WO2019196904A1 - 一种喹唑啉二酮类化合物及其应用和一种农药除草剂 - Google Patents

一种喹唑啉二酮类化合物及其应用和一种农药除草剂 Download PDF

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WO2019196904A1
WO2019196904A1 PCT/CN2019/082267 CN2019082267W WO2019196904A1 WO 2019196904 A1 WO2019196904 A1 WO 2019196904A1 CN 2019082267 W CN2019082267 W CN 2019082267W WO 2019196904 A1 WO2019196904 A1 WO 2019196904A1
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compound
weeds
quinazolinedione
present
formula
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PCT/CN2019/082267
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English (en)
French (fr)
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杨光富
何波
王现全
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山东先达农化股份有限公司
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Priority to JP2021504565A priority Critical patent/JP7082709B2/ja
Publication of WO2019196904A1 publication Critical patent/WO2019196904A1/zh

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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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • 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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • 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
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
    • 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
    • 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
    • A01N43/84—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 six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4
    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/18—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing a —O—CO—N< group, or a thio analogue thereof, directly attached to a heterocyclic or cycloaliphatic ring
    • 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
    • A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
    • A01N57/10—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-oxygen bonds or phosphorus-to-sulfur bonds
    • A01N57/16—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-oxygen bonds or phosphorus-to-sulfur bonds containing heterocyclic radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • C07H17/02—Heterocyclic radicals containing only nitrogen as ring hetero atoms

Definitions

  • the present invention relates to the field of pesticide herbicides, and in particular to a quinazolinedione compound and the use of the quinazolinedione compound and a pesticide herbicide containing the quinazolinedione compound.
  • P-hydroxyphenylpyruvate dioxygenase (4-HPPD) was identified as a herbicide target in the 1990s.
  • 4-HPPD is widely present in aerobic organisms and is mainly involved in the metabolism of tyrosine in organisms.
  • the metabolite of tyrosine produces urinary acid against hydroxyphenylpyruvate under the action of 4-HPPD, which is further converted into plastoquinone and tocopherol.
  • Protamine and tocopherol are important precursors for plant photosynthesis. Therefore, by inhibiting the synthesis of plastoquinone and tocopherol in plants, the normal photosynthesis of plants is hindered, and the plants are albino and die.
  • Herbicides targeting HPPD are highly efficient, low toxicity, environmentally friendly and safe for later crops. Therefore, 4-HPPD herbicides are a class of herbicides with great research value and development prospects.
  • CN104557739A first screened HPPD-like inhibitor molecules containing quinazolinedione fragments.
  • the structure of representative substances is as follows. This substance is mainly used to control weeds in sorghum fields, etc.:
  • WO 2017/140612 A1 further discloses a series of HPPD-like inhibitor molecules on the basis of this, however, the biological activity test results of the specific compounds are not provided in this prior art.
  • Rice is a very important food crop.
  • the control of weeds in rice fields plays an important role in improving rice yield and solving the world food crisis.
  • malignant weeds in the paddy fields, resistant alfalfa, and thousands of gold seriously affect the normal growth of rice, especially the development of resistant alfalfa is very rapid, and it is increasingly difficult to control the resistant alfalfa in the future. .
  • An object of the present invention is to provide a novel HPPD-based inhibitor which has excellent control effects on weeds in crop fields such as paddy fields and high safety against crops.
  • a first aspect of the present invention provides a quinazolinedione compound having a structure represented by the formula (I):
  • R is H or a group represented by the formula (I-1).
  • the quinazolinedione compound of the present invention has the structure shown by the following compound 1:
  • the quinazolinedione compound of the present invention has the structure shown by the following compound 2:
  • the inventors of the present invention have found that the compounds 1 and 2 provided by the present invention have significantly better herbicidal activity relative to the structurally similar compounds provided by the prior art, and the reference samples provided hereinafter, in particular, The compounds 1 and 2 provided by the present invention also have significantly higher crop safety. Further, the inventors of the present invention have also found that the compound 1 of the present invention is excellent in crop safety against corn and wheat, and the compound 2 of the present invention is safer against the crops (for example, rice) relative to the compound 1. Sex.
  • the method for synthesizing the quinazolinedione compound represented by the formula (I) is not particularly limited, and those skilled in the art can obtain a suitable preparation formula according to the compound structure provided by the present invention in combination with the synthesis method in the chemical field ( The method of the quinazolinedione compound shown in I) is not described herein.
  • a second aspect of the invention provides the use of the quinazolinedione compound of the first aspect for controlling weeds.
  • the weeds include valerian, thousand gold, foxtail, crabgrass, stalked wheat, brome, wild oats, maiden, japan, ryegrass, rice, cassia grass, and Bovine flower, Xanthium, sedge, big nest, anti-branched stalk, fake physalis, sputum, purslane, hedgehog, Bidens, double-spotted gar, rice lychee, water bamboo leaves, wild At least one of Ciku, Alisma, Yujiu, Eulania, Papyrus, Firefly, and Shaped Sedge.
  • a third aspect of the invention provides the use of the quinazolinedione compound of the first aspect for controlling at least one weed selected from the group consisting of grass weeds, broadleaf weeds, and sedge weeds.
  • the broadleaf weeds include amaranth, gray cabbage, ramie, rice balsam, cassia grass, morning glory, Xanthium, amaranth, pseudo-acid syrup, calf, dent At least one of cockroach, hedgehog, water bamboo leaves, wild sage, diarrhea, rain long flower, comfrey, ragweed and sedge.
  • the sedge includes flamingo, sedge, and the like.
  • the grass weeds include valerian, thousand gold, foxtail, crabgrass, stalked wheat, brome, wild oats, maiden, japan, ryegrass, sedge At least one of the big nest vegetables, the Bidens, the double-spotted gar, and the rice Lee.
  • a fourth aspect of the invention provides the use of the quinazolinedione compound of the first aspect as a pesticide herbicide.
  • a fifth aspect of the invention provides a pesticide herbicide comprising an active ingredient and an auxiliary agent, the active ingredient comprising at least one of the quinazolinedione compounds described in the above first aspect.
  • the active ingredient is contained in an amount of from 1 to 99.9999% by weight.
  • the pesticide herbicide is in a form selected from the group consisting of at least one of an emulsifiable concentrate, a suspending agent, a wettable powder, a powder, a granule, a liquid, a bait, a mother liquor, and a mother powder.
  • the suspending agent may, for example, include a dry suspending agent, a dispersible oil suspending agent, and an aqueous emulsion.
  • Excipients in the pesticide herbicides of the present invention include, but are not limited to, surfactants, protective colloids, binders, thickeners, thixotropic agents, penetrants, chelating agents, dyes, colorants, polymers, and the like, for example It can also be other conventional auxiliaries that act as carriers.
  • a carrier herein refers to one or more organic, inorganic, natural, or synthetic materials. They aid in the administration of the active ingredient, which is generally inert and must be agriculturally acceptable, especially acceptable for treatment plants.
  • the carrier may be solid, such as: clay, natural or synthetic silicates, silica, resins, waxes, solid fertilizers, etc.; or liquid, such as: water, alcohols, ketones, petroleum fractions, aromatic hydrocarbons or Wax hydrocarbons, chlorinated hydrocarbons, liquefied gases, and the like.
  • the components of the surfactants of the present invention include emulsifiers, dispersants or wetting agents which may be ionic or nonionic. Examples which may be mentioned are: polyacrylates, lignosulfonates, phenolsulfonic or naphthalenesulfonates, ethylene oxide and aliphatic alcohols or with aliphatic acids or with aliphatic amines and substituted phenols (especially Is a polymer of alkylphenol or aryl phenol), sulfonic acid succinate, taurine derivative and phosphate ester of alcohol or polyhydroxyethylated phenol phosphate, alkyl sulfonate, alkyl aryl Sulfonate, alkyl sulfate, lauryl ether sulfate, fatty alcohol sulfate, and sulfated hexadecane-seven-octadecyl alcohol and sulfated fatty alcohol glycol ether, in addition
  • the method for preparing the pesticide herbicide is not particularly limited, and those skilled in the art can prepare by using a conventional preparation method in the field of pesticides to form a corresponding reagent.
  • the pesticide herbicides of the present invention include, but are not limited to, those used in crops by, for example, spraying.
  • the quinazolinedione compound provided by the invention and the pesticide herbicide containing the quinazolinedione compound have all the advantages of the HPPD herbicide, and are environmentally friendly, and the crops are safe, low in dosage and quick in quick-acting property. It has the advantages of wide herbicide spectrum and high safety.
  • the quinazolinedione compounds provided by the present invention exhibit excellent crop safety for at least one of corn, wheat, and rice.
  • the quinazolinedione compound provided by the invention has high herbicidal activity against grass weeds, broadleaf weeds and sedge weeds, especially for weeds in rice, corn and wheat planting areas.
  • grass weeds broadleaf weeds and sedge weeds
  • broad-leaved weeds water bamboo leaves, wild sage, diarrhea, rain
  • sedge firefly, sedge, etc.
  • the present invention selects the following materials as reference samples:
  • the method for preparing the compound 1, the compound 2 and the aforementioned reference sample of the present invention can be referred to, for example, the synthesis method mentioned in CN104557739A, and the type of the raw material can be changed only depending on the substituent.
  • the preparation methods of the compound 1 and the compound 2 are provided below, and the raw materials involved in the following preparation examples are of analytical purity:
  • 1,3-Dimethyl-5-pyrazolone (174.5 mmol) and DCM (350 mL) were added to a reaction flask under ice water.
  • the dropwise addition of triethylamine (348.9 mmol) was continued dropwise and stirring was continued at this temperature for 15 minutes.
  • the dichloromethane solution of the above acid chloride was quickly added dropwise to the reaction system, and the dropping time was controlled to about 5 minutes. After the addition was completed, the reaction was continued for 15 min.
  • the TLC tracks the progress of the reaction until the starting material disappears.
  • a solid precipitated in the reaction system and the solid obtained by suction filtration was dissolved in dichloromethane and allowed to stand at 0 ° C for 12 hours.
  • the filter residue was removed by suction filtration, and the residue was evaporated to give a white solid.
  • Greenhouse bioactivity assays were performed using the aforementioned reference samples and the compounds of the invention.
  • a certain amount of the original drug was weighed by an analytical balance, dissolved in DMF containing 1% by weight of Tween-80 emulsifier to prepare a 1% by weight mother liquor, and then diluted with distilled water to a different concentration of the stock solution for use.
  • Test weeds see Table 2.
  • Use post-emergence stem and leaf spray take 7cm inner diameter paper cup, install composite soil (garden soil: seedling substrate, 1:2, v/v) to 3/4, directly sow weed grass, cover soil 0.2cm, wait until long 4-5 leaf period alternate.
  • the reference sample and the compound of the present invention are all in accordance with 10 g.ai/mu; mesotrione according to the dose of 10 g.ai/mu in the automatic spray tower, and the target crop leaf liquid is dried and then transferred to the greenhouse for cultivation (temperature The results were maintained at 25-28 ° C and the humidity was maintained at 70%. The results were investigated after 30 days and the results are shown in Table 2.
  • Fresh weight inhibition rate (%) (control fresh weight - treated fresh weight) / control fresh weight ⁇ 100
  • herbicidal activity resistance, mild inhibition, mild whitening, mild malformation, severe malformation, complete whitening, complete death, etc.
  • Grade G same control, resistance, control effect is less than 10%
  • Grade F - growth has a slight effect, slight inhibition, poor activity, and the control effect is 10% to less than 20%;
  • Grade E - growth has an effect, slight whitening, poor activity, and the control effect is 20% to less than 50%;
  • Grade D - growth has an effect, slight deformity, moderate activity, and the control effect is 50% to less than 70%;
  • Grade C more sensitive, severely deformed, with good activity, and the control effect is 70% to less than 90%;
  • Grade B extremely sensitive, completely whitened, good activity, screening, control effect is 90% to less than 100%
  • Compound D1 - Compound D11 has lower control effect on test weeds than the compound of the present invention, and the difference in the control effect of each compound on different weeds is more obvious.
  • the compound D8 and the compound D11 have substantially no control effect on the test weeds.
  • the herbicidal activity of the synthesized compound D12 to the compound D15 is remarkably superior.
  • the N,N-diethylformyl fragment was cyclized, and it was widely used in pesticides and medicines and had good biological activity.
  • the five- or six-membered ring synthesizes compound D16 to compound D19, however, the herbicidal activity of this series of compounds is substantially lost.
  • the formyl group is retained to introduce other substituted alkyl groups such as an alkoxy group, a three-membered ring, a four-membered ring, a five-membered ring and a six-membered ring.
  • the herbicidal activity of the derivatives of the furan ring and the thiophene ring is optimal, and is similar to the herbicidal activity of the compound of the present invention.
  • the N,N-diethylformyl fragment has an important effect on increasing the herbicidal activity of the HPPD-based inhibitor of the present invention.
  • a certain amount of the original drug was weighed by an analytical balance, dissolved in DMF containing 1% by weight of Tween-80 emulsifier to prepare a 1% by weight mother liquor, and then diluted with distilled water to a different concentration of the stock solution for use.
  • Potting method See Table 3, Table 4a, Table 4b for the target. Take a 6cm inner diameter flowerpot, install composite soil (garden soil: seedling substrate, 1:2, v/v) to 3/4, directly seed the test target seed (bud rate ⁇ 85%), cover soil 0.2cm, to be tested The target is long until the 3 leaf stage is reserved. Each compound was applied to the automatic spray tower at a dose of 2, 4, 8 g. ai/mu. After the target foliar solution was dried, it was transferred to a greenhouse for cultivation. The results were investigated after 30 days. The results are shown in Table 3, Table 4a, and Table. 4b.
  • the investigation method was the same as in Test Example 1.
  • Crop safety test results showed that compound D25-compound D30 had obvious phytotoxicity to the tested crops (indica, japonica) and could not be further developed as a green, safe and selective herbicide.
  • the compound of the present invention exhibits excellent crop safety for at least one of rice, corn and wheat, and has an outstanding effect on the control of main weeds in rice fields, and can be industrially developed as a candidate drug molecule.
  • Test Example 3 Further testing of the activity of Compound 2
  • a certain amount of the original drug was weighed by an analytical balance, dissolved in DMF containing 1% by weight of Tween-80 emulsifier to prepare a 1% by weight mother liquor, and then diluted with distilled water to a different concentration of the stock solution for use.
  • Potting method See Table 5 and Table 6 for the tested targets. Take a 6cm inner diameter flowerpot, install composite soil (garden soil: seedling substrate, 1:2, v/v) to 3/4, directly weed test weed seeds (bud rate ⁇ 85%), cover soil 0.2cm, wait for miscellaneous The grass grows to around 3 leaves and is ready for use. Each compound was applied to the automatic spray tower at doses of 2.5, 5.0 and 10 g a.i./mu, and the foliar liquid was dried and transferred to a greenhouse for cultivation. The results were investigated after 30 days, and the results are shown in Tables 5 to 6.
  • the investigation method was the same as in Test Example 1.
  • Test Example 4 Further testing the safety of the compounds of the present invention
  • a certain amount of the original drug was weighed by an analytical balance, dissolved in DMF containing 1% by weight of Tween-80 emulsifier to prepare a 1% by weight mother liquor, and then diluted with distilled water to a different concentration of the stock solution for use.
  • Potting method See Table 7 for test targets. Take a 6cm inner diameter flowerpot, install composite soil (garden soil: seedling substrate, 1:2, v/v) to 3/4, directly sow the above test crop seeds (bud rate ⁇ 85%), cover soil 0.2cm, wait until long Reserve until about 3 leaves. Each compound was applied to the automatic spray tower at doses of 2.5, 5.0 and 10 g a.i./mu, and the foliar liquid was dried and transferred to a greenhouse for cultivation. The results were investigated after 30 days, and the results are shown in Table 7.
  • the investigation method was the same as in Test Example 1.
  • Compound 2 showed excellent crop safety for rice.
  • Compound 2 has excellent control effect on the main weeds in paddy fields, especially the control effect on Qianjin and resistant valerian, which can effectively solve the problem of difficult control of resistance to psyllium in paddy fields.
  • the N,N-diethylformyl fragment was introduced into the compound 1 to synthesize the compound 2, and the introduction of the fragment not only maintained the biological activity of the original molecule, but also increased the crop selection of the original molecule.
  • Sex highly safe for rice. It is fully stated that the fragment has very good biological functions.
  • Test Example 5 Further testing the safety of the compound
  • a certain amount of the original drug was weighed with an analytical balance (0.0001 g), dissolved in 1% by weight of a mother liquor containing 1% by weight of Tween-80 emulsifier, and then diluted with distilled water to a stock solution of different concentrations for use.
  • Potting method See Table 8 for test targets. Take a 6cm inner diameter flowerpot, install composite soil (garden soil: seedling substrate, 1:2, v/v) to 3/4, directly sow the above-mentioned test target seeds (bud rate ⁇ 85%), cover soil 0.2cm, wait It will be used up to around 1-2 leaves. Each compound was applied to the automatic spray tower at doses of 2.5, 5.0 and 10 g a.i./mu, and the foliar liquid was dried and transferred to a greenhouse for cultivation. The results were investigated after 30 days, and the results are shown in Table 8.
  • the investigation method was the same as in Test Example 1.
  • Crop test 6 kinds of rice (four leaves and one heart), Ningjing 48, Longjing 29, Y Liangyou, Huanghuazhan, Yuyou 2 and Yanyou 6 were tested.
  • Test method 20 m 2 was used as a plot, and each treatment was repeated 3 times.
  • the stem and leaf were sprayed 12 days after the live broadcast of the rice, and the water was applied for 48 hours after the application, and the water was kept for 5-7 days.
  • the compounds provided by the present invention have good control effects on weeds in crop fields such as paddy fields and excellent safety against crops.

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Abstract

本发明涉及农药除草剂领域，公开了一种喹唑啉二酮类化合物及其应用和一种农药除草剂，本发明的喹唑啉二酮类化合物具有式(I)所示的结构，R为H或者为式(I-1)所示的基团。本发明提供的喹唑啉二酮类化合物具有优异的除草活性和优异的作物安全性。

Description

一种喹唑啉二酮类化合物及其应用和一种农药除草剂 技术领域
本发明涉及农药除草剂领域，具体涉及一种喹唑啉二酮类化合物以及该喹唑啉二酮类化合物的应用和一种含有该喹唑啉二酮类化合物的农药除草剂。
背景技术
对羟基苯基丙酮酸双加氧酶(4-HPPD)在上个世纪90年代被确认为除草剂作用靶标。
4-HPPD广泛存在于需氧生物体内，其主要参与生物体内酪氨酸的代谢。在植物体内，酪氨酸的代谢产物对羟基苯基丙酮酸在4-HPPD的作用下生成尿黑酸，尿黑酸进一步转化成质体醌和生育酚。质体醌和生育酚是植物光合作用的重要前体。因此，通过抑制植物体内质体醌和生育酚的合成，阻碍植物的正常光合作用，致使植物发生白化症状而死亡。以HPPD为靶标的除草剂具有高效，低毒，对环境友好和对后茬作物安全性好等特点。因此，4-HPPD除草剂是一类非常具有研究价值和发展前景的除草剂。
2015年，CN104557739A首次筛选出含有喹唑啉二酮片段的HPPD类抑制剂分子，其代表性物质的结构如下，该物质主要用于防治高粱田等中的杂草：
Figure PCTCN2019082267-appb-000001
随后，WO2017/140612A1在此基础上进一步公开了一系列HPPD类抑制剂分子，然而，在该现有技术中并未提供具体化合物的生物活性测试结果。
水稻是非常重要的粮食作物，水稻田杂草的防治，对提高水稻产量及解决世界粮食危机问题具有非常重要的作用。现阶段，水稻田的恶性杂草稗草，抗性稗草，千金子等严重影响水稻的正常生长，尤其是抗性稗草发展的非常迅速，未来对抗性稗草的防治难度越来越大。
因此，提供对水稻田等中的杂草具有良好的防效以及高的安全性的新型HPPD类抑制剂具有重要意义。
发明内容
本发明的目的是提供对水稻田等农作物种植地中的杂草具有优异的防效以及对农作物具有高的安全性的新型HPPD类抑制剂。
为了实现上述目的，本发明的第一方面提供一种喹唑啉二酮类化合物，该化合物具有式(I)所示的结构：
Figure PCTCN2019082267-appb-000002
其中，在式(I)中，R为H或者为式(I-1)所示的基团。
当所述R为H时，本发明的喹唑啉二酮类化合物即为以下化合物1所示的结构：
Figure PCTCN2019082267-appb-000003
当所述R为式(I-1)所示的基团时，本发明的喹唑啉二酮类化合物即为以下化合物2所示的结构：
Figure PCTCN2019082267-appb-000004
本发明的发明人发现，本发明提供的化合物1和化合物2相对于现有技术提供的结构接近的化合物，以及相对于本文的后文中提供的参照样本均明显具有更好的除草活性，特别地，本发明提供的化合物1和化合物2还明显具有更高的作物安全性。进一步地，本发明的发明人还发现，本发明的化合物1对玉米和小麦的作物安全性非常优异，并且，本发明的化合物2相对于化合物1对田间作物(例如水稻)具有更高的安全性。
本发明对合成式(I)所示的喹唑啉二酮类化合物的方法没有特别的限定，本领域技术人员根据本发明提供的化合物结构结合化学领域内的合成方法能够获得合适的制备式(I)所示的喹唑啉二酮类化合物的方法，本发明在此不再一一赘述。
本发明的第二方面提供第一方面所述的喹唑啉二酮类化合物在防治杂草中的应用。
优选地，所述杂草包括稗草、千金子、狗尾草、马唐、节节麦、雀麦、野燕麦、看麦娘、日本看麦娘、黑麦草、饭包草、决明草、牵牛花、苍耳、莎草、大巢菜、反枝苋、假酸浆、鳢肠、马齿苋、刺苋、鬼针草、双穗雀稗、稻李氏禾、水竹叶、野慈姑、泽泻、雨久花、鸭跖草、鸭舌草、萤蔺、异型莎草等中的至少一种。
本发明的第三方面提供第一方面所述的喹唑啉二酮类化合物在防治选自禾本科杂草、阔叶杂草和莎草科杂草中的至少一种杂草中的应用。
优选地，在本发明中，所述阔叶杂草包括苋菜、灰菜、苘麻、饭包草、决明草、牵牛、苍耳、反枝苋、假酸浆、鳢肠、马齿苋、刺苋、水竹叶、野慈姑、泽泻、雨久花、鸭跖草、鸭舌草和莎草中的至少一种。所述莎草包括萤蔺、异型莎草等。
优选地，在本发明中，所述禾本科杂草包括稗草、千金子、狗尾草、马唐、节节麦、雀麦、野燕麦、看麦娘、日本看麦娘、黑麦草、莎草、大巢菜、鬼针草、双穗雀稗、稻李氏禾中的至少一种。
本发明的第四方面提供第一方面所述的喹唑啉二酮类化合物作为农药除草剂的应用。
本发明的第五方面提供一种农药除草剂，该农药除草剂由活性成分和辅料组成，所述活性成分包括前述第一方面中所述的喹唑啉二酮类化合物中的至少一种。
优选地，在所述农药除草剂中，所述活性成分的含量为1～99.9999重量％。
优选情况下，所述农药除草剂的剂型选自乳油、悬浮剂、可湿性粉剂、粉剂、粒剂、水剂、毒饵、母液和母粉中的至少一种。
所述悬浮剂例如可以包括干悬浮剂、可分散油悬浮剂和水乳剂。
本发明的所述农药除草剂中的辅料包括但不限于表面活性剂、保护胶体、粘合剂、增稠剂、 触变剂、渗透剂、螯合剂、染料、着色剂和聚合物等，例如还可以为充当载体的其它常规助剂。
本文中的载体表示一种或多种有机物、无机物、天然产物或合成的物质。它们有助于活性成分的施用，该载体一般是惰性的且必须是农业上可以接受的，特别是可以被处理植物所接受的。载体可以是固体的，如：陶土、天然或合成的硅酸盐、二氧化硅、树脂、蜡、固体肥料等；或者是液体的，如：水，醇类、酮类、石油馏分、芳烃或蜡烃、氯代烃、液化气等。
本发明所述表面活性剂的成分包括乳化剂，分散剂或润湿剂，它们可以是离子型的或非离子型的。可提及的实例是：聚丙烯酸盐、木质素磺酸盐、苯酚磺酸或萘磺酸盐、环氧乙烷与脂肪族醇或与脂肪族酸或与脂肪族胺与取代的苯酚(特别是烷基苯酚或芳基苯酚)的聚合物、磺酸琥珀酸盐、牛磺酸衍生物及醇的磷酸酯或多羟基乙基化的苯酚磷酸酯、烷基磺酸酯盐、烷基芳基磺酸盐、烷基硫酸盐、月桂基醚硫酸盐、脂肪醇硫酸盐、以及硫酸化十六-十七-十八烷醇以及硫酸化脂肪醇乙二醇醚，此外还有萘或萘磺酸与苯酚和甲醛的缩合物、聚氧乙烯辛基苯甲醚、乙氧基化异辛基醚、辛基酚或壬基酚、烷基苯基聚乙二醇醚、三丁基苯基聚乙二醇醚、三硬酯基苯基聚乙二醇醚、烷基芳基聚醚醇、醇和脂肪醇/氧化乙烯缩合物、乙氧基化蓖麻油、聚氧乙烯烷基醚、乙氧基化聚氧丙烯、月桂醇聚乙二醇醚缩醛、山梨醇酯、木素亚硫酸盐废液、以及蛋白质、变性蛋白、多糖、疏水改性淀粉、聚乙烯醇、聚羧酸盐、聚氧烷基化物、聚乙烯胺、聚乙烯吡咯烷酮以及共聚物。
本发明对制备所述农药除草剂的方法没有特别的限制，本领域技术人员可以采用农药领域内常规的制备方法进行制备以形成相应的试剂。
本发明所述的农药除草剂包括但不限于通过例如喷雾的方法用于农作物。
本发明提供的喹唑啉二酮类化合物及含有该喹唑啉二酮类化合物的农药除草剂具有HPPD类除草剂的全部优点，并且具有环境友好，后茬作物安全、用量低、速效性好、杀草谱广、安全性高等优点。
特别地，本发明提供的喹唑啉二酮类化合物对玉米、小麦和水稻中的至少一种表现出了优良的作物安全性。
本发明提供的喹唑啉二酮类化合物对禾本科杂草、阔叶杂草和莎草科杂草具有很高的除草活性，尤其是对水稻、玉米和小麦种植地内杂草的防效显著，例如对水稻田中的禾本科杂草(稗草、千金子、双穗雀稗、狗尾草、马唐、稻李氏禾等)；阔叶杂草(水竹叶、野慈姑、泽泻、雨久花、鸭跖草、鸭舌草等)；莎草(萤蔺、异型莎草等)等。
具体实施方式
在本文中所披露的范围的端点和任何值都不限于该精确的范围或值，这些范围或值应当理解为包含接近这些范围或值的值。对于数值范围来说，各个范围的端点值之间、各个范围的端点值和单独的点值之间，以及单独的点值之间可以彼此组合而得到一个或多个新的数值范围，这些数值范围应被视为在本文中具体公开。
本发明选用以下物质作为参照样本：
Figure PCTCN2019082267-appb-000005
Figure PCTCN2019082267-appb-000006
Figure PCTCN2019082267-appb-000007
Figure PCTCN2019082267-appb-000008
制备本发明的化合物1、化合物2和前述参照样本的方法例如可以参照CN104557739A中提到的合成方法，仅是根据取代基的不同，改变原料种类即可。
根据一种优选的具体实施方式，以下提供化合物1和化合物2的制备方法，以下制备例中涉及的原料均为分析纯：
制备例1：采用如下合成路线合成化合物1
Figure PCTCN2019082267-appb-000009
化合物2a的制备：将2-甲基-6-氨基苯甲酸(即为化合物1a)(100mmol)溶于乙酸(1200ml)中，搅拌下滴加1mol/L的ICl乙酸溶液，滴加完毕继续搅拌反应2h。反应过程中会析出大量固体，TLC跟踪反应进程，反应完毕后。减压抽滤除去滤液，所得固体用乙酸500mL洗涤两次，干燥后即得灰白色固体，收率93％。
化合物3a的制备：氮气保护下，将化合物2a(20mmol)，吡啶30ml加入到100mL两颈瓶中。搅拌至固体完全溶解后，缓慢向反应体系中加入间氯苯基异氰酸酯(25mmol)。将反应液加热到100℃反应24小时。反应完毕后，反应液冷却至室温后缓慢加入冰水中并搅拌30分钟，所得固体抽滤、水洗、乙醚洗，干燥后即得化合物3a，产率为92％。
化合物4a的制备：将化合物3a(12mmol)，DMF(36mL)和K 2CO 3(14mmol)加入到反应瓶中。搅拌反应30min后，缓慢滴加硫酸二甲酯(24mmol)，滴加完毕后室温搅拌反应过夜。TLC跟踪反应进程，反应完毕后，反应液缓慢倒入200mL冰水中。并剧烈搅拌30min，所得固体抽滤、水洗、乙醚洗涤，干燥后即得化合物4a，产率87％。
化合物5a的制备：将4a(12mmol)，CuCN(24mmol)加入到反应瓶中，氮气保护下加入60mL干燥的DMF，将体系加热到回流并反应约12h。TLC跟踪反应进程，反应完毕后减压蒸馏除去DMF，冷却后向反应瓶中加入60mL丙酮并剧烈搅拌30min，过滤除去反应瓶中不溶性的固体。滤液浓缩后得到白色固体，粗产率为85％；
化合物6a的制备：将粗产品5a(10mmol)溶于乙酸(29mL)、水(124mL)，三氟甲磺酸(7.3mL)中，搅拌下缓慢滴加98mL浓硫酸。滴加完毕后，升温到回流并反应12h，TLC跟踪反应进程。反应完毕后将体系冷却到室温，并倒入到200mL冰水中剧烈搅拌30min。所得固体抽滤、水洗干燥后即得化合物5a，粗产率88％。
化合物7a的制备：将化合物6a(116.3mmol)，重蒸的DCM(581.5ml)加入到1000mL反应瓶中，冰水浴下缓慢滴加草酰氯(174.5mmol)；滴加完毕后，继续搅拌15min。缓慢滴加10滴DMF到反应体系中，滴加入完毕后，冰水浴下继续搅拌反应2h至固体完全溶解。反应完毕后减压脱除溶剂。将所制备的酰氯溶于200mL干燥的DCM中备用。
冰水浴下将1,3-二甲基-5-吡唑酮(174.5mmol)，DCM(350mL)加入到反应瓶中。缓慢滴加三乙胺(348.9mmol)滴加完毕后继续在该温度下继续搅拌15分钟。迅速将上述酰氯的二氯甲烷溶液滴加到该反应体系中，滴加时间控制在5min左右。滴加完毕后，继续反应15min。TLC跟踪反应进程至原料消失。反应完毕后，反应体系中析出固体，抽滤所得固体溶于二氯甲烷中并置于0℃下静置12小时。抽滤除去滤渣，剩余液体减压蒸馏得到白色固体，产率为92％。
化合物1的制备：将化合物7a(45.7mmol)，干燥的乙腈685.5mL加入到反应瓶中。依次向反 应液中加入三乙胺(91.4mmol)，丙酮氰醇(1.5ml)。搅拌下将上述反应体系加热到80℃，反应约30h。TLC跟踪反应进程至原料消失。反应完毕后，减压蒸馏除去溶剂，所得固体溶于二氯甲烷中，并用1M HCl溶液洗涤二氯甲烷有机相。分液收集有机相，有机相干燥脱溶后固体用甲醇重结晶。产率为94％。
制备例2：化合物2的制备方法
将化合物1(91.3mmol)溶于THF(457ml)，依次加入三乙胺(182.7mmol)，N,N-二乙基甲酰氯(182.7mmol)和DMAP(27.4mmol)。升温至回流5小时，待反应完成后，冷却恢复至室温后，0℃下静置2小时，抽滤除去固体，滤液减压蒸馏后所得固体用乙醚重结晶即得粗产物，粗产物用二氯甲烷溶解并用水洗涤二氯甲烷有机相两次，减压蒸馏除去溶剂，所得固体再用乙醚重结晶，产率91％。
上述参照样本中的化合物的制备方法参照前述制备例1和制备例2。
上述参照样本以及本发明的化合物的表征数据分别列于表1中：
表1：化合物结构表征数据
Figure PCTCN2019082267-appb-000010
Figure PCTCN2019082267-appb-000011
Figure PCTCN2019082267-appb-000012
Figure PCTCN2019082267-appb-000013
采用前述参照样本以及本发明的化合物进行温室生物活性试验。
测试例1：温室普筛实验
用分析天平称取一定量的原药，用含1重量％吐温-80乳化剂的DMF溶解配成1重量％的母液，然后用蒸馏水稀释至不同浓度的储液备用。
供试杂草：参见表2。采用苗后茎叶喷雾：取内径7cm纸杯，装复合土(菜园土：育苗基质，1：2，v/v)至3/4处，直接播种杂草草种，覆土0.2cm，待长至4-5叶期备用。参照样本以及本发明的化合物均按照10g.a.i/mu；硝磺草酮按照10g.a.i/mu剂量在自动喷雾塔施药后，待测试靶标作物叶面药液晾干后移入温室培养(温度保持为25-28℃，湿度保持为70％)，30天后调查结果，结果列于表2中。
调查方法：试验处理30天后目测靶标受害症状及生长抑制情况，并称地上部分鲜重，计算鲜重抑制率(％)，用鲜重抑制率表示防效(％)。
鲜重抑制率(％)＝(对照鲜重-处理鲜重)/对照鲜重×100
除草活性评价(耐药、轻微抑制、轻微白化、轻微畸形、严重畸形、完全白化、完全死亡等症状)：
G级-同对照，耐药，防效为小于10％；
F级-生长稍有影响，轻微抑制，活性差，防效为10％至小于20％；
E级-生长有影响，轻微白化，活性差，防效为20％至小于50％；
D级-生长有影响，轻微畸形，活性中等，防效为50％至小于70％；
C级-较敏感，严重畸形，活性较好，防效为70％至小于90％；
B级-极敏感，完全白化，活性好，进筛，防效为90％至小于100％；
A级-完全死亡，活性好，防效为100％。
表2：温室普筛除草活性实验结果
化合物编号 剂量/g.a.i/mu 狗尾草 稗草 苋菜 藜
1 10 A A A A
2 10 A A A A
D1 10 C D C D
D2 10 C D E E
D3 10 B D D E
D4 10 D F C B
D5 10 C C B C
D6 10 B B B B
D7 10 F F C C
D8 10 G G G G
D9 10 E D C E
D10 10 E D F B
D11 10 G F G G
D12 10 A F A A
D13 10 A F A A
D14 10 B E B B
D15 10 B E B B
D16 10 G E C E
D17 10 F C C E
D18 10 G E G G
D19 10 E D E D
D20 10 B B C E
D21 10 B A A E
D22 10 A D E E
D23 10 G G G G
D24 10 E E C E
D25 10 A B A A
D26 10 A B A A
D27 10 A A A A
D28 10 A B A B
D29 10 A A A A
D30 10 B A A A
D31 10 A B A E
D32 10 A B B E
D33 10 A C A D
D34 10 A C A A
D35 10 D E C D
D36 10 B B C B
D37 10 A B B C
D38 10 A A B C
D39 10 B C B B
D40 10 E B D D
D41 10 B B C D
D42 10 A D A A
D43 10 A E A A
D44 10 D E B B
D45 10 D E B B
硝磺草酮 10 F A A A
上述除草活性测试结果表明，本发明的化合物1和化合物2对杂草具有优异的防效。而且，本发明的化合物尤其对狗尾草的防治效果优于商品化药剂硝磺草酮。
比较化合物D1-化合物D11，相对于本发明的化合物，化合物D1-化合物D11对测试杂草的防治效果均低于本发明的化合物，且各个化合物对不同杂草的防效差异较为明显。尤其是化合物D8和化合物D11对测试杂草基本无防治效果。
进一步地，对本发明的化合物的结构中的吡唑环片段进行取代基的修饰，引入甲基、乙基、丙基、环丙基时，所合成的化合物D12到化合物D15的除草活性明显优于相应的原药化合物D36到化合物D39。这从侧面说明本发明的发明人特别发现的N,N-二乙基甲酰基片段对提高HPPD类抑制剂的除草活性具有明显的促进作用。
为了进一步验证N,N-二乙基甲酰基片段对生物活性的促进作用，将N,N-二乙基甲酰基片段进行环化处理，选取在农药和医药中广泛存在且具有较好生物活性的五元或六元环，合成化合物D16到化合物D19，然而，该系列化合物的除草活性基本丧失。在此基础上，保留甲酰基引入其他取代的烷基，例如烷氧基、三元环、四元环、五元环和六元环。普筛实验中，以呋喃环和噻吩环的衍生物的除草活性最优，与本发明的化合物的除草活性接近。
通过对比分析，引入三元环或四元环时(化合物D21、化合物D22、化合物D23、化合物D24)，除草活性普遍降低，当引入其他取代的烷基，例如烷氧基时，除草活性相对于原药分子有所提高，对禾本科杂草的防治效果与本发明的化合物相当，但对阔叶杂草的防治效果要差于本发明的化合物。
综合分析，N,N-二乙基甲酰基片段对提高本发明的HPPD类抑制剂的除草活性具有重要的作用。
测试例2：温室初筛实验
用分析天平称取一定量的原药，用含1重量％吐温-80乳化剂的DMF溶解配成1重量％的母液，然后用蒸馏水稀释至不同浓度的储液备用。
采用盆栽法：供试靶标参见表3、表4a、表4b。取内径6cm花盆，装复合土(菜园土：育苗基质，1：2，v/v)至3/4处，直接播种供试靶标种子(芽率≥85％)，覆土0.2cm，待测试靶标长至3叶期左右备用。各化合物按照2、4、8g.a.i/mu剂量在自动喷雾塔施药后，待测试靶标叶面药液晾干后移入温室培养，30天后调查结果，结果列于表3、表4a、表4b中。
调查方法与测试例1中相同。
表3：代表化合物除草活性初筛实验结果
Figure PCTCN2019082267-appb-000014
Figure PCTCN2019082267-appb-000015
表4a：代表化合物对水稻安全性初筛实验结果
Figure PCTCN2019082267-appb-000016
Figure PCTCN2019082267-appb-000017
表4b：代表化合物对玉米和小麦的安全性初筛实验结果
Figure PCTCN2019082267-appb-000018
Figure PCTCN2019082267-appb-000019
分析初筛实验结果，并且对比普筛实验结果，可以看出，化合物D25-化合物D30对普筛的杂草的防效较为理想且与本发明的化合物的防效差别不太明显。
进一步的初筛实验结果发现，随着使用剂量的降低，化合物D25-化合物D30对狗尾草和稗草的防效普遍降低，而本发明的化合物1和化合物2随着使用剂量的降低对狗尾草和稗草仍然能够达到理想的防治效果。
作物安全性测试结果表明，化合物D25-化合物D30对测试的作物(籼稻、粳稻)均有明显的药害现象，并不能作为绿色、安全和选择性除草剂进行进一步的开发。
对玉米和小麦的作物安全性测试结果表明，化合物D25-化合物D30对测试的作物均有明显的药害现象，并不能作为绿色、安全和选择性除草剂进行进一步的开发。
而本发明的化合物对水稻、玉米和小麦中的至少一种表现出优异的作物安全性且对水稻田主要杂草防治效果非常突出，可作为候选药物分子进行产业化开发。
测试例3：进一步测试化合物2的活性
用分析天平称取一定量的原药，用含1重量％吐温-80乳化剂的DMF溶解配成1重量％的母液，然后用蒸馏水稀释至不同浓度的储液备用。
采用盆栽法：供试靶标参见表5和表6。取内径6cm花盆，装复合土(菜园土：育苗基质，1：2，v/v)至3/4处，直接播种测试杂草种子(芽率≥85％)，覆土0.2cm，待杂草长至3叶期左右备用。各化合物按照2.5、5.0和10g a.i./mu剂量在自动喷雾塔施药后，待叶面药液晾干后移入温室培养，30天后调查结果，结果列于表5-表6中。
调查方法与测试例1中相同。
表5：化合物2的除草活性二次实验结果
剂量/g.a.i/mu 狗尾草 苋菜 藜 千金子 苘麻
2.5 B A A A A
5.0 A A A A A
10.0 A A A A A
表6：化合物2对抗性稗草的除草活性
Figure PCTCN2019082267-appb-000020
测试例4：进一步测试本发明的化合物的安全性
用分析天平称取一定量的原药，用含1重量％吐温-80乳化剂的DMF溶解配成1重量％的母液，然后用蒸馏水稀释至不同浓度的储液备用。
采用盆栽法：供试靶标参见表7。取内径6cm花盆，装复合土(菜园土：育苗基质，1：2，v/v) 至3/4处，直接播种上述测试作物种子(芽率≥85％)，覆土0.2cm，待长至3叶期左右备用。各化合物按照2.5、5.0和10g a.i./mu剂量在自动喷雾塔施药后，待叶面药液晾干后移入温室培养，30天后调查结果，结果列于表7中。
调查方法与测试例1中相同。
表7：化合物2对不同作物的安全性
Figure PCTCN2019082267-appb-000021
进一步的作物安全性测试表明，化合物2对水稻表现出优异的作物安全性。同时，化合物2对水稻田的主要杂草具有优异的防效，尤其是对千金子和抗性稗草的防治效果是非常突出的，能够有效的解决水稻田抗性稗草防治难的问题。
从化合物的结构分析，在化合物1的基础上引入N,N-二乙基甲酰基片段合成化合物2，该片段的引入不仅能保持原有分子的生物活性，还增加了原有分子的作物选择性(对水稻表现出高度的安全性)。充分说明该片段具有非常好的生物功能。
测试例5：进一步测试化合物的安全性
用分析天平(0.0001g)称取一定量的原药，用含1重量％吐温-80乳化剂的DMF溶解配成1重量％的母液，然后用蒸馏水稀释至不同浓度的储液备用。
采用盆栽法：供试靶标参见表8。取内径6cm花盆，装复合土(菜园土：育苗基质，1：2，v/v)至3/4处，直接播种上述供试靶标种子(芽率≥85％)，覆土0.2cm，待长至1-2叶期左右备用。各化合物按照2.5、5.0和10g a.i./mu剂量在自动喷雾塔施药后，待叶面药液晾干后移入温室培养，30天后调查结果，结果列于表8中。
调查方法与测试例1中相同。
结果列于表8中。
表8：化合物2对不同品种水稻的安全性
Figure PCTCN2019082267-appb-000022
分析上述测试结果发现，本发明的化合物2对稗草、狗尾草、千金子等的防治效果显著，同时对水稻表现出优异的安全性。后期的进一步作物安全性评估发现，化合物2对不同品种的水稻表现出优异的作物安全性，具有非常好的应用前景。
测试例6：田间试验
作物试验：供试了6种水稻(四叶一心)、宁粳48、龙粳29、Y两优、黄华占、糯优2号、糯优6号。
杂草试验：参见表9-表10
测试方法：以20m 2为一个小区，每个处理重复3次，在水稻直播后12天茎叶喷雾处理，施 药后48h上水，保水5-7天。
处理后20天，观察处理区与对照区域，用目测法，按照与测试例1相同的调查方法统计杂草的防效和作物的安全性。
实验地点：海南三亚
结果列于表9-表10中。
表9：化合物2的田间除草活性实验结果
Figure PCTCN2019082267-appb-000023
表10：化合物2的田间实验结果
Figure PCTCN2019082267-appb-000024
上述结果表明，在5g.a.i/亩使用量下，化合物2使得稗草4天后白化明显，且对千金子特效。
在同等的条件下，针对供试6种水稻(四叶一心)：宁粳48、龙粳29、Y两优、黄华占、糯优2号、糯优6号，应用本发明的化合物2时，水稻均不会产生白化现象，没有药害。
综上，本发明提供的化合物对水稻田等农作物种植地中的杂草具有良好的防效以及对作物具有优异的安全性。
以上详细描述了本发明的优选实施方式，但是，本发明并不限于此。在本发明的技术构思范围内，可以对本发明的技术方案进行多种简单变型，包括各个技术特征以任何其它的合适方式进行组合，这些简单变型和组合同样应当视为本发明所公开的内容，均属于本发明的保护范围。

Claims (9)

  1. 一种喹唑啉二酮类化合物，该化合物具有式(I)所示的结构：
    Figure PCTCN2019082267-appb-100001
    其中，在式(I)中，R为H或者为式(I-1)所示的基团。
  2. 根据权利要求1所述的化合物，其中，在式(I)中，R为H。
  3. 根据权利要求1所述的化合物，其中，在式(I)中，R为式(I-1)所示的基团。
  4. 权利要求1-3中任意一项所述的喹唑啉二酮类化合物在防治杂草中的应用。
  5. 权利要求1-3中任意一项所述的喹唑啉二酮类化合物在防治选自禾本科杂草、阔叶杂草和莎草科杂草中的至少一种杂草中的应用。
  6. 权利要求1-3中任意一项所述的喹唑啉二酮类化合物作为农药除草剂的应用。
  7. 一种农药除草剂，该农药除草剂由活性成分和辅料组成，所述活性成分包括权利要求1-3中任意一项所述的喹唑啉二酮类化合物中的至少一种。
  8. 根据权利要求7所述的农药除草剂，其中，所述活性成分的含量为1～99.9999重量％。
  9. 根据权利要求7或8所述的农药除草剂，其中，所述农药除草剂的剂型选自乳油、悬浮剂、可湿性粉剂、粉剂、粒剂、水剂、毒饵、母液和母粉中的至少一种。
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