Sorbic hydrazide compound as well as preparation method and application thereof

Abstract

The invention relates to the technical field of plant antibacterial agents, in particular to a sorbic hydrazide compound, a preparation method and application. The sorbic hydrazide compound is a compound as shown in a formula I or a formula II, or an isotope derivative of the sorbic hydrazide compound and a pesticide acceptable salt. The sorbic hydrazide compound has broad-spectrum inhibitory activity on phytopathogens such as plant pathogenic fungi, and has excellent inhibitory activity on more than ten kinds of plant pathogenic fungi, especially on oomycetes and ascomycetes pathogenic fungi such as downy mildew bacteria and powdery mildew bacteria. The sorbic hydrazide compound has the advantages of easily available raw materials, simple preparation, low cost and no toxicity to animals and plants, and can be used as an effective component or a synergistic component for development and application of a novel green efficient agricultural antibacterial agent.

Description

Technical Field

[0001] This application relates to the field of plant antibacterial agents, specifically to a sorbitol hydrazide compound, its preparation method, and its application. Background Technology

[0002] Pesticides are essential inputs in food production, playing a crucial role in ensuring high and stable crop yields. Statistics show that plant pathogenic fungal infections reduce global crop yields by 20% annually, with an additional 10% reduction after harvest. This not only causes enormous economic losses for farmers but also seriously threatens global food security.

[0003] The application of fungicides is currently the most effective measure for controlling pathogenic fungi in plants, saving significant losses annually. As an important agricultural input, fungicides play a crucial role in ensuring food security, agricultural product quality, and ecological environmental safety. Currently, there are nearly two hundred commercially available fungicides; however, with the long-term and extensive use of traditional fungicides, resistance has become an increasingly prominent problem. The development of novel fungicides is an effective way to address these issues. Summary of the Invention

[0004] To address the technical problems existing in the prior art, this application provides a sorbitol hydrazine compound, its preparation method, and its application. The sorbitol hydrazine compound exhibits highly efficient and broad-spectrum inhibitory activity against plant pathogens, especially plant pathogenic fungi.

[0005] In a first aspect, this application provides a sorbitol hydrazine compound, which is a compound represented by Formula I or Formula II, or an isotopic derivative thereof, and a pesticide-acceptable salt thereof. ; The double bonds in Formulas I and II have an E configuration; Each R is independently selected from halogen, alkyl, haloalkyl, and alkyloxy groups; n can be 1, 2, 3, 4 or 5.

[0006] In one set of embodiments, the alkyl group is a C1-C8 alkyl group; preferably a C1-4 alkyl group, more preferably a C1-3 alkyl group, such as methyl, ethyl, n-propyl, or isopropyl.

[0007] In one set of embodiments, the halogen is selected from fluorine, chlorine, bromine, and iodine.

[0008] In one set of embodiments, each R is independently selected from fluorine, chlorine, bromine, iodine, methyl, ethyl, isopropyl, methoxy, and trifluoromethyl.

[0009] In one set of implementations, n = 1 or 2.

[0010] In one set of embodiments, n=2, and each R is independently selected from halogens; preferably, each R is independently selected from fluorine and chlorine.

[0011] In one set of embodiments, n=1, and each R is independently selected from halogen, alkyl, alkyloxy, haloalkyl; preferably, each R is independently selected from fluorine, chlorine, bromine, iodine, methyl, ethyl, isopropyl, methoxy, trifluoromethyl.

[0012] In one set of embodiments, in Formula I, -(R)n is 2-fluoro, 3-fluoro, 4-fluoro, 2-chloro, 3-chloro, 4-chloro, 3-bromo, 4-bromo, 4-iodine, 2-trifluoromethyl, 3-trifluoromethyl, 3-methyl, 4-methyl, 4-ethyl, 4-isopropyl, 3-methoxy, 2,4-difluoro, 2,5-difluoro, 3,4-difluoro, 3,5-difluoro, 2,4-dichloro, or 3,4-dichloro.

[0013] In a second aspect, this application provides a method for preparing the sorbitol hydrazide compounds described in the first aspect, comprising the following steps: condensing sorbic acid of formula III with substituted phenylhydrazine or naphthylhydrazine, or their corresponding hydrochloride, sulfate or acetate, to obtain the compound shown in formula I or formula II; .

[0014] The structural formula of the substituted phenylhydrazine or its corresponding hydrochloride is: The type and position of (R)n correspond to those of the compound shown in Formula I; the structural formula of naphthalenehydrazine or its corresponding hydrochloride is... .

[0015] In one set of embodiments, sorbic acid of Formula III undergoes a direct condensation reaction with substituted phenylhydrazine or naphthalenehydrazine, or their corresponding hydrochloride, sulfate or acetate, in the presence of a condensing agent to obtain the compound shown in Formula I or Formula II.

[0016] Further, the molar ratio of sorbic acid to substituted phenylhydrazine or naphthylhydrazine, or the molar ratio of sorbic acid to the hydrochloride, sulfate or acetate of substituted phenylhydrazine or naphthylhydrazine, is (1.0-1.5):1.0, preferably (1.2-1.4):1.0. The condensing agent includes 1-ethyl-3-dimethylaminopropylcarbodiimide hydrochloride (EDCI) and 1-hydroxybenzotriazole (HOBT); the molar ratio of EDCI to HOBT is (1.0-1.5):(0.04-0.5), preferably (1.2-1.4):(0.05-0.1); the molar ratio of sorbic acid to EDCI is (1.0-1.5):(1.0-1.5), preferably 1:1. The condensation reaction is carried out in an organic solvent; the organic solvent is one or more of N,N-dimethylformamide, tetrahydrofuran, and acetonitrile; the preferred ratio of the substituted phenylhydrazine or naphthylhydrazine, or its hydrochloride, sulfate, or acetate, to the solvent is 5 mmol:(20-30) mL. When sorbic acid undergoes a condensation reaction with the hydrochloride, sulfate, or acetate of the substituted phenylhydrazine or naphthylhydrazine, the condensation reaction is also carried out under the condition of adding triethylamine; the molar ratio of sorbic acid to triethylamine is (1.0-1.5):(1.0-2.0). The preferred temperature of the condensation reaction is 10-50°C, and the preferred time is 2 h. The condensation reaction process preferably includes the following steps: after dissolving the substituted phenylhydrazine or naphthylhydrazine in the solvent, EDCI, HOBT, and sorbic acid are added sequentially under ice-water bath and stirring conditions, and the mixture is stirred at room temperature until the reaction is complete, followed by concentration under reduced pressure. The condensation reaction process preferably includes the following steps: mixing sorbic acid, EDCI, HOBT and solvent, stirring until the solid is completely dissolved, cooling the resulting mixture to 0°C, adding the hydrochloride, sulfate or acetate of substituted phenylhydrazine or naphthalenehydrazine and triethylamine, and stirring at room temperature until the reaction is complete.

[0017] In one set of embodiments, sorbic acid of Formula III is first reacted with isobutyl chloroformate or benzyl chloroformate to generate an active acid anhydride ester, and then reacted with substituted phenylhydrazine or naphthalenehydrazine, or their corresponding hydrochloride, sulfate or acetate, to obtain the compound shown in Formula I or Formula II.

[0018] Further, sorbic acid of Formula III reacts with isobutyl chloroformate or benzyl chloroformate under alkaline conditions to generate an active acid anhydride ester. Then, substituted phenylhydrazine or naphthylhydrazine, or their corresponding hydrochloride, sulfate, or acetate, is added to react and yield the compound of Formula I or Formula II. The alkaline conditions refer to the presence of an inorganic or organic base. The organic base is DIEA, triethylamine, pyridine, or DMAP, and the inorganic base is an alkali metal hydroxide or alkaline earth metal hydroxide, preferably triethylamine. Preferably, the ratio of sorbic acid: isobutyl chloroformate or benzyl chloroformate: base: substituted phenylhydrazine or naphthylhydrazine, or their corresponding hydrochloride, sulfate, or acetate is 1.0:1.0–1.5:1–2.5:0.8–1.5, more preferably 1.0:1.0–1.2:1.5–2.5:1.0. The reaction solvent is preferably dichloromethane or ethyl acetate. The ratio of sorbic acid to the reaction solvent is: sorbic acid : solvent = 1.0 (g) : 20-100 (mL), preferably 1.0 (g) : 40-50 (mL). The temperature for both steps is -5 to 30 °C, preferably 0 to 5 °C. The reaction process preferably includes the following steps: dissolving sorbic acid in the solvent, adding triethylamine, stirring at room temperature, and then adding isobutyl chloroformate or benzyl chloroformate under stirring in an ice-water bath, followed by the addition of substituted phenylhydrazine or naphthylhydrazine, or their corresponding hydrochloride, sulfate, or acetate salts for further reaction.

[0019] In a third aspect, this application also provides a bactericidal composition containing at least one of the sorbitol hydrazide compounds described in the first aspect of this application as an active ingredient; and optionally a pesticide-acceptable carrier and / or adjuvant.

[0020] The bactericidal composition of this application can be applied in the form of a formulation, wherein the sorbitol hydrazine compound is dissolved or dispersed in a carrier as an active component or formulated into a formulation for easier dispersion when used as a bactericidal composition. The bactericidal composition can be formulated into various liquid formulations, such as soluble powders, dispersible liquids, emulsifiable concentrates, suspensions, aqueous suspensions, microemulsions, emulsions, water-in-oil emulsions, and water-dispersible granules. When the bactericidal composition of this application is applied in the form of a formulation, the mass percentage of the sorbitol hydrazine compound is preferably 200-500 mg / L, more preferably 300-400 mg / L.

[0021] The bactericidal composition of this application may contain one or more other insecticides, fungicides, herbicides, plant growth regulators, or fertilizers.

[0022] This application also discloses the use of the sorbitol hydrazide compounds described in the first aspect or the bactericidal compositions described in the third aspect for controlling plant diseases caused by plant pathogens; preferably for use in agriculture, forestry, horticulture, and sanitation.

[0023] In one set of embodiments, an effective amount of the sorbitol hydrazine compound as described above, or the fungicide composition as described above, is applied to plants, plant propagation materials, or subsequently grown plant organs and cultivation media, cultivation materials, or cultivation spaces; or an effective amount of the sorbitol hydrazine compound as described above, or the fungicide composition as described above, is used to prevent or control pathogenic fungi in wood roots.

[0024] Preferably, an effective amount of the sorbitol hydrazide compound as described above or the fungicide composition as described above is applied to the leaves, stems, roots, seeds, or soil.

[0025] In one set of embodiments, the pathogen is preferably a pathogenic fungus, including but not limited to Ascomycota, Basidiomycota, Plasmodiophoromycota, Oomycota, Chytridiomycota, Zygomycota, and Deuteromycota; preferably, it is an Ascomycota or Oomycota pathogenic fungus, such as Ascomycetes or Oomycetes. Preferably, the plant pathogen is *Fusarium graminearum*, *Early blight*, *Black spot*, *Red spot*, *Curvularia*, *Curvularia*, *Anthracnose*, *Fungiella*, *Rhizoctonia solani*, *Rhizoctonia solani*, *Rhizoctonia solani*, *Rhizoctonia solani*, *Powdery mildew*, *White mold*, *Downy mildew*, or *Gray mold*.

[0026] In one set of embodiments, the plant diseases are wheat scab, tomato early blight, Chinese cabbage black spot, tobacco red spot, corn curvature blight, apple anthracnose, apple rot, rice blast, apple ring rot, melon powdery mildew, konjac white mold, grape downy mildew, and grape gray mold.

[0027] The sorbitol hydrazide compounds described in the first aspect of this application or the bactericidal compositions described in the third aspect can be used in conjunction with one or more other insecticides, fungicides, herbicides, plant growth regulators, or fertilizers.

[0028] The beneficial effects of this invention are as follows: This invention synthesizes a class of sorbitol hydrazide compounds that exert a highly efficient and broad-spectrum inhibitory effect on a variety of plant pathogenic fungi by inhibiting succinate dehydrogenase and disrupting cell membrane and mycelial structures. These compounds have the advantages of simple structure, easy large-scale preparation, and non-toxicity to plants and animals. They can be used as active ingredients or synergistic ingredients in the development and application of novel green and efficient agricultural antibacterial agents.

[0029] The sorbitol hydrazide compounds described in this application exhibit broad-spectrum antibacterial activity against plant pathogens such as pathogenic fungi, particularly against Fusarium graminearum (wheat scab), early blight pathogen (tomato), black spot pathogen (cabbage), red spot pathogen (tobacco), curvularia spp. (corn), anthracnose pathogen (apple), apple rot pathogen (apple), rice blast pathogen (rice), apple ring rot pathogen (apple), powdery mildew pathogen (melon), white mold pathogen (konjac), downy mildew pathogen (grape), and gray mold pathogen (grape).

[0030] Analysis showed that sorbitol phenylhydrazine compounds or sorbitol naphthylhydrazine compounds with substituents on the benzene ring exhibited significantly enhanced inhibitory activity against plant pathogens compared to compound 1 (sorbitol phenylhydrazine). Some compounds showed control efficacy of over 80% against powdery mildew in melons and downy mildew in grapes at a concentration of 300 ppm, and can be used as effective or synergistic components in plant antibacterial drugs. Detailed Implementation

[0031] The alkyl group in the term "alkyloxy group", the alkyl group in "haloalkyl group", and "alkyl" refer to a monovalent saturated aliphatic hydrocarbon group, preferably containing 1-20, 1-18, 1-16, 1-12, or 1-10 carbon atoms, more preferably 1-8 carbon atoms (C1-8 alkyl) straight-chain or branched group (the number of carbon atoms is between 1 and 8, specifically 1, 2, 3, 4, 5, 6, 7, or 8), more preferably containing 1-6 carbon atoms (i.e., C1-6 alkyl, the number of carbon atoms is between 1 and 6, specifically 1, 2, 3, 4, 5, or 6). Examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, neopentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, n-heptyl, n-octyl, etc. The term "alkyloxy group" refers to an alkyl-O- group.

[0032] The term "halogen" refers to F, Cl, Br, and I. The sorbitol hydrazide compounds described in this application are interpreted as including compounds of Formula I or Formula II, their isotopic derivatives, or pesticide-acceptable salts thereof. The isotopic derivatives of these compounds or pesticide-acceptable salts thereof are obtained using conventional techniques in the art and exert the same or similar effects in vitro and in vivo through substantially the same mechanism of action as the compounds described herein.

[0033] The term "isotope derivative" refers to compounds of the present invention that can exist in an isotopically traced or enriched form, containing one or more atoms whose atomic weights or mass numbers differ from the atomic weights or mass numbers of the most abundant atoms found in nature. Isotopes can be radioactive or non-radioactive. Isotopes of atoms such as hydrogen, carbon, phosphorus, sulfur, fluorine, chlorine, bromine, and iodine include, but are not limited to: 2 H, 3 H, 13 C, 14 C, 15 N, 18 O, 32 P, 35 S, 18 F, 36 Cl, 80 Br and 125 I. Compounds containing these and / or other isotopes are within the scope of this invention. The isotopically labeled compounds of this invention can be prepared using general methods well known to those skilled in the art.

[0034] The term "pesticide-acceptable salt" refers to a salt obtained by reacting the sorbitol hydrazide compound of this application with a chemically acceptable acid, wherein the chemically acceptable acid can be an inorganic acid (such as hydrochloric acid, sulfuric acid, phosphoric acid, or hydrobromic acid) or an organic acid (such as oxalic acid, maleic acid, fumaric acid, malic acid, tartaric acid, citric acid, or benzoic acid); the pesticide-acceptable salt can also be a salt obtained by reacting the sorbitol hydrazide compound of this application with a chemically acceptable base, wherein the chemically acceptable base can be an inorganic base (such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, or potassium bicarbonate) or an organic base (such as trimethylamine, triethylamine, etc.).

[0035] The term "pesticide-acceptable carrier" includes, but is not limited to, surfactants, including ionic and nonionic surfactants. The surfactants include emulsifiers, dispersants, or wetting agents. Specifically, the emulsifiers may be polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, polyoxyethylene fatty amines, and commercially available emulsifiers; the dispersants include sodium lignosulfonate, dispersing agents, calcium lignosulfonate, or methylnaphthalenesulfonate formaldehyde condensate, etc.; the wetting agents include sodium lauryl sulfate, sodium dodecylbenzenesulfonate, or alkylnaphthalenesulfonate, etc. The pesticide-acceptable carrier includes solid carriers and / or liquid carriers. Preferably, the solid carrier includes natural or synthetic clays and silicates, such as natural silica and diatomaceous earth; magnesium silicate, such as talc; magnesium aluminum silicate, such as kaolinite, montmorillonite, and mica; white carbon black, calcium carbonate, light calcium carbonate; calcium sulfate; limestone; sodium sulfate; and amine salts such as ammonium sulfate and hexamethylenediamine. Preferably, the liquid carrier comprises water and an organic solvent; when water is used as a solvent or diluent, the organic solvent can be used as an auxiliary agent or antifreeze additive. Preferably, the organic solvent includes aromatic hydrocarbons (e.g., benzene, xylene, or toluene), chlorinated hydrocarbons (e.g., chlorobenzene, vinyl chloride, chloroform, or dichloromethane), aliphatic hydrocarbons (e.g., petroleum fractions, cyclohexane, or light mineral oil), alcohol solvents (e.g., isopropanol, butanol, ethylene glycol, glycerol, or cyclohexanol), ether solvents, ester solvents, ketone solvents (e.g., acetone, cyclohexanone, or N-methylpyrrolidone), or dimethylformamide, etc.

[0036] The bactericide composition can be formulated by mixing the active component with a liquid carrier and / or a solid carrier, and by adding surfactants (such as emulsifiers, dispersants, stabilizers, and wetting agents), as well as other additives (such as adhesives, defoamers, and oxidants).

[0037] According to this application, the sorbitol hydrazide compound can be used in conjunction with one or more other insecticides, fungicides, herbicides, plant growth regulators or fertilizers, and the components can be applied simultaneously, sequentially or separately.

[0038] The present invention will be further illustrated below with reference to embodiments; however, these embodiments do not limit the scope of the invention. Unless otherwise stated, all reactants used in the embodiments are commercially available or can be prepared by methods known in the literature or as detailed in the description; the instruments and equipment used in the synthesis experiments and product analysis are all conventional instruments and equipment commonly used in organic synthesis.

[0039] Those skilled in the art will understand that the compounds of this invention can also be synthesized using other synthetic routes. Although the specific starting materials and conditions in the synthetic routes have been described below, they can be easily replaced with other similar starting materials and conditions. Furthermore, the preparation methods described below can be further modified according to the disclosure of this invention using conventional chemical methods well known to those skilled in the art. For example, appropriate groups may be protected during the reaction process, etc. Examples 1-24 The structural formulas of sorbitol hydrazide compounds are: ; The double bonds in Formulas I and II have an E configuration; Examples 1-23 are structures shown in Formula I, and the types and positions of -(R)n are shown in Table 1. Example 24 is a compound shown in Formula II.

[0040] Table 1. Compounds from Examples 1-24

[0041] Preparation methods of the compounds in Examples 1-24: In a reaction flask, sorbic acid (1.12 g, 10 mmol) was dissolved in dichloromethane (50 mL), followed by the addition of triethylamine (15 or 25 mmol), and the mixture was stirred at room temperature for 10 minutes. The reaction solution was then cooled to 0°C in an ice-water bath, and isobutyl chloroformate or benzyl chloroformate (12 mmol) was added. Stirring continued for 1 h to generate the active acid anhydride ester. Then, phenylhydrazine, substituted phenylhydrazine, or naphthylhydrazine (10 mmol), or their corresponding hydrochloride, sulfate, or acetate (10 mmol), was added, and the mixture was stirred at 0°C for 4 h until the reaction was complete. Dichloromethane (100 mL) was added to the reaction flask, and the mixture was washed once each with saturated sodium bicarbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The mixture was filtered, and the solvent was removed from the filtrate under reduced pressure. The petroleum ether-ethyl acetate mixture in the resulting residue was recrystallized to obtain the sorbitol hydrazide compound.

[0042] The structural formulas of phenylhydrazine, substituted phenylhydrazine, or their corresponding hydrochlorides are as follows: The type and position of -(R)n correspond to the sorbitol hydrazide compounds in Examples 1-23 (n=0 in Example 1); the structural formula of naphthylhydrazide or its corresponding hydrochloride is .

[0043] Specifically, when phenylhydrazine, substituted phenylhydrazine, or naphthylhydrazine is used as a reactant, the amount of triethylamine is 15 mmol; when phenylhydrazine, substituted phenylhydrazine, or naphthylhydrazine hydrochloride, sulfate, or acetate is used as a reactant, the amount of triethylamine is 25 mmol.

[0044] The physicochemical properties and nuclear magnetic resonance spectral data of the compounds in Examples 1-24 are as follows: Example 1, chemically named trans,trans-N'-phenyl-2,4-hexadienoyl hydrazine (referred to as compound 1): pale yellow solid, yield 89%, melting point 158.6°C. 159.3 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.77 (s, 1H), 7.78 (s, 1H), 7.15–7.06 (m, 3H), 6.71–6.67 (m, 3H), 6.26 (ddd, J = 15.1, 10.7, 1.6Hz, 1H), 6.14 (dd, J = 15.1, 6.7 Hz, 1H), 6.00 (d, J = 15.2 Hz, 1H), 1.81 (dd, J =6.6, 1.3 Hz, 3H).

[0045] Example 2, chemical name trans,trans-N'-(2-fluorophenyl)-2,4-hexadienoyl hydrazine (denoted as compound 2): white powder, yield 83%, melting point 133.1°C. 133.6 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.83 (s, 1H),7.69 (s, 1H), 7.13–7.04 (m, 2H), 6.98 (td, J = 7.7, 1.4 Hz, 1H), 6.75–6.68 (m,2H), 6.27 (ddd, J = 15.2, 10.7, 1.6 Hz, 1H), 6.21–6.11 (m, 1H), 6.00 (d, J = 15.2Hz, 1H), 1.82 (dd, J = 6.6, 1.3 Hz, 3H).

[0046] Example 3, chemically named trans,trans-N'-(3-fluorophenyl)-2,4-hexadienoyl hydrazine (referred to as compound 3): pale yellow powder, yield 84%, melting point 150.3°C. 151.1 °C; 1 H NMR (400 MHz, DMSO-d 6) d 9.82 (d, J = 2.7Hz, 1H), 8.10 (d, J = 2.8 Hz, 1H), 7.17–7.07 (m, 2H), 6.53–6.44 (m, 2H), 6.40(dt, J = 11.7, 2.3 Hz, 1H), 6.27 (ddd, J = 15.1, 10.7, 1.6 Hz, 1H), 6.16 (dq, J =15.3, 6.5 Hz, 1H), 5.98 (d, J = 15.2 Hz, 1H), 1.82 (dd, J = 6.6, 1.3 Hz, 3H).

[0047] Example 4, chemically named trans,trans-N'-(4-fluorophenyl)-2,4-hexadienoyl hydrazine (referred to as compound 4): white powder, yield 82%, melting point 159.2°C. 159.8 °C; 1 H NMR (400 MHz, DMSO- d6 ) d 9.80 (d, J = 3.3Hz, 1H), 7.77 (d, J = 3.3 Hz, 1H), 7.09 (dd, J = 15.2, 10.7 Hz, 1H), 7.01–6.93(m, 2H), 6.74–6.63 (m, 2H), 6.31–6.09 (m, 2H), 5.98 (d, J = 15.2 Hz, 1H), 1.82(d, J = 6.6, 1.3 Hz, 3H).

[0048] Example 5, chemically named trans,trans-N'-(2-chlorophenyl)-2,4-hexadienoyl hydrazine (referred to as compound 5): white powder, yield 65%, melting point 174.0°C. 174.8 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.93 (d, J = 2.4Hz, 1H), 7.50 (d, J= 2.4 Hz, 1H), 7.28 (dd, J = 7.9, 1.5 Hz, 1H), 7.17–7.08 (m,2H), 6.77–6.69 (m, 2H), 6.28 (ddd, J = 15.1, 10.7, 1.6 Hz, 1H), 6.22–6.12 (m,1H), 6.02 (d, J = 15.0 Hz, 1H), 1.82 (dd, J = 6.6, 1.3 Hz, 3H).

[0049] Example 6, chemically named trans,trans-N'-(3-chlorophenyl)-2,4-hexadienoyl hydrazine (referred to as compound 6): pale yellow powder, yield 66%, melting point 166.7℃. 167.1 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.83 (d, J = 2.7Hz, 1H), 8.11 (d, J = 2.7 Hz, 1H), 7.17–7.07 (m, 2H), 6.71 (dt, J = 7.8, 1.2 Hz, 1H), 6.64 (dd, J = 7.7, 1.2 Hz, 2H), 6.27 (ddd, J = 15.1, 10.6, 1.5 Hz, 1H), 6.16(dq, J = 15.2, 6.5 Hz, 1H), 5.98 (d, J = 15.2 Hz, 1H), 1.82 (dd, J = 6.6, 1.3 Hz, 3H).

[0050] Example 7, chemical name trans,trans-N'-(4-chlorophenyl)-2,4-hexadienoyl hydrazine (denoted as compound 7): pale yellow powder, yield 65%, melting point 118.5°C. 119.1 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.81 (d, J = 2.8Hz, 1H), 7.99 (d, J= 2.8 Hz, 1H), 7.19–7.14 (m, 2H), 7.09 (dd, J = 15.2, 10.7Hz, 1H), 6.71–6.66 (m, 2H), 6.26 (ddd, J = 15.1, 10.7, 1.6 Hz, 1H), 6.16 (dq, J =8.5, 6.5 Hz, 1H), 5.98 (d, J = 15.2 Hz, 1H), 1.81 (dd, J = 6.6, 1.3 Hz, 3H).

[0051] Example 8, chemically named trans,trans-N'-(3-bromophenyl)-2,4-hexadienoyl hydrazine (referred to as compound 8): pale yellow powder, yield 75%, melting point 176.0°C. 176.7 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.98 (d, J = 2.3Hz, 1H), 7.44 (dd, J = 8.4, 1.5 Hz, 1H), 7.28 (d, J = 2.6 Hz, 1H), 7.22–7.08 (m,2H), 6.73–6.67 (m, 2H), 6.30–6.14 (m, 2H), 6.01 (d, J = 15.2 Hz, 1H), 1.82 (dd, J = 6.6, 1.3 Hz, 3H).

[0052] Example 9, chemically named trans,trans-N'-(4-bromophenyl)-2,4-hexadienoyl hydrazine (referred to as compound 9): white powder, yield 72%, melting point 122.3°C. 122.9 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.81 (d, J = 2.9Hz, 1H), 8.00 (d, J = 2.8 Hz, 1H), 7.31–7.26 (m, 2H), 7.09 (dd, J= 15.2, 10.6Hz, 1H), 6.66–6.61 (m, 2H), 6.31–6.08 (m, 2H), 5.97 (d, J = 15.2 Hz, 1H), 1.81(dd, J = 6.6, 1.3 Hz, 3H).

[0053] Example 10, chemically named trans,trans-N'-(4-iodophenyl)-2,4-hexadienoyl hydrazine (referred to as compound 10): white powder, yield 72%, melting point 125.0°C. 125.7 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.80 (d, J = 2.8Hz, 1H), 8.00 (d, J = 2.8 Hz, 1H), 7.45–7.40 (m, 2H), 7.09 (dd, J = 15.2, 10.6Hz, 1H), 6.55–6.51 (m, 2H), 6.26 (ddd, J = 15.1, 10.8, 1.6 Hz, 1H), 6.21–6.12(m, 1H), 5.97 (d, J = 15.2 Hz, 1H), 1.81 (dd, J = 6.5, 1.3 Hz, 3H).

[0054] Example 11, chemically named trans,trans-N'-(2,4-difluorophenyl)-2,4-hexadienoyl hydrazine (referred to as compound 11): pale yellow powder, yield 73%, melting point 138.8°C. 139.5 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.83 (t, J = 3.5 Hz, 1H), 7.62 (d, J = 5.9 Hz, 1H), 7.20–7.02 (m, 2H), 6.92–6.84 (m, 1H), 6.71 (td, J = 8.0, 6.4, 4.5 Hz, 1H), 6.32–6.09 (m, 2H), 5.98 (dd, J= 15.2, 6.4Hz, 1H), 1.80 (t, J = 6.4 Hz, 3H).

[0055] Example 12, chemically named trans,trans-N'-(2,5-difluorophenyl)-2,4-hexadienoyl hydrazine (referred to as compound 12): white powder, yield 64%, melting point 144.3°C. 144.9 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.86 (s,1H), 8.04 (s, 1H), 7.17–7.06 (m, 2H), 6.51–6.39 (m, 2H), 6.33–6.11 (m, 2H),6.00 (d, J = 15.2 Hz, 1H), 1.82 (d, J = 6.5 Hz, 3H).

[0056] Example 13, chemically named trans,trans-N'-(3,4-difluorophenyl)-2,4-hexadienoyl hydrazine (denoted as compound 13): white powder, yield 66%, melting point 142.0°C. 142.8 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.82 (q, J =3.9, 3.3 Hz, 1H), 8.00 (q, J = 3.9, 3.3 Hz, 1H), 7.24–7.04 (m, 2H), 6.67–6.43(m, 2H), 6.32–6.11 (m, 2H), 5.97 (dt, J = 15.3, 3.4 Hz, 1H), 1.81 (d, J = 6.3 Hz, 3H).

[0057] Example 14, chemically named trans,trans-N'-(3,5-difluorophenyl)-2,4-hexadienoyl hydrazine (denoted as compound 14): white powder, yield 69%, melting point 148.6°C. 149.5 °C; 1 H NMR (400 MHz, DMSO- d 6) d9.86 (s,1H), 8.04 (s, 1H), 7.17–7.11 (m, 1H), 7.11–7.06 (m, 1H), 6.52–6.37 (m, 2H), 6.32–6.22 (m, 1H), 6.23–6.11 (m, 1H), 6.00 (d, J = 15.2 Hz, 1H), 1.82 (d, J = 6.5Hz, 3H).

[0058] Example 15, chemically named trans,trans-N'-(2,4-dichlorophenyl)-2,4-hexadienoyl hydrazine (referred to as compound 15): white powder, yield 73%, melting point 172.2°C. 173.0 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.96 (d, J =2.2 Hz, 1H), 7.70 (d, J = 2.1 Hz, 1H), 7.41 (d, J = 2.4 Hz, 1H), 7.21 (dd, J = 8.8, 2.4 Hz, 1H), 7.13 (dd, J = 15.2, 10.7 Hz, 1H), 6.70 (d, J = 8.8 Hz, 1H), 6.33 –6.22 (m, 1H), 6.22–6.11 (m, 1H), 6.01 (d, J = 15.2 Hz, 1H), 1.82 (dd, J = 6.6, 1.2 Hz, 3H).

[0059] Example 16, chemically named trans,trans-N'-(3,4-dichlorophenyl)-2,4-hexadienoyl hydrazine (denoted as compound 16): white powder, yield 84%, melting point 193.3°C. 194.4 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.88 (d, J =2.7 Hz, 1H), 8.26 (d, J = 2.5 Hz, 1H), 7.35 (d, J= 8.8 Hz, 1H), 7.12 (dd, J =15.2, 10.6 Hz, 1H), 6.82 (d, J = 2.7 Hz, 1H), 6.68 (dd, J = 8.8, 2.7 Hz, 1H),6.32 – 6.23 (m, 1H), 6.22–6.11 (m, 1H), 6.01 (d, J = 15.2 Hz, 1H), 1.82 (d, J =6.4 Hz, 3H).

[0060] Example 17, chemically named trans,trans-N'-(2-trifluoromethylphenyl)-2,4-hexadienoylhydrazine (referred to as compound 17): pale pink powder, yield 65%, melting point 153.5°C. 153.9 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.98(d, J = 2.0 Hz, 1H), 7.58 (d, J = 1.9 Hz, 1H), 7.51–7.40 (m, 2H), 7.13 (dd, J =15.2, 10.7 Hz, 1H), 6.87 (dd, J = 8.1, 6.0 Hz, 2H), 6.27 (dd, J = 10.7, 1.6 Hz,1H), 6.24–6.13 (m, 1H), 6.02 (d, J = 15.2 Hz, 1H), 1.82 (d, J = 6.5 Hz, 3H).

[0061] Example 18, chemically named trans,trans-N'-(3-trifluoromethylphenyl)-2,4-hexadienoylhydrazine (referred to as compound 18): white powder, yield 65%, melting point 144.6°C. 145.1 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.90 (d, J = 2.6 Hz, 1H), 8.28 (d, J = 2.7 Hz, 1H), 7.36 (t, J= 7.9 Hz, 1H), 7.11 (dd, J =15.2, 10.7 Hz, 1H), 7.03–6.99 (m, 1H), 6.97–6.91 (m, 2H), 6.28 (ddd, J = 15.1,10.7, 1.6 Hz, 1H), 6.22–6.14 (m, 1H), 6.00 (d, J = 15.2 Hz, 1H), 1.82 (dd, J =6.6, 1.2 Hz, 3H).

[0062] Example 19, chemically named trans,trans-N'-(3-methylphenyl)-2,4-hexadienoyl hydrazine (referred to as compound 19): white powder, yield 82%, melting point 135.5°C. 135.9 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.74 (d, J =2.8 Hz, 1H), 7.70 (d, J = 3.1 Hz, 1H), 7.12–6.98 (m, 2H), 6.53 – 6.47 (m, 3H), 6.26 (ddd, J = 15.1, 10.7, 1.6 Hz, 1H), 6.19–6.10 (m, 1H), 5.99 (d, J = 15.2 Hz,1H), 2.20 (s, 3H), 1.81 (dd, J = 6.6, 1.4 Hz, 3H).

[0063] Example 20, chemically named trans,trans-N'-(4-methylphenyl)-2,4-hexadienoyl hydrazide (denoted as compound 20): white powder, yield 82%, melting point 126.2°C. 126.8 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.74 (s,1H), 7.62 (s, 1H), 7.20 (dd, J = 15.2, 10.6 Hz, 1H), 6.99 (d, J = 8.3 Hz, 2H), 6.70 (d, J= 8.4 Hz, 2H), 6.30–6.22 (m, 1H), 6.20–6.11 (m, 1H), 5.97 (d, J = 15.2Hz, 1H), 2.22 (s, 3H), 1.85 (d, J = 6.5 Hz, 3H).

[0064] Example 21, chemically named trans,trans-N'-(4-ethylphenyl)-2,4-hexadienoyl hydrazine (denoted as compound 21): yellow powder, yield 74%, melting point 134.2°C. 135.0 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.74 (s,1H), 7.62 (s, 1H), 7.07 (dd, J = 15.2, 10.7 Hz, 1H), 6.97 (d, J = 8.4 Hz, 2H), 6.62 (d, J = 8.4 Hz, 2H), 6.30 – 6.21 (m, 1H), 6.15 (dq, J = 8.6, 6.5 Hz, 1H), 5.98 (d, J = 15.2 Hz, 1H), 2.46 (t, J = 7.6 Hz, 2H), 1.81 (dd, J = 6.7, 1.3 Hz, 3H), 1.11 (t, J = 7.6 Hz, 3H).

[0065] Example 22, chemically named trans,trans-N'-(4-isopropylphenyl)-2,4-hexadienoyl hydrazide (denoted as compound 22): yellow powder, 70% yield, melting point 142.1°C. 143.0 °C; 1 H NMR (500 MHz, DMSO- d 6) d 9.76 (s,1H), 7.62 (s, 1H), 7.14–7.07 (m, 1H), 7.03 (d, J = 8.2 Hz, 2H), 6.66 (d, J = 8.2Hz, 2H), 6.32–6.25 (m, 1H), 6.19 (t, J= 6.7 Hz, 1H), 6.02 (d, J = 15.2 Hz, 1H), 2.79 (h, J = 6.8 Hz, 1H), 1.84 (d, J = 7.1 Hz, 3H), 1.17 (d, J = 6.9 Hz, 6H).

[0066] Example 23, chemically named trans,trans-N'-(3-methoxyphenyl)-2,4-hexadienoyl hydrazine (referred to as compound 23): white powder, yield 71%, melting point 120.2°C. 121.0 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.75 (d, J =3.1 Hz, 1H), 7.79 (d, J = 3.1 Hz, 1H), 7.12 – 7.00 (m, 2H), 6.30–6.23 (m, 4H), 6.15 (dd, J = 15.1, 6.6 Hz, 1H), 5.98 (d, J = 15.1 Hz, 1H), 3.67 (s, 3H), 1.81(dd, J = 6.5, 1.4 Hz, 3H).

[0067] Example 24, chemically named trans,trans-N'-(2-naphthyl)-2,4-hexadienoyl hydrazide (denoted as compound 24): white powder, yield 59%, melting point 177.2°C. 177.9 °C; 1 H NMR (400 MHz, DMSO- d 6) d 9.92 (d, J = 2.9Hz, 1H), 8.11 (d, J = 2.8 Hz, 1H), 7.71 (dd, J = 8.5, 3.8 Hz, 2H), 7.62 (d, J = 8.2Hz, 1H), 7.34 (ddd, J = 8.2, 6.8, 1.3 Hz, 1H), 7.23–7.06 (m, 3H), 6.90 (d, J=2.2 Hz, 1H), 6.28 (dd, J = 10.8, 1.7 Hz, 1H), 6.17 (dd, J = 15.1, 6.7 Hz, 1H), 6.06 (d, J = 15.2 Hz, 1H), 1.83 (d, J = 6.0 Hz, 3H).

[0068] Bioactivity test examples In vitro antibacterial activity test: In vitro antibacterial activity was determined using the linear mycelial growth rate method. The tested pathogens were: *Fusarium graminearum* (XC), *Early blight* (FZ), *Black spot* (BH), *Red spot* (YC), *Curvularia zedoaria* (YW), *Anthracnose* (PT), *Blastophytes* (SD), *Rhizoctonia solani* (PL), and *White rot* (MB) of *Amorphophallus konjac*. The culture medium was PDA. The tested compounds were prepared at a specific concentration using 5% (v / v) dimethyl sulfoxide (DMSO). The test solutions were mixed with a certain volume of sterile PDA medium to obtain a test medium containing 20 mg / L of the tested compound. Each experiment was performed in triplicate, and the antibacterial activity was expressed as the average inhibition rate. Standards of the antibacterial agents carbendazim and cyazofamid were used as positive controls.

[0069] The average inhibition rates of compounds 1-24 against the various pathogens mentioned above are shown in Table 2. Table 2. Average inhibition rates (%) of compounds 1-24 against various plant pathogens.

[0070] Pot experiment on resistance to downy mildew: Preparation of the test solution: Dissolve the test compound in an appropriate amount of dimethyl sulfoxide (DMSO) containing 10% (w / w) OP-10 (octylphenol polyoxyethylene ether-10) to prepare a stock solution of 150 mg / mL. Before the test, dilute with water 500 times to obtain a test solution of 300 mg / L.

[0071] Assay method: Using *Phyllostachys edulis* as the test fungus and potted grapevines as the test plants, the antibacterial activity of the compounds was determined using the leaf spore germination method. The spores of the test fungus were prepared into 10... 5A suspension with a spore count / mL concentration was sprayed onto the underside of grape leaves for inoculation. After inoculation, the plants were first placed in a high-humidity isolation room at room temperature for 24 hours, then transferred to a greenhouse with controlled humidity and temperature for 48 hours, and finally placed in a high-humidity environment for 24 hours. Afterward, the plants were moved to a natural environment, and after the surface moisture on the leaves had naturally evaporated, infected leaves were removed from the plants and sprayed with the test solution. After the leaf surface moisture had naturally evaporated, the petioles were immersed in water, and then incubated in a high-humidity environment for 72 hours. The experimental results were evaluated by comparing the percentage of spore-covered area on the leaves of the experimental and control groups.

[0072] Pot experiment on resistance to powdery mildew: Preparation of the test solution: Dissolve the test compound in an appropriate amount of dimethyl sulfoxide (DMSO) containing 10% by mass of OP-10 to prepare a stock solution of 150 mg / mL. Before the test, dilute with water 500 times to obtain a test solution of 300 mg / L.

[0073] Test leaves: Using *Powdery mildew fungus* as the test fungus and melon seedlings as the test plants, the antibacterial activity of the compound was determined using the leaf spore germination method. The specific method was basically the same as the pot antibacterial test for downy mildew fungus mentioned above. Thirty melon seedlings were used in each experiment, grown in sterilized compost. The melon plants inoculated with the *Powdery mildew* spore suspension were placed in a high-humidity environment for 24 hours, and then sprayed with the test solution. Five days later, the antibacterial effect was evaluated using the same method as the pot antibacterial test for downy mildew fungus mentioned above.

[0074] The control indices of compounds 2, 4, 6, 7, 8, 9, 10, 11, 13 and 16 against grape downy mildew and melon powdery mildew are shown in Table 3.

[0075] Table 3. Control index of compounds against grape downy mildew and melon powdery mildew*

[0076] Note: In the table, *0 indicates that the efficacy is less than 50%, 1 indicates that the efficacy is 50-80%, and 2 indicates that the efficacy is greater than 80%.

[0077] As shown in Tables 2 and 3, at a concentration of 20 μg / mL, most of the tested compounds exhibited highly efficient and broad-spectrum in vitro inhibitory activity against the nine tested plant pathogens. Compared to compound 1 (sorbitol phenylhydrazine), sorbitol phenylhydrazine compounds with substituents on the benzene ring showed significantly enhanced inhibitory activity against plant pathogens. Some compounds showed control efficacy exceeding 80% against powdery mildew of melon and downy mildew of grape at a concentration of 300 ppm, demonstrating potential applications in the preparation of plant antimicrobial agents and serving as active or synergistic components for such agents.

[0078] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

[0079] Furthermore, various embodiments of the present invention can be combined arbitrarily, as long as they do not violate the spirit of the present invention, and should also be considered as part of the content disclosed in the present invention. The above-described embodiments only illustrate one implementation of this application, and their descriptions are relatively specific and detailed, but they should not be construed as limiting the scope of the patent application. It should be noted that those skilled in the art can make several modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application.

Claims

1. A sorbitol hydrazide compound, which is a compound represented by Formula I or Formula II, or an isotopic derivative thereof, and a pesticide-acceptable salt thereof. ； The double bonds in Formulas I and II have an E configuration; Each R is independently selected from halogen, alkyl, haloalkyl, and alkyloxy groups; n can be 1, 2, 3, 4 or 5.

2. The sorbitol hydrazide compound according to claim 1, characterized in that, The alkyl group is a C1-C8 alkyl group, and the halogen is selected from fluorine, chlorine, bromine, and iodine.

3. The sorbitol hydrazide compound according to claim 1, characterized in that, Each R is independently selected from fluorine, chlorine, bromine, iodine, methyl, ethyl, isopropyl, methoxy, and trifluoromethyl.

4. The sorbitol hydrazide compound according to claim 1, characterized in that, In Formula I, -(R)n is 2-fluoro, 3-fluoro, 4-fluoro, 2-chloro, 3-chloro, 4-chloro, 3-bromo, 4-bromo, 4-iodine, 2-trifluoromethyl, 3-trifluoromethyl, 3-methyl, 4-methyl, 4-ethyl, 4-isopropyl, 3-methoxy, 2,4-difluoro, 2,5-difluoro, 3,4-difluoro, 3,5-difluoro, 2,4-dichloro, or 3,4-dichloro.

5. The method for preparing sorbitol hydrazide compounds according to any one of claims 1-4, characterized in that, It includes the following steps: Sorbic acid of Formula III is condensed with substituted phenylhydrazine or naphthylhydrazine, or their corresponding hydrochloride, sulfate or acetate, to obtain the compound shown in Formula I or Formula II. 。 6. The preparation method according to claim 5, characterized in that, Sorbic acid of Formula III undergoes a direct condensation reaction with substituted phenylhydrazine or naphthylhydrazine, or their corresponding hydrochloride, sulfate or acetate, in the presence of a condensing agent; or sorbic acid of Formula III first reacts with isobutyl chloroformate or benzyl chloroformate to generate an active acid anhydride ester, and then reacts with substituted phenylhydrazine or naphthylhydrazine, or their corresponding hydrochloride, sulfate or acetate, to obtain the compound shown in Formula I or Formula II.

7. A bactericidal composition, characterized in that, It contains at least one of the sorbitol hydrazide compounds according to any one of claims 1-4 as an active ingredient, and optionally a pesticide-acceptable carrier and / or adjuvant.

8. The application of the sorbitol hydrazide compound according to any one of claims 1-4 or the bactericidal composition according to claim 7, characterized in that, Used to control plant diseases caused by plant pathogens.

9. The application according to claim 8, characterized in that, The plant pathogen is a plant pathogenic fungus. Preferably, the plant pathogenic fungus is selected from the phyla Plasmomycota, Oomycota, Chytridiomycota, Zygomycota, Ascomycota, Basidiomycota, and Deuteromycota.

10. The application according to claim 9, characterized in that, The plant pathogens are selected from the following pathogens: wheat scab, tomato early blight, Chinese cabbage black spot, tobacco red spot, corn curvature spores, apple anthracnose, apple rot, rice blast, apple ring spot, melon powdery mildew, konjac white mold, grape downy mildew, and grape gray mold.

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