CN117069673A - Oxadiazole compound and application thereof - Google Patents

Oxadiazole compound and application thereof Download PDF

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Publication number
CN117069673A
CN117069673A CN202310079272.4A CN202310079272A CN117069673A CN 117069673 A CN117069673 A CN 117069673A CN 202310079272 A CN202310079272 A CN 202310079272A CN 117069673 A CN117069673 A CN 117069673A
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acid
compound
general formula
compounds
halogen
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张立新
王�锋
张静
裴鸿艳
康卓
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Shenyang University of Chemical Technology
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Shenyang University of Chemical Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01G—HORTICULTURE; CULTIVATION OF VEGETABLES, FLOWERS, RICE, FRUIT, VINES, HOPS OR SEAWEED; FORESTRY; WATERING
    • A01G13/00—Protecting plants
    • 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
    • A01N43/82—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 three ring hetero atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Environmental Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Zoology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Plant Pathology (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Dentistry (AREA)
  • Agronomy & Crop Science (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Toxicology (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

The invention discloses an oxadiazole compound with a novel structure, which is shown in a general formula I:

Description

Oxadiazole compound and application thereof
Technical Field
The invention belongs to the field of agricultural bactericides. In particular to an oxadiazole compound and application thereof.
Background
Patent WO2017174158A1, WO2017076935A1, WO2013008162A1 relate to oxadiazoles and their use as fungicides; however, the activity of these compounds is still unsatisfactory, and there is a need to continuously develop new compounds having higher activity.
In the prior art, the oxadiazole compounds and the bactericidal activity thereof shown in the invention are not reported.
Disclosure of Invention
The invention aims to provide oxadiazole compounds capable of controlling various plant fungal diseases and application thereof in preparing medicines for controlling germs in agriculture and other fields.
In order to achieve the above purpose, the technical scheme of the invention is as follows:
an oxadiazole compound shown in a general formula I:
in formula I:
X 1 、X 2 each independently selected from hydrogen, halogen or C 1 -C 6 An alkyl group;
n is selected from 2, 3 or 4;
R 1 、R 2 、R 3 、R 4 、R 5 each independently selected from hydrogen, halogen, cyano, nitro, C 1 -C 6 Alkyl, halogenated C 1 -C 6 Alkyl, C 3 -C 6 Cycloalkyl, C 1 -C 6 Alkoxy, halo C 1 -C 6 Alkoxy, C 1 -C 6 Alkylthio or halogen C 1 -C 6 Alkylthio;
or salts of compounds of formula I.
In one possible implementation, in formula I,
X 1 、X 2 each independently selected from hydrogen, halogen or C 1 -C 4 An alkyl group;
n is selected from 2, 3 or 4;
R 1 、R 2 、R 3 、R 4 、R 5 each independently selected from hydrogen, halogen, cyano, nitro, C 1 -C 4 Alkyl, halogenated C 1 -C 4 Alkyl, C 3 -C 6 Cycloalkyl, C 1 -C 4 Alkoxy, halo C 1 -C 4 Alkoxy, C 1 -C 4 Alkylthio or halogen C 1 -C 4 Alkylthio;
or salts of compounds of the general formula I with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.
In one possible implementation, in formula I,
X 1 、X 2 each independently selected from hydrogen, fluorine, chlorine, bromine, methyl or ethyl;
n is selected from 2, 3 or 4;
R 1 、R 2 、R 3 、R 4 、R 5 each independently selected from hydrogen, halogen, cyano, nitro, C 1 -C 4 Alkyl, halogenated C 1 -C 4 Alkyl, C 3 -C 6 Cycloalkyl, C 1 -C 4 Alkoxy, halo C 1 -C 4 Alkoxy, C 1 -C 4 Alkylthio or halogen C 1 -C 4 Alkylthio;
or salts of compounds of the general formula I with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.
In one possible implementation, in formula I,
X 1 、X 2 each independently selected from hydrogen, fluorine, chlorine, bromine, methyl or ethyl;
n is selected from 2, 3 or 4;
R 1 、R 2 、R 3 、R 4 、R 5 each independently selected from hydrogen, fluoro, chloro, bromo, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, monochloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, dibromomethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, 2-trifluoroethyl, heptafluoroisopropyl, perfluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-trifluoroethoxy, methylthio, ethylthio, trifluoromethylthio or 2, 2-trifluoroethylthio;
or salts of compounds of the general formula I with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.
In one possible implementation, the compound of formula I is selected from the group consisting of the following table compounds having a structure as in formula I and X 1 、X 2 、n、R 1 、R 2 、R 3 、R 4 And R is 5 As shown in the table:
in the definitions of the compounds of the general formula given above, the terms used in the collection generally represent the following substituents:
halogen: refers to fluorine, chlorine, bromine or iodine.
Alkyl: straight or branched alkyl groups such as methyl, ethyl, n-propyl, isopropyl or the different butyl, pentyl or hexyl isomers.
Cycloalkyl: refers to a substituted or unsubstituted cyclic alkyl group such as cyclopropyl, cyclopentyl or cyclohexyl; substituents such as methyl, halogen, and the like.
Haloalkyl: straight or branched alkyl groups, the hydrogen atoms on these alkyl groups may be partially or fully substituted by halogen, such as monochloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, dibromomethyl, tribromomethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, 2-trifluoroethyl, heptafluoroisopropyl, perfluoroethyl, and the like.
An alkoxy group: a linear or branched alkyl group, linked to the structure via an oxygen atom bond, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy and the like.
Haloalkoxy: the hydrogen atoms on the alkoxy groups may be partially or fully substituted by halogen, such as chloromethoxy, dichloromethoxy, trichloromethoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, 2-trifluoroethoxy and the like.
Alkylthio: a linear or branched alkyl group linked to the structure via a sulfur atom bond, such as methylthio, ethylthio, and the like.
Haloalkylthio: the hydrogen atoms on the alkylthio group may be partially or entirely substituted with halogen, such as chloromethylthio, difluoromethylthio, trifluoromethylthio, 2-trifluoroethylthio and the like.
Some of the compounds of the general formula I according to the present invention are shown in tables 1 to 18, but the present invention is by no means limited to these compounds.
Table 1: in the general formula I, when X 1 ＝X 2 When n=2, R 1 、R 2 、R 3 、R 4 、R 5 Is different fromThe substituents are shown in Table 1 and represent the compound numbers 1.1-1.160.
TABLE 1
Table 2: in the general formula I, when X 1 ＝X 2 When n=3, the substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, the representative compounds are numbered 2.1-2.160, corresponding in sequence to 1.1-1.160 of Table 1.
Table 3: in the general formula I, when X 1 ＝X 2 When n=4, the substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, representative compounds numbered 3.1-3.160 correspond to Table 1, in turn, 1.1-1.160.
Table 4: in the general formula I, when X 1 ＝F，X 2 When n=2, the substituent R 1 、R 2 、R 3 、R 4 、R 5 In accordance with Table 1, representative compound numbers 4.1-4.160,which in turn correspond to tables 1.1-1.160 of table 1.
Table 5: in the general formula I, when X 1 ＝F，X 2 When n=3, the substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, representative compounds are numbered 5.1-5.160, corresponding in sequence to Table 1 from 1.1-1.160.
Table 6: in the general formula I, when X 1 ＝F，X 2 When n=4, the substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, representative compounds numbered 6.1-6.160 correspond to Table 1, in turn, 1.1-1.160.
Table 7: in the general formula I, when X 1 ＝H，X 2 When n=2, the substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, representative compounds numbered 7.1-7.160 correspond to Table 1, in turn, 1.1-1.160.
Table 8: in the general formula I, when X 1 ＝H，X 2 When n=3, the substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, representative compounds are numbered 8.1-8.160, corresponding in sequence to Table 1 from 1.1-1.160.
Table 9: in the general formula I, when X 1 ＝H，X 2 When n=4, the substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, representative compounds numbered 9.1-9.160 correspond to Table 1, in turn, 1.1-1.160.
Table 10: in the general formula I, when X 1 ＝CH 3 ，X 2 When n=2, the substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, representative compounds numbered 10.1-10.160 correspond to Table 1, in turn, 1.1-1.160.
Table 11: in the general formula I, when X 1 ＝CH 3 ，X 2 When n=3, the substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, representative compounds are numbered 11.1-11.160, corresponding in sequence to Table 1 from 1.1-1.160.
Table 12: in the general formula I, when X 1 ＝CH 3 ，X 2 When n=4, the substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, representative compounds numbered 12.1-12.160 correspond to Table 1, in turn, 1.1-1.160.
Table 13: in the general formula I, when X 1 ＝H，X 2 ＝CH 3 And n=2, substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, representative compounds numbered 13.1-13.160 correspond to Table 1, in turn, 1.1-1.160.
Table 14: in the general formula I, when X 1 ＝H，X 2 ＝CH 3 And n=3, substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, representative compounds are numbered 14.1-14.160, corresponding in sequence to Table 1 from 1.1-1.160.
Table 15: in the general formula I, when X 1 ＝H，X 2 ＝CH 3 And n=4, substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, representative compounds are numbered 15.1-15.160, corresponding in sequence to Table 1 from 1.1-1.160.
Table 16: in the general formula I, when X 1 ＝X 2 When n=2, the substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, representative compounds numbered 16.1-16.160 correspond to Table 1, in turn, 1.1-1.160.
Table 17: in the general formula I, when X 1 ＝X 2 When n=3, the substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, representative compounds numbered 17.1-17.160 correspond to Table 1, in turn, 1.1-1.160.
Table 18: in the general formula I, when X 1 ＝X 2 When n=4, the substituent R 1 、R 2 、R 3 、R 4 、R 5 In agreement with Table 1, representative compounds are numbered 18.1-18.160, corresponding in sequence to Table 1 from 1.1-1.160.
The compounds of the general formula I according to the invention can be prepared in the following manner (in which the radicals are as defined above, unless otherwise indicated):
step 1: preparation of Compounds of formula III
The compound of the general formula II is reacted with thionyl chloride, oxalyl chloride, carbonyl chloride, phosphoryl chloride, phosphorus pentachloride, phosphorus trichloride, triphosgene and the like by adopting a conventional method, so that the compound of the general formula III can be prepared.
Step 2: preparation of Compounds of formula V
Reacting a compound of the general formula III with a compound of the general formula IV in a suitable solvent at a temperature ranging from-10 ℃ to the boiling point of the solvent for 0.5 to 48 hours to obtain a compound of the general formula V; the reaction may be carried out in the presence of a base.
Step 3: preparation of Compounds of formula VI
The compound of the general formula V can be prepared into the compound of the general formula VI by adopting a conventional method through hydrochloric acid hydrolysis and salification.
Step 4: preparation of Compounds of formula I
The compound of the general formula I can be prepared by reacting the compound of the general formula VI with the compound of the general formula VII in a proper solvent under the action of alkali at the temperature of-10 ℃ to the boiling point of the solvent for 0.5-48 hours.
In the above reaction, suitable solvents may be aromatic hydrocarbons such as benzene, toluene, and xylene, ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone, halogenated hydrocarbons such as chloroform, and methylene chloride, esters such as methyl acetate, and ethyl acetate, ethers such as tetrahydrofuran, dioxane, diethyl ether, and 1, 2-dimethoxyethane, polar solvents such as water, acetonitrile, N-dimethylformamide, N-methylpyrrolidone, and dimethylsulfoxide, or a mixed solvent of the above solvents; the bases may be the same or different organic bases such as trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine, N-diisopropylmethylamine, N-diisopropylethylamine, etc.
The sources of the raw materials and intermediates involved in the preparation method are as follows:
the compounds of the general formula II can be prepared by known methods, for example, as reported in WO2015185485, WO2017076935, WO2017211652, WO2017211650, WO2017093019, WO2017076739, WO2013008162 or CN113788800, etc.
The compounds of the formula IV, the compounds of the formula VII and other conventional starting materials and reagents are generally commercially available and may also be prepared by conventional methods.
The compound shown in the general formula I is used for preventing and treating diseases caused by various fungi such as oomycetes, basidiomycetes, ascomycetes, fungi imperfecti and the like on various crops, for example, has good prevention effect on diseases such as cucumber downy mildew, cucumber gray mold, cucumber anthracnose, cucumber powdery mildew, tomato early blight, tomato late blight, pepper blight, grape downy mildew, grape white rot, apple ring rot, apple alternaria leaf spot, rice sheath blight, rice blast, wheat rust, wheat leaf spot, wheat powdery mildew, rape sclerotinia, corn small spot, soybean rust and the like at a lower dosage.
Due to their positive properties, the above-mentioned compounds can be advantageously used for protecting crops, domestic animals and breeding stock of agricultural and horticultural importance, as well as the environment frequently seen by humans from pathogens.
The amount of the compound used to achieve the desired effect will vary depending upon various factors such as the compound used, the crop to be protected, the type of pest, the degree of infection, the climatic conditions, the method of application, the dosage form employed, and the like.
A dosage of 5 g-5 kg of compound per hectare provides adequate control.
The invention also includes bactericides containing the compound shown as the general formula I as an active component. The weight percentage of active components in the bactericide is between 0.1 and 99 percent. The bactericide also comprises carriers and assistants acceptable in agriculture, forestry and sanitation.
The germicides of the present invention may be applied in the form of a formulation. The compounds of the general formula I are dissolved or dispersed as active ingredients in carriers and/or adjuvants or formulated into preparations for easier dispersion when used as a bactericide.
The compounds of the general formula I are used as active components, and can be prepared into various preparation types according to the well-known mode in the field, including aqueous agents, soluble liquid agents, emulsifiable concentrates, microemulsions, aqueous emulsions, suspending agents, suspended seed coating agents, dispersible oil suspending agents, ultra-low volume agents, powders, wettable powders, soluble powders, emulsifiable powders, granules, water dispersible granules, soluble granules, emulsifiable granules, dry suspending agents, effervescent granules, floating granules, tablets, soluble tablets, effervescent tablets, microcapsule powders and microcapsule suspending agents, and the selection of the preparation type depends on the physical, chemical and biological characteristics of the compounds of the general formula I in any case.
The fungicidal preparations of the compounds of the general formula I according to the invention can be prepared by customary processes, i.e. by mixing the active substances with liquid or solid carriers and adding one or more surfactants, such as emulsifiers, dispersants, wetting agents, thickeners, stabilizers, defoamers, etc. Typically the composition comprises at least one carrier and at least one surfactant. In each case, a uniform distribution of the active components of the compositions according to the invention should be ensured.
The water aqua is prepared by uniformly mixing a compound shown in the general formula I, a surfactant and water to form uniform and transparent liquid. Typically contains 5 to 50% active ingredient, 5 to 20% emulsifier, 0 to 10% other additives such as penetrant, and the balance water.
The soluble liquid is prepared by uniformly mixing a compound shown in the general formula I, a surfactant and a non-aqueous polar solvent to form uniform transparent liquid. The soluble liquid formulation typically contains 5 to 60% active ingredient, 5 to 20% emulsifier, 0 to 10% other additives such as penetrant, and the balance of liquid carrier.
The emulsifiable concentrate is prepared by uniformly mixing a compound shown in the general formula I, a surfactant and an organic solvent to form a homogeneous oily liquid. Emulsifiable concentrates usually contain 1 to 70% active ingredient, 5 to 20% emulsifier, 0 to 10% other additives such as penetrants, stabilizers, and the balance of liquid carrier.
The microemulsion is prepared by uniformly mixing a compound shown in the general formula I, a surfactant, water and an organic solvent to form uniform transparent liquid. Microemulsions typically contain 1-50% active ingredient, 5-30% emulsifier, 2-10% antifreeze, 0-10% other additives such as penetrants, stabilizers, and the balance of liquid carrier.
The aqueous emulsion is prepared by uniformly mixing a compound of the general formula I, a surfactant and an organic solvent to prepare an oil phase; mixing water and antifreezing agent together to obtain water phase. And (3) shearing the oil phase at a high speed by using a high-shearing emulsifying machine, and slowly adding the water phase into the oil phase to obtain the uniformly dispersed aqueous emulsion. Typically contains 5-50% active ingredient, 5-20% emulsifier, 2-5% antifreeze agent, and the balance of liquid carrier.
The suspending agent is prepared by uniformly mixing a compound shown in the general formula I, a dispersing agent, a wetting agent, an antifreezing agent and water, and then sanding the mixture through a sand mill to obtain stable non-sedimentary flowable liquid. Suspending agents typically contain 5 to 50% active ingredient, 2 to 10% dispersant, 2 to 5% wetting agent, 2 to 5% antifreeze, 0 to 10% other additives such as defoamers, thickeners, preservatives, and the balance of liquid carrier.
The suspension seed coating agent is prepared by uniformly mixing a compound shown in the general formula I, a dispersing agent, a wetting agent, a film forming agent and water, and then sanding the mixture through a sand mill to obtain stable non-deposition flowable liquid. The suspended seed coating agent generally contains 1-50% of active ingredient, 2-10% of dispersing agent, 2-5% of wetting agent, 2-5% of antifreezing agent, 2-10% of film forming agent, 0-10% of other additives such as defoamer, thickener, preservative, warning color and the balance of liquid carrier.
The dispersible oil suspending agent is prepared by uniformly mixing a compound of the general formula I, a surfactant and an oil-based carrier, and then sanding the mixture by a sand mill to obtain a stable non-sedimentary flowable liquid. Dispersible oil suspensions typically comprise 5 to 50% active ingredient, 5 to 30% surfactant, 0 to 10% other additives such as thickeners, stabilizers, and the balance of liquid carrier.
The ultra-low volume agent is prepared by uniformly mixing the compound of the general formula I, the surfactant and the organic solvent, and processing the mixture into a uniform transparent oil phase. Typically contains 1 to 30% active ingredient, 5 to 30% emulsifier, 0 to 10% other additives such as stabilizers, and the balance of liquid carrier.
The powder is prepared by mixing the compound of the general formula I, an auxiliary agent and a carrier, and crushing the mixture. Powders generally contain 5 to 85% of the active ingredient, 5 to 10% of the dispersing agent, 0 to 10% of other additives such as stabilizers, and the balance of the solid carrier.
The wettable powder is prepared by mixing a compound shown in a general formula I, a dispersing agent, a wetting agent and a carrier, and crushing the mixture. Wettable powders normally contain 5 to 85% active ingredient, 5 to 10% dispersant, 1 to 10% wetting agent, 0 to 10% other additives such as stabilizers, and the balance solid carriers.
The soluble powder is prepared by mixing the compound of the general formula I, a dispersing agent, a wetting agent and a carrier, and crushing the mixture. Soluble powders generally contain 5 to 80% active ingredient, 5 to 10% dispersant, 1 to 10% wetting agent, 0 to 10% other additives such as stabilizers, and the balance solid carrier.
The emulsifiable powder is prepared by mixing a compound shown in the general formula I, a surfactant and an organic solvent to prepare a uniform transparent oil phase, and then uniformly spraying the oil phase on a pre-crushed carrier. Emulsifiable powders generally contain 5 to 50% active ingredient, 5 to 30% emulsifier, 5 to 10% wetting dispersant, 0 to 15% organic solvent, and the balance solid carrier.
The granules are prepared by mixing the compound of the general formula I, an auxiliary agent and a carrier, kneading, granulating, drying and coating. Granules generally contain 0.5 to 20% active ingredient, 0.1 to 10% binder, 0 to 10% other additives such as stabilizers, and the balance of solid carrier.
The water dispersible granule is prepared by mixing a compound of a general formula I, a dispersing agent, a wetting agent, a disintegrating agent and a carrier, and then kneading, granulating and drying. The water dispersible granule generally contains 5-85% of active ingredient, 1-10% of dispersing agent, 1-10% of wetting agent, 0.1-10% of binder, 0-10% of other additives such as disintegrating agent, stabilizing agent and the balance of solid carrier.
The soluble granule is prepared by mixing compound of formula I, dispersant, wetting agent, disintegrating agent, and carrier, kneading, granulating, and drying. The soluble granules generally contain 5 to 85% of active ingredient, 1 to 10% of dispersant, 1 to 10% of wetting agent, 0.1 to 10% of binder, 0 to 10% of other additives such as disintegrants, stabilizers, and the balance of solid carrier.
The emulsifiable granules are prepared by mixing a compound shown in a general formula I, a surfactant and an organic solvent to prepare a uniform transparent oil phase, then uniformly spraying the oil phase on a carrier which is crushed in advance, kneading, granulating and drying. Emulsifiable granules generally contain 5 to 50% of the active ingredient, 5 to 30% of the emulsifier, 5 to 10% of the wetting dispersant, 0 to 15% of the organic solvent, 0 to 10% of other additives such as disintegrants, stabilizers, binders, and the balance of the solid carrier.
The dry suspending agent is prepared by uniformly mixing a compound shown in the general formula I, a dispersing agent, a wetting agent, a carrier and water, sanding by a sand mill, and spray drying after sanding. Dry suspending agents typically contain 5 to 80% active ingredient, 2 to 20% dispersant, 2 to 10% wetting agent, 0 to 10% other additives such as defoamers, thickeners, and the balance of solid carrier.
The effervescent granule is prepared by mixing the compound of the general formula I, wetting dispersant, effervescent disintegrant and carrier, kneading, and granulating. Effervescent granules generally contain 0.5 to 30% of active ingredient, 2 to 20% of wetting dispersant, 2 to 20% of effervescent disintegrant, 0 to 10% of other additives such as stabilizers, binders, and the balance of solid carrier.
The floating granule is prepared by mixing the compound of the general formula I, wetting dispersant, floating beads and carrier, kneading and granulating. Floating granules generally contain 0.5 to 30% of active ingredient, 2 to 20% of wetting dispersant, 5 to 20% of floating beads, 0 to 10% of other additives such as stabilizers, binders, disintegrants, and the balance of solid carrier.
The tablet is prepared by mixing the compound of the general formula I, a dispersing agent, a wetting agent, a disintegrating agent and a carrier, kneading, tabletting and drying. Tablets typically contain 5 to 50% active ingredient, 1 to 10% dispersing agent, 1 to 10% wetting agent, 0.1 to 10% binder, 0 to 10% other additives such as disintegrants, stabilizers, and the balance solid carrier.
The soluble tablet is prepared by mixing the compound shown in the general formula I, a dispersing agent, a wetting agent, a disintegrating agent and a carrier, kneading, tabletting and drying. Soluble tablets typically contain 5 to 50% active ingredient, 1 to 10% dispersant, 1 to 10% wetting agent, 0.1 to 10% binder, 0 to 10% other additives such as disintegrants, stabilizers, and the balance solid carrier.
The effervescent tablet is prepared by mixing the compound of the general formula I, wetting dispersant, effervescent disintegrant and carrier, kneading, and tabletting. Effervescent tablets typically contain 0.5 to 30% active ingredient, 2 to 20% wetting and dispersing agent, 2 to 20% effervescent disintegrant, 0 to 10% other additives such as stabilizers, binders, and the balance solid carrier.
The microcapsule powder is prepared by dissolving a compound shown in a general formula I in a solvent, adding an emulsifying agent and a wall material into the solvent, and uniformly stirring to obtain an oil phase; adding a dispersing agent into water to obtain a water phase; adding the oil phase to the aqueous phase under high speed agitation to form an oil-in-water emulsion; adding curing agent into the emulsion under stirring, heating, maintaining the temperature to form capsules, filtering and drying. Microcapsule powders generally contain 0.5 to 30% of active ingredient, 2 to 10% of emulsifier, 2 to 10% of wetting dispersant, 5 to 30% of other additives such as wall material, defoamer, curing agent, stabilizer, and the balance of solid carrier.
The microcapsule suspending agent is prepared by dissolving a compound of a general formula I in a solvent, adding an emulsifying agent and a wall material into the solvent, and uniformly stirring the mixture to obtain an oil phase; adding a dispersing agent into water to obtain a water phase; adding the oil phase to the aqueous phase under high speed agitation to form an oil-in-water emulsion; and adding a curing agent into the emulsion under stirring, heating and preserving heat to form a capsule, so as to form the microcapsule suspending agent. Microcapsule suspending agents typically contain 0.5 to 30% active ingredient, 2 to 10% emulsifier, 2 to 10% wetting dispersant, 5 to 30% other additives such as wall material, defoamer, preservative, thickener, curing agent, stabilizer, and the balance of liquid carrier.
The fungicidal formulations of the compounds of the general formula I according to the invention may be formulated using (liquid or solid) carriers and various adjuvants known to those skilled in the art. Examples include, but are not limited to, the following types of substances.
Suitable surfactants in the bactericidal formulation of the compounds of formula I of the invention may be emulsifiers, dispersants or wetting agents; may be one or more of nonionic and ionic. The ionic surfactant is selected from sulfonates, sulfates, carboxylates, phosphates, succinates, lignosulfonates, acrylamide-acrylic acid copolymers, etc. The nonionic surfactant is selected from fatty alcohol polyoxyethylene ether, alkylphenol polyoxyethylene ether, fatty amine polyoxyethylene ether, fatty acid polyoxyethylene ether, alcohol ester and polyoxyethylene ether thereof, alkyl polyethylene glycol ether, alkyl phenyl polyethylene glycol ether, fatty amide and polyoxyethylene ether thereof, alkanolamide and polyoxyethylene ether thereof, polyoxyethylene polyoxypropylene ether block copolymer, sodium alkyl naphthalene sulfonate fatty alcohol polyoxyethylene ether, sorbitan fatty acid ester polyoxyethylene ether and the like.
The surfactant may be one or more selected from the group consisting of: sodium or calcium lignosulfonate, polyoxyethylene (N20) phenethyl phenol ether oleate, alkylaryl polyoxyethylene polyoxypropylene ether, tristyrylphenol polyoxyethylene (N20) ether phosphate triethanolamine salt, agro 0201B, agro 0203B, agro-100 #, agro-600 #, agro-700 #, agro-1601 #, agro-AEO-3, agro-AEO-5, agro-AEO-7, agro-T-20, agro-T-80, agro-T-85, agro-S-80, agro-S-85, agro-NP-7, agro-NP-10, agro-NP-15, agro-OX-2681, agro-OX-8686, agro-OX-690, agro-2201 #, polycarboxylate dispersant GY-D800, polycarboxylate dispersant GY-D04, polycarboxylate dispersant GY-D02, alkyl naphthalene sulfonate formaldehyde condensate (NNO) Naphthol sulfonic acid formaldehyde condensate sodium salt, alkylphenol polyoxyethylene polyoxypropylene ether, styrene maleic anhydride, methyl naphthalene sulfonic acid formaldehyde condensate, castor oil ethylene oxide adduct, alkylphenol polyoxyethylene polyoxypropylene ether, alkyl-diglycol ether-sodium sulfonate, N-methyl-oleoyl-sodium taurate, detergent LS, sodium methylenenaphthalene sulfonate, sodium oleate methyl aminoethyl sulfonate, dispersant SP-28F, dispersant SP-SC3, darlinger dispersant D909S, alkylaryl polyoxyethylene ether, dodecyl polyoxyethylene ether phosphate, alkylphenol polyoxyethylene ether formaldehyde condensate, dibutyl naphthalene sulfonate sodium (nekal BX), dibutyl naphthalene sulfonic acid formaldehyde condensate, dispersant SD-811, dispersant SD815, dispersant SK-24, detergent LS, dispersing agent SK-20TX, dispersing agent SK-5218, dispersing agent SK-33H, dispersing agent SK-10LX, dispersing agent SK-551, dispersing agent Atlox 4913, dispersing agent EL-20, dispersing agent EL-40, dispersing agent EL-90, dispersing agent YUS-NV1203, dispersing agent YUS-NV1420, dispersing agent YUS-WG4, dispersing agent YUS-TG285, dispersing agent YUS-WP1, dispersing agent YUS-110, dispersing agent YUS-EP60P, dispersing agent YUS-CH1100, dispersing agent SP-OF3468, dispersing agent SP-OF3472, dispersing agent SP-2728, dispersing agent SP-SC29, dispersing agent SUpragil MNS/90, dispersing agent sopaphor FD, dispersing agent YUS-FS1, dispersing agent YUS-PQ100, dispersing agent YUS-WG5, YUS-D935, octylphenol polyoxyethylene ether sulfate, morwet EFW, wetting agent Igepal/10, wetting agent OPONL-T/P, wetting agent Rhodaser 860/P, wetting agent SP-SC-32B, wetting agent SW2, wetting agent SW-sodium dodecyl sulfate, and the like.
Suitable liquid carriers in the bactericidal formulation of the compound of the general formula I of the invention can be one or more of water, organic solvent and oily medium. Suitable organic solvents are selected from aromatic hydrocarbons, chlorinated aromatic hydrocarbons, aliphatic hydrocarbons, chlorinated aliphatic hydrocarbons, alcohols and their ethers and esters, ketones and the like, such as benzene, xylene, toluene, alkylbenzenes, alkylnaphthalenes, chlorobenzene, vinyl chloride, trichloroethane, methylene chloride, chloroform, carbon tetrachloride, polychloroethane, petroleum fractions, cyclohexane, methanol, ethanol, isopropanol, butanol, ethylene glycol, propylene glycol, glycerol, sorbitol, benzyl alcohol, furfuryl alcohol, cyclohexanol, acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, N-methyl-pyrrolidone, tributyl phosphate, dimethylformamide, dimethyl sulfoxide and the like. Suitable oily media are selected from soybean oil, methyl oleate, light mineral oil, liquid paraffin, kerosene, turpentine, and the like.
Suitable solid carriers in the bactericidal formulation of the compounds of formula I of the invention include natural or synthetic. May be selected from, but not limited to, clays, rock powder, chalk, quartz, clays, montmorillonite, sodium sulfate, silica, diatomaceous earth, pumice, gypsum, talc, bentonite, kaolin, attapulgite, light calcium carbonate, china clay, montmorillonite, magnesium aluminum silicate, activated clay, white carbon black, ammonium sulfate, benzofuran resins, perphosphates, alumina, calcite, marble, pumice, and the like, suitable particulate carriers include crushed and fractionated natural rocks such as sepiolite and dolomite and synthetic particulates made from organic and inorganic powders.
Suitable binders, thickeners include synthetic or natural water soluble polymers. Can be selected from, but not limited to, carbomethyl alcohol, polyvinyl acetate, xanthan gum, gelatin, gum arabic, polyvinylpyrrolidone, magnesium aluminum silicate, polyvinyl alcohol, polyethylene glycol, phenolic resin, shellac, methylcellulose, soluble starch, carboxymethyl cellulose, sodium alginate, etc., and added to the formulation in the form of powder, granule, or latex.
Suitable defoamers may be selected from, but are not limited to, defoamers SAG1522, silicones, C8-10 fatty alcohols, phosphates, C10-20 saturated fatty acids (e.g., capric acid), amides, and the like.
Suitable antifreeze agents may be selected from, but are not limited to, ethanol, isopropanol, ethylene glycol, propylene glycol, glycerol, diethylene glycol, ethylene glycol butyl ether, propylene glycol butyl ether, ethylene glycol butyl ether acetate, urea, and the like.
Suitable penetrants may be selected from, but are not limited to, silicones, penetrant T, penetrant JFC, and the like.
Suitable film formers include natural products and modifications thereof and synthetic polymers. Can be selected from, but not limited to, sodium carboxymethyl starch, soluble starch, phosphorylated starch, oxidized starch, chitosan and derivatives thereof, polypropylene graft copolymer, xanthan gum, sodium alginate, agar, gelatin, acacia, polyethylene glycol, polyvinyl alcohol, polyvinyl acetate, polyacrylamide, polyvinylpyrrolidone, polyacrylic acid, etc.
Suitable preservatives may be selected from, but are not limited to, sodium benzoate, prednisone, potassium sorbate, and the like.
Suitable disintegrants may be selected from, but are not limited to, sodium carboxymethyl starch, sodium cross-linked carboxymethyl cellulose, modified starch, cross-linked polyvinylpyrrolidone, ammonium sulfate, sodium chloride, ammonium chloride, and the like.
The effervescent disintegrants may be acidic and/or basic components, wherein the acidic component may be selected from organic acids, inorganic acids, for example: tartaric acid, citric acid, salicylic acid, phosphoric acid, and the like; the alkaline component may be selected from basic carbonates, for example: sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, ammonium bicarbonate, and the like.
Suitable guard colors may be selected from, but are not limited to, inorganic pigments such as iron oxide, titanium oxide, or Prussian blue; organic dyes such as a Li Zhalin, acid scarlet G, basic rose essence, azo dyes, metal phthalocyanines, and the like.
Suitable wall materials include one or more of natural polymer materials, semisynthetic polymer materials and fully synthetic polymer materials. The natural polymer material can be selected from, but not limited to, gelatin, acacia, agar, alginate, chitosan, fibrin, zein, etc.; the semisynthetic polymer material can be selected from but not limited to methyl (ethyl) cellulose, carboxymethyl cellulose (sodium), cellulose acetate, esters thereof, partial glycerides, and the like; the fully synthetic polymeric material may be selected from, but is not limited to, polyacrylic resins, urea-formaldehyde resins, polyamides, polyesters, polymethyl methacrylates, polyureas, polyurethanes, and the like.
Suitable curing agents include one or more of polyols, polyamines. The polyhydric alcohol may be selected from, but is not limited to, ethylene glycol, glycerol, 1, 2-propanediol, 1, 4-butanediol, diethylene glycol, polyethylene glycol 200, polyethylene glycol 400, polyethylene glycol 600, and the like; the polyamine may be selected from, but is not limited to, ethylenediamine, propylenediamine, hexamethylenediamine, diethylenetriamine, triethylenetetramine, ethanolamine, diethanolamine, triethanolamine, hexamethylenetetramine, isophoronediamine, and the like.
The bactericidal preparation of the compound shown in the general formula I can be diluted by a user or directly sprayed by water before use, and can also be directly used.
The technical scheme of the invention also comprises a method for preventing and controlling germs: the germicides of the present invention are applied to the pathogens or their growth medium. A more suitable effective amount is typically selected to be from 10 to 1000 grams per hectare, with an effective amount of from 10 to 500 grams per hectare being preferred.
It should be understood that various changes and modifications can be made within the scope of the invention as defined in the appended claims.
Detailed Description
The following specific examples serve to further illustrate the invention, but the invention is by no means limited to these examples. (the raw materials used are commercially available unless otherwise noted)
Synthetic examples
According to the synthetic route, the compounds shown in the general formula I of the invention can be prepared and obtained respectively by adopting different raw material compounds, and the following is further specifically described:
example 1: preparation of intermediate N- (2-ethylamino) -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide hydrochloride (VI-1):
to the reaction flask were added 1.36g (5.27 mmol) of 4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzoic acid (intermediate II-1, prepared by the method reported in WO 2015185485) and 20mL of thionyl chloride, and the mixture was heated under reflux for 4 hours; after TLC monitoring reaction, decompression evaporation is carried out to remove thionyl chloride to obtain an intermediate III-1.
Into another reaction flask, 0.82g (5.12 mmol) of N-tert-butoxycarbonyl ethylenediamine (intermediate IV-1), 0.54g (5.34 mmol) of triethylamine and 20mL of dichloromethane are added, and the temperature is reduced by 0-5 ℃ in an ice bath; dropwise adding the intermediate III-1 prepared in the previous step (diluted with 10mL of dichloromethane) into the reaction solution under stirring, and stirring for reaction for 1 hour; after TLC monitoring, the reaction was completed, desolventized under reduced pressure, and 1.66g of a white solid, namely intermediate V-1, was obtained after column chromatography of the residue.
After 1.66g of intermediate V-1 prepared in the previous step is dissolved by 40mL of ethyl acetate, 10mL of concentrated hydrochloric acid is slowly added dropwise into the mixture under stirring, and solid is continuously separated out in the process; the solid was filtered, washed with a suitable amount of ethyl acetate and dried to give 0.89g of a white solid, namely intermediate N- (2-ethylamino) -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide hydrochloride (VI-1).
Example 2: preparation of intermediate N- (3-propylamino) -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide hydrochloride (VI-2):
with reference to the synthetic method of example 1, intermediate III-1 and intermediate IV-2 undergo a condensation reaction to obtain intermediate V-2, which is then treated with concentrated hydrochloric acid to obtain intermediate VI-2.
Example 3: preparation of intermediate N- (4-butylamino) -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide hydrochloride (VI-3):
with reference to the synthetic method of example 1, intermediate III-1 and intermediate IV-3 undergo a condensation reaction to form intermediate V-2, which is then treated with concentrated hydrochloric acid to form intermediate VI-3.
Example 4: preparation of Compound 1.1
Into a reaction flask were added 0.20g (0.59 mmol) of N- (2-ethylamino) -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide hydrochloride (intermediate VI-1), 0.18g (1.78 mmol) of triethylamine and 10mL of dichloromethane, and the temperature was reduced by 0 to 5℃in an ice bath; to the reaction solution was added dropwise 0.09g (0.64 mmol) of benzoyl chloride (diluted with 15mL of methylene chloride) with stirring, and the mixture was allowed to react for 2 hours with stirring; after the TLC monitoring reaction was completed, the solution was removed under reduced pressure, and the residue was subjected to column chromatography to give 0.17g of a white solid, namely, compound 1.1.
Compound 1.1 1 H NMR and liquid mass data were as follows:
1 H NMR(400MHz,DMSO-d 6 )δ8.84(t,1H),8.61(t,1H),8.19–8.14(m,2H),8.10–8.05(m,2H),7.88–7.83(m,2H),7.55–7.42(m,3H),3.52–3.42(m,4H)。LC-MS(m/z,ESI):403.24(M-H) - 。
example 5: preparation of Compound 1.2
Compound 1.2 (white solid) was obtained by the synthesis method of reference example 4. Compound 1.2 1 H NMR and liquid mass data were as follows:
1 H NMR(400MHz,DMSO-d 6 )δ8.79(s,1H),8.42(s,1H),8.17(d,2H),8.07(d,2H),7.69–7.59(m,1H),7.57–7.47(m,1H),7.33–7.21(m,2H),3.47(s,4H)。LC-MS(m/z,ESI):423.13(M+H) + 。
example 6: preparation of Compound 1.3
Compound 1.3 (white solid) was obtained by the synthesis method of reference example 4. Compound 1.3 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,Chloroform-d)δ8.24–8.19(m,2H),7.99–7.95(m,2H),7.59–7.52(m,2H),7.46–7.40(m,1H),7.32(s,1H),7.24–7.19(m,1H),7.07(s,1H),3.81–3.73(m,4H)。LC-MS(m/z,ESI):423.12(M+H) + 。
example 7: preparation of Compound 1.4
Compound 1.4 (white solid) was obtained by the synthesis method of example 4. Compound 1.4 1 The H NMR data are as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.83(s,1H),8.63(s,1H),8.16(d,2H),8.06(d,2H),7.96–7.87(m,2H),7.29(t,2H),3.47(s,4H)。LC-MS(m/z,ESI):423.12(M+H) + 。
example 8: preparation of Compound 1.5
Compound 1.5 (white solid) was obtained by the synthesis method of reference example 4. Compound 1.5 1 The H NMR data are as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.77(t,1H),8.55(t,1H),8.20–8.15(m,2H),8.10–8.05(m,2H),7.51–7.36(m,4H),3.53–3.41(m,4H)。LC-MS(m/z,ESI):439.01(M+H) + 。
example 9: preparation of Compound 1.6
Compound 1.6 (white solid) was obtained by the synthesis method of example 4. Compound 1.6 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.83(t,1H),8.73(t,1H),8.18–8.14(m,2H),8.08–8.04(m,2H),7.88(t,1H),7.80(dt,1H),7.60–7.58(m,1H),7.50(t,1H),3.49–3.43(m,4H)。LC-MS(m/z,ESI):439.00(M+H) + 。
example 10: preparation of Compound 1.7
Compound 1.7 (white solid) was obtained by the synthesis method of example 4. Compound 1.7 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.83(t,1H),8.70(t,1H),8.19–8.15(m,2H),8.09–8.04(m,2H),7.89–7.85(m,2H),7.57–7.52(m,2H),3.50–3.44(m,4H)。LC-MS(m/z,ESI):439.08(M+H) + 。
example 11: preparation of Compound 1.8
Compound 1.8 (white solid) was obtained by the synthesis method of reference example 4. Compound 1.8 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.76(t,1H),8.54(t,1H),8.20–8.14(m,2H),8.10–8.05(m,2H),7.64(d,1H),7.47–7.41(m,2H),7.38–7.32(m,1H),3.52–3.40(m,4H)。LC-MS(m/z,ESI):482.98(M+H) + 。
example 12: preparation of Compound 1.14
Compound 1.14 (white solid) was obtained by the synthesis method of reference example 4. Compound 1.14 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,DMSO-d 6 )δ10.08(s,1H),8.83(t,1H),8.18–8.10(m,3H),7.98–7.94(m,2H),7.80–7.76(m,2H),7.70(td,1H),3.93(dd,2H),3.59(q,2H)。LC-MS(m/z,ESI):430.09(M+H) + 。
example 13: preparation of Compound 1.15
Compound 1.15 (white solid) was obtained by the synthesis method of reference example 4. Compound 1.15 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.88–8.80(m,2H),8.26(t,1H),8.19–8.13(m,3H),8.09–8.04(m,2H),8.01(dt,1H),7.70(t,1H),3.53–3.45(m,4H)。LC-MS(m/z,ESI):430.13(M+H) + 。
example 14: preparation of Compound 1.16
Compound 1.16 (white solid) was obtained by the synthesis method of reference example 4. Compound 1.16 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.90–8.81(m,2H),8.19–8.14(m,2H),8.09–8.04(m,2H),8.02–7.94(m,4H),3.53–3.44(m,4H)。LC-MS(m/z,ESI):430.13(M+H) + 。
example 15: preparation of Compound 1.17
Compound 1.17 (white solid) was obtained by the synthesis method of reference example 4. Compound 1.17 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,Chloroform-d)δ8.82(t,1H),8.79(t,1H),8.20–8.15(m,2H),8.10–8.06(m,2H),8.03(dd,1H),7.80(td,1H),7.72–7.64(m,2H),3.51–3.41(m,4H)。LC-MS(m/z,ESI):450.09(M+H) + 。
example 16: preparation of Compound 1.20
Compound 1.20 (white solid) was obtained by the synthesis method of reference example 4. Compound 1.20 1 The H NMR data are as follows:
1 H NMR(400MHz,DMSO-d 6 )δ8.84(t,1H),8.54(t,1H),8.18(d,2H),8.09(d,2H),7.78(d,2H),7.28(d,2H),3.49(s,4H),2.37(s,3H).
example 17: preparation of Compound 1.21
Compound 1.21 (white solid) was obtained by the synthesis method of reference example 4. Compound 1.21 1 The H NMR data are as follows:
1 H NMR(400MHz,DMSO-d 6 )δ8.83(t,1H),8.56(t,1H),8.17(d,2H),8.09(d,2H),7.69(s,1H),7.67–7.62(m,1H),7.37–7.32(m,2H),3.53–3.44(m,4H),2.37(s,3H).
example 18: preparation of Compound 1.22
Compound 1.22 (white solid) was obtained by the synthesis method of reference example 4. Compound 1.22 1 The H NMR data are as follows:
1 H NMR(400MHz,DMSO-d 6 )δ8.84(t,1H),8.54(t,1H),8.18(d,2H),8.09(d,2H),7.78(d,2H),7.28(d,2H),3.54–3.43(m,4H),2.36(s,3H).
example 19: preparation of Compound 1.35
Compound 1.35 (white solid) was obtained by the synthesis method of reference example 4. Compound 1.35 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.78(t,1H),8.62(t,1H),8.19–8.15(m,2H),8.10–8.05(m,2H),7.77(d,1H),7.73(t,1H),7.64(t,1H),7.59(d,1H),3.49–3.41(m,4H)。LC-MS(m/z,ESI):473.09(M+H) + 。
example 20: preparation of Compound 1.41
Compound 1.41 (white solid) was obtained by the synthesis method of example 4. Compound 1.41 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,Chloroform-d)δ8.38(t,1H),8.21(dd,1H),8.19–8.15(m,2H),8.10(t,1H),8.04–7.99(m,2H),7.50–7.44(m,1H),7.08(td,1H),7.00–6.96(m,1H),3.97(s,3H),3.82–3.67(m,4H)。LC-MS(m/z,ESI):435.14(M+H) + 。
example 21: preparation of Compound 1.53
Compound 1.53 (white solid) was obtained by the synthesis method of reference example 4. Compound 1.53 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.77(t,1H),8.42(t,1H),8.17(d,2H),8.08(d,2H),7.46–7.38(m,2H),7.33(d,1H),7.18(t,1H),3.52–3.39(m,4H),2.37(s,3H)。LC-MS(m/z,ESI):449.20(M-H) - 。
example 22: preparation of Compound 1.68
Compound 1.68 (white solid) was obtained by the synthesis method of reference example 4. Compound 1.68 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.84(t,1H),8.81(d,1H),8.19–8.15(m,2H),8.09–8.04(m,3H),7.82(dd,1H),7.76(d,1H),3.52–3.43(m,4H)。LC-MS(m/z,ESI):472.99(M+H) + 。
example 23: preparation of Compound 2.1
Compound 2.1 (white solid) was obtained by the synthesis method of reference example 4. Compound 2.1 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.74(t,1H),8.50(t,1H),8.20–8.14(m,2H),8.09–8.04(m,2H),7.87–7.81(m,2H),7.55–7.43(m,3H),3.41–3.28(m,4H),1.86–1.77(m,2H),。LC-MS(m/z,ESI):419.12(M+H) + 。
example 24: preparation of Compound 2.2
Compound 2.2 (white solid) was obtained by the synthesis method of example 4. Compound 2.2 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.73(t,1H),8.36(t,1H),8.16(d,2H),8.07(d,2H),7.62(t,1H),7.57–7.48(m,1H),7.34–7.23(m,2H),3.45–3.26(m,4H),1.87–1.73(m,2H)。LC-MS(m/z,ESI):437.28(M+H) + 。
example 25: preparation of Compound 2.5
Compound 2.5 (white solid) was obtained by the synthesis method of reference example 4. Compound 2.5 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.72(s,1H),8.47(s,1H),8.12(dd,4H),7.61–7.29(m,4H),3.58–3.18(m,4H),1.94–1.69(m,2H)。LC-MS(m/z,ESI):453.20(M+H) + 。
example 26: preparation of Compound 2.41
Reference examplesSynthesis of 4 gave Compound 2.41 (white solid). Compound 2.41 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.76(t,1H),8.35(t,1H),8.20–8.14(m,2H),8.11–8.05(m,2H),7.75(dt,1H),7.49–7.43(m,1H),7.13(dd,1H),7.02(td,1H),3.44–3.29(m,4H),1.83–1.73(m,2H)。LC-MS(m/z,ESI):449.14(M+H) + 。
example 27: preparation of Compound 3.5
Compound 3.5 (white solid) was obtained by the synthesis method of reference example 4. Compound 3.5 1 H NMR and liquid mass data were as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.72(t,1H),8.43(t,1H),8.16(d,2H),8.06(d,2H),7.52–7.32(m,4H),3.42–3.20(m,4H),1.70–1.50(m,4H)。LC-MS(m/z,ESI):467.21(M+H) + 。
example 28: preparation of Compound 3.41
Compound 3.5 (white solid) was obtained by the synthesis method of reference example 4. Compound 3.5 1 The H NMR data are as follows:
1 H NMR(600MHz,DMSO-d 6 )δ8.73(t,1H),8.20–8.13(m,3H),8.09–8.03(m,2H),7.70(dd,1H),7.47–7.42(m,1H),7.11(d,1H),7.01(td,1H),3.86(s,3H),3.36–3.28(m,4H),1.67–1.52(m,4H)。
biological Activity assay
Example 29: determination of bactericidal Activity against Soy rust
Protection activity test method: the method for measuring the compound to be measured by living potted plant is characterized in that a sample of the compound to be measured is dissolved by a small amount of solvent (the type of the solvent such as acetone, methanol, DMF and the like, and is selected according to the dissolving capacity of the solvent to the sample, the volume ratio of the solvent amount to the spraying amount is equal to or less than 0.05), the solution is diluted by water containing 0.1% Tween 80, and a clear solution of the solvent is additionally arranged as a blank control. The liquid to be tested is sprayed on the disease host plants (the host plants are standard pot seedlings cultivated in a greenhouse) on a crop sprayer, and disease inoculation is carried out after 24 hours. According to the disease characteristics, inoculating a disease plant to be subjected to temperature control and moisture preservation culture, then placing the inoculated plant into a climatic chamber for culture, and transferring the plant into a greenhouse for culture after the disease is infected; disease plants not requiring moisture culture are directly inoculated and cultivated in a greenhouse. The disease control effect of the compound is assessed after the control is sufficiently ill (typically a week).
The in vivo protective activity against soybean rust is as follows:
the prevention effect of the compounds 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.14, 1.15, 1.16, 1.17, 1.20, 1.21, 1.22, 1.35, 1.41, 1.53, 1.68, 2.1, 2.2, 2.5, 2.41, 3.5 and 3.41 on soybean rust is not less than 90% when the concentration of the liquid medicine is 200 mg/L;
the prevention effect of the compounds 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.14, 1.16, 1.17, 1.20, 1.21, 1.22, 1.35, 1.41, 1.53, 2.1, 2.2, 2.5, 2.41, 3.5 and 3.41 on soybean rust is not less than 90 percent when the concentration of the liquid medicine is 100 milligrams/liter;
the prevention effect of the compounds 1.1, 1.2, 1.3, 1.4, 1.5, 1.7, 1.8, 1.14, 1.16, 1.17, 1.21, 1.22, 1.35, 1.41, 1.53, 2.1, 2.2, 2.5, 2.41, 3.5 and 3.41 on soybean rust is not less than 90% when the concentration of the liquid medicine is 25 mg/L;
when the concentration of the liquid medicine is 6.25 mg/L, the prevention effect of the compounds 1.1, 1.2, 1.5, 1.14, 1.21, 1.22, 1.35, 1.41 and 2.2 on soybean rust is not less than 90%;
when the concentration of the liquid medicine is 3.125 mg/L, the prevention effect of the compounds 1.5 and 1.14 on soybean rust is not less than 90 percent.

Claims (8)

1. An oxadiazole compound is characterized by being shown in a general formula I:
in formula I:
X 1 、X 2 each independently selected from hydrogen, halogen or C 1 -C 6 An alkyl group;
n is selected from 2, 3 or 4;
R 1 、R 2 、R 3 、R 4 、R 5 each independently selected from hydrogen, halogen, cyano, nitro, C 1 -C 6 Alkyl, halogenated C 1 -C 6 Alkyl, C 3 -C 6 Cycloalkyl, C 1 -C 6 Alkoxy, halo C 1 -C 6 Alkoxy, C 1 -C 6 Alkylthio or halogen C 1 -C 6 Alkylthio;
or salts of compounds of formula I.
2. A compound according to claim 1, wherein in formula I,
X 1 、X 2 each independently selected from hydrogen, halogen or C 1 -C 4 An alkyl group;
n is selected from 2, 3 or 4;
R 1 、R 2 、R 3 、R 4 、R 5 each independently selected from hydrogen, halogen, cyano, nitro, C 1 -C 4 Alkyl, halogenated C 1 -C 4 Alkyl, C 3 -C 6 Cycloalkyl, C 1 -C 4 Alkoxy, halo C 1 -C 4 Alkoxy, C 1 -C 4 Alkylthio or halogen C 1 -C 4 Alkylthio;
or salts of compounds of the general formula I with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.
3. A compound according to claim 2, wherein in formula I,
X 1 、X 2 each independently selected from hydrogen, fluorine, chlorine, bromine, methyl or ethyl;
n is selected from 2, 3 or 4;
R 1 、R 2 、R 3 、R 4 、R 5 each independently selected from hydrogen, halogen, cyano, nitro, C 1 -C 4 Alkyl, halogenated C 1 -C 4 Alkyl, C 3 -C 6 Cycloalkyl, C 1 -C 4 Alkoxy, halo C 1 -C 4 Alkoxy, C 1 -C 4 Alkylthio or halogen C 1 -C 4 Alkylthio;
or salts of compounds of the general formula I with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.
4. A compound according to claim 3, wherein in formula I,
X 1 、X 2 each independently selected from hydrogen, fluorine, chlorine, bromine, methyl or ethyl;
n is selected from 2, 3 or 4;
R 1 、R 2 、R 3 、R 4 、R 5 each independently selected from the group consisting of hydrogen, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, monochloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, dibromomethyl, tribromomethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, 2-trifluoroethyl, heptafluoroisopropyl, perfluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxyOxy, 2-trifluoroethoxy, methylthio, ethylthio, trifluoromethylthio or 2, 2-trifluoroethylthio;
or salts of compounds of the general formula I with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.
5. The compound according to any one of claims 1 to 4, wherein the compound is selected from the group consisting of compounds having the structure according to formula I and X 1 、X 2 、n、R 1 、R 2 、R 3 、R 4 And R is 5 As shown in the table:
6. use of a compound of the general formula I according to claim 1 as fungicide in the agricultural, forestry or hygiene sector.
7. A bactericidal composition characterized in that: the composition comprises the compound of the general formula I as defined in claim 1 and an agriculturally acceptable carrier, wherein the weight percentage of active components in the composition is 0.1-99%.
8. A method for controlling pathogens, characterized by: a fungicidal effective amount of the fungicidal composition of claim 7 applied to a crop or a growing medium or locus of a crop.
CN202310079272.4A 2022-05-16 2023-02-08 Oxadiazole compound and application thereof Pending CN117069673A (en)

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