3-hydroxypyrazole substituted nicotinate compound and application thereof

Abstract

The invention provides a compound represented by a formula I, and salts and stereoisomers thereof, # imgabs0 #, r1, R2, m and n are defined in the specification. The compound disclosed by the invention has better bactericidal activity and better application prospect.

Description

Technical Field

[0001] The invention belongs to the field of pesticide chemistry, and specifically relates to a 3-hydroxypyrazole nicotinate derivative and a preparation method and application thereof. Background Art

[0002] In modern crop production, fungicides play a vital role in preventing and controlling plant pathogens, reducing disease losses and increasing crop yields. However, with the widespread use of fungicides, the problem of pathogen resistance is becoming increasingly serious. At present, fungicides that have been used for a long time and in large quantities in the pesticide market generally have varying degrees of resistance, which significantly reduces their inhibitory effect on current pathogens. Therefore, the development of new structural fungicides that are highly sensitive to current pathogens is crucial to contemporary agricultural production. Summary of the invention

[0003] The invention provides a substituted 3-hydroxypyrazole nicotinic acid ester compound with excellent bactericidal activity.

[0004] Specifically, the present invention provides a compound of formula I, a salt thereof and a stereoisomer thereof,

[0005]

[0006] in;

[0007] R1 is selected from H, halogen, nitro, cyano, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, C3-C6 cycloalkyl, -O-C3-C6 cycloalkyl, C1-C6 alkylamino, halogenated C1-C6 alkylamino, di(C1-C6 alkyl)amino, -NHC3-C6 cycloalkyl, halogenated di(C1-C6 alkyl)amino, di(C1-C6 alkyl)aminocarbonyl, C1-C6 ... - C6 alkylthio, -S-C3-C6 cycloalkyl, halogenated C1-C6 alkylthio, C2-C6 alkenyl, C2-C6 alkynyl, C2-C6 alkenyloxy, halogenated C2-C6 alkenyloxy, C2-C6 alkynyloxy, halogenated C2-C6 alkynyloxy, C1-C6 alkylsulfonyl, halogenated C1-C6 alkylsulfonyl, C1-C6 alkylcarbonyl, -OCOC1-C6 alkyl, halogenated C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl;

[0008] R2 is selected from halogen, nitro, cyano, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, C3-C6 cycloalkyl, -O-C3-C6 cycloalkyl, C1-C6 alkylamino, halogenated C1-C6 alkylamino, di(C1-C6 alkyl)amino, -NHC3-C6 cycloalkyl, halogenated di(C1-C6 alkyl)amino, di(C1-C6 alkyl)aminocarbonyl, C1-C C2-C6 alkylthio, -S-C3-C6 cycloalkyl, halogenated C1-C6 alkylthio, C2-C6 alkenyl, C2-C6 alkynyl, C2-C6 alkenyloxy, halogenated C2-C6 alkenyloxy, C2-C6 alkynyloxy, halogenated C2-C6 alkynyloxy, C1-C6 alkylsulfonyl, halogenated C1-C6 alkylsulfonyl, C1-C6 alkylcarbonyl, -OCOC1-C6 alkyl, halogenated C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl;

[0009] m is a natural number from 1 to 4;

[0010] n is a natural number from 0 to 4.

[0011] The present invention also provides a composition comprising the compound of formula I and its salt and stereoisomer thereof and at least one auxiliary agent.

[0012] The present invention also provides use of the compound I, its salt, its stereoisomer and the composition of the present invention in preventing and controlling plant diseases.

[0013] Beneficial Effects

[0014] The compound of the invention has excellent bactericidal effect and has broad application prospects in preventing and controlling diseases of crops. DETAILED DESCRIPTION

[0015] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention. Unless otherwise expressly stated, throughout the specification and claims, the term "comprising" or its variations such as "including" or "including" will be understood to include the stated components or steps, without excluding other material components or steps.

[0016] In addition, in order to better illustrate the present invention, numerous specific details are given in the following detailed description.

[0017] Those skilled in the art will appreciate that the present invention can be implemented without certain specific details. In some embodiments, raw materials, methods, means, etc. that are well known to those skilled in the art are not described in detail in order to highlight the main purpose of the present invention.

[0018] When the compounds of the present invention are capable of existing in tautomeric forms, the above and below references to

[0019] The compounds described are to be understood as also comprising the corresponding tautomeric forms, even if these are not explicitly mentioned in each case.

[0020] If the compounds of the formula I according to the invention have functional groups which can be ionized, they can also be used in the form of their agriculturally acceptable salts or mixtures thereof.

[0021] The term "C1-C6 alkyl" as used herein refers to, for example, a straight or branched chain alkyl group containing 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, neopentyl or n-hexyl, but is not limited thereto.

[0022] In the present invention, "C1-C6 alkoxy" refers to, for example, a straight chain or branched alkoxy group containing 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentyloxy, neopentyloxy, or n-hexyloxy, but is not limited thereto.

[0023] In the present invention, "C 1- The term "C6 alkylthio group" refers to, for example, a straight or branched chain alkylthio group containing 1 to 6 carbon atoms, such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, sec-butylthio, tert-butylthio, n-pentylthio, isopentylthio, or n-hexyl, but is not limited thereto.

[0024] In the present invention, "C3-C6 cycloalkyl" refers to a cycloalkyl group containing 3-6 carbon atoms, wherein the cycloalkyl group is monocyclic, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc., but not limited thereto.

[0025] In the present invention, "C1-C6 alkylsulfonyl" refers to a straight chain or branched chain alkylsulfonyl group containing 1 to 6 carbon atoms.

[0026] For example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, secondary butylsulfonyl and tertiary butylsulfonyl, but are not limited thereto. Examples of halogenated alkylsulfonyl are alkyl- and / or fluorine-halogenated substituents thereof, such as difluoromethylsulfonyl, trifluoromethylsulfonyl, chlorodifluoromethylsulfonyl, etc., but are not limited thereto.

[0027] In the present invention, "C2-C6 alkenyl" refers to a straight chain or branched alkenyl group containing 2-6 carbon atoms, which contains one or more double bonds, for example, vinyl, 1-propenyl, 1,3-butadienyl, etc., but is not limited thereto.

[0028] The "C2-C6 alkynyl group" in the present invention refers to a straight chain or branched chain containing 2 to 6 carbon atoms and may have a triple bond at any position.

[0029] The "C2-C6 alkenyloxy group" of the present invention refers to an alkenyloxy group containing 2 to 6 carbon atoms, for example, vinyloxy group, but is not limited thereto.

[0030] The "C2-C6 alkynyloxy group" of the present invention refers to an alkynyloxy group containing 2 to 6 carbon atoms, for example, ethynyloxy group and 1-propynyloxy group, but is not limited thereto.

[0031] The "C1-C6 alkylcarbonyl group" of the present invention refers to a straight chain or branched chain alkyl acyl group containing 1 to 6 carbon atoms, for example, formyl, acetyl, etc., but is not limited thereto.

[0032] In the present invention, halogenated C1-C6 alkyl, halogenated C1-C6 alkoxy, halogenated C1-C6 alkylamino, halogenated di(C1-C6 alkyl)amino, halogenated C1-C6 alkylthio, halogenated C2-C6 alkenyloxy, halogenated C2-C6 alkynyloxy, halogenated C1-C6 alkylsulfonyl, halogenated C1-C6 alkylcarbonyl, etc., indicate that the relevant groups are substituted with halogen. For example, halogenated C1-C6 alkyl indicates a chain length of 1 to 6 carbon atoms. The alkyl group is substituted with halogen, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1,1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl and 2,2,2-trichloroethyl; preferably fluoromethyl, difluoromethyl, trifluoromethyl, trichloromethyl, difluorochloromethyl and dichlorofluoromethyl, etc., but not limited thereto. For example, Examples of halogenated C1-C6 alkoxy groups include monofluoromethoxy, difluoromethoxy, trifluoromethoxy, chloromethoxy, dichloromethoxy, trichloromethoxy, 2,2,2-trifluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, pentafluoroethoxy, 1,1-difluoro-2,2,2-trichloroethoxy, 2,2,3,3-tetrafluoroethoxy and 2,2,2-trichloroethoxy; preferably, fluoromethoxy, difluoromethoxy, trifluoromethoxy, trichloromethoxy, difluorochloromethoxy and dichlorofluoromethoxy and the like, but are not limited thereto.

[0033] In the present invention, halogen is usually fluorine, chlorine, bromine or iodine, preferably fluorine, bromine or chlorine.

[0034] The compounds of formula I in each case in free form or in salt form, and where appropriate their tautomers, may be present in the form of one of the possible isomers or as a mixture of these, for example in the form of pure isomers, such as enantiomers and / or diastereomers, or as isomer mixtures, such as enantiomeric mixtures, for example racemates, diastereomeric mixtures or racemic mixtures, depending on the number, absolute and relative configuration of the asymmetric carbon atoms present in the molecule, and / or on the configuration of the non-aromatic double bonds present in the molecule; the invention relates to these pure isomers, and also to all possible isomer mixtures and the invention should be understood in this sense in each case above and below (even if no specific mention is made of stereochemical details in each case). Therefore, the invention covers all such isomers and tautomers and their mixtures in all proportions, together with isotopic forms, such as deuterated compounds.

[0035] The present invention also encompasses salts or N-oxides of each compound of Formula I.

[0036] One of ordinary skill in the art will also appreciate that because salts of chemical compounds exist in equilibrium with their corresponding non-salt forms in the environment and under physiological conditions, the salts also have the biological utility of the non-salt form.

[0037] Therefore, the various salts of the compound of the present invention (and the active ingredient used in combination with the active ingredient of the present invention) can be used for preventing and treating plant diseases and insect pests. The salts among the salts allowed in agriculture and / or physiology include acid addition salts formed with the following inorganic or organic acids, such as hydrobromic acid, hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, acetic acid, butyric acid, fumaric acid, lactic acid, maleic acid, malonic acid, oxalic acid, propionic acid, salicylic acid, tartaric acid, 4-toluenesulfonic acid or valeric acid. Suitable salts among the salts allowed in agriculture and / or physiology can also be salts whose cations do not adversely affect the plant disease prevention and treatment effect of the compound with formula I. Therefore, especially suitable cations are ions of alkali metals (including sodium, potassium and lithium), ions of alkaline earth metals (including calcium and magnesium), and ions of transition metals (including manganese, copper, iron, zinc, cobalt, lead, silver, nickel).

[0038] Specifically, the present invention first provides a compound of formula I, a salt thereof and a stereoisomer thereof,

[0039]

[0040] in;

[0041] R1 is selected from H, halogen, nitro, cyano, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, C3-C6 cycloalkyl, -O-C3-C6 cycloalkyl, C1-C6 alkylamino, halogenated C1-C6 alkylamino, di(C1-C6 alkyl)amino, -NHC3-C6 cycloalkyl, halogenated di(C1-C6 alkyl)amino, di(C1-C6 alkyl)aminocarbonyl, C1-C C2-C6 alkylthio, -S-C3-C6 cycloalkyl, halogenated C1-C6 alkylthio, C2-C6 alkenyl, C2-C6 alkynyl, C2-C6 alkenyloxy, halogenated C2-C6 alkenyloxy, C2-C6 alkynyloxy, halogenated C2-C6 alkynyloxy, C1-C6 alkylsulfonyl, halogenated C1-C6 alkylsulfonyl, C1-C6 alkylcarbonyl, -OCOC1-C6 alkyl, halogenated C1-C6 alkylcarbonyl or C1-C6 alkoxycarbonyl;

[0042] R2 is selected from halogen, nitro, cyano, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, C3-C6 cycloalkyl, -O-C3-C6 cycloalkyl, C1-C6 alkylamino, halogenated C1-C6 alkylamino, di(C1-C6 alkyl)amino, -NHC3-C6 cycloalkyl, halogenated di(C1-C6 alkyl)amino, di(C1-C6 alkyl)aminocarbonyl, C1-C6 One of alkylthio, -S-C3-C6 cycloalkyl, halogenated C1-C6 alkylthio, C2-C6 alkenyl, C2-C6 alkynyl, C2-C6 alkenyloxy, halogenated C2-C6 alkenyloxy, C2-C6 alkynyloxy, halogenated C2-C6 alkynyloxy, C1-C6 alkylsulfonyl, halogenated C1-C6 alkylsulfonyl, C1-C6 alkylcarbonyl, -OCOC1-C6 alkyl, halogenated C1-C6 alkylcarbonyl or C1-C6 alkoxycarbonyl;

[0043] m is a natural number from 1 to 4;

[0044] n is a natural number from 0 to 4.

[0045] In some technical schemes, R1 is selected from one of H, fluorine, chlorine, bromine, nitro, cyano, methyl, trifluoromethyl, methoxy, trifluoromethoxy, dimethylamino, methoxycarbonyl or methylcarbonyloxy; preferably H and chlorine.

[0046] In some technical schemes, R2 is selected from one of fluorine, chlorine, bromine, nitro, cyano, methyl, trifluoromethyl, methoxy, trifluoromethoxy, dimethylamino, methoxycarbonyl and methylcarbonyloxy; preferably chlorine.

[0047] In some technical solutions, m is 1, 2, 3 or 4; preferably m is 1, 2 or 3.

[0048] In some technical solutions, n is 0, 1, 2, 3 or 4, preferably 0, 1, 2 or 3.

[0049] Particularly preferred compounds of formula I according to the present invention are selected from the following compounds:

[0050]

[0051] The present invention also provides a composition comprising the compound of formula I, its salt and stereoisomer thereof and at least one auxiliary agent.

[0052] The present invention also provides the use of the compound I, its salt and stereoisomers thereof and the composition of the present invention in preventing and controlling plant diseases.

[0053] General synthesis process

[0054] In this specification, if there is any difference between chemical name and chemical structure, the structure is dominant. Generally, the compounds of the present invention can be prepared by the methods described in the present invention, unless further specified. The following synthetic schemes and examples are used to further illustrate the content of the present invention.

[0055] Those skilled in the art will recognize that the chemical reactions described herein can be used to appropriately prepare many other compounds of the invention, and other methods for preparing the compounds of the invention are considered to be within the scope of the invention. For example, the synthesis of non-exemplified compounds according to the invention can be successfully accomplished by those skilled in the art through modification methods, such as appropriate protection of interfering groups, by utilizing other known reagents (except those described herein), or by making some conventional modifications to the reaction conditions. In addition, the reactions disclosed herein or known reaction conditions are also recognized to be applicable to the preparation of other compounds of the invention.

[0056] The compounds of the present invention can be prepared by the following synthetic route:

[0057]

[0058] Wherein, R1, R2, m and n are as defined above in Formula I.

[0059] A specific synthesis process is that the compound of formula III reacts with an acylating agent to generate an acylated product, and the acylated product reacts with the compound of formula III in the presence of a base to synthesize compound I. Preferably, the above reaction is carried out in an organic solvent, the acylating agent is: thionyl chloride, oxalyl chloride, the organic solvent is dichloroethane, dichloromethane, toluene, chloroform, chlorobenzene and acetonitrile, etc., the base is triethylamine, pyridine, potassium carbonate, sodium carbonate, 3-methylpyridine, etc., and the reaction temperature is 0-100°C.

[0060] The present invention also provides a composition comprising the compound of formula II of the present invention and at least one auxiliary agent selected from the group consisting of a surfactant, a solid diluent and a liquid diluent.

[0061] The present invention relates to the use of the compound or a composition containing the compound as a fungicide in agriculture or gardening, for controlling or preventing useful plants from being damaged by diseases.

[0062] The diseases described in the present invention include the following diseases, but are not limited to these:

[0063] Oomycetes, such as Pythium, Pseudoperonospora, Phytophthora, Peronospora, Peronophythora, and other genera; Deuteromycetes, such as Fusarium, Rhizoctonia, Colletotrichum, Curyularia, and other genera; Ascomycetes, such as Cochliobolus, Gibberella, Erysiphe, Valsa, Claviceps, Taphrina, Venturia, Mycosphaerella, Neovossia, and other genera; and other pathogens that cause plant diseases, such as bacteria. Examples of related diseases caused by related pathogens include but are not limited to: wheat stem rot, wheat root rot, wheat eyebrow blight, wheat fusarium wilt, wheat rot, wheat take-all disease, corn bacterial wilt, corn seedling blight, corn stem rot, corn rot and other soil-borne diseases.

[0064] The plant objects to which the compounds of the present invention can be used are not particularly limited; for example, cereals (e.g., rice, barley, wheat, rye, oats, corn, sorghum, etc.), legumes (soybeans, adzuki beans, broad beans, peas, peanuts, etc.), fruit trees / fruits (apples, citrus, pears, grapes, peaches, Japanese apricots, cherries, walnuts, apricots, bananas, strawberries, etc.), vegetables (cabbage, tomatoes, spinach, cabbage, lettuce, onions, green onions, green peppers, etc.), root vegetables (carrots, potatoes, sweet potatoes, radish, lotus root, turnip, etc.), industrial crops (cotton, paper mulberry, knotweed, rapeseed, beet, hop, sugarcane, sugar beet, olive, rubber, coffee, tobacco, tea, etc.), berries (pumpkin, cucumber, watermelon, melon, etc.), forage (orchard grass, milo, timothy, alfalfa, purple lucerne, etc.), lawn grass (Korean zoysia, bentgrass, etc.), spices (lavender, rosemary, thyme, parsley, pepper, ginger, etc.), and flowers (chrysanthemum, rose, orchid, etc.).

[0065] The compounds of the present invention can generally be used as active ingredients of pesticides in compositions, i.e., formulations, which usually also include pesticide-acceptable surfactants and carriers. The carriers can be solid carriers or liquid carriers.

[0066] Suitable solid carriers include natural or synthetic clays and silicates, such as natural silica and diatomaceous earth; magnesium silicates, such as talc; magnesium aluminum silicates, such as kaolinite, kaolin, montmorillonite and mica; white carbon, calcium carbonate, light calcium carbonate; calcium sulfate; limestone; sodium sulfate; ammonium salts, such as ammonium sulfate, hexamethylenediamine and urea, etc.

[0067] Liquid carriers include water and organic solvents. When water is used as a solvent or diluent, organic solvents can also be used as adjuvants or antifreeze additives. Useful liquefied gaseous fillers or carriers are those liquids that are gaseous at standard temperature and standard pressure, such as aerosol propellants, such as halogenated hydrocarbons, butane, propane, nitrogen and carbon dioxide, etc.

[0068] Suitable organic solvents include aromatic hydrocarbons, such as benzene, xylene, toluene, etc.; chlorinated hydrocarbons, such as chlorobenzene, vinyl chloride, chloroform, methylene chloride, etc.; aliphatic hydrocarbons, such as petroleum fractions, cyclohexane, light mineral oil; alcohols, such as isopropanol, butanol, ethylene glycol, glycerol and cyclohexanol, etc.; and their ethers and esters; ketones, such as acetone, cyclohexanone, dimethylformamide and N-methyl-pyrrolidone, vegetable oils, such as soybean oil, rapeseed oil and cottonseed oil, etc.

[0069] Suitable surfactants (adjuvants, emulsifiers, dispersants, protective colloids, wetting agents and binders) include all customary ionic and nonionic substances, for example ethoxylated nonylphenols, polyalkylene glycol ethers of linear or branched alcohols, reaction products of alkylphenols with ethylene oxide and / or propylene oxide, reaction products of fatty acid amines with ethylene oxide and / or propylene oxide, and also fatty acid esters, alkylsulfonates, alkyl sulfates, alkyl ether sulfates, alkyl ether phosphates, aryl sulfates, ethoxylated arylalkylphenols (for example tristyrylphenol ethoxylates), and ethoxylated and propoxylated arylalkylphenols, for example sulfated and phosphated arylalkylphenol-ethoxylates and -ethoxy- and -propoxylates. Other examples are natural and synthetic water-soluble polymers, such as ligninsulfonates, gelatin, gum arabic, phospholipids, starch, hydrophobically modified starch and cellulose derivatives, in particular cellulose esters and cellulose ethers, and polyvinyl alcohol, polyvinyl acetate, polyvinyl pyrrolidone, polyacrylic acid, polymethacrylic acid and copolymers of (meth)acrylic acid and (meth)acrylic esters, and copolymers of methacrylic acid and methacrylic esters neutralized with alkali metal hydroxides, and condensates of optionally substituted naphthalenesulfonates with formaldehyde. The presence of a surfactant is necessary if one of the active ingredients and / or one of the inert carriers is insoluble in water and application is carried out in water.

[0070] The pesticide sterilization of the present invention can be prepared by a general method. For example, the active substance is mixed with a liquid solvent and / or a solid carrier, and a surfactant such as an emulsifier, a dispersant, a stabilizer, a wetting agent is added at the same time, and other auxiliary agents such as a binder, a defoamer, a foaming agent, an antioxidant, a crystallization inhibitor, a viscosity modifier, a suspending agent, a spray drop regulator, a pigment, a neutralizer and a buffer, a corrosion inhibitor, a dye, a flavoring agent, a spreading agent, a penetration aid, a micronutrient, a dispersant, a thickener, a freezing point depressant, an antimicrobial agent, etc. can also be added.

[0071] The pesticide fungicide of the present invention can be applied in the form of its formulation or in a use form prepared therefrom, such as capsule suspensions, fine granules, foams, pastes, suspension concentrates, emulsion concentrates, soluble concentrates, suspensions, wettable powders, soluble powders, powders and granules, water-soluble and water-dispersible granules or tablets, etc., but are not limited thereto.

[0072] The formulation of the present invention may also contain other components, such as other fungicides, insecticides, herbicides, plant growth regulators, attractants, acaricides, nematicides, fertilizers, safeners, etc., which can be formulated with liquid fertilizers or solid, granular fertilizer carriers such as ammonium nitrate, urea, etc. or mixed with fine sand or soil.

[0073] When the pesticide composition containing the compound of formula I of the present invention is used to prevent and treat plant diseases in the form of emulsifiable concentrate, wettable powder or microemulsion, these preparations are usually applied by diluting them with water to a concentration of the active ingredient [i.e., the compound of formula I] in the range of 0.01 to 5000 ppm. Granules or powders, etc., can be applied without dilution. The results of the study show that the compound of formula I of the present invention has an inhibition rate or lethality of at least 50% against certain diseases at a concentration of 0.01 to 100 ppm (0.01 mg / L to 100 mg / L), preferably 0.01 ppm to 10 ppm.

[0074] 1) Preparation Example

[0075] Generally, the compounds of the present invention can be prepared by the methods described in the present invention, unless otherwise specified. The raw materials, reagents, etc. used to prepare the compounds of the present invention are commercially available or can be prepared by conventional methods in the art.

[0076] Example 1 Preparation of I-01

[0077]

[0078] At 25°C, nicotinic acid (0.1 mol, 12.3 g, 1.0 eq.), oxalyl chloride (0.11 mol, 14.0 g, 1.1 eq.) and 100 ml of acetonitrile were added to a three-necked flask (250 ml) equipped with a thermometer and mechanical stirring. The temperature was raised to reflux for 3 hours. After the acetonitrile was removed under negative pressure, 100 ml of acetonitrile and 3-methylpyridine (0.12 mol, 11.2 g, 1.2 eq.) were added. The system temperature was maintained at 25°C, and 1-(4-chlorophenyl)-3-pyrazolol (0.1 mol, 19.5 g, 1.0 eq.) was added. After completion, stirring was continued for 2 hours. The reaction was complete as tracked by TLC. The solvent was removed under negative pressure, an appropriate amount of water was added, stirred, filtered, and dried to obtain 29.9 g of an off-white solid with a yield of 95.0%.

[0079] NMR data

[0080] 1 H NMR(400MHz,DMSO-d6)δ9.16(d,J=1.4Hz,1H),8.74(dd,J=7.6,1.6Hz,1H),8.16(m,J=7.5,1.5Hz,1H),7 .94(d,J=7.5Hz,1H),7.62–7.55(m,2H),7.51(t,J=7.5Hz,1H),7.28–7.21(m,2H),5.93(d,J=7.5Hz,1H). 13C NMR (100MHz, DMSO-d6) δ163.12,154.04,152.84,151.62,140.50,138.28,130.98,129.42,124.56,123.56,120.19,120.08,105.92.

[0081] Preparation of Example 2I-02

[0082]

[0083] At 25°C, 2-chloronicotinic acid (0.1 mol, 15.7 g, 1.0 eq.), oxalyl chloride (0.11 mol, 14.0 g, 1.1 eq.) and 100 ml of acetonitrile were added to a three-necked flask (250 ml) equipped with a thermometer and mechanical stirring. The temperature was raised to reflux for 3 hours. After the acetonitrile was removed under negative pressure, 100 ml of acetonitrile and 3-methylpyridine (0.12 mol, 11.2 g, 1.2 eq.) were added. The system temperature was maintained at 25°C, and 1-(4-chlorophenyl)-3-pyrazolol (0.1 mol, 19.5 g, 1.0 eq.) was added. After completion, stirring was continued for 2 hours. The reaction was complete as tracked by TLC. The solvent was removed under negative pressure, an appropriate amount of water was added, stirred, filtered, and dried to obtain 31.0 g of an off-white solid with a yield of 93.0%.

[0084] NMR data

[0085] 1 H NMR (400MHz, DMSO-d6) δ8.72(dd,J=4.8,2.0Hz,1H),8.62(d,J=2.7Hz,1H),8.57(dd,J=7.8,1.9H z,1H),7.92–7.81(m,2H),7.69(dd,J=7.8,4.8Hz,1H),7.64–7.54(m,2H),6.63(d,J=2.7Hz,1H). 13 C NMR (100MHz, DMSO-d6) δ161.60,156.26,153.88,149.32,141.97,138.46,131.04,130.43,130.02,125.22,123.93,120.14,100.14.

[0086] Example 3 Preparation of I-10

[0087]

[0088] At 25°C, 6-chloronicotinic acid (0.1 mol, 15.7 g, 1.0 eq.), oxalyl chloride (0.11 mol, 14.0 g, 1.1 eq.) and 100 ml of acetonitrile were added to a three-necked flask (250 ml) equipped with a thermometer and mechanical stirring. The temperature was raised to reflux for 3 hours. After the acetonitrile was removed under negative pressure, 100 ml of acetonitrile and 3-methylpyridine (0.12 mol, 11.2 g, 1.2 eq.) were added. The system temperature was maintained at 25°C, and 1-(3-chlorophenyl)-3-pyrazolol (0.1 mol, 19.5 g, 1.0 eq.) was added. After completion, stirring was continued for 2 hours. The reaction was complete as tracked by TLC. The solvent was removed under negative pressure, an appropriate amount of water was added, stirred, filtered, and dried to obtain 31.2 g of an off-white solid with a yield of 93.4%.

[0089] NMR data

[0090] 1 H NMR (400MHz, DMSO-d6) δ8.62(d,J=1.6Hz,1H),7.94(d,J=7.6Hz,1H),7.88(dd,J=7.5,1.5Hz,1H),7.56(m, J=7.3,1.5Hz,1H),7.52(t,J=1.5Hz,1H),7.30–7.24(m,2H),7.19(t,J=7.4Hz,1H),5.94(d,J=7.5Hz,1H). 13 C NMR (100 MHz, DMSO-d 6 )δ162.62,152.44,150.20,142.02,132.68,130.16,123.28,121.70,121.66,120.09,120.07,119.96,105.88,105.80.

[0091] The compounds in Table 1 below of the present invention were synthesized according to the above method.

[0092] Table 1 Preferred compounds of the present invention

[0093]

[0094] II) Bioactivity Assay 1. In vitro fungus

[0095] 1.1 Test Target

[0096] Fusarium graminearum (FG), Pseudomonas graminearum (FP), Colletotrichum spp. (CG), Blightella spp. (BS), Phytophthora capsici (PC), Rhizoctonia solani (RC), Brown rot fungus (MF)

[0097] 1.2 Test Method

[0098] The mycelium growth method (NY / T 1156.2-2006) was used to prepare the compounds I-01 to I-15 of the present invention at concentrations of 100, 50, 25, 12.5, 6.25, 3.125, and 1.5625 (ppm), respectively. The in vitro inhibitory concentration (EC) of each compound on the fungi Fusarium graminearum (FG), Pseudomonas graminearum (FP), Colletotrichum sphaerocephala (CG), Bletilla striata (BS), Phytophthora capsici (PC), Rhizoctonia solani (RC), and Folium sphaerocephalae (MF) was calculated based on the test data. 50 ).

[0099] 1.3 Test Results

[0100] Table 2 Effects of the compounds of the present invention on relevant test targets

[0101]

[0102] It can be seen from Table 1 that the compounds of the present invention have a relatively good inhibitory effect on pathogens. The inhibitory concentration of compound I-01 on wheat root rot umbilical helminth reached 16.6ppm, and the inhibitory concentration on Fusarium graminearum reached 19.8ppm. The inhibitory concentration of compound I-02 on mango anthracnose reached 6.6ppm. The inhibitory concentration of compound I-10 on pseudo-Fusarium graminearum reached 8.8ppm, and the inhibitory concentration on wheat leaf rust reached 8.9ppm.

[0103] 2. In vivo assay

[0104] 2.1 Test Target

[0105] Corn rust fungus

[0106] 2.2 Test Method

[0107] Corn rust in vivo assay: corn seedlings were grown in plastic pots (15 cm diameter x 10 cm) under greenhouse conditions, 10 per pot. Corn buds were used for testing after growing the third leaf. Test compound (100 mg / L, 50 mg / L, 10 mg / L) was sprayed on the corn seedlings. One day later, plants were inoculated by spraying corn rust spore suspension and then stored in a moisturizing box. When the blank control treated seedlings had obvious disease symptoms, the incidence was recorded and the control effect was calculated by the in vivo test prevention formula.

[0108] The formulas for the disease index and control effect of the in vivo test are as follows:

[0109]

[0110] Where: X represents the disease index, N irepresents the number of diseased leaves at each level, i represents the relative level value, and N represents the total number of leaves surveyed.

[0111]

[0112] Where: P represents the control effect, CK represents the disease index of the blank control, and PT represents the disease index of the drug treatment.

[0113] Table 3 The efficacy of the compounds of the present invention on corn rust

[0114]

[0115] / indicates not tested

[0116] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. A compound of formula I, its salt and stereoisomers thereof, in; R1 is selected from H, halogen, nitro, cyano, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, C3-C6 cycloalkyl, -O-C3-C6 cycloalkyl, C1-C6 alkylamino, halogenated C1-C6 alkylamino, di(C1-C6 alkyl)amino, -NHC3-C6 cycloalkyl, halogenated di(C1-C6 alkyl)amino, di(C1-C6 alkyl)aminocarbonyl, C1-C6 ... - C6 alkylthio, -S-C3-C6 cycloalkyl, halogenated C1-C6 alkylthio, C2-C6 alkenyl, C2-C6 alkynyl, C2-C6 alkenyloxy, halogenated C2-C6 alkenyloxy, C2-C6 alkynyloxy, halogenated C2-C6 alkynyloxy, C1-C6 alkylsulfonyl, halogenated C1-C6 alkylsulfonyl, C1-C6 alkylcarbonyl, -OCOC1-C6 alkyl, halogenated C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl; R2 is selected from halogen, nitro, cyano, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, C3-C6 cycloalkyl, -O-C3-C6 cycloalkyl, C1-C6 alkylamino, halogenated C1-C6 alkylamino, di(C1-C6 alkyl)amino, -NHC3-C6 cycloalkyl, halogenated di(C1-C6 alkyl)amino, di(C1-C6 alkyl)aminocarbonyl, C1-C C2-C6 alkylthio, -S-C3-C6 cycloalkyl, halogenated C1-C6 alkylthio, C2-C6 alkenyl, C2-C6 alkynyl, C2-C6 alkenyloxy, halogenated C2-C6 alkenyloxy, C2-C6 alkynyloxy, halogenated C2-C6 alkynyloxy, C1-C6 alkylsulfonyl, halogenated C1-C6 alkylsulfonyl, C1-C6 alkylcarbonyl, -OCOC1-C6 alkyl, halogenated C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl; m is a natural number from 1 to 4; n is a natural number from 0 to 4.

2. The compound of formula I, its salt and stereoisomer thereof according to claim 1, characterized in that: R1 is selected from one of H, fluorine, chlorine, bromine, nitro, cyano, methyl, trifluoromethyl, methoxy, trifluoromethoxy, dimethylamino, methoxycarbonyl or methylcarbonyloxy; preferably H and chlorine.

3. The compound of formula I, its salt and stereoisomer thereof according to claim 1, characterized in that: R2 is selected from one of fluorine, chlorine, bromine, nitro, cyano, methyl, trifluoromethyl, methoxy, trifluoromethoxy, dimethylamino, methoxycarbonyl and methylcarbonyloxy; preferably chlorine.

4. The compound of formula I, its salt and stereoisomer thereof according to claim 1, characterized in that: m is 1, 2 or 3.

5. The compound of formula I, its salt and stereoisomer thereof according to claim 1, characterized in that: n is 0, 1, 2 or 3.

6. The compound of formula I, its salt and stereoisomer thereof according to claim 1, characterized in that: The compound of formula I is selected from the following compounds:

7. A composition, characterized in that The invention comprises the compound of formula I as claimed in any one of claims 1 to 6, its salt and stereoisomer thereof and at least one auxiliary agent.

8. Use of the compound I according to any one of claims 1 to 6, its salt and stereoisomers thereof, and the composition according to claim 7 in preventing and controlling plant diseases.

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