234.

[0029] Example 2 Compound 2 Preparation

[0030] Compound 2 is prepared using the same method as compound 1.

[0031] 1 H NMR (400MHz, CDCl3): δ9.45(1H),8.35(1H),8.21-33(2H),7.75-7.95(4H),7.25-7.35(4H),7.11-7.20(5H).HRMS(ESI)m / z calcd for C 25 H 18 FN4O(M+H)+ 409.1465, found 409.1510.

[0032] Example 3 Compound 3 Preparation

[0033] Compound 3 is prepared using the same method as compound 1.

[0034] 1 H NMR (400MHz, CDCl3): δ9.46 (1H), 8.22-8.31 (2H), 7.74-7.91 (4H), 7.22-7.38 (4H), 7.10-7.21 (4H). HRMS (ESI) m / z calcd for C 25 H 16 Cl2N3O2(M+H) + 460.0620, found 460.0635.

[0035] Example 4 Compound 4 Preparation

[0036] Compound 4 was prepared using the same method as compound 1.

[0037] 1 H NMR (400MHz, CDCl3): δ9.46(1H),8.36(1H),8.20-8.31(2H),7.72-7.85(4H),7.23-7.31(4H),7.10-7.18(4H).HRMS(ESI)m / z calcd for C 25 H 17 ClN4O(M+H) + 459.0779, found 459.0785.

[0038] Example 5 Compound 5 Preparation

[0039] Compound 5 was prepared using the same method as compound 1.

[0040] 1 H NMR (400MHz, CDCl3): δ9.45(1H),8.20-8.30(2H),7.72-7.81(4H),7.20-7.28(4H),7.12-7.22(4H).HRMS(ESI)m / z calcd for C 25 H 16 Cl2N3O2(M+H) +460.0620, found 460.0627.

[0041] Example 6 Compound 6 Preparation

[0042] Compound 6 was prepared using the same method as compound 1.

[0043] 1 H NMR (400MHz, CDCl3): δ9.44(1H),8.34(1H),8.20-8.30(2H),7.71-7.81(4H),7.22-7.31(4H),7.12-7.18(4H).HRMS(ESI)m / z calcd for C 25 H 17 Cl2N4O(M+H) + 459.0779, found 459.0781.

[0044] Example 7: Determination of the fungicidal activity of phenazine amide compounds against plant pathogenic fungi.

[0045] 1. Tested plant pathogenic fungi

[0046] 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.

[0047] 2. Experimental Methods

[0048] Determination of relative mycelial inhibition rate (%) using the toxic culture medium method:

[0049] First, the phenazine amide compounds were diluted with sterile water and then mixed with PDA medium. The final concentration of the phenazine amide compounds was determined by a two-fold dilution method. A series of uniformly thick plates containing the drug were prepared, with sterile water as a blank control. Each treatment was repeated three times. After the medium solidified, the tested mycelial fungi were inoculated onto the solidified medium and incubated at 27-28℃ for 3-5 days. The diameter of the mycelial cakes was 0.4 cm. The colony diameter was measured using the cross-crossing method, and the mycelial growth inhibition rate was calculated.

[0050]

[0051] 3. Experimental Results

[0052] The results of the inhibitory activity assay of phenazine amide compounds against plant pathogenic fungi are shown in Table 1. As can be seen from Table 1, phenazine amide compounds also exhibit good inhibitory effects against plant pathogenic fungi.

[0053] Table 1. Relative inhibition rates (%) of compounds 1-7 against plant pathogenic fungi at 20 mg / L

[0054]

[0055]

[0056] Note: Chemical structure of compound 7: In general formula (1), X is an oxygen atom and R is a hydrogen atom.

[0057] In summary, the phenazine amide compounds of this invention exhibit good broad-spectrum fungicidal activity against plant pathogenic fungi, and their development into highly efficient new green pesticides has broad prospects.

Claims

1. A phenoxazinamide compound characterized in that, The structure of the phenoxazine amide compound is shown in formula (I): ， （I）； X is an oxygen atom; R is at least one of a fluorine atom, a chlorine atom, and a bromine atom, or R is two chlorine atoms.

2. The use of the phenoxazine amide compound according to claim 1, characterized in that, The application includes an application in preventing and treating plant diseases caused by fungi; the fungi are Sclerotinia sclerotiorum.

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