Spirocyclic ketal derivatives, processes for their preparation and uses thereof

Abstract

The present application relates to a spirocyclic ketal derivative and its preparation method and use. Specifically, a compound of formula (I), or a pesticidally acceptable salt thereof, or an optical isomer is provided, and the compound of the present application has excellent inhibitory effect on plant pathogenic fungi.

Description

Technical Field

[0001] This invention belongs to the field of pesticide technology, specifically relating to a spirocyclic ketal derivative with bactericidal activity, its preparation method, and its uses. Background Technology

[0002] Food is fundamental to human survival, and with the continuous increase in the world's population, the pressure on food production is growing. In the process of food production, diseases, pests, weeds, and other harmful organisms are the main factors affecting crop production and reducing grain yield and quality. Therefore, controlling crop diseases is key to increasing grain production. Pesticides are a powerful means of suppressing diseases.

[0003] Fungicides, as a member of the pesticide family, are a class of agents used to control plant diseases caused by various pathogenic microorganisms. They are a collective term for agents that kill or inhibit the growth of pathogens without hindering normal plant growth, and constitute an important type of pesticide. However, with the widespread use of fungicides, pathogens are increasingly developing resistance to these agents, thus necessitating the research of more novel fungicides to address this problem. Summary of the Invention

[0004] The purpose of this invention is to provide a novel spirocyclic ketal derivative with excellent bactericidal activity, its preparation method, and its uses.

[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 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 heteroaryl), substituted or unsubstituted C 6-10 A 5-6 membered heteroaryl group, either substituted or unsubstituted; wherein the substitution refers to one or more (e.g., 1, 2, 3, or 4) H atoms on the group being independently substituted by a substituent selected from the group consisting of: C 1-6 Alkyl, C 1-6 Halogenated alkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, amino groups, NH-C 1-4Alkyl and N(C) 1-4 Alkyl)2;

[0010] R 1 Selected from H, halogens, substituted or unsubstituted C 1-8 Alkyl, unsubstituted C 2-8 alkenyl, unsubstituted C 2-8 Alkyne group, substituted or unsubstituted C 3-8 cycloalkyl, substituted or unsubstituted C 0-4 Alkylene-R 3a C, substituted or unsubstituted 0-4 imide-R 3b C, substituted or unsubstituted 0-4 Ethyne-R 3c , where R 3a R 3b and R 3c Each is independently selected from substituted or unsubstituted C 3-8 Cycloalkyl, substituted or unsubstituted 3-8 membered heterocyclic groups, substituted or unsubstituted C 6-10 Aryl, substituted or unsubstituted 5-10 membered heteroaryl; wherein the substitution refers to one or more (e.g., 1, 2, 3 or 4) H atoms on the group being independently substituted by substituents selected from the group consisting of: C 1-6 Alkyl, C 1-6 Halogenated alkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, amino groups, NH-C 1-4 Alkyl and N(C) 1-4 Alkyl)2;

[0011] Ring A is selected from substituted or unsubstituted 5-7 membered heterocyclic groups containing at least one O atom, substituted or unsubstituted 5-7 membered heterocyclic groups containing at least one O atom, and C. 6-10 Aryl, substituted or unsubstituted 5-7 membered heterocyclic groups containing at least one O atom and 5-6 membered heteroaryl; wherein the substitution refers to one or more (e.g., 1, 2, 3 or 4) H atoms on the group being independently selected from the group consisting of R atoms from the following group. 3 Replacement: H, C 1-6 Alkyl, C 1-6 Halogenated alkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, substituted or unsubstituted phenyl groups, substituted or unsubstituted benzyl groups, amino groups, NH-C 1-4 Alkyl and N(C) 1-4 Alkyl)2;

[0012] R 2 Selected from hydrogen, halogen, substituted or unsubstituted C 1-8Alkyl or substituted or unsubstituted phenyl groups, wherein the substitution refers to one or more (e.g., 1, 2, 3, or 4) H atoms on the group being independently substituted by substituents selected from the group consisting of: C 1-6 Alkyl, C 1-6 Halogenated alkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, amino groups, NH-C 1-4 Alkyl and N(C) 1-4 Alkyl)2.

[0013] In another preferred example, R 1 Selected from substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted 5-10 heteroaryl groups, substituted or unsubstituted C 1-4 imide-C 6-10 aryl, wherein the substitution refers to one or more (e.g., 1, 2, 3, or 4) H atoms on the group being independently substituted by a substituent selected from the group consisting of: C 1-6 Alkyl, C 1-6 Halogenated alkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, amino groups, 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 of formulas II-X:

[0015]

[0016] In the formula, R 1 R 2 R 3 As defined above, R and X are independent of each other. 3 It can be 0, 1, 2, 3, or 4.

[0017] In another preferred embodiment, R 4 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 Alkyl group, wherein the substitution refers to one or more (e.g., 1, 2, 3, or 4) H atoms on the group being 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 alkyl, hydroxyl, amino, NH-C 1-4 Alkyl, N(C)1-4 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 imide-C 6-10 Aryl, substituted or unsubstituted 5-10 membered heteroaryl groups, wherein the substitution refers to one or more (e.g., 1, 2, 3 or 4) H atoms on the group being independently substituted by substituents selected from the group consisting of: C 1-6 Alkyl, nitro, cyano, halogen, C 1-6 Alkoxy, C 1-6 Halogenated alkyl, hydroxyl, amino, NH-C 1-4 Alkyl, N(C) 1-4 Alkyl)2.

[0019] In another preferred embodiment, R 2 Selected from hydrogen, substituted or unsubstituted C 1-8 Alkyl, wherein the substitution refers to one or more (e.g., 1, 2, 3, or 4) H atoms on the group being 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 groups, C 1-6 Halogenated alkyl, 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 or heteroaryl group independently contains one, two, or three heteroatoms selected from O, N, and S.

[0021] In another preferred embodiment, R 4 For 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 Selected from substituted or unsubstituted phenyl groups, substituted or unsubstituted C groups 1-2 alkylene-phenyl, substituted or unsubstituted C 1-2An alkenyl-phenyl group, a substituted or unsubstituted five- or six-membered heterocyclic group, preferably wherein the substitution refers to one or more (e.g., 1, 2, 3, or 4) H atoms on the group being independently substituted by a substituent selected from the group consisting of: C 1-4 Alkyl, nitro, cyano, halogen, C 1-4 Alkoxy, C 1-4 Halogenated alkyl groups.

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

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

[0025] In another preferred embodiment, R 2 Let H be the number of 'R', and R be the number of 'R'. 3 For H.

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

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

[0028]

[0029]

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

[0031] A 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 and 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-described compound, or a pesticide-acceptable salt thereof, or an optical isomer and a geometric isomer thereof, 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] A third aspect of the invention provides the use of the compound of the first aspect, or a pesticide-acceptable salt thereof, or an optical isomer thereof, or the agricultural composition of claim 4, in the preparation of an agricultural fungicide.

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

[0037] Compound a and compound b or compound c react under solvent and acid catalyst conditions to obtain compound I:

[0038]

[0039] Among them, R 1 R 2 R 3 X is independent of what is defined in the first aspect of the invention.

[0040] Y represents 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 protic acid or a Lewis acid, selected from one or more of the following: o-nitrobenzoic acid, m-nitrobenzoic acid, diphenyl phosphate, diphenylsulfonamide, trifluoroacetic acid, trichloroacetic acid, acetic acid, phosphoric acid, hydrochloric acid, sulfuric acid, boron trifluoride diethyl ether complex, ferric 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 to 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 following specific steps: under nitrogen protection, adding a compound of formula a, formula b, or formula c and an acid catalyst such as scandium trifluoromethanesulfonate into a dry reaction vessel, adding a solvent such as CH2Cl2, and reacting the mixture at room temperature to obtain the product.

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

[0047] The molar ratio of compound a to 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 this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Detailed Implementation

[0049] Through extensive and in-depth research, and by conducting numerous screenings and tests, the inventors have developed a novel spirocyclic ketal derivative with excellent bactericidal activity, along with its preparation method and applications. This invention is based on this foundation.

[0050] the term

[0051] Unless otherwise defined, 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 pertains.

[0052] As used herein, the terms “containing” or “including (comprise)” can be open-ended, semi-closed, or closed. In other words, the terms also include “consistently made of” or “composed of”.

[0053] 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" indicates that the alkyl group has 1 to 6 carbon atoms.

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

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

[0056] The term "alkyl" refers to a straight-chain or branched, unsubstituted alkyl group having 1-8 carbon atoms (i.e., C46-C56). 1-8 Alkyl groups, preferably hydrocarbon groups with 1-6 carbon atoms (i.e., C16, C26, C36, C46, ​​C56, C6 ... 1-6 Alkyl groups, more preferably hydrocarbon groups with 1-4 carbon atoms (i.e., C4 groups). 1-4 Alkyl). 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, etc.

[0057] The term "alkenyl" refers to a group having 2-8 carbon atoms (i.e., C64-C84). 2-8 alkenyl), preferably 2-6 carbon atoms (i.e., C 2-6 Alkenyl) or 2-4 carbon atoms (i.e., C) 2-4 Alkenyl groups are straight-chain or branched hydrocarbon groups having 1-2 carbon-carbon double bonds. Examples of alkenyl groups include, but are not limited to, vinyl, propenyl, and butadienyl (including 1,2-butadienyl and 1,3-butadienyl).

[0058] The term "alkynyl" refers to a group having 2-8 carbon atoms (i.e., C24-C24). 2-8 (Alkyne group), preferably 2-6 carbon atoms (i.e., C10, C20, C30, C40, C50, C60, C60, C70, C6 ... 2-6 (alkynyl group) or 2-4 carbon atoms (i.e., C46) 2-4 Alkyne group, and has 1-2 carbon-carbon triple bonds in a straight-chain or branched hydrocarbon group.

[0059] The term "alkylene" refers to a saturated divalent hydrocarbon group derived from an alkyl group as defined above by losing two hydrogen atoms (i.e., C46). 1-6 Alkylene group, preferably a hydrocarbon group with 1-4 carbon atoms (i.e., C464-C ... 1-4 Alkylene), more preferably 1-3 carbon atoms (i.e., C10-C2 ... 1-3Alkylenes. Examples of "alkylenes" include, but are not limited to, methylene, ethylene, isopropylene, etc. Alkenylenes and yntylides are divalent groups derived from alkenyl and yntylide groups as defined above by losing two hydrogen atoms.

[0060] The term "cycloalkyl" refers to a non-aromatic, saturated, or partially unsaturated cyclic hydrocarbon group, which may be substituted by one or more substituents as described in this application, having 3-6 carbon atoms to form a monocyclic ring or 7-12 carbon atoms to form a bicyclic ring. As used herein, cycloalkyl groups have 3 to 8 cyclic carbon atoms (i.e., C64-C ... 3-8 cycloalkyl groups or 3 to 6 cyclic carbon atoms (i.e., C164-C ... 3-6 Cycloalkyl. Examples of monocyclic cycloalkyl groups 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, and cyclooctyl. Exemplary bridged bicyclic cycloalkyl groups include, but are not limited to, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, and 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 groups have 6 to 10 ring carbon atoms (i.e., C64 ... 6-10 Aryl groups comprise bicyclic groups, wherein the bicyclic group includes an aromatic ring (such as benzo[a]carbon ring) that is fused to a saturated or partially unsaturated carbocyclic or heterocyclic structure. 3-6 Aromatic groups typically 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 term "aryl" includes structures with aryl rings fused to cycloalkyl or heterocycloalkyl groups.

[0062] The terms “heterocyclic,” “heterocyclic,” “heterocyclic group,” and “heterocyclic alkyl” refer to optionally substituted, fully saturated, or partially unsaturated (e.g., containing one or two double bonds) non-aromatic cyclic groups, which can be 3-7 membered monocyclic, 7-11 membered bicyclic, or 10-15 membered tricyclic systems, having at least one heteroatom in at least one carbon-containing ring. Each ring of a heteroatom-containing heterocyclic group may have one, two, or three heteroatoms selected from oxygen, nitrogen, and sulfur. As used herein, heterocyclic groups have 3 to 10 ring atoms (i.e., 3-10 membered heterocyclic groups), 3 to 8 ring atoms (i.e., 3-8 membered heterocyclic groups), 3 to 7 ring atoms, or 3 to 6 ring atoms (i.e., 3-6 membered heterocyclic groups), or 5 to 6 ring atoms (i.e., 5-6 membered heterocyclic groups). The "heterocyclic group" may be substituted by one or more of the substituents described in this application. Examples of "heterocyclic groups" include, but are not limited to, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, morpholino, thiomorpholino, piperazinyl, homopiperazinyl, propylene oxide, imidazoalkyl, 3-azabicyclo[3.1.0]hexyl, 3-azabicyclo[4.1.0]heptyl, azabicyclo[2.2.2]hexyl, N-pyridylurea, pyrimidinoneyl, and 1,1-dioxo-thiomorpholinyl.

[0063] The term "heteroaryl" or "heteroary ring" refers to a heteroaryl system containing one or more heteroatoms selected from oxygen, nitrogen, and sulfur, including monocyclic, bicyclic, or polycyclic fused systems. The heteroaryl group can be substituted by one or more substituents as described in this application. As used herein, the heteroaryl group can 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., ...). (5-6 membered heteroaryl). A heteroaryl group may have 1 to 3 cyclic heteroatoms, 1 to 2 cyclic heteroatoms, or 1 cyclic heteroatomum, wherein the cyclic heteroatoms are independently selected from oxygen, nitrogen, and sulfur. Examples of "heteroaryl" include, but are not limited to, pyrroleyl, pyridyl, pyrazolyl, imidazolyl, pyrazinyl, imidazopyridyl, benzofuranyl, pyrimidinyl, triazolyl, tetrazolyl, furanyl, thiophenyl, thiazolyl, quinolinyl, isoquinolinyl, indoleyl, etc.

[0064] The term "substituted" means that one or more hydrogen atoms in a specific group are substituted by any of the substituents mentioned in this specification. Unless otherwise specified, "substituted" means that one or more (e.g., 2, 3, or 4) hydrogen atoms on a group are independently substituted by a group selected from the group consisting of: C 1-6 Alkyl, C 1-6 Halogenated alkyl, nitro, cyano, halogen, hydroxyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, amino groups, NH-C 1-4 Alkyl and N(C) 1-4 Alkyl)2.

[0065] Active ingredients

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

[0067]

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

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

[0070] This invention aims to include salts of compounds. A “pesticide-acceptable salt” can have more than one charged atom, and the multiple charged atoms can have multiple balanced ions. In an exemplary embodiment, the salt form of the compound is produced, which can transform other oily or viscous compounds into more easily handled solid substances. 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 also affecting biological properties such as bioavailability, pharmacokinetics, and pharmacodynamics. Therefore, any salt form, such as pharmaceutically acceptable salts of the compounds of the present invention, including salts of inorganic acids or organic acids, is within the scope of this invention. Simultaneously, various crystal forms of pharmaceutically acceptable salts of the compounds of the present invention are also within the scope of this invention. Any prodrug of the compounds of the present invention is also within the scope of this invention. For example, R and R t It can be any group that can be cleaved in vivo to produce amines (such as primary or secondary amines).

[0071] As used herein, the term "pesticide-acceptable salt" refers to those salts that, within reasonable medical judgment, are suitable for contact with human and lower animal tissues without excessive toxicity, irritation, allergic reactions, etc., and that are proportionate to a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. Pharmaceutically acceptable salts of the compounds of this 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 reacting an amino group with an inorganic acid (such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid) or with an organic acid (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, hydrogen sulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, gluconate, glyceryl phosphate, gluconate, hemisulfate, heptaate, hexanoate, hydroiodate, 2-hydroxy-ethanesulfonate, lacturonate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, dihydroxynaphthalate, pectate, persulfate, 3-phenylpropionate, phosphate, neopentanoate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc.

[0072] A solvate is a combination or complex of one or more solvent molecules with a compound 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 can exist in a non-solventized form or in a solvated form with pharmaceutically acceptable solvents such as water and ethanol; therefore, the present invention will include both solvated and non-solventized forms.

[0073] Some compounds exist as tautomers. These tautomers exist in equilibrium with each other. For example, amide-containing compounds can exist in equilibrium with imine tautomers. Regardless of which tautomer is exhibited, and regardless of the equilibrium nature between the tautomers, those skilled in the art will understand that a compound comprises all or every tautomer of the compound. Therefore, amide-containing compounds should be understood as including their imine tautomers. Similarly, imine-containing compounds should be understood as including their amide tautomers.

[0074] The compounds of the present invention may contain an asymmetric center or a chiral center, and thus exist in various stereoisomeric forms. The compounds may be chiral, racemic, or may exist as compositions comprising one or more stereoisomers. The present invention includes enantiomers, diastereomers, racemic mixtures, enantiomer-rich mixtures, and diastereomer-rich mixtures. All stereoisomeric forms of the compounds of the present invention, including but not limited to diastereomers, enantiomers, and sterically hindered isomers, and mixtures thereof, such as racemic mixtures, will form part of the present invention. Additionally, the asymmetric carbon atom may be present in a substituent such as an alkyl group. All such isomers and mixtures thereof are intended to be included within the present invention. If a specific enantiomer of a compound of the present invention is desired, it can be prepared by asymmetric synthesis or by derivatization with a chiral auxiliary agent, wherein the resulting diastereomeric mixture is isolated and the auxiliary group is cleaved 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, it can form a diastereomeric salt with a suitable optically active acid or base. The diastereomer thus formed can then be resolved by fractional crystallization or chromatography known in the art, and the pure enantiomer can subsequently be recovered. Furthermore, the separation of enantiomers and diastereomers can be achieved using chromatography with a chiral stationary phase.

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

[0076] In this document, unless otherwise stated, the structures described 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 may be used, for example, as analytical tools or probes in bioassays. Any formula or structure given herein is also intended to represent both the unlabeled and isotopically labeled forms of the compounds. Isotopically labeled compounds have the structures described by the formulas given herein, except that one or more atoms are replaced by atoms having selected atomic masses or mass numbers. Examples of isotopes that may be incorporated into the compounds of this disclosure include, but are not limited to, 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 isotope-labeled compounds disclosed herein, for example, those doped with radioactive isotopes such as 3 H and 14 Compounds of C can be used in metabolic studies, reaction kinetic 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 patient radiotherapy.

[0077] Compositions and their applications

[0078] The terms "active substance of the present invention" or "active compound of the present invention" refer to the compound of the present invention, its optical isomer, or a pesticide-acceptable salt, which has significant bactericidal activity, broad bactericidal spectrum, and strong stability.

[0079] Therefore, this invention provides the use of the active ingredient of this invention as an agricultural fungicide and for the prevention and control of plant pathogens.

[0080] Plant pathogens that can be used in this invention include (but are not limited to): Blumeria graminis, Podosphaera leucotricha, Sphaerotheca fulliginea, Uncinula necator, Gymnosporangium sabinae, Hemileiavastatrix, Phakopsora pachyrhizi or Phakopsora meibomian, Puccinia recondite, Puccinia graminis or Puccinia striiformis, Uromyces ndiculatus, Albugocandida, Bremia lactucae, Peronospora pisi, Phytophthora *Infestans*, *Plasmopat*, *Pythium ultimum*, *Pseudoperonospora humuli* or *Pseudoperonospora cubensis*, *Alternaria solan*, *Cercosporabeticola*, *Cladosporium cucumerinum*, *Cochliobolus sativus* or *Cochliobolus miyabeanus*, *Colletotrichumlindemuthanium*, *Cycloconium*, *Diaporthe citri*, *Gloeosporium laeticolor*, *Glomerella cingulata*, *Guignardia bidwell*, *Leptosphaeria* maculans, or Le tosphaeria nodorum, Magnaphtheria grisea, My cosphaerella graminicola, Mycosphaerella arachifoliaThe fungi causing banana black streak leaf spot include *Mycosphaerella fijiensis*, *Phaeosphaeria nodorum*, *Pyrenophora teres* or *Pyrenophora tritici repentis*, *Ramularia collo cygnI* or *Ramularia areola*, *Rhynchosporiusecalis*, *Septoriaapii* or *eptoria lycopercisi*, *Typhula incarnata*, *Venturia inaequalis*, *Corticium graminearum*, *Fusarium oxysporum*, *Gaeumannomyces graminIs*, *Rhizoctonia solani*, and *Sarocladium*. *Sclerotium oryzae*, *Closporium tapesiae*, *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*, *Botrytiscinerea*, *Penicillium expansum*, *Rhizopus* stolonifer, Sclerotinia sclerotiorum, Verticillium alboatrum, Alternaria brassicicola, Aphanomyceseuteiches, Ascochytalentis, Aspergillus flavus, Cladosporium herbarum, Cochliobolus sativus, Colletotrichum coccodes, Fusarium, Gibberella zeae, Macrophomina phaseolina, Monographella nivalis, Penicillium expansum, Phomalingam, Phopsis sojae, Phytophthora cactorum, Pyrenophora graminea, Pyricularia oryzae, Pythium ultimum, Rhizoctonia solan, Rhizopus *Sclerotium rolfsii*, *Septorianodorum*, *Typhulaincarnata*, *Verticillium dahliae*, *Nectria galligena*, *Monilinia laxa*, *Exobasidium vexans*, *Taphrina deformans*, *Phaemoniellaclam dospora*, *Eutypa lata*, *Ganoderma boninense*, *Rigidoporus linosus*, *Botrytis cinerea*, *Rhizoctonia solani*, *Helminthosporium* *Plasmodiophora brassicae*, *Xanthomonas campestris* pv. oryzae, *Pseudomonas syringa* pv. lachrymans, *Pseudomonas syringa* pv. lachrymans, *Erwinia*, *Erwinia amyloliquefaciens*.(amy lovora), preferably Fusarium graminearum, rice sheath blight, cucumber gray mold, and rapeseed sclerotinia.

[0081] The active ingredients of this invention can be prepared in conventional ways into fungicide compositions, such as solutions, emulsions, foams, powders, pastes, and granules. Aerosols are microcapsules of natural or synthetic materials impregnated with the active ingredients in polymers. Other applications include seed coating formulations, preparations for use with combustion devices such as fumigation cartridges, fumigation pans, and fumigation canisters, as well as ULV cold and hot fog formulations.

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

[0083] Liquids are generally suitable as diluents or carriers, such as aromatic hydrocarbons like xylene, toluene, or alkylnaphthalenes; chlorinated aromatic or aliphatic hydrocarbons like chlorobenzene, vinyl chloride, or dichloromethane; aliphatic hydrocarbons like cyclohexane or paraffin; alcohols like ethanol or ethylene glycol and their ethers or polymers; ketones like acetone, methyl ethyl ketone, methyl isobutyl ketone, or cyclohexanone; and other polar solvents like N,N-dimethylformamide, dimethyl sulfoxide, or water.

[0084] Liquefied gas diluents or carriers refer to liquids that become gaseous at normal temperature and pressure, such as aerosol propellants, halogenated hydrocarbons, and 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 silicates, silicates, and alumina. Solid carriers for granulation are aged and graded natural zircon, such as calcite, pumice, marble, sepiolite, and dolomite, as well as inorganic and organic coarse powders synthesized into granules. Organic materials include sawdust, coconut husks, corncobs, and tobacco stalks and their crushed particles.

[0086] Nonionic and anionic emulsifiers can be used as emulsifiers and / or foam forming agents, 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 and methylcellulose.

[0087] Binders such as carboxymethyl cellulose and natural or synthetic polymers in powder, granule or emulsion form, such as gum arabic, polyethylene and polyethylene acetate, may be used in the formulation.

[0088] Colorants can include inorganic dyes such as iron oxide, cobalt oxide, and Prussian blue; organic dyes such as azo dyes or metallic titanium cyanide dyes; and trace nutrients such as salts of iron, manganese, zinc, boron, copper, cobalt, and aluminum.

[0089] The active compounds of the present invention can be used in mixtures with other active compounds, including insecticides, baits, acaricides, nematicides and / or growth regulators.

[0090] The active compounds of the present invention can be mixed with synergists to enhance the activity of the compounds of the present invention.

[0091] These formulations typically contain 0.001-99.999% by weight, preferably 0.1-99.9% by weight, and more preferably 0.5-90% by weight of the active compound of the present invention in the bactericidal composition. The energy content of the active compound in dosage forms prepared from commercial formulations 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 compound a and compound b or compound c. The conditions of the method, such as raw materials, solvent, temperature, acid, ratio, and reaction time, can be selected as needed, for example (but not limited to) the following examples.

[0094]

[0095] Among them, R 1 R 2 R 3 X is independent of what is defined in the first aspect of the invention.

[0096] Y represents 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 protic acid or a Lewis acid, selected from one or more of the following: o-nitrobenzoic acid, m-nitrobenzoic acid, diphenyl phosphate, diphenylsulfonamide, trifluoroacetic acid, trichloroacetic acid, acetic acid, phosphoric acid, hydrochloric acid, sulfuric acid, boron trifluoride diethyl ether complex, ferric 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 to 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 following specific steps: under nitrogen protection, adding a compound of formula a, formula b, or formula c and an acid catalyst such as scandium trifluoromethanesulfonate into a dry reaction vessel, adding a solvent such as CH2Cl2, and reacting the mixture at room temperature to obtain the product.

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

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

[0104] The main advantages of this invention include:

[0105] The spirocyclic ketal compounds of this invention are characterized by high efficiency, low toxicity, safety for non-target organisms, easy degradation in the environment, and low resistance to harmful organisms, making them very suitable as new agricultural fungicides.

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

[0107] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. Percentages and parts are by weight unless otherwise stated.

[0108] The target products in Examples 1 to 17 below 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0110]

[0111] After placing a magnetic stir bar in a 10 mL Schlenk reaction tube and drying the tube, 2,3-dioxopyrrolidine (27.7 mg, 0.1 mmol), isochoric ketal (16.4 mg, 0.1 mmol), and scandium trifluoromethanesulfonate (4.9 mg, 0.01 mmol) were added sequentially under nitrogen protection. Redistilled CH2Cl2 (1.5 mL) was then added, and the mixture was stirred at room temperature. Under TLC monitoring, the mixture was stirred at room temperature until the reaction was complete, and then the reaction was stopped. The product was purified by thin-layer chromatography (developing solvent: petroleum ether / ethyl acetate). The target product was confirmed by NMR spectroscopy and high-resolution mass spectrometry.

[0112] Its physicochemical properties are as follows: white powder, yield 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0114]

[0115] The specific operating steps are the same as in Example 1. Its physicochemical 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0117]

[0118] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white powder, yield 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0120]

[0121] The specific operating steps are the same as in Example 1. Its physicochemical 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0123]

[0124] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white powder, yield 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0126]

[0127] The specific operating steps are the same as in Example 1. Its physicochemical 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0129]

[0130] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white powder, yield 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0132]

[0133] The specific operating steps are the same as in Example 1. Its physicochemical 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0135]

[0136] The specific operating steps are the same as in Example 1. Its physicochemical 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0138]

[0139] The specific operating steps are the same as in Example 1. Its physicochemical 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0141]

[0142] The specific operating steps are the same as in Example 1. Its physicochemical 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0144]

[0145] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white powder, yield 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0147]

[0148] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white powder, yield 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0150]

[0151] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white powder, yield 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0153]

[0154] The specific operating steps are the same as in Example 1. Its physicochemical 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0156]

[0157] The specific operating steps are the same as in Example 1. Its physicochemical 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0159]

[0160] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 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'-styryl-3',4',5',6'-tetrahydro-7'H-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0162]

[0163] The specific operating steps are the same as in Example 1. Its physicochemical 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-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0165]

[0166] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white powder, yield 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-spirocyclic [isobenzofuran-1,2'-pyrrolidone[2,3-c]pyrrole]

[0168]

[0169] The specific operating steps are the same as in Example 1. Its physicochemical 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'-styryl-3',4',5',6'-tetrahydro-7'H-spirocyclic [isobenzofuran-1,2'-pyrrolidone[2,3-c]pyrrole]

[0171]

[0172] The specific operating steps are the same as in Example 1. Its physicochemical 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-styryl)-3',4',5',6'-tetrahydro-7'H-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0174]

[0175] The specific operating steps are the same as in Example 1. Its physicochemical 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-styryl)-3',4',5',6'-tetrahydro-7'H-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0177]

[0178] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: yellow powder, yield 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-styryl)-3',4',5',6'-tetrahydro-7'H-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0180]

[0181] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white powder, yield 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'-styryl-3',4',5',6'-tetrahydro-7'H-spirocyclic [isochroman-1,2'-pyrrolidone[2,3-c]pyrrole]

[0183]

[0184] The specific operating steps are the same as in Example 1. Its physicochemical properties are as follows: white powder, yield 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 spirocyclic ketal derivatives

[0186] The in vitro antibacterial activity was evaluated using the plate inhibition of mycelial growth rate method. Test strains, including *Rhizoctonia solani*, *Sclerotinia sclerotiorum*, *Fusarium graminearum*, and *Gyromitra esculenta*, were activated on PDA plates. Compounds were prepared as 100 mg / L PDA plates. Test strains were prepared into 5 mm diameter mycelial discs and placed in the center of the plate. The plates were incubated at 25°C until the test strains in the control plates reached near the edge. The colony diameter on each plate was measured using the cross-sectional method, and the inhibition rate of the compounds on mycelial growth was calculated. The inhibition rates of each compound are shown in Table 2. The inhibition rate against diseases was calculated using the following formula:

[0187]

[0188] Table 2. Antibacterial activity of spirocyclic ketal derivatives at 100 ppm

[0189]

[0190]

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

[0192] The inhibition rates of the exemplary compounds against *Sclerotinia sclerotinia* and *Botrytis cinerea* at concentrations of 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 determined using the above method. The EC50 values ​​are shown in Table 3 using SPSS software. 50 value.

[0193] Table 3. EC50 of exemplary compounds against *Sclerotinia sclerotinia* and *Gyromitra esculenta*. 50 value

[0194]

[0195] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A compound, or a pesticide-acceptable salt thereof, characterized in that, The compound has a structure of formula (IV) or formula (VII): In various forms: X is NR 4 ; R 4 Selected from substituted or unsubstituted C 1-8 Alkyl, substituted or unsubstituted C 1-8 Alkoxy, substituted or unsubstituted -C 1-4 Alkylene-C 6-10 aryl, substituted or unsubstituted C 6-10 aryl; wherein the substitution refers to one or more H atoms on the group being independently substituted by a substituent selected from the group consisting of: C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogens, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups; R 1 Selected from substituted or unsubstituted C 1-8 Alkyl, unsubstituted C 2-8 alkenyl, unsubstituted C 2-8 alkynyl group; Or R 1 Selected from substituted or unsubstituted phenyl groups, substituted or unsubstituted -C groups. 1-2 Alkylene-phenyl, substituted or unsubstituted -C2-alkenylene-phenyl, substituted or unsubstituted five- or six-membered heterocyclic groups containing one, two, or three heteroatoms selected from O, N, and S, wherein the substitution refers to one or more H atoms on the group being independently substituted by substituents selected from the group consisting of: C 1-4 Alkyl, nitro, cyano, halogen, C 1-4 Alkoxy, C 1-4 Halogenated alkyl groups; Where R 3 It can be 0, 1, 2 or 3, and R 3 Select independently from the following group: C 1-6 Alkyl, C 1-6 Halogenated alkyl groups, halogen C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups; R 2 Selected from hydrogen, halogen, substituted or unsubstituted C 1-8 Alkyl, wherein the substitution means that one or more H atoms on the group are independently substituted by substituents selected from the group consisting of: halogens; The compound in question is not: .

2. The compound of claim 1, or a pesticide-acceptable salt thereof, characterized in that, R 1 Selected from substituted or unsubstituted phenyl groups, and substituted or unsubstituted five- or six-membered heterocyclic groups containing one, two, or three heteroatoms selected from O, N, and S, wherein the substitution refers to one or more H atoms on the group being independently substituted by substituents selected from the group consisting of: C 1-4 Alkyl, nitro, cyano, halogen, C 1-4 Alkoxy, C 1-4 Halogenated alkyl groups.

3. The compound of claim 1, or a pesticide-acceptable salt thereof, characterized in that, R 1 The -C2-eneyl-phenyl group is substituted or unsubstituted, wherein the substitution refers to one or more H atoms on the group being independently substituted by substituents selected from the group consisting of: C 1-4 Alkyl, nitro, cyano, halogen, C 1-4 Alkoxy, C 1-4 Halogenated alkyl groups.

4. The compound of claim 1, or a pesticide-acceptable salt thereof, characterized in that, R 4 Selected from C 1-8 Alkyl, -C1 alkylene, -C6 aryl, C6 aryl or C 1-8 Alkyl group.

5. The compound of claim 1, or a pesticide-acceptable salt thereof, characterized in that, R 2 Selected from hydrogen or C 1-8 alkyl.

6. The compound of claim 1, or a pesticide-acceptable salt thereof, characterized in that, R 3 C 1-4 alkyl.

7. The compound of claim 1, or a pesticide-acceptable salt thereof, characterized in that, The compounds are selected from the group consisting of: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。 8. An agricultural composition comprising: The compound as claimed in claim 1, or a pesticide-acceptable salt thereof; And a pesticide-acceptable carrier.

9. Use of the compound of claim 1, or a pesticide-acceptable salt thereof, or the agricultural composition of claim 8, in the preparation of an agricultural fungicide; wherein the fungus is selected from one or more of the group consisting of: rice sheath blight pathogen (… Rhizoctonia solani ), wheat sheath blight fungus ( Rhizoctonia cerealis ), rapeseed sclerotinia pathogen ( Sclerotinia scleotiorum ), wheat scab ( Fusarium graminearum ), tomato gray mold ( Botrytis cinerea ), rice seedling bacterium ( Fusarium fujikuroi ), potato dry rot pathogen ( Fusarium sulphureum ), Sclerotium truncatum ( Sclerotinia trifoliolum ), Sclerotium sclerotiorum ( Sclerotinia minor ).

10. A method for preparing the compound of claim 1, or a pesticide-acceptable salt thereof, comprising the steps of: Compound a and compound b or compound c react under solvent and acid catalyst conditions to obtain compound I: ， in, R 1 R 2 R 3 X is independently as defined in claim 1, and the compound of formula I has the structure of formula (IV) or formula (VII) as defined in claim 1; Y represents halogen or OR 5 R 5 It is H, C1-6 alkyl or C6-10 aryl.

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