Spiro ketal derivative and preparation method and application thereof

Abstract

The invention relates to a spiro ketal derivative as well as a preparation method and application thereof. Specifically, the invention provides a compound as shown in formula (I), or a pharmaceutically acceptable salt or an optical isomer thereof, and the compound has an excellent inhibition effect on plant pathogenic fungi. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the technical field of pesticides, and in particular relates to a spiroketal derivative with fungicidal activity and a preparation method and use thereof. Background Art

[0002] Food is the basis of human survival. With the continuous increase of world population, the pressure of food production is increasing. In the process of food production, diseases, insect pests, weeds and other harmful organisms are the main factors affecting crop production and reducing food yield and quality. Therefore, controlling the occurrence of crop diseases is the key to increasing food yield. Among them, pesticides are a powerful means to inhibit diseases.

[0003] Fungicides, as a member of the pesticide family, are a class of agents used to prevent and treat plant diseases caused by various pathogenic microorganisms. They are a general term for agents that kill pathogens or inhibit their growth, but do not hinder the normal growth of plants. They are an important type of pesticide. However, with the widespread use of fungicides, the resistance of pathogens to these agents is growing, so there is an urgent need to study more new fungicides to solve this problem. Summary of the invention

[0004] The purpose of the present invention is to provide a spiroketal derivative with novel structure and excellent bactericidal activity, and a preparation method and use thereof.

[0005] In a first aspect, the present invention provides a compound of formula (I), or a pesticide-acceptable salt thereof, or an optical isomer thereof,

[0006]

[0007] in:

[0008] X is NR 4 or O;

[0009] R 4 is selected from hydrogen, substituted or unsubstituted C 1-8 Alkyl, substituted or unsubstituted C 1-8 Alkoxy, substituted or unsubstituted C 1-4 Alkyl-(C 6-10 aryl or 5-6 membered heteroaryl), substituted or unsubstituted C 6-10 Aryl or substituted or unsubstituted 5-6 membered heteroaryl; wherein the substitution means that one or more (such as 1, 2, 3 or 4) H on the group is independently substituted by a substituent selected from the following group: C 1-6 Alkyl, C 1-6 Haloalkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, amino, NH-C 1-4Alkyl and N(C 1-4 Alkyl)2;

[0010] R 1 is selected from H, halogen, substituted or unsubstituted C 1-8 Alkyl, unsubstituted C 2-8 Alkenyl, unsubstituted C 2-8 Alkynyl, substituted or unsubstituted C 3-8 Cycloalkyl, substituted or unsubstituted C 0-4 Alkylene-R 3a , substituted or unsubstituted C 0-4 Alkenylene-R 3b , substituted or unsubstituted C 0-4 Alkynylidene-R 3c , where R 3a , R 3b and R 3c Each independently selected from substituted or unsubstituted C 3-8 Cycloalkyl, substituted or unsubstituted 3-8 membered heterocyclic group, substituted or unsubstituted C 6-10 Aryl, substituted or unsubstituted 5-10 membered heteroaryl; wherein the substitution means that one or more (such as 1, 2, 3 or 4) H on the group is independently substituted by a substituent selected from the following group: C 1-6 Alkyl, C 1-6 Haloalkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, amino, NH-C 1-4 Alkyl and N(C 1-4 Alkyl)2;

[0011] Ring A is selected from a substituted or unsubstituted 5-7 membered heterocyclic group containing at least one O atom, a substituted or unsubstituted 5-7 membered heterocyclic group containing at least one O atom, and C 6-10 Aryl, substituted or unsubstituted 5-7 membered heterocyclyl containing at least one O atom and 5-6 membered heteroaryl; wherein the substitution means that one or more (such as 1, 2, 3 or 4) H on the group is independently selected from the following R 3 Replacement: H, C 1-6 Alkyl, C 1-6 Haloalkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 haloalkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, amino, NH-C 1-4 Alkyl and N(C 1-4 Alkyl)2;

[0012] R 2 is selected from hydrogen, halogen, substituted or unsubstituted C 1-8Alkyl or substituted or unsubstituted phenyl, wherein the substitution means that one or more (such as 1, 2, 3 or 4) H on the group is independently substituted by a substituent selected from the following group: C 1-6 Alkyl, C 1-6 Haloalkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, amino, NH-C 1-4 Alkyl and N(C 1-4 Alkyl)2.

[0013] In another preferred embodiment, R 1 is selected from substituted or unsubstituted C 6-10 Aryl, substituted or unsubstituted 5-10 membered heteroaryl, substituted or unsubstituted C 1-4 Alkenylene-C 6-10 Aryl, wherein the substitution refers to one or more (such as 1, 2, 3 or 4) H on the group is independently substituted by a substituent selected from the group consisting of: C 1-6 Alkyl, C 1-6 Haloalkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, amino, NH-C 1-4 Alkyl and N(C 1-4 Alkyl)2.

[0014] In another preferred embodiment, the compound has a structure shown in any one of Formula II-X:

[0015]

[0016] In the formula, R 1 , R 2 , R 3 and X are each independently as defined above, R 3 0, 1, 2, 3 or 4.

[0017] In another preferred embodiment, R 4 is selected from hydrogen, substituted or unsubstituted C 1-8 Alkyl, substituted or unsubstituted C 1-4 Alkylene-C 6-10 Aryl, substituted or unsubstituted C 6-10 Aryl, substituted or unsubstituted C 1-8 Alkoxy, wherein the substitution refers to one or more (such as 1, 2, 3 or 4) H on the group is independently substituted by a substituent selected from the following group: 1-6 Alkyl, nitro, cyano, halogen, C 1-6 Alkoxy, C 1-6 Haloalkyl, hydroxyl, amino, NH-C 1-4 Alkyl, N(C1-4 Alkyl)2.

[0018] In another preferred embodiment, R 1 Selected from substituted or unsubstituted C 1-8 Alkyl, substituted or unsubstituted C 0-2 Alkylene-C 6-10 Aryl, substituted or unsubstituted C 1-2 Alkenylene-C 6-10 Aryl, substituted or unsubstituted 5-10 membered heteroaryl, wherein the substitution refers to one or more (such as 1, 2, 3 or 4) H on the group being independently substituted by a substituent selected from the following group: C 1-6 Alkyl, nitro, cyano, halogen, C 1-6 Alkoxy, C 1-6 Haloalkyl, hydroxyl, amino, NH-C 1-4 Alkyl, N(C 1-4 Alkyl)2.

[0019] In another preferred embodiment, R 2 is selected from hydrogen, substituted or unsubstituted C 1-8 Alkyl, wherein the substitution means that one or more (such as 1, 2, 3 or 4) H on the group is independently substituted by a substituent selected from the group consisting of: C 1-6 Alkyl, nitro, cyano, halogen, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, C 1-6 Haloalkyl, hydroxyl, amino, NH-C 1-4 Alkyl, N(C 1-4 Alkyl)2, preferably R 2 For H.

[0020] In another preferred embodiment, each heterocyclic group or heteroaryl group independently contains 1, 2 or 3 heteroatoms selected from O, N and S.

[0021] In another preferred embodiment, R 4 is substituted or unsubstituted C 1-4 Alkyl, substituted or unsubstituted C 1-4 Alkoxy, substituted or unsubstituted C1 alkylene-phenyl, substituted or unsubstituted phenyl, preferably R 4 C 1-4 alkyl.

[0022] In another preferred embodiment, R 1 is selected from substituted or unsubstituted phenyl, substituted or unsubstituted C 1-2 Alkylene-phenyl, substituted or unsubstituted C 1-2Alkenylene-phenyl, substituted or unsubstituted five-membered or six-membered heterocyclic group, preferably, wherein the substitution means that one or more (such as 1, 2, 3 or 4) H on the group is independently substituted by a substituent selected from the following group: C 1-4 Alkyl, nitro, cyano, halogen, C 1-4 Alkoxy, C 1-4 Halogenated alkyl.

[0023] In another preferred embodiment, R 3 Independently selected from H, C 1-4 Alkyl, C 1-4 Haloalkyl, nitro, fluorine, chlorine, bromine, iodine, C 1-4 Alkoxy, C 1-4 Haloalkoxy, preferably R 3 Independently selected from H, C 1-4 Alkyl, C 1-4 Haloalkyl, fluorine, chlorine.

[0024] In another preferred embodiment, R 2 Selected from hydrogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl.

[0025] In another preferred embodiment, R 2 is H, and R 3 For H.

[0026] In another preferred embodiment, the compound has a structure shown in Formula VII.

[0027] In another preferred embodiment, the compound is selected from the following group:

[0028]

[0029]

[0030] In another preferred embodiment, R 1 , R 2 , R 3 and X are independently selected from the corresponding groups in the specific compounds described above.

[0031] The second aspect of the present invention provides an agricultural composition comprising:

[0032] The first aspect provides a compound of formula I, or a pesticide-acceptable salt thereof, or an optical isomer and a geometric isomer thereof; and a pesticide-acceptable carrier and / or excipient.

[0033] In another preferred embodiment, the agricultural composition comprises 0.001-99.999 wt % of the above compound, or its pesticide acceptable salt, or its optical isomer and geometric isomer, preferably 0.01-99 wt % or 0.1-90 wt %.

[0034] In another preferred embodiment, the pesticide composition is in the form of various conventional pesticide formulations, such as bait, powder, aqueous solution, and emulsion.

[0035] The third aspect of the present invention provides use of the compound of the first aspect, or its pesticide acceptable salt, or optical isomer, or the agricultural composition of claim 4 in the preparation of an agricultural fungicide.

[0036] The fourth aspect of the present invention provides a method for preparing the compound of the first aspect, comprising the steps of:

[0037] The compound of formula a and the compound of formula b or the compound of formula c react under the conditions of a solvent and an acid catalyst to obtain a compound of formula I:

[0038]

[0039] Among them, R 1 , R 2 , R 3 and X are independently as defined in the first aspect of the present invention,

[0040] Y is halogen or OR 5 , R 5 It is H, C1-6 alkyl, C6-10 aryl.

[0041] In the above formula, the solvent used is independently selected from one or more of the following: acetonitrile (CH3CN), tetrahydrofuran (THF), benzene, toluene, ethyl acetate, trifluorotoluene, 1,2-dichloroethane (DCE), dichloromethane (CH2Cl2), 1,4-dioxane, methyl tert-butyl ether, cyclopentyl methyl ether, N-methylpyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, preferably dichloromethane (CH2Cl2).

[0042] In another preferred embodiment, the acid catalyst used in the reaction is independently a protonic acid or a Lewis acid, selected from one or more of the following: o-nitrobenzoic acid, m-nitrobenzoic acid, diphenyl phosphate, diphenylsulfonimide, trifluoroacetic acid, trichloroacetic acid, acetic acid, phosphoric acid, hydrochloric acid, sulfuric acid, boron trifluoride ether complex, iron trifluoromethanesulfonate, scandium trifluoromethanesulfonate, zinc trifluoromethanesulfonate, ytterbium trifluoromethanesulfonate, lanthanum trifluoromethanesulfonate, cerium trifluoromethanesulfonate, neodymium trifluoromethanesulfonate, europium trifluoromethanesulfonate, dysprosium trifluoromethanesulfonate, lutetium trifluoromethanesulfonate, erbium trifluoromethanesulfonate, gadolinium trifluoromethanesulfonate, preferably scandium trifluoromethanesulfonate and trifluoroacetic acid, more preferably scandium trifluoromethanesulfonate;

[0043] In another preferred embodiment, the reaction temperature is -20-100°C, preferably 25±5°C.

[0044] In another preferred embodiment, the reaction time is 1-48 hours, preferably 24±6 hours.

[0045] In another preferred embodiment, the method includes the specific steps of: under nitrogen protection, adding a compound of formula a, a compound of formula b or a compound of formula c and an acid catalyst such as scandium trifluoromethanesulfonate into a dry reaction container, adding a solvent such as CH2Cl2, and reacting the mixture at room temperature to obtain a product.

[0046] The molar ratio of the compound of formula a: the compound of formula b or the compound of formula c is 1:1 to 1:2, preferably 1:1-1.2;

[0047] The molar ratio of the compound of formula a to the acid catalyst is 1:0.05 to 1:0.25, preferably 1:0.1-0.15.

[0048] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described below (such as embodiments) can be combined with each other to form a new or preferred technical solution. Due to space limitations, they will not be described one by one here. DETAILED DESCRIPTION

[0049] After extensive and in-depth research, a large number of screenings and tests, the inventors have provided a spiroketal derivative with novel structure and excellent fungicidal activity, as well as a preparation method and use thereof, and completed the present invention on this basis.

[0050] the term

[0051] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0052] As used herein, the term "comprising" or "including (comprising)" may be open, semi-closed and closed. In other words, the term also includes "consisting essentially of" or "consisting of".

[0053] The prefix "C u-v " indicates that the following groups have u to v carbon atoms, such as "C 1-6 " can be C1, C2, C3, C4, C5 or C6. For example, "C 1-6 "Alkyl" means that the alkyl group has 1 to 6 carbon atoms.

[0054] The term "plurality" refers to 2 or more, such as 2, 3, 4, 5 or 6.

[0055] The term "halogen" or "halo" refers to fluorine, chlorine, bromine, iodine.

[0056] The term "alkyl" refers to a straight or branched chain unsubstituted alkyl having 1 to 8 carbon atoms (i.e., C 1-8 Alkyl), preferably a hydrocarbon group of 1 to 6 carbon atoms (i.e., C 1-6 Alkyl), more preferably hydrocarbon group of 1 to 4 carbon atoms (i.e., C 1-4 Examples of "alkyl" include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl and 3-methylpentyl, and the like.

[0057] The term "alkenyl" refers to an alkenyl group having 2 to 8 carbon atoms (i.e., C 2-8 alkenyl), preferably 2-6 carbon atoms (i.e., C 2-6 alkenyl) or 2-4 carbon atoms (i.e., C 2-4 The alkylene group is a straight or branched hydrocarbon group having 1 to 2 carbon-carbon double bonds. Examples of alkylene groups include, but are not limited to, vinyl, propenyl, butadienyl (including 1,2-butadienyl and 1,3-butadienyl).

[0058] The term "alkynyl" refers to a group having 2 to 8 carbon atoms (i.e., C 2-8 Alkynyl), preferably 2-6 carbon atoms (i.e., C 2-6 Alkynyl) or 2-4 carbon atoms (i.e., C 2-4 alkynyl), and a straight or branched hydrocarbon group having 1 to 2 carbon-carbon triple bonds.

[0059] The term "alkylene" refers to a saturated divalent hydrocarbon radical (i.e., C 1-6 Alkylene), preferably a hydrocarbon group of 1 to 4 carbon atoms (i.e., C 1-4 Alkylene), more preferably 1-3 carbon atoms (i.e., C 1-3Examples of "alkylene" include, but are not limited to, methylene, ethylene, isopropylene, and the like. Alkenylene and alkynylene are divalent groups derived from alkenyl and alkynyl as defined above, respectively, by losing two hydrogen atoms.

[0060] The term "cycloalkyl" refers to a non-aromatic, saturated or partially unsaturated cyclic hydrocarbon group, which may be arbitrarily substituted with one or more substituents described herein, and which has 3-6 carbon atoms to form a monocyclic ring, or 7-12 carbon atoms to form a bicyclic ring. As used herein, a cycloalkyl group has 3 to 8 ring carbon atoms (i.e., C 3-8 Cycloalkyl) or 3 to 6 ring carbon atoms (i.e. C 3-6 Cycloalkyl). Examples of monocyclic cycloalkyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-1-enyl, 1-cyclopent-2-enyl, 1-cyclopent-3-enyl, cyclohexyl, 1-cyclohex-1-enyl, cycloheptyl, cyclooctyl. Exemplary bridged bicyclic cycloalkyls include, but are not limited to, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane.

[0061] The terms "aromatic ring" and "aryl" refer to aromatic carbocyclic groups having a single ring (e.g., monocyclic) or multiple rings (e.g., bicyclic or tricyclic), including fused systems. As used herein, aryl has 6 to 10 ring carbon atoms (i.e., C 6-10 Aryl includes bicyclic groups including an aromatic ring fused to a saturated or partially unsaturated carbocyclic or heterocyclic ring (e.g., benzo[C] 3-6 Cycloalkyl or benzo 4-6 membered heterocyclyl). Typical aryl groups include but are not limited to the following groups: benzene, naphthalene, anthracene, biphenyl, 1,2-dihydronaphthalene, 1,2,3,4-tetrahydronaphthyl, 2,3-dihydrobenzofuranyl, etc. The "aryl" category includes structures of aryl rings fused to cycloalkyl and heterocycloalkyl.

[0062] The terms "heterocycle", "heterocyclic", "heterocyclyl" and "heterocycloalkyl" refer to an optionally substituted, fully saturated or partially unsaturated (e.g., containing one or two double bonds) non-aromatic ring group, for example, it can be a 3-7 membered monocyclic ring, a 7-11 membered bicyclic ring or a 10-15 membered tricyclic ring system, which has at least one heteroatom in at least one carbon atom-containing ring. Each ring of the heterocyclic group containing a heteroatom can have 1, 2 or 3 heteroatoms selected from oxygen, nitrogen and sulfur. As used herein, the heterocyclic group has 3 to 10 ring atoms (i.e., 3-10 membered heterocyclic group), 3 to 8 ring atoms (i.e., 3-8 membered heterocyclic group), 3-7 ring atoms or 3 to 6 ring atoms (i.e., 3-6 membered heterocyclic group) or 5 to 6 ring atoms (i.e., 5-6 membered heterocyclic group). The “heterocyclyl” may be arbitrarily substituted with one or more substituents described herein. Examples of the “heterocyclyl” include, but are not limited to, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, morpholino, thiomorpholino, piperazinyl, homopiperazinyl, glycidyl, imidazolidinyl, 3-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[4.1.0]heptanyl, azabicyclo[2.2.2]hexanyl, N-pyridylurea, pyrimidinone and 1,1-dioxo-thiomorpholinyl.

[0063] The term "heteroaryl" or "heteroaromatic ring" refers to a heteroaromatic system containing one or more heteroatoms selected from oxygen, nitrogen and sulfur, including monocyclic, bicyclic or polycyclic fused systems. The heteroaryl group may be optionally substituted with one or more substituents described herein. As used herein, the heteroaryl group may have 5 to 10 ring atoms (i.e., 5-10 membered heteroaryl), 5 to 8 ring atoms (i.e., 3-8 membered heteroaryl), or 5 to 6 ring atoms (i.e., The heteroaryl group may have 1 to 3 ring heteroatoms, 1 to 2 ring heteroatoms, or 1 ring heteroatom, wherein the ring heteroatoms are independently selected from oxygen, nitrogen, and sulfur. Examples of "heteroaryl" include, but are not limited to, pyrrolyl, pyridyl, pyrazolyl, imidazolyl, pyrazinyl, imidazopyridyl, benzofuranyl, pyrimidinyl, triazolyl, tetrazolyl, furanyl, thienyl, thiazolyl, quinolyl, isoquinolyl, indolyl, and the like.

[0064] The term "substituted" means that one or more hydrogen atoms in a specific group are replaced by any substituent mentioned in the present specification. If not specifically stated, "substituted" means that one or more (such as 2, 3 or 4) hydrogen atoms on the group are independently replaced by a group selected from the following group: 1-6 Alkyl, C 1-6 Haloalkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, amino, NH-C 1-4 Alkyl and N(C 1-4 Alkyl)2.

[0065] Active ingredients

[0066] The present invention provides a compound of formula (I), an optical isomer thereof, or a pesticide-acceptable salt thereof:

[0067]

[0068] Among them, R 1 , R 2 , R 3 and X are as defined above.

[0069] In another preferred embodiment, the compound is any one of the compounds in the examples.

[0070] The present invention is intended to include salts of compounds. A "pesticide-acceptable salt" may have more than one charged atom, and multiple charged atoms may have multiple counterions. In an exemplary embodiment, a salt form of the compound is produced that can convert an otherwise oily or viscous compound into a more easily handled solid material. In another exemplary embodiment, converting the free base of the compound of the present invention into the corresponding salt can increase the solubility of the compound in an aqueous medium, while being able to affect biological properties such as bioavailability, pharmacokinetics, and pharmacodynamics. Therefore, any salt form, such as a pharmaceutically acceptable salt of the compound of the present invention, including a salt of an inorganic acid or a salt of an organic acid is within the scope of the present invention. At the same time, various crystalline forms such as the pharmaceutically acceptable salts of the compound of the present invention are also within the scope of the present invention. Any prodrug of the compound of the present invention is also within the scope of the present invention. For example, R and R t It may be any group that is cleavable in vivo to produce an amine, such as a primary or secondary amine.

[0071] As used herein, the term "agrichemically acceptable salt" refers to salts that are suitable for contact with the tissues of humans and lower animals without excessive toxicity, irritation, allergic reactions, etc. and commensurate with a reasonable benefit / risk ratio within the scope of reasonable medical judgment. Pharmaceutically acceptable salts are well known in the art. Pharmaceutically acceptable salts of the compounds of the present invention include those derived from suitable inorganic and organic acids and bases. Examples of pesticide-acceptable non-toxic acid addition salts are salts formed by amino groups with inorganic acids (such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid) or with organic acids (such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid) or by using other methods used in the art (such as ion exchange). Other pharmaceutically acceptable salts include, but are not limited to, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, and the like.

[0072] Solvate refers to a combination or complex of one or more solvent molecules and the compounds of the present invention. Examples of solvents that form solvates include, but are not limited to, water, isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, and ethanolamine. The compounds of the present invention may exist in a non-solvated form or in a solvated form with a pharmaceutically acceptable solvent such as water, ethanol, etc., so the present invention will include both solvated and non-solvated forms.

[0073] Some compounds exist as tautomers. Tautomers are in equilibrium with each other. For example, amide-containing compounds can exist in equilibrium with imidic acid tautomers. No matter which tautomer is shown, no matter how the equilibrium properties between tautomers are, it is understood by those of ordinary skill in the art that compounds contain all or each tautomer of the compound. Therefore, amide-containing compounds are understood to contain their imidic acid tautomers. Similarly, imidic acid-containing compounds are understood to contain their amide tautomers.

[0074] The compounds of the present invention may contain asymmetric centers or chiral centers, and therefore different stereoisomeric forms exist. The compounds may be chiral, racemic or may exist as compositions comprising one or more stereoisomers. The present invention includes enantiomers, diastereomers, racemic mixtures, mixtures enriched in enantiomers and mixtures enriched in diastereomers. All stereoisomeric forms of the compounds of the present invention, including but not limited to diastereomers, enantiomers and hindered isomers, and mixtures thereof such as racemic mixtures, will form a part of the present invention. In addition, asymmetric carbon atoms may be present in substituents such as alkyl. All of these isomers and mixtures thereof are intended to be included in the present invention. If a specific enantiomer of the compounds of the present invention is desired, it may be prepared by asymmetric synthesis, or by derivatization with a chiral auxiliary, wherein the resulting diastereomeric mixture is separated and the auxiliary group is split to provide a pure desired enantiomer. Alternatively, when the molecule contains a basic functional group such as an amino group, or an acidic functional group such as a carboxyl group, diastereomeric salts may be formed with an appropriate optically active acid or base, followed by separation of the diastereomers so formed by fractional crystallization or chromatography known in the art, and subsequent recovery of the pure enantiomers. In addition, separation of enantiomers and diastereomers may be achieved using chromatography on a chiral stationary phase.

[0075] In this article, when the stereochemistry of any particular chiral atom is not determined, all stereoisomers are considered. In addition, the present invention relates to all geometric and positional isomers. The compounds of this invention can exist in different tautomeric forms, and all these forms are included within the scope of the present invention. All stereoisomers of the compounds of this invention are expected to include mixtures or pure or substantially pure forms.

[0076] In this article, unless otherwise stated, structures depicted herein are also intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. In addition to therapeutic uses, such compounds can be used, for example, as analytical tools or probes in biological assays. Any formula or structure given herein is also intended to represent unlabeled forms of the compound as well as isotopically labeled forms. Isotopically labeled compounds have structures described by the formulas given herein, except that one or more atoms are replaced by atoms with selected atomic masses or mass numbers. Examples of isotopes that can be incorporated into the compounds of the present disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine, such as, but not limited to, 2 H (deuterium, D), 3 H (tritium), 11 C. 13 C. 14 C. 15 N. 18 F. 31 P. 32 P. 35 S.36 Cl and 125 I. Various isotopically labeled compounds of the present disclosure, for example, incorporating radioactive isotopes such as 3 H and 14 C, can be used in metabolic studies, reaction kinetics studies, detection or imaging techniques such as positron emission tomography (PET) or single photon emission computed tomography (SPECT), including drug or substrate tissue distribution analysis or radiotherapy of patients.

[0077] Composition and application thereof

[0078] The term "active substance of the present invention" or "active compound of the present invention" refers to the compound of the present invention, its optical isomers, or pesticide-acceptable salts, which have significant fungicidal activity, a broad fungicidal spectrum, and strong stability.

[0079] Therefore, the present invention provides the use of the active ingredient of the present invention as an agricultural fungicide for controlling plant pathogens.

[0080] Plant pathogens that can be used in the present invention include (but are not limited to): Blumeria graminis, Podosphaera leucotricha, Sphaerotheca fuliginea, Uncinula necator, Gymnosporangium sabinae, Hemileia vastatrix, Phakopsora pachyrhizi or Phakopsora meibomian, Puccinia recondite, Puccinia graminis or Puccinia striiformis, Uromyces ndiculatus, Albugocandida, Bremia lactucae, Peronospora pisi, Phytophthora infestans. infestans, Plasmopat, Pythium ultimum, Pseudoperonospora humuli or Pseudoperonospora cubensis, Alternaria solan, Cercosporabeticola, Cladosporium cucumerinum, Cochliobolus sativus or Cochliobolus miyabeanus, Colletotrichum lindemuthan ium, Cycloconium, Diaporthe citri, Gloeosporium laeticolor, Glomerella cingulata, Guignardia bidwell, Leptosphaeria maculans or Le tosphaeria nodorum, Magnaporthe grisea, Mycosphaerella graminicola, Mycosphaerellaarachidicola or Mycosphaerella fijiensis, Phaeosphaeria nodorum, Pyrenophora teres or Pyrenophora tritici repentis, Ramularia collo cygnI or Ramularia areola, Rhynchosporiusecalis, Septoria apii or Septoria lycopercisi, Typhula incarnata, Venturia inaequalis, Corticium graminearum, Fusarium oxysporum, Gaeumannomyces graminIs, Rhizoctonia solani, Sarocladium oryzae), Sclerotium oryzae, Tapesia acuformid, Thielaviopsis basicola, Alternaria spp., Aspergillus flavus, Cladosporium spp., Claviceps purpurea, Fusarium culmorum, Gibberella zeae, Monographella alis, Sphacelotheca reiliana, Tilletia caries, Urocystis occulta, Ustilago nuda, Aspergillus flavus, Botrytis cinerea, Penicillium expansum, Rhizopus stolonifer), Sclerotinia sclerotiorum, Verticillium alboatrum, Alternaria brassicicola, Aphanomyceseuteiches), Ascochytalentis, Aspergillus flavus, Cladosporium herbarum, Cochliobolus sativus, Colletotrichum coccodes, Fusarium, Gibberellazeae, Macrophomina phaseolina, Monographella nivalis, Penicillium expansum, Phomalingam, Phomopsis sojae, Phytophthora cactorum, Pyrenophora graminea, Pyricularia oryzae, Pythiumultimum, Rhizoctonia solan, Rhizopus oryzae oryzae), Sclerotium rolfsii, Septorianodorum, Typhulaincarnata, Verticillium dahliae, Nectriagalligena, Monilinia laxa, Exobasidium vexans, Taphrina deformans, Phaemoniellaclam dospora, Eutypa lata, Ganoderma boninense, Rigidoporus linosus, Botrytis cinerea, Rhizoctonia solani, Helminthosporium soi), Plasmodiophora brassicae, Xanthomonas, Xanthomonas campestris pv. oryzae, Pseudomonas, such as Pseudomonas syringae pv. lachrymans, Erwinia, such as Erwinia amylovoraamy lovora), preferably wheat fusarium rust, rice sheath blight, cucumber gray mold, rapeseed sclerotinia.

[0081] The active substances of the present invention can be prepared into fungicide compositions in conventional manner, such as solutions, emulsions, foams, powders, pastes and granules. Aerosols are microcapsules of natural or synthetic materials impregnated with active substances, in polymers. Coating compounds for seeds, preparations for use with combustion devices, such as fumigation cartridges, fumigation trays and fumigation pots, and ULV cold mist and hot mist preparations.

[0082] These preparations can be produced by known methods, such as mixing the active compound with an extender, which is a liquid, liquefied gas or solid diluent or carrier and can be mixed with any surfactant to form a formulation. In addition, when water is used as an extender, an organic solvent can be used as a cosolvent.

[0083] When a liquid is used as a diluent or carrier, it is basically suitable, such as aromatic hydrocarbons, such as xylene, toluene or alkylnaphthalene; chlorinated aromatic or aliphatic hydrocarbons, such as chlorobenzene, vinyl chloride or methylene chloride; aliphatic hydrocarbons, such as cyclohexane or paraffin; alcohols, such as ethanol or ethylene glycol and their ethers or polymers; ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; other polar solvents, such as N,N-dimethylformamide, dimethyl sulfoxide or water.

[0084] Liquefied gas diluents or carriers refer to liquids that will become gases at normal temperature and pressure, such as aerosol propellants, such as halogenated hydrocarbons as well as butane, propane, nitrogen and carbon dioxide.

[0085] Solid carriers can be ground natural minerals such as clay, quartz, talc, montmorillonite, activated clay, kaolin or diatomaceous earth, and ground synthetic minerals such as dispersed silicic acid, silicates and alumina. Solid carriers for particles are aged and graded natural zircons such as calcite, pumice, marble, sepiolite and dolomite, as well as inorganic and organic coarse powders and synthetic particles, organic materials include sawdust, coconut shells, corn cobs and tobacco stems and crushed particles thereof, etc.

[0086] Nonionic and anionic emulsifiers can be used as emulsifiers and / or foam formers, such as polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers, alkylaryl polyethylene glycols, alkyl sulfonates, alkyl sulfates, aryl sulfonates and albumin hydrolysates. Dispersants include lignin sulfite waste liquor and methylcellulose.

[0087] Binders such as carboxymethylcellulose and natural or synthetic polymers in the form of powders, granules or emulsions, such as gum arabic, polyethylene and polyvinyl acetate, may be used in the formulations.

[0088] Colorants that may be used include inorganic dyes such as iron oxide, cobalt oxide and Prussian blue; organic dyes such as azo dyes or metal phthalocyanine dyes, and trace nutrients such as salts of iron, manganese, zinc, boron, copper, cobalt and aluminum.

[0089] The active compound of the present invention can be used in a mixture with other active compounds, and the other types of compounds include insecticides, baits, miticides, nematicides and / or growth regulators.

[0090] The active compounds of the present invention can be used in a mixture with synergists to enhance the activity of the compounds of the present invention.

[0091] These preparations usually contain 0.001-99.999% by weight, preferably 0.1-99.9% by weight, more preferably 0.5-90% by weight of the active compound of the present invention. The content of the active compound in the use form prepared from the commercial preparations can vary within a wide range.

[0092] Preparation method of the compound of the present invention

[0093] The target compound of the present invention can be obtained by reacting a compound of formula a with a compound of formula b or a compound of formula c. The conditions of the method, such as raw materials, solvent, temperature, acid, ratio, reaction time can be selected as needed, for example, reference can be made to (but not limited to) the following examples.

[0094]

[0095] Among them, R 1 , R 2 , R 3 and X are independently as defined in the first aspect of the present invention,

[0096] Y is halogen or OR 5 , R 5 It is H, C1-6 alkyl, C6-10 aryl.

[0097] In the above formula, the solvent used is independently selected from one or more of the following: acetonitrile (CH3CN), tetrahydrofuran (THF), benzene, toluene, ethyl acetate, trifluorotoluene, 1,2-dichloroethane (DCE), dichloromethane (CH2Cl2), 1,4-dioxane, methyl tert-butyl ether, cyclopentyl methyl ether, N-methylpyrrolidone, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, preferably dichloromethane (CH2Cl2).

[0098] In another preferred embodiment, the acid catalyst used in the reaction is independently a protonic acid or a Lewis acid, selected from one or more of the following: o-nitrobenzoic acid, m-nitrobenzoic acid, diphenyl phosphate, diphenylsulfonimide, trifluoroacetic acid, trichloroacetic acid, acetic acid, phosphoric acid, hydrochloric acid, sulfuric acid, boron trifluoride ether complex, iron trifluoromethanesulfonate, scandium trifluoromethanesulfonate, zinc trifluoromethanesulfonate, ytterbium trifluoromethanesulfonate, lanthanum trifluoromethanesulfonate, cerium trifluoromethanesulfonate, neodymium trifluoromethanesulfonate, europium trifluoromethanesulfonate, dysprosium trifluoromethanesulfonate, lutetium trifluoromethanesulfonate, erbium trifluoromethanesulfonate, gadolinium trifluoromethanesulfonate, preferably scandium trifluoromethanesulfonate and trifluoroacetic acid, more preferably scandium trifluoromethanesulfonate;

[0099] In another preferred embodiment, the reaction temperature is -20-100°C, preferably 25±5°C.

[0100] In another preferred embodiment, the reaction time is 1-48 hours, preferably 24±6 hours.

[0101] In another preferred embodiment, the method includes the specific steps of: under nitrogen protection, adding a compound of formula a, a compound of formula b or a compound of formula c and an acid catalyst such as scandium trifluoromethanesulfonate into a dry reaction container, adding a solvent such as CH2Cl2, and reacting the mixture at room temperature to obtain a product.

[0102] The molar ratio of the compound of formula a: the compound of formula b or the compound of formula c is 1:1 to 1:2, preferably 1:1-1.2;

[0103] The molar ratio of the compound of formula a to the acid catalyst is 1:0.05 to 1:0.25, preferably 1:0.1-0.15.

[0104] The main advantages of the present invention include:

[0105] The spiroketal compounds of the present invention have the characteristics of high efficiency, low toxicity, safety to non-target organisms, easy degradation in the environment, and no resistance to harmful organisms, and are very suitable as new agricultural fungicides.

[0106] Based on the preparation method of the present invention, a spirocyclic ketal compound containing a pyrrolidone skeleton can be synthesized in one step using simple and readily available raw materials, and the operation is simple, the yield is high, and the substrate range is wide.

[0107] The present invention will be further described below in conjunction with specific implementation. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. The experimental methods in the following examples without specifying specific conditions are usually based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are calculated by weight.

[0108] The target products in the following Examples 1 to 17 were confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0109] Example 1 Synthesis of 6'-benzyl-4'-phenyl-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0110]

[0111] After placing a magnetic stirrer in a 10mL Schlenk reaction tube, the reaction tube was dried, and then 2,3-dioxypyrrolidine (27.7mg, 0.1mmol), isochromanol ketal (16.4mg, 0.1mmol) and scandium trifluoromethanesulfonate (4.9mg, 0.01mmol) were added in sequence under nitrogen protection, and redistilled CH2Cl2 (1.5mL) was added and stirred at room temperature. Under TLC monitoring, the mixture was stirred at room temperature until the reaction was complete and then stopped, and the product was purified by thin layer chromatography (developing solvent was petroleum ether / ethyl acetate). The target product was confirmed by nuclear magnetic resonance spectrum and high-resolution mass spectrometry.

[0112] Its physical and chemical properties are as follows: white powder, yield is 93%, 1 H NMR(400MHz, CDCl3)δ7.40–7.36(m,1H),7.34–7.27(m,4H),7.26–7.23(m,4H),7.22–7.20 (m,1H),7.17–7.12(m,1H),4.75(d,J=15.0Hz,1H),4.49(d,J=15.0Hz,1H),4.30(dd,J=11. 8,5.9Hz,1H),4.04–3.90(m,2H),3.62–3.38(m,2H),3.11(ddd,J=17.9,12.6,5.9Hz,1H), 2.67(dd,J=16.4,2.8Hz,1H), 2.42(dd,J=13.6,11.8Hz,1H), 2.25(dd,J=13.6,5.9Hz,1H).

[0113] Example 2 Synthesis of 4',6'-diphenyl-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0114]

[0115] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield 90%, 1H NMR (400MHz, CDCl3) δ7.67 (d, J = 8.2Hz, 2H), 7.42–7.35 (m, 3H), 7.33–7.29 (m, 5H), 7. 25–7.21(m,2H),7.16(d,J=6.7Hz,1H),7.07(t,J=7.4Hz,1H),4.30(dd,J=11.8,5.9Hz ,1H),4.18–4.09(m,2H),4.07–3.98(m,2H),3.13(ddd,J=17.9,12.6,5.9Hz,1H),2.68 (dd,J=16.5,2.7Hz,1H),2.48(dd,J=13.7,11.8Hz,1H),2.32(dd,J=13.7,5.9Hz,1H).

[0116] Example 3 Synthesis of 6'-methyl-4'-phenyl-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0117]

[0118] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield is 92%, 1 H NMR (400MHz, CDCl3) δ7.38–7.33(m,3H),7.30–7.22(m,5H),7.14(d,J=7.3Hz,1H),4.27(dd,J=11.8,5.9Hz,1H),4.06–3.95(m,2H),3.70–3.55(m, 2H), 3.11(ddd,J=17.9,12.6,6.1Hz,1H),3.02(s,3H),2.66(dd,J=16.5,2.8Hz,1H),2.43(dd,J=13.7,11.8Hz,1H),2.26(dd,J=13.6,5.9Hz,1H).

[0119] Example 4 Synthesis of 6'-propyl-4'-phenyl-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0120]

[0121] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield 91%, 1H NMR (400MHz, CDCl3) δ7.39–7.33(m,3H),7.30–7.27(m,2H),7.26–7.17(m,3H),7.14(d,J= 7.3Hz,1H),4.28(dd,J=11.8,5.9Hz,1H),4.09–3.90(m,2H),3.74–3.53(m,2H),3.43–3.3 2(m,2H),3.11(ddd,J=17.9,12.7,5.9Hz,1H),2.66(dd,J=16.4,2.8Hz,1H),2.43(dd,J=1 3.6,11.8Hz,1H),2.26(dd,J=13.6,5.9Hz,1H),1.63–1.50(m,2H),0.89(t,J=7.3Hz,3H).

[0122] Example 5 Synthesis of 6'-tert-butyl-4'-phenyl-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0123]

[0124] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield is 89%, 1 H NMR (400MHz, CDCl3) δ7.57–7.48(m,3H),7.45–7.36(m,5H),7.29(d,J=7.6Hz,1H),4.49–4.35(m,1H),4.22–4.08(m,2H),3.91–3. 69(m,2H),3.25(ddd,J=16.6,12.7,5.3Hz,1H),2.87–2.74(m,1H),2.59–2.48(m,1H),2.38(dd,J=13.8,6.0Hz,1H),1.57(s,9H)..

[0125] Example 6 Synthesis of 6'-methoxy-4'-phenyl-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0126]

[0127] The specific operation steps are the same as in Example 1. Its physical and chemical properties are as follows: white powder, yield 90%, 1H NMR (400MHz, CDCl3) δ7.39–7.27(m,5H),7.26–7.18(m,3H),7.16–7.12(m,1H),4.25(ddd,J=12.7,11.2,2.9Hz,1H),4.01(dt,J=11.6,6.3Hz,2H), 3.94–3.78(m,5H),3.11(ddd,J=18.0,12.8,5.9Hz,1H),2.66(dd,J=16.4,2.8Hz,1H),2.45(dd,J=13.7,11.8Hz,1H),2.27(dd,J=13.7,5.9Hz,1H).

[0128] Example 7 Synthesis of 6'-methyl-4'-(3-nitro-phenyl)-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0129]

[0130] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield is 87%, 1 H NMR (400MHz, CDCl3) δ8.20–8.13(m,2H),7.66–7.61(m,1H),7.60–7.54(m,1H),7.36(d d,J=7.5,1.7Hz,1H),7.28–7.22(m,2H),7.18–7.12(m,1H),4.27(dd,J=11.7,5.9Hz,1H 1H),4.24–4.16(m,1H),3.99(dd,J=11.2,5.7Hz,1H),3.74–3.53(m,2H),3.17–3.06(m,1H),3.04( s,3H),2.67(dd,J=16.5,2.8Hz,1H),2.42(dd,J=13.5,11.7Hz,1H),2.30(dd,J=13.6,5.9Hz,1H).

[0131] Example 8 Synthesis of 6'-methyl-4'-(2-fluoro-phenyl)-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0132]

[0133] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield 96%, 1H NMR (400MHz, CDCl3) δ7.36 (dd, J=7.5, 1.7Hz, 1H), 7.27–7.19 (m, 4H), 7.17–7.05 (m, 3H ),4.38(dd,J=11.9,5.8Hz,1H),4.27(ddd,J=12.6,11.2,2.9Hz,1H),3.99(dd,J=11.2 ,5.7Hz,1H),3.77–3.54(m,2H),3.12(ddd,J=17.8,12.0,5.9Hz,1H),3.03(s,3H),2.6 6(dd,J=16.3,2.7Hz,1H),2.50(dd,J=13.4,11.9Hz,1H),2.24(dd,J=13.4,5.8Hz,1H);

[0134] Example 9 Synthesis of 6'-methyl-4'-(4-cyano-phenyl)-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0135]

[0136] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield 94%, 1 H NMR(400MHz, CDCl3) δ7.69(d,J=8.2Hz,2H),7.45–7.40(m,2H),7.36(dd,J=7.6,1.6Hz,1H ),7.30–7.21(m,2H),7.17(d,J=7.4Hz,1H),4.27(dd,J=11.7,5.9Hz,1H),4.14(dd,J=11.7 ,5.9Hz,1H),4.01(dd,J=11.2,5.7Hz,1H),3.70(d,J=18.1Hz,1H),3.58(d,J=18.1Hz,1H), 2.69(dd,J=16.5,2.7Hz,1H), 2.40(dd,J=13.6,11.7Hz,1H), 2.29(dd,J=13.6,5.9Hz,1H).

[0137] Example 10 Synthesis of 6'-methyl-4'-(2-bromo-phenyl)-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0138]

[0139] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield 95%,1 H NMR(400MHz, CDCl3)δ7.58(d,J=8.0Hz,1H),7.37–7.31(m,2H),7.28–7.18(m ,4H),7.17–7.10(m,2H),4.71–4.55(m,1H),4.31–4.17(m,1H),4.00(dd,J=1 1.2,5.8Hz,1H),3.78–3.59(m,2H),3.13(ddd,J=17.9,9.3,4.9Hz,1H),3.04 (s,3H),2.66(dd,J=16.4,2.8Hz,1H),2.41–2.32(m,1H),2.30–2.21(m,1H).

[0140] Example 11 Synthesis of 6'-methyl-4'-(3-fluoro-phenyl)-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0141]

[0142] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield 93%, 1 H NMR (400MHz, CDCl3) δ7.37–7.31(m,2H),7.30–7.18(m,3H),7.16–7.13(m,1H),7.07–7.04(m,1 H),7.01–6.95(m,2H),4.26(ddd,J=12.6,11.2,2.9Hz,1H),4.04(dd,J=11.8,5.9Hz,1H),3.98( ddd,J=11.1,5.9,1.1Hz,1H),3.75–3.53(m,2H),3.11(ddd,J=17.8,12.5,5.9Hz,1H),3.03(s, 3H), 2.66 (dd, J=16.3, 2.8Hz, 1H), 2.40 (dd, J=13.6, 11.7Hz, 1H), 2.26 (dd, J=13.6, 5.9Hz, 1H);

[0143] Example 12 Synthesis of 6'-methyl-4'-(3-methoxy-phenyl)-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0144]

[0145] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield is 86%,1 H NMR (400MHz, CDCl3) δ7.36 (dd, J=7.4, 1.7Hz, 1H), 7.26–7.19 (m, 3H), 7.14 (d, J=7.3 Hz,1H),6.87–6.79(m,3H),4.27(dd,J=13.7,11.8Hz,1H),4.04–3.93(m,2H),3.82( s,3H),3.73–3.58(m,2H),3.11(ddd,J=17.8,12.6,6.0Hz,1H),3.02(s,3H),2.66(d d,J=16.4,2.7Hz,1H),2.43(dd,J=13.7,11.8Hz,1H),2.26(dd,J=13.7,5.9Hz,1H).

[0146] Example 13 Synthesis of 6'-methyl-4'-(2-methyl-phenyl)-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0147]

[0148] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield is 93%, 1 H NMR(400MHz, CDCl3)δ7.36–7.30(m,1H),7.28–7.19(m,3H),7.18–7.10(m,4H),4 .31(dd,J=11.7,6.0Hz,1H),4.28–4.21(m,1H),4.01–3.92(m,1H),3.74–3.57(m ,2H),3.12(ddd,J=17.7,12.5,6.0Hz,1H),3.03(s,3H),2.66(dd,J=16.4,2.8Hz ,1H),2.39(s,3H),2.32(dd,J=13.5,11.7Hz,1H),2.23(dd,J=13.5,6.0Hz,1H).

[0149] Example 14 Synthesis of 6'-methyl-4'-(4-trifluoromethyl-phenyl)-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0150]

[0151] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield is 92%, 1H NMR (400MHz, CDCl3) δ7.63(d,J=8.1Hz,2H),7.40(d,J=8.0Hz,2H),7.34(dd,J=7.5,1.6Hz ,1H),7.26–7.22(m,2H),7.17–7.12(m,1H),4.27(ddd,J=12.6,11.2,2.9Hz,1H),4.12(dd, J=11.8,5.9Hz,1H),4.02–3.94(m,1H),3.72–3.49(m,2H),3.17–3.06(m,1H),3.03(s,3H) ,2.67(dd,J=16.4,2.8Hz,1H),2.41(dd,J=13.6,11.7Hz,1H),2.27(dd,J=13.6,5.9Hz,1H)

[0152] Example 15 Synthesis of 6'-methyl-4'-(4-fluoro-phenyl)-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0153]

[0154] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield 91%, 1 H NMR(400MHz, CDCl3)δ7.35(d,J=7.5Hz,1H),7.26–7.21(m,4H),7.14(d,J=7 .4Hz,1H),7.05(t,J=8.4Hz,2H),4.26(dd,J=11.8,6.0Hz,1H),4.07–3.95(m ,2H),3.72–3.51(m,2H),3.18–3.06(m,1H),3.02(s,3H),2.66(dd,J=16.5,2 .8Hz, 1H), 2.38 (dd, J=13.6, 11.8Hz, 1H), 2.25 (dd, J=13.6, 6.0Hz, 1H); (m).

[0155] Example 16 Synthesis of 6'-methyl-4'-(4-methyl-phenyl)-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0156]

[0157] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield 95%, 1H NMR(400MHz, CDCl3)δ7.35(d,J=7.4Hz,1H),7.25–7.20(m,2H),7.18–7.12(m ,5H),4.23(dd,J=11.8,5.9Hz,1H),4.03–3.93(m,2H),3.69–3.53(m,2H),3. 11(ddd,J=17.8,12.6,5.7Hz,1H),3.01(s,3H),2.66(dd,J=16.6,2.8Hz,1H) ,2.41(dd,J=13.6,11.8Hz,1H),2.35(s,3H),2.25(dd,J=13.6,5.9Hz,1H)..

[0158] Example 17 Synthesis of 6'-methyl-4'-thienyl-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0159]

[0160] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: yellow powder, yield is 87%, 1 H NMR(400MHz, CDCl3)δ7.37(dd,J=7.1,2.0Hz,1H),7.27–7.21(m,3H),7.17–7.11(m,1H),7. 00–6.93(m,2H),4.41(dd,J=11.9,5.7Hz,1H),4.26(ddd,J=12.6,11.1,2.9Hz,1H),3.97(d d,J=11.1,5.8Hz,1H),3.80–3.59(m,2H),3.10(ddd,J=17.8,9.2,4.4Hz,1H),3.03(s,3H), 2.66(dd,J=16.4,2.8Hz,1H), 2.51(dd,J=13.5,11.8Hz,1H), 2.36(dd,J=13.5,5.7Hz,1H).

[0161] Example 18 Synthesis of 6'-methyl-4'-phenylvinyl-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0162]

[0163] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: yellow powder, yield 78%, 1H NMR (400MHz, CDCl3) δ7.39–7.31(m,5H),7.26–7.12(m,4H),6.62(d,J=15.7Hz,1H),6 .10(dd,J=15.7,9.0Hz,1H),4.24(ddd,J=12.7,11.1,2.9Hz,1H),3.95(dd,J=11.3,5. 7Hz,1H),3.89–3.78(m,2H),3.73–3.60(m,1H),3.16–3.09(m,1H),3.05(s,3H),2.65 (dd,J=16.3,2.8Hz,1H),2.27(dd,J=13.6,11.3Hz,1H),2.16(dd,J=13.6,5.7Hz,1H).

[0164] Example 19 Synthesis of 6'-methyl-4'-tert-butyl-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0165]

[0166] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield is 83%, 1 H NMR(400MHz, CDCl3)δ7.38–7.33(m,1H),7.25(t,J=6.1Hz,2H),7.16–7.11(m,1H),4.24–4.14(m,1H),4.09–3.87(m,3H),3 .08(s,4H),2.65(ddd,J=15.0,14.2,4.2Hz,2H),2.13(dd,J=12.6,12.6Hz,1H),2.00(dd,J=13.4,5.7Hz,1H),1.00(s,9H).

[0167] Example 20 Synthesis of 3,3,6'-trimethyl-4'-phenyl-3',4',5',6'-tetrahydro-7'H-spiro[isobenzofuran-1,2'-pyrrolidone[2,3-c]pyrrole]

[0168]

[0169] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield 81%, 1H NMR (400MHz, CDCl3) δ7.45–7.24(m,8H),7.18(d,J=7.5Hz,1H),4.19–4.09(m,1H),3.69(dd,J=18.2,1.7Hz,1H),3.55(dd, J=18.2,10.0Hz,1H),2.99(s,3H),2.51(dd,J=13.3,12.1Hz,1H),2.28(dd,J=13.3,5.8Hz,1H),1.64(s,3H),1.58(s,3H).

[0170] Example 21 Synthesis of 3,3,6'-trimethyl-4'-phenylvinyl-3',4',5',6'-tetrahydro-7'H-spiro[isobenzofuran-1,2'-pyrrolidone[2,3-c]pyrrole]

[0171]

[0172] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield 85%, 1 H NMR (400MHz, CDCl3) δ7.45–7.27(m,8H),7.18(d,J=7.4Hz,1H),6.65(d,J=15.6Hz,1H),6.13(dd,J=15.7,8.9Hz,1H),3.83(s,2H), 3.78(dd,J=18.6,12.5Hz,1H),3.03(s,3H),2.34(dd,J=13.2,11.6Hz,1H),2.19(dd,J=13.2,5.8Hz,1H),1.62(s,3H),1.56(s,3H).

[0173] Example 22 Synthesis of 6'-methyl-4'-(4-fluoro-phenylvinyl)-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0174]

[0175] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield 69%, 1H NMR (400MHz, CDCl3) δ7.38–7.19(m,5H),7.15(dd,J=7.1,1.8Hz,1H),7.07–6.94(m,2H),6.58( d,J=15.7Hz,1H),6.01(dd,J=15.7,9.0Hz,1H),4.23(ddd,J=12.7,11.1,2.9Hz,1H),3.95(ddd, J=11.2,5.9,1.0Hz,1H),3.83(d,J=1.4Hz,2H),3.65(td,J=10.2,6.1Hz,1H),3.16–3.08(m,1H ),3.06(s,3H),2.69–2.61(m,1H),2.27(dd,J=13.6,11.4Hz,1H),2.16(dd,J=13.5,6.0Hz,1H).

[0176] Example 23 Synthesis of 6'-methyl-4'-(4-chloro-phenylvinyl)-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0177]

[0178] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: yellow powder, yield is 87%, 1 H NMR (400MHz, CDCl3) δ7.63–7.21 (m, 8H), 6.62 (d, J = 15.7Hz, 1H), 6.10 (dd, J = 15. 7,9.0Hz,1H),4.24(ddd,J=12.7,11.1,2.9Hz,1H),3.95(dd,J=11.3,5.7Hz,1H), 3.89–3.78(m,2H),3.73–3.60(m,1H),3.16–3.09(m,1H),3.05(s,3H),2.65(dd, J=16.3,2.8Hz,1H),2.27(dd,J=13.6,11.3Hz,1H),2.16(dd,J=13.6,5.7Hz,1H).

[0179] Example 24 Synthesis of 6'-methyl-4'-(4-methyl-phenylvinyl)-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0180]

[0181] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield is 86%,1 H NMR(400MHz, CDCl3)δ7.34(dd,J=7.0,2.1Hz,1H),7.30–7.20(m,5H),7.19–7.10(m,3H),6.58(d, J=15.7Hz,1H),6.04(dd,J=15.7,9.0Hz,1H),4.24(ddd,J=12.6,11.1,2.9Hz,1H),3.95(dd,J=11 .2,5.7Hz,1H),3.82(s,2H),3.64(td,J=10.3,6.2Hz,1H),3.17–3.06(m,1H),3.05(s,3H),2.65( dd,J=16.4,2.7Hz,1H),2.34(s,3H),2.26(dd,J=13.6,11.3Hz,1H),2.16(dd,J=13.6,6.0Hz,1H).

[0182] Example 25 Synthesis of 6'-methyl-3'-propyl-4'-phenylvinyl-3',4',5',6'-tetrahydro-7'H-spiro[isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0183]

[0184] The specific operation steps are the same as those in Example 1. Its physical and chemical properties are as follows: white powder, yield is 73%, 1 H NMR (400MHz, CDCl3) δ7.43–7.18(m,8H),7.12(dt,J=5.7,3.3Hz,1H),6.58(dd,J=15.9,9.7Hz,1H),6.43(d,J=1 5.9Hz,1H),4.17(ddd,J=13.1,11.0,2.7Hz,1H),4.01–3.95(m,1H),3.86(d,J=17.8Hz,1H),3.74(d,J=18.1Hz,1 H),3.32(dd,J=9.8,6.1Hz,1H),3.09–2.95(m,4H),2.58(dd,J=16.2,2.5Hz,1H),2.50(ddd,J=11.2,6.2,2.6Hz, 1H), 1.10 (dddd, J=16.4, 12.9, 8.8, 6.3Hz, 2H), 0.86 (ddtd, J=11.7, 9.5, 4.6, 2.3Hz, 2H), 0.70 (t, J=7.2Hz, 3H).

[0185] Example 26 Determination of antibacterial activity of spiroketal derivatives

[0186] The plate inhibition mycelium growth rate method was used to evaluate the in vitro antibacterial activity. The test strains were selected for activation on PDA plates, including rice sheath blight, rapeseed sclerotinia, wheat fusarium, and cucumber gray mold. The compound was prepared into a 100 mg / L PDA drug-containing plate, and the test strain was made into a 5 mm diameter bacterial cake and placed in the center of the drug-containing culture dish. It was cultured at a constant temperature of 25°C until the test strain of the blank control dish grew close to the edge of the culture dish. The colony diameter of each drug-containing plate was measured by the cross method, and the inhibition rate of the compound on mycelium growth was calculated. The inhibition rate of each compound is shown in Table 2 below. The inhibition rate of the disease was calculated according to the following formula:

[0187]

[0188] Table 2 Antibacterial activity of spiroketal derivatives at 100 ppm

[0189]

[0190]

[0191] It can be seen that the compounds of the present invention have excellent fungicidal activity.

[0192] The inhibition rates of the exemplary compounds against Sclerotinia sclerotiorum and Botrytis cinerea of ​​cucumber at 25 ppm, 12.5 ppm, 6.25 ppm, 3.725 ppm, 1.6 ppm, 0.8 ppm, 0.4 ppm, 0.2 ppm and 0.1 ppm were measured by the above method, and the EC values ​​shown in Table 3 were calculated by SPSS software. 50 value.

[0193] Table 3 EC values ​​of exemplary compounds against Sclerotinia sclerotiorum and Botrytis cinerea 50 value

[0194]

[0195] All documents mentioned in the present invention are cited as references in this application, just as each document is cited as reference individually. In addition, it should be understood that after reading the above teachings of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the claims attached to this application.

Claims

1. A compound of formula (I), or a pesticide-acceptable salt thereof, or an optical isomer thereof, in: X is NR 4 or O; R 4 is selected from hydrogen, substituted or unsubstituted C 1-8 Alkyl, substituted or unsubstituted C 1-8 Alkoxy, substituted or unsubstituted C 1-4 Alkyl-(C 6-10 aryl or 5-6 membered heteroaryl), substituted or unsubstituted C 6-10 Aryl or substituted or unsubstituted 5-6 membered heteroaryl; wherein the substitution means that one or more (such as 1, 2, 3 or 4) H on the group is independently substituted by a substituent selected from the following group: C 1-6 Alkyl, C 1-6 Haloalkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, amino, NH-C 1-4 Alkyl and N(C 1-4 Alkyl)2; R 1 is selected from H, halogen, substituted or unsubstituted C 1-8 Alkyl, unsubstituted C 2-8 Alkenyl, unsubstituted C 2-8 Alkynyl, substituted or unsubstituted C 3-8 Cycloalkyl, substituted or unsubstituted C 0-4 Alkylene-R 3a , substituted or unsubstituted C 0-4 Alkenylene-R 3b , substituted or unsubstituted C 0-4 Alkynylidene-R 3c , where R 3a , R 3b and R 3c Each independently selected from substituted or unsubstituted C 3-8 Cycloalkyl, substituted or unsubstituted 3-8 membered heterocyclic group, substituted or unsubstituted C 6-10 Aryl, substituted or unsubstituted 5-10 membered heteroaryl; wherein the substitution means that one or more (such as 1, 2, 3 or 4) H on the group is independently substituted by a substituent selected from the following group: C 1-6 Alkyl, C 1-6 Haloalkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, amino, NH-C 1-4 Alkyl and N(C 1-4 Alkyl)2; Ring A is selected from a substituted or unsubstituted 5-7 membered heterocyclic group containing at least one O atom, a substituted or unsubstituted 5-7 membered heterocyclic group containing at least one O atom, and C 6-10 Aryl, substituted or unsubstituted 5-7 membered heterocyclyl containing at least one O atom and 5-6 membered heteroaryl; wherein the substitution means that one or more (such as 1, 2, 3 or 4) H on the group is independently selected from the following R 3 Replacement: H, C 1-6 Alkyl, C 1-6 Haloalkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 haloalkoxy, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, amino, NH-C 1-4 Alkyl and N(C 1-4 Alkyl)2; R 2 is selected from hydrogen, halogen, substituted or unsubstituted C 1-8 Alkyl or substituted or unsubstituted phenyl, wherein the substitution means that one or more (such as 1, 2, 3 or 4) H on the group is independently substituted by a substituent selected from the following group: C 1-6 Alkyl, C 1-6 Haloalkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, amino, NH-C 1-4 Alkyl and N(C 1-4 Alkyl)2.

2. The compound of formula (I) according to claim 1, or its pesticide acceptable salt, or optical isomer, characterized in that: R 1 is selected from substituted or unsubstituted C 6-10 Aryl, substituted or unsubstituted 5-10 membered heteroaryl, substituted or unsubstituted C 1-4 Alkenylene-C 6-10 Aryl, wherein the substitution refers to one or more (such as 1, 2, 3 or 4) H on the group is independently substituted by a substituent selected from the group consisting of: C 1-6 Alkyl, C 1-6 Haloalkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, amino, NH-C 1-4 Alkyl and N(C 1-4 Alkyl)2.

3. The compound of formula (I) according to claim 1, or its pesticide acceptable salt, or optical isomer, characterized in that: The compound has a structure shown in any one of formula II-X: In the formula, R 1 , R 2 , R 3 and X are each independently as defined above, R 3 0, 1, 2, 3 or 4.

4. The compound of formula (I) according to claim 1, or its pesticide acceptable salt, or optical isomer, characterized in that: R 4 is selected from hydrogen, substituted or unsubstituted C 1-8 Alkyl, substituted or unsubstituted C 1-4 Alkylene-C 6-10 Aryl, substituted or unsubstituted C 6-10 Aryl, substituted or unsubstituted C 1-8 Alkoxy, wherein the substitution refers to one or more (such as 1, 2, 3 or 4) H on the group is independently substituted by a substituent selected from the following group: 1-6 Alkyl, nitro, cyano, halogen, C 1-6 Alkoxy, C 1-6 Haloalkyl, hydroxyl, amino, NH-C 1-4 Alkyl, N(C 1-4 Alkyl)2.

5. The compound of formula (I) according to claim 1, or its pesticide acceptable salt, or optical isomer, characterized in that: R 2 is selected from hydrogen, substituted or unsubstituted C 1-8 Alkyl, wherein the substitution means that one or more (such as 1, 2, 3 or 4) H on the group is independently substituted by a substituent selected from the group consisting of: C 1-6 Alkyl, nitro, cyano, halogen, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 1-6 Haloalkyl, hydroxyl, amino, NH-C 1-4 Alkyl, N(C 1-4 Alkyl)2, preferably R 2 For H.

6. The compound of formula (I) according to claim 1, or its pesticide acceptable salt, or optical isomer, characterized in that: R 3 Independently selected from H, C 1-4 Alkyl, C 1-4 Haloalkyl, nitro, fluorine, chlorine, bromine, iodine, C 1-4 Alkoxy, C 1-4 Haloalkoxy, preferably R 3 Independently selected from H, C 1-4 Alkyl, C 1-4 Haloalkyl, fluorine, chlorine.

7. The compound of formula (I) according to claim 1, or its pesticide acceptable salt, or optical isomer, characterized in that: The compound is selected from the group consisting of:

8. An agricultural composition comprising: A compound of formula I as claimed in claim 1, or a pesticide-acceptable salt thereof, or an optical isomer or geometric isomer thereof; and a pesticide-acceptable carrier and / or excipient.

9. Use of the compound according to claim 1, or its pesticide acceptable salt or optical isomer, or the agricultural composition according to claim 8 in the preparation of an agricultural fungicide.

10. A method for preparing the compound according to claim 1, comprising the steps of: The compound of formula a and the compound of formula b or the compound of formula c react under the conditions of a solvent and an acid catalyst to obtain a compound of formula I: in, R 1 , R 2 , R 3 and X is independently as defined in claim 1, Y is halogen or OR 5 , R 5 It is H, C1-6 alkyl, C6-10 aryl.

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