Thiazole oxime ether compounds and uses thereof

Abstract

The present application discloses a novel thiazole oxime ether compound with the structure shown in general formula I, wherein the definitions of the substituents are described in the specification. The compound of general formula I has excellent biological activity, and has good control effect on plant bacterial diseases and fungal diseases, and also has good insecticidal activity on agricultural pests. The present application includes the use of the compound of general formula I as a fungicide and an insecticide in agriculture and other fields.

Description

Technical Field

[0001] This invention belongs to the field of agricultural chemicals. Specifically, it relates to a thiazolyl oxime ether compound and its uses. Background Technology

[0002] Heterocyclic compounds possess highly efficient, low-toxicity, and broad-spectrum biological activities. Most of the bioactive compounds reported in patent literature have heterocyclic structures, with thiazoles being an important five-membered nitrogen- and sulfur-containing heterocyclic compound. Oxime ether derivatives are also a class of compounds with broad-spectrum biological activity, widely used in pesticides, herbicides, and fungicides. Since the introduction of the first commercially available oxime ether fungicide, cymoxanil, by DuPont in 1974, new commercial varieties have continuously emerged, such as azoxystrobin and oxime acetamiprid.

[0003] Patent CN106916084A discloses the following compound CK1 (compound number 107 in Table 1 of CN106916084A), which has good activity against bacterial and fungal diseases.

[0004]

[0005] In the prior art, there are no reports on thiazoxime ether compounds and their biological activities, such as those described in this invention. Summary of the Invention

[0006] The purpose of this invention is to provide a novel thiazoxime ether compound that can be used to prepare drugs for the prevention and control of pests and diseases in agriculture and other fields.

[0007] To achieve the above objectives, the technical solution of the present invention is as follows:

[0008] A thiazolyl oxime ether compound, as shown in general formula I:

[0009]

[0010] In the formula:

[0011] n is selected from 0, 1, or 2;

[0012] A is selected from CN or (C=O)NH2;

[0013] Z is selected from hydrogen, unsubstituted or substituted C1-C6 straight-chain or branched alkyl groups, wherein the following groups are halogen, cyano, trifluoromethyl, trifluoromethoxy, hydroxy, nitro, and amino.

[0014] R is selected from hydrogen, halogen, cyano, C1-C6 straight-chain or branched alkyl, unsubstituted or substituted aryl;

[0015] W is selected from hydrogen, halogen, cyano, nitro, unsubstituted or substituted C1-C. 10 Alkyl, unsubstituted or substituted C1-C 10 Alkenyl, unsubstituted or substituted C1-C 10 Alkyne, unsubstituted or substituted cycloalkyl, unsubstituted or substituted alkoxy, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl.

[0016] The preferred compounds in this invention are those in general formula I.

[0017] n is selected from 0, 1, or 2;

[0018] A is selected from CN;

[0019] Z is selected from hydrogen, unsubstituted or substituted C1-C3 straight-chain or branched alkyl groups, wherein the following groups are halogen, cyano, trifluoromethyl, trifluoromethoxy, hydroxy, nitro, and amino.

[0020] R is selected from hydrogen, cyano, and C1-C6 straight-chain or branched alkyl groups;

[0021] W is selected from hydrogen, halogen, cyano, nitro, unsubstituted or halogenated C1-C8 alkyl, C3-C6 cycloalkyl, unsubstituted or halogenated C2-C8 alkenyl, unsubstituted or halogenated C2-C8 alkynyl, unsubstituted or halogenated C1-C8 alkoxy, unsubstituted or halogenated phenyl, pyridinyl, pyrazolyl, thiazolyl, isothiazolyl, isoxazolyl or thiadiazolyl, wherein the following groups are halogen, cyano, nitro, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C1-C8 alkylthio, C1-C8 haloalkylthio or phenyl.

[0022] Further optional compounds in this invention are: those in general formula I.

[0023] n is selected from 0, 1, or 2;

[0024] A is selected from CN;

[0025] Z is selected from hydrogen, methyl, or ethyl;

[0026] R is selected from hydrogen, methyl, or ethyl;

[0027] W is selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C6 cycloalkyl, C2-C4 haloalkenyl, C1-C3 alkoxy, C1-C3 alkyl, unsubstituted or substituted with any of the following groups: phenyl, pyridyl or thiazolyl, wherein the following groups are halogen, cyano, nitro, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio or phenyl.

[0028] Further optional compounds in this invention are: those in general formula I.

[0029] n is selected from 0, 1, or 2;

[0030] A is selected from CN;

[0031] Z is selected from hydrogen;

[0032] R is selected from hydrogen;

[0033] W is selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C6 cycloalkyl, C2-C4 haloalkenyl, unsubstituted or substituted phenyl, pyridyl or thiazolyl, wherein the following groups are halogen, cyano, nitro, C1-C3 alkyl, C1-C3 haloalkyl or phenyl.

[0034] In the definitions of general formula compounds given above, the terms used in the compilation generally represent the following substituents:

[0035] Unsubstituted means that all substituents are hydrogen.

[0036] Halogens: refer to fluorine, chlorine, bromine or iodine.

[0037] Alkyl: Straight-chain or branched alkyl, such as methyl, ethyl, n-propyl, isopropyl or different butyl, pentyl or hexyl isomers.

[0038] Halogenated alkyl groups: straight-chain or branched alkyl groups in which hydrogen atoms may be partially or completely replaced by halogens, such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, heptafluoroisopropyl, etc.

[0039] Cycloalkyl: substituted or unsubstituted cyclic alkyl groups, such as cyclopropyl, cyclopentyl or cyclohexyl; substituents such as methyl, halogen, etc.

[0040] Alkenyl groups include straight-chain or branched alkenes, such as vinyl, 1-propenyl, 2-propenyl and various butenyl, pentenyl and hexenyl isomers; alkenyl groups also include polyenes such as 1,2-propadienyl and 2,4-hexadienyl.

[0041] Haloalkenyl: An alkenyl group in which at least one or more hydrogen atoms can be replaced by halogen atoms.

[0042] Alkynyl groups include straight-chain or branched alkynes, such as ethynyl, 1-propynyl and various butynyl, penynyl and hexynyl isomers; alkynyl groups also include groups composed of multiple triple bonds, such as 2,5-hexadiynyl.

[0043] Halogenated alkynyl group: an alkynyl group in which at least one or more hydrogen atoms can be replaced by a halogen atom.

[0044] Alkoxy groups: straight-chain or branched alkyl groups, which are attached to the structure by oxygen atoms, such as methoxy, ethoxy, tert-butoxy, etc.

[0045] Halogenated alkoxy groups: straight-chain or branched alkoxy groups in which the hydrogen atoms can be partially or completely replaced by halogens, such as chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, trifluoroethoxy, etc.

[0046] Alkylthio group: a straight-chain or branched alkyl group that is attached to the structure by a sulfur atom bond, such as methylthio and ethylthio.

[0047] Halogenated alkylthio groups: straight-chain or branched alkylthio groups, in which hydrogen atoms can be partially or completely replaced by halogens, such as difluoromethylthio and trifluoroethylthio.

[0048] Alkoxyalkyl: alkyl-O-alkyl-, for example CH3OCH2-.

[0049] Halogenated alkoxyalkyl groups: straight-chain or branched alkoxyalkyl groups in which hydrogen atoms may be partially or completely replaced by halogens, such as chloromethoxymethyl, dichloromethoxymethyl, trichloromethoxymethyl, fluoromethoxymethyl, difluoromethoxymethyl, trifluoromethoxymethyl, chlorofluoromethoxymethyl, trifluoroethoxymethyl, etc.

[0050] Aryl: A monocyclic or polycyclic aromatic group having 6-20 carbon atoms, such as phenyl or naphthyl.

[0051] Heteroaryl groups: monocyclic or polycyclic heteroaryl groups having 1-20 carbon atoms and 1-4 heteroatoms selected from N, S, and O, such as pyrroloyl, furanyl, thiopheneyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyridazinoneyl, indolyl, benzofuranyl, benzooxazolyl, benzothiopheneyl, benzothiazolyl, benzoisooxazolyl, benzoisothiazolyl, benzoimidazolyl, benzopyrazolyl, quinoxolinyl, etc.

[0052] Some of the compounds of general formula I in this invention are shown in Table 1, but this invention is by no means limited to these compounds.

[0053] Table 1

[0054]

[0055]

[0056]

[0057]

[0058] The spectral data and physicochemical properties of some compounds are as follows:

[0059] Table 2

[0060]

[0061]

[0062] The compound of general formula I of the present invention can be prepared by the following method, wherein, unless otherwise specified, the definitions of each group in the formula are the same as above.

[0063] Method 1:

[0064] The compound of the present invention represented by general formula (I) (n is 1 or 2) can be prepared by oxidizing the compound of the present invention (n is 0).

[0065]

[0066] The compound of the present invention represented by general formula (I) (n is 1) can be prepared by oxidizing the compound of the present invention (n is 0). The compound of general formula I (n is 0) is reacted with an oxidizing agent in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain the compound of general formula I (n is 1). Suitable solvents include dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, THF, DMF, DMSO, or water, etc. Oxidizing agents include sodium periodate or m-chloroperoxybenzoic acid, etc.

[0067] The compound of the present invention represented by general formula (I) (n is 2) can be prepared by oxidizing the compound of the present invention (n is 1). The compound of general formula I (n is 1) is reacted with an oxidant in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain the compound of general formula I (n is 2). Suitable solvents include dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, THF, DMF, DMSO, or water, etc., and oxidants include m-chloroperoxybenzoic acid or hydrogen peroxide solution, etc.

[0068] The compound of the present invention represented by general formula (I) (n is 2) can be prepared by oxidizing the compound of the present invention (n is 0). The compound of general formula I (n is 0) is reacted with an oxidant in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain the compound of general formula I (n is 2). Suitable solvents include dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, THF, DMF, DMSO, or water, etc. Oxidants include m-chloroperoxybenzoic acid or hydrogen peroxide solution, etc.

[0069]

[0070] The compound of the present invention represented by general formula (I) can be prepared by reacting intermediates M1 and M3 in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours. Suitable solvents include dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, THF, DMF, DMSO, or water. Q represents a cation, such as Na. + K + CS + Ag + or NH4 + wait

[0071]

[0072] Intermediate M1 can be prepared by reacting intermediate M2 with 1,3-dichloroacetone in a suitable solvent at temperatures ranging from -10°C to the solvent's boiling point for 0.5–48 hours. Suitable solvents include dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, THF, DMF, DMSO, or water.

[0073]

[0074] Intermediate M2 can be prepared by reacting intermediates M4 and M5 in a suitable solvent at temperatures ranging from -10°C to the solvent's boiling point for 0.5–48 hours. Suitable solvents include dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, THF, DMF, DMSO, or water. Y represents a cation, such as Na. + K + CS + Ag + or NH4 + etc. LG represents the leaving group, and a suitable leaving group can be selected from halogens or other conventional leaving groups, such as methanesulfonic acid group or toluenesulfonic acid group, etc.

[0075] Method 2:

[0076]

[0077] The compound of the present invention represented by general formula (I) (n is 1) can be prepared by reacting intermediates M6 and M3 in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours. Suitable solvents include dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, THF, DMF, DMSO, or water, etc. Q represents a cation, such as Na. + K + CS + Ag + or NH4 + wait.

[0078]

[0079] The compound of the present invention represented by general formula (I) (n = 2) can be prepared by reacting intermediates M7 and M3 in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5–48 hours. Suitable solvents include dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, THF, DMF, DMSO, or water. Q represents a cation, such as Na. + K + CS + Ag + or NH4 + wait.

[0080]

[0081] M6 can be prepared by oxidizing M1. M1 reacts with an oxidizing agent in a suitable solvent at temperatures ranging from -10°C to the solvent's boiling point for 0.5–48 hours to produce M6. Suitable solvents include dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, THF, DMF, DMSO, or water, etc. Oxidizing agents include sodium periodate or m-chloroperoxybenzoic acid, etc.

[0082] M7 can be prepared by oxidizing M6. M6 reacts with an oxidant in a suitable solvent at temperatures ranging from -10°C to the solvent's boiling point for 0.5–48 hours to produce M7. Suitable solvents include dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, THF, DMF, DMSO, or water, while oxidants include m-chloroperoxybenzoic acid or hydrogen peroxide solution.

[0083] M7 can be prepared by oxidizing M1. M1 reacts with an oxidant in a suitable solvent at temperatures ranging from -10°C to the solvent's boiling point for 0.5–48 hours to produce M7. Suitable solvents include dichloromethane, chloroform, carbon tetrachloride, hexane, benzene, toluene, methanol, ethanol, ethyl acetate, acetonitrile, dioxane, THF, DMF, DMSO, or water, while oxidants include m-chloroperoxybenzoic acid or hydrogen peroxide solution.

[0084] The raw material intermediates M3 and M5 can be purchased or prepared by known methods (e.g., CN103804321 or Tetrahedron Letters (2015), 56(44), 6097-6099, etc.).

[0085] The compounds of this invention are used for controlling plant diseases. They can be used to prevent and control diseases caused by various fungi such as Oomycetes, Basidiomycetes, Ascomycetes, and Deuteromycetes on a variety of crops. For example, at low doses, they have good control effects on diseases such as cucumber downy mildew, cucumber gray mold, cucumber anthracnose, cucumber powdery mildew, tomato early blight, tomato late blight, pepper blight, grape downy mildew, grape white rot, apple ring rot, apple leaf spot, rice sheath blight, rice blast, wheat rust, wheat leaf spot, wheat powdery mildew, rapeseed sclerotinia rot, and corn leaf spot.

[0086] The compounds of this invention also have excellent bactericidal activity and can be used to prevent and control a variety of bacterial plant diseases, such as bacterial wilt, bacterial blight, canker, soft rot, bacterial angular leaf spot, bacterial stripe, leaf blight, wildfire, and bacterial scab.

[0087] The compounds of this invention also possess good insecticidal activity, capable of controlling invertebrate pests, including animal populations such as arthropods, including insects and spiders, and nematodes, which may infest plants and cause significant damage to the infested plants, as well as ectoparasites that may infect animals, especially warm-blooded animals such as mammals or birds, or other higher animals such as reptiles, amphibians, or fish, thereby causing significant damage to the infested animals. The invertebrate pests controlled by the compounds of this invention include, but are not limited to:

[0088] Lepidoptera: Cotton bollworm (Heliothis spp.), cotton bollworm (Helicoverpa spp.), noctuid moth (Spodoptera spp.), armyworm (Mythimna unipuncta), cutworm (Agrotis ipsilon), diamondback moth (Earias spp.), pink-striped noctuid moth (Trichoplusia ni), bean noctuid moth (Anticarsia gemmatalis), mint leafminer (Rachiplusia nu), diamondback moth (Plutella xylostella), rice stem borer (Chilo spp.), rice stem borer (Scirpophaga incertulas), Chinese stem borer (Sesamia inferens), rice leaf roller (Cnaphalocrocismedinalis), corn borer (Ostrinia nubilalis), codling moth (Cydia pomonella), peach fruit moth (Carposina niponensis), cotton brown-banded leafroller (Adoxophyes) Orana, Archipargyrospilus, Pandemis heparana, Epinotia aporema, Eupoecilia ambiguella, Lobesia botrana, Polychrosis biteana, Pectinophora gossypiella, Pierisrapae, Phyllonorycter spp., Leucopteramalifoliella, Phyllocnisitis citrella, and Podoptera exigua Hübner;

[0089] Coleoptera: Leaf beetle (Diabrotica spp.), potato leaf beetle (Leptinotarsa ​​decemlineata), rice leaf beetle (Oulema oryzae), boll weevil (Anthonomus grandis), rice water weevil (Lissorhoptrus oryzophilus), wireworm click beetle (Agriotes spp.), Melanotus communis, Japanese beetle (Popillia japonica), round-headed rhinoceros beetle (Cyclocephala spp.), flour beetle (Tribolium spp.);

[0090] Hemiptera: Aphids (Aphis spp.), Tobacco Aphid (Myzus Persicae), Rhopalosiphum spp., Plantain Aphid (Dysaphis plantaginea), Citrus Aphid (Toxoptera spp.), Alfalfa Aphid (Aphis craccivora Koch), Euphorbia Aphid (Macrosiphum euphorbiae), Eggplant Aphid (Aulacorthum solani), Wheat Aphid (Sitobion avenae), Wheat Aphid (Metopolophium dirhodum), Wheat Aphid (Schizaphis graminum), Wheat Aphid (Brachycolus noxius), Black-tailed Leafhopper (Nephotettix spp.), Brown Planthopper (Nilaparvata lugens), White-backed Planthopper (Sogatella furcifera), Gray Planthopper (Laodelphaxstriatellus), Tobacco Whitefly (Bemisiatabaci), Greenhouse Whitefly (Trialeurodes) Vaporariorum, Aleurodes proletella, Aleurothrixus floccosus, Quadraspidiotus perniciosus, Unaspis yanonenses, Ceroplastes rubens, Aonidiella aurantii;

[0091] Hemiptera: Mirid bug (Lygus spp.), Eurygaster maura, Green rice bug (Nezaraviridula), Piezodorus guildingi, Rice stink bug (Leptocorisa varicornis), Temperate bed bug (Cimexlectularius), Tropical bed bug (Cimex hemipterus);

[0092] Thysanoptera: Western flower thrips (Frankliniella occidentalis), thrips (Thrips spp.), and yellow thrips (Scirtothrips dorsalis);

[0093] Isoptera: *Reticulitermes flavipes*, *Coptotermes formosanus*, *Reticulitermes virginicus*, *Heterotermes aureus*, *Reticulitermes hesperus*, *Coptotermes frenchii*, *Shedorhinotermes spp.*, *Reticulitermes santonensis*, *Reticulitermes grassei*, *Reticulitermes banyulensis*, *Reticulitermes speratus*, *Reticulitermes hageni*, *Reticulitermes tibialis*, *Zootermopsis spp.*, *Incisitermes spp.*, *Marginitermes spp.*, *Macrotermes spp.*, *Microcerotermes* spp.), and savage termites (Microtermes spp.);

[0094] Diptera: Leafminer (Liriomyza spp.), Housefly (Musca domestica), Aedes spp., Culex spp., Anopheles spp., Toilet fly (Fannia spp.), Stomoxys spp.;

[0095] Hymenoptera: Red ants (Iridomyrmex humilis), fire ants (Solenopsis spp.), pharaoh ants (Monomorium pharaonis), Atta spp., harvester ants (Pogonomyrmex spp.), carpenter ants (Camponotus spp.), small house ants (Monomorium spp.), stink house ants (Tapinoma sessile), pavement ants (Tetramorium spp.), Xylocapa spp., wasps (Vespula spp.), long-legged wasps (Polistes spp.);

[0096] Chachophaga (chewing lice);

[0097] Lice (sucking lice): pubic lice (Pthirus pubis), lice (Pediculus spp.);

[0098] Orthoptera (locusts, crickets): Black locust (Melanoplus spp.), Oriental migratory locust (Locus tamigratoria), desert locust (Schistocerca gregaria), mole cricket (Gryllotalpidae);

[0099] Cockroaches (order Blattatus): Oriental cockroach (Blatta orientalis), German cockroach (Blattella germanica), American cockroach (Periplaneta americana), long-bearded cockroach (Supella longipalpa), Australian cockroach (Periplaneta australasiae), brown-spotted cockroach (Periplaneta brunnea), Pennsylvania wood cockroach (Parcoblatta pennsylvanica), black-breasted cockroach (Periplaneta fuliginosa), sugarcane cockroach (Pycnoscelus surinamensis);

[0100] Order Siphonaptera: flea (Ctenophalides spp.), human flea (Pulex irritans);

[0101] The order Acari includes the families Tetranychidae, Eupodidae, Eriophyiade, Phytoseiidae, and Acaridae, specifically including but not limited to the following: Tetranychus spp., Panonychus spp., Tetranychus cinnabarinus, Eotetranychus carpini, Tetranychus urticae Koch., Phyllostachys oleivora, Aculus pelekassi, Brevipalpus phoenicis, Boophilus spp., Dermacentor variabilis, Rhipicephalus sanguineus, Amblyomma americanum, and Ixodes. spp.), feline anal mite (Notoedres cati), scabies mite (Sarcoptes scabiei), dust mite (Dermatophagoides spp.);

[0102] Nematoda: *Dirofilaria immitis*, *Meloidogynes* pp., *Heterodera* spp., *Hoplolaimus columbus*, *Belonolaimus* spp., *Pratylenchus* spp., *Rotylenchus reniformis*, *Criconemella ornata*, *Ditylenchus* spp., *Aphelenchoides besseyi*, and *Hirschmanniella* spp. (rice paddy root nematode). Detailed Implementation

[0103] The following specific embodiments are used to further illustrate the present invention, but are not intended to limit the present invention.

[0104] Synthesis Examples

[0105] Example 1: Preparation of Compound 1

[0106]

[0107] In a 50 mL reaction flask, 2.5 g of iodoethane (16.03 mmol), 1.77 g of ammonium dithiocarbamate (16.03 mmol), and 25 mL of ethanol were added. The mixture was heated to reflux and monitored by TLC (ethyl acetate:petroleum ether = 1:3). After the reaction was complete, the ethanol was removed by vacuum distillation. The residue was purified by column chromatography (ethyl acetate:petroleum ether = 1:3 as eluent, 100-140 mesh silica gel produced by Qingdao Marine Biochemical Plant Branch) to obtain 0.8 g of a yellow oily substance, with a yield of 41%.

[0108]

[0109] Add the intermediate obtained in the previous step (0.65 g, 5.36 mmol), 1,3-dichloropropanone (0.68 g, 5.36 mmol), and 15 mL of ethanol to a 50 mL reaction flask. Heat to reflux and monitor the reaction by TLC (ethyl acetate: petroleum ether = 1:5). After the reaction is complete, remove the ethanol under reduced pressure. Purify the residue by column chromatography (ethyl acetate: petroleum ether = 1:5 as eluent, 100-140 mesh silica gel produced by Qingdao Marine Biochemical Plant Branch) to obtain 0.82 g of yellow oil, yield 79%.

[0110]

[0111] The product from the previous step (0.53 g, 2.74 mmol), sodium malononitrile oxime ether (0.12 g, 0.98 mmol), and 15 mL of acetonitrile were added to a 50 mL reaction flask. The mixture was heated to 70 °C and monitored by TLC (ethyl acetate: petroleum ether = 1:3). After the reaction was complete, the acetonitrile was removed by vacuum distillation. The residue was purified by column chromatography (ethyl acetate: petroleum ether = 1:3 as eluent, 100-140 mesh silica gel produced by Qingdao Marine Biochemical Plant Branch) to obtain 0.46 g, with a yield of 67%.

[0112] Example 2: Preparation of compounds 2 and 3

[0113]

[0114] The product from the previous step (0.38 g, 1.51 mmol), m-chloroperoxybenzoic acid (0.39 g, 2.26 mmol), and 20 mL of dichloromethane were added to a 50 mL reaction flask. The mixture was stirred at room temperature and monitored by TLC (ethyl acetate: petroleum ether = 1:1). After the reaction was complete, the dichloromethane was removed by vacuum distillation. The residue was purified by column chromatography (ethyl acetate: petroleum ether = 1:1 as eluent, 100-140 mesh silica gel produced by Qingdao Marine Biochemical Plant Branch) to obtain 0.13 g of compound (2) and 0.15 g of compound (3), with yields of 32% and 35%, respectively.

[0115] Example 3: Preparation of Compound 40

[0116]

[0117] 4-Chloromethyl-3,5-dimethylisoxazole (1.6 g, 10.99 mmol), ammonium dithiocarbamate (1.21 g, 10.99 mmol), and 25 mL of ethanol were added to a 50 mL reaction flask. The mixture was heated to reflux and monitored by TLC (ethyl acetate:petroleum ether = 1:3). After the reaction was complete, the ethanol was removed by vacuum distillation. The residue was purified by column chromatography (ethyl acetate:petroleum ether = 1:3 as eluent, 100-140 mesh silica gel produced by Qingdao Marine Biochemical Plant Branch) to obtain 1.43 g of intermediate, with a yield of 64%.

[0118]

[0119] Add the intermediate obtained in the previous step (1.25 g, 6.18 mmol), 1,3-dichloropropanone (0.78 g, 6.18 mmol), and 15 mL of ethanol to a 50 mL reaction flask. Heat to reflux and monitor the reaction by TLC (ethyl acetate: petroleum ether = 1:5). After the reaction is complete, remove the ethanol under reduced pressure. Purify the residue by column chromatography (ethyl acetate: petroleum ether = 1:3 as eluent, 100-140 mesh silica gel produced by Qingdao Marine Biochemical Plant Branch) to obtain 1.03 g of intermediate, yield 61%.

[0120]

[0121] The product from the previous step (0.96 g, 3.49 mmol), sodium malononitrile oxime ether (0.41 g, 3.50 mmol), and 15 mL of acetonitrile were added to a 50 mL reaction flask. The mixture was heated to 60 °C and monitored by TLC (ethyl acetate: petroleum ether = 1:3). After the reaction was complete, the acetonitrile was removed by vacuum distillation. The residue was purified by column chromatography (ethyl acetate: petroleum ether = 1:3 as eluent, 100-140 mesh silica gel produced by Qingdao Marine Biochemical Plant Branch) to obtain 0.75 g, with a yield of 64%.

[0122] Example 4: Preparation of compounds 41 and 42

[0123]

[0124] The product from the previous step (0.53 g, 1.59 mmol), m-chloroperoxybenzoic acid (0.42 g, 2.43 mmol), and 20 mL of dichloromethane were added to a 50 mL reaction flask. The mixture was stirred at room temperature and monitored by TLC (ethyl acetate: petroleum ether = 1:1). After the reaction was complete, the dichloromethane was removed by vacuum distillation. The residue was purified by column chromatography (ethyl acetate: petroleum ether = 1:1 as eluent, 100-140 mesh silica gel produced by Qingdao Marine Biochemical Plant Branch) to obtain 0.21 g of compound (41) and 0.23 g of compound (42), with yields of 38% and 40%, respectively.

[0125] Bioactivity assay

[0126] Example 5: Determination of efficacy against plant bacterial diseases

[0127] The in vivo pot assay method was used. The test compound was dissolved in a small amount of N,N-dimethylformamide and diluted with water to the required concentration. The compound was sprayed onto the surface of the plant material, and after the surface solution was air-dried in a cool place, the pathogenic bacteria cultured to the stable growth stage were sprayed onto the surface of the plant material. The plant material was then placed in a greenhouse for humidified culture. Usually, the culture lasted for about ten days. After the control group had fully developed disease, the control efficacy was investigated.

[0128] The test results are as follows:

[0129] At a concentration of 600 mg / L, compounds 19, 23, and 29 showed a control efficacy of over 75% against bacterial angular leaf spot in cucumber.

[0130] At a concentration of 600 mg / L, compounds 2, 19, and 21 showed a control efficacy of over 70% against melon fruit spot disease.

[0131] At a concentration of 150 mg / L, compounds 1, 19, 21, 29, and 36 showed a control efficacy of over 80% against citrus canker.

[0132] Example 6: Determination of efficacy against plant fungal diseases

[0133] The live potted plant assay method involves dissolving the compound sample in a small amount of solvent (such as acetone, methanol, DMF, etc., selected based on its solubility in the sample; the volume ratio of solvent to spray volume should be equal to or less than 0.05), then diluting it with water containing 0.1% Tween 80 to prepare the test solution of the required concentration. The compound of this invention is then used for foliar spraying at the designed concentration. A blank control (sprayed with water) is also included, with three replicates. The day after treatment, the plants are inoculated with pathogens. After inoculation, the plants are placed in an artificial climate chamber for humidified cultivation (temperature: 25°C during the day, 20°C at night, relative humidity 95-99%). After 24 hours of cultivation, the experimental materials are transferred to a greenhouse for further cultivation. Plants that do not require humidified cultivation are directly inoculated and cultivated in the greenhouse. After the control group has developed sufficient disease (usually within one week), the efficacy of the compound control is evaluated. The results are based on "A Manual of Assessment Keys for Plant Diseases" compiled by the American Plant Pathology Society, and are represented by 100-0, with "100" representing no disease and "0" representing the most severe disease severity.

[0134] Efficacy against cucumber downy mildew:

[0135] Among the tested compounds, the following compounds, at a concentration of 400 ppm, showed good control efficacy against cucumber downy mildew, with a control efficacy ≥80%.

[0136] Following the above method, compounds 15, 18, 29, and 38 were selected and compared with the known compound CK1 in parallel for the control of cucumber downy mildew. The experimental results are shown in Table 3.

[0137] Table 3

[0138]

[0139] Efficacy against wheat scab:

[0140] Among the tested compounds, the following compounds, at a concentration of 400 ppm, showed good control efficacy against wheat scab, with a control efficacy ≥80%.

[0141] Efficacy against cucumber anthracnose:

[0142] Among the tested compounds, the following compounds, at a concentration of 400 ppm, showed good control effects against cucumber anthracnose, with a control efficacy ≥80%.

[0143] Efficacy against corn rust:

[0144] Among the tested compounds, the following compounds, at a concentration of 400 ppm, showed good control effects against corn rust, with a control efficacy ≥80%.

[0145] Example 7: Insecticidal Activity Assay

[0146] Based on the solubility of the compound to be tested, dissolve it in acetone or dimethyl sulfoxide, and then prepare 50 mL of the test solution of the required concentration with 0.1% Tween 80 solution. The content of acetone or dimethyl sulfoxide in the total solution shall not exceed 10%.

[0147] Determination of the activity against armyworms:

[0148] Select fresh corn leaves from the middle section, cut them into 3 cm segments, and immerse them in the prepared solution for 10 seconds. After air-drying, place them in a 9 cm diameter petri dish lined with filter paper. Inoculate healthy, uniform 3rd instar insects into each treatment, with 14 insects per treatment. The experiment was repeated 4 times, with a water treatment as a blank control. After treatment, the insects were placed in an indoor environment at 24℃, 60%-70% relative humidity, and natural light. After 72 hours, the number of surviving insects was counted, and the mortality rate was calculated.

[0149] Among the tested compounds, compounds 2, 13, 15, 21, 23, 24, 26, 27, 28, 29, 34, 35, 40, 41, and 42 showed good control efficacy against armyworms at a concentration of 600 mg / L, with a mortality rate of over 80%.

[0150] Determination of activity against diamondback moth:

[0151] Select cabbage leaves grown at room temperature, remove the surface wax layer, and punch holes to create circular leaf discs with a diameter of 2 cm. Immerse the leaf discs in the prepared solution for 10 seconds, air dry, and then place them in 9 cm diameter petri dishes lined with filter paper. Inoculate healthy, uniform second-instar insects into each treatment, with 10 insects per treatment. The experiment is repeated 4 times, with a water treatment serving as a blank control. After treatment, incubate the leaves indoors at 24℃, 60%-70% relative humidity, and natural light. After 72 hours, count the number of surviving insects and calculate the mortality rate.

[0152] Among the tested compounds, compounds 2, 13, 15, 21, 23, 24, 25, 26, 27, 34, 35, 40, and 41 showed good control efficacy against diamondback moth at a concentration of 600 mg / L, with a mortality rate of over 80%.

Claims

1. A thiazolyl oxime ether compound, characterized in that: The compound is shown in general formula I: I In the formula: n is selected from 0, 1, or 2; A is selected from CN; Z is selected from hydrogen; R is selected from hydrogen; W is selected from hydrogen, unsubstituted or halogen-substituted C1-C8 alkyl, C3-C6 cycloalkyl, unsubstituted or halogen-substituted C2-C8 alkenyl, or phenyl, pyridinyl, thiazolyl, or isoxazolyl groups arbitrarily substituted with the following groups, wherein the following groups are halogen, cyano, nitro, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkoxy, C1-C8 haloalkoxy, C1-C8 alkylthio, C1-C8 haloalkylthio, or phenyl.

2. The compound according to claim 1, characterized in that, In general formula I, n is selected from 0, 1, or 2; A is selected from CN; Z is selected from hydrogen; R is selected from hydrogen; W is selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C6 cycloalkyl, C2-C4 haloalkenyl, unsubstituted or substituted phenyl, pyridyl, isoxazolyl or thiazolyl, wherein the following groups are halogen, cyano, nitro, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio or phenyl.

3. The compound according to claim 2, characterized in that, In general formula I, n is selected from 0, 1, or 2; A is selected from CN; Z is selected from hydrogen; R is selected from hydrogen; W is selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C6 cycloalkyl, C2-C4 haloalkenyl, unsubstituted or substituted phenyl, pyridyl, isoxazolyl or thiazolyl, wherein the following groups are halogen, cyano, nitro, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 haloalkyl or phenyl.

4. The compound according to claim 3, characterized in that, In general formula I, n is selected from 0, 1, or 2; A is selected from CN; Z is selected from hydrogen; R is selected from hydrogen; W is selected from hydrogen, methyl, ethyl, isopropyl, unsubstituted or substituted with any of the following groups: phenyl, pyridyl, isoxazolyl or thiazolyl, wherein the following groups are halogen, cyano, nitro, methyl, ethyl, methoxy, trifluoromethoxy, trifluoromethyl or phenyl.

5. The compound according to claim 3, characterized in that, I The compound is of formula I, where A is CN, Z is H, n is 0, R is H, and W is (Cl)2C=CH-. Alternatively, the compound is of formula I, where A is CN, Z is H, n is 1, R is H, and W is (Cl)2C=CH-; Alternatively, the compound is of formula I, where A is CN, Z is H, n is 2, R is H, and W is (Cl)2C=CH-; Alternatively, the compound is of formula I, where A is CN, Z is H, n is 0, R is H, and W is F2C=CF-CH2-; Alternatively, the compound is of formula I, where A is CN, Z is H, n is 1, R is H, and W is F2C=CF-CH2-; Alternatively, the compound is of formula I, where A is CN, Z is H, n is 2, R is H, and W is F2C=CF-CH2-.

6. The use of a thiazoxime ether compound according to claim 1 as a fungicide or insecticide in agriculture and forestry.

7. A method for preventing and controlling pests and diseases, characterized in that: Applying a fungicide or insecticide effective dose of the compound as described in claim 1 to a crop or its growing medium or location.

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