Substituted oxazole compound as well as preparation method and application thereof in preventing and treating plant diseases

Abstract

The invention relates to an oxazole compound as shown in a formula (I), a preparation method thereof and application of the oxazole compound in prevention and treatment of plant diseases. Particularly relates to an oxazole compound capable of inhibiting formation of fungus and oomycete appressorium, a preparation method of the oxazole compound and application of the oxazole compound to prevention and treatment of plant diseases caused by fungi and oomycetes.

Description

Technical Field

[0001] This invention relates to substituted oxazole compounds, methods for their preparation, and their use in the prevention and control of plant diseases; more specifically, this invention relates to substituted oxazole compounds that can inhibit the formation of fungal and oomycete appressoriums, methods for their preparation, and their use in the prevention and control of plant diseases caused by fungi and oomycetes. Background Technology

[0002] 70-80% of plant diseases are caused by fungi and oomycetes. A single plant can be affected by several or even dozens of different fungi and oomycetes causing diseases. For example, rice diseases such as sheath blight, rice blast, rice false smut, sesame spot, and bakanae disease; wheat diseases such as Fusarium head blight, powdery mildew, stripe rust, stem rust, leaf rust, root rot, and sheath blight; and corn diseases such as large leaf spot, small leaf spot, stem base rot, rust, sheath blight, Curvularia leaf spot, head smut, and powdery mildew are all caused by fungi. These fungal diseases account for over 90% of the area affected and the losses caused by crop diseases. Besides fungal diseases, diseases caused by oomycetes are also serious in many crops, such as potato late blight, soybean Phytophthora blight, pepper Phytophthora blight, grape downy mildew, and cucumber downy mildew.

[0003] For plant diseases caused by fungi and oomycetes, chemical agents are generally used as the primary means of control. Commonly used fungicides in chemical control include Bordeaux mixture, chlorothalonil, thiophanate-methyl, carbendazim, azoxystrobin, pyraclostrobin, prochloraz, and tricyclazole. Among these, Bordeaux mixture, chlorothalonil, azoxystrobin, prochloraz, and tricyclazole are used as protectants, while those with both protectant and curative effects include chlorothalonil, thiophanate-methyl, carbendazim, and pyraclostrobin.

[0004] Protectants and therapeutic agents have diverse molecular structures, but most include nitrogen-containing heterocyclic structures. Common examples include imidazoles, pyrazoles, 1,2,4-triazoles, isothiazoles, isoxazoles, thiazoles, pyridines, and pyrimidines. Nitrogen heterocyclic compounds possess advantages such as high efficiency, low toxicity, good selectivity, and diverse biological activities. Oxazoles, five-membered aromatic heterocycles containing nitrogen and oxygen atoms, are important structural units in many bioactive molecules. Commonly used oxazole structures in agricultural compounds are isoxazoles and oxazolidinones. Common oxazole fungicides include oxadiazon, pyridaben, oxadixyl, and oxazolidinone. Currently, research reports on isoxazoles and oxazolidinones are extensive, but there are no reports on the use of oxazole compounds in preventing diseases caused by fungi and oomycetes on crops.

[0005]

[0006] Most diseases caused by fungi and oomycetes are primarily spread in the field via asexual spores. Many fungi or oomycetes, such as the conidia of *Pyrrosia oryzae* and *Anthracnose*, germinate on the surface of landed plants, forming appressoriums at the tips of the germination tubes. These appressoriums then enter plant tissues through turgor pressure, causing disease. Appressoriums are a specific infection structure formed by many plant and animal pathogenic fungi; therefore, numerous studies are exploring the molecular mechanisms of fungal appressorium formation to provide targets for the development of green fungicides. Currently, tricyclazole is a first-line drug for controlling rice blast in agricultural production. It controls the disease by inhibiting melanin formation during the maturation stage of *Pyrrosia oryzae* appressoriums. Apart from this, there are currently few other commercially available fungicides targeting the appressorium stage. Therefore, developing inhibitors targeting this stage is of great significance for the development of agricultural fungicides.

[0007] Current common methods for evaluating the fungicidal activity of candidate compounds include measuring the inhibition rate of the candidate compound on the growth of vegetative mycelia of pathogenic fungi, and then inferring its control effect on pathogenic fungi. However, this method cannot fully reflect the effect of candidate compounds, especially for pathogenic fungi and oomycetes that infect through specific infection structures, such as appressoria. Taking the model pathogen *Pyrrosia oryzae* as an example, relevant literature reports that the growth rate of *Pyrrosia oryzae* vegetative mycelia is not significantly correlated with its pathogenicity, while conidial germination, germ tube growth, and appressorium formation and maturation directly determine the pathogenicity of *Pyrrosia oryzae*.

[0008] Because pathogenic bacteria in nature can develop resistance to certain fungicides, or because some fungicides can cause environmental problems during use, developing fungicides with better application properties is a problem faced by this field. Summary of the Invention

[0009] In view of the disadvantages of the prior art, the purpose of this invention is to provide an oxazole compound containing aryl ethers that can prevent and control plant diseases caused by fungi and oomycetes.

[0010] Therefore, the first aspect of the present invention provides compounds of formula (I), their stereoisomers, racemates, tautomers, isotope labels, nitrogen oxides, agriculturally acceptable salts or esters, solvates, or solvates of agriculturally acceptable salts:

[0011]

[0012] in,

[0013] R1 and R2 independently represent H, either unsubstituted or represented by one, two or more Rs. 10 The following groups are substituted independently of each other: C1-C 12 Alkyl, C2-C12 alkenyl, C2-C 12 alkynyl group, C3-C 20 Cycloalkyl, 3-20 membered heterocyclic groups, C6-C 20 Aryl, 5-20 heteroaryl, C1-C 12 Alkyloxy, C1-C 12 Alkyl carbonyl, -C(O)OC1-C 12 Alkyl groups; or R1 and R2 together with the N atom to which they are attached to form an unsubstituted or substituted compound, or one, two or more R atoms. 11 3-20 membered heterocyclic groups that are substituted independently of each other;

[0014] Each R 10 Whether they are the same or different, they represent H, Cl-C independently of each other. 12 Alkyl, C2-C 12 alkenyl, C2-C 12 alkynyl group, C3-C 20 cycloalkyl, C1-C 12 Alkyl C3-C 20 cycloalkyl, C1-C 12 Alkyl C6-C 20 Aryl, carboxyl, ester, hydroxyl, hydroxyl C1-C 12 Alkyl, amino, -NH (C1-C) 12 Alkyl), -N(C1-C 12 Alkyl group, amide group, nitro group, CN group, azide group, azide group C group 1- C 12 Alkyl, oxo (=O), halogen, mercapto, hydroxyl, -CHO, wherein the carbon chain of the alkyl, alkenyl, or ynyl group, or the ring atom of the cycloalkyl group, may be optionally interrupted by an oxygen atom, a nitrogen atom, or a sulfur atom, or may be optionally oxosubstituted.

[0015] Each R 11 Whether they are the same or different, they represent H, Cl-C independently of each other. 12 Alkyl, C2-C 12 alkenyl, C2-C 12 alkynyl group, C3-C 20 cycloalkyl, C1-C 12 Alkyl carbonyl, C2-C 12 alkenyl carbonyl, C3-C 20 cycloalkyl carbonyl, C6-C 20 aryl carbonyl, di(C1-C) 12 (alkyl)amino-C1-C 12 Alkyl group, wherein the carbon atom of the alkyl, alkenyl, or alkynyl group, or the ring atom of the cycloalkyl group, may optionally be surrounded by one, two, or more hydroxyl groups, C1-C2. 12 Alkyl carbonyloxy group, C1-C12 Alkyloxycarbonyl, C2-C 12 alkynyloxy group, azide group -C1-C 12 Alkyloxy-C1-C 12 Alkyloxy, amino-C1-C 12 Alkyloxy-C1-C 12 Alkyloxy, C1-C 12 Alkyloxycarbonyl-C1-C 12 Alkyloxy-C1-C 12 Alkyloxy, C1-C 12 Alkyloxycarbonyl C1-C 12 Alkyl substitution.

[0016] R3 indicates that it is unsubstituted or replaced by one, two or more R's. 12 The following groups are substituted independently of each other: C6-C 20 Aryl or 5-20 heteroaryl groups;

[0017] Each R 12 The same or different, representing H, halogens, and C1-C independently of each other. 12 Alkyloxy, C6-C 20 aryloxy group, C1-C 12 Alkyl carbonyl, -C(O)OC1-C 12 Alkyl, -C(O)N(C1-C) 12 Alkyl)2;

[0018] According to some embodiments of the present invention, the compound of formula (I) has the structure of formula (IA) or (IB):

[0019]

[0020] Where R1 and R2 are defined in equation (I), R 121 R 122 R 123 R 124 R 125 Independent of each other, like R 12 Defined.

[0021] According to some embodiments of the invention, R1 and R2 independently represent H, either unsubstituted or represented by one, two or more Rs. 10 The following groups are substituted independently of each other: C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C 12 Cycloalkyl, 3-10 membered heterocyclic, C6-C 10aryl, 5-10 heteroaryl, C1-C6 alkyloxy, C1-C6 alkylcarbonyl, -C(O)OC1-C6 alkyl; or R1 and R2 together with the N atom to which they are attached to form an unsubstituted or substituted compound. 11 3-10 membered heterocyclic groups that are substituted independently of each other.

[0022] According to some embodiments of the present invention, R1 and R2 independently represent H, C1-C6 alkyl, C1-C6 alkyloxy, C1-C6 alkylcarbonyl, -C(O)OC1-C6 alkyl, 5-8 heteroaryl, C6-C 10 Aryl, C6-C 10 aryl-C1-C6 alkyl; or R1 and R2 together with the N atom to which they are attached form an unsubstituted compound or are formed by one, two or more R atoms. 11 3-6 membered heterocyclic groups that are substituted independently of each other.

[0023] According to some embodiments of the invention, R1 and R2 independently represent H, methyl, n-butyl, tert-butyl, methoxy, pyridin-3-yl, -C(O)OCH3, acetyl, benzyl, phenyl; or R1 and R2 together with the N atom to which they are attached form a pyrrolidinyl, morpholino-4-yl, or unsubstituted or substituted form with an R 11 Substituted piperidinyl or piperazine group; preferably, with an R 11 The substituted piperazine group is R at the 4-position. 11 Substituted piperazine group; preferably, by an R 11 The substituted piperidinyl group is R-substituted at the 4-position. 11 Substituted piperidinyl group.

[0024] According to some embodiments of the present invention, R 10 Indicates C1-C6 alkyl or C6-C 10 Aryl; more preferably, R 10 This indicates methyl, ethyl, n-propyl, isopropyl, and phenyl.

[0025] According to some embodiments of the present invention, R 11 Represents H, C1-C6 alkyl, C1-C6 alkyl carbonyl, C5-C7 cycloalkyl carbonyl, C6-C 10 Aryl carbonyl, C2-C6 alkenyl carbonyl, di(C1-C6 alkyl)amino-C1-C6 alkyl.

[0026] According to some embodiments of the present invention, R 11 It represents H, methyl, ethyl, isopropyl, acetyl, acryloyl, di(ethylamino)ethyl, cyclopentylformyl, and benzoyl.

[0027] According to some embodiments of the invention, R3 represents unsubstituted or replaced by one, two or more R's. 12 The following groups are substituted independently of each other: C6-C 10 Aryl, 5-10 heteroaryl;

[0028] According to some embodiments of the present invention, each R 12 Same or different, independently representing H, halogen, C1-C6 alkyloxy group, C6-C 10 Aryloxy, C1-C6 alkyl carbonyl, -C(O)OC1-C6 alkyl, -C(O)N(C1-C6 alkyl)2.

[0029] According to some embodiments of the invention, R3 represents unsubstituted or replaced by one, two or more R's. 12 The following groups can be substituted independently of each other: phenyl, pyridyl, thienyl, furanyl, benzothienyl, quinolinyl;

[0030] According to some embodiments of the present invention, each R 12 They can be the same or different, and can be represented independently as H, F, Cl, methoxy, acetyl, phenoxy, -C(O)OCH3, -C(O)N(CH3)2.

[0031] Preferably, the compounds of formula (I) of the present invention have the structures shown in Tables 1-6.

[0032] A second aspect of the present invention provides a pesticide composition, such as a fungicide, herbicide, or plant protectant composition, comprising one, two, or more of the following: a compound of formula (I) as an active ingredient; a stereoisomer, a racemate, a tautomer, an isotope label, a nitrogen oxide; an agriculturally acceptable salt or ester; a solvate; or a solvate of an agriculturally acceptable salt.

[0033] According to some embodiments of the invention, the pesticide composition is a fungicide containing a compound selected from formula (I) and optionally an agriculturally acceptable adjuvant. Preferably, the pesticide composition serves as a plant protectant for preventing or protecting plants from plant diseases, including rice blast, rice false smut, anthracnose, Phytophthora blight, and / or Fusarium head blight. More preferably, the diseases are selected from rice blast, rice false smut, pepper anthracnose, strawberry gray mold, corn anthracnose, potato late blight, pepper Phytophthora blight, and / or wheat Fusarium head blight.

[0034] According to some embodiments of the present invention, the active ingredient in the composition, preferably a compound of formula (I), its stereoisomers, racemates, tautomers, isotope labels, nitrogen oxides, agriculturally acceptable salts or esters, solvates, or solvates of agriculturally acceptable salts, is present in a weight percentage of 0.1-99.9%, for example, 0.5-99%.

[0035] According to some embodiments of the invention, the composition may further include one, two, or more of agricultural and / or forestry and / or animal husbandry and / or horticultural carriers.

[0036] According to some embodiments of the present invention, the composition can be administered in the form of a formulation.

[0037] For example, compounds of formula (I) are dissolved or dispersed in a carrier or formulated as active ingredients to facilitate dispersion when used as herbicides.

[0038] According to some embodiments of the present invention, the formulation includes, but is not limited to, the following forms: granules, wettable powders, oil suspensions, water suspensions, water emulsions, aqueous solutions, emulsifiable concentrates, or microcapsules, etc.

[0039] According to some embodiments of the present invention, a liquid or solid carrier and optionally a surfactant may also be added to the composition.

[0040] The third aspect of the invention provides the use of one, two or more of the following: compounds of formula (I), stereoisomers, racemates, tautomers, isotopic markers, nitrogen oxides, agriculturally acceptable salts or esters, solvates or solvates of agriculturally acceptable salts, for the prevention and control of rice blast, rice false smut, pepper anthracnose, strawberry gray mold, corn anthracnose, potato late blight, pepper Phytophthora blight and / or wheat scab.

[0041] According to some embodiments of the present invention, the effective amount of the compound of formula (I) according to the present invention, its stereoisomers, racemates, tautomers, isotopic labels, nitrogen oxides, agriculturally acceptable salts or esters, solvates or solvates of agriculturally acceptable salts is from 10 g to 1000 g per hectare, preferably from 20 g to 500 g per hectare.

[0042] Beneficial effects of the present invention

[0043] This invention discloses an oxazole derivative that has the activity of inhibiting the formation of appressorium in fungi and oomycetes. Studies have shown that compounds of formula (I) can effectively inhibit the germination of conidia, germ tube growth, or appressorium formation in fungi and oomycetes.

[0044] The inventors have discovered that oxazole compounds can effectively prevent pathogens from infecting plants by inhibiting conidial germination, germ tube growth, or appressorium formation, and can thus be used to control highly damaging plant diseases, including rice blast, rice false smut, late blight, anthracnose, gray mold, and scab, providing a new option for plant protection drugs.

[0045] The inventors have discovered that the oxazole compounds of the present invention, having a specific structure, can effectively inhibit the formation of pathogenic fungi and oomycete appressoria at concentrations of 10-1000 ppm.

[0046] The inventors have discovered that the oxazole compounds of the present invention, having a specific structure, can produce corresponding control effects on rice blast and potato late blight when applied in the field at concentrations of 10-1000 ppm.

[0047] Terms and Explanations

[0048] Unless otherwise specified, all technical and technical terms herein have the same meaning as commonly understood by one of ordinary skill in the art. Unless otherwise specified, all patent and non-patent literature or otherwise disclosed material cited in whole or in part herein are incorporated herein by reference.

[0049] In this article, when describing one, two, or more species, "more species" should refer to the case of more than 2, such as representing integers greater than or equal to 3, such as 3, 4, 5, 6, 7, 8, 9, or 10.

[0050] In this document, the term "optional" means either the presence or absence of the feature.

[0051] The term "halogen" refers to fluorine, chlorine, bromine, and iodine.

[0052] Term "C" 1- C 12 "Alkyl" refers to a straight-chain and branched saturated hydrocarbon group having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 carbon atoms, including methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, n-hexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl, or 1,2-dimethylbutyl, or their isomers.

[0053] Term "C" 1- C 12"Alkoxy" refers to -OC 1- C 12 Alkyl, wherein C 1- C 12 Alkyl groups are defined as described above. Non-limiting examples of alkoxy groups include: methoxy, ethoxy, propoxy, butoxy, cyclopropoxy, cyclobutoxy, cyclopentoxy, and cyclohexyloxy.

[0054] It should be understood that references (including Carey and Sundberg, "Advanced Organic Chemistry 4") may be included. TH Definitions of standard chemical terms can be found in ED. "Vols. A (2000) and B (2001), Plenum Press, New York". Unless otherwise stated, conventional methods within the scope of the art, such as mass spectrometry, NMR, IR and UV / Vis spectroscopy, and pharmacological methods, are used. Unless otherwise specifically defined, the terms used herein in the relevant descriptions of analytical chemistry, organic synthetic chemistry, and pharmaceutical and medicinal chemistry are those known in the art. Standard techniques may be used in chemical synthesis, chemical analysis, drug preparation, formulation and delivery, and in the treatment of patients. For example, reactions and purifications may be carried out using the manufacturer's instructions for use of kits, or in accordance with methods known in the art or the descriptions in this application. The techniques and methods described herein are generally carried out in accordance with conventional methods well known in the art, based on the descriptions in the various summary and more specific literatures cited and discussed in this specification. In this specification, groups and their substituents may be selected by those skilled in the art to provide stable structural moieties and compounds.

[0055] As used herein, the term "agriculturally acceptable salt" refers to a salt that retains the biological potency of the specified compound's free acid and free base and has no adverse effects in biological or other respects. Agriculturally acceptable salts in this application include salts generally usable in agriculture, forestry, animal husbandry, and / or horticulture, such as sodium, potassium, calcium, and zinc salts. Agriculturally acceptable salts specifically refer to salts in which the acidic and / or basic groups in the parent compound have been converted into salt form.

[0056] Agriculturally acceptable salts include, but are not limited to, inorganic or organic base salts derived from acidic groups such as carboxyl, sulfonyl, phenolic hydroxyl, etc. Agriculturally acceptable salts according to the invention can be synthesized from a parent compound, i.e., by reacting an acidic group in the parent compound with a suitable amount of base, for example, 1-4 equivalents of base, in a solvent system; or similarly, in the presence of a basic group such as an amino group in the parent compound, by forming salts with a suitable inorganic or organic acid; and in the case where the parent compound contains both an acidic center (e.g., a carboxyl group) and a basic center (e.g., an amino group), it can also form an inner salt. Suitable salts are listed in Remingtong's Pharmaceutical Sciences, 17. th See, for example, sodium salts, in Mack Publishing Company, Easton, Pa., 1985, p. 1418 and Journal of Pharmaceutical Science, 66, 2 (1977).

[0057] The compounds of the present invention may exist as solvates (such as hydrates), wherein the compounds of the present invention contain a polar solvent, particularly, for example, water, methanol, or ethanol, as a structural element of the lattice of the compound. The amount of the polar solvent, particularly water, may be stoichiometric or non-stoichiometric.

[0058] Depending on their molecular structure, the compounds of the present invention can be chiral, and therefore may exist in various enantiomeric forms. Thus, these compounds can exist in racemic or optically active forms. The compounds of the present invention or their intermediates can be isolated as enantiomers by chemical or physical methods known to those skilled in the art, or used in this form for synthesis. In the case of racemic amines, diastereomers are obtained from the mixture by reaction with an optically active resolving agent. Examples of suitable resolving agents are optically active acids, such as tartaric acid in R and S forms, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid, suitable N-protected amino acids (e.g., N-benzoylproline or N-benzenesulfonylproline), or various optically active camphorsulfonic acids. Chromatographic enantiomeric resolution can also be advantageously performed using optically active resolving agents (e.g., dinitrobenzoylphenylglycine immobilized on silica gel, cellulose triacetate, or other carbohydrate derivatives or chiral derivatized isobutylene ester polymers). Suitable eluents for this purpose are aqueous or alcoholic solvent mixtures, such as hexane / isopropanol / acetonitrile.

[0059] The term "tautomer" refers to a functional group isomer resulting from the rapid movement of an atom between two positions within a molecule. The compounds of this invention can exhibit tautomerism. Tautomers can exist in two or more interconvertible forms. Proton-transfer tautomers arise from the migration of covalently bonded hydrogen atoms between two atoms. Tautomers generally exist in equilibrium form; attempts to isolate a single tautomer typically yield a mixture whose physicochemical properties are consistent with those of the mixture of compounds. The equilibrium position depends on the intramolecular chemical characteristics. For example, in many aliphatic aldehydes and ketones such as acetaldehyde, the ketone form is dominant; while in phenols, the enol form is dominant. This invention encompasses all tautomeric forms of the compounds.

[0060] The corresponding stable isomers can be separated using known methods, such as extraction, filtration, or column chromatography.

[0061] The term "fungicide" as used herein includes chemicals and / or preparations that can effectively control and / or kill pathogenic microorganisms harmful to plants, such as bacteria, fungi, oomycetes, rickettsiae, mycoplasma, viruses, and / or algae.

[0062] The term "pesticide composition" means a mixture containing one, two or more of the compounds described herein or their agriculturally acceptable salts or precursors, along with other active or inactive components such as excipients, particularly, for example, a carrier and excipients.

[0063] Due to their positive properties, compounds of formula (I) can be advantageously used to protect important crops in arable and non-arable land, as well as environments frequently visited by humans, from harmful pathogens.

[0064] To achieve the desired effect, the amount of compound (I) used varies depending on various factors, such as the compound used, the crop being protected, the type of harmful pathogen, the degree of infection, climatic conditions, the application method, and the formulation used.

[0065] The selection of dosage forms or compositional components described herein should be consistent with the physical properties of the active ingredient, the method of application, and environmental factors such as soil type, humidity, and temperature.

[0066] Useful dosage forms include liquids such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and / or suspensions), etc., which can optionally be thickened into a gel. Useful dosage forms also include solids such as powders, granules, tablets, pills, films, etc., which can be water-dispersible (“wettable”) or water-soluble. Active ingredients can be microencapsulated and re-formed into suspensions or solid dosage forms; alternatively, the entire dosage form of the active ingredient can be encapsulated. Encapsulation can control or delay the release of the active ingredient. Sprayable formulations can be diluted in a suitable medium, with a spray volume of approximately one hundred to several hundred liters per hectare. High-concentration compositions are primarily used as intermediates for further processing.

[0067] Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, and Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended applications. All formulations may contain small amounts of additives to reduce foaming, clumping, corrosion, microbial growth, etc., or thickeners to increase viscosity.

[0068] Surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, sulfonated dialkyl succinates, alkyl sulfates, alkylbenzene sulfonates, organosilanes, N,N-dialkyl taurates, lignin sulfonates, naphthalene sulfonates with aldehyde condensates, polycarboxylate esters, and polyoxyethylene / polyoxypropylene block copolymers.

[0069] Solid diluents include, for example, clays such as bentonite, montmorillonite, magnesia, kaolin, starch, sugar, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate, sodium bicarbonate, and sodium sulfate; liquid diluents include, for example, water, N,N-dimethylformamide, dimethyl sulfone, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffin wax, alkylbenzene, alkylnaphthalene, olive oil, castor oil, linseed oil, tung oil, sesame oil, corn oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil, and cocoa butter, fatty acid esters; ketones such as cyclohexanone, 2-heptanone, isophorone, and 4-hydroxy-4-methyl-2-pentanone; and alcohols such as methanol, cyclohexanol, dodecyl alcohol, and tetrahydrofuran alcohol.

[0070] Solutions, suspensions, and emulsions can be prepared by simply mixing the components. Powders and fine powders can be prepared by mixing and grinding, usually in a hammer mill or hydraulic mill. Suspensions are generally prepared by wet milling.

[0071] In this document, for certain applications of the composition, such as in agriculture, one, two or more other fungicides, insecticides, acaricides, herbicides, plant growth regulators, plant protectants or fertilizers may be added to the composition of the present invention, thereby producing additional advantages and effects.

[0072] Compounds of formula (I) may be used in their unaltered form or preferably in combination with carriers and excipients commonly used in the pharmaceutical field.

[0073] Therefore, the present invention also relates to compositions for preventing or protecting against plant pathogenic microorganisms, comprising a compound of formula (I) and an inert carrier, and a method for preventing or protecting useful plants from infection by plant pathogenic microorganisms, wherein the composition comprising a compound of formula (I) as an active ingredient and an inert carrier is applied to a plant, to a portion thereof or to its location.

[0074] For this purpose, the compound of formula (I) and the inert carrier are conveniently formulated in known ways as emulsifiable concentrates, coating pastes, direct-spray or direct-dilutable solutions, diluent emulsions, wettable powders, soluble powders, powders, granules, and, for example, encapsulation in polymeric substances. Similar to the type of composition, the application method, such as spraying, atomizing, dusting, spreading, coating, or pouring, is selected according to the target object and the primary environment. The composition may also contain other adjuvants such as stabilizers, defoamers, viscosity modifiers, binders or thickeners, as well as fertilizers, micronutrient donors, or other formulations used to achieve specific effects.

[0075] Suitable carriers and adjuvants can be solid or liquid and are substances useful in formulation technology, such as natural or recycled minerals, solvents, dispersants, wetting agents, thickeners, binders, or fertilizers.

[0076] The formulation, i.e., the composition comprising a compound of formula (I) and a solid or liquid adjuvant as required, is prepared in a known manner: typically by tightly mixing and / or grinding the compound with an extender, such as a solvent, a solid carrier, and optionally a surfactant compound.

[0077] Agricultural chemical formulations typically include 0.1 to 99% by weight, preferably 0.1 to 95% by weight, of a compound of formula (I), 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid or liquid adjuvant, and 0 to 25% by weight, preferably 0.1 to 25% by weight, of a surfactant.

[0078] The oxazole derivatives described in this invention can be combined with any one or two or more pesticide active ingredients commonly used in the art for the prevention and control of diseases in agricultural, forestry, and horticultural plants.

[0079] The active ingredient of the pesticide may be selected from: benzothiadiazole, thiamethoxam, thiamethoxam, methyl thiamethoxam, 4-methyl-1,2,3-thiadiazole-5-carboxylic acid, sodium 4-methyl-1,2,3-thiadiazole-5-carboxylate, ethyl 4-methyl-1,2,3-thiadiazole-5-carboxylate, DL-β-aminobutyric acid, isothiazamide, 3,4-dichloroisothiazolium-5-carboxylic acid, sodium 3,4-dichloroisothiazolium-5-carboxylate, ethyl 3,4-dichloroisothiazolium-5-carboxylate, ribavirin, antofenfen, ningnanmycin, salicylic acid, cymoxanil, thiram, zinc thiram, mancozeb, aluminum fosetyl-aluminum, thiophanate-methyl, chlorothalonil, dichlorvos, iprodione, benzyl benzoate, thiophanate-methyl, thiophanate-methyl, metalaxyl, flumorph, dimethomorph, high-efficiency metalaxyl. High-efficiency benzalkonium chloride, cyhalofop-butyl, sulfadiazine, mesotrione, thiabendazole, chlorothalonil, cyprothiophanate-methyl, cycloflufenoxam, cyclopyridamole, cyhalofop-butyl, silthiabendazole, carbendazim, oxychlorpyrifos, methyl thiophanate, fluopyram, furazolidone, thiabendazole, cyprothiophanate-methyl, pyraclostrobin, bifenthiophanate-methyl, fluopyram, fluoxastrobin Fluopyram, fluopyram aniline, benzyl-fluoroquinolone, isothiazamide, fluopyram hydroxylamine, fluopyram, fluopyram, diyrylamide, benzylamide, ethoxysulfuron, iprodione, pyraclostrobin, fenpyroxime, fluopyram, fenpyroxime, fenpyroxime, pyraclostrobin, fenpyroxime, fenpyroxime, oxadiazon, fenpyroxime, fenpyroxime, oxadiazon, fenpyroxime, oxadiazon, fenpyroxime, cyclophosphamide, ciprofloxacin Azoxystrobin, difenoconazole, tebuconazole, high-efficiency tebuconazole, fluconazole, cyproconazole, fluquinazole, flusilazole, fenbendazole, hexaconazole, imidacloprid, tebuconazole, tebuconazole, propiconazole, thiophanate-methyl, tebuconazole, tetraflufenazole, triazole, tebuconazole, bifenthrin, thiamethoxam, fenbendazole, imazalil, high-efficiency imazalil, prochloraz, fluconazole Cyazofamid, imidacloprid, oxadiazon, isoprothiolane, oxadiazon, pyraclostrobin, hymexazol, cymoxanil, thiamethoxam, tebuconazole, benzothiazoline, dodecyl morpholine, butyl morpholine, tridemorpholine, seed dressing agent, fludioxonil, fluazinam, pyridaben, cyclopyridamole, fluazinam, pyridaben, pyrimethanil, fluazinam, pyrimethanil, pyrimethanil, chlorobenzyl Pyrimidinol, Fluoropyrimidinol, Acaricide, Dicyananthraquinone, Ethoxyquinoline, Hydroxyquinoline, Propoxyquinoline, Phenoxyquinoline, Ethoxycarb, Isopropylamine, Benzylamine, Cymoxanil, Sulfocarb, Dichlorvos, Isoprothiolane, Pyridaben, Methyl thiophanate, Miconazole, Kasugamycin, Polyoxin, Polyoxin, Validamycin, Jinggangmycin, Streptomycin, Metalaxyl, Furazolidone, Benzopyrazosulfan, Furazolidone, Carbendazim, Benomyl, Thiophanate-methyl, Triadimefon, Ethylpyrimethanil Sulfate, Dimethomorph, Ethylpyrimethanil, Captan, Captan, Ethylpyridinium Chloride, Fluorochlorothalonil, Isopyridaben, Chlorothalonil, Isoprothiolane, Isoprothiolane, Effluox, Pentachloronitrobenzene, Propineb, Aluminum Trisphosphonate, Sulfur, Bordeaux mixture, Copper sulfate, Copper oxychloride, Cuprous oxide, Copper hydroxideBenomyl, pendimethalin, pyridaben, tetrachlorophthalide, quinclorac, spirocycline, tricyclazole, pyrazosulfuron, doxycycline, biguanide octyl salt, biguanide octylamine, chlorfenapyr, benzylsulfonamide, toluenesulfonamide, indole ester, sodium dichloroisocyanurate, quinclorac, allylbenzylthiazide, bromonitol, iodomethyl, methylparaben, dimethoate, dazomet, dichloroisopropyl ether, thiamethoxam, fenpropathrin, chlorpyrifos, fenpropathrin, thiamethoxam, thiocarbamate, thiocarbamate, thiocarbamate, thiocarbamate, thiocarbamate, thiocarbamate, thiocarbamate, thiocarbamate, dichloropropene, dichloroisonicotinic acid, allylisothiazide, etc. Detailed Implementation

[0080] The preparation method of the present invention will be further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanatory of the present invention and should not be construed as limiting the scope of protection of the present invention. All technical solutions implemented based on the content of the present invention are covered within the scope of protection intended by the present invention.

[0081] Unless otherwise specified, the experimental methods used in the following examples are conventional methods in the art; the reagents, raw materials, instruments, equipment, etc. used in the following examples are all commercially available.

[0082] Reagents used

[0083] Except for ethyl acetate, petroleum ether, and dichloromethane, all other reagents were used after being treated to be anhydrous and oxygen-free. The synthetic precursors used were purchased from Bidex Pharmaceuticals, Energie Chemicals, and Aladdin Group, and the metal catalysts used were purchased from Saan Chemicals.

[0084] Instruments and equipment

[0085] Measurements were performed using both a Bruker DPX500 and a Varian Mercury 400 nuclear magnetic resonance spectrometer. 1 H, 13 C 19 F NMR spectrum, in which 1 H NMR and 13 In the 10⁻⁶ C NMR analysis, tetramethylsilane (TMS) was used as an internal standard, and all chemical shifts were expressed in ppm. High-resolution mass spectrometry was performed using a Bruker Apex IV FTMS spectrometer and a Thermo Q-Exactive HRMS instrument. Infrared spectroscopy was performed using a Nicolet AVATAR 330FT-IR spectrometer.

[0086] The synthesis, bioactivity, and related applications of the representative 2,5-oxazole compounds of formula (I) of the present invention are illustrated by way of preparation examples and biological examples.

[0087] Based on the following general synthetic routes I-III, those skilled in the art can synthesize and characterize the various compounds listed in Tables 1-6 using the corresponding conventional and known starting materials.

[0088] General synthetic route I (applicable to the preparation of compounds numbered A, B, or C in Tables 1-3 below):

[0089]

[0090] The substituted aryl carboxylic acid (20.0 mmol) was placed in a reaction flask, and 30.0 mL of dichloromethane was added. While stirring, N,N'-carbonyldiimidazole (30.0 mmol) and propargylamine (22.0 mmol) were added. After the reaction was complete as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compound GA-1.

[0091] Compound GA-1 (10.0 mmol) was placed in a reaction flask, and diphenyldiselenoether (1.0 mmol), 10.0 mL of acetonitrile and water (10.0 mmol) were added. 1-Chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octane di(tetrafluoroborate) salt (22.0 mmol) was added with stirring. After the reaction was complete as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compound GA-2.

[0092] Compound GA-2 (10.0 mmol) was placed in a reaction flask, and 10.0 mL of methanol was added. Sodium borohydride (15.0 mmol) was then added with stirring. After the reaction was complete as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compound GA-3.

[0093] Compound GA-3 (10.0 mmol) was placed in a reaction flask, and 10.0 mL of dichloromethane was added. Then, 15.0 mmol of thionyl chloride was added with stirring. After the reaction was complete as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compound GA-4.

[0094] Nitrophenol (5.0 mmol) substituted at the para (for compounds in series A), meta (for compounds in series B), or ortho (for compounds in series C) position was placed in a reaction flask. 8.0 mL of N,N-dimethylformamide was added, followed by the addition of cesium carbonate (15.0 mmol) and compound GA-4 (5.0 mmol) with stirring. The reaction was monitored by TLC until complete. After concentration, the mixture was extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined. The mixture was dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compound GA-5.

[0095] Compound GA-5 (1.0 mmol) was placed in a reaction flask, and 2.5 mL of ethanol and 2.5 mL of water were added. While stirring, reduced iron powder (5.0 mmol) and ammonium chloride (5.0 mmol) were added. TLC showed that the starting material largely disappeared. The mixture was extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compound GA-6.

[0096] Compound GA-6 (0.5 mmol) was placed in a reaction flask, and 3.0 mL of solvent was added. Then, with stirring, a base and compound R1-X or R2-Y or X-R1-R2-Y (0.75 mmol) were added, and the reaction was carried out at the appropriate temperature. After the reaction was completed, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compounds numbered A, B, or C in Tables 1-3 below.

[0097] General Synthetic Route II (applicable to the preparation of compounds numbered A, B, or C in Tables 1-3 below):

[0098]

[0099] The substituted aryl carboxylic acid (20.0 mmol) was placed in a reaction flask, and 30.0 mL of dichloromethane was added. While stirring, N,N'-carbonyldiimidazole (30.0 mmol) and propargylamine (22.0 mmol) were added. After the reaction was complete as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compound GB-1.

[0100] Compound GB-1 (10.0 mmol) was placed in a reaction flask, and diphenyldiselenoether (1.0 mmol), 10.0 mL of acetonitrile and water (10.0 mmol) were added. 1-Chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octane di(tetrafluoroborate) salt (22.0 mmol) was added with stirring. After the reaction was complete as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compound GB-2.

[0101] Compound GB-2 (10.0 mmol) was placed in a reaction flask, and 10.0 mL of methanol was added. Sodium borohydride (15.0 mmol) was then added with stirring. After the reaction was complete as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compound GB-3.

[0102] Compound GB-3 (10.0 mmol) was placed in a reaction flask, and 10.0 mL of dichloromethane was added. Then, 15.0 mmol of thionyl chloride was added with stirring. After the reaction was completed by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compound GB-4.

[0103] A 5.0 mmol para-(for compounds in series A), meta-(for compounds in series B), or ortho-(for compounds in series C) substituted bromophenol was placed in a reaction flask. 8.0 mL of N,N-dimethylformamide was added, followed by the addition of 15.0 mmol cesium carbonate and compound GB-4 (5.0 mmol) with stirring. After the reaction was complete as detected by TLC, the mixture was concentrated, extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined. The mixture was dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compound GB-5.

[0104] Compound GB-5 (1.0 mmol) was placed in a Schlenk reaction flask, and 1.5 mL of 1,4-dioxane was added, followed by N2 purging. Tris(dibenzylacetone)dipalladium (0.05 mmol), 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl (0.10 mmol), amino compound NHR1R2 (1.50 mmol), and sodium tert-butoxide (1.6 mmol) were added sequentially, followed by N2 purging three times. TLC analysis showed a significant disappearance of the starting material. Extraction was performed with water and dichloromethane, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue separated by column chromatography to obtain compounds numbered A, B, or C in Tables 1–3 below.

[0105] General Synthetic Route III (applicable to the preparation of compounds numbered D, E, or F in Tables 4-6 below):

[0106]

[0107] The substituted aryl carboxylic acid (20.0 mmol) was placed in a reaction flask, and 30.0 mL of dichloromethane was added. While stirring, N,N'-carbonyldiimidazole (30.0 mmol) and propargylamine (22.0 mmol) were added. After the reaction was complete as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compound GC-1.

[0108] Compound GC-1 (10.0 mmol) was placed in a reaction flask, and diphenyldiselenoether (1.0 mmol), 10.0 mL of acetonitrile and water (10.0 mmol) were added. 1-Chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octane di(tetrafluoroborate) salt (22.0 mmol) was added with stirring. After the reaction was complete as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compound GC-2.

[0109] Compound GC-2 (10.0 mmol) was placed in a reaction flask, and 10.0 mL of methanol was added. Sodium borohydride (15.0 mmol) was then added with stirring. After the reaction was complete as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compound GC-3.

[0110] Compound GC-3 (10.0 mmol) was placed in a reaction flask, and 10.0 mL of dichloromethane was added. Then, 15.0 mmol of thionyl chloride was added with stirring. After the reaction was completed by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compound GC-4.

[0111] 5.0 mmol of tert-butyl (hydroxyphenyl)piperazine-1-carboxylate, substituted at the para (for compounds in series D), meta (for compounds in series E), or ortho (for compounds in series F) position relative to the hydroxyl group on the benzene ring, was placed in a reaction flask. 8.0 mL of N,N-dimethylformamide was added, followed by the addition of cesium carbonate (15.0 mmol) and compound GC-4 (5.0 mmol) with stirring. After the reaction was complete as detected by TLC, the mixture was concentrated, extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined. The residue was separated by column chromatography to obtain compound GC-5.

[0112] Compound GC-5 (1.0 mmol) was placed in a reaction flask, and a 4 M, 2.0 mL solution of 1,4-dioxane in hydrochloric acid was added. The mixture was stirred and allowed to react at room temperature. After the reaction was complete as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain compound GC-6.

[0113] Compound GC-6 (0.5 mmol) was placed in a reaction flask, and 2.0 mL of dichloromethane was added. Triethylamine (1.0 mmol) was then added while stirring, followed by the addition of the corresponding compound R. 11 -LG (0.75 mmol, where LG is the corresponding leaving group), reaction at room temperature. After the reaction was complete as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, and the residue was separated by column chromatography to obtain compounds numbered D, E, or F in Tables 4–6 below.

[0114] Compound Examples

[0115] In the following description, those skilled in the art can synthesize the compounds of the present invention by referring to the general synthetic routes A to E described above, based on the preparation examples. The series of compounds numbered starting with A, B, C, D, E, F, G, and H correspond to the following general formulas:

[0116] A: B:

[0117] C: D:

[0118] E: F:

[0119] In the following lists 1-6, "Me" represents methyl, "Et" represents ethyl, "iPr" represents isopropyl, "nBu" represents n-butyl, "tBu" represents tert-butyl, "3-Py" represents pyridin-3-yl, and "Ac" represents acetyl.

[0120] Example 1

[0121]

[0122] first step:

[0123]

[0124] 10.0 g of compound a1-1 was placed in a reaction flask, 100 mL of dichloromethane was added, and stirring was started. 12.7 g of N,N'-carbonyldiimidazole and 3.2 g of propargylamine were added at room temperature, and the reaction was allowed to proceed overnight at room temperature. After the reaction was completed as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, and separated by column chromatography to obtain 10.3 g of compound a1-2.

[0125] Step Two:

[0126]

[0127] 10.0 g of compound a1-2 was placed in a reaction flask, and 1.37 g of diphenyldiselenes, 50 mL of acetonitrile, and 0.79 g of water were added. 34.16 g of 1-chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octane di(tetrafluoroborate) salt was added with stirring, and the reaction was carried out at room temperature for 12 hours. After the reaction was complete as detected by TLC, the mixture was extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined, dried over anhydrous sodium sulfate, and separated by column chromatography. 8.60 g of compound a1-3 was obtained by column chromatography.

[0128] Step 3:

[0129]

[0130] 8.0 g of compound a1-3 was placed in a reaction flask, 40 mL of methanol was added, and 1.88 g of sodium borohydride was added with stirring. After 2 hours of reaction, TLC was used to detect the completion of the reaction. The mixture was extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined, dried over anhydrous sodium sulfate, and separated by column chromatography to obtain 7.50 g of compound a1-4.

[0131] Step 4:

[0132]

[0133] 7.0 g of compound a1-4 was placed in a reaction flask, 35 mL of dichloromethane was added, and 3.12 mL of thionyl chloride was added with stirring. After the reaction was completed by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, and separated by column chromatography to obtain 6.5 g of compound a1-5.

[0134] Step 5:

[0135]

[0136] 1.0 g of 3-nitrophenol was placed in a reaction flask, and 20 mL of N,N-dimethylformamide was added. 7.04 g of cesium carbonate and 1.89 g of compound a1-5 were added with stirring. The reaction was monitored by TLC until complete. The mixture was extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined. The mixture was dried over anhydrous sodium sulfate and separated by column chromatography to obtain 2.15 g of compound a1-6.

[0137] Step 6:

[0138]

[0139] 250 mg of compound a1-6 was placed in a reaction flask, and 2.5 mL of ethanol and 2.5 mL of water were added. 192 mg of reduced iron powder and 183 mg of ammonium chloride were added with stirring, and the reaction was carried out at 60°C. TLC showed that the starting material had largely disappeared. The mixture was extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined. The mixture was dried over anhydrous sodium sulfate and separated by column chromatography to obtain 115 mg of compound a1-7.

[0140] Step 7:

[0141]

[0142] 100 mg of compound a1-7 was placed in a reaction flask, 3.0 mL of tetrahydrofuran was added, and 12.9 mg of sodium hydride was added with stirring. After reacting for 30 minutes, 28 μL of iodomethane was added, and the reaction was allowed to proceed at room temperature. The reaction was detected by TLC after completion. The mixture was extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined. The resulting solution was obtained by preparative thin-layer chromatography to yield 43 mg of compound B-002.

[0143] Example 2

[0144]

[0145] first step:

[0146]

[0147] 10.0 g of compound a2-1 was placed in a reaction flask, 100 mL of dichloromethane was added, and stirring was started. 12.7 g of N,N'-carbonyldiimidazole and 3.2 g of propargylamine were added at room temperature, and the reaction was allowed to proceed overnight at room temperature. After TLC detection, the reaction was extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined, dried over anhydrous sodium sulfate, and separated by column chromatography to give 10.3 g of compound a2-2, with a yield of 86%.

[0148] Step Two:

[0149]

[0150] 10.0 g of compound a2-2 was placed in a reaction flask, and 1.37 g of diphenyldiselenes, 50 mL of acetonitrile, and 0.79 g of water were added. 34.16 g of 1-chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octane di(tetrafluoroborate) salt was added with stirring, and the reaction was carried out at room temperature for 12 hours. After the reaction was complete as detected by TLC, the mixture was extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined, dried over anhydrous sodium sulfate, and separated by column chromatography. 8.60 g of compound a2-3 was obtained by column chromatography.

[0151] Step 3:

[0152]

[0153] 8.0 g of compound a2-3 was placed in a reaction flask, 40 mL of methanol was added, and 1.88 g of sodium borohydride was added with stirring. After 2 hours of reaction, TLC was used to detect the completion of the reaction. The mixture was extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined, dried over anhydrous sodium sulfate, and separated by column chromatography to obtain 7.50 g of compound a2-4.

[0154] Step 4:

[0155]

[0156] 7.0 g of compound a2-4 was placed in a reaction flask, 35 mL of dichloromethane was added, and 3.12 mL of thionyl chloride was added with stirring. After the reaction was completed by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, and separated by column chromatography to obtain 6.5 g of compound a2-5.

[0157] Step 5:

[0158]

[0159] 1.0 g of 3-bromophenol was placed in a reaction flask, and 20 mL of N,N-dimethylformamide was added. While stirring, 5.65 g of cesium carbonate and 1.52 g of compound a2-5 were added. The reaction was monitored by TLC until complete. The mixture was extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined. The mixture was dried over anhydrous sodium sulfate and separated by column chromatography to obtain 1.94 g of compound a2-6.

[0160] Step 6:

[0161]

[0162] 200 mg of compound a2-6 was placed in a reaction flask, and 4.0 mL of 1,4-dioxane, 71.0 mg of 3-aminopyridine, 23.0 mg of tridibenzylacetone dipalladium, 24.0 mg of 2-dicyclohexylphosphine-2',4',6'-triisopropylbiphenyl, and 77.0 mg of sodium tert-butoxide were added. The mixture was purged with nitrogen three times and reacted at 110°C. After 12 hours of reaction, the product was detected by TLC. 10 mL of water was added, and the mixture was extracted three times with 10 mL of dichloromethane. The combined organic layers were washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate. Preparative thin-layer chromatography yielded 76 mg of compound B-011.

[0163] Using a method similar to that of Example 1 or Example 2, and referring to general synthetic routes I-II, the compounds numbered starting with A, B, and C in Tables 1-3 below can be obtained by substituting the starting materials.

[0164] Table 1 shows compounds of formula A according to the present invention.

[0165]

[0166] Table 2 shows compounds of formula B according to the present invention.

[0167]

[0168]

[0169] Table 3 shows compounds of formula C according to the present invention.

[0170]

[0171] Example 3

[0172]

[0173] first step:

[0174]

[0175] 1.0 g of compound a3-1 was placed in a reaction flask, 10 mL of dichloromethane was added, and stirring was started. 1.99 g of N,N'-carbonyldiimidazole and 496 mg of propargylamine were added at room temperature, and the reaction was allowed to proceed overnight at room temperature. After the reaction was complete as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, and separated by column chromatography to give 1.17 g of compound a3-2.

[0176] Step Two:

[0177]

[0178] 200 mg of compound a3-2 was placed in a reaction flask, and 39 mg of diphenyldiselenoether, 4.0 mL of acetonitrile, and 23 mg of water were added. 0.98 g of 1-chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octane di(tetrafluoroborate) salt was added with stirring, and the reaction was carried out at room temperature for 12 hours. After the reaction was complete as detected by TLC, the mixture was extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined, dried over anhydrous sodium sulfate, and separated by column chromatography. Column chromatography yielded 183 mg of compound a3-3.

[0179] Step 3:

[0180]

[0181] 180 mg of compound a3-3 was placed in a reaction flask, 4.0 mL of methanol was added, and 59 mg of sodium borohydride was added with stirring. After 2 hours of reaction, TLC was used to detect the completion of the reaction. The mixture was extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined, dried over anhydrous sodium sulfate, and separated by column chromatography to obtain 145 mg of compound a3-4.

[0182] Step 4:

[0183]

[0184] 140 mg of compound a3-4 was placed in a reaction flask, 4.0 mL of dichloromethane was added, and 0.50 mL of thionyl chloride was added with stirring. After the reaction was completed by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, and separated by column chromatography to obtain 120 mg of compound a3-5.

[0185] Step 5:

[0186]

[0187] 172 mg of 1-(3-hydroxyphenyl)-piperazine-4-carboxylic acid tert-butyl ester was placed in a reaction flask, and 5.0 mL of N,N-dimethylformamide was added. With stirring, 605 mg of cesium carbonate and 120 mg of compound a3-5 were added. After the reaction was complete as detected by TLC, water and dichloromethane were added for extraction, followed by washing with saturated brine. The combined organic layers were dried over anhydrous sodium sulfate and separated by column chromatography to obtain 210 mg of compound a3-6.

[0188] Step 6:

[0189]

[0190] 200 mg of compound a3-6 was placed in a reaction flask, and 4.0 mL of 1,4-dioxane was added. 1.0 mL of concentrated hydrochloric acid was added with stirring. After 3 hours of reaction, TLC analysis showed the reaction was complete. The mixture was concentrated, and the pH was adjusted to 9.0 using saturated sodium carbonate solution. Extraction was performed with water and dichloromethane, followed by washing with saturated brine. The organic layers were combined, dried over anhydrous sodium sulfate, and separated by column chromatography to obtain 140 mg of compound a3-7.

[0191] Step 7:

[0192]

[0193] 100 mg of compound a1-7 was placed in a reaction flask, and 3.0 mL of dichloromethane was added. While stirring, 124 μL of triethylamine and 42 μL of dimethyl sulfate were added, and the reaction was allowed to proceed at room temperature. After 5 hours of reaction, TLC was used to determine the completeness of the reaction. The reaction was quenched with sodium hydroxide solution (2M), and the mixture was extracted with water and dichloromethane, washed with saturated brine, and the organic layers were combined. The mixture was dried over anhydrous sodium sulfate, concentrated, and then separated by preparative thin-layer chromatography to obtain 47 mg of compound E-001.

[0194] Using a method similar to that in Example 3, and referring to General Synthetic Route III, the compounds numbered D, E, and F in Tables 4-6 below can be obtained by substituting the starting materials.

[0195] Table 4 shows compounds of formula D according to the present invention.

[0196]

[0197] Table 5 shows compounds of formula E according to the present invention.

[0198]

[0199]

[0200] Table 6 shows compounds of formula F according to the present invention.

[0201]

[0202] Table 7: Compound Structure Characterization Data

[0203] Table 7 shows the mass spectrometry data of the compounds listed in Tables 1-6 or 1 H-NMR data. Unless otherwise specified, deuterated chloroform (CDCl3) or deuterated dimethyl sulfoxide (DMSO-d6) is used as the test solvent.

[0204] In Table 7 and throughout the following description, "NMR" refers to nuclear magnetic resonance spectroscopy, and "MS" represents mass spectrometry. The following abbreviations will also be used:

[0205] s = single peak, br = broad peak, d = double peak, dd = double double peak, t = triple peak, td = triple double peak, q = quartet, m = multiple peak.

[0206] Table 7

[0207]

[0208]

[0209]

[0210]

[0211]

[0212]

[0213]

[0214] Biological Examples

[0215] Given that *Pyrrosia lingua* typically infects plants via appressorium-mediated infection and can be cultured artificially indoors, *Pyrrosia lingua* can be used as a model pathogen to test the inhibitory effects of the compounds of this invention on conidial germination, germ tube growth, or appressorium formation. The relevant activities of the compounds of this invention are illustrated by the following examples.

[0216] Biological Example G1: Inhibitory effect of oxazole compounds on conidial germination and appressorium formation of *Pyrrosia lingua*

[0217] a. Pathogen to be tested: Pyricularia oryzae strain P131

[0218] b. Test methods:

[0219] 1) Production of conidia of *Magnaporum oryzae*: The *Magnaporum oryzae* strain P131 was inoculated onto tomato-oat agar plates (OTA) and incubated at 28°C under constant temperature and light. After 3-5 days, the *Magnaporum oryzae* colonies on the OTA were thoroughly broken up and then evenly spread onto new OTA plates, and incubated at 28°C under constant temperature and light. When new hyphae are visible to the naked eye growing on the surface of the culture medium (usually 1-2 days), the hyphae are gently broken up with a cotton swab, rinsed with sterile water, and dried. The culture dish is then covered with a single layer of gauze and incubated at 28°C under light for 48 hours, resulting in the production of a large number of conidia on the surface of the OTA.

[0220] 2) Preparation of *Blastomyces oryzae* conidia suspension: Elute the culture from the OTA with sterile water, filter through three layers of lens paper, and the filtrate is the conidia suspension. Adjust the conidia concentration in the conidia suspension to 2 × 10⁻⁶ using a hemocytometer. 5 per mL.

[0221] 3) The test compounds were added to the conidial suspension at different concentration gradients to prepare working concentrations of 25 ppm and 12.5 ppm, and then spotted sequentially onto hydrophobic glass slides. Four spots were spotted on each slide, and the slides were kept in the dark and moist. Twelve hours after inoculation, the conidial germination rate and appressorium formation rate were observed and counted under a microscope.

[0222] 4) Statistics and Analysis: Three inoculation points were counted on each hydrophobic slide. At each inoculation point, the number of germinations of 100 conidia and the number of appressorium formations at its center were counted. The average of the three sets of data was calculated to obtain the conidia germination rate and appressorium formation rate.

[0223] Table 8 shows data for biological examples G1 of some compounds in Tables 1-6, where “-” indicates no inhibitory effect at 25 ppm, “+” indicates an inhibitory effect of less than 40% at 25 ppm, “++” indicates an inhibitory effect of more than 40% at 25 ppm, and “+++” indicates an inhibitory effect of more than 40% at 12.5 ppm.

[0224] Table 8

[0225]

[0226]

[0227]

[0228] Biological Example G2: Control of Rice Blast by Oxazole Compounds—Rice Pot Experiment

[0229] Preparation of rice: Take four-leaf, one-heart rice seedlings of the susceptible variety CO39 and place them in an inoculation box for later use.

[0230] Production of conidia of *Magnaporum oryzae*: *Magnaporum oryzae* strain P131 was inoculated onto tomato-oat agar plates (OTA) and incubated at 28°C under constant temperature and light. After 3-5 days, the *Magnaporum oryzae* colonies on the OTA were thoroughly broken up and then evenly spread onto new OTA plates, and incubated at 28°C under constant temperature and light. When new mycelia are visibly growing on the surface of the culture medium (generally 1-2 days), the mycelia are gently broken up with a cotton swab, rinsed with sterile water, and dried. The culture dish is then covered with a single layer of gauze and incubated at 28°C under light for 48 hours, resulting in the production of numerous conidia on the OTA surface.

[0231] Preparation of *Magnapordica oryzae* conidia suspension: Elute the culture from the OTA with sterile water, filter through three layers of lens paper, and the filtrate is the conidia solution. Centrifuge at 5000 rpm at room temperature for 5 minutes. Resuspend the precipitated conidia in gelatin, and adjust the conidia concentration to 5 × 10⁻⁶ using a hemocytometer. 4 per mL.

[0232] Preparation of the test compound solution: The mother liquor of the test compound was added to the prepared rice blast fungus conidial solution and diluted to a working concentration of 200 ppm.

[0233] Spray inoculation: A mixture of rice blast fungus conidia and a small-molecule fungicide was sprayed onto susceptible rice varieties Xiangwanxian 11 and CO39, with 15 mL of the mixture sprayed onto each treatment. The mixture was incubated in the dark under moist conditions for 36 hours, followed by normal incubation. The control efficacy of the test compounds against rice blast was evaluated 7 days after inoculation.

[0234] Table 9 shows data for biological examples G2 of some of the compounds in Tables 1-6.

[0235] Rice blast leaf blast disease surveys were conducted according to the agricultural industry standard "Technical Regulations for Field Monitoring of Rice Blast Resistance" (NYT3685-2020). Specific standards are as follows: Grade 0: No disease on the entire leaf; Grade 1: Small brown necrotic spots on the leaf; Grade 2: Larger brown necrotic spots (1mm-2mm in diameter) on the leaf, but no typical lesions; Grade 3: Typical rice blast lesions, lesion area <2%; Grade 4: Typical rice blast lesions, 2% ≤ lesion area <5%; Grade 5: Typical rice blast lesions, 5% ≤ lesion area <10%; Grade 6: Typical rice blast lesions, 10% ≤ lesion area <25%; Grade 7: Typical rice blast lesions, 25% ≤ lesion area <50%; Grade 8: Typical rice blast lesions, 50% ≤ lesion area <75%; Grade 9: Typical rice blast lesions, lesion area ≥75%.

[0236] Table 9

[0237]

[0238]

[0239] Biological Example G3: Control Effect of Oxazole Compounds on Potato Late Blight—Potato Pot Experiment

[0240] Potato preparation: After normal cultivation, seedlings of the potato late blight susceptible variety "Desiree" are placed in an inoculation box for later use.

[0241] Potato late blight sporangium preparation: Select the medium-strength strain "MZ", culture it on a suitable culture medium, and after sporangia are produced, wash the sporangia with sterile water, filter it with double-layer gauze to make a sporangium suspension, place it at a low temperature of 4℃ in the dark for 3 hours, and store it for later use.

[0242] Preparation of sporangium suspension: Adjust the prepared sporangium solution treated with sterile water at 4℃ to prepare a concentration of 4×10⁻⁶. 3 A suspension of cells / mL.

[0243] Preparation of spray working solution: Dilute the mother liquor of the compound to be tested with water to a working concentration of 200 ppm.

[0244] Spray inoculation: Before inoculation, the plants to be treated were placed in an artificial climate greenhouse at 20℃ for acclimatization 4 hours in advance. After acclimatization, the working solution was evenly sprayed on both sides of the leaves of the treated plants. Two plants were treated per treatment, and each plant was sprayed with 60 mL of the working solution. After air drying with the working solution, the plants were cultured normally for 24 hours. Then, the plants were sprayed with the prepared sporangium suspension. After 24 hours of dark treatment, the plants were cultured under normal light (20℃, 18h light / 6h dark). The disease situation was observed at any time. The control effect of the test compound on potato late blight was evaluated after 7 days.

[0245] Table 10 shows the data for biological example G3 of some compounds in Tables 1-6. The severity of potato late blight was investigated according to the grading criteria as follows: Grade 0: No lesions; Grade 1: Lesion area less than 5% of the total leaf area; Grade 3: Lesion area 6%-10% of the total leaf area; Grade 5: Lesion area 11%-20% of the total leaf area; Grade 7: Lesion area 21%-50% of the total leaf area; Grade 9: Lesion area more than 50% of the total leaf area.

[0246] Table 10

[0247] compound Disease level B-004 1 D-004 5 E-005 0 E-006 1 E-009 3 E-019 1 E-021 3

[0248] Biological Example G4: Control Effect of Oxazole Compounds on Anthracnose in Maize—Maize Pot Experiment

[0249] Preparation of corn: Cultivate corn Mo17 seedlings to the three-leaf and one-heart stage, and place them in an inoculation box for later use.

[0250] Anthrax conidia preparation: *Anthracis granatum* strain M2 was selected. Edge hyphae of the isolated anthracis fungus were transferred to fresh PDA + 0.1% YE agar plates and cultured for 4 days. The hyphae growing on the plates were broken with sterile cotton swabs to promote conidia production. Conidia were then transferred to sterile water and vortexed. Subsequently, 50 μL of the conidia suspension was added dropwise to WA agar plates, spread dry with a spreader, and incubated in the dark at 28°C. After conidia germination, each germinated conidia was individually picked up under a stereomicroscope and cultured in fresh PDA medium in the dark at 28°C.

[0251] Preparation of anthrax conidia suspension: Elute the culture from the PDA with sterile water, filter through three layers of lens paper, the filtrate is the conidia solution, and adjust the conidia concentration to 1×10⁻⁶ using a hemocytometer. 5 per mL.

[0252] Preparation of spray inoculation working solution: Dilute the mother liquor of the test compound with water to a working concentration of 200 ppm.

[0253] Spray inoculation: Spray the working solution evenly onto the leaf surface until the leaves are covered with droplets. Use 3 plants per treatment. After the solution has air-dried naturally, inoculate with a conidial suspension. After inoculation, transfer to a humidity chamber for dark incubation for 24 hours, and then incubate at 25°C, light, and 80% humidity. Evaluate the control effect of the test compound 5 days after inoculation.

[0254] Table 11 shows the data for biological examples G4 of some compounds in Tables 1-2. The disease severity of maize anthracnose was investigated according to the following grading standards: Grade 0: No symptoms; Grade 1: Small brown spots or lesions less than 5% of leaf area; Grade 3: Nearly circular or spindle-shaped brown lesions covering 5%–10% of leaf area; Grade 5: Black necrotic spots or patches of lesions covering 11%–25% of leaf area; Grade 7: Enlarging black necrotic spots or leaf margin necrosis covering 26%–50% of leaf area; Grade 9: Lesions covering more than 50% of leaf area, or leaf necrosis.

[0255] Table 11

[0256] compound Disease level B-004 1 D-004 3 E-005 0 E-006 1 E-009 3 E-019 1 E-020 3

[0257] Biological Example G5: Control of Gray Mold in Strawberries by Oxazole Compounds—Strawberry Fruit Experiment

[0258] Preparation of strawberries: "Hongyan" strawberry fruits are disinfected with alcohol and then placed in an inoculation box for later use.

[0259] Preparation of Botrytis cinerea conidia suspension: Elute the culture grown on the PDA for 7 days with sterile water, filter through three layers of lens paper, the filtrate is the conidia suspension, and adjust the conidia concentration to 1×10 using a hemocytometer. 5 per mL.

[0260] Preparation of inoculation working solution: Add the mother liquor of the compound to be tested to the prepared Botrytis cinerea spore solution and dilute it to a working concentration of 100 ppm.

[0261] Inoculation: Make a 3mm diameter, 10mm deep hole in the shoulder of each strawberry fruit and inject 6ml of working solution. Five fruits are treated per inoculation. Subsequent inoculated treatments are cultured at 21℃ in the dark for 12 hours, then transferred to 12h / 12h light / dark alternating conditions. Observe daily for disease development. Evaluate the control efficacy of the test compound 5 days after inoculation.

[0262] Table 12 shows the data of biological example G5 of the compound of the present invention. The disease status of strawberry gray mold was investigated according to the grading standard as follows: Grade 0: No disease; Grade 1: Lesion area accounts for less than 5% of the fruit area; Grade 3: Lesion area accounts for 5% to 10% of the fruit area; Grade 5: Lesion area accounts for 11% to 25% of the fruit area; Grade 7: Lesion area accounts for 26% to 50% of the fruit area; Grade 9: Lesion area accounts for more than 50% of the fruit area, or leaves wither.

[0263] Table 12

[0264] compound Disease level B-004 1 D-004 5 E-005 0 E-006 0 E-009 1 E-019 3 E-021 1

[0265] Biological Example G6: Control Effect of Oxazole Compounds on Wheat Fusarium Head Blight—Wheat Pot Experiment

[0266] Preparation of wheat: The wheat variety "Fielder" was cultured normally until the ear and grain flowering stage, and then placed in an inoculation box for later use.

[0267] Preparation of Fusarium spore suspension: Fusarium spore cakes grown on PDA medium for 5 days were placed in CM liquid medium and incubated at 28℃ and 180 rpm for 7 days. The solution was filtered through three layers of lens paper; the filtrate was the spore suspension. The conidial concentration was adjusted to 1×10⁻⁶ using a hemocytometer. 5 per mL.

[0268] Preparation of inoculation working solution: Add the mother liquor of the compound to be tested to the prepared Fusarium spore solution and dilute it to a working concentration of 200 ppm.

[0269] Inoculation: Using a pipette, inject 10 mL of working solution into wheat ears before flowering, 5 ears per treatment. Afterward, maintain humidity for two days and then culture normally. Observe daily for disease development, and evaluate the control effect of the test compound 14 days after inoculation.

[0270] Table 13 shows the data of biological example G6 of the compound of the present invention. The disease of wheat scab was investigated with reference to the grading standard, and the specific standard is as follows: Grade 0: no disease; Grade 1: less than 5% of the total number of diseased grains; Grade 3: 5% to 10% of the total number of diseased grains; Grade 5: 11% to 25% of the total number of diseased grains; Grade 7: 26% to 50% of the total number of diseased grains; Grade 9: more than 50% of the total number of diseased grains.

[0271] Table 13

[0272] compound Disease level B-004 3 D-004 5 E-005 0 E-006 1 E-009 0 E-019 1 E-021 0

[0273] Biological Example G7: Control Effect of Oxazole Compounds on Phytophthora blight in Peppers—Pot Experiment with Peppers

[0274] Preparation of chili peppers: After two weeks of normal cultivation, the "horn pepper" seedlings are placed in an inoculation box for later use.

[0275] Preparation of *Fusarium graminearum* spore suspension: *Phytophthora capsici* strain BYA5 was cultured on PDA medium for 10 days. After soaking in a small amount of sterile water, it was placed in the dark at 4°C for 3 hours and stored for later use. The treated sporangia solution was adjusted with sterile water at 4°C to a concentration of 1×10⁻⁶. 5 A suspension of cells / mL.

[0276] Preparation of the inoculation working solution: Dilute the mother liquor of the test compound with water to a working concentration of 200 ppm.

[0277] Inoculation: Five plants were treated per treatment. Each plant was sprayed with 20 mL of the compound working solution and allowed to air dry naturally. Then, the roots were drenched with 10 mL of the prepared spore suspension. After 24 hours of dark treatment, the plants were cultured under normal light (20℃, 18 hours light / 6 hours dark). Disease development was observed at all times. The control effect of the test compound on pepper blight was evaluated after 5-7 days.

[0278] Table 14 shows the data for biological example G8 of the compounds of the present invention (average values ​​for each treatment). The investigation of pepper blight disease was conducted according to the agricultural industry standard "Technical Specification for Identification of Pepper Disease Resistance Part 1: Technical Specification for Identification of Pepper Disease Resistance" (NY / T2060.1-2011), with the following specific standards: Grade 0: No symptoms; Grade 1: Slight blackening of the seedling root and stem, leaves do not wilt or wilt recoverably; Grade 2: Blackening of the seedling root and stem up to 1-2 cm, leaves wilt irreversibly, lower leaves occasionally fall off; Grade 3: Blackening of the seedling root and stem exceeding 2 cm, leaves obviously wilted or obvious leaf drop; Grade 4: Blackening and constriction of the seedling root and stem, all leaves except the growing point fall off or the plant wilts; Grade 5: Plant dies.

[0279] Table 14

[0280] compound Disease level B-004 3 D-004 2 E-005 1 E-006 1 E-009 2 E-019 3 E-021 2

[0281] Biological Example G8: Control Effect of Oxazole Compounds on Rice False smut—Rice Field Trial

[0282] Test location: Donggang City, Liaoning Province

[0283] Rice variety: Liaoxing No. 1

[0284] Preparation of spray working solution: Add the stock solution of the compound to be tested to water and dilute it to a working concentration of 600 ppm and 300 ppm.

[0285] Experimental protocol: The working solution was transferred to a handheld sprayer, and the first application was carried out at the heading stage, followed by a second application at the heading stage. A disease survey was conducted 30 days after the second application to evaluate the control effect.

[0286] Table 15 shows the data of biological example G8 of the compound of the present invention. The disease condition of rice false smut was investigated according to the grading standard, the disease index was calculated and the control efficacy was calculated.

[0287] Table 15

[0288] compound Concentration (ppm) Number of diseased ears (plant) Diseased ear rate % Disease index % efficacy <![CDATA[H2O]]> - 114 0.5429 0.29 - E-005 600 12 0.0889 0.04 87.38±0.87 E-005 300 33 0.2 0.06 77.28±2.48

[0289] Biological Example G9: Control of Rice False smut by oxazole compounds—Rice field trial

[0290] Test location: Xianfeng City, Hubei Province

[0291] Rice variety: Yixiangyou 66

[0292] Preparation of spray working solution: Add the stock solution of the compound to be tested to water and dilute it to a working concentration of 600 ppm and 300 ppm.

[0293] Experimental protocol: The working solution was transferred to a handheld sprayer, and the first application was carried out at the heading stage, followed by a second application at the heading stage. A disease survey was conducted 30 days after the second application to evaluate the control effect.

[0294] Table 16 shows the data of biological example G9 of the compound of the present invention. The disease condition of rice false smut was investigated with reference to the grading standard, the disease index was calculated and the control efficacy was calculated.

[0295] Table 16

[0296] compound Concentration (ppm) Number of diseased ears (plant) Diseased ear rate % Disease index % efficacy CK (Shimizu) - 54 24 13.65 - E-005 600 12 5.33 2.03 85.13±1.57 E-005 300 19 8.44 3.05 77.66±3.22

[0297] The above description provides an exemplary account of the implementation methods of the technical solution disclosed herein. It should be understood that the scope of protection of this disclosure is not limited to the above-described embodiments. Any modifications, equivalent substitutions, or improvements made by those skilled in the art within the spirit and principles of this disclosure should be included within the scope of protection of the claims of this application.

Claims

1. The compound represented by formula (I), its stereoisomers, racemates, tautomers, isotopic labels, nitrogen oxides, agriculturally acceptable salts or esters, solvates, or solvates of agriculturally acceptable salts: in, R1 and R2 independently represent H, either unsubstituted or represented by one, two or more Rs. 10 The following groups are substituted independently of each other: C1-C 12 Alkyl, C2-C 12 alkenyl, C2-C 12 alkynyl group, C3-C 20 Cycloalkyl, 3-20 membered heterocyclic groups, C6-C 20 Aryl, 5-20 heteroaryl, C1-C 12 Alkyloxy, C1-C 12 Alkyl carbonyl, -C(O)OC1-C 12 Alkyl groups; or R1 and R2 together with the N atom to which they are attached to form an unsubstituted or substituted compound, or one, two or more R atoms. 11 3-20 membered heterocyclic groups that are substituted independently of each other; Each R 10 Whether they are the same or different, they represent H, Cl-C independently of each other. 12 Alkyl, C2-C 12 alkenyl, C2-C 12 alkynyl group, C3-C 20 cycloalkyl, C1-C 12 Alkyl C3-C 20 cycloalkyl, C1-C 12 Alkyl C6-C 20 Aryl, carboxyl, ester, hydroxyl, hydroxyl C1-C 12 Alkyl, amino, -NH (C1-C) 12 Alkyl), -N(C1-C 12 Alkyl group, amide group, nitro group, CN group, azide group, azide group C group 1- C 12 Alkyl, oxo (=O), halogen, mercapto, hydroxyl, -CHO, wherein the carbon chain of the alkyl, alkenyl, or ynyl group, or the ring atom of the cycloalkyl group, may be optionally interrupted by an oxygen atom, a nitrogen atom, or a sulfur atom, or may be optionally oxosubstituted. Each R 11 Whether they are the same or different, they represent H, Cl-C independently of each other. 12 Alkyl, C2-C 12 alkenyl, C2-C 12 alkynyl group, C3-C 20 cycloalkyl, C1-C 12 Alkyl carbonyl, C2-C 12 alkenyl carbonyl, C3-C 20 cycloalkyl carbonyl, C6-C 20 aryl carbonyl, di(C1-C) 12 (alkyl)amino-C1-C 12 Alkyl group, wherein the carbon atom of the alkyl, alkenyl, or alkynyl group, or the ring atom of the cycloalkyl group, may optionally be surrounded by one, two, or more hydroxyl groups, C1-C2. 12 Alkyl carbonyloxy group, C1-C 12 Alkyloxycarbonyl, C2-C 12 alkynyloxy group, azide group -C1-C 12 Alkyloxy-C1-C 12 Alkyloxy, amino-C1-C 12 Alkyloxy-C1-C 12 Alkyloxy, C1-C 12 Alkyloxycarbonyl-C1-C 12 Alkyloxy-C1-C 12 Alkyloxy, C1-C 12 Alkyloxycarbonyl C1-C 12 Alkyl substitution; R3 indicates that it is unsubstituted or replaced by one, two or more R's. 12 The following groups are substituted independently of each other: C6-C 20 Aryl or 5-20 membered heteroaryl, phenyl, pyridyl, thienyl, furanyl, benzothienyl, quinolinyl; Each R 12 The same or different, representing H, halogens, and C1-C independently of each other. 12 Alkyloxy, C6-C 20 aryloxy group, C1-C 12 Alkyl carbonyl, -C(O)OC1-C 12 Alkyl, -C(O)N(C1-C) 12 Alkyl)2.

2. The compound of formula (I) according to claim 1, its stereoisomers, racemates, tautomers, isotope-labeled compounds, nitrogen oxides, agriculturally acceptable salts or esters, solvates, or solvates of agriculturally acceptable salts, wherein, The compound of formula (I) has the structure of formula (I) as follows: R1, R2, and R3 are defined in equation (I).

3. The compound of formula (I) according to claim 1 or 2, its stereoisomers, racemates, tautomers, isotope-labeled compounds, nitrogen oxides, agriculturally acceptable salts or esters, solvates, or solvates of agriculturally acceptable salts, wherein, Compounds of formula (I) have the structure of formula (IA) or (IB): Where R1 and R2 are defined in equation (I), R 121 R 122 R 123 R 124 R 125 Independent of each other, like R 12 Defined.

4. The compound of formula (I) according to any one of claims 1 to 3, its stereoisomers, racemates, tautomers, isotope-labeled compounds, nitrogen oxides, agriculturally acceptable salts or esters, solvates, or solvates of agriculturally acceptable salts, wherein, R1 and R2 independently represent H, either unsubstituted or represented by one, two or more Rs. 10 The following groups are substituted independently of each other: C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C 12 Cycloalkyl, 3-10 membered heterocyclic, C6-C 10 aryl, 5-10 heteroaryl, C1-C6 alkyloxy, C1-C6 alkylcarbonyl, -C(O)OC1-C6 alkyl; or R1 and R2 together with the N atom to which they are attached to form an unsubstituted or substituted compound. 11 3-10 membered heterocyclic groups that are substituted independently of each other; Preferably, R1 and R2 independently represent H, C1-C6 alkyl, C1-C6 alkyloxy, C1-C6 alkylcarbonyl, -C(O)OC1-C6 alkyl, 5-8 heteroaryl, C6-C 10 Aryl, C6-C 10 aryl-C1-C6 alkyl; or R1 and R2 together with the N atom to which they are attached form an unsubstituted compound or are formed by one, two or more R atoms. 11 3-6 membered heterocyclic groups that are substituted independently of each other; Preferably, R1 and R2 independently represent H, methyl, n-butyl, tert-butyl, methoxy, pyridin-3-yl, -C(O)OCH3, acetyl, benzyl, phenyl; or R1 and R2 together with the N atom to which they are attached form a pyrrolidinyl, morpholino-4-yl, or unsubstituted or enclosed by an R 11 Substituted piperidinyl or piperazine group; preferably, with an R 11 The substituted piperazine group is R at the 4-position. 11 Substituted piperazine group; preferably, by an R 11 The substituted piperidinyl group is R-substituted at the 4-position. 11 Substituted piperidinyl group; Preferably, R 10 Indicates C1-C6 alkyl or C6-C 10 Aryl; more preferably, R 10 This indicates methyl, ethyl, n-propyl, isopropyl, and phenyl.

5. The compound of formula (I) according to any one of claims 1 to 4, its stereoisomers, racemates, tautomers, isotope-labeled compounds, nitrogen oxides, agriculturally acceptable salts or esters, solvates, or solvates of agriculturally acceptable salts, wherein, R 11 Represents H, C1-C6 alkyl, C1-C6 alkyl carbonyl, C5-C7 cycloalkyl carbonyl, C6-C 10 aryl carbonyl, C2-C6 alkenyl carbonyl, di(C1-C6 alkyl)amino-C1-C6 alkyl; According to some embodiments of the present invention, R 11 It represents H, methyl, ethyl, isopropyl, acetyl, acryloyl, di(ethylamino)ethyl, cyclopentylformyl, and benzoyl.

6. The compound of formula (I) according to any one of claims 1 to 5, its stereoisomers, racemates, tautomers, isotope-labeled compounds, nitrogen oxides, agriculturally acceptable salts or esters, solvates, or solvates of agriculturally acceptable salts, wherein, R3 indicates that it is unsubstituted or replaced by one, two or more R's. 12 The following groups are substituted independently of each other: C6-C 10 Aryl, 5-10 heteroaryl; Preferably, each R 12 Same or different, independently representing H, halogen, C1-C6 alkyloxy group, C6-C 10 aryloxy, C1-C6 alkyl carbonyl, -C(O)OC1-C6 alkyl, -C(O)N(C1-C6 alkyl)2; Preferably, R3 represents unsubstituted or substituted by one, two or more Rs. 12 The following groups can be substituted independently of each other: phenyl, pyridyl, thienyl, furanyl, benzothienyl, quinolinyl; Preferably, each R 12 They can be the same or different, and can be represented independently as H, F, Cl, methoxy, acetyl, phenoxy, -C(O)OCH3, -C(O)N(CH3)2.

7. The compound of formula (I) according to any one of claims 1 to 6, its stereoisomers, racemates, tautomers, isotope-labeled compounds, nitrogen oxides, agriculturally acceptable salts or esters, solvates, or solvates of agriculturally acceptable salts, wherein, The compounds of formula (I) have the structures shown in Tables 1-6.

8. A pesticide composition, such as a fungicide, herbicide, or plant protectant composition, comprising, as an active ingredient, one, two, or more of a compound of formula (I) according to any one of claims 1 to 7, its stereoisomer, racemate, tautomer, isotope label, nitrogen oxide, agriculturally acceptable salt or ester, solvate, or a solvate of an agriculturally acceptable salt.

9. The pesticide composition according to claim 8, wherein the pesticide composition is a fungicide, the fungicide containing a compound of formula (I) according to any one of claims 1 to 7 and optional agriculturally acceptable adjuvants; Preferably, the pesticide composition is used as a plant protectant to prevent or protect plants from plant diseases, including rice blast, rice false smut, anthracnose, Phytophthora blight, gray mold, and / or Fusarium head blight. More preferably, the disease is selected from rice blast, rice false smut, pepper anthracnose, strawberry gray mold, corn anthracnose, potato late blight, pepper phytosis and / or wheat scab.

10. Use of one, two or more of the following: a compound of formula (I) according to any one of claims 1 to 7, its stereoisomers, racemates, tautomers, isotope labels, nitrogen oxides, agriculturally acceptable salts or esters, solvates, or solvates of agriculturally acceptable salts, for the prevention and control of rice blast, rice false smut, pepper anthracnose, strawberry gray mold, maize anthracnose, potato late blight, pepper Phytophthora blight, and / or wheat scab.

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