CN112745312B - Pyridazinone isoxazole methyl ether compound and application thereof - Google Patents
Pyridazinone isoxazole methyl ether compound and application thereof Download PDFInfo
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- CN112745312B CN112745312B CN201911043927.2A CN201911043927A CN112745312B CN 112745312 B CN112745312 B CN 112745312B CN 201911043927 A CN201911043927 A CN 201911043927A CN 112745312 B CN112745312 B CN 112745312B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
Abstract
The invention discloses a pyridazinone isoxazole methyl ether compound which is shown as a general formula I:
Description
Technical Field
The present invention belongs to the field of agricultural bactericide. In particular to a pyridazinone isoxazole methyl ether compound and application thereof.
Background
Patent DE3824210a1 discloses that compounds of the following general formula have molluscicidal activity:
patent US4929617A discloses that compounds of the following general formula have insecticidal activity:
the pyridazinone isoxazole methyl ether compound and the application thereof as a bactericide are not reported.
Disclosure of Invention
The modern agricultural production needs to continuously develop new pesticides with novel structures and excellent performances. The invention aims to provide a pyridazinone isoxazole methyl ether compound capable of controlling various pathogenic bacteria, which can be applied to agriculture to prepare and control various diseases of crops.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a pyridazinone isoxazole methyl ether compound is shown as a general formula I:
in the formula:
R 1 selected from hydrogen, C 1 -C 12 Alkyl, halo C 1 -C 12 Alkyl radical, C 3 -C 12 Cycloalkyl radical, C 1 -C 12 Alkoxy radical C 1 -C 12 Alkyl radical, C 1 -C 12 Alkylamino radical C 1 -C 12 Alkyl, hydroxy C 1 -C 12 Alkyl radical, C 2 -C 12 Alkenyl, halo C 2 -C 12 Alkenyl radical, C 2 -C 12 Alkynyl, halo C 2 -C 12 Alkynyl, C 1 -C 12 Alkoxycarbonyl radical C 1 -C 12 Alkyl or dimethylamino C 1 -C 12 An alkyl group;
R 2 selected from halogens;
R 3 、R 4 may be the same or different and are each selected from hydrogen or C 1 -C 6 An alkyl group;
r is selected from halogen, hydroxyl, amino, cyano, nitro and C 1 -C 12 Alkyl, halo C 1 -C 12 Alkyl radical, C 1 -C 12 Alkoxy, halo C 1 -C 12 Alkoxy radical, C 3 -C 12 Cycloalkyl radical, C 1 -C 12 Alkylamino, halogeno C 1 -C 12 Alkylamino radical, di (C) 1 -C 12 Alkyl) amino, halo-di (C) 1 -C 12 Alkyl) amino, C 1 -C 12 Alkylthio, halo C 1 -C 12 Alkylthio radical, C 2 -C 12 Alkenyl, halo C 2 -C 12 Alkenyl radical, C 2 -C 12 Alkynyl, halo C 2 -C 12 Alkynyl, C 2 -C 12 Alkenyloxy, halogeno C 2 -C 12 Alkenyloxy radical, C 2 -C 12 Alkynyloxy, halo C 2 -C 12 Alkynyloxy, C 1 -C 12 Alkylsulfonyl, halo C 1 -C 12 Alkylsulfonyl radical, C 1 -C 12 Alkylcarbonyl, halo C 1 -C 12 Alkylcarbonyl group, C 1 -C 12 Alkoxycarbonyl, halogeno C 1 -C 12 Alkoxycarbonyl group, C 1 -C 12 Alkylamino carbonyl, di (C) 1 -C 12 Alkyl) aminocarbonyl, C 1 -C 12 Alkoxy radical C 1 -C 12 Alkyl, halo C 1 -C 12 Alkoxy radical C 1 -C 12 Alkyl radical, C 1 -C 12 Alkylcarbonyloxy, halo C 1 -C 12 Alkylcarbonyloxy, C 1 -C 12 Alkoxycarbonyloxy, halo C 1 -C 12 Alkoxycarbonyloxy, C 1 -C 12 Alkylsulfonyloxy, halo C 1 -C 12 Alkylsulfonyloxy, C 1 -C 12 Alkoxy radical C 1 -C 12 Alkoxy or halo C 1 -C 12 Alkoxy radical C 1 -C 12 Alkoxy, n ═ 0,1, 2, 3, 4, or 5;
x is selected from O or NR 3 ；
Carbon atom C 1 And C 2 Connected by single or double bonds.
Preferred compounds of the invention include: in the general formula I
R 1 Selected from hydrogen, C 1 -C 8 Alkyl, halo C 1 -C 8 Alkyl radical, C 3 -C 8 Cycloalkyl radical, C 2 -C 8 Alkenyl, halo C 2 -C 8 Alkenyl radical, C 2 -C 8 Alkynyl, halo C 2 -C 8 Alkynyl or C 1 -C 8 Alkoxycarbonyl radical C 1 -C 8 An alkyl group;
R 2 selected from halogens;
R 3 、R 4 may be the same or different and are each selected from hydrogen or C 1 -C 6 An alkyl group;
r is selected from halogen, hydroxyl, amino, cyano, nitro and C 1 -C 8 Alkyl, halo C 1 -C 8 Alkyl radical, C 1 -C 8 Alkoxy, halo C 1 -C 8 Alkoxy radical, C 3 -C 8 Cycloalkyl radical, C 1 -C 8 Alkylamino, halogeno C 1 -C 8 Alkylamino radical, di (C) 1 -C 8 Alkyl) amino, halo-di (C) 1 -C 8 Alkyl) amino, C 1 -C 8 Alkylthio, halo C 1 -C 8 Alkylthio radical, C 2 -C 8 Alkenyl radical, C 2 -C 8 Alkynyl, C 2 -C 8 Alkenyloxy, halogeno C 2 -C 8 Alkenyloxy radical, C 2 -C 8 Alkynyloxy, halo C 2 -C 8 Alkynyloxy, C 1 -C 8 Alkylsulfonyl, halo C 1 -C 8 Alkylsulfonyl radical, C 1 -C 8 Alkylcarbonyl, halo C 1 -C 8 Alkylcarbonyl group, C 1 -C 8 Alkoxycarbonyl, halo C 1 -C 8 Alkoxycarbonyl group, C 1 -C 8 Alkylamino carbonyl, di (C) 1 -C 8 Alkyl) aminocarbonyl, C 1 -C 8 Alkoxy radical C 1 -C 8 Alkyl, halo C 1 -C 8 Alkoxy radical C 1 -C 8 Alkyl radical, C 1 -C 8 Alkylcarbonyloxy, halo C 1 -C 8 Alkylcarbonyloxy, n ═ 0,1, 2, or 3;
x is selected from O orNR 3 ；
Carbon atom C 1 And C 2 Connected by single or double bonds.
Further preferred compounds are: in the general formula I
R 1 Selected from hydrogen, C 1 -C 8 Alkyl, halo C 1 -C 8 Alkyl radical, C 3 -C 8 Cycloalkyl, C 2 -C 8 Alkenyl or C 2 -C 8 An alkynyl group;
R 2 selected from fluorine, chlorine, bromine or iodine;
R 3 、R 4 may be the same or different and are each selected from hydrogen or C 1 -C 6 An alkyl group;
r is selected from fluorine, chlorine, bromine, iodine, hydroxyl, amino, cyano, nitro and C 1 -C 8 Alkyl, halo C 1 -C 8 Alkyl radical, C 1 -C 8 Alkoxy, halo C 1 -C 8 Alkoxy radical, C 3 -C 8 Cycloalkyl, C 1 -C 8 Alkylamino, halogeno C 1 -C 8 Alkylamino radical, di (C) 1 -C 8 Alkyl) amino, halo-di (C) 1 -C 8 Alkyl) amino, C 1 -C 8 Alkylthio, halogeno C 1 -C 8 Alkylthio radical, C 2 -C 8 Alkenyl radical, C 2 -C 8 Alkynyl, C 2 -C 8 Alkenyloxy, halogeno C 2 -C 8 Alkenyloxy radical, C 2 -C 8 Alkynyloxy, halo C 2 -C 8 Alkynyloxy, C 1 -C 8 Alkylsulfonyl, halo C 1 -C 8 Alkylsulfonyl radical, C 1 -C 8 Alkylcarbonyl, halo C 1 -C 8 Alkylcarbonyl group, C 1 -C 8 Alkoxycarbonyl, halo C 1 -C 8 Alkoxycarbonyl group, C 1 -C 8 Alkylamino carbonyl, di (C) 1 -C 8 Alkyl) aminocarbonyl, C 1 -C 8 Alkylcarbonyloxy, halo C 1 -C 8 Alkylcarbonyloxy, n ═ 0,1, 2 or 3;
x is selected from O or NR 3 ；
Carbon atom C 1 And C 2 Connected by a single or double bond.
Still further preferred compounds are: in the general formula I
R 1 C selection 1 -C 4 An alkyl group;
R 2 selected from chlorine or bromine;
R 3 、R 4 may be the same or different and are each selected from hydrogen or C 1 -C 3 An alkyl group;
r is selected from fluorine, chlorine, bromine, cyano, nitro and C 1 -C 4 Alkyl, halo C 1 -C 4 Alkyl radical, C 1 -C 4 Alkoxy, halo C 1 -C 4 Alkoxy radical, C 3 -C 4 Cycloalkyl radical, C 1 -C 4 Alkylamino, halogeno C 1 -C 4 Alkylamino radical, di (C) 1 -C 4 Alkyl) amino, halo-di (C) 1 -C 4 Alkyl) amino, C 1 -C 4 Alkylthio, halo C 1 -C 4 Alkylthio radical, C 1 -C 4 Alkylcarbonyl, halo C 1 -C 4 Alkylcarbonyl group, C 1 -C 4 Alkoxycarbonyl, halogeno C 1 -C 4 Alkoxycarbonyl, n ═ 0,1, 2, or 3;
x is selected from O or NR 3 ；
Carbon atom C 1 And C 2 Connected by single or double bonds.
Further preferred compounds are: in the general formula I
R 1 Methyl, ethyl, n-propyl, isopropyl, n-butyl and tert-butyl are selected;
R 2 selected from chlorine or bromine;
R 3 、R 4 may be the same or different and is independently selected from hydrogen or methyl;
r is selected from fluorine, chlorine, bromine, cyano, nitro and C 1 -C 4 Alkyl, halo C 1 -C 4 Alkyl radical, C 1 -C 4 Alkoxy, halo C 1 -C 4 Alkoxy radical, C 1 -C 4 Alkylcarbonyl, halo C 1 -C 4 Alkylcarbonyl group, C 1 -C 4 Alkoxycarbonyl, halo C 1 -C 4 Alkoxycarbonyl, n ═ 0,1, 2, or 3;
x is selected from O;
carbon atom C 1 And C 2 Connected by single or double bonds.
In the definitions of the compounds of the general formula I given above, the terms used in the collection generally represent the following substituents:
halogen: refers to fluorine, chlorine, bromine or iodine. Alkyl groups: straight-chain or branched alkyl, such as methyl, ethyl, propyl, isopropyl, n-butyl or tert-butyl. Halogenated alkyl groups: straight-chain or branched alkyl groups in which the hydrogen atoms may be partially or completely substituted by halogen atoms, such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, etc. Cycloalkyl groups: substituted or unsubstituted cyclic alkyl groups, such as cyclopropyl, cyclopentyl or cyclohexyl. Alkenyl: substituents formed by replacement of one single carbon-carbon bond by a double carbon-carbon bond in an alkyl radical, e.g. CH 2 ＝CH-、CH 2 CHCH-. Halogenated alkenyl groups: and a substituent formed by substituting a part or all of hydrogen atoms of the alkenyl group with a halogen atom. Alkynyl: and a substituent formed by replacing one carbon-carbon single bond in the alkyl by a carbon-carbon triple bond, such as ethynyl and propargyl. Halogenated alkynyl group: and a substituent formed by substituting a part or all of hydrogen atoms of the alkynyl group with a halogen atom. An alkylcarbonyl group: the alkyl radical being bound to the structure via a carbonyl group, e.g. CH 3 CO-，CH 3 CH 2 CO-. Halogenated alkylcarbonyl group: the hydrogen atoms of the alkyl group of the alkylcarbonyl group may be partially or fully substituted with halogen atoms, e.g. CF 3 CO-. Alkoxy groups: straight or branched chain alkyl groups attached to the structure via oxygen atom linkages. Haloalkoxy groups: straight-chain or branched alkoxy groups in which the hydrogen atoms may be partially or completely replaced by halogen atoms, such as chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, trifluoroethoxy, etc. Alkylamino group: straight or branched chain alkyl, linked to the structure via a nitrogen atom. Haloalkylamino: straight-chain or branched alkylamino radicals in which the alkyl radical is presentThe hydrogen atoms in the above may be partially or wholly replaced with halogen atoms. Alkylthio group: straight or branched chain alkyl groups attached to the structure via a sulfur atom. Haloalkylthio: straight-chain or branched alkylthio groups in which the hydrogen atoms in these alkyl groups may be partially or wholly replaced by halogen atoms, such as chloromethylthio, dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio, trifluoromethylthio, chlorofluoromethylthio and the like. Alkoxycarbonyl group: alkyl-O-CO-. An alkylamino carbonyl group: alkyl-N-CO-.
Some of the compounds of the present invention can be illustrated by the specific compounds listed in tables 1 and 4, but these compounds do not limit the present invention.
When X is O, carbon atom C 1 And C 2 When connected by a double bond, the compounds of formula I can be represented by formula IA, specific compounds of which are shown in Table 1.
2: when X is O, carbon atom C 1 And C 2 When connected by a single bond, the compounds of formula I may be represented by formula IB, and the substituents representing compounds IB1 to IB516 are in accordance with the corresponding substituents of compounds IA1 to IA516, respectively, in table 1.
3: when X is NH, a carbon atom C 1 And C 2 When connected by a double bond, the compounds of the formula I can be usedEach substituent representing compounds IC1 to IC516 is represented by general formula IC and corresponds to the corresponding substituent of compounds IA1 to IA516 in table 1, respectively.
4: when X is NH, carbon atom C 1 And C 2 When connected by a single bond, the compounds of formula I may be represented by formula ID, and the substituents representing compounds ID1 to ID516 are identical to the corresponding substituents of compounds IA1 to IA516, respectively, in table 1.
The compound represented by the general formula I is prepared by reacting an intermediate represented by a general formula II and an intermediate represented by a general formula III under alkaline conditions, or reacting an intermediate represented by a general formula IV and an intermediate represented by a general formula V under alkaline conditions, wherein Hal represents a halogen atom, and other substituents are as defined above:
the reaction is carried out in a suitable solvent, which may be selected from, for example, tetrahydrofuran, acetonitrile, toluene, xylene, benzene, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, acetone, or butanone.
Suitable bases can be selected from, for example, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, triethylamine, pyridine, sodium methoxide, sodium ethoxide, sodium hydride, potassium or sodium tert-butoxide, etc.
The reaction temperature may be between room temperature and the boiling temperature of the solvent, and is generally from 20 to 120 ℃.
The reaction time is from 30 minutes to 20 hours, usually from 1 to 10 hours.
The intermediate ii can be prepared from intermediate IV according to the method described in WO2018072736, and intermediate IV is a commercially available product. Intermediates III and V can be prepared according to known methods, for example as described in references Molecules 2017,22(5)690, US2019225621A1 or US6093736A, etc.
Compared with the compounds containing pyridazinone and isoxazole structures disclosed in the prior art, the compounds of the general formula I have obvious difference in structural characteristics and different applications. The compound has good bactericidal activity and wide application prospect.
The compound of the general formula I shows excellent activity on various pathogenic bacteria in the agricultural field. Therefore, the technical scheme of the invention also comprises the application of the compound shown in the general formula I in preparing bactericidal drugs in agriculture and other fields.
The examples of diseases mentioned below are intended only to illustrate the invention, but in no way limit it.
The compounds of the general formula I can be used for controlling the following diseases: oomycete diseases such as downy mildew (cucumber downy mildew, rape downy mildew, soybean downy mildew, beet downy mildew, sugarcane downy mildew, tobacco downy mildew, pea downy mildew, loofah downy mildew, wax gourd downy mildew, melon downy mildew, Chinese cabbage downy mildew, spinach downy mildew, radish downy mildew, grape downy mildew, onion downy mildew), white rust (rape white rust, Chinese cabbage white rust), damping-off (rape damping-off, tobacco damping-off, tomato damping-off, pepper damping-off, eggplant damping-off, cucumber damping-off, cotton seedling damping-off), cotton rot (hot pepper rot, loofah sponge rot, wax gourd blight), epidemic diseases (broad bean blight, cucumber blight, pumpkin blight, melon blight, hot pepper, leek blight, garlic blight, cotton blight, tomato blight, etc.; diseases caused by fungi imperfecti, such as blight (sweet potato wilt, cotton wilt, sesame wilt, castor wilt, tomato wilt, bean wilt, cucumber wilt, silk gourd wilt, pumpkin wilt, winter melon wilt, watermelon wilt, sweet melon wilt, hot pepper wilt, broad bean wilt, rape wilt, soybean wilt), root rot (hot pepper root rot, eggplant root rot, bean root rot, cucumber root rot, bitter gourd root rot, cotton black root rot, broad bean root rot), damping off (seedling blight of cotton, sesame damping off, hot pepper damping off, cucumber damping off, cabbage damping off), anthracnose of cucumber (sorghum anthracnose, cotton anthracnose, kenaf, jute anthracnose, flax anthracnose, mulberry diseases, pepper, eggplant diseases, bean diseases, anthracnose, and cabbage damping off), anthracnose of tobacco, eggplant diseases, anthracnose, and vegetable diseases, Balsam pear anthracnose, pumpkin anthracnose, wax gourd anthracnose, watermelon anthracnose, melon anthracnose, litchi anthracnose), verticillium wilt (cotton verticillium wilt, sunflower verticillium wilt, tomato verticillium wilt, hot pepper verticillium wilt, eggplant verticillium wilt), scab (pumpkin scab, wax gourd scab, melon scab), gray mold (boll gray mold, red ramie gray mold, tomato gray mold, hot pepper gray mold, bean gray mold, celery gray mold, spinach gray mold, kiwi gray mold), brown spot (cotton brown spot, jute brown spot, beet brown spot, peanut brown spot, pepper brown spot, wax gourd brown spot, soybean brown spot, sunflower brown spot, pea brown spot, broad bean brown spot), black spot (flax brown spot, rape black spot, sesame black spot, sunflower black spot, castor black spot, tomato black spot, tomato black spot, tomato black spot, tomato black spot, tomato black spot, tomato, Pepper black spot, eggplant black spot, bean black spot, cucumber black spot, celery black spot, carrot black rot, carrot black spot, apple black spot, peanut black spot), spot blight (tomato spot blight, pepper spot blight, celery spot blight), early blight (tomato early blight, pepper early blight, eggplant early blight, potato early blight, celery early blight), ring spot (soybean ring spot, sesame ring spot, bean ring spot), leaf blight (sesame leaf blight, sunflower leaf blight, watermelon leaf blight, melon leaf blight), stem base rot (tomato stem base rot, bean stem base rot), and others (corn round spot, kenaf waist fold, rice blast, black sheath disease, sugarcane eye spot, cotton boll aspergillosis, peanut crown rot, soybean stem blight, soybean black spot, melon northern leaf blotch, tea leaf spot, black spot, peanut net spot, red leaf spot, tomato black spot, potato black spot, tomato black spot, tomato black spot, tomato spot, etc, Pepper white spot, white gourd leaf spot, celery black rot, spinach heart rot, kenaf leaf mold, kenaf spot, jute stem spot, soybean purple spot, sesame leaf spot, castor gray spot, tea brown leaf spot, eggplant brown speck, kidney bean red spot, bitter gourd leukoderma, watermelon spot, jute rot, sunflower root stem rot, kidney bean carbon rot, soybean target spot, eggplant corynespora leaf spot, cucumber target spot, tomato leaf mold, eggplant leaf mold, broad bean red spot, etc.), and the like; basidiomycete diseases such as rust (wheat stripe rust, wheat stalk rust, wheat leaf rust, peanut rust, sunflower rust, sugarcane rust, leek rust, onion rust, chestnut rust, soybean rust), smut (maize head smut, maize smut, sorghum head smut, sorghum loose smut, sorghum stalk smut, chestnut kernel smut, sugarcane head smut, kidney bean rust) and others (such as wheat sharp eyespot, rice sheath blight, etc.); ascomycetes diseases, such as powdery mildew (wheat powdery mildew, rape powdery mildew, sesame powdery mildew, sunflower powdery mildew, beet powdery mildew, eggplant powdery mildew, pea powdery mildew, loofah powdery mildew, pumpkin powdery mildew, wax gourd powdery mildew, melon powdery mildew, grape powdery mildew, broad bean powdery mildew), sclerotinia sclerotiorum (flax sclerotinia sclerotiorum, rape sclerotinia sclerotiorum, soybean sclerotinia sclerotiorum, peanut sclerotinia sclerotiorum, tobacco sclerotinia sclerotiorum, pepper sclerotinia sclerotiorum, eggplant sclerotinia sclerotiorum, bean sclerotinia sclerotiorum, pea sclerotiorum, cucumber sclerotiorum, bitter gourd sclerotinia sclerotiorum, wax gourd sclerotinia sclerotiorum, watermelon sclerotinia sclerotiorum, celery sclerotiorum), scab (scab of black star, pear scab) and the like.
Owing to their positive properties, the abovementioned compounds can be used advantageously for protecting crops, livestock and breeding animals of agricultural and horticultural importance, as well as the environment which is frequently encountered by humans, against harmful bacteria.
The amount of the compound used to achieve the desired effect will vary depending on factors such as the compound used, the crop to be protected, the type of pest, the extent of infection, the climatic conditions, the method of application, and the dosage form employed.
A dose of 10 g to 5 kg of compound per hectare provides adequate control.
The technical scheme of the invention also comprises a method for preventing and controlling germs, which comprises the following steps: the bactericidal composition is applied to the germs or the growth medium thereof. Preferably, an effective amount of 10 g to 1000 g per hectare is selected, and an effective amount of 20 g to 500 g per hectare is selected.
For certain applications, for example, agriculture, one or more other fungicides, insecticides, acaricides, herbicides, plant growth regulators or fertilizers, etc., can be added to the fungicidal compositions of the present invention, thereby providing additional advantages and effects.
It should be understood that various changes and modifications may be made within the scope of the present invention as defined by the claims.
Detailed Description
The following specific examples are intended to further illustrate the invention, but the invention is by no means limited to these examples.
Synthetic examples
Example 1: preparation of Compound 1A39
0.40g (0.002mol) of 2-tert-butyl-4-chloro-5-hydroxypyridazin-3 (2H) -one and 0.55g (0.004mol) of potassium carbonate were put in a reaction flask, and 15mL of N, N-Dimethylformamide (DMF) was added thereto, followed by stirring, 3mL of a DMF solution of 0.46g (0.002mol) of 5- (chloromethyl) -3- (4-chlorophenyl) isothiazole was added dropwise at 60 ℃ and the reaction was carried out while maintaining the temperature at 80 ℃. After TLC monitoring reaction, the reaction liquid is poured into water, extracted twice by ethyl acetate, organic phases are combined and washed by water, dried and decompressed for desolventizing, and the residue is purified by column chromatography (eluent is ethyl acetate and petroleum ether (boiling range is 60-90 ℃) with volume ratio of 1:5) to obtain the compound 1A39 as white solid with melting point of 155.1 ℃.
1 H NMR (600MHz, internal standard TMS, solvent CDCl 3 )δ(ppm)7.80(s,1H),7.76(d,J＝8.5Hz,2H), 7.46(d,J＝8.5Hz,2H),6.72(s,1H),5.43(s,2H),1.65(s,9H)。
Implementation 2: preparation of Compound 1B39
Taking 0.42g (0.002mol) of (3- (4-chlorphenyl) -4, 5-dihydroisoxazol-5-yl methanol and 1.30g (0.004mol) of cesium carbonate into a reaction bottle, adding 15mL of N, N-Dimethylformamide (DMF) into the reaction bottle, stirring, adding 0.48g (0.002mol) of 2-tert-butyl-4, 5-dichloropyridazin-3 (2H) -one, keeping the temperature at 100 ℃, monitoring the reaction by TLC, pouring the reaction liquid into water, extracting twice with ethyl acetate, combining organic phases, washing with water, drying, decompressing and desolventizing, and purifying the residue by column chromatography (eluent is ethyl acetate and petroleum ether (boiling range is 60-90 ℃) at a volume ratio of 1:5) to obtain a compound 1B39 which is a white solid and has a melting point of 143.6 ℃.
1 H NMR (600MHz, internal standard TMS, solvent CDCl 3 )δ(ppm)7.76(s,1H),7.62(d,J＝8.5Hz,2H), 7.40(d,J＝8.5Hz,2H),5.12(dq,J＝6.7,4.5Hz,1H),4.38(d,J＝4.5Hz,2H),3.48(ddd,J＝
23.5,16.7,8.8Hz,2H),1.64(s,9H)。
Other compounds of the invention may be prepared by reference to the above examples.
Physical property data and nuclear magnetic data of some of the compounds ( 1 H NMR, 600MHz, internal standard TMS, solvent CDCl 3 Ppm) are as follows:
compound 1a 1: yellow solid, mp 129.6 ℃. δ 7.83-7.81(m,3H), 7.48-7.47 (m,3H),6.74(s, 1H),5.44(s,2H),1.65(s, 9H).
Compound 1a 25: yellow solid, mp 131.1 ℃. δ 8.69-8.52 (m,1H),8.33(dd, J ═ 8.2,1.2Hz,1H), 8.17(d, J ═ 7.8Hz,1H),7.68(t, J ═ 8.0Hz,1H),7.66(s,1H),6.71(s,1H),4.39(s,2H),1.64(s, 9H).
Compound 1a 27: pale yellow solid, melting point 127.6 ℃. δ 8.08(s,1H),8.02(d, J ═ 7.7Hz,1H),7.81(s, 1H),7.74(d, J ═ 7.6Hz,1H),7.62(t, J ═ 7.7Hz,1H),6.80(s,1H),5.46(s,2H),1.65(s, 9H).
Compound 1a 38: white solid, melting point 141.2 ℃. δ 7.85-7.78 (m,3H),7.17(t, J ═ 8.6Hz,2H),6.71 (s,1H),5.43(s,2H),1.65(s, 9H).
Compound 1a 42: pale yellow solid, mp 153.8 ℃. δ 7.94(d, J ═ 8.2Hz,2H), 7.81-7.72 (m,3H), 6.79(s,1H),5.46(s,2H),1.65(s, 9H).
Compound 1a 43: yellow solid, mp 166.2 ℃. δ 8.35(d, J ═ 7.9Hz,3H),8.02(d, J ═ 8.0Hz,2H), 7.81(s,1H),6.83(s,1H),5.47(s,2H),1.66(s, 9H).
Compound 1a 44: white solid, mp 153.3 ℃. δ 7.81(s,1H),7.70(d, J ═ 7.3Hz,2H),7.27(d, J ═ 7.3Hz,2H),6.71(s,1H),5.42(s,2H),2.41(s,3H),1.65(s, 9H).
Compound 1a 47: white solid, melting point 140.0 ℃. δ 7.88-7.66 (m,3H),7.49(d, J ═ 6.9Hz,2H),6.71 (s,1H),5.43(s,2H),1.65(s,9H),1.35(s, 9H).
Compound 1a 48: white solid, melting point 155.9 ℃. δ 7.94(d,2H),7.81(s,1H),7.75(d,2H),6.79(s, 1H),5.46(s,2H),1.65(s, 9H).
Compound 1a 49: white solid, melting point 133.2 ℃. δ 7.80(s,1H),7.75(d, J ═ 8.8Hz,2H),6.99(d, J ═ 8.8Hz,2H),6.68(s,1H),5.42(s,2H),3.86(s,3H),1.65(s, 9H).
Compound 1a 50: white solid, melting point 152.4 ℃. δ 7.86(d, J ═ 8.2Hz,2H),7.80(s,1H),7.33(d, J ═ 8.1Hz,2H),6.74(s,1H),5.44(s,2H),1.65(s, 9H).
Compound 1a 60: white solid, melting point 141.9 ℃. δ 7.82(s,1H),7.71(d, J ═ 8.3Hz,1H),7.54(s,1H), 7.37(d, J ═ 8.4Hz,1H),6.91(s,1H),5.45(s,2H),1.65(s, 9H).
Compound 1a 75: white solid, melting point 141.9 ℃. δ 7.83(s,1H),7.32(s,1H),7.18(dd, J ═ 16.6,7.8 Hz,2H),6.60(s,1H),5.44(s,2H),2.42(s,3H),2.36(s,3H),1.65(s, 9H).
Compound 1a 76: pale yellow solid, melting point 147.3 ℃. δ 7.81(s,1H),7.77(d, J ═ 2.3Hz,1H),7.44(d, J ═ 8.6Hz,1H),7.40(d, J ═ 2.3Hz,1H),6.92(s,1H),5.45(s,2H),1.65(s, 9H).
Compound 1a 80: brown solid, m.p. 168.0 ℃. δ 8.53(d, J ═ 2.7Hz,1H),8.19(dd, J ═ 8.8,2.7Hz, 1H),7.91(d, J ═ 8.8Hz,1H),7.82(s,1H),6.94(s,1H),5.48(s,2H),1.66(s, 9H).
Compound 1a 90: brown solid, m.p. 170.2 ℃. δ 7.81(s,1H),7.42(d, J ═ 1.9Hz,1H),7.30(dd, J ═ 8.3,1.9Hz,1H),6.94(d, J ═ 8.3Hz,1H),6.70(s,1H),5.42(s,2H),3.96(s,3H),3.94(s,3H), 1.65(s, 9H).
Compound 1B 25: brown oil. δ 8.45(s,1H),8.30(d, J ═ 8.2Hz,1H),8.09(d, J ═ 7.9Hz,1H), 7.77(s,1H),7.63(t, J ═ 8.0Hz,1H), 5.23-5.17 (m,1H),4.43(ddd, J ═ 38.2,10.7,4.1Hz,2H), 3.57(ddd, J ═ 23.6,16.7,8.9Hz,2H),1.64(s, 9H).
Compound 1B 27: brown oil. δ 7.91(s,1H),7.88(s,1H),7.76(s,1H),7.69(s,1H),7.56(s, 1H),5.17(dq, J ═ 6.9,4.4Hz,1H), 4.48-4.31 (m,2H),3.54(ddd, J ═ 23.6,16.7,8.9Hz,2H),1.64(s, 9H).
Compound 1B 42: brown solid, mp 157.8 ℃. δ 7.79(d, J ═ 8.6Hz,2H),7.75(s,1H),7.72(d, J ═ 8.5Hz,2H),5.18(td, J ═ 11.0,4.2Hz,1H),4.41(ddd, J ═ 28.1,10.6,4.2Hz,2H),3.52(ddd, J ═ 23.7,16.7,8.9Hz,2H),1.64(s, 9H).
Compound 1B 43: brown solid, melting point 142.0 ℃. δ 7.79(d, J ═ 8.6Hz,2H),7.75(s,1H),7.72(d, J ═ 8.5Hz,2H),5.18(td, J ═ 11.0,4.2Hz,1H),4.41(ddd, J ═ 28.1,10.6,4.2Hz,2H),3.52(ddd, J ═ 23.7,16.7,8.9Hz,2H),1.64(s, 9H).
Compound 1B 44: brown oil. δ 7.77(s,1H),7.57(d, J ═ 8.1Hz,2H),7.22(d, J ═ 8.0Hz,2H), 5.09(td, J ═ 11.2,4.9Hz,1H), 4.40-4.33 (m,2H),3.48(ddd, J ═ 23.4,16.7,8.7Hz,2H),2.39(s, 3H),1.64(s, 9H).
Compound 1B 47: brown solid, melting point 138.0 ℃. δ 7.77(s,1H),7.62(d, J ═ 8.3Hz,2H),7.44(d, J ═ 8.3Hz,2H),5.10(td, J ═ 11.0,4.8Hz,1H),4.36(ddd, J ═ 26.9,10.5,4.8Hz,2H),3.49(ddd, J ═ 23.4,16.7,8.7Hz,2H),1.64(s,9H),1.34(s, 9H).
Compound 1B 50: brown solid, m.p. 122.3 ℃. δ 7.76(s,1H),7.72(d, J ═ 8.8Hz,2H),7.27(d, J ═ 9.0Hz,2H),5.14(dq, J ═ 6.7,4.5Hz,1H),4.39(d, J ═ 4.5Hz,2H),3.50(ddd, J ═ 23.5,16.7, 8.8Hz,2H),1.64(s, 9H).
Compound 1B 60: white solid, melting point 122.3 ℃. δ 7.78(s,1H),7.60(d, J ═ 8.4Hz,1H),7.47(s,1H), 7.30(d, J ═ 8.4Hz,1H),5.14(td, J ═ 10.6,4.2Hz,1H),4.40(ddd, J ═ 41.2,10.6,4.1Hz,2H), 3.66(ddd, J ═ 24.0,17.3,8.9Hz,2H),1.64(s, 9H).
Compound 1B 76: brown oil. δ 7.78(s,1H),7.66(s,1H),7.37(d, J ═ 8.5Hz,1H),7.34(d, J ═ 8.9Hz,1H),5.15(s,1H),4.40(dd, J ═ 29.5,10.0Hz,2H), 3.80-3.53 (m,2H),1.65(s, 9H).
Compound 1B 80: brown oil. δ 10.45(s,1H),8.25(dd, J ═ 9.1,2.6Hz,1H),8.19(d, J ═ 2.6Hz,1H), 7.74(s,1H),7.15(d, J ═ 9.1Hz,1H),5.19(m,1H), 4.55-4.34 (m,2H),3.69(ddd, J ═ 23.6, 13.9,6.3Hz,2H),1.62(s, 9H).
Meanwhile, other compounds shown in the general formula I of the invention can be obtained by replacing corresponding raw materials according to the contents described in the above synthetic examples or by the preparation method described in the contents of the invention.
Examples of measurement of biological Activity
The compound of the invention has good activity to various germs in the agricultural field.
Example 3: measurement of fungicidal Activity
The bactericidal activity of the compound sample of the invention for measuring various fungal diseases of plants is determined as follows:
a living pot culture determination method is adopted, namely a compound sample to be detected is dissolved by a small amount of solvent (the type of the solvent is acetone, methanol, DMF and the like, and is selected according to the dissolving capacity of the solvent on the sample, the volume ratio of the solvent amount to the liquid spraying amount is equal to or less than 0.05), and the solution is diluted by water containing 0.1 percent of Tween 80 to prepare the liquid to be detected with the required concentration. The solution to be tested is sprayed on diseased host plants (the host plants are standard potted seedlings cultured in a greenhouse) on a crop sprayer, and disease inoculation is carried out after 24 hours. According to the characteristics of diseases, inoculating the disease plants needing temperature and moisture control culture, then culturing in an artificial climate chamber, transferring into a greenhouse for culture after the diseases are infected, and directly inoculating and culturing the disease plants without moisture control culture in the greenhouse. The compound disease control effect evaluation is carried out after the control is sufficiently ill (usually, one week).
The results of the activity test of some compounds are as follows:
activity against cucumber downy mildew:
at a dose of 400ppm, compounds IA1, IA25, IA38, IA39, IA43, IA48, IA50, IA80, IB39, IB42, IB60, etc. have 100% activity against cucumber downy mildew.
At a dose of 100ppm, the activity of compounds IA1, IA25, IA38, IA39, IA43, etc. on cucumber downy mildew is 100%.
At a dose of 25ppm, the activity of compounds IA1, IA25, IA38, IA39, IA43 etc. on cucumber downy mildew is 100%.
At a dose of 6.25ppm, the activity of compounds IA1, IA38, IA39, IA43 etc. on cucumber downy mildew is higher than 95%.
Activity against cucumber anthracnose:
at a dose of 400ppm, the activity of compounds IA27, IA43, IA48 etc. on cucumber anthracnose was 100%.
Activity against wheat powdery mildew:
at a dose of 400ppm, compounds IA43, IA50, IB47, etc. had 100% activity against wheat powdery mildew.
At a dose of 100ppm, the activity of compound IA43, etc. on wheat powdery mildew is not less than 80%.
Activity against corn rust:
at a dose of 400ppm, compound IA1, etc. had 100% activity against corn rust.
At a dose of 100ppm, the activity of the compound IA1 and the like on corn rust is not less than 80%.
Claims (7)
1. Pyridazinone isoxazole methyl ether compounds are shown as a general formula I:
in the formula:
R 1 selected from hydrogen, C 1 -C 12 Alkyl, halo C 1 -C 12 An alkyl group;
R 2 selected from halogens;
R 3 、R 4 are each selected from hydrogen;
r is selected from halogen, nitro and C 1 -C 12 Alkyl, halo C 1 -C 12 Alkyl radical, C 1 -C 12 Alkoxy, halo C 1 -C 12 Alkoxy, n ═ 0,1, 2;
x is selected from O;
carbon atom C 1 And C 2 Are connected by a double bond.
2. The compound of claim 1, wherein:
R 1 selected from hydrogen, C 1 -C 8 Alkyl, halo C 1 -C 8 An alkyl group;
R 2 selected from halogens;
R 3 、R 4 are respectively selected from hydrogen;
r is selected from halogen, nitro and C 1 -C 8 Alkyl, halo C 1 -C 8 Alkyl radical, C 1 -C 8 Alkoxy, halo C 1 -C 8 Alkoxy, n ═ 0,1, 2;
x is selected from O;
carbon atom C 1 And C 2 Are connected by a double bond.
3. The compound of claim 2, wherein: in the general formula I
R 1 Selected from hydrogen, C 1 -C 8 Alkyl, halo C 1 -C 8 An alkyl group;
R 2 selected from fluorine, chlorine, bromine or iodine;
R 3 、R 4 are respectively selected from hydrogen;
r is selected from fluorine, chlorine, bromine, iodine, nitro and C 1 -C 8 Alkyl, halo C 1 -C 8 Alkyl radical, C 1 -C 8 Alkoxy, halo C 1 -C 8 Alkoxy, n ═ 0,1, 2;
x is selected from O;
carbon atom C 1 And C 2 Are connected by a double bond.
4. A compound according to claim 3, characterized in that: in the general formula I
R 1 C selection 1 -C 4 An alkyl group;
R 2 selected from chlorine or bromine;
R 3 、R 4 are each selected from hydrogen;
r is selected from fluorine, chlorine, bromine, nitro and C 1 -C 4 Alkyl, halo C 1 -C 4 Alkyl radical, C 1 -C 4 Alkoxy, halo C 1 -C 4 Alkoxy, n ═ 0,1, 2;
x is selected from O;
carbon atom C 1 And C 2 Are connected by a double bond.
5. The compound of claim 4, wherein: in the general formula I
R 1 Methyl, ethyl, n-propyl, isopropyl, n-butyl and tert-butyl are selected;
R 2 selected from chlorine or bromine;
R 3 、R 4 are each selected from hydrogen;
r is selected from fluorine, chlorine, bromine, nitro and C 1 -C 4 Alkyl, halo C 1 -C 4 Alkyl radical, C 1 -C 4 Alkoxy, halo C 1 -C 4 Alkoxy, n ═ 0,1, 2;
x is selected from O;
carbon atom C 1 And C 2 Are connected by a double bond.
6. The use of a compound of the general formula I according to claim 1 for the preparation of a fungicide in the agricultural field.
7. A germicidal composition, characterized by: the composition comprises an active component and an agriculturally acceptable carrier, wherein the weight percentage of the active component in the composition is 0.5-90%, and the active component contains the compound of the general formula I in the claim 1.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4837217A (en) * | 1985-04-19 | 1989-06-06 | Nissan Chemical Industries, Ltd. | Pyridazinone derivatives, preparation thereof, and insecticidal, acaricidal, nematicidal, fungicidal compositions |
| EP0351589A2 (en) * | 1988-07-16 | 1990-01-24 | BASF Aktiengesellschaft | 3(2H)-Pyridazinone derivatives for controlling snails |
| US4929617A (en) * | 1987-12-12 | 1990-05-29 | Basf Aktiengesellschaft | 2-tert-butyl-5-isoxazolylmethylthio-3(2H)-pyridazin-3-one |
| CN1561728A (en) * | 2004-03-24 | 2005-01-12 | 华东理工大学 | Oxazole pyridazine and its derivative form and use |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4837217A (en) * | 1985-04-19 | 1989-06-06 | Nissan Chemical Industries, Ltd. | Pyridazinone derivatives, preparation thereof, and insecticidal, acaricidal, nematicidal, fungicidal compositions |
| US4929617A (en) * | 1987-12-12 | 1990-05-29 | Basf Aktiengesellschaft | 2-tert-butyl-5-isoxazolylmethylthio-3(2H)-pyridazin-3-one |
| EP0351589A2 (en) * | 1988-07-16 | 1990-01-24 | BASF Aktiengesellschaft | 3(2H)-Pyridazinone derivatives for controlling snails |
| CN1561728A (en) * | 2004-03-24 | 2005-01-12 | 华东理工大学 | Oxazole pyridazine and its derivative form and use |
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