Acethydrazide compound containing quinazoline-4 (3H)-ketone structure, preparation method of acethydrazide compound and application of acethydrazide compound in bactericide

Abstract

The invention relates to acethydrazide compounds containing a quinazoline-4 (3H)-ketone structure as shown in a formula I-1 or agronomically acceptable salts of the acethydrazide compounds, a preparation method of the acethydrazide compounds or the agronomically acceptable salts and application of the acethydrazide compounds or the agronomically acceptable salts as plant fungicides. # imgabs0 #

Description

Technical Field

[0001] The invention relates to an acylhydrazide compound and the technical field of plant fungicides, and specifically relates to an acetylhydrazide compound containing a quinazoline-4(3H)-one structure and a preparation method and application thereof. Background Art

[0002] Plant pathogenic fungi pose a serious threat to national food security and stability, and fungicides are the most direct and effective way to alleviate fungal diseases. According to the Fungicide Resistance Action Committee (FRAC), there are more than 230 small molecule fungicides that have been commercialized, of which 25 are the fastest-updated SDHI fungicides. In recent years, with the increasing tension in arable land resources, the importance of unit output of arable land has become increasingly prominent, which has promoted the sustainable development of the global fungicide industry. However, with the long-term use of traditional fungicides, the resistance of pathogens has increased. For example, QoI, MBC, DMI, SDHI and other types of fungicides have successively developed resistance. Therefore, the development of new fungicides with novel structures and unique targets is an effective way to alleviate pathogen resistance.

[0003] In order to develop a novel and efficient fungicide, the present invention designed and synthesized for the first time a novel acetohydrazide compound containing a quinazoline-4(3H)-one structure, using the fungicidal quinazoline-4(3H)-one reported in the literature and the acylhydrazide structure with excellent fungicidal activity found in previous work (Fang et al. J. Agric. Food Chem., 2023, 71, 920; Chen et al. J. Agric. Food Chem., 2023, 71, 12333) as the parent skeleton. The biological activity test found that the target compound showed fungicidal activity comparable to or even better than that of the control drugs carbendazim, tebuconazole, and fluopyram.

[0004] The present invention has important guiding significance for developing novel acetylhydrazine candidate fungicide molecules containing quinazoline-4(3H)-one structure, and provides a new prevention and control strategy for alleviating the increasingly serious drug resistance of agricultural pathogenic fungi. Summary of the invention

[0005] The technical problem to be solved in the first aspect of the present invention is to provide a compound represented by formula I-1 or an agriculturally acceptable salt thereof,

[0006]

[0007] Among them, R 1 Selected from the following groups: C 1 -C 6 Straight or branched chain alkyl or C 6 -C 10Any of the aromatic groups;

[0008] R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 Independently selected from the following groups: hydrogen, halogen, C 1 -C 6 Straight chain or branched alkyl, halogenated C 1 -C 6 Any of a straight chain or branched chain alkyl group.

[0009] Further, wherein said R 1 is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, hexyl, phenyl or naphthyl;

[0010] and / or, the R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 independently selected from the following groups: hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, hexyl, CFH 2 -、CF 2 H-, CF 3 -、CH 3 CFH-、CH 3 CF 2 - or CH 3 CF 2 -.

[0011] Furthermore, the R 1 Selected from -CH 3 , -C 2 H 5 , -Phenyl;

[0012] and / or, the R 2 Selected from -H;

[0013] and / or, R 3 Select from -F;

[0014] and / or, R 4 Selected from -H;

[0015] and / or, R 5 Selected from -H;

[0016] and / or, R 6 Any one selected from -H, -F or -Cl;

[0017] and / or, R 7 Select any one of -H or -F;

[0018] and / or, R 8 Any one selected from -H, -F or -Cl;

[0019] and / or, R 9 Selected from -H;

[0020] and / or, R 10 Selected from -H.

[0021] Further preferably, it is selected from the following compound structures:

[0022]

[0023]

[0024] The technical problem to be solved in the second aspect of the present invention is to provide a method for preparing the compound represented by formula I-1 or an agriculturally acceptable salt thereof, characterized in that it comprises the following steps:

[0025] Step (1): anthranilic acid 1 is dissolved in an organic solvent and reacted with isothiocyanate under alkaline conditions to prepare a 2-thioquinazolinone compound 2; the 2-thioquinazolinone compound 2 is further reacted with sulfonyl chloride to prepare a 2-chloroquinazolin-4(3H)-one compound 3; wherein the chemical structures of compound 1, compound 2 and compound 3 are as follows:

[0026]

[0027] Step (2): Boc-protected glycine 4 is dissolved in an organic solvent and condensed with substituted phenylhydrazine under condensing agent conditions to prepare acylhydrazine compound 5; compound 5 is dissolved in an organic solvent and treated with acid to remove the Boc protecting group to prepare 2-aminoacetylhydrazine compound 6; compound 6 is dissolved in an organic solvent and reacted with compound 3 under alkaline conditions to prepare an acetylhydrazine compound of formula I-1 containing a quinazoline-4(3H)-one structure; wherein compound 4, compound 5, compound 6 and the chemical structure are as follows:

[0028]

[0029] Among them, Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6 and the substituted group R in Formula I-1 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 The definitions are the same as above.

[0030] Preferably, the organic solvent in step (1) or step (2) is selected from one or more of N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, methanol, ethanol, ethyl acetate, dichloromethane, chloroform, toluene, acetone, methyl tert-butyl ether, and diethyl ether, preferably dimethyl sulfoxide;

[0031] Furthermore, in step (1) or step (2), the base is selected from an organic base or an inorganic base, the inorganic base is selected from one or two or more of sodium hydrogen, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide or lithium hydroxide; the organic base is selected from one or two or more of N,N-diisopropylethylamine, triethylamine, pyridine, lithium diisopropylamide, n-(C1-6 alkyl) lithium, lithium hexamethyldisilazane, potassium hexamethyldisilazane, sodium hexamethyldisilazane, lithium tetramethylpiperidinium, potassium butoxide, potassium pentoxide and potassium pentoxide;

[0032] Furthermore, in step (2), the acid is selected from an organic acid or an inorganic acid, the inorganic acid is selected from one or two of hydrochloric acid and sulfuric acid; the organic acid is selected from one or two or more of formic acid, acetic acid, trifluoroacetic acid, trichloroacetic acid, and p-toluenesulfonic acid;

[0033] And / or, the condensing agent in step (2) is selected from 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 4-dimethylaminopyridine or 2-(1H-benzotriazol L-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate and N,N-diisopropylethylamine.

[0034] The technical problem to be solved in the third aspect of the present invention is to provide an agrochemical composition, which contains a fungicidal effective amount of a compound having a structure shown in Formula I-1 or an agronomically acceptable salt thereof.

[0035] Preferably, the composition further comprises at least one additional active ingredient and / or an agrochemically acceptable diluent or carrier.

[0036] The technical problem to be solved in the fourth aspect of the present invention is to provide a method for controlling or preventing useful plants from being infected by plant pathogenic microorganisms, wherein a fungicidally effective amount of the aforementioned compound of formula I-1 or a composition containing such a compound as an active ingredient is applied to the plant, its part or its location.

[0037] The technical problem to be solved in the fifth aspect of the present invention is the use of the aforementioned compound having formula I-1 as a fungicide, preferably as a plant antibacterial agent.

[0038] Surprisingly, it has been found that novel compounds of formula I-1 have a very advantageous level of biological activity for practical purposes for protecting plants against diseases caused by fungi.

[0039] The following is an explanation and description of the terms of the present invention:

[0040] Rhizoctonia solani is a widely distributed soil-borne pathogenic fungus that can infect a variety of plants, including corn, causing sheath blight.

[0041] Sclerotinia sclerotiorum can cause necrosis of the stems, leaves and flowers of plants, forming sclerotia, causing serious damage to crops such as rapeseed.

[0042] Botrytis cinerea is a common plant pathogenic fungus that can infect a variety of plants, including pepper, causing gray mold disease.

[0043] Alternaria sp. is a genus of fungi that cause leaf spot and fruit rot in a variety of plants.

[0044] Apple anthracnose (Colletotrichum gloeosporioides) causes anthracnose in apple and some other plants and is an important economic crop disease.

[0045] Rice blast fungus usually refers to the fungus that causes rice blast disease, such as Magnaporthe oryzae, which poses a serious threat to rice crops.

[0046] The compounds and derivatives provided in the present invention can be named according to the IUPAC (International Union of Pure and Applied Chemistry) or CAS (Chemical Abstracts Service, Columbus, OH) nomenclature system.

[0047] Definitions of terms used in the present invention: Unless otherwise stated, the initial definitions provided for groups or terms in this document apply to the groups or terms throughout the specification; for terms that are not specifically defined in this document, the meaning that a person skilled in the art can give them should be given based on the disclosure and context.

[0048] "Substitution" refers to the replacement of a hydrogen atom in a molecule by another different atom or molecule.

[0049] The minimum and maximum carbon atom content of a hydrocarbon group is indicated by a prefix, for example, the prefix C1-b alkyl indicates any alkyl group containing from "a" to "b" carbon atoms. Thus, for example, "C1-4 alkyl" refers to an alkyl group containing 1 to 4 carbon atoms.

[0050] "Alkyl" refers to a saturated hydrocarbon chain having a specified number of member atoms. For example, C1-6 alkyl refers to an alkyl group having 1 to 6 member atoms, such as 1 to 4 member atoms. The alkyl group can be straight or branched. Representative branched alkyl groups have one, two or three branches. The alkyl group may be optionally substituted with one or more substituents as defined herein. Alkyl includes methyl, ethyl, propyl (n-propyl and isopropyl), butyl (n-butyl, isobutyl and tert-butyl), pentyl (n-pentyl, isopentyl and neopentyl) and hexyl. The alkyl group may also be part of other groups, such as C1-C6 alkoxy.

[0051] "Halogen" is fluorine, chlorine, bromine or iodine.

[0052] "Halogen alkyl" refers to an alkyl group in which the hydrogen atoms may be replaced by one or more halogen atoms. For example, C1-4 halogen alkyl refers to an alkyl group containing 1 to 4 carbon atoms in which the hydrogen atoms are replaced by one or more halogen atoms.

[0053] C6-C10 aryl refers to a group of aromatic compounds containing 6 to 10 carbon atoms. These groups can be monocyclic or fused bicyclic structures and have a conjugated π electron system. For example, phenyl (C6H5-) and naphthyl (C10H7-) etc.

[0054] In certain cases, the compounds of formula I-1 according to the invention are in free form, oxidized form (such as N-oxide) or salt form (such as agriculturally acceptable salt form). N-oxide is an oxidized form of a tertiary amine or an oxidized form of a nitrogen-containing heteroaromatic compound.

[0055] The term "agronomically acceptable salt" refers to the above-mentioned compound or its stereoisomer, acidic and / or basic salts formed with inorganic and / or organic acids and bases, also including zwitterionic salts (inner salts), and also including quaternary ammonium salts, such as alkylammonium salts. These salts can be directly obtained in the final separation and purification of the compound. It can also be obtained by mixing the above-mentioned compound, or its stereoisomer, with a certain amount of acid or base appropriately (such as equivalent). These salts may form precipitation in the solution and be collected by filtering, or be recovered after solvent evaporation, or be obtained by freeze drying after reaction in an aqueous medium. The salt described in the present invention can be the hydrochloride, sulfate, citrate, benzenesulfonate, hydrobromide, hydrofluoride, phosphate, acetate, propionate, succinate, oxalate, malate, succinate, fumarate, maleate, tartrate or trifluoroacetate of the compound.

[0056] Compounds of formula I-1 are used in the relevant field as active ingredients, for example, for controlling plant pests, or on non-living materials for controlling spoilage microorganisms or organisms potentially harmful to humans. The novel compounds of formula I-1 are characterized by excellent activity at low application rates, good plant tolerance and environmental friendliness. They have very useful therapeutic, preventive and systemic properties and can be used to protect cultivated plants. Compounds of formula I-1 can be used to inhibit or destroy pests that occur on plants or plant parts (fruits, flowers, leaves, stems, tubers, roots) of different useful plant crops, while also protecting, for example, those plant parts that grow later from the invasion of phytopathogenic microorganisms.

[0057] The term "plant" refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, leaves and fruits.

[0058] The compound of formula I-1 can be the sole active ingredient of the composition, or it can be mixed with one or more additional active ingredients (such as pesticides, fungicides, synergists, herbicides or plant growth regulators) as appropriate. In some cases, the additional active ingredients can lead to unexpected synergistic activity.

[0059] Examples of suitable additional active ingredients include acyclic amino acid fungicides, aliphatic nitrogen fungicides, amide fungicides, aniline fungicides, antibiotic fungicides, and the like.

[0060] A formulation, e.g. a composition comprising a compound of formula I-1 and a solid or liquid adjuvant or a monomer for encapsulating a compound of formula I-1, can be prepared in a known manner, typically by intimately mixing and / or grinding the compound with extenders such as solvents, solid carriers and, optionally, surface-active compounds (surfactants).

[0061] Typically, the formulations comprise from 0.01% to 90% by weight of active ingredient, from 0 to 20% of agriculturally acceptable surfactant and from 10% to 99.99% of solid or liquid formulation inerts and adjuvants.

[0062] The composition of the invention can be used in any conventional form, for example, in the form of a two-pack, an emulsion concentrate (EC), a suspension concentrate (SC), a suspoemulsion (SE), a capsule suspension (CS), a water-dispersible granule (WG), an emulsifiable granule (EG), an oil-in-water emulsion (EO), an oil-in-water emulsion (EW), a microemulsion (ME), an oil dispersible suspension (OD), an oil suspension concentrate (OF), an oil-soluble liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension concentrate (SU), an ultra-low volume liquid (UL), a master dose (TK), a dispersible concentrate (DC), a wettable powder (WP) or any technically feasible formulation in combination with an agriculturally acceptable adjuvant.

[0063] Obviously, according to the above contents of the present invention, in accordance with common technical knowledge and customary means in the art, without departing from the above basic technical ideas of the present invention, other various forms of modification, replacement or change may be made.

[0064] Beneficial technical effects of the present invention:

[0065] 1. The present invention provides an acetylhydrazine compound containing a quinazoline-4(3H)-one structure. The quinazoline-4(3H)-one with fungicidal activity reported in the literature and the acylhydrazine structure with excellent fungicidal activity found in previous work are used as the parent skeleton, and a novel acetylhydrazine compound containing a quinazoline-4(3H)-one structure is designed and synthesized for the first time. The compounds of the present invention have good fungicidal activity, and some compounds show better antibacterial rates against specific plant pathogens than commercial agents such as carbendazim, tebuconazole, and fluopyram. The results have important guiding significance for exploring new and efficient fungicides.

[0066] 2. In vitro fungicidal activity results show that the compounds of the present invention exhibit excellent fungicidal activity against corn sheath blight, with the inhibition rate of most compounds exceeding 90% or even reaching 100%, and the EC of some compounds 50 The values ​​were comparable to those of the commercial agent carbendazim. In addition, some compounds also showed excellent fungicidal activity against rapeseed sclerotinia, apple anthracnose, pepper gray mold and Alternaria alternata. For example, the EC values ​​of compounds W3, W13 and W19 against apple anthracnose were 50The values ​​were 4.12μg / mL, 2.94μg / mL and 5.79μg / mL, respectively, which were significantly lower than 14.3μg / mL of the commercial agent tebuconazole, indicating that its inhibitory activity against apple anthracnose was significantly higher than that of tebuconazole. BRIEF DESCRIPTION OF THE DRAWINGS

[0067] Figure 1 The inhibitory effect of compound I-3 on the growth of apple anthracnose colonies at different concentrations of the drug treatment;

[0068] Figure 2 The inhibitory effect of compound I-13 on the growth of pepper gray mold colonies at different concentrations of the drug treatment;

[0069] Figure 3 The inhibitory effect of compound I-8 on the growth of Alternaria alternata colonies at different drug treatment concentrations;

[0070] Figure 4 The in vivo control effects of compounds I-13, I-19, carbendazim (CD) and tebuconazole (TA) on sheath blight at a treatment concentration of 200 μg / mL. DETAILED DESCRIPTION

[0071] The present invention is further illustrated by the following examples, but is not intended to be limiting of the present invention.

[0072] Intermediate Example 1: Synthesis of 6-fluoro-3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(1H)-one

[0073]

[0074] 2-Amino-5-fluorobenzoic acid (1.0 g, 6.4 mmol), phenyl isothiocyanate (0.96 g, 7.1 mmol), and triethylamine (0.82 mL) were added to ethanol (20 mL), and the system was heated to 80°C for 3 hours, and the reaction was monitored by TLC. After the reaction was completed, it was cooled to room temperature, and the solid was precipitated by standing, filtered, and the filter cake was dried to obtain a white solid with a yield of 97%.

[0075] Intermediate Example 2: Synthesis of 6-fluoro-3-phenyl-2-chloroquinazoline-4(3H)-one

[0076]

[0077] Sulfonyl chloride (0.30 mL) was added dropwise to a solution of 6-fluoro-3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(1H)-one (1.0 g, 3.7 mmol) in chloroform (10 mL). The system was heated to 60 ° C for 3 hours and the reaction was monitored by TLC. After the reaction was completed, it was cooled to room temperature, ice water was added to quench the reaction, and it was extracted with dichloromethane (50 mL × 3). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography to obtain a white solid product. The eluent was petroleum ether and ethyl acetate in a volume ratio of 20:1, and the yield was 64%.

[0078] Intermediate Example 3: Synthesis of tert-butyl (2-(2-(2-fluorophenyl)hydrazinyl)-2-oxoethyl)carbamate

[0079]

[0080] Boc-glycine (3.00 g, 17.1 mmol), 2-fluorophenylhydrazine hydrochloride (3.06 g, 18.8 mmol), EDCI (3.94 g, 20.6 mmol) and DMAP (5.23 g, 42.8 mmol) were added to DMSO (10 mL), stirred at room temperature for 5 hours, and the reaction was monitored by TLC. After the reaction was completed, it was diluted with water, the pH was adjusted to 5-7 with dilute hydrochloric acid, and then extracted with dichloromethane (50 mL × 3). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo, and the residue was purified by column chromatography to obtain a white solid product. The eluent was petroleum ether and ethyl acetate in a volume ratio of 1:1, and the yield was 87%.

[0081] Intermediate Example 4: Synthesis of 2-amino-N'-(2-fluorophenyl)acetylhydrazine

[0082]

[0083] Dissolve tert-butyl (2-(2-(2-fluorophenyl)hydrazine)-2-oxoethyl)carbamate (4.23 g, 14.9 mmol) in dichloromethane (10 mL), add trifluoroacetic acid (12.69 mL) dropwise at room temperature, stir and react for 1 hour at room temperature, and monitor the reaction by TLC. After the reaction is completed, fully concentrate under vacuum, dissolve the residue in water, and adjust the pH to 7-9 with potassium carbonate. Concentrate in vacuo to remove water, add methanol to the residue and ultrasonicate, filter to remove insoluble matter, and concentrate the filtrate in vacuo. The residue is purified by column chromatography to obtain a white solid product, the eluent is dichloromethane and methanol, the volume ratio is 10:1, and the yield is 93%.

[0084] Example 1: Synthesis of 2-((6-fluoro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)amino)-N'-(2-fluorophenyl)acetylhydrazine

[0085]

[0086] 6-Fluoro-3-phenyl-2-chloroquinazolin-4(3H)-one (0.3g, 1.1mmol), 2-amino-N'-(2-fluorophenyl)acetohydrazide (0.44g, 2.4mmol) and triethylamine (0.29mL) were dissolved in DMSO (10mL), and the system was heated to 80°C for 6 hours, and the reaction was monitored by TLC. After the reaction was completed, water was added for dilution, and solids were precipitated, which were filtered and the filter cake was purified by column chromatography to obtain a white solid product. The eluent was dichloromethane and methanol in a volume ratio of 20:1, and the yield was 61%.

[0087] The derivatives prepared by using different raw materials according to the preparation methods of intermediate Examples 1 to 4 and Example 5 are listed in Table 1. 1 HNMR, 13 See Table 2 for CNMR (Bruker AV-500 spectrometer using tetramethylsilane as the internal standard) and melting point data.

[0088] Table 1 Structure of target compound I-1

[0089]

[0090]

[0091]

[0092] Table 2 NMR and melting point data of some target compounds

[0093]

[0094]

[0095]

[0096]

[0097]

[0098]

[0099]

[0100] Effect Example 1

[0101] The derivatives provided by the present invention were used to test the fungicidal activity, and the test objects were corn sheath blight (Rhizoctonia solani), rapeseed sclerotinia (Sclerotiniasclerotiorum), pepper gray mold (Botrytis cinerea), chain dung (Alternaria sp.), apple anthracnose (Colletotrichum gloeosporioides) and rice blast (Magnaportheoryzae), and the test method was the colony growth diameter inhibition method. The test method is as follows:

[0102] Accurately weigh 5.0 mg of the target compound and place it in a 1.5 mL centrifuge tube, add 2 drops of dimethyl sulfoxide to dissolve, and then dilute to 10 mL with 0.1% Tween 80 aqueous solution to obtain 500 μg / mL of the mother solution to be tested. Take 1 mL of the mother solution to be tested and mix it evenly with 9 mL of PDA medium to obtain a drug-containing medium with a test concentration of 50 μg / mL. Use a 7 mm diameter puncher to take the corresponding bacterial cake and place it in the drug-containing medium. Culture it at 25 ° C for 72 hours. Calculate the antibacterial rate of the compound based on the colony diameter. Distilled water is a negative control, and fluopyram, carbendazim and tebuconazole are positive controls. Repeat each treatment three times, and calculate the average and standard deviation.

[0103] The test results of the above in vitro bactericidal activity are shown in Table 3:

[0104] Table 3 Inhibition rate of in vitro bactericidal activity of some target compounds I (%)

[0105]

[0106]

[0107] The results of in vitro fungicidal activity showed that most of the target compounds showed excellent fungicidal activity against corn sheath blight, for example, the inhibition rates of compounds I-1 to I-5, I-8 to I-13, and I-17 to I-21 were all higher than 90% or even 100%. Compound I-13 showed a broad-spectrum fungicidal activity, with inhibition rates higher than 80% against the six tested pathogens. Although most compounds had weak inhibitory activity against apple anthracnose, compounds I-3 and I-19 showed excellent antibacterial activity, with inhibition rates of 94.6% and 98.6%, respectively, which were higher than the positive control agents fluopyram, carbendazim, and tebuconazole. In addition, some compounds also showed excellent fungicidal activity against rapeseed sclerotinia, pepper gray mold, Alternaria alternata, and rice blast. For example, the inhibition rates of compounds I-9 and I-10 against Sclerotinia sclerotiorum of rapeseed were 95.6% and 96.6%, the inhibition rates of compounds I-10 and I-13 against Botrytis cinerea of ​​pepper were 89.6% and 94.3%, the inhibition rates of compounds I-3 and I-19 against Alternaria alternata were 91.5% and 92.9%, and the inhibition rates of compounds I-5 and I-20 against Pyricularia oryzae of rice were 91.5% and 94.0%. Figure 1 The inhibitory effect of compound I-3 on the growth of apple anthracnose bacteria colonies at different concentrations of the drug treatment; Figure 1 Figure 2 The inhibitory effect of compound I-13 on the growth of pepper gray mold colonies at different concentrations of the agent treatment; Figure of the specification Figure 3 The graph shows the inhibitory effect of compound I-8 on the growth of Alternaria alternata colonies at different drug treatment concentrations.

[0108] The structure-activity relationship showed that the introduction of 2-F, 4-Cl and 2,4-diCl groups on the benzene ring on the right side of the hydrazide bridge was unfavorable to the fungicidal activity of the target compound, while the introduction of 4-F or 3,4-diF groups helped to improve the fungicidal activity of the target compound.

[0109] Effect Example 2

[0110] EC is carried out using the derivatives with excellent in vitro bactericidal activity provided by the present invention 50 The test objects are selected from corn sheath blight (Rhizoctonia solani), pepper gray mold (Botrytis cinerea), chain bacteria (Alternaria sp.) and apple anthracnose (Colletotrichum gloeosporioides). The test method is as follows:

[0111] Accurately weigh 5.0 mg of the target compound and place it in a 1.5 mL centrifuge tube. Add 2 drops of dimethyl sulfoxide to dissolve it, then dilute it to 10 mL with 0.1% Tween 80 aqueous solution to obtain a 500 μg / mL mother solution to be tested, and then dilute it in sequence using the two-fold dilution method to prepare 250, 125, 62.5, 31.25 and 15.625 μg / mL drug-containing solutions. Take 1 mL of the solution to be tested and mix it evenly with 9 mL of PDA culture medium to obtain drug-containing culture media with test concentrations of 50, 25, 12.5, 6.25, 3.125 and 1.5625 μg / mL, respectively. Use a 7 mm diameter puncher to take the corresponding bacterial cake and place it in the drug-containing culture medium. Culture it at 25 ° C for 3-7 days. Calculate the antibacterial rate of the compound at each test concentration based on the colony growth diameter, and then construct a regression equation to calculate the EC of each compound. 50 value.

[0112] The above in vitro bactericidal activity EC 50 The test results of the values ​​are shown in Table 4:

[0113] Table 4 In vitro fungicidal activity EC of some target compounds I 50 value

[0114]

[0115] EC 50 The results showed that some compounds showed fungicidal activity comparable to or even superior to that of commercial agents. For example, compounds I-12 and I-21 showed fungicidal activity comparable to that of carbendazim against corn sheath blight, and EC 50 The values ​​were 0.51 μg / mL and 0.60 μg / mL, respectively. The fungicidal activity EC values ​​of compounds I-3, I-13 and I-19 against apple anthracnose 50 The values ​​were 4.12 μg / mL, 2.94 μg / mL and 5.79 μg / mL, respectively, which were significantly better than the commercial agent tebuconazole of 14.3 μg / mL. In addition, the fungicidal activity of the compounds shown in Table 4 against pepper gray mold was not much different from that of the commercial agent tebuconazole, and the fungicidal activity against Alternaria alternata was comparable to that of the commercial agent tebuconazole, and even better than that of the commercial agent fluopyram. For example, the EC of compound I-24 against Alternaria alternata was 50 The value is 0.24 μg / mL, which is lower than 0.92 μg / mL of fluopyram. The above results show that this type of new structure is helpful for the development of new and efficient hydrazide fungicide candidate agents.

[0116] Effect Example 3

[0117] The derivatives with excellent in vitro fungicidal activity provided by the present invention were used to evaluate the in vivo control effect, and the test object was Rhizoctonia solani. The test method is as follows:

[0118] Accurately weigh 4.0 mg of the target compound and place it in a 1.5 mL centrifuge tube. Add 2 drops of dimethyl sulfoxide to dissolve it, then dilute it to 20 mL with a 0.1% Tween 80 aqueous solution to obtain a 200 μg / mL mother solution to be tested. Spray the drug-containing solution evenly onto wheat seedlings of uniform growth. After the solvent evaporates completely, inoculate with sheath blight. Place the wheat seedlings inoculated with pathogens in an environment with a temperature of 28°C and a humidity of 80% for 7 days, and observe the infection of the wheat seedlings. Use distilled water as a negative control, carbendazim and tebuconazole as positive controls, and repeat 3 times for each treatment.

[0119] The results of in vivo control showed that in the distilled water treatment group, the wheat seedlings were seriously infected and the leaves curled; while in the drug treatment group, the wheat seedlings grew healthily and had no obvious signs of infection, revealing that this type of compound has a significant control effect on sheath blight. Figure 4 The in vivo control effect of compounds I-13 and I-19 on sheath blight at a treatment concentration of 200 μg / mL.

[0120] The above is only a preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Claims

1. A compound represented by formula I-1 or an agriculturally acceptable salt thereof, in, R 1 Selected from the following groups: C1-C6 straight chain or branched alkyl or C6-C 10 Any of the aromatic groups; R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 Independently selected from the following groups: any one of hydrogen, halogen, C1-C6 straight chain or branched chain alkyl, and halogenated C1-C6 straight chain or branched chain alkyl.

2. The compound according to claim 1, wherein R 1 is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, hexyl, phenyl or naphthyl; and / or, the R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 Independently selected from the following groups: hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, hexyl, CFH2-, CF2H-, CF3-, CH3CFH-, CH3CF2- or CH3CF2-.

3. The compound according to claim 1, wherein R 1 Any one selected from -CH3, -C2H5, -Phenyl; and / or, the R 2 Selected from -H; and / or, R 3 Select from -F; and / or, R 4 Selected from -H; and / or, R 5 Selected from -H; and / or, R 6 Selected from any one of -H, -F or -Cl; and / or, R 7 Select any one of -H or -F; and / or, R 8 Any one selected from -H, -F or -Cl; and / or, R 9 Selected from -H; and / or, R 10 Selected from -H.

4. The compound according to claim 1, selected from the following compound structures:

5. A method for preparing the compound of formula I-1 or an agriculturally acceptable salt thereof according to any one of claims 1 to 4, characterized in that: It includes the following steps: Step (1): anthranilic acid 1 is dissolved in an organic solvent and reacted with isothiocyanate under alkaline conditions to prepare a 2-thioquinazolinone compound 2; the 2-thioquinazolinone compound 2 is further reacted with sulfonyl chloride to prepare a 2-chloroquinazolin-4(3H)-one compound 3; wherein the chemical structures of compound 1, compound 2 and compound 3 are as follows: Step (2): Boc-protected glycine 4 is dissolved in an organic solvent and condensed with substituted phenylhydrazine under condensing agent conditions to prepare acylhydrazine compound 5; compound 5 is dissolved in an organic solvent and treated with acid to remove the Boc protecting group to prepare 2-aminoacetylhydrazine compound 6; compound 6 is dissolved in an organic solvent and reacted with compound 3 under alkaline conditions to prepare an acetylhydrazine compound of formula I-1 containing a quinazoline-4(3H)-one structure; wherein compound 4, compound 5, compound 6 and the chemical structure are as follows: Among them, Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6 and the substituted group R in Formula I-1 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 The definition is the same as any one of claims 1-4.

6. The preparation method according to claim 5, characterized in that: The organic solvent in step (1) or step (2) is selected from one or more of N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, methanol, ethanol, ethyl acetate, dichloromethane, chloroform, toluene, acetone, methyl tert-butyl ether, and diethyl ether, preferably dimethyl sulfoxide; And / or, in step (1) or step (2), the base is selected from an organic base or an inorganic base, the inorganic base is selected from one or two or more of sodium hydrogen, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide or lithium hydroxide; the organic base is selected from one or two or more of N,N-diisopropylethylamine, triethylamine, pyridine, lithium diisopropylamide, n-(C1-6 alkyl) lithium, lithium hexamethyldisilazane, potassium hexamethyldisilazane, sodium hexamethyldisilazane, lithium tetramethylpiperidinium, potassium butoxide, potassium pentoxide and potassium pentoxide; And / or, in step (2), the acid is selected from an organic acid or an inorganic acid, the inorganic acid is selected from one or two of hydrochloric acid and sulfuric acid; the organic acid is selected from one or two or more of formic acid, acetic acid, trifluoroacetic acid, trichloroacetic acid and p-toluenesulfonic acid; And / or, the condensing agent in step (2) is selected from 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 4-dimethylaminopyridine or 2-(1H-benzotriazol L-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate and N,N-diisopropylethylamine.

7. An agrochemical composition, comprising a fungicidal effective amount of the compound having the structure represented by formula I-1 according to any one of claims 1 to 4 or an agronomically acceptable salt thereof.

8. The composition according to claim 7, further comprising at least one additional active ingredient and / or an agrochemically acceptable diluent or carrier.

9. A method for controlling or preventing infection of useful plants by phytopathogenic microorganisms, wherein a fungicidally effective amount of a compound of formula I-1 according to any one of claims 1 to 4 or a composition comprising such a compound as active ingredient is applied to the plants, parts thereof or the locus thereof.

10. Use of a compound of formula I-1 according to any one of claims 1 to 4 as a fungicide, preferably as a plant antimicrobial agent.

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