Pyrimidine-containing aryl pyrazole oxime ether compound as well as preparation method and application thereof

Abstract

The invention discloses an aryl pyrazole oxime ether compound containing pyrimidine. The structure of the aryl pyrazole oxime ether compound is shown as a general formula I, wherein the definition of each substituent group in a # imgabs0 # formula is shown in the specification. In addition, the invention also discloses a synthesis method of the aryl pyrazole oxime ether compound containing pyrimidine. In addition, the compound provided by the invention has broad-spectrum bactericidal activity, and has an excellent control effect on wheat powdery mildew. Meanwhile, the compound disclosed by the invention shows good insecticidal activity and has a relatively high fatality rate on plutella xylostella, mythimna separata and the like.

Description

Technical Field

[0001] The invention belongs to the field of agricultural bactericides, insecticides and acaricides, and specifically relates to a pyrimidine-containing aryl pyrazole oxime ether compound and a preparation method and application thereof. Background Art

[0002] Arylpyrazole oxime ether derivatives are an important class of nitrogen-containing heterocyclic compounds that have been studied extensively in recent years. Many pesticides containing this structure play an important role in the prevention and control of crop diseases and insect pests. Their unique mode of action, good environmental compatibility and broad-spectrum biological activity have made arylpyrazole oxime ether compounds a hot spot in the research of new pesticide creation. A typical example of this type of compound is fenpyroximate (EP0234045), which has a strong contact killing effect on a variety of harmful mites, has the highest activity against young mites, and has a long lasting effect. Its structural formula is as follows:

[0003]

[0004] Pyrimidine compounds are an important class of fungicides developed since the 1950s. They act as mitochondrial complex I electron transfer inhibitors and are particularly effective against various diseases caused by Botrytis cinerea. They are one of the few fungicides for which resistance has not yet been reported. These properties indicate that pyrimidines are a class of compounds with potential for the discovery of pesticide candidate varieties. For example, the fungicide cyprodinil developed by Syngenta has good control effects on gray mold, powdery mildew and black spot (EP 310550); and diflumetorim, which was registered in Japan in 1997, has excellent control effects on wheat powdery mildew and rust (EP 0370704).

[0005]

[0006] Therefore, in order to continue to search for compounds with excellent biological activity from arylpyrazole oxime ether derivatives, we plan to adopt the principle of active substructure splicing to rationally combine the substituted pyrimidine group with the arylpyrazole oxime ether skeleton, and disclose a class of pyrimidine-containing arylpyrazole oxime ether compounds with good fungicidal and insecticidal activities. Summary of the invention

[0007] The purpose of the present invention is to provide a pyrimidine-containing aromatic pyrazole oxime ether compound that can control a variety of pathogens, pests and mites, and a preparation method thereof, and use thereof in preparing drugs for preventing and controlling pathogens or pests and mites in agriculture or other fields, thereby enriching the application types of pyrazole oxime derivatives in the agricultural field and achieving good bactericidal and insecticidal activity.

[0008] To achieve the above purpose, the present invention adopts the following technical solution:

[0009] The present invention provides a pyrimidine-containing aryl pyrazole oxime ether compound, the structure of which is shown in general formula I;

[0010]

[0011] Wherein, R1 is selected from any one of hydrogen, halogen, cyano, nitro, amino, carboxyl, C1-C4 alkyl, halogenated C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 alkoxy or halogenated C1-C4 alkoxy;

[0012] The R2 is selected from any one of hydrogen, halogen, cyano, nitro, amino, carboxyl, formyl, C1-C4 alkyl, halogenated C1-C4 alkyl or C1-C4 alkoxy;

[0013] The Rn is n substituents R on the benzene ring, wherein n is selected from an integer from 0 to 5, and when n is 0, the ring is unsubstituted; when n is greater than 1, R may be the same or different;

[0014] The R is selected from any one of halogen, amino, cyano, nitro, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy or halogenated C1-C4 alkoxy;

[0015] In the definition of compounds of general formula I given above, the terms used are generally defined as follows:

[0016] Halogen: refers to fluorine, chlorine, bromine or iodine;

[0017] Amino group: -NH2;

[0018] Cyano: -CN;

[0019] Nitro: -NO 2；

[0020] Carboxyl: -COOH;

[0021] Formyl: -CHO;

[0022] Alkyl: straight-chain or branched alkyl, such as methyl, ethyl, propyl, isopropyl, n-butyl or tert-butyl;

[0023] Haloalkyl: straight or branched chain alkyl groups, on which hydrogen atoms may be partially or completely replaced by halogen atoms, for example, chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, etc. Alkoxy: straight or branched chain alkyl groups, connected to the structure via oxygen atom bonds.

[0024] Cycloalkyl: substituted or unsubstituted cyclic alkyl, such as cyclopropyl, cyclopentyl or cyclohexyl. Substituents include methyl, halogen, etc.

[0025] Alkoxy: A straight or branched chain alkyl group attached to the structure via an oxygen atom.

[0026] Haloalkoxy: a straight or branched alkoxy group in which the hydrogen atoms may be partially or completely substituted by halogen atoms, for example, chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, trifluoroethoxy, and the like.

[0027] Further, the R1 is selected from any one of hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, amino, carboxyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, monofluoromethyl, monochloromethyl, difluoromethyl, trifluoromethyl or trifluoroethyl;

[0028] The R2 is selected from any one of hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, amino, carboxyl, formyl, methyl, ethyl, methoxy or ethoxy;

[0029] The Rn is n substituents R on the benzene ring, wherein n is selected from an integer from 0 to 5, and when n is 0, the ring is unsubstituted; when n is greater than 1, R may be the same or different;

[0030] R is selected from fluorine, chlorine, bromine, iodine, amino, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy or trifluoroethoxy;

[0031] Further, the R1 is selected from any one of chlorine, methyl, ethyl or difluoromethyl;

[0032] The R2 is selected from any one of hydrogen, chlorine or methyl;

[0033] The Rn is n substituents R on the benzene ring, wherein n is selected from an integer from 0 to 5, and when n is 0, the ring is unsubstituted; when n is greater than 1, R may be the same or different;

[0034] The R is selected from any one of fluorine, chlorine, bromine, nitro, methyl, methoxy or trifluoromethyl;

[0035] Furthermore, the present invention provides a method for preparing a pyrimidine-containing aryl pyrazole oxime ether compound of general formula I:

[0036]

[0037] Intermediates II and III react under basic conditions in a suitable solvent to obtain a compound of formula I.

[0038] Part of the intermediate II is commercially available or can be prepared by known methods, for example, by the methods described in JP2000007662, US4977264, US6090815, US20040092402, JP09124613, US5468751, US4985426, US4845097, Journal of the American Chemical Society (1957), 79, 1455, Journal of Chemical Society (1955), p. 3478-3481.

[0039] The compound represented by intermediate III can be prepared by known methods, for details, see WO2024141128, Life Sciences (2012), 90, 910, Science of Synthesis (2002), 12, 15, etc.

[0040] Further,

[0041] The molar ratio of the intermediate II to the intermediate III is 1:1;

[0042] The base used in the reaction is any one of potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, triethylamine, pyridine, sodium methoxide, sodium ethoxide, sodium hydride, potassium tert-butoxide or sodium tert-butoxide;

[0043] The solvent is any one of tetrahydrofuran, 1,4-dioxane, acetonitrile, toluene, xylene, benzene, N,N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, acetone or butanone;

[0044] The reaction temperature is 20°C to 100°C;

[0045] The reaction time is 30 min to 20 h, preferably 1-10 h.

[0046] Furthermore, the compound of general formula I shows excellent activity against a variety of pathogens in agriculture or other fields, and also shows good activity against insect pests and mites. Therefore, the present application also provides a use of a pyrimidine-containing aryl pyrazole oxime ether compound in the preparation of a fungicide or insecticide and acaricide drug.

[0047] The examples of diseases mentioned below are only used to illustrate the present invention, but they are by no means limiting.

[0048] The compounds of general formula I can be used to prevent and control the following diseases: Oomycete diseases, such as downy mildew (cucumber downy mildew, rape downy mildew, soybean downy mildew), white rust (rape white rust, cabbage white rust), late blight (potato late blight, tomato late blight), etc.; Deuteromycete diseases, such as wilt (tomato wilt, bean wilt, cucumber wilt), root rot (pepper root rot, eggplant root rot, bean root rot, cucumber root rot, bitter melon root rot, cotton black root rot, broad bean root rot), damping-off (cotton seedling damping-off, sesame damping-off, pepper damping-off, cucumber damping-off, cabbage damping-off), anthracnose (cucumber anthracnose, bitter melon anthracnose, western Anthracnose of cucurbit, wax gourd, watermelon, melon, and litchi), gray mold (cotton boll gray mold, hemp gray mold, tomato gray mold), etc.; basidiomycete diseases, such as rust (wheat stripe rust, wheat stem rust, wheat leaf rust, flower rust, sunflower rust, sugarcane rust, soybean rust), etc.; ascomycete diseases, such as powdery mildew (wheat powdery mildew, rapeseed powdery mildew, sesame powdery mildew), sclerotinia (soybean sclerotinia, peanut sclerotinia, tobacco sclerotinia, pepper sclerotinia, eggplant sclerotinia, bean sclerotinia, pea sclerotinia, cucumber sclerotinia, bitter melon sclerotinia), scab (apple scab, pear scab), etc.

[0049] The compounds shown in general formula I can be used to control the following pests:

[0050] Coleoptera (Beetles): Acanthoscelides spp. (Weevils), Acanthoscelides obtectus (Common Pea Weevils), Agrilus planipennis (Willow Ash Borer), Agriotes spp. (Wireworms), Anoplophora glabripennis (Asian Longhorn Beetle), Anthonomus spp. (Curculidae), Anthonomus grandis (Cotton Bollworm), Aphidius spp., Apion spp. (Weevils), Apogonia spp. (Grubs), Atacnius sprctulus (Black Velvet Beetle), Atomaria linearis (Pygmy Beetle), mangold beetle) etc.

[0051] Dermaptcra (earwigs).

[0052]

[0043] Dictyoptera (cockroaches): Blattella germanica (German cockroach), Blatta orientalis (Oriental cockroach), Parcoblatta pennylvanica, etc.

[0053] Diptera (flies): Aedes spp. (mosquitoes), Agromyzafrontella (alfalfa blotch leafminer), Agromyza spp. (leaf miner), Anastrepha spp. (fruit flies), Anastrepha suspensa (Caribbean fruit fly), Anopheles spp. (mosquitoes), Batrocera spp. (fruit flies), etc.

[0054] Hemiptera (Stinkbugs): Acrosternum hilare (green stinkbug), Blissus leucopterus (chinch bug), Calocoris norvegicus (potato mirid), Cimex hemipterus (tropical bed bug), Cimex lectularius (bed hug), Hesperus, etc.

[0055] Homoptera (aphids, scale flies, whiteflies, leafhoppers): Acrythosiphon pisum (pea aphid), Adelges spp. (adelgids), Aleurodes proletella (cabbage whitefly), Aleurodicus disperses, Aleurothrixus flccosus (woolly whitefly), Aluacaspis spp., etc.

[0056] Lepidoptera (moths and butterflies): Achoeajanata, Adoxophyes spp., Adoxophyes orana, Agrotis spp. (cutworms), Agrotis ipsilon (black cutworm), Alabama argillacea (cotton leafworm), Amorbia cuneana, Amyelosis transitella (navel orangeworm), Anacamptodes defectaria, Anarsia lineatella (peach twig borer), tobacco coindicate, etc.

[0057] Due to their positive properties, the above-mentioned compounds can be advantageously used for protecting important agricultural and horticultural crops, livestock and breeding stock, as well as the environment frequented by humans from pathogens, insect pests and acarids.

[0058] To obtain the desired effect, the amount of compound used will vary depending on factors such as the compound used, the crop to be protected, the type of pest, the degree of infestation, climatic conditions, the method of application, and the formulation employed.

[0059] Doses of 10 g to 5 kg of compound per hectare provide adequate control.

[0060] Furthermore, the present application also provides a use of a pyrimidine-containing aryl pyrazole oxime ether compound prepared according to the above preparation method in the preparation of a fungicide drug.

[0061] Furthermore, the present invention also includes a bactericidal, insecticidal and acaricidal composition with the compound of general formula I as an active component. The weight percentage of the active component in the bactericidal, insecticidal and acaricidal composition is between 0.1% and 99%. The bactericidal, insecticidal and acaricidal composition also includes a carrier acceptable for agriculture, forestry and hygiene.

[0062] The composition of the present invention can be applied in the form of a preparation. The compound shown in general formula I is dissolved or dispersed in a carrier as an active ingredient or formulated into a preparation so that it is easier to disperse when used as a bactericidal or insecticidal agent. For example, these chemical preparations can be made into wettable powders, oil suspensions, water suspensions, aqueous emulsions, aqueous solutions or emulsifiable concentrates. In these compositions, at least one liquid or solid carrier is added, and when necessary, a suitable surfactant can be added.

[0063] Furthermore, the technical solution of the present invention also includes a method for using the bactericidal, insecticidal and acaricidal composition: applying the bactericidal, insecticidal and acaricidal composition of the present invention to the pathogens or their growth medium.

[0064] Furthermore, the effective amount of the bactericidal, insecticidal and acaricidal composition is usually selected to be 10 to 1000 grams per hectare, and the preferred effective amount is 20 to 500 grams per hectare.

[0065] Furthermore, the technical scheme of the present invention also includes the use of the composition in the preparation of drugs for preventing and treating pathogens, insect pests and mites. For certain applications, such as in agriculture, one or more other fungicides, insecticides and miticides, herbicides, plant growth regulators or fertilizers can be added to the bactericidal, insecticidal and miticide composition of the present invention, thereby producing additional advantages and effects. It is clear that various changes and modifications can be made within the scope defined by the claims of the present invention.

[0066] Through the above technical solution, the beneficial effects of the present invention are:

[0067] The pyrimidine-containing aryl pyrazole oxime ether compounds disclosed in the present invention show excellent control effects on sterilization, insecticide and acaricide, and show excellent activity against cucumber downy mildew that often occurs in agricultural production activities. In addition, compound Ic also shows good activity against pests such as diamondback moth, armyworm and peach aphid. Therefore, the pyrimidine-containing aryl pyrazole oxime ether compounds also show good activity against pests. Due to its positive characteristics, the pyrimidine-containing aryl pyrazole oxime ether compounds are used in the preparation of bactericides or insecticides and acaricides and bactericidal, insecticide and acaricide compositions with the pyrimidine-containing aryl pyrazole oxime ether compounds as active components, which can be advantageously used to protect important crops, livestock and breeding animals in agriculture and horticulture, and environments frequented by humans from damage by pathogens, insects and acaricides. DETAILED DESCRIPTION

[0068] The following specific examples are used to further illustrate the present invention, but the present invention is by no means limited to these examples (unless otherwise noted, all raw materials used are commercially available).

[0069] Synthesis Example

[0070] Example 1: Synthesis of Intermediate II

[0071] Part of the intermediate II is commercially available or can be prepared by known methods, for example, by the methods described in JP2000007662, US4977264, US6090815, US20040092402, JP09124613, US5468751, US4985426, US4845097, Journal of the American Chemical Society (1957), 79, 1455, Journal of Chemical Society (1955), p. 3478-3481.

[0072] 1. Synthesis of intermediate 4,5-dichloro-6-methylpyrimidine (one of intermediates II)

[0073] 1) Preparation of 4-hydroxy-5-chloro-6-difluoromethylpyrimidine

[0074]

[0075] Under stirring at room temperature, slowly add a methanol solution of sodium methoxide (8.8g, 0.16mol) to a methanol solution (50mL) of formamidine acetate (11.5g, 0.11mol), and continue stirring at room temperature for 2h. Then, add the intermediate ethyl 2-chloro-4,4-difluoro-3-oxobutyrate (13.6g, 68mmol) to the above solution, and continue stirring at room temperature for 5-7h. After the reaction is completed by TLC monitoring, the solvent is evaporated under reduced pressure, the pH is adjusted to 5-6 with hydrochloric acid, and an orange-yellow solid is obtained by suction filtration. The aqueous phase is extracted with (3×50mL) ethyl acetate, dried over anhydrous magnesium sulfate, filtered, and desolventized. The residue is dissolved in 50mL ethyl acetate, left overnight, and filtered to obtain 8.1g of an orange-yellow solid. The yield is 66.00%.

[0076] 2) Preparation of 4,5-dichloro-6-difluoromethylpyrimidine

[0077]

[0078] 4-Hydroxy-5-chloro-6-difluoromethylpyrimidine (9.0 g, 50 mmol) was dissolved in toluene (50 mL) solution, and phosphorus oxychloride (50 mL) was added dropwise to the reaction flask under stirring. After the addition, the temperature was raised and refluxed for reaction for 5-7 h. After the reaction was completed by TLC monitoring, toluene and excess phosphorus oxychloride were evaporated under reduced pressure, and the reactants were poured into ice water under stirring. The aqueous phase was extracted with (3×50 mL) ethyl acetate, and the organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and desolventized. The residue was separated by column chromatography (eluent was ethyl acetate and petroleum ether, volume ratio was 1:5) to obtain 8.8 g of yellow liquid, with a yield of 88.50%.

[0079] Example 2: Synthesis of Intermediate III

[0080] The compound represented by intermediate III can be prepared by known methods, for details, see WO2024141128, Life Sciences (2012), 90, 910, Science of Synthesis (2002), 12, 15, etc.

[0081] 1. Synthesis of Intermediate (E)-1-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)ethanone O-(2-aminoethyl)oxime hydrochloride (one of Intermediates III)

[0082] 1) Preparation of 1-(3-chlorophenyl)-1H-pyrazole

[0083]

[0084] 3-Chlorophenylhydrazine hydrochloride (17.9 g, 0.1 mol) was dissolved in ethanol (100 mL), and then 1,1,3,3-tetramethoxypropane (16.4 g, 0.1 mol) was added to the mixture, and then the temperature was raised to 100 ° C and refluxed for 4 h. After the reaction was completed, it was cooled to room temperature and then concentrated under reduced pressure. The residue was layered with ethyl acetate (60 mL) and water (60 mL), the organic phase was separated, and the aqueous phase was extracted twice with ethyl acetate (2×40 mL). The organic phases were then combined, washed with water and saturated brine, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and purified by column chromatography (eluent: petroleum ether (60 ° C-90 ° C) / ethyl acetate = 20:1) to obtain 15.2 g of a yellow solid with a yield of 85%.

[0085] 2) Preparation of 1-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)ethanone

[0086]

[0087] 1-(3-chlorophenyl)-1H-pyrazole (14.3g, 80mmol) was dissolved in 20mL of excess acetic anhydride, and then concentrated sulfuric acid (0.43mL, 8mmol) was slowly added to the mixture, and the temperature was raised to 120℃ for 6h. After the reaction was completed, it was cooled to room temperature, and then concentrated under reduced pressure to spin out the acetic anhydride and concentrated sulfuric acid. The residue was layered with ethyl acetate (60mL) and water (60mL), and the organic phase was separated, and the aqueous phase was extracted twice with ethyl acetate (2×40mL). Then the organic phases were combined, washed with water and saturated brine, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and purified by column chromatography (eluent: petroleum ether (60℃…90℃) / ethyl acetate = 10:1) to obtain 15.5g of a yellow oil with a yield of 88%.

[0088] 3) Preparation of (E)-1-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)ethanone oxime

[0089]

[0090] 1-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)ethanone (11.0 g, 50 mmol) was dissolved in ethanol (50 mL), and then hydroxylamine hydrochloride (5.2 g, 75 mmol) and sodium acetate (10.3 g, 125 mmol) were added to the mixture, and the mixture was heated to 95 ° C and stirred overnight. After the reaction was completed, it was cooled to room temperature and then concentrated under reduced pressure. The residue was layered with ethyl acetate (40 mL) and water (40 mL), and the organic phase was separated, and the aqueous phase was extracted twice with ethyl acetate (2×20 mL). Then the organic phases were combined, washed with water and saturated brine, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and purified by column chromatography (eluent: petroleum ether (60 ° C…90 ° C) / ethyl acetate = 4:1) to obtain 11.0 g of a white solid with a yield of 93%.

[0091] 4) Preparation of N-Boc-2-bromoethylamine

[0092]

[0093] 20.5g (0.1mol) of bromoethylamine bromide was placed in 80mL of tetrahydrofuran, and 10.08g (0.12mol) of sodium bicarbonate and 50mL of water were added in sequence. 21.80g (0.1mol) of di-tert-butyl dicarbonate was added dropwise under stirring at room temperature. After the addition was completed, the reaction was continued for 4-10h. After the reaction was completed, the solvent was evaporated under reduced pressure, and (3×50mL) of ethyl acetate was added for extraction. The organic phase was washed with 50mL of saturated brine, and 21.84g of colorless oily liquid was obtained after solvent removal, with a yield of 97.50%.

[0094] 5) Preparation of tert-butyl (E)-(2-(((1-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)ethylidene)amino)oxy)ethyl)carbamate

[0095]

[0096] N-Boc-2-bromoethylamine (2.2 g, 10 mmol) and (E)-1-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)ethanone oxime (2.4 g, 10 mmol) were added to 50 mL of DMF, potassium carbonate (1.7 g, 12 mmol) was added, and the mixture was heated to 90°C for 4-10 h. After the reaction was completed as monitored by TLC, the solvent was evaporated under reduced pressure, and ethyl acetate (3×50 mL) was added for extraction. The organic phase was washed with saturated brine (50 mL), and the residue after solvent removal was subjected to column chromatography (eluent: ethyl acetate and petroleum ether, volume ratio: 1:6) to obtain 3.3 g of a yellow solid with a yield of 87%.

[0097] 6) Preparation of (E)-1-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)ethanone O-(2-aminoethyl)oxime hydrochloride

[0098]

[0099] Tert-butyl (E)-(2-(((1-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)ethylidene)amino)oxy)ethyl)carbamate (1.9 g, 5 mmol) was added to ethyl acetate (50 mL), and concentrated hydrochloric acid (6 mL) was added dropwise under stirring at room temperature. The solid dissolved and stirring was continued for 4-5 h. After the reaction was completed as monitored by TLC, the solvent was evaporated under reduced pressure, and dichloromethane (10 mL) was added and stirred for 0.5 h. The mixture was filtered, and the filter cake was washed with dichloromethane to obtain 1.2 g of a light yellow solid with a yield of 77%.

[0100] Example 3: Preparation of Compound Ia

[0101]

[0102] (E)-1-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)ethanone O-(2-aminoethyl)oxime hydrochloride (315 mg, 1 mmol) and potassium carbonate (170 mg, 1.2 mmol) were added to DMF (20 mL), and then 4,5-dichloro-6-difluoromethylpyrimidine (199 mg, 1 mmol) was added thereto, and the reaction mixture was heated to 90°C for 2-6 hours. After the reaction was completed by TLC monitoring, the reaction mixture was added to water and extracted with ethyl acetate, and the organic phase was washed with water and saturated brine in turn, dried, filtered, and desolventized under reduced pressure. The residue was purified by column chromatography (eluent was ethyl acetate and petroleum ether (boiling range 60-90°C), volume ratio was 1:4) to obtain 352 mg of white oil, with a yield of 80%.

[0103] NMR data( 1 HNMR, 600 MHz, internal standard TMS, ppm), compound Ia: 1H NMR (600MHz, CDCl3) δ8.56(s,1H),8.11(s,1H),7.97(s,1H),7.76(t,J=2.1Hz,1H),7.59(ddd,J=8.2,2.2,0.9Hz,1H),7.40(t,J=8.1Hz ,1H),7.30(ddd,J=8.0,2.0,0.9Hz,1H),6.71(t,J=53.7Hz,1H),6.39(s,1H),4.40(t,J=4.9Hz,2H),3.90(q,J=5.1Hz,2H),2.22(s,3H).

[0104] Other compounds of the present invention can be prepared by referring to the above Examples 1, 2, and 3. Physical properties and NMR data of some compounds ( 1 HNMR, 600 MHz, internal standard TMS, ppm) is as follows:

[0105]

[0106] Compound Ib: white oil; 1 H NMR (600MHz, CDCl3) δ8.54(d,J=8.1Hz,2H),8.04(s,1H),7.70(d,J=8.0Hz,2H),7.48(t,J=7.8Hz,2H),7.35(t,J=7.5Hz,1H),6.80…6.59(m,2H),4.47…

[0107] 4.40(m,2H),3.92(q,J=5.4Hz,2H),2.29(s,3H).

[0108]

[0109] Compound Ic: yellow oil; 1 H NMR (600MHz, CDCl3) δ8.55(s,1H),8.07(s,1H),7.95(s,1H),7.66(dd,J=8.9,4.5Hz,2H),7.16(t,J=8.5Hz ,2H),6.71(t,J=53.7Hz,1H),6.42(t,J=5.2Hz,1H),4.41-4.37(m,2H),3.90(q,J=5.1Hz,2H),2.22(s,3H).

[0110]

[0111] Compound Id: light yellow oil; 1H NMR (600MHz, CDCl3) δ8.43(s,1H),8.08(s,1H),7.95(s,1H),7.66(dd,J=9.0,4.6Hz,2H),7.18…7.15(m,2H),6. 08(s,1H),4.39…4.36(m,2H),3.85(q,J=5.2Hz,2H),2.78(q,J=7.6Hz,2H),2.22(s,3H),1.25(t,J=7.6Hz,3H).

[0112]

[0113] Compound 1e: yellow oil; 1 H NMR (600MHz, CDCl3) δ8.57(s,1H),8.41(s,1H),8.03(s,1H),7.69(d,J=8.0Hz,2H),7.50-7.46(m,2H),7.35(t,J=7.3Hz ,1H),6.17(s,1H),4.45-4.42(m,2H),3.88(q,J=5.1Hz,2H),2.76(q,J=7.6Hz,2H),2.29(s,3H),1.24(t,J=7.5Hz,3H).

[0114] Biological Activity Assay Example

[0115] The compound of the invention shows good activity against various pathogens, insect pests and mites in the agricultural field.

[0116] Example 4: Bactericidal activity assay

[0117] The samples of the compounds of the present invention were used to test the in vitro antibacterial activity or in vivo protective effect on various fungal diseases of plants. The results of the fungicidal activity test are shown in the following examples.

[0118] In vivo protective activity assay

[0119] The determination method is as follows: adopt the living potted plant determination method, that is, the sample of the compound to be tested is dissolved with a small amount of solvent (the type of solvent is such as acetone, methanol, DMF, etc., and is selected according to its solubility for the sample, and the volume ratio of the amount of solvent to the amount of spraying liquid is equal to or less than 0.05), and diluted with water containing 0.1% Tween 80 to prepare the required concentration of the test solution. On the crop sprayer, the test solution is sprayed on the disease host plant (the host plant is a standard potted seedling cultivated in a greenhouse), and the disease is inoculated 24 hours later. According to the characteristics of the disease, the diseased plants that need to be cultivated with temperature control and moisture retention are inoculated and placed in an artificial climate chamber for cultivation. After the disease infection is completed, they are moved to the greenhouse for cultivation. The diseased plants that do not need moisture retention cultivation are directly inoculated and cultivated in the greenhouse. After the control is fully diseased (usually one week), the disease prevention effect of the compound is evaluated.

[0120] The in vivo protective activity test results of some compounds are as follows:

[0121] (1) In vivo protective activity against cucumber downy mildew:

[0122] At a dosage of 400 ppm: Compounds Ib, Id, etc. had a 100% protective effect against cucumber downy mildew;

[0123] (2) In vivo protective activity against wheat powdery mildew:

[0124] The results of some tests on the in vivo protective activity against wheat powdery mildew are shown in Table 1:

[0125] Table 1 The protective effect of some compounds on wheat powdery mildew

[0126]

[0127] (3) In vivo protective activity against cucumber anthracnose:

[0128] At a dosage of 400 ppm: Compounds: Ic and others have a protective effect of more than 80% against cucumber anthracnose;

[0129] Example 5: Insecticidal and acaricidal activity assay

[0130] The compounds of the present invention were used to carry out insecticidal activity tests on several insects. The test method is as follows:

[0131] The test compound was dissolved in a mixed solvent of acetone / methanol (1:1) and then diluted with water containing 0.1% (wt) Tween 80 to the desired concentration.

[0132] The insecticidal activity was determined by the Airbrush spray method, with Plutella xylostella, Armyworm and Myzus persicae as targets.

[0133] (1) Determination of activity against Plutella xylostella

[0134] Test method: Use a punch to punch cabbage leaves into leaf discs with a diameter of 2 cm and use an Airbrush spray to treat them at a pressure of 10 psi (about 0.7 kg / cm 2 ), spray each leaf disc on both sides, with a spray volume of 0.5 ml. After drying in the shade, 10 2nd-instar test insects were inoculated in each treatment, and each treatment was repeated 3 times. After treatment, they were placed in an observation room at 25°C and a relative humidity of 60-70%. After 72 hours, the number of surviving insects was investigated and the mortality rate was calculated.

[0135] Some test results on diamondback moth are shown in Table 2:

[0136] Table 2 Mortality of compound Ib to Plutella xylostella

[0137]

[0138] (2) Determination of the activity against armyworms;

[0139] Test method: Cut corn leaves into 2 cm long segments and spray them with airbrush at a pressure of 10 psi (about 0.7 kg / cm 2 ), spray each leaf segment on both sides, with a spray volume of 0.5 ml. After drying in the shade, 10 2nd-instar test insects were inoculated in each treatment, and each treatment was repeated 3 times. After treatment, they were placed in an observation room at 25°C and a relative humidity of 60-70%. After 72 hours, the number of surviving insects was investigated and the mortality rate was calculated.

[0140] Some test results on armyworms are shown in Table 3:

[0141] Table 3 The lethality of some compounds to armyworms

[0142]

[0143] By comparison, it was found that the mortality rate of compound Ib to armyworms exceeded that of the commercial variety avermectin and was basically the same as that of tetrachlorantraniliprole.

[0144] (3) Determination of activity against green peach aphids

[0145] Determination method: Take a 6cm diameter culture dish, cover the bottom of the dish with a layer of filter paper, and add a proper amount of tap water to keep it moist. Cut a cabbage leaf of appropriate size (about 3cm in diameter) with 15 to 30 aphids from the cabbage plant where peach aphids are cultured, remove the winged aphids and the aphids on the front of the leaf, and place the leaf with the back facing up in the culture dish. The pressure of the airbrush spray treatment is 10psi (about 0.7kg / cm 2 ), the spray volume was 0.5 ml, and each treatment was repeated 3 times. After treatment, the insects were placed in an observation room at 25°C and a relative humidity of 60-70%. After 48 hours, the number of surviving insects was counted and the mortality rate was calculated.

[0146] Some of the test results on green peach aphid are as follows:

[0147] At a dosage of 600 ppm, the mortality rate of compound Ic to peach aphid was 100%.

[0148] The embodiments described above are only preferred embodiments of the present invention and are only used to explain the present invention, not to limit the scope of implementation of the present invention. For those skilled in the art, other implementation methods can certainly be easily made by replacement or modification based on the technical contents disclosed in this specification. Therefore, all changes and improvements made on the principles of the present invention should be included in the scope of the patent application of the present invention.

Claims

1. A pyrimidine-containing aryl pyrazole oxime ether compound, characterized in that: The general structural formula of the pyrimidine-containing aryl pyrazole oxime ether compound is shown in I: Wherein, R1 is selected from any one of hydrogen, halogen, cyano, nitro, amino, carboxyl, C1-C4 alkyl, halogenated C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 alkoxy or halogenated C1-C4 alkoxy; The R2 is selected from any one of hydrogen, halogen, cyano, nitro, amino, carboxyl, formyl, C1-C4 alkyl, halogenated C1-C4 alkyl or C1-C4 alkoxy; The Rn is n substituents R on the benzene ring, wherein n is selected from an integer from 0 to 5, and when n is 0, the ring is unsubstituted; when n is greater than 1, R may be the same or different; The R is selected from any one of halogen, amino, cyano, nitro, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy or halogenated C1-C4 alkoxy.

2. The pyrimidine-containing aryl pyrazole oxime ether compound according to claim 1, characterized in that: The R1 is selected from any one of hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, amino, carboxyl, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, monofluoromethyl, monochloromethyl, difluoromethyl, trifluoromethyl or trifluoroethyl; The R2 is selected from any one of hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, amino, carboxyl, formyl, methyl, ethyl, methoxy or ethoxy; The Rn is n substituents R on the benzene ring, wherein n is selected from an integer from 0 to 5, and when n is 0, the ring is unsubstituted; when n is greater than 1, R may be the same or different; The R is selected from fluorine, chlorine, bromine, iodine, amino, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy or trifluoroethoxy.

3. The pyrimidine-containing aryl pyrazole oxime ether compound according to claim 1, characterized in that: The R1 is selected from any one of chlorine, methyl, ethyl or difluoromethyl; The R2 is selected from any one of hydrogen, chlorine or methyl; The Rn is n substituents R on the benzene ring, wherein n is selected from an integer from 0 to 5, and when n is 0, the ring is unsubstituted; when n is greater than 1, R may be the same or different; The R is selected from any one of fluorine, chlorine, bromine, nitro, methyl, methoxy or trifluoromethyl.

4. A method for preparing a pyrimidine-containing aryl pyrazole oxime ether compound according to claim 1, characterized in that: Intermediates II and III react in a solvent under alkaline conditions to obtain a compound of formula I.

5. The method for preparing a pyrimidine-containing aryl pyrazole oxime ether compound according to claim 4, characterized in that: The molar ratio of the intermediate II to the intermediate III is 1:1; the base used in the reaction is any one of potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, triethylamine, pyridine, sodium methoxide, sodium ethoxide, sodium hydride, potassium tert-butoxide or sodium tert-butoxide; The solvent is any one of tetrahydrofuran, 1,4-dioxane, acetonitrile, toluene, xylene, benzene, N,N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, acetone or butanone; The reaction temperature is 20°C to 100°C; The reaction time is 30 min to 20 h.

6. Use of a pyrimidine-containing aryl pyrazole oxime ether compound according to any one of claims 1 to 4 in the preparation of fungicides or insecticides and acaricides.

7. A bactericidal, insecticidal and acaricidal composition, characterized in that: The active component contains the pyrimidine-containing aryl pyrazole oxime ether compound as claimed in any one of claims 1 to 4, and the weight percentage of the active component in the fungicide is 0.1-99%.

8. A method for using the bactericidal, insecticidal and acaricidal composition according to claim 7, characterized in that: The bactericidal, insecticidal and acaricidal composition is applied to the pathogens or their growth medium.

9. The method for using the bactericidal, insecticidal and acaricidal composition according to claim 8, characterized in that: The effective amount of the bactericidal, insecticidal and acaricidal composition is 10 g to 1000 g per hectare.

10. Use of the bactericidal, insecticidal and acaricidal composition according to claim 7 in the preparation of drugs for preventing and controlling pathogens, insect pests and acarids.

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