Application of pyridazinone isoxazole methyl sulfide compound as bactericide
阅读说明：本技术 一种哒嗪酮异恶唑甲硫醚类化合物用作杀菌剂的用途 (Application of pyridazinone isoxazole methyl sulfide compound as bactericide ) 是由 李慧超 关爱莹 李志念 芦志成 王军锋 杨金龙 刘长令 于 2019-10-30 设计创作，主要内容包括：本发明公开了一种哒嗪酮异恶唑甲硫醚类化合物用作杀菌剂的用途,结构如通式I所示：式中各取代基的定义见说明书。通式I化合物对农业领域中的多种病菌表现出很好的活性,尤其是对黄瓜霜霉病、黄瓜炭疽病和玉米锈病等具有优异的防治效果。(The invention discloses an application of pyridazinone isoxazole methyl sulfide compounds as bactericides, which has a structure shown as a general formula I:)
1. Application of pyridazinone isoxazole methyl ether compounds shown as a general formula I as bactericides is disclosed.
2. The use of pyridazinone isoxazole methyl ether compounds according to claim 1 as fungicides is characterized in that: the pyridazinone isoxazole methyl ether compound shown in the general formula I has the following structure:
in the formula:
R1selected from hydrogen, C1-C12Alkyl, halo C1-C12Alkyl radical, C3-C12Cycloalkyl radical, C1-C12Alkoxy radical C1-C12Alkyl radical, C1-C12Alkylamino radical C1-C12Alkyl, hydroxy C1-C12Alkyl radical, C2-C12Alkenyl, halo C2-C12Alkenyl radical, C2-C12Alkynyl, halo C2-C12Alkynyl, C1-C12Alkoxycarbonyl radical C1-C12Alkyl or dimethylamino C1-C12An alkyl group;
R2selected from halogens;
R3、R4may be the same or different and are each selected from hydrogen or C1-C6An alkyl group;
r is selected from halogen, hydroxyl, amino, cyano, nitro and C1-C12Alkyl, halo C1-C12Alkyl radical, C1-C12Alkoxy, halo C1-C12Alkoxy radical, C3-C12Cycloalkyl radical, C1-C12Alkylamino, halogeno C1-C12Alkylamino radical, di (C)1-C12Alkyl) amino, halo-di (C)1-C12Alkyl) amino, C1-C12Alkylthio, halo C1-C12Alkylthio radical, C2-C12Alkenyl, halo C2-C12Alkenyl radical, C2-C12Alkynyl, halo C2-C12Alkynyl, C2-C12Alkenyloxy, halogeno C2-C12Alkenyloxy radical, C2-C12Alkynyloxy, halo C2-C12Alkynyloxy, C1-C12Alkylsulfonyl, halo C1-C12Alkylsulfonyl radical, C1-C12Alkylcarbonyl, halo C1-C12Alkylcarbonyl group, C1-C12Alkoxycarbonyl, halo C1-C12Alkoxycarbonyl group, C1-C12Alkylamino carbonyl, di (C)1-C12Alkyl) aminocarbonyl, C1-C12Alkoxy radical C1-C12Alkyl, halo C1-C12Alkoxy radical C1-C12Alkyl radical, C1-C12Alkylcarbonyloxy, halo C1-C12Alkylcarbonyloxy, C1-C12Alkoxycarbonyloxy, halo C1-C12Alkoxycarbonyloxy, C1-C12Alkylsulfonyloxy, halo C1-C12Alkylsulfonyloxy, C1-C12Alkoxy radical C1-C12Alkoxy or halo C1-C12Alkoxy radical C1-C12Alkoxy, n ═ 0, 1, 2, 3, 4, or 5.
3. Use according to claim 2, characterized in that: in the general formula I
R1Is selected fromHydrogen, C1-C8Alkyl, halo C1-C8Alkyl radical, C3-C8Cycloalkyl radical, C2-C8Alkenyl or C2-C8An alkynyl group;
R2selected from fluorine, chlorine, bromine or iodine;
R3、R4may be the same or different and are each selected from hydrogen or C1-C6An alkyl group;
r is selected from fluorine, chlorine, bromine, iodine, hydroxyl, amino, cyano, nitro and C1-C8Alkyl, halo C1-C8Alkyl radical, C1-C8Alkoxy, halo C1-C8Alkoxy radical, C3-C8Cycloalkyl radical, C1-C8Alkylamino, halogeno C1-C8Alkylamino radical, di (C)1-C8Alkyl) amino, halo-di (C)1-C8Alkyl) amino, C1-C8Alkylthio, halo C1-C8Alkylthio radical, C2-C8Alkenyl radical, C2-C8Alkynyl, C2-C8Alkenyloxy, halogeno C2-C8Alkenyloxy radical, C2-C8Alkynyloxy, halo C2-C8Alkynyloxy, C1-C8Alkylsulfonyl, halo C1-C8Alkylsulfonyl radical, C1-C8Alkylcarbonyl, halo C1-C8Alkylcarbonyl group, C1-C8Alkoxycarbonyl, halo C1-C8Alkoxycarbonyl group, C1-C8Alkylamino carbonyl, di (C)1-C8Alkyl) aminocarbonyl, C1-C8Alkylcarbonyloxy, halo C1-C8Alkylcarbonyloxy, n ═ 0, 1, 2 or 3.
4. Use according to claim 3, characterized in that: in the general formula I
R1C selection1-C4An alkyl group;
R2selected from chlorine or bromine;
R3、R4may be the same or different and are each selected from hydrogen or C1-C3An alkyl group;
r is selected from fluorine, chlorine, bromine, cyano, nitro and C1-C4Alkyl, halo C1-C4Alkyl radical, C1-C4Alkoxy, halo C1-C4Alkoxy radical, C3-C4Cycloalkyl radical, C1-C4Alkylamino, halogeno C1-C4Alkylamino radical, di (C)1-C4Alkyl) amino, halo-di (C)1-C4Alkyl) amino, C1-C4Alkylthio, halo C1-C4Alkylthio radical, C1-C4Alkylcarbonyl, halo C1-C4Alkylcarbonyl group, C1-C4Alkoxycarbonyl, halo C1-C4Alkoxycarbonyl, n ═ 0, 1, 2, or 3.
5. Use according to claim 4, characterized in that: in the general formula I
R1Methyl, ethyl, n-propyl, isopropyl, n-butyl and tert-butyl are selected;
R2selected from chlorine or bromine;
R3、R4may be the same or different and is independently selected from hydrogen or methyl;
r is selected from fluorine, chlorine, bromine, cyano, nitro and C1-C4Alkyl, halo C1-C4Alkyl radical, C1-C4Alkoxy, halo C1-C4Alkoxy radical, C1-C4Alkylcarbonyl, halo C1-C4Alkylcarbonyl group, C1-C4Alkoxycarbonyl, halo C1-C4Alkoxycarbonyl, n ═ 0, 1, 2, or 3.
6. Use according to claims 1-5, characterized in that: the compound shown in the general formula I is applied to preparing fungicide.
7. The bactericidal, insecticidal and acaricidal composition is characterized by comprising the following components in parts by weight: 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 a compound shown in a general formula I.
Technical Field
The present invention belongs to the field of agricultural bactericide. In particular to application of a pyridazinone isoxazole methyl sulfide compound as a bactericide.
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 application of the pyridazinone isoxazole methyl ether compound as a bactericide is not reported in documents.
Disclosure of Invention
The invention aims to provide a new application of a pyridazinone isoxazole methyl ether compound shown as a general formula I.
The technical scheme of the invention is as follows:
the application of the pyridazinone isoxazole methyl ether compound in preparing the bactericide has a structure shown as a general formula I:
in the formula:
R1selected from hydrogen, C1-C12Alkyl, halo C1-C12Alkyl radical, C3-C12Cycloalkyl radical, C1-C12Alkoxy radical C1-C12Alkyl radical, C1-C12Alkylamino radical C1-C12Alkyl, hydroxy C1-C12Alkyl radical, C2-C12Alkenyl, halo C2-C12Alkenyl radical, C2-C12Alkynyl, halo C2-C12Alkynyl, C1-C12Alkoxycarbonyl radical C1-C12Alkyl or dimethylamino C1-C12An alkyl group;
R2selected from halogens;
R3、R4may be the same or different and are each selected from hydrogen or C1-C6An alkyl group;
r is selected from halogen, hydroxyl, amino, cyano, nitro and C1-C12Alkyl, halo C1-C12Alkyl radical, C1-C12Alkoxy, halo C1-C12Alkoxy radical, C3-C12Cycloalkyl radical, C1-C12Alkylamino, halogeno C1-C12Alkylamino radical, di (C)1-C12Alkyl) amino, halo-di (C)1-C12Alkyl) amino, C1-C12Alkylthio, halo C1-C12Alkylthio radical, C2-C12Alkenyl, halo C2-C12Alkenyl radical, C2-C12Alkynyl, halo C2-C12Alkynyl, C2-C12Alkenyloxy, halogeno C2-C12Alkenyloxy radical, C2-C12Alkynyloxy, halo C2-C12Alkynyloxy, C1-C12Alkylsulfonyl, halo C1-C12Alkylsulfonyl radical, C1-C12Alkylcarbonyl, halo C1-C12Alkylcarbonyl group, C1-C12Alkoxycarbonyl, halo C1-C12Alkoxycarbonyl group, C1-C12Alkylamino carbonyl, di (C)1-C12Alkyl) aminocarbonyl, C1-C12Alkoxy radical C1-C12Alkyl, halo C1-C12Alkoxy radical C1-C12Alkyl radical, C1-C12Alkylcarbonyloxy, halo C1-C12Alkylcarbonyloxy, C1-C12Alkoxycarbonyloxy, halo C1-C12Alkoxycarbonyloxy, C1-C12Alkylsulfonyloxy, halo C1-C12Alkylsulfonyloxy, C1-C12Alkoxy radical C1-C12Alkoxy or halo C1-C12Alkoxy radical C1-C12Alkoxy, n ═ 0, 1, 2, 3, 4, or 5.
Preferred compounds of the invention include: in the general formula I
R1Selected from hydrogen, C1-C8Alkyl, halo C1-C8Alkyl radical, C3-C8Cycloalkyl radical, C2-C8Alkenyl or C2-C8An alkynyl group;
R2selected from fluorine, chlorine, bromine or iodine;
R3、R4may be the same or different and are each selected from hydrogen or C1-C6An alkyl group;
r is selected from fluorine, chlorine, bromine, iodine, hydroxyl, amino, cyano, nitro and C1-C8Alkyl, halo C1-C8Alkyl radical, C1-C8Alkoxy, halo C1-C8Alkoxy radical, C3-C8Cycloalkyl radical, C1-C8Alkylamino, halogeno C1-C8Alkylamino radical, di (C)1-C8Alkyl) amino, halo-di (C)1-C8Alkyl) amino, C1-C8Alkylthio, halo C1-C8Alkylthio radical, C2-C8Alkenyl radical, C2-C8Alkynyl, C2-C8Alkenyloxy, halogeno C2-C8Alkenyloxy radical, C2-C8Alkynyloxy, halo C2-C8Alkynyloxy, C1-C8Alkylsulfonyl, halo C1-C8Alkylsulfonyl radical, C1-C8Alkylcarbonyl, halo C1-C8Alkylcarbonyl group, C1-C8Alkoxycarbonyl, halo C1-C8Alkoxycarbonyl group, C1-C8Alkylamino carbonyl, di (C)1-C8Alkyl) aminocarbonyl, C1-C8Alkylcarbonyloxy, halo C1-C8Alkylcarbonyloxy, n ═ 0, 1, 2 or 3.
Further preferred compounds are: in the general formula I
R1C selection1-C4An alkyl group;
R2selected from chlorine or bromine;
R3、R4may be the same or different and are each selected from hydrogen or C1-C3An alkyl group;
r is selected from fluorine, chlorine, bromine, cyano, nitro and C1-C4Alkyl, halo C1-C4Alkyl radical, C1-C4Alkoxy, halo C1-C4Alkoxy radical, C3-C4Cycloalkyl radical, C1-C4Alkylamino, halogeno C1-C4Alkylamino radical, di (C)1-C4Alkyl) amino, halo-di (C)1-C4Alkyl) amino, C1-C4Alkylthio, halo C1-C4Alkylthio radical, C1-C4Alkylcarbonyl, halo C1-C4Alkylcarbonyl group, C1-C4Alkoxycarbonyl, halo C1-C4Alkoxycarbonyl, n ═ 0, 1, 2, or 3.
Further preferred compounds are: in the general formula I
R1Methyl, ethyl, n-propyl, isopropyl, n-butyl and tert-butyl are selected;
R2selected from chlorine or bromine;
R3、R4may be the same or different and is independently selected from hydrogen or methyl;
r is selected from fluorine, chlorine, bromine, cyano, nitro and C1-C4Alkyl, halo C1-C4Alkyl radical, C1-C4Alkoxy, halo C1-C4Alkoxy radical, C1-C4Alkylcarbonyl, halo C1-C4Alkylcarbonyl group, C1-C4Alkoxycarbonyl, halo C1-C4Alkoxycarbonyl, n ═ 0, 1, 2, or 3.
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 groups, 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 and the like. 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. CH2＝CH-、CH2CHCH-. 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. CH3CO-，CH3CH2CO-. Halogenated alkylcarbonyl group: the hydrogen atoms of the alkyl group of the alkylcarbonyl group may be partially or fully substituted by halogen atoms, e.g. CF3CO-. 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, and the like. Alkylamino group: straight or branched chain alkyl, linked to the structure via a nitrogen atom. Haloalkylamino: straight-chain or branched alkylamino, the hydrogen atoms on these alkyl groups may be partially or completely substituted by 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 described by the specific compounds listed in Table 1, but these compounds do not limit the present invention.
TABLE 1
The compound represented by the general formula I is prepared by reacting an intermediate represented by the general formula II and an intermediate represented by the general formula III 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 may 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, and the like.
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.
Intermediate II can be prepared by following the procedure described in patent US 4877787. The intermediate III can be prepared according to a known method, for example, a method described in references, such as Molecules 2017,22(5)690, US2019225621A1 or US 6093736A.
The compound of the general formula I is used for preparing bactericidal drugs in agriculture or 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.; fungi imperfecti diseases such as wilt (sweet potato wilt, cotton wilt, sesame wilt, castor wilt, tomato wilt, bean wilt, cucumber 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 rot, cucumber root rot, bitter gourd root rot, cotton black root rot, broad bean root rot), damping off (seedling blight of cotton, sesame seedling blight, hot pepper seedling blight, cucumber damping off, cabbage stalk rot), anthracnose (sorghum anthracnose, cotton anthracnose, kenaf anthracnose, jute anthracnose, flax anthracnose, tobacco anthracnose, mulberry leaf, hot pepper, bean disease, cucumber anthracnose, red sesame anthracnose, jute anthracnose, flax anthracnose, tobacco anthracnose, eggplant disease, hot pepper anthracnose, vegetable bean disease, and cucumber blight, 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, 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 spot, Pepper white spot disease, white gourd leaf spot disease, celery black rot disease, spinach heart rot disease, kenaf leaf mold disease, kenaf spot disease, jute stem spot disease, soybean purple spot disease, sesame leaf spot disease, castor gray spot disease, tea brown leaf spot disease, eggplant brown orbicular spot disease, kidney bean red spot disease, bitter gourd leukoderma, watermelon spot disease, jute bottom rot disease, sunflower root stem rot disease, kidney bean carbon rot disease, soybean target spot disease, eggplant rod spore leaf spot disease, cucumber target spot disease, tomato leaf mold, eggplant leaf mold, broad bean red spot disease 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.); ascomycetous 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, towel gourd powdery mildew, pumpkin powdery mildew, wax gourd powdery mildew, melon powdery mildew, grape powdery mildew, broad bean powdery mildew), sclerotinia rot (flax sclerotinia rot, rape sclerotinia rot, soybean sclerotinia rot, peanut sclerotinia rot, tobacco sclerotinia rot, pepper sclerotinia rot, eggplant sclerotinia rot, kidney bean sclerotinia rot, pea sclerotinia rot, cucumber sclerotinia rot, bitter gourd sclerotinia rot, wax gourd sclerotinia rot, watermelon sclerotinia rot, celery sclerotinia rot), scab (apple scab, 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 being 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.
For practical use in agriculture, it is often beneficial to use compositions containing one or more compounds of formula I. Therefore, the invention also comprises a bactericidal, insecticidal and acaricidal composition which takes the compound shown as the general formula I as an active component. The weight percentage of the active components in the bactericidal composition is between 0.5 and 99 percent, and the bactericidal composition also comprises a carrier which is acceptable in agriculture, forestry and sanitation.
The technical scheme of the invention also comprises a method for preventing and controlling germs, which comprises the following steps: the bactericidal composition of the invention 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.
The compound of the general formula I has wide bactericidal spectrum and better control effect on various pathogenic bacteria such as cucumber downy mildew, anthracnose, corn rust and the like, so the compound of the general formula I has wider application prospect when being used as a bactericide.
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 1
0.40g (0.002mol) of 2-tert-butyl-4-chloro-5-mercaptopyridazin-3 (2H) -one and 0.55g (0.004mol) of potassium carbonate are put into a reaction bottle, 15mL of N, N-Dimethylformamide (DMF) is added and stirred, 3mL of DMF solution of 0.46g (0.002mol) of 5- (chloromethyl) -3-phenylisothiazole is added dropwise at 60 ℃, and the reaction is carried out under the condition of heat preservation at 80 ℃. After TLC monitoring reaction, pouring the reaction liquid into water, extracting twice with ethyl acetate, combining organic phases, washing with water, drying, decompressing, desolventizing, and purifying the residue by column chromatography (eluent is ethyl acetate and petroleum ether (boiling range 60-90 ℃) with volume ratio of 1:5) to obtain compound 1, yellow solid.
1H NMR (600MHz, internal standard TMS, solvent CDCl3)δ(ppm)δ7.78(dd,J＝8.9,5.3Hz,2H),7.65(s,1H),7.15(t,J＝8.7Hz,2H),6.57(s,1H),4.35(s,2H),1.63(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 (1H NMR, 600MHz, internal standardTMS, solvent CDCl3Ppm) are as follows:
compound 25: yellow solid, mp 136.9 ℃. δ 8.66(t, J ═ 1.8Hz,1H), 8.40-8.28 (m,1H),8.20(dd, J ═ 6.6,1.3Hz,1H),7.81(s,1H),7.69(t, J ═ 8.0Hz,1H),6.85(s,1H),5.47(s,2H),1.66(s, 9H).
Compound 27: a white solid. δ 8.04(s,1H),7.99(d, J ═ 7.8Hz,1H),7.72(d, J ═ 7.8Hz,1H),7.65(s,1H),7.61(d, J ═ 7.8Hz,1H),6.66(s,1H),4.38(s,2H),1.63(s, 9H).
Compound 38: white solid, melting point 165.3 ℃. δ 7.78(dd, J ═ 8.9,5.3Hz,2H),7.65(s,1H),7.15(t, J ═ 8.7Hz,2H),6.57(s,1H),4.35(s,2H),1.63(s, 9H).
Compound 43: brown solid, m.p. 168.7 ℃. δ 8.33(d, J ═ 8.8Hz,3H),7.98(d, J ═ 8.8Hz,2H),7.65(s,1H),6.69(s,1H),4.39(s,2H),1.63(s, 9H).
Compound 44: white solid, melting point 158.8 ℃. δ 7.73-7.61 (m,3H),7.27(d, J ═ 5.2Hz,2H),6.58(s,1H),4.34(s,2H),2.40(s,3H),1.63(s, 9H).
Compound 48: white solid, melting point 168.0 ℃. δ 7.91(d, J ═ 7.4Hz,2H),7.73(d, J ═ 7.7Hz,2H),7.65(s,1H),6.65(s,1H),4.37(s,2H),1.63(s, 9H).
Compound 49: white solid, melting point 147.6 ℃. δ 7.72(d, J ═ 8.7Hz,2H),7.66(s,1H),6.97(d, J ═ 8.7Hz,2H),6.55(s,1H),4.34(s,2H),3.86(s,3H),1.63(s, 9H).
Compound 60: white solid, melting point 104.3 ℃. δ 7.74-7.61 (m,2H),7.51(s,1H), 7.40-7.28 (m,1H),6.74(s,1H),4.38(s,2H),1.63(d, J ═ 3.3Hz, 9H).
Compound 75: white solid, melting point 116.7 ℃. δ 7.68(s,1H),7.29(s,1H),7.17(q, J ═ 7.8Hz,2H),6.45(s,1H),4.37(s,2H),2.40(s,3H),2.35(s,3H),1.64(d, J ═ 4.8Hz, 9H).
Compound 90: white solid, melting point 124.8 ℃. δ 7.66(s,1H),7.39(d, J ═ 1.5Hz,1H),7.26(dd, J ═ 8.3,1.7Hz,1H),6.92(d, J ═ 8.3Hz,1H),6.57(s,1H),4.34(s,2H),3.95(s,3H),3.93(s,3H),1.63(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:
the living potted plant determination method is adopted, i.e. a sample of the compound to be tested is dissolved by a small amount of solvent (the type of the solvent is acetone, methanol, DMF, etc., and is selected according to the dissolving capacity of the solvent to the sample, and the volume ratio of the solvent amount to the liquid spraying amount is equal to or less than 0.05), and diluted by water containing 0.1 percent of Tween 80 to prepare the liquid to be tested 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, the activity of compounds 1, 25, 38 etc. against cucumber downy mildew was 100% and the activity of compounds 43, 60 etc. against cucumber downy mildew was higher than 80%.
At a dose of 25ppm, the activity against cucumber downy mildew of compounds 1, 25, etc. is 100%.
At a dose of 6.25ppm, the activity of compound 1 etc. against cucumber downy mildew is 100%.
Activity against cucumber anthracnose:
at a dose of 400ppm, compounds 38, 43, 48, 60, etc. had 100% activity against cucumber anthracnose.
Activity against corn rust:
at a dose of 400ppm, the activity of compounds 1, 48, 60, etc. on corn rust was 100%.
At a dose of 25ppm, the activity of the compound 1 and the like on the corn rust is not less than 80%.
At a dose of 6.25ppm, the activity of the compound 1 and the like on corn rust is not less than 70%.