N-pyrazole-4-yl benzamide derivative of diphenyl ether fragment containing halogen-mixed substituent as well as preparation method and application of N-pyrazole-4-yl benzamide derivative

Abstract

The invention discloses an N-pyrazole-4-yl benzamide derivative of a diphenyl ether fragment containing a halogen-mixed substituent group and a preparation method and application thereof, and relates to the field of pesticide bactericides, and the structural general formula is as shown in formula (I). A bacteriostatic activity test is carried out on plant pathogenic fungi by using the pyrazole amide derivative disclosed by the invention, and a test result shows that the compounds have a good bacteriostatic effect on the plant pathogenic fungi such as pyricularia oryzae, fusarium graminearum, cucumber target leaf spot bacteria, rhizoctonia solani and botrytis cinerea; the invention provides a direction for further development of a novel succinate dehydrogenase inhibitor.

Description

Technical Field

[0001] This invention relates to the field of pesticides and fungicides, specifically to an N-pyrazole-4-ylbenzamide derivative containing a diphenyl ether fragment with mixed halogen substituents, a method for preparing an N-pyrazole-4-ylbenzamide derivative containing a diphenyl ether fragment with mixed halogen substituents, the application of the N-pyrazole-4-ylbenzamide derivative containing a diphenyl ether fragment prepared by this method as a succinate dehydrogenase inhibitor, and a fungicide. Background Technology

[0002] The healthy development of agriculture is frequently threatened by plant diseases. According to relevant statistics, approximately 1 billion tons of crops worldwide are affected by diseases each year, resulting in product losses of 20-30%, which seriously restricts the safe production of crops. With the frequent use of fungicides, harmful organisms develop varying degrees of resistance to them, making it urgent to develop pesticides with new mechanisms of action.

[0003] Succinate dehydrogenase inhibitors (SDHIs) are fungicides that work by acting on succinate dehydrogenase in the mitochondrial respiratory electron transport chain of pathogens. They interfere with the activity of succinate dehydrogenase, preventing the pathogens from effectively generating ATP. This leads to insufficient energy supply, metabolic disorders, and increased oxidative stress, effectively inhibiting the growth of pathogens and ultimately causing their death, thus achieving the purpose of disease control.

[0004] Succinate dehydrogenase inhibitors have the following advantages: high efficiency and broad spectrum, low toxicity, slow resistance development, long-lasting protection, good environmental friendliness, and the ability to be used in combination with other pesticides to improve integrated pest management. These characteristics make them of significant application value in agriculture, plant protection, and certain medical treatments, especially in combating drug-resistant pathogens and protecting the environment, where they demonstrate remarkable advantages.

[0005] From 1996 to 2025, 25 SDHIs have been launched, of which 52% (13 / 25) contain a pyrazole ring; and 16% (4 / 25) are benzamide inhibitors. Therefore, designing and synthesizing novel pyrazole amide derivatives has important research significance and value. Summary of the Invention

[0006] The purpose of this invention is to provide a novel N-pyrazole-4-benzamide derivative whose molecular structure includes a diphenyl ether fragment with mixed halogen substituents. This invention demonstrates an excellent synthetic method and its application potential in the field of sterilization, thereby addressing the problem mentioned in the background art that half of the existing succinate dehydrogenase inhibitors are pyrazole amide compounds, which have various drawbacks, thus necessitating the development of novel succinate dehydrogenase inhibitors with novel structures.

[0007] To achieve the above objectives, the present invention provides, in a first aspect, an N-pyrazole-4-ylbenzamide derivative containing a diphenyl ether fragment with mixed halogen substituents, the general structural formula of which is shown in formula (I):

[0008] ,

[0009] In equation (I),

[0010] R1 is CHF2 or CF3, and R2 is H or a halogen;

[0011] R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 Each is independently selected from H, -CH3, -OCH3, amino, nitro, or halogen, and if chosen as a halogen, R7, R8, R9, R 10 and R 11 These are different halogen atoms.

[0012] The second aspect of the present invention provides a method for synthesizing a class of pyrazole carboxamide derivatives, the method comprising the following steps: contacting a compound of formula (II-1) with a compound of formula (II-2) to obtain a compound of formula (I);

[0013]

[0014] Among them, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 The definition is consistent with that described above in this invention. The conditions for contacting the compound represented by formula (Ⅱ-I) with the compound represented by formula (Ⅱ-2) are: temperature of 0-60°C and time of 1-48h.

[0015] A method for preparing a pyrazole carboxamide compound includes the following steps:

[0016] I) Using N,N-dimethylformamide (DMF) as solvent, aminophenol and aryl halogenated compounds with halogen substituents were reacted with potassium carbonate at 110 °C to obtain compound 1a-h;

[0017] II) Using acetic anhydride as a solvent, compounds 2a-b were mixed with triethyl orthoformate and refluxed to obtain compounds 3a-b;

[0018] III) Using ethyl acetate as a solvent, compounds 3a-b were mixed with methylhydrazine and added, and the mixture was heated under reflux to obtain compound 4a-b;

[0019] IV) Using an aqueous solution of sodium hydroxide as a solvent, compound 4a-b was added to a flask, heated under reflux, and acidified with hydrochloric acid to obtain compound 5a-b;

[0020] V) Using thionyl chloride as a solvent, compound 5a-b was added to a flask and heated under reflux to obtain compound 6a-b;

[0021] VI) Using dichloromethane and triethylamine as solvents, compounds 6a-b and 1a-h were mixed and added, and the mixture was reacted at room temperature to obtain the desired target product 7a-p;

[0022] The reaction process is as follows:

[0023]

[0024]

[0025] Among them, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 The definition is consistent with that of the present invention.

[0026] Further, in step I), the aryl halide, substituted aminophenol, and potassium carbonate are mixed in a molar ratio of 1:1:2; in step II), the molar ratio of compound 2a-b to triethoxymethane is 1:2; in step III), the molar ratio of compound 3a-b to methylhydrazine is 1:1; in step IV), the molar ratio of compound 4a-b to lithium hydroxide is 1:1; and in step VI), the molar ratio of compound 6a-b to 1a-h is 1.5:1.

[0027] In a third aspect, the present invention provides an N-pyrazole-4-ylbenzamide derivative of formula (I) containing a diphenyl ether fragment with mixed halogen substituents, prepared by the method described above.

[0028] Specifically, the compound represented by formula (I) of this invention is selected from any one of the following:

[0029] Compound 1: R1 is CF3; R2, R3, R4, R5, R6, R9, R 10 and R 11 All are H; and R7 is F, R8 is Br;

[0030] Compound 2: R1 is CF3; R2, R3, R4, R5, R6, R8, R 10 and R 11 All are H; and R7 is F, R9 is Br;

[0031] Compound 3: R1 is CF3; R2, R3, R4, R5, R6, R8, R9 and R 11 Both are H; and R7 is F, R 10 For Br;

[0032] Compound 4: R1 is CF3; R2, R3, R4, R5, R6, R8, R9 and R 10 Both are H; and R7 is F, R 11 For Br;

[0033] Compound 5: R1 is CF3; R2, R3, R4, R5, R6, R7, R 10 and R 11 All are H; and R8 is F, R9 is Br;

[0034] Compound 6: R1 is CF3; R2, R3, R4, R5, R6, R7, R9 and R 11 Both are H; and R8 is F, R 10 For Br;

[0035] Compound 7: R1 is CF3; R2, R3, R4, R5, R6, R8, R 10 and R 11 Both are H; and R7 is F, R8 is Cl. ;

[0036] Compound 8: R1 is CF3; R2, R3, R4, R5, R6, R9, R 10 and R 11 Both are H; and R7 is F, R9 is Cl;

[0037] Compound 9: R1 is CF3; R2, R3, R4, R5, R6, R8, R9 and R 11 Both are H; and R7 is F, R 10 For Cl;

[0038] Compound 10: R1 is CF3; R2, R3, R4, R5, R6, R8, R9 and R 10 Both are H; and R7 is F, R 11 For Cl;

[0039] Compound 11: R1 is CF3; R2, R3, R4, R5, R6, R7, R 10 and R 11 Both are H; and R8 is F, R9 is Cl;

[0040] Compound 12: R1 is CF3; R2, R3, R4, R5, R6, R7, R9 and R 11 Both are H; and R8 is F, R 10 For Cl;

[0041] Compound 13: R1 is CF3; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is F, and R9 is Br;

[0042] Compound 14: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is F, R 10 For Br;

[0043] Compound 15: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is F, R 11 For Br;

[0044] Compound 16: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is F, R 10 For Br;

[0045] Compound 17: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is F, R 11 For Br;

[0046] Compound 18: R1 is CF3; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Br, and R9 is F;

[0047] Compound 19: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Br, R 10 For F;

[0048] Compound 20: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Br, R 11 For F;

[0049] Compound 21: R1 is CF3; R2, R3, R4, R5, R6, R7 and R11 All are H; and R8 is F, R9 is Br, R 10 For F;

[0050] Compound 22: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Br, R 11 For F;

[0051] Compound 23: R1 is CF3; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is F, and R9 is Cl;

[0052] Compound 24: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is F, R 10 For Cl;

[0053] Compound 25: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is F, R 11 For Cl;

[0054] Compound 26: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is F, R 10 For Cl;

[0055] Compound 27: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is F, R 11 For Cl;

[0056] Compound 28: R1 is CF3; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Cl, and R9 is F;

[0057] Compound 29: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Cl, R 10 For F;

[0058] Compound 30: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Cl, R 11 For F;

[0059] Compound 31: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Cl, R 10 For F;

[0060] Compound 32: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Cl, R 11 For F;

[0061] Compound 33: R1 is CF3; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Cl, and R9 is Cl;

[0062] Compound 34: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Cl, R 10 For Cl;

[0063] Compound 35: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Cl, R 11 For Cl;

[0064] Compound 36: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Cl, R 10 For Cl;

[0065] Compound 37: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Cl, R 11 For Cl;

[0066] Compound 38: R1 is CF3; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Br, and R9 is Br;

[0067] Compound 39: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Br, R 10 For Br;

[0068] Compound 40: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 10All are H; and R7 is F, R8 is Br, R 11 For Br;

[0069] Compound 41: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Br, R 10 For Br;

[0070] Compound 42: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Br, R 11 For Br;

[0071] Compound 43: R1 is CF3; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Cl, and R9 is Br;

[0072] Compound 44: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Cl, R 10 For Br;

[0073] Compound 45: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Cl, R 11 For Br;

[0074] Compound 46: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Cl, R 10 For Br;

[0075] Compound 47: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Cl, R 11 For Br;

[0076] Compound 48: R1 is CF3; R2, R3, R4, R5, R6 and R 11 All are H; and R7 is F, R8 is F, R9 is F, R 10 For Br;

[0077] Compound 49: R1 is CF3; R2, R3, R4, R5, R6 and R 10 All are H; and R7 is F, R8 is F, R9 is F, R 11 For Br;;

[0078] Compound 50: R1 is CF3; R2, R3, R4, R5, R6 and R 11 All are H; and R7 is F, R8 is F, R9 is F, R 10 For Cl;

[0079] Compound 51: R1 is CF3; R2, R3, R4, R5, R6 and R 10 All are H; and R7 is F, R8 is F, R9 is F, R 11 For Cl;

[0080] Compound 52: R1 is CF3; R2, R3, R4, R5, R6, and R7 are all H; and R7 is F, R8 is F, R9 is Br, R 10 For Cl;

[0081] Compound 53: R1 is CF3; R2, R3, R4, R5, R6, and R7 are all H; and R8 is F, R9 is F, and R 10 For Br, R 11 For Cl;

[0082] Compound 54: R1 is CF3; R2, R3, R4, R5, R6, and R7 are all H; and R7 is F, R8 is F, R9 is Br, R 10 For Br;

[0083] Compound 55: R1 is CF3; R2, R3, R4, R5, R6, and R7 are all H; and R8 is F, R9 is F, and R 10 For Cl, R 11 For Cl;

[0084] Compound 56: R1 is CF3; R2, R3, R4, R5, R6, and R7 are all H; and R7 is F, R8 is F, R9 is F, and R 10 For F, R 10 For Cl;

[0085] Compound 57: R1 is CF3; R2, R3, R4, R5, R6, and R7 are all H; and R7 is F, R8 is F, R9 is F, and R 10 For F, R 10 For Br;

[0086] Compound 58: R1 is CHF2; R2, R3, R4, R5, R6, R9, R 10 and R 11 All are H; and R7 is F, R8 is Br;

[0087] Compound 59: R1 is CHF2; R2, R3, R4, R5, R6, R8, R 10 and R11 All are H; and R7 is F, R9 is Br;

[0088] Compound 60: R1 is CHF2; R2, R3, R4, R5, R6, R8, R9 and R 11 Both are H; and R7 is F, R 10 For Br;

[0089] Compound 61: R1 is CHF2; R2, R3, R4, R5, R6, R8, R9 and R 10 Both are H; and R7 is F, R 11 For Br;

[0090] Compound 62: R1 is CHF2; R2, R3, R4, R5, R6, R7, R 10 and R 11 All are H; and R8 is F, R9 is Br;

[0091] Compound 63: R1 is CHF2; R2, R3, R4, R5, R6, R7, R9 and R 11 Both are H; and R8 is F, R 10 For Br;

[0092] Compound 64: R1 is CHF2; R2, R3, R4, R5, R6, R8, R 10 and R 11 Both are H; and R7 is F, R8 is Cl. ;

[0093] Compound 65: R1 is CHF2; R2, R3, R4, R5, R6, R9, R 10 and R 11 Both are H; and R7 is F, R9 is Cl;

[0094] Compound 66: R1 is CHF2; R2, R3, R4, R5, R6, R8, R9 and R 11 Both are H; and R7 is F, R 10 For Cl;

[0095] Compound 67: R1 is CHF2; R2, R3, R4, R5, R6, R8, R9 and R 10 Both are H; and R7 is F, R 11 For Cl;

[0096] Compound 68: R1 is CHF2; R2, R3, R4, R5, R6, R7, R 10 and R 11 Both are H; and R8 is F, R9 is Cl;

[0097] Compound 69: R1 is CHF2; R2, R3, R4, R5, R6, R7, R9 and R 11 Both are H; and R8 is F, R 10 For Cl;

[0098] Compound 70: R1 is CHF2; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is F, and R9 is Br;

[0099] Compound 71: R1 is CHF2; R2 is CF3; R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is F, R 10 For Br;

[0100] Compound 72: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is F, R 11 For Br;

[0101] Compound 73: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is F, R 10 For Br;

[0102] Compound 74: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is F, R 11 For Br;

[0103] Compound 75: R1 is CHF2; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Br, and R9 is F;

[0104] Compound 76: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Br, R 10 For F;

[0105] Compound 77: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Br, R 11 For F;

[0106] Compound 78: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 11All are H; and R8 is F, R9 is Br, R 10 For F;

[0107] Compound 79: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Br, R 11 For F;

[0108] Compound 80: R1 is CHF2; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is F, and R9 is Cl;

[0109] Compound 81: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is F, R 10 For Cl;

[0110] Compound 82: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is F, R 11 For Cl;

[0111] Compound 83: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is F, R 10 For Cl;

[0112] Compound 84: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is F, R 11 For Cl;

[0113] Compound 85: R1 is CHF2; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Cl, and R9 is F;

[0114] Compound 86: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Cl, R 10 For F;

[0115] Compound 87: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Cl, R 11 For F;

[0116] Compound 88: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Cl, R 10 For F;

[0117] Compound 89: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Cl, R 11 For F;

[0118] Compound 90: R1 is CHF2; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Cl, and R9 is Cl;

[0119] Compound 91: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Cl, R 10 For Cl;

[0120] Compound 92: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Cl, R 11 For Cl;

[0121] Compound 93: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Cl, R 10 For Cl;

[0122] Compound 94: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Cl, R 11 For Cl;

[0123] Compound 95: R1 is CHF2; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Br, and R9 is Br;

[0124] Compound 96: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Br, R 10 For Br;

[0125] Compound 97: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R10 All are H; and R7 is F, R8 is Br, R 11 For Br;

[0126] Compound 98: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Br, R 10 For Br;

[0127] Compound 99: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Br, R 11 For Br;

[0128] Compound 100: R1 is CHF2; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Cl, and R9 is Br;

[0129] Compound 101: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Cl, R 10 For Br;

[0130] Compound 102: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Cl, R 11 For Br;

[0131] Compound 103: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Cl, R 10 For Br;

[0132] Compound 104: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Cl, R 11 For Br;

[0133] Compound 105: R1 is CHF2; R2, R3, R4, R5, R6 and R 11 All are H; and R7 is F, R8 is F, R9 is F, R 10 For Br;

[0134] Compound 106: R1 is CHF2; R2, R3, R4, R5, R6 and R 10 All are H; and R7 is F, R8 is F, R9 is F, R11 For Br;;

[0135] Compound 107: R1 is CHF2; R2, R3, R4, R5, R6 and R 11 All are H; and R7 is F, R8 is F, R9 is F, R 10 For Cl;

[0136] Compound 108: R1 is CHF2; R2, R3, R4, R5, R6 and R 10 All are H; and R7 is F, R8 is F, R9 is F, R 11 For Cl;

[0137] Compound 109: R1 is CHF2; R2, R3, R4, R5, R6, and R7 are all H; and R7 is F, R8 is F, R9 is Br, R 10 For Cl;

[0138] Compound 110: R1 is CHF2; R2, R3, R4, R5, R6 and R7 are all H; and R8 is F, R9 is F, R 10 For Br, R 11 For Cl;

[0139] Compound 111: R1 is CHF2; R2, R3, R4, R5, R6, and R7 are all H; and R7 is F, R8 is F, R9 is Br, R 10 For Br;

[0140] Compound 112: R1 is CHF2; R2, R3, R4, R5, R6 and R7 are all H; and R8 is F, R9 is F, R 10 For Cl, R 11 For Cl;

[0141] Compound 113: R1 is CHF2; R2, R3, R4, R5, R6, and R7 are all H; and R7 is F, R8 is F, R9 is F, R 10 For F, R 10 For Cl;

[0142] Compound 114: R1 is CHF2; R2, R3, R4, R5, R6, and R7 are all H; and R7 is F, R8 is F, R9 is F, R 10 For F, R 10 It is Br.

[0143] The fourth aspect of this invention provides the application of the aforementioned benzamide derivatives as succinate dehydrogenase inhibitors.

[0144] The fifth aspect of this invention provides a fungicide composed of an active ingredient and excipients, wherein the active ingredient is at least one of the aforementioned benzamide derivatives of this invention, and the content of the active ingredient is 1-99.9% by weight. This fungicide can effectively inhibit rice blast fungus, wheat scab fungus, cucumber target spot fungus, rice sheath blight fungus, and gray mold fungus, providing a highly efficient novel candidate compound for the creation of novel fungicides.

[0145] Furthermore, the formulation of the bactericide is selected from at least one of emulsifiable concentrate, suspension concentrate, wettable powder, powder, granule, aqueous solution, poison bait, mother liquor, and master powder.

[0146] Compared with the prior art, the present invention has the following advantages:

[0147] 1. Highly efficient and broad-spectrum bactericidal activity. This invention synthesized a series of compounds and verified their antibacterial activity. The results showed that these compounds had excellent inhibitory effects on rice sheath blight pathogens, and the bioactivity of some compounds surpassed that of commercially available pyrazole amide fungicides, and they also exhibited inhibitory effects on a variety of plant fungi.

[0148] 2. Simple structure and easy preparation. The synthesis of the succinate dehydrogenase inhibitor in this invention requires only 6 steps, and the raw materials are readily available and the process is controllable. Detailed Implementation

[0149] The following detailed description of the technical solution and advantages of the present invention, in conjunction with the specific embodiments described, is provided. Unless otherwise specified, all reagents and agents used in the following experiments were purchased commercially, and all experimental methods employed are conventional methods in the art.

[0150] The following are only some examples of specific embodiments of the present invention. Obviously, the present invention is not limited to the following embodiments and many variations are possible. Therefore, any obvious modifications or improvements made by those skilled in the art based on the disclosure of the present invention are within the scope of protection claimed by the present invention.

[0151] The compound synthesized in this invention is an improvement on pyrazole carbamide fungicides, and the design concept is as follows:

[0152] Electronic effects: Mixed halogen substituents attract electrons through inductive effects (-I effect), altering the electron density distribution of the molecule and enhancing its reactivity to electrophilic reagents. Simultaneously, some halogens (such as fluorine) may also donate electrons to the molecule through conjugation effects (+M effect), regulating the molecule's reactivity and stability, effectively extending the compound's lifespan and activity, and enhancing its inhibitory effect on pathogenic fungi.

[0153] Inhibition effect: The bond energy of carbon-fluorine bonds is much greater than that of carbon-hydrogen bonds, resulting in better molecular stability of compounds containing carbon-fluorine bonds. Therefore, fluorine pesticides generally have good thermal and light stability, are not easily decomposed in organisms, and have a long-lasting effect, thus inhibiting the growth of pests, diseases, and weeds.

[0154] Osmotic effect: The outer electrons of fluorine atoms are arranged relatively densely, making them less susceptible to external influences. This gives them good repulsion and dispersion properties, as well as hydrophobicity and lipid solubility, which makes fluorine-containing compounds have good permeability in biological bodies.

[0155] Mixed halogen substituents can significantly enhance the performance of inhibitors through multiple mechanisms. The introduction of mixed halogen substituents can also improve the chemical stability and anti-metabolic capacity of the molecule, thereby prolonging the in vivo half-life and improving its bioavailability. Furthermore, mixed halogen substituents can regulate the hydrophilic / lipophilic balance of the molecule, improving its bioavailability and optimizing drug distribution in vivo, thus enhancing its targeting and specificity against succinate oxidoreductase. In summary, mixed halogen substituents provide a powerful molecular optimization tool for the design of succinate oxidoreductase inhibitors, significantly improving their biological activity, stability, and selectivity. In pesticide applications, this stability is particularly important for extending pesticide shelf life and reducing environmental pollution.

[0156] This invention adopts the classic structure of commercially available succinate dehydrogenase inhibitors, using pyrazolamide as the backbone. A carbonyl group and mixed halogen atoms are introduced into the hydrophobic portion (biphenyl) of the succinate dehydrogenase inhibitor. In the development of molecularly targeted pesticides, binding energy is a parameter that expresses the energy released when a small molecule binds to a protein. The higher the energy released, the tighter the binding to the protein, and the better the effect may be. After calculating the binding energy, it was found that the binding energy decreased from -6.2 kcal / mol to -9.8 kcal / mol (using software ChemDraw and AutoDockTool), therefore this backbone may have better biological activity. Therefore, this invention designs and provides this series of compounds.

[0157] Specifically, the synthetic route for N-pyrazol-4-ylbenzamide derivatives containing diphenyl ether fragments with mixed halogen substituents is shown below:

[0158]

[0159] According to the technical solution of this invention, the structural formula of intermediate 1a-h mentioned in this invention is as follows:

[0160]

[0161] Synthetic Step I, Synthesis of Intermediate 1a-h: An aryl halide (10 mmol), halogenated aminophenol (10 mmol), and anhydrous potassium carbonate (2.765 g, 20 mmol) were added to a three-necked flask. 20 mL of N,N-dimethylformamide (DMF) was then added to the flask. The mixture was stirred at 110 °C for 12 hours in air. After the reaction of the starting materials was complete as monitored by TLC, the mixture was cooled to room temperature and diluted with 100 mL of dichloromethane. The solutions were then extracted with 50 mL of 1 M sodium hydroxide solution, 100 mL of distilled water, and 50 mL of physiological saline, respectively. The organic phase was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and then subjected to column chromatography (petroleum ether:ethyl acetate = 20:1) to obtain intermediate 1a-h. Yield: 90%.

[0162] According to the technical solution of this invention, the structural formula of intermediate 3a-b mentioned in this invention is as follows:

[0163]

[0164] Synthesis step II, synthesis of intermediate 3a-b: Compound 2a-b (1 mmol) and triethyl orthoformate (3 mmol) were added to a round-bottom flask, followed by acetic anhydride (6 mmol). The mixture was heated to 120 °C and reacted for 6 h. After the reaction of the starting materials was complete as monitored by TLC, the solvent was removed under reduced pressure, and the crude product was separated by column chromatography to obtain a pale yellow oil.

[0165] According to the technical solution of the present invention, the general structural formula of the main intermediates 4a-b mentioned in the present invention is as follows:

[0166]

[0167] In synthesis step III, the general method for preparing intermediate 4a-b is as follows: 3a-b (0.041 mol) is added dropwise to an ethyl acetate solution of methylhydrazine (0.041 mol). The mixture is stirred at 5 °C for 1 h, and then stirred further at reflux for 3 h. After the reaction of the starting materials is complete as monitored by TLC, the mixture is cooled to room temperature and concentrated. The residue is recrystallized in EtOH to obtain intermediate 4a-b, which requires no further purification.

[0168] According to the technical solution of this invention, the general structural formula of intermediate 5a-b mentioned in this invention is as follows:

[0169]

[0170] Synthesis step IV, the general preparation method of intermediate 5a-b is as follows: add intermediate 4a-b (2.5 mmol) and 50 mL of NaOH (30 mmol) H2O solution to a three-necked flask, react the mixture at room temperature for 12 hours, and after the reaction of the starting materials is complete by monitoring by TLC, add 6N HCl to adjust the pH of the solution to obtain white solid intermediate 5a-b.

[0171] According to the technical solution of the present invention, the general structural formula of intermediate 6a-b mentioned in the present invention is as follows:

[0172]

[0173] Synthesis step V, the general preparation method of intermediate 6a-b is as follows: Under N2 atmosphere protection, 10 mL of thionyl chloride and compound 5a-b (5 mmol) are added to a three-necked flask. The mixture is heated under reflux at 80 °C for 3 hours. After the reaction of the starting materials is complete by monitoring by TLC, the thionyl chloride is removed by distillation. Then, the residual thionyl chloride is removed by distillation twice with toluene (2 × 10 mL) to obtain intermediate 6a-b. Intermediate 6a-b is dissolved in 8 mL of dichloromethane for later use.

[0174] According to the technical solution of this invention, the general structural formula of the main target product 7a-p mentioned in this invention is as follows:

[0175]

[0176] Synthesis step VI, the general preparation method for the target product 7a-p, is as follows: Intermediate 1a-h (3.33 mmol) is dissolved in 8 mL of dichloromethane and 2 mL of triethylamine in a round-bottom flask, cooled to 0°C, and stirred until dissolved at no more than 5°C. Then, a dichloromethane solution containing intermediate 6a-b is added dropwise to the round-bottom flask. The final mixture is stirred at room temperature for 3-6 hours. After the reaction is complete as monitored by TLC, triethylamine hydrochloride is removed by filtration. The filtrate is extracted once with water and once with physiological saline. The organic phase is dried over anhydrous magnesium sulfate, and the solvent is removed by vacuum concentration to obtain the crude product. The crude product is purified by column chromatography (petroleum ether: ethyl acetate) to obtain the target product 7a-p. This invention relates to N-pyrazol-4-ylbenzamide derivatives containing diphenyl ether fragments with mixed halogen substituents.

[0177] Antibacterial activity test of the product obtained in the embodiments of the present invention

[0178] Test method:

[0179] (1) Experimental subjects: Fusarium graminearum (wheat scab), Pyricularia oryzae (rice blast fungus), Rhizoctonia solani (rice sheath blight fungus), Corynespora cassiicola (cucumber target spot fungus), and Botrytis cinerea (gray mold fungus).

[0180] (2) Experimental treatment: In this invention, the mycelial growth rate inhibition method was used to test the in vitro inhibitory activity of N-pyrazole-4-ylbenzamide derivatives containing diphenyl ether fragments with mixed halogen substituents against five plant pathogenic fungi.

[0181] (3) Experimental method: First, the five plant pathogenic fungi mentioned above were cultured in PDA for 7 days and then prepared for use. Next, each target product and control agent were prepared into a 10000 mg / L stock solution using methanol (analytical grade) and sterile water, respectively. The agents were added to PDA medium at the concentrations shown in Table 1 to prepare drug-containing plates. A PDA blank control with sterile water was set up, and each treatment was replicated 4 times. After cooling and solidification, mycelial blocks (5 mm) of the five plant pathogenic fungi were inoculated in the center of the medium and placed in a 25℃ mold incubator for dark incubation. After incubation in a constant temperature incubator at 25℃ for 48 h, the colony diameter (mm) was measured using the cross-cross method. It should be noted that if contamination is found, the test must be repeated.

[0182] Table 1. Determination of target product 7a-t and chlorfenapyr concentration

[0183]

[0184]

[0185] Finally, the mycelial growth inhibition rate (IR) was calculated, with chlorfenapyr as a positive control and sterile PDA water as a blank control. The specific formula is as follows:

[0186] IR(%)=(CT) / (C-5mm)×100%.

[0187] C represents the colony diameter in the blank medium, and T represents the colony diameter after treatment with an N-pyrazole-4-ylbenzamide derivative containing a diphenyl ether fragment with mixed halogen substituents, or the colony diameter in the positive control. The results are shown in Table 2.

[0188] Table 2. Results of in vitro antibacterial activity assays of the target product 7a-p and the control group against plant pathogens.

[0189]

[0190]

[0191] Note: CK1 is chlorfluazuron, and CK2 is the blank control group.

[0192] As shown in Table 2, the N-pyrazol-4-ylbenzamide derivatives containing diphenyl ether fragments with mixed halogen substituents exhibit significant antifungal activity against the selected fungi. Among all the target compounds, most showed in vitro antifungal activity exceeding 60% against the five fungi, with compound 7k exhibiting the most prominent antifungal activity, showing inhibition rates of 92.1% and 98.6% against *Botrytis cinerea* and *Botrytis cinerea*, respectively.

[0193] A preliminary structure-activity relationship analysis was performed on the antifungal activity of compounds 7a-p. Comparison of the antifungal activities of the compounds in Table 2 shows that, under the same pyrazole carboxylic acid group, compounds with electron-donating substituents on the benzene ring have lower antifungal activity than those with electron-withdrawing substituents. Ortho-substituted benzene ring compounds have lower antifungal activity than para- or meta-substituted benzene ring compounds. On the other hand, comparison of the antifungal activities of compounds 7a and 7b, 7c and 7d, 7e and 7f in Table 1 shows that, under the same pyrazoleamine group, trifluoromethylpyrazole amide compounds have lower antifungal activity than difluoromethylpyrazole amide compounds. Furthermore, comparison of the antifungal activity data reveals that different substituents on the pyrazole ring have a significant impact on the broad spectrum of antifungal activity of the compounds.

[0194] After initial screening, compounds with inhibition rates exceeding 60% were subjected to EC assays at different concentration gradients. 50 The test was conducted with chlorfluazuron as the positive control. Finally, the EC50 was calculated using linear regression analysis between the inhibition rate and the logarithmic values ​​of the series of agent concentrations. 50 Values. The results are shown in Table 3.

[0195] Table 3. EC50 values ​​of the target compounds' anti-plant pathogen activity.

[0196]

[0197] As can be seen from the table, the pyrazole amide derivatives involved in this invention have a good inhibitory effect on plant pathogenic fungi such as rice sheath blight, rice blast fungus, and cucumber target spot fungus.

[0198] In summary, when the compounds of the present invention are used as agents against plant pathogenic fungi, they can be mixed with a permissible carrier or diluent in water to formulate them into various commonly used formulations, such as emulsions, hydrating agents, flowable agents, and water-soluble agents, for use against plant pathogens. The pyrazole amide derivatives involved in the present invention can be prepared into novel fungicides.

[0199] The preferred embodiments of the present invention have been described in detail, but the present invention is not limited to the specific details of the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution, and these modifications are all within the protection scope of the present invention.

[0200] It should be noted that the specific technical features mentioned in the above embodiments can be combined in any suitable manner without conflict. To avoid repetition, this invention has not listed all possible combinations.

[0201] Furthermore, different embodiments of the present invention can be combined in any way, and as long as such combination does not violate the basic idea of ​​the present invention, such combination should also be regarded as part of the present invention.

Claims

1. An N-pyrazol-4-ylbenzamide derivative containing a diphenyl ether fragment with mixed halogen substituents, characterized in that, The derivative has the structure shown in formula (Ⅰ): Equation (I) In equation (Ⅰ), R1 is either -CF3 or -CHF2; R2 is selected from H, halogen R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 Each is independently selected from H, -CH3, amino, nitro, or halogen, and if halogen is chosen, R7, R8, R9, R... 10 and R 11 These are different halogen atoms.

2. The derivative according to claim 1, characterized in that, The compound represented by formula (Ⅰ) is selected from any one of the following: Compound 1: R1 is CF3; R2, R3, R4, R5, R6, R9, R 10 and R 11 All are H; and R7 is F, R8 is Br; Compound 2: R1 is CF3; R2, R3, R4, R5, R6, R8, R 10 and R 11 All are H; and R7 is F, R9 is Br; Compound 3: R1 is CF3; R2, R3, R4, R5, R6, R8, R9 and R 11 Both are H; and R7 is F, R 10 For Br; Compound 4: R1 is CF3; R2, R3, R4, R5, R6, R8, R9 and R 10 Both are H; and R7 is F, R 11 For Br; Compound 5: R1 is CF3; R2, R3, R4, R5, R6, R7, R 10 and R 11 All are H; and R8 is F, R9 is Br; Compound 6: R1 is CF3; R2, R3, R4, R5, R6, R7, R9 and R 11 Both are H; and R8 is F, R 10 For Br; Compound 7: R1 is CF3; R2, R3, R4, R5, R6, R8, R 10 and R 11 All are H; and R7 is F, R8 is Cl; Compound 8: R1 is CF3; R2, R3, R4, R5, R6, R9, R 10 and R 11 Both are H; and R7 is F, R9 is Cl; Compound 9: R1 is CF3; R2, R3, R4, R5, R6, R8, R9 and R 11 Both are H; and R7 is F, R 10 For Cl; Compound 10: R1 is CF3; R2, R3, R4, R5, R6, R8, R9 and R 10 Both are H; and R7 is F, R 11 For Cl; Compound 11: R1 is CF3; R2, R3, R4, R5, R6, R7, R 10 and R 11 Both are H; and R8 is F, R9 is Cl; Compound 12: R1 is CF3; R2, R3, R4, R5, R6, R7, R9 and R 11 Both are H; and R8 is F, R 10 For Cl; Compound 13: R1 is CF3; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is F, and R9 is Br; Compound 14: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is F, R 10 For Br; Compound 15: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is F, R 11 For Br; Compound 16: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is F, R 10 For Br; Compound 17: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is F, R 11 For Br; Compound 18: R1 is CF3; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Br, and R9 is F; Compound 19: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Br, R 10 For F; Compound 20: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Br, R 11 For F; Compound 21: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Br, R 10 For F; Compound 22: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Br, R 11 For F; Compound 23: R1 is CF3; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is F, and R9 is Cl; Compound 24: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is F, R 10 For Cl; Compound 25: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is F, R 11 For Cl; Compound 26: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is F, R 10 For Cl; Compound 27: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is F, R 11 For Cl; Compound 28: R1 is CF3; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Cl, and R9 is F; Compound 29: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Cl, R 10 For F; Compound 30: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Cl, R 11 For F; Compound 31: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Cl, R 10 For F; Compound 32: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Cl, R 11 For F; Compound 33: R1 is CF3; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Cl, and R9 is Cl; Compound 34: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Cl, R 10 For Cl; Compound 35: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Cl, R 11 For Cl; Compound 36: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Cl, R 10 For Cl; Compound 37: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Cl, R 11 For Cl; Compound 38: R1 is CF3; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Br, and R9 is Br; Compound 39: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Br, R 10 For Br; Compound 40: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Br, R 11 For Br; Compound 41: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Br, R 10 For Br; Compound 42: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Br, R 11 For Br; Compound 43: R1 is CF3; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Cl, and R9 is Br; Compound 44: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Cl, R 10 For Br; Compound 45: R1 is CF3; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Cl, R 11 For Br; Compound 46: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Cl, R 10 For Br; Compound 47: R1 is CF3; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Cl, R 11 For Br; Compound 48: R1 is CF3; R2, R3, R4, R5, R6 and R 11 All are H; and R7 is F, R8 is F, R9 is F, R 10 For Br; Compound 49: R1 is CF3; R2, R3, R4, R5, R6 and R 10 All are H; and R7 is F, R8 is F, R9 is F, R 11 For Br;; Compound 50: R1 is CF3; R2, R3, R4, R5, R6 and R 11 All are H; and R7 is F, R8 is F, R9 is F, R 10 For Cl; Compound 51: R1 is CF3; R2, R3, R4, R5, R6 and R 10 All are H; and R7 is F, R8 is F, R9 is F, R 11 For Cl; Compound 52: R1 is CF3; R2, R3, R4, R5, R6, and R7 are all H; and R7 is F, R8 is F, R9 is Br, R 10 For Cl; Compound 53: R1 is CF3; R2, R3, R4, R5, R6, and R7 are all H; and R8 is F, R9 is F, and R 10 For Br, R 11 For Cl; Compound 54: R1 is CF3; R2, R3, R4, R5, R6, and R7 are all H; and R7 is F, R8 is F, R9 is Br, R 10 For Br; Compound 55: R1 is CF3; R2, R3, R4, R5, R6, and R7 are all H; and R8 is F, R9 is F, and R 10 For Cl, R 11 For Cl; Compound 56: R1 is CF3; R2, R3, R4, R5, R6, and R7 are all H; and R7 is F, R8 is F, R9 is F, and R... 10 For F, R 10 For Cl; Compound 57: R1 is CF3; R2, R3, R4, R5, R6, and R7 are all H; and R7 is F, R8 is F, R9 is F, and R 10 For F, R 10 For Br; Compound 58: R1 is CHF2; R2, R3, R4, R5, R6, R9, R 10 and R 11 All are H; and R7 is F, R8 is Br; Compound 59: R1 is CHF2; R2, R3, R4, R5, R6, R8, R 10 and R 11 All are H; and R7 is F, R9 is Br; Compound 60: R1 is CHF2; R2, R3, R4, R5, R6, R8, R9 and R 11 Both are H; and R7 is F, R 10 For Br; Compound 61: R1 is CHF2; R2, R3, R4, R5, R6, R8, R9 and R 10 Both are H; and R7 is F, R 11 For Br; Compound 62: R1 is CHF2; R2, R3, R4, R5, R6, R7, R 10 and R 11 All are H; and R8 is F, R9 is Br; Compound 63: R1 is CHF2; R2, R3, R4, R5, R6, R7, R9 and R 11 Both are H; and R8 is F, R 10 For Br; Compound 64: R1 is CHF2; R2, R3, R4, R5, R6, R8, R 10 and R 11 All are H; and R7 is F, R8 is Cl; Compound 65: R1 is CHF2; R2, R3, R4, R5, R6, R9, R 10 and R 11 Both are H; and R7 is F, R9 is Cl; Compound 66: R1 is CHF2; R2, R3, R4, R5, R6, R8, R9 and R 11 Both are H; and R7 is F, R 10 For Cl; Compound 67: R1 is CHF2; R2, R3, R4, R5, R6, R8, R9 and R 10 Both are H; and R7 is F, R 11 For Cl; Compound 68: R1 is CHF2; R2, R3, R4, R5, R6, R7, R 10 and R 11 Both are H; and R8 is F, R9 is Cl; Compound 69: R1 is CHF2; R2, R3, R4, R5, R6, R7, R9 and R 11 Both are H; and R8 is F, R 10 For Cl; Compound 70: R1 is CHF2; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is F, and R9 is Br; Compound 71: R1 is CHF2; R2 is CF3; R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is F, R 10 For Br; Compound 72: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is F, R 11 For Br; Compound 73: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is F, R 10 For Br; Compound 74: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is F, R 11 For Br; Compound 75: R1 is CHF2; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Br, and R9 is F; Compound 76: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Br, R 10 For F; Compound 77: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Br, R 11 For F; Compound 78: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Br, R 10 For F; Compound 79: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Br, R 11 For F; Compound 80: R1 is CHF2; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is F, and R9 is Cl; Compound 81: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is F, R 10 For Cl; Compound 82: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is F, R 11 For Cl; Compound 83: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is F, R 10 For Cl; Compound 84: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is F, R 11 For Cl; Compound 85: R1 is CHF2; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Cl, and R9 is F; Compound 86: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Cl, R 10 For F; Compound 87: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Cl, R 11 For F; Compound 88: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Cl, R 10 For F; Compound 89: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Cl, R 11 For F; Compound 90: R1 is CHF2; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Cl, and R9 is Cl; Compound 91: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Cl, R 10 For Cl; Compound 92: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Cl, R 11 For Cl; Compound 93: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Cl, R 10 For Cl; Compound 94: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Cl, R 11 For Cl; Compound 95: R1 is CHF2; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Br, and R9 is Br; Compound 96: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Br, R 10 For Br; Compound 97: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Br, R 11 For Br; Compound 98: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Br, R 10 For Br; Compound 99: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Br, R 11 For Br; Compound 100: R1 is CHF2; R2, R3, R4, R5, R6, R 10 and R 11 All are H; and R7 is F, R8 is Cl, and R9 is Br; Compound 101: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 11 All are H; and R7 is F, R8 is Cl, R 10 For Br; Compound 102: R1 is CHF2; R2, R3, R4, R5, R6, R9 and R 10 All are H; and R7 is F, R8 is Cl, R 11 For Br; Compound 103: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 11 All are H; and R8 is F, R9 is Cl, R 10 For Br; Compound 104: R1 is CHF2; R2, R3, R4, R5, R6, R7 and R 10 All are H; and R8 is F, R9 is Cl, R 11 For Br; Compound 105: R1 is CHF2; R2, R3, R4, R5, R6 and R 11 All are H; and R7 is F, R8 is F, R9 is F, R 10 For Br; Compound 106: R1 is CHF2; R2, R3, R4, R5, R6 and R 10 All are H; and R7 is F, R8 is F, R9 is F, R 11 For Br;; Compound 107: R1 is CHF2; R2, R3, R4, R5, R6 and R 11 All are H; and R7 is F, R8 is F, R9 is F, R 10 For Cl; Compound 108: R1 is CHF2; R2, R3, R4, R5, R6 and R 10 All are H; and R7 is F, R8 is F, R9 is F, R 11 For Cl; Compound 109: R1 is CHF2; R2, R3, R4, R5, R6, and R7 are all H; and R7 is F, R8 is F, R9 is Br, R 10 For Cl; Compound 110: R1 is CHF2; R2, R3, R4, R5, R6 and R7 are all H; and R8 is F, R9 is F, R 10 For Br, R 11 For Cl; Compound 111: R1 is CHF2; R2, R3, R4, R5, R6, and R7 are all H; and R7 is F, R8 is F, R9 is Br, R 10 For Br; Compound 112: R1 is CHF2; R2, R3, R4, R5, R6 and R7 are all H; and R8 is F, R9 is F, R 10 For Cl, R 11 For Cl; Compound 113: R1 is CHF2; R2, R3, R4, R5, R6 and R7 are all H; and R7 is F, R8 is F, R9 is F, R 10 For F, R 10 For Cl; Compound 114: R1 is CHF2; R2, R3, R4, R5, R6, and R7 are all H; and R7 is F, R8 is F, R9 is F, R 10 For F, R 10 It is Br.

3. A method for preparing N-pyrazol-4-ylbenzamide derivatives containing diphenyl ether fragments with mixed halogen substituents, characterized in that, This type of benzamide derivative has the structure shown in formula (I). The method includes: contacting the compound shown in formula (II-1) with the compound shown in formula (II-2) to obtain the compound of formula (I); Among them, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 The definition is consistent with that of any one of claims 1-2.

4. The method according to claim 3, characterized in that, It also includes preparing the compound shown in formula (Ⅱ-1) according to the following steps: (1) The compound shown in formula (II-3) is subjected to a first contact with anhydrous ethanol under low temperature conditions, followed by extraction, drying and other post-treatments to obtain an intermediate. The intermediate is then subjected to a multi-step reaction to obtain the compound shown in formula (II-4). (2) The compound shown in formula (Ⅱ-4) is brought into a second contact with thionyl chloride to the compound shown in formula (Ⅱ-1); The definitions of R1, R2 and R3 in formulas (II-3) and (II-4) are consistent with those in any one of claims 1-2.

5. The method according to claim 3 or 4, wherein, The conditions for contacting the compound shown in formula (Ⅱ-1) with the compound shown in formula (Ⅱ-2) are: temperature 0-60℃ and time 1-48h.

6. N-pyrazole-4-ylbenzamide derivatives containing diphenyl ether fragments prepared by the method according to any one of claims 1-3.

7. The use of the N-pyrazole-4-ylbenzamide derivative containing a diphenyl ether fragment with mixed halogen substituents as described in any one of claims 1-3 or 6 as a succinate dehydrogenase inhibitor.

8. A bactericide, comprising an active ingredient and excipients, characterized in that, The active ingredient is at least one of the N-pyrazole-4-ylbenzamide derivatives containing mixed halogen-substituted diphenyl ether fragments as described in any one of claims 1-3 or 6; the content of the active ingredient is 1-99.9% by weight.

9. The bactericide according to claim 8, characterized in that, The formulation of the bactericide is selected from at least one of emulsifiable concentrate, suspension concentrate, wettable powder, powder, granules, aqueous solution, poison bait, mother liquor, and master powder.

10. The application of the fungicide as described in claim 8 or 9 in inhibiting rice blast fungus, wheat scab fungus, cucumber target spot fungus, rice sheath blight fungus, and gray mold fungus.

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