Benzoylhydrazine compounds, their synthesis methods and applications

Abstract

This invention relates to the field of pesticide fungicides, and discloses benzoyl hydrazine compounds, their synthesis methods, and applications. The benzoyl hydrazine derivatives have the structure shown in Formula I. The benzoyl hydrazine derivatives of this invention possess the advantages of novel structure, low toxicity, and highly efficient fungicidal activity, and have great application prospects as fungicides.

Description

Technical Field

[0001] This invention relates to the field of pesticides and fungicides, specifically to the design of a class of benzoyl hydrazine compounds with fungicidal activity, their synthesis methods, and applications. Background Technology

[0002] Succinate dehydrogenase inhibitors (SDHI) fungicides have become one of the most promising classes of fungicides in recent years due to their high efficiency, broad-spectrum fungicidal activity, and environmental friendliness, attracting the attention of major agrochemical companies worldwide. Currently, commercially available SDHI fungicides mainly include: pyrazolamides, pyrazinamides, benzamides, methomyl amides, oxadiene amides, thiazolidinamides, and pyridine amides. In 2003, BASF launched the first broad-spectrum SDHI inhibitor, boscalid, which is active against almost all types of fungal diseases and is highly effective in controlling powdery mildew, gray mold, sclerotinia rot, and various rot diseases. It quickly became a multi-million dollar product; its acid fraction is 2-chloropyridine. Summary of the Invention

[0003] Currently, the core components of inhibitors targeting succinate dehydrogenase are mainly composed of heterocyclic carboxylic acid fragments and hydrophobic amine fragments, such as... Figure 1 Because existing targeted succinate dehydrogenase inhibitors have simple molecular skeletons, many pathogens have developed resistance during practical applications. To obtain a novel lead structure for a targeted succinate dehydrogenase inhibitor with excellent bactericidal activity, this invention, through research, selects a diaryl ether fragment as the core skeleton and introduces a carboxylic acid group onto the aryl ether fragment, forming a novel diaryl ether formic acid structural segment that replaces the heterocyclic carboxylic acid segment in cyazofamid. Furthermore, the amino group is converted to hydrazine, increasing the flexibility of the molecule and altering the metabolic pathway of the original amide fragment, aiming to obtain a more efficient and broad-spectrum novel bactericide. Unlike previous heterocyclic amide fragments, the novel formic acid hydrazine fragment can also serve as the molecular skeleton for targeted succinate dehydrogenase inhibitors, and activity evaluation has confirmed that this type of derivative has excellent bactericidal activity. Some highly active compounds can be used as candidates for novel bactericides for further industrial development. Therefore, this invention is proposed.

[0004] The purpose of this invention is to provide a method for preparing and applying a class of compounds containing benzoyl hydrazine, which have a high control effect on fungal diseases on crops.

[0005] To achieve the above objectives, a first aspect of the present invention provides a class of compounds containing benzoylhydrazine, having the structure shown in Formula I:

[0006]

[0007] In Equation I,

[0008] R 1 Selected from C1-C 12 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C substituted with halogen 12 Alkyl, phenyl, naphthyl, pyridyl, furanyl, thiophene, pyrazolyl, imidazoleyl, substituted or unsubstituted phenyl, benzyl, naphthyl, pyridyl, furanyl, thiophene, pyrazolyl, imidazoleyl, substituted or unsubstituted C3-C8 heterocycles;

[0009] R 2 Selected from H, C1-C 12 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C substituted with halogen 12 Alkyl, substituted or unsubstituted phenyl, benzyl, naphthyl, pyrrolyl, furanyl, tetrahydrofuranyl, thienyl, thiazolyl, imidazolyl, pyrazolyl, oxazolyl, valproicinyl, pyridyl, pyranyl, piperidinyl, piperazinyl, pyridazinyl, pyrimidinyl, caprolactamyl, C3-C8 heterocycles;

[0010] R 3 Selected from H, C1-C 12 Alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C substituted with halogen 12 Alkyl, substituted or unsubstituted phenyl, benzyl, naphthyl, pyrrolyl, furanyl, tetrahydrofuranyl, thienyl, thiazolyl, imidazolyl, pyrazolyl, oxazolyl, valproicinyl, pyridyl, pyranyl, piperidinyl, piperazinyl, pyridazinyl, pyrimidinyl, caprolactamyl, C3-C8 heterocycles;

[0011] R 4 Selected from H, halogen, hydroxyl, amino, mercapto, cyano, nitro, C1-C8 alkyl, halogen-substituted C1-C8 alkyl, C1-C8 alkoxy, C1-C8 alkylamine, C1-C8 alkhiol, halogen-substituted C1-C8 alkoxy, phenyl, benzyl, naphthyl, pyridyl, furanyl, thiophene, pyrazolyl, imidazolyl, phenyl, benzyl, naphthyl, pyridyl, furanyl, thiophene, pyrazolyl, imidazolyl, and C3-C8 heterocycles substituted with or unsubstituted by C1-C8 alkyl and / or halogen;

[0012] And R 1 R 2 R 3 R 4The substituents in each group are independently selected from one or more of the following: halogen, hydroxyl, amino, mercapto, cyano, nitro, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl substituted by halogen, C1-C6 alkoxy substituted by halogen, and phenoxy substituted by halogen and / or alkyl.

[0013] n = 0, 1, 2, 3, 4, 5, 6, 7, 8

[0014] Z = C,O,S

[0015] Q is selected from any group in X1-X3 below, and Q is in any substitution position on the aromatic ring;

[0016]

[0017] Among them, A in X1-X3 1 A 2 A 3 Each of the following is independently selected from H, halogen, hydroxyl, amino, mercapto, cyano, nitro, C1-C8 alkyl, halogen-substituted C1-C8 alkyl, C1-C8 alkoxy, halogen-substituted C1-C8 alkoxy, phenyl, benzyl, naphthyl, pyridyl, furanyl, thiophene, pyrazolyl, imidazolyl, phenyl, benzyl, naphthyl, pyridyl, furanyl, thiophene, pyrazolyl, imidazolyl, and C3-C8 heterocycles substituted with or unsubstituted by C1-C8 alkyl and / or halogen;

[0018] In X1-X6, A 1 A 2 A 3 A 4 A 5 A 6 It can be monosubstituted or polysubstituted;

[0019] n1=0,1,2,3,4,5,6.

[0020] Preferably, R 1 The following are phenyl, 2-bromo-phenyl, 2-chloro-phenyl, 4-methyl-phenyl, 4-ethyl-phenyl, 4-methoxy-phenyl, 4-chloro-phenyl, 4-bromo-phenyl, 4-fluoro-phenyl, 2,5-dimethyl-phenyl, 2,6-dichloro-phenyl, 3,4-dichloro-phenyl, 3-methyl-phenyl, 4-hydroxy-phenyl, 4-cyano-phenyl, 4-nitro-phenyl, 4-monofluoromethyl-phenyl, 4-difluoromethyl-phenyl, and 4-trifluoromethyl-phenyl;

[0021] R 2 For H, CH3, R 3For H, CH3, R 4 CH2, H, Z O, S, Q -4-benzyl, -4-(4-hydroxy)-phenyl, -4-(4-methoxy)-phenyl, -4-pyridyl-4-pyrimidinyl, -4-pyridyl, -4-pyrimidinyl, -3-pyrimidinyl, -2-pyrimidinyl, -3-pyridinyl, -2-pyrimidinyl;

[0022] Preferably, R 1 The following are phenyl, 2-bromo-phenyl, 2-chloro-phenyl, 4-methyl-phenyl, 4-ethyl-phenyl, 4-methoxy-phenyl, 4-chloro-phenyl, 4-bromo-phenyl, 4-fluoro-phenyl, 2,5-dimethyl-phenyl, 2,6-dichloro-phenyl, 3,4-dichloro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 4-hydroxy-phenyl, 4-methoxy-phenyl, 4-cyano-phenyl, 4-nitro-phenyl, 4-monofluoromethyl-phenyl, 4-difluoromethyl-phenyl, and 4-trifluoromethyl-phenyl;

[0023] R 2 For H, CH3, R 3 For H, CH3, R 4 H represents H, Z represents O or S, and Q represents -4-benzyl, -4-(4-hydroxy)-phenyl, -4-(4-methoxy)-phenyl, -4-pyridyl, or -4-pyrimidinyl.

[0024] More preferably, the substituents are as follows:

[0025] R 1 The following are phenyl, 2-bromo-phenyl, 2-chloro-phenyl, 4-methyl-phenyl, 4-ethyl-phenyl, 4-methoxy-phenyl, 4-chloro-phenyl, 4-bromo-phenyl, 4-fluoro-phenyl, 2,5-dimethyl-phenyl, 2,6-dichloro-phenyl, 3,4-dichloro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 4-hydroxy-phenyl, 4-methoxy-phenyl, 4-cyano-phenyl, 4-nitro-phenyl, 4-monofluoromethyl-phenyl, 4-difluoromethyl-phenyl, and 4-trifluoromethyl-phenyl;

[0026] R 2 For H, CH3, R 3 For H, CH3, R 4 H represents H, Z represents O or S, and Q represents -4-benzyl, -4-(4-hydroxy)-phenyl, -4-(4-methoxy)-phenyl, -4-pyridyl, or -4-pyrimidinyl.

[0027] More preferably, but not limited to, the following compounds:

[0028] Compound H24001: R 1 It is 4-chloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0029] Compound H24002: R 1 It is 2,5-dimethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0030] Compound H24003: R 1 It is 4-bromo-phenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0031] Compound H24004: R 1 It is 3-methyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0032] Compound H24005: R 1 It is a phenyl group, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0033] Compound H24006: R 1 It is 4-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0034] Compound H24007: R 1 It is 2-bromo-phenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl compound H24008: R 1 It is 4-methyl-phenyl, n=0, R 2 For H, R 3 For H, R 4H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0035] Compound H24009: R 1 It is 2-chloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0036] Compound H24010: R 1 It is 4-trifluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0037] Compound H24011: R 1 It is 2-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0038] Compound H24O12: R 1 It is 4-cyano-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0039] Compound H24O13: R 1 It is 4-nitrophenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0040] Compound H24O14: R 1 It is 4-difluoromethyl-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0041] Compound H24O15: R 1 It is 4-monofluoromethyl-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0042] Compound H24O16: R1 It is 4-chloro-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0043] Compound H24O17: R 1 It is 4-bromo-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0044] Compound H24018: R 1 It is a phenyl group, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0045] Compound H24019: R 1 It is 4-fluoro-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0046] Compound H24O20: R 1 It is 4-methoxy-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0047] Compound H24O21: R 1 It is 4-hydroxy-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0048] Compound H24O22: R 1 It is 4-trifluoromethyl-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0049] Compound H24O23: R 1 It is 4-methyl-phenyl, n=1, R 2 For H, R 3 For H, R 4H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0050] Compound H24O24: R 1 It is 4-ethyl-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0051] Compound H24O25: R 1 It is 4-cyano-phenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-(4-hydroxy)-phenyl;

[0052] Compound H24O26: R 1 It is 4-nitrophenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-(4-hydroxy)-phenyl;

[0053] Compound H24O27: R 1 It is 4-chloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-(4-hydroxy)-phenyl;

[0054] Compound H24O28: R 1 It is 4-bromo-phenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-(4-hydroxy)-phenyl;

[0055] Compound H24O29: R 1 It is a phenyl group, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-(4-hydroxy)-phenyl;

[0056] Compound H24O30: R 1 It is 4-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-(4-hydroxy)-phenyl;

[0057] Compound H24O31: R 1It is 4-methoxy-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-(4-hydroxy)-phenyl;

[0058] Compound H24O32: R 1 It is 4-hydroxy-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-(4-hydroxy)-phenyl;

[0059] Compound H24O33: R 1 It is 4-trifluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-(4-hydroxy)-phenyl;

[0060] Compound H24O34: R 1 It is 4-methyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-(4-hydroxy)-phenyl;

[0061] Compound H24O35: R 1 It is 4-ethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-(4-hydroxy)-phenyl;

[0062] Compound H24O36: R 1 It is 2,6-dichloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0063] Compound H24O37: R 1 It is 3,4-dichloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0064] Compound H24O38: R 1 It is 4-methoxy-phenyl, n=0, R 2 For H, R 3 For H, R 4H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0065] Compound H24O39: R 1 It is 2-fluoro-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24040: R 1 It is 4-methyl-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24041: R 1 It is 2-methyl-5-chloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0066] Compound H24O42: R 1 It is 3-chloro-4-methyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl;

[0067] Compound H24O43: R 1 It is 4-cyano-phenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-benzyl;

[0068] Compound H24O44: R 1 It is 4-nitrophenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-benzyl;

[0069] Compound H24O45: R 1 It is 4-difluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-benzyl;

[0070] Compound H24O46: R 1 It is 4-monofluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4H is H, Z is O, and Q is -4-benzyl;

[0071] Compound H24047: R 1 It is 4-chloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-benzyl;

[0072] Compound H24048: R 1 It is 4-bromo-phenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-benzyl;

[0073] Compound H24049: R 1 It is a phenyl group, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-benzyl;

[0074] Compound H24050: R 1 It is 4-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-benzyl;

[0075] Compound H24051: R 1 It is 4-methoxy-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-benzyl;

[0076] Compound H24052: R 1 It is 4-hydroxy-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-benzyl;

[0077] Compound H24053: R 1 It is 4-trifluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-benzyl;

[0078] Compound H24054: R 1 It is 4-methyl-phenyl, n=0, R 2 For H, R 3 For H, R 4H is H, Z is O, and Q is -4-benzyl;

[0079] Compound H24055: R 1 It is 4-ethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-benzyl;

[0080] Compound H24056: R 1 It is 4-cyano-phenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyridinyl;

[0081] Compound H24057: R 1 It is 4-nitrophenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyridinyl;

[0082] Compound H24058: R 1 It is 4-difluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyridinyl;

[0083] Compound H24059: R 1 It is 4-monofluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyridinyl;

[0084] Compound H24O60: R 1 It is 4-chloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyridinyl;

[0085] Compound H24061: R 1 It is 4-bromo-phenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyridinyl;

[0086] Compound H24O62: R 1 It is a phenyl group, n=0, R 2 For H, R 3 For H, R4 H is H, Z is O, and Q is -4-pyridinyl;

[0087] Compound H24O63: R 1 It is 4-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyridinyl;

[0088] Compound H24O64: R 1 It is 4-methoxy-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyridinyl;

[0089] Compound H24065: R 1 It is 4-hydroxy-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyridinyl;

[0090] Compound H24066: R 1 It is 4-trifluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyridinyl;

[0091] Compound H24067: R 1 It is 4-methyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyridinyl;

[0092] Compound H24068: R 1 It is 4-ethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyridinyl;

[0093] Compound H24069: R 1 It is 4-cyano-phenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyrimidinyl;

[0094] Compound H24070: R 1 It is 4-nitrophenyl, n = 0, R 2 For H, R3 For H, R 4 H is H, Z is O, and Q is -4-pyrimidinyl;

[0095] Compound H24071: R 1 It is 4-difluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyrimidinyl;

[0096] Compound H24072: R 1 It is 4-monofluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyrimidinyl; Compound H24073: R 1 It is 4-chloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyrimidinyl;

[0097] Compound H24074: R 1 It is 4-bromo-phenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyrimidinyl;

[0098] Compound H24075: R 1 It is a phenyl group, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyrimidinyl;

[0099] Compound H24076: R 1 It is 4-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyrimidinyl;

[0100] Compound H24077: R 1 It is 4-methoxy-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyrimidinyl; Compound H24078: R 1 It is 4-hydroxy-phenyl, n=0, R 2 For H, R 3 For H, R 4H is H, Z is O, and Q is -4-pyrimidinyl;

[0101] Compound H24079: R 1 It is 4-trifluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyrimidinyl; Compound H24080: R 1 It is 4-methyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyrimidinyl;

[0102] Compound H24081: R 1 It is 4-ethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyrimidinyl;

[0103] Compound H24082: R 1 It is 4-cyano-phenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0104] Compound H24083: R 1 It is 4-nitrophenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0105] Compound H24084: R 1 It is 4-difluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl; Compound H24085: R 1 It is 4-monofluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl; Compound H24086: R 1 It is 4-chloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0106] Compound H24087: R1 It is 4-bromo-phenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0107] Compound H24088: R 1 It is a phenyl group, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0108] Compound H24089: R 1 It is 4-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0109] Compound H24090: R 1 It is 4-methoxy-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl; Compound H24091: R 1 It is 4-hydroxy-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0110] Compound H24092: R 1 It is 4-trifluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl; Compound H24093: R 1 It is 4-methyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0111] Compound H24094: R 1 It is 4-ethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0112] Compound H24095: R 1 It is 4-trifluoromethyl-phenyl, n=0, R 2For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyridyl; Compound H24096: R 1 It is 4-methyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0113] Compound H24097: R 1 It is 4-chloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0114] Compound H24098: R 1 It is 4-bromo-phenyl, n = 0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0115] Compound H24099: R 1 It is a phenyl group, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0116] Compound H24100: R 1 It is 4-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0117] Compound H24101: R 1 It is 4-cyano-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0118] Compound H24102: R 1 It is 4-nitrophenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0119] Compound H24103: R 1 It is 4-difluoromethyl-phenyl, n=1, R 2 For H, R 3For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl; Compound H24104: R 1 It is 4-monofluoromethyl-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl; Compound H24105: R 1 It is 4-chloro-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0120] Compound H24106: R 1 It is 4-bromo-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0121] Compound H24107: R 1 It is a phenyl group, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0122] Compound H24108: R 1 It is 4-fluoro-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0123] Compound H24109: R 1 It is 4-methoxy-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl; Compound H24110: R 1 It is 4-hydroxy-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0124] Compound H24111: R 1 It is 4-trifluoromethyl-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl; Compound H24112: R 1It is 4-methyl-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0125] Compound H24113: R 1 It is 4-ethyl-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl;

[0126] Compound H24114: R 1 It is 4-trifluoromethyl-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0127] Compound H24115: R 1 It is 4-methyl-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0128] Compound H24116: R 1 It is 4-chloro-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0129] Compound H24117: R 1 It is 4-bromo-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0130] Compound H24118: R 1 It is a phenyl group, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0131] Compound H24119: R 1 It is 4-fluoro-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0132] Compound H24120: R1 It is 4-trifluoromethyl-phenyl, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0133] Compound H24121: R 1 It is 4-methyl-phenyl, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0134] Compound H24123: R 1 It is 4-chloro-phenyl, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0135] Compound H24124: R 1 It is 4-bromo-phenyl, n = 0, R 2 CH3, R 3 CH3, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0136] Compound H24125: R 1 It is a phenyl group, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0137] Compound H24126: R 1 It is 4-fluoro-phenyl, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is S, and Q is -4-pyridinyl;

[0138] Compound H24127: R 1 It is 4-trifluoromethyl-phenyl, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is O, and Q is -4-pyrimidinyl;

[0139] Compound H24128: R 1 It is 4-methyl-phenyl, n=0, R 2 CH3, R 3 CH3, R 4H is H, Z is O, and Q is -4-pyrimidinyl;

[0140] Compound H24129: R 1 It is 4-chloro-phenyl, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is O, and Q is -4-pyrimidinyl;

[0141] Compound H24130: R 1 It is 4-bromo-phenyl, n = 0, R 2 CH3, R 3 CH3, R 4 H is H, Z is O, and Q is -4-pyrimidinyl;

[0142] Compound H24131: R 1 It is a phenyl group, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is O, and Q is -4-pyrimidinyl;

[0143] Compound H24132: R 1 It is 4-fluoro-phenyl, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is O, and Q is -4-pyrimidinyl;

[0144] Compound H24133: R 1 It is 4-trifluoromethyl-phenyl, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is O, and Q is -2-pyrimidinyl;

[0145] Compound H24134: R 1 It is 4-chloro-phenyl, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is O, and Q is -3-pyrimidinyl;

[0146] Compound H24135: R 1 It is 4-bromo-phenyl, n = 0, R 2 CH3, R 3 CH3, R 4 H is H, Z is O, and Q is -2-pyridinyl;

[0147] Compound H24136: R 1 It is 4-fluoro-phenyl, n=0, R 2CH3, R 3 CH3, R 4 H is H, Z is O, and Q is -3-pyridinyl;

[0148] Compound H24137: R 1 It is 4-trifluoromethyl-phenyl, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is O, and Q is -4-(4-methoxy)-phenyl;

[0149] Compound H24138: R 1 It is 4-methyl-phenyl, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is O, and Q is -4-(4-methoxy)-phenyl;

[0150] Compound H24139: R 1 It is 4-chloro-phenyl, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is O, and Q is -4-(4-methoxy)-phenyl;

[0151] Compound H24140: R 1 It is 4-bromo-phenyl, n = 0, R 2 CH3, R 3 CH3, R 4 H is H, Z is O, and Q is 4-(4-methoxy)-phenyl;

[0152] Compound H24141: R 1 It is a phenyl group, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is O, and Q is -4-(4-methoxy)-phenyl;

[0153] Compound H24142: R 1 It is 4-fluoro-phenyl, n=0, R 2 CH3, R 3 CH3, R 4 H is H, Z is O, and Q is -4-(4-methoxy)-phenyl;

[0154] Compound H24143: R 1 It is 4-fluoro-phenyl, n=0, R 2 for R 3 for R4 H is H, Z is O, and Q is -4-(4-methoxy)-phenyl.

[0155] Compound H24144: R 1 It is 4-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is CH2, and Q is -4-(4-hydroxy)-phenyl.

[0156] Compound H24145: R 1 It is 4-fluoro-phenyl, n=0, R 2 for R 3 for R 4 H is ZCH2, and Q is -4-(4-hydroxy)-phenyl.

[0157] The terminology of this invention is explained below.

[0158] "C1-C8 alkyl" refers to alkyl groups with a total number of carbon atoms of 1-8, including straight-chain alkyl groups, branched alkyl groups, or cycloalkyl groups. For example, it can be a straight-chain alkyl group, a branched alkyl group, or a cycloalkyl group with a total number of carbon atoms of 1, 2, 3, 4, 5, 6, 7, or 8. Examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclopropyl, methylcyclopropyl, ethylcyclopropyl, cyclobutyl, methylcyclobutyl, ethylcyclobutyl, cyclopentyl, methylcyclopentyl, ethylcyclopentyl, cyclohexyl, methylcyclohexyl, ethylcyclohexyl, etc.

[0159] In this invention, "C1-C8 alkoxy group" refers to an alkoxy group having 1-8 carbon atoms, such as methyloxy, ethyloxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, tert-butyloxy, n-pentyloxy, isopentyloxy, n-hexyloxy, cyclopropyloxy, methylcyclopropyloxy, ethylcyclopropyloxy, cyclopentyloxy, methylcyclopentyloxy, and cyclohexyloxy.

[0160] In this invention, "C1-C" 12 "Alkylamino" indicates an amino group with alkyl substitution having 1-12 carbon atoms, which can be mono- and / or dialkyl-substituted, wherein the alkyl group can be the same and / or different when dialkyl-substituted.

[0161] In this invention, "C1-C" 12"Alkyl mercapto" indicates an alkyl mercapto group with 1-12 carbon atoms, such as methyl mercapto, ethyl mercapto, n-propyl mercapto, isopropyl mercapto, n-butyl mercapto, isobutyl mercapto, tert-butyl mercapto, n-pentyl mercapto, isopentyl mercapto, n-hexyl mercapto, cyclopropyl mercapto, methylcyclopropyl mercapto, ethylcyclopropyl mercapto, cyclopentyl mercapto, methylcyclopentyl mercapto, cyclohexyl mercapto, etc.

[0162] In this invention, "C2-C6 alkenyl" refers to a monoalkenyl, dienyl, or polyalkenyl group having 1-6 carbon atoms, such as vinyl, n-propenyl, isopropenyl, n-butenyl, n-dibutenyl, isobutenyl, tert-butenyl, n-pentenyl, 1,3-pentadienyl, isopentenyl, n-hexenyl, 1,3-hexadienyl, cyclopropenyl, methylcyclopropenyl, ethylcyclopropenyl, cyclopentenyl, methylcyclopentenyl, and cyclohexenyl.

[0163] In this invention, "C2-C6 alkynyl" refers to a mono-alkynyl, di-alkynyl, or poly-alkynyl group having 1-6 carbon atoms. Examples include ethynyl, n-propynyl, isopropynyl, n-butynyl, n-dibutynyl, isobutynyl, tert-butynyl, n-pentynyl, 1,3-pentadiynyl, isopentenynyl, n-hexynyl, 1,3-hexadiynyl, cyclopropynyl, methylcyclopropynyl, ethylcyclopropynyl, cyclopentynyl, methylcyclopentynyl, and cyclohexynyl.

[0164] In this invention, the term "substituted or unsubstituted C3-C8 heterocycle" refers to a heterocycle containing at least one of N, O, and S.

[0165] In this invention, "halogen" means at least one element selected from fluorine, chlorine, bromine, and iodine.

[0166] The present invention does not particularly limit the method of synthesizing the benzoyl hydrazine compound shown in formula (I). Those skilled in the art can obtain suitable methods for preparing the derivatives shown in formula (I) by combining the compound structure provided by the present invention with the synthesis methods in the field of chemistry. The present invention will not elaborate on these methods here.

[0167] A second aspect of the present invention provides a pesticide fungicide composed of an active ingredient and excipients, wherein the active ingredient includes at least one of the compounds containing benzoyl hydrazine as described in the first aspect above.

[0168] The content of the active ingredient is 1 to 99.9999% by weight; preferably, the content of the active ingredient is 1 to 50% by weight; more preferably, the content of the active ingredient is 20 to 40% by weight.

[0169] Specifically, the formulation of the pesticide fungicide is selected from one of the following: emulsifiable concentrate, suspension concentrate, wettable powder, powder, granule, aqueous solution, poison bait, mother liquor, and mother powder.

[0170] The present invention also provides the application of the compound as a pesticide fungicide in the prevention and control of plant diseases.

[0171] Specifically, the target crops for prevention and control are selected from corn, wheat, soybean, rice, rapeseed, and peanut crops; the plant diseases are caused by one or more pathogenic fungi and / or bacteria.

[0172] More specifically, the plant disease is selected from at least one of the following bacterial diseases: bacterial leaf blight, bacterial basal rot, bacterial brown streak, bacterial leaf spot, bacterial brown spot, bacterial wilt, and bacterial stem rot; or at least one of the following fungal diseases: damping-off, root rot, downy mildew, white rust, blight, cottony blight, Fusarium head blight, powdery mildew, anthracnose, leaf spot, black spot, smut, rust, sheath blight, damping-off, gray mold, and rapeseed sclerotinia stem rot.

[0173] The present invention also provides a method for synthesizing the derivative containing the benzoylhydrazine fragment, characterized by comprising the following steps:

[0174]

[0175] Step I:R 4 The substituted p-fluorobenzonitrile was added together with the Q-OH or Q-SH derivative into the solvent and reacted under alkaline conditions at 25-120°C for 2-24 hours. After the reaction was completed, water and ethyl acetate were added for extraction, the organic phase was collected and dried, the solvent was removed by vacuum distillation, and column chromatography was used to obtain intermediate 2.

[0176] Step II: Intermediate 2 is dissolved in an aqueous methanol solution, excess sodium hydroxide is added, and the reaction is carried out at 25-120℃ for 2-24 hours; after the reaction is completed, water and ethyl acetate are added for extraction, the aqueous phase is collected and the pH is adjusted to 1-2 with hydrochloric acid, the solid is allowed to precipitate, and the solid is obtained by filtration.

[0177] Step III: Intermediate 3 and hydrazine hydrochloride are dissolved in dichloromethane, and then condensing agent HATU and triethylamine are added. The reaction is carried out at 25-120℃ for 2-24 hours; after the reaction is completed, sodium bicarbonate aqueous solution and ethyl acetate are added for extraction, the organic phase is collected and dried, the solvent is removed by vacuum distillation, and column chromatography is used to obtain derivative 4;

[0178] Step IV: Dissolve derivative 4 in DMF, add base and halogen, and react at 25-120℃ for 2-24 hours; after the reaction is complete, extract with water and ethyl acetate, collect the organic phase and dry it, remove the solvent by vacuum distillation, and obtain the target compound by column chromatography.

[0179] This invention offers the following advantages: It presents a novel molecular framework targeting SDH inhibitors, providing a new direction for subsequent drug development. This novel molecular framework exhibits extremely high inhibitory activity against the tested pathogens. At a dose of 50 μg / mL, its control effect on tomato gray mold is comparable to that of the positive control agent, boscalid. Furthermore, as it is a novel molecular framework, it holds promise for overcoming pathogen resistance issues. The compounds in this invention have simple structures, are easy to prepare, and exhibit high activity, demonstrating excellent potential for commercial application. Attached Figure Description

[0180] Figure 1 This invention relates to the development strategy of cyazofamid and the design concept of the compound.

[0181] Figure 2 The antifungal activity of compounds H24001, H24003, H24006, H24008, H24010, cyazofamid, and FY21001 in petri dishes was measured at a dose of 10 μg / mL. A blank plate without any added drugs served as the control group.

[0182] Figure 3 The control effect of H24006 on Sclerotinia sclerotinia, the pathogen of rapeseed.

[0183] Figure 4 The inhibitory effect of H24006 on tomato gray mold. Detailed Implementation

[0184] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0185] Example 1: Synthesis of compound H24001

[0186] The method is as follows:

[0187]

[0188] Step a: General method for synthesizing 4-(4-hydroxyphenoxy)benzonitrile

[0189] Hydroquinone (1.65 g, 15 mmol) and potassium carbonate (2.76 g, 20 mmol) were added to 20 mL of DCM solvent, stirred, and heated to approximately 110 °C for 30 min. Then, p-fluorobenzonitrile (1.21 g, 10 mmol) was added, and the reaction was carried out for at least 4 h. Thin-layer chromatography was used to monitor the silica gel plate. After the reaction was completed, 80 mL of water and 150 mL of ethyl acetate were added to the reaction system, and the mixture was extracted three times with a 250 mL separating funnel, followed by washing three times with saturated brine. The organic phase was then collected. The organic phase was dried over anhydrous sodium sulfate. Finally, the solvent was evaporated to dryness using a rotary evaporator to obtain solid intermediate II.

[0190] Step b: Synthesis of 4-(4-hydroxyphenoxy)benzoic acid

[0191] Sodium hydroxide (0.8 g, 20 mmol) and intermediate II (1.05 g, 20 mmol) were added to a reaction flask containing 20 mL of THF:water (1:1). The flask was placed in an oil bath, and a condenser was inserted to heat the mixture to 85 °C overnight. Thin-layer chromatography was used to monitor the reaction. After the reaction was complete, 20 mL of water and 50 mL of ethyl acetate were added to the reaction mixture to extract the aqueous phase three times, collecting the aqueous phase. Then, concentrated hydrochloric acid was added dropwise to the aqueous phase under ice bath conditions, and the mixture was continuously stirred with a glass rod until the solid completely precipitated (pH = 1-2). Finally, the mixture was filtered through a Bush funnel, washed three times with water, and dried in an oven at 100 °C to obtain solid intermediate III.

[0192] Step c: Synthesis of compounds H24001–H24024

[0193] Intermediate 3 (0.50 g, 2.17 mmol), DCM (6 mL), and p-chlorophenylhydrazine hydrochloride (0.364 g, 2.2 mmol) were added to a 100 mL round-bottom flask. After stirring to dissolve, HATU (0.99 g, 2.61 mmol) and triethylamine (0.44 g, 4.35 mmol) were added to the reaction system. The mixture was stirred at room temperature for 2 hours, and the reaction was monitored by thin-layer chromatography. Sodium bicarbonate solution (20 mL) was added to the reaction system with stirring, and the organic phase was collected. The aqueous layer was extracted approximately twice with DCM (15 mL). The organic layers were then combined, dried over anhydrous sodium sulfate, and purified by column chromatography (petroleum ether / EtOAc = 2 / 1) to obtain the target compound.

[0194] Derivatives containing different Q fragments were synthesized using the above synthetic method. The specific synthetic route is as follows:

[0195]

[0196] Example 2: Synthesis of compound H24120

[0197] The method is as follows:

[0198]

[0199] 4-Hydroxypyridine (1.65 g, 15 mmol) and potassium carbonate (2.76 g, 20 mmol) were added to 20 mL of solvent DCM, stirred, and heated to approximately 110 °C for 30 min. Then, p-fluorobenzonitrile (1.21 g, 10 mmol) was added, and the reaction was carried out for at least 4 h. The silica gel plate was monitored by thin-layer chromatography. After the reaction was completed, 80 mL of water and 150 mL of ethyl acetate were added to the reaction system, and the mixture was extracted three times with a 250 mL separating funnel, followed by washing three times with saturated brine. The organic phase was collected and dried over anhydrous sodium sulfate. Finally, the solvent was evaporated to dryness using a rotary evaporator to obtain solid intermediate I-2.

[0200] Sodium hydroxide (0.8 g, 20 mmol) and intermediate I-2 (1.05 g, 20 mmol) were added to a reaction flask containing 20 mL of THF:water (1:1). The flask was placed in an oil bath, and a condenser was inserted to heat the mixture to 85 °C overnight. Thin-layer chromatography was used to monitor the reaction. After the reaction was complete, 20 mL of water and 50 mL of ethyl acetate were added to the reaction mixture to extract the aqueous phase three times, collecting the aqueous phase. Then, concentrated hydrochloric acid was added dropwise to the aqueous phase under ice bath conditions, with continuous stirring using a glass rod until the solid completely precipitated (pH = 1-2). Finally, the mixture was filtered through a Bush funnel, washed three times with water, and dried in a 100 °C oven to obtain solid intermediate I-3.

[0201] In a 100 mL round-bottom flask, intermediate I-3 (0.50 g, 2.17 mmol), DCM (6 mL), and p-chlorophenylhydrazine hydrochloride (0.364 g, 2.2 mmol) were added. After stirring to dissolve, HATU (0.99 g, 2.61 mmol) and triethylamine (0.44 g, 4.35 mmol) were added to the reaction system. The mixture was stirred at room temperature for 2 hours, and the reaction was monitored by thin-layer chromatography. Sodium bicarbonate solution (20 mL) was added to the reaction system with stirring, and the organic phase was collected. The aqueous layer was extracted approximately twice with DCM (15 mL). The organic layers were then combined, dried over anhydrous sodium sulfate, and purified by column chromatography (petroleum ether / EtOAc = 2 / 1) to give I-4.

[0202] In a 100 mL round-bottom flask, intermediate I-4 (2.0 mmol), DMF (10 mL), and cesium carbonate (6 mmol) were added and stirred until dissolved. Iodomethane (6 mmol) was then added to the reaction mixture. The mixture was stirred at room temperature until the reaction was complete. Sodium bicarbonate solution (20 mL) was added to the reaction mixture while stirring to quench the reaction. The mixture was extracted approximately twice with ethyl acetate (15 mL). The organic layers were then combined, dried over anhydrous sodium sulfate, and purified by column chromatography (petroleum ether / EtOAc = 2 / 1) to obtain the target compound.

[0203] Example 3: Synthesis of compound H24143

[0204] The method is as follows:

[0205]

[0206] Hydroquinone (1.65 g, 15 mmol) and potassium carbonate (2.76 g, 20 mmol) were added to 20 mL of DCM solvent, stirred, and heated to approximately 110 °C for 30 min. Then, p-fluorobenzonitrile (1.21 g, 10 mmol) was added, and the reaction was carried out for at least 4 h. Thin-layer chromatography was used to monitor the silica gel plate. After the reaction was completed, 80 mL of water and 150 mL of ethyl acetate were added to the reaction system, and the mixture was extracted three times with a 250 mL separating funnel, followed by washing three times with saturated brine. The organic phase was then collected and dried over anhydrous sodium sulfate. Finally, the solvent was evaporated to dryness using a rotary evaporator to obtain solid intermediate II-2.

[0207] Sodium hydroxide (0.8 g, 20 mmol) and intermediate II-2 (1.05 g, 20 mmol) were added to a reaction flask containing 20 mL of THF:water (1:1). The flask was placed in an oil bath, and a condenser was inserted to heat the mixture to 85 °C overnight. Thin-layer chromatography was used to monitor the reaction. After the reaction was complete, 20 mL of water and 50 mL of ethyl acetate were added to the reaction mixture for extraction three times, and the aqueous phase was collected. Then, concentrated hydrochloric acid was added dropwise to the aqueous phase under ice bath conditions, and the mixture was continuously stirred with a glass rod until the solid completely precipitated (pH = 1-2). Finally, the mixture was filtered through a Bush funnel, washed three times with water, and dried in an oven at 100 °C to obtain solid intermediate II-3.

[0208] Intermediate II-3 (0.50 g, 2.17 mmol), DCM (6 mL), and p-fluorophenylhydrazine hydrochloride (0.364 g, 2.2 mmol) were added to a 100 mL round-bottom flask. After stirring to dissolve, HATU (0.99 g, 2.61 mmol) and triethylamine (0.44 g, 4.35 mmol) were added to the reaction system. The mixture was stirred at room temperature for 2 hours, and the reaction was monitored by thin-layer chromatography. Sodium bicarbonate solution (20 mL) was added to the reaction system with stirring, and the organic phase was collected. The aqueous layer was extracted approximately twice with DCM (15 mL). The organic layers were then combined, dried over anhydrous sodium sulfate, and purified by column chromatography (petroleum ether / EtOAc = 2 / 1) to give compound II-4.

[0209] In a 100 mL round-bottom flask, intermediate II-4 (2.0 mmol), DMF (10 mL), and triethylamine (6 mmol) were added and stirred until dissolved. Allyl bromide (6 mmol) was then added to the reaction mixture. The mixture was stirred at room temperature until the reaction was complete. Sodium bicarbonate solution (20 mL) was added to the reaction mixture while stirring to quench the reaction. The mixture was extracted approximately twice with ethyl acetate (15 mL). The organic layers were then combined, dried over anhydrous sodium sulfate, and purified by column chromatography (petroleum ether / EtOAc = 2 / 1) to obtain the target compound.

[0210] Example 4: Synthesis of compound H24139

[0211] The method is as follows:

[0212]

[0213] The synthesis methods for steps a, b, and c are the same as those in Example 3. The synthesis method for step d is as follows:

[0214] In a 100 mL round-bottom flask, intermediate II-4 (2.0 mmol), DMF (10 mL), and cesium carbonate (6 mmol) were added and stirred until dissolved. Iodomethane (8 mmol) was then added to the reaction mixture. The mixture was stirred at room temperature until the reaction was complete. Sodium bicarbonate solution (20 mL) was added to the reaction mixture while stirring to quench the reaction. The mixture was extracted approximately twice with ethyl acetate (15 mL). The organic layers were then combined, dried over anhydrous sodium sulfate, and purified by column chromatography (petroleum ether / EtOAc = 2 / 1) to obtain the target compound.

[0215] The benzoyl hydrazine derivatives of the present invention were synthesized according to the above method. Table 1 below lists the structural characterization data of some compounds of the present invention.

[0216] Table 1. Physical properties and spectral characterization of specific compounds of Formula I

[0217]

[0218]

[0219]

[0220]

[0221] Example 5: Screening for antifungal activity

[0222] The effects of the target compound on *Rhizoctonia solani*, *Sclerotinia sclerotiorum*, *Fusarium graminearum*, and *Botrytis cinerea* of tomato were determined using the mycelial growth rate method. The compound was dissolved in DMSO and added to quantitative PDA medium (100g glucose, 1000g potato, 72g agar, 5L ultrapure water) to prepare plates with a final concentration of 10μg / mL containing the compound and plates without the compound as blank controls. Cyclosulfuron was used as a positive control. Mycelial cakes were inoculated into the center of the plates containing the compound and the blank control plates, respectively. The samples were incubated in a dark incubator at 25℃ for 3-5 days. When the diameter of the control colony exceeded 5cm, the colony diameter of the sample was measured using the cross-sectional method. Inhibition rate (%) = [(control colony diameter - treated colony diameter) / (control colony diameter - 0.5)] × 100 (0.5 is the diameter of the filter cake (cm)).

[0223] In this invention, the commercially available fungicide boscalid and another compound, FY21001, reported in Chinese patent ZL 202111251111.6, were selected as positive controls. Most compounds showed better inhibitory activity against the tested pathogens than FY21001, especially compound H24006, which exhibited 100% inhibitory activity against Fusarium graminearum (wheat scab) and Sheath blight (rice wilt), outperforming both the control fungicide boscalid and FY21001.

[0224] The structure of compound FY21001 is as follows:

[0225]

[0226] Table 2. Antibacterial activity of some Formula I derivatives on plates

[0227]

[0228]

[0229] Data are reported as mean ± SD of three biological replicates. Different letters correspond to different treatments in Tukey's HSD test with p < 0.05, indicating significant differences between treatments and the references at the same concentration.

[0230] Example 6: Screening for antifungal activity

[0231] The inhibitory effect of the target compound on the growth of *Sclerotinia sclerotinia*, the causal agent of rapeseed disease, was determined using the mycelial growth rate method. The compound was dissolved in DMSO and added to a quantitative PDA medium (100g glucose, 1000g potato, 72g agar, 5L ultrapure water) to prepare plates with a final concentration of 10μg / mL. Plates containing the drug and those without the drug served as blank controls. Cyclocarboxamide was used as a positive control. Mycelial cakes were inoculated into the center of both the drug-containing and blank control plates. The samples were incubated in a dark incubator at 25℃ for 3-5 days. When the diameter of the control colonies exceeded 5cm, the colony diameter of the sample was measured using the cross-sectional method. Inhibition rate (%) = [(control colony diameter - treated colony diameter) / (control colony diameter - 0.5)] × 100 (where 0.5 is the diameter of the filter cake (cm)).

[0232] Table 3. Preliminary screening of the antibacterial activity of some Formula I derivatives against Sclerotinia sclerotiorum var. sclerotiorum as determined by mycelial growth method.

[0233] H24012 90 H24013 85 H24014 90 H24015 80 H24016 80 H24017 90 H24022 95 H24025 95 H24027 70 H24030 85 H24033 85 H24047 90 H24050 85 H24053 85 H24063 75 H24066 70 H24076 70 H24079 85 H24089 85 H24100 85 H24108 85 H24119 90 H24119 60 H24143 60

[0234] Example 7: EC 50 Value determination

[0235] EC 50 The results of the value determination showed that compound H24006 had an EC50 effect on four pathogens. 50 The EC50 values ​​of compounds H24001, H24003, and H24010 were all superior to the positive control (Table 4). 50 The values ​​were all superior to those of boscalid, and compound H24008 showed better EC50 values ​​against tomato gray mold. 50 The values ​​are comparable to those of boscalid. Compounds H24001, H24003, and H24008 exhibit EC50 values ​​against Fusarium graminearum, the causal agent of wheat blight. 50 The values ​​were all superior to those of boscalid (Table 4).

[0236] Table 4. Results of EC50 determination of highly active compounds

[0237]

[0238] Example 8: In vivo inhibition test of sclerotinia stem rot in rapeseed

[0239] Select healthy rapeseed leaves of similar size and place them in a plastic box lined with damp filter paper. Wrap the petioles with water-soaked cotton to maintain humidity. Simultaneously, prepare aqueous solutions of compound H24006 at concentrations of 50, 100, and 200 μg / mL (containing 0.5% DMSO and 0.05% Tween 80). Use equal concentrations of cyazofamid and FY21001 as positive controls, and an aqueous solution without the compound as a blank control. Spray the three concentrations of the compound solution, the positive control solution, and the blank control solution evenly onto the rapeseed leaf surface using a small spray bottle. Perform three replicates for each treatment and incubate in a humidified environment for 12 hours. Using a sterile pipette tip, scrape two symmetrical circular lesions from the center of the leaf epidermis, and add 20 μL of water. Then, inoculate the activated sclerotinia sclerotinia pathogen onto the circular lesions using a toothpick, and add another 20 μL of water. Maintain humidity on the leaves and incubate in the dark at 25°C for 2-3 days, then measure the diameter of the lesions. The inhibition rate is calculated as follows: Inhibition rate = [average diameter of lesions in the control group] - [average diameter of lesions in the treatment group] / average diameter of lesions in the control group × 100%.

[0240] Example 9: In vivo inhibition test of tomato gray mold

[0241] Select tomato fruits of uniform size and smooth surface, then wash and soak them for 3 minutes before placing them in a plastic box. Prepare aqueous solutions of compound H24006 at concentrations of 50, 100, and 200 μg / mL (containing 0.5% DMSO and 0.05% Tween 80). Use the same concentrations of cyazofamid and FY21001 as a positive control, and an aqueous solution without the compound as a blank control. Use a small spray bottle to evenly spray the three concentrations of compound aqueous solutions, the positive control aqueous solution, and the blank control aqueous solution onto the surface of the tomato fruits. Perform three replicates for each treatment and incubate in a moist environment for 12 hours. Use a sterile toothpick to scrape the top of the tomato until the flesh is exposed. Inoculate the wound with the activated tomato gray mold fungus using a toothpick, keep the leaves moist, and then cover with plastic wrap. Finally, incubate in the dark at 25℃ for 2-3 days and measure the diameter of the lesions. The inhibition rate is calculated as follows: Inhibition rate = [average diameter of lesions in the control group] - [average diameter of lesions in the treatment group] / average diameter of lesions in the control group × 100%.

[0242] Mycelial growth inhibition experiments confirmed that H24006 exhibited superior antifungal activity compared to other compounds, with an inhibition rate exceeding 90% against the mycelial growth of four pathogenic fungi. Furthermore, compounds H24001, H24003, H24008, and F15 also showed inhibition rates exceeding 75% against the four tested pathogenic fungi. The EC50 values ​​of compound H24006 against the four pathogens were also superior to the positive control. In vivo, H24006 demonstrated excellent control effects against Sclerotinia sclerotinia in rapeseed and gray mold in tomato, making it a potential candidate fungicide for industrial development.

[0243] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A compound containing benzoylhydrazine, the compound having the structure shown in Formula I, ； I； Selected from compounds with substituents defined as follows: Compound H24001: R 1 is 4-chloro-phenyl, n = 0, R 2 is H, R 3 is H, R 4 is H, Z is O, Q is -4-(4-hydroxy)-phenyl; Compound H24002: R 1 is 2,5-dimethyl-phenyl, n = 0, R 2 is H, R 3 is H, R 4 is H, Z is O, Q is -4-(4-hydroxy)-phenyl; Compound H24003: R 1 It is 4-bromo-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24004: R 1 It is 3-methyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24005: R 1 For phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24006: R 1 It is 4-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24007: R 1 It is 2-bromo-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24008: R 1 It is 4-methyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24009: R 1 It is 2-chloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24010: R 1 It is 4-trifluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24011: R 1 It is 2-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24O12: R 1 It is 4-cyano-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24O13: R 1 It is 4-nitro-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24O14: R 1 It is 4-difluoromethyl-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24O15: R 1 It is 4-monofluoromethyl-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24O16: R 1 It is 4-chloro-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24O17: R 1 It is 4-bromo-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24O22: R 1 It is 4-trifluoromethyl-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24O25: R 1 It is 4-cyano-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-(4-hydroxy)-phenyl; Compound H24O27: R 1 It is 4-chloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-(4-hydroxy)-phenyl; Compound H24O30: R 1 It is 4-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-(4-hydroxy)-phenyl; Compound H24O33: R 1 It is 4-trifluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-(4-hydroxy)-phenyl; Compound H24O36: R 1 It is 2,6-dichloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24O37: R 1 It is 3,4-dichloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24O38: R 1 It is 4-methoxy-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24O39: R 1 It is 2-fluoro-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24040: R 1 It is 4-methyl-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24041: R 1 It is 2-methyl-5-chloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24O42: R 1 It is 3-chloro-4-methyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-(4-hydroxy)-phenyl; Compound H24047: R 1 It is 4-chloro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-benzyl; Compound H24050: R 1 It is 4-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-benzyl; Compound H24053: R 1 It is 4-trifluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-benzyl; Compound H24O63: R 1 It is 4-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyridinyl; Compound H24066: R 1 It is 4-trifluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyridinyl; Compound H24076: R 1 It is 4-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyrimidinyl; Compound H24079: R 1 It is 4-trifluoromethyl-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is O, and Q is -4-pyrimidinyl; Compound H24089: R 1 It is 4-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl; Compound H24100: R 1 It is 4-fluoro-phenyl, n=0, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyridinyl; Compound H24108: R 1 It is 4-fluoro-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyrimidinyl; Compound H24119: R 1 It is 4-fluoro-phenyl, n=1, R 2 For H, R 3 For H, R 4 H is H, Z is S, and Q is -4-pyridinyl; Compound H24143: R 1 It is 4-fluoro-phenyl, n=0, R 2 for R 3 for R 4 H is H, Z is O, and Q is -4-(4-methoxy)-phenyl.

2. A pesticide fungicide, comprising an active ingredient and excipients, wherein the active ingredient includes at least one of the benzoyl hydrazine compounds of claim 1.

3. The pesticide fungicide according to claim 2, characterized in that, The content of the active ingredient is 1 to 99.9999 by weight.

4. The pesticide fungicide according to claim 2, characterized in that, The content of the active ingredient is 1 to 50% by weight.

5. The pesticide fungicide according to claim 4, characterized in that, The content of the active ingredient is 20-40% by weight.

6. The pesticide fungicide according to any one of claims 2 to 5, characterized in that, The formulation of the pesticide fungicide is selected from one of the following: emulsifiable concentrate, suspension concentrate, wettable powder, powder, granule, aqueous solution, poison bait, mother liquor, and mother powder.

7. The application of the benzoyl hydrazine compounds according to claim 1 as pesticide fungicides for the prevention and control of plant diseases.

8. The application according to claim 7, characterized in that, The target crops for prevention and control are selected from corn, wheat, soybean, rice, rapeseed, and peanut crops; the plant diseases are caused by one or more pathogenic fungi and / or bacteria.

9. The application according to claim 8, characterized in that, The plant diseases mentioned are selected from at least one of the following bacterial diseases: bacterial leaf blight, bacterial basal rot, bacterial brown streak, bacterial leaf streak, bacterial brown spot, bacterial wilt, and bacterial stem rot; or at least one of the following fungal diseases: damping-off, root rot, downy mildew, white rust, blight, cottony blight, Fusarium head blight, powdery mildew, anthracnose, leaf spot, black spot, smut, rust, sheath blight, damping-off, gray mold, and sclerotinia rot of rapeseed.

10. The method for synthesizing benzoyl hydrazine compounds according to claim 1, characterized in that, Includes the following steps: ； Step I:R 4 The substituted p-fluorobenzonitrile was added together with the Q-OH or Q-SH derivative into the solvent and reacted under alkaline conditions at 25-120°C for 2-24 hours. After the reaction was completed, water and ethyl acetate were added for extraction, the organic phase was collected and dried, the solvent was removed by vacuum distillation, and column chromatography was used to obtain intermediate 2. Step II: Intermediate 2 is dissolved in an aqueous methanol solution, excess sodium hydroxide is added, and the reaction is carried out at 25-120℃ for 2-24 hours; after the reaction is completed, water and ethyl acetate are added for extraction, the aqueous phase is collected and the pH is adjusted to 1-2 with hydrochloric acid, the solid is allowed to precipitate, and the solid is obtained by filtration. Step III: Intermediate 3 and hydrazine hydrochloride are dissolved in dichloromethane, and then condensing agent HATU and triethylamine are added. The mixture is reacted at 25-120℃ for 2-24 hours. After the reaction is completed, sodium bicarbonate aqueous solution and ethyl acetate are added for extraction. The organic phase is collected and dried. The solvent is removed by vacuum distillation, and the derivative 4 is obtained by column chromatography. Step IV: Dissolve derivative 4 in DMF, add base and halogen, and react at 25-120℃ for 2-24 hours; after the reaction is complete, extract with water and ethyl acetate, collect the organic phase and dry it, remove the solvent by vacuum distillation, and obtain the target compound by column chromatography.

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