WO2020199980A1 - 一种喹啉羧酸类化合物及其制备方法与用途 - Google Patents

一种喹啉羧酸类化合物及其制备方法与用途 Download PDF

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WO2020199980A1
WO2020199980A1 PCT/CN2020/080890 CN2020080890W WO2020199980A1 WO 2020199980 A1 WO2020199980 A1 WO 2020199980A1 CN 2020080890 W CN2020080890 W CN 2020080890W WO 2020199980 A1 WO2020199980 A1 WO 2020199980A1
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formula
salt
compound
compound represented
compounds
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PCT/CN2020/080890
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English (en)
French (fr)
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许辉
唐剑峰
迟会伟
吴建挺
韩君
刘莹
赵宝修
张振国
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山东省联合农药工业有限公司
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Publication of WO2020199980A1 publication Critical patent/WO2020199980A1/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
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A01N43/42—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings condensed with carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
    • C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4

Definitions

  • the invention belongs to the technical field of agricultural bactericides, and specifically relates to a quinoline carboxylic acid compound and a preparation method and application thereof.
  • the present invention provides a quinoline carboxylic acid compound represented by the following formula (I) or a pesticide acceptable salt thereof,
  • R 1 is selected from halogen
  • R 2 is selected from C 1 -C 16 alkyl, C 3 -C 12 cycloalkyl or C 1 -C 16 haloalkyl.
  • R 1 is selected from fluorine, chlorine, bromine or iodine
  • R 2 is selected from C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl or C 1 -C 6 haloalkyl.
  • R 1 is selected from halogen
  • R 2 is selected from C 2 -C 4 alkyl, C 3 -C 6 cycloalkyl or C 2 -C 4 haloalkyl.
  • R 1 is selected from fluorine, chlorine, bromine or iodine
  • R 2 is selected from C 2 -C 4 alkyl, C 3 -C 6 cycloalkyl or C 2 -C 4 haloalkyl.
  • R 1 is selected from F, Cl, Br or I;
  • R 2 is selected from CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )(CH 2 CH 3 ), C(CH 3 ) 3 , CH 2 CH 2 Cl, CH 2 CHF 2 , CH 2 CF 3 , CH 2 CH 2 CCl 3 ,
  • the salt of the compound represented by the general formula (I) is selected from sodium salt, potassium salt, ammonium salt, calcium salt or zinc salt.
  • R 1 is selected from F or Cl
  • R 2 is selected from CH 2 CH 3 , CH 2 CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH 2 CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH(CH 3 )(CH 2 CH 3 ), C(CH 3 ) 3 , CH 2 CF 3 ,
  • the salt of the compound represented by the general formula (I) is selected from sodium salt, potassium salt or ammonium salt.
  • the compound of formula (I) is selected from the following compounds,
  • the present invention also provides a method for preparing the compound of formula (I) as described above, which comprises reacting a compound of formula (II) with a compound of formula (III) to obtain a compound of formula (I),
  • L is selected from leaving groups, such as halogen atoms, such as fluorine, chlorine, bromine or iodine.
  • the reaction can be carried out in the presence of a base; the base is selected from organic bases or inorganic bases; the organic base can be selected from one, two or two of triethylamine, pyridine, etc. More kinds, the inorganic base can be selected from one or two of sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium hydride, sodium or potassium, etc. Or more.
  • the reaction can be carried out in a solvent;
  • the solvent can be selected from one, two or more of aromatic hydrocarbon solvents, amide solvents, sulfone solvents, etc., for example, toluene One, two or more of N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide or dimethylsulfoxide.
  • the temperature of the reaction is preferably 50°C to 130°C.
  • the compound represented by formula (II) can also be reacted with the metal salt (III-1) of the compound represented by formula (III) to obtain the compound represented by formula (I),
  • R 1 and R 2 have the above definitions;
  • L is selected from a leaving group, such as a halogen atom, such as fluorine, chlorine, bromine or iodine; and
  • M is selected from an alkali metal, such as sodium or potassium.
  • the reaction may be carried out in a solvent;
  • the solvent may be selected from one, two or more of aromatic hydrocarbon solvents, amide solvents, sulfone solvents, etc., for example, toluene One, two or more of N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide or dimethylsulfoxide.
  • the temperature of the reaction is preferably 50°C to 150°C.
  • the compound represented by formula (II) can be commercially available or can be prepared by known methods.
  • R 1 has the above-mentioned definition;
  • L is selected from leaving groups such as halogen atoms such as fluorine, chlorine, bromine or iodine.
  • the corresponding benzoyl acetate (VII) is prepared by the reaction of the starting material substituted acetophenone (VIII) with dimethyl or ethyl carbonate, and then the corresponding acrylic acid is prepared by the reaction of (VII) with trialkyl orthoformate Ester (VI), (VI) and cyclopropylamine are reacted to prepare amino acrylate (IV), (IV) is ring-bonded under alkaline conditions to prepare quinoline carboxylate (V), (V) is hydrolyzed to prepare quinoline carboxylic acid (II).
  • reaction can be carried out with reference to prior art documents or similar methods.
  • the preparation method of the present invention can be selected according to suitable reaction conditions and raw materials in each case. For example, it can replace only one substituent with another substituent according to the present invention in a one-step reaction, or can use according to the present invention in the same reaction step.
  • the other substituents of the invention replace multiple substituents.
  • the compounds are not available through the above routes, they can be prepared by deriving other compounds of formula (I) or by conventionally changing the synthetic routes.
  • reaction mixture is worked up in a conventional manner, such as by mixing with water, phase separation and purification of the crude product by chromatography, for example on alumina or silica gel.
  • the present invention also provides a method for preparing the agrochemically acceptable salt of the compound represented by formula (I), and the agrochemically acceptable salt can be prepared by a known method.
  • the alkali salt of carboxylic acid can be treated with a suitable alkali to obtain the agrochemically acceptable salt of the compound represented by formula (I).
  • the preparation method is as follows: the compound represented by formula (I) is reacted with a base (such as sodium hydroxide, potassium hydroxide, calcium hydroxide, zinc hydroxide, potassium carbonate, sodium carbonate or ammonia, etc.) in a solvent such as water or methanol , Can easily obtain the pesticide acceptable salt of the compound represented by general formula (I).
  • the above preparation methods can obtain a mixture of isomers of the compound represented by formula (I). If pure isomers are required, conventional methods such as crystallization or chromatography can be used for separation.
  • the present invention also provides the use of at least one of the compound represented by formula (I) or its agrochemically acceptable salt for preparing a bactericide, which is used in the agricultural field.
  • the present invention also provides the use of at least one of the compound represented by formula (I) or its agrochemically acceptable salt as a bactericide, and the bactericide is used in the agricultural field.
  • the present invention also provides a composition comprising as an active ingredient at least one of the compound represented by formula (I) or its agrochemically acceptable salt.
  • the present invention also provides the use of the composition as a bactericide, which can be used in the agricultural field.
  • the composition is a bactericidal composition.
  • the bactericide is preferably a crop bactericide or a plant bactericide.
  • the present invention also provides a method for controlling bacteria (such as phytopathogenic bacteria) or diseases caused by them, which comprises adding an effective amount of at least one of the compound represented by formula (I) or its pesticide acceptable salt or The composition is applied to the growth medium of bacteria or diseases.
  • bacteria such as phytopathogenic bacteria
  • diseases caused by them which comprises adding an effective amount of at least one of the compound represented by formula (I) or its pesticide acceptable salt or The composition is applied to the growth medium of bacteria or diseases.
  • the compound represented by formula (I) can be used to control the following bacteria or diseases caused by them:
  • Gram-negative bacteria Erwinia (causes pear fire blight, etc.); Pectinella (causes soft rot in cruciferous vegetables, potato black shank, etc.); Diggia (causes sweet potato stem rot) , Corn bacterial stalk rot, rice bacterial basal rot, potato black shank, pear rust, etc.); Pantoea (causing corn bacterial wilt, corn pantobacter leaf spot, adzuki bean bacterial leaf Blight, stone fruit canker, etc.); Pseudomonas (causing peach canker, pea bacterial phytophthora, cruciferous bacterial black spot, tomato bacterial leaf spot, tomato bacterial spot, rapeseed Bacterial black spot, sesame bacterial angular leaf spot, cucumber bacterial angular leaf spot, tobacco wildfire, corn bacterial brown spot, corn bacterial brown spot, broad bean bacterial stem blight, soybean bacterial spot, Bacterial spot blight of beet,
  • fragariae, bacterial canker of poplar, etc. Agrobacterium (causes root cancer in Rosaceae plants, etc.); xylem (causes grape Pierce disease and citrus versicolor chlorosis) ; Phlebbacterium (causing citrus yellow dragon disease, etc.); Enterobacter (causing poplar blight, etc.); Xylobacter (causing grape bacterial blight, etc.).
  • Gram-positive bacteria Corynebacterium (causes potato ring rot, tomato bacterial canker, alfalfa bacterial wilt, corn wilt, wheat bacterial mosaic, etc.); Streptomyces (mould) bacteria (causes potato Scab, etc.); Brevibacterium (causes bean bacterial wilt, tulip yellow spot, bean wilt, etc.); Arthrobacter (causes American wintergreen leaf blight, etc.); Rhodococcus (causes sweet pea banding disease) Etc.); Bacillus (causing corn bacillus leaf spot, wheat white leaf streak, etc.); Laceyella (causing Dactylis honey head disease, etc.).
  • the above-mentioned compounds can be advantageously used to protect important crops or plants in agriculture and horticulture, so as to prevent them from being damaged by bacterial pathogens.
  • the dosage of the compound varies due to various factors, such as the compound used, the crop to be protected, the type of pest, the degree of infection, climatic conditions, the application method, and the dosage form used.
  • formulations or composition components described herein should be consistent with the physical properties of the active ingredients, application methods and environmental factors such as soil type, humidity and temperature.
  • the dosage forms include liquids such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspensions), etc., which may optionally be thickened into a jelly.
  • the dosage forms also include solids such as powders, powders, granules, tablets, pills, films, etc., which can be water-dispersible ("wettable") or water-soluble.
  • the active ingredient can be microencapsulated and then made into a suspension or solid dosage form; in addition, the entire dosage form of the active ingredient can also be encapsulated. Capsules can control or delay the release of active ingredients.
  • Sprayable formulations can be diluted in a suitable medium, and the spray volume used is about one hundred to several hundred liters per hectare. The high concentration composition is mainly used as an intermediate for further processing.
  • Typical solid diluents are introduced in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are introduced in Marsden, SolventsGuide, 2nd Ed., Interscience, New York, 1950. McCutcheon's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, and Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, lists surfactants And recommended apps. All formulations can contain a small amount of additives to reduce foam, prevent caking, corrosion, prevent the growth of microorganisms, etc., or add thickeners to increase viscosity.
  • Surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, sulfonated dialkyl succinates, alkyl sulfates, Alkylbenzene sulfonate, organosilane, N,N-dialkyl taurate, lignosulfonate, naphthalene sulfonate with aldehyde condensate, polycarboxylate and polyoxyethylene/polyoxypropylene intercalation Segment copolymer.
  • Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silicon dioxide, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate, sodium bicarbonate, sodium sulfate ;
  • Liquid diluents include, for example, water, N,N-dimethylformamide, dimethyl sulfone, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffin, alkylbenzene, alkylnaphthalene, Olive oil, castor oil, linseed oil, tung oil, sesame oil, corn oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil and cocoa oil, fatty acid esters, ketones such as cyclohexanone, 2-heptanone, isophor Ketone and 4-hydroxy-4-methyl-2-pentanone, and alcohols such as
  • Solutions can be prepared by simply mixing the components.
  • Powders and fine powders can be prepared by mixing or grinding, usually in hammer mills or liquid energy mills.
  • Suspensions are generally prepared by wet milling, such as the method described in US 3060084.
  • Granules and pills are prepared by spraying the effective substance onto the newly made granular carrier or by granulating technology. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, 147-48; Perry's Chemical Engineer's Handbook, 4TH Ed., McGraw-Hill, New York, 1963, 8-57; and WO 9113546.
  • Pills are prepared as described in US4172714, water-dispersible and water-soluble granules are prepared as described in US4144050, US3920442 and DE3246493, and tablets are as described in US5180587, US5232701 and US5208030 Method to prepare.
  • the film can be prepared by the methods described in GB2095558 and US 3299566.
  • compositions such as in agriculture, one, two or more other fungicides, insecticides and acaricides, herbicides can be added to the composition of the present invention.
  • Plant growth regulators or fertilizers, etc. which can produce additional advantages and effects.
  • groups and their substituents can be selected by those skilled in the art to provide stable structural parts and compounds.
  • substituents When a substituent is described by a conventional chemical formula written from left to right, the substituent also includes chemically equivalent substituents obtained when the structural formula is written from right to left. For example, CH 2 O is equivalent to OCH 2 .
  • halogen refers to fluorine, chlorine, bromine or iodine.
  • C 1- C 16 alkyl group is understood to mean a linear or branched chain having 1 to 16 carbon atoms, saturated monovalent hydrocarbon radical, preferably a C 1- C 10 alkyl group.
  • C1 - C10 alkyl is understood to preferably mean a linear or branched saturated monovalent hydrocarbon group having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms.
  • the alkyl group is, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl Group, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl, 1,2-dimethylbutyl, etc.
  • the group has 1, 2, 3, 4, 5, 6 carbon atoms ("C 1- C 6 alkyl"), such as methyl, ethyl, propyl, butyl, isopropyl , Isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, more particularly, the group has a linear or branched saturated monovalent hydrocarbon group with 2, 3 or 4 carbon atoms, such as methyl, Ethyl, propyl, butyl, isopropyl, isobutyl, sec-butyl, tert-butyl, or their isomers.
  • C 1- C 6 alkyl such as methyl, ethyl, propyl, butyl, isopropyl , Isobutyl, sec-butyl, tert-butyl, pentyl, hexyl
  • the group has a linear or branched saturated monovalent hydrocarbon group with 2, 3 or 4 carbon atoms,
  • alkyl is defined as “C 1- C 16 alkyl” is equally applicable to other terms comprising “C 1- C 16 alkyl group", for example, the term “C 1- C 16 haloalkyl” and the like.
  • C 3- C 12 cycloalkyl group is understood as meaning a saturated monovalent monocyclic or bicyclic hydrocarbon ring having 3 to 12 carbon atoms, preferably “C 3- C 10 cycloalkyl.”
  • C3 - C10 cycloalkyl should be understood to mean a saturated monovalent monocyclic or bicyclic hydrocarbon ring having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms.
  • the C3 - C10 cycloalkyl group may be a monocyclic hydrocarbon group, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl or cyclodecyl, or Bicyclic hydrocarbon groups such as decalin ring.
  • the group has 3, 4, 5, 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl.
  • haloalkyl should be understood as straight or branched chain alkyl groups, the hydrogen atoms on these alkyl groups are partially or completely replaced by halogen atoms, such as CF 3 CH 2 -.
  • Pesticide acceptable salt refers to a salt that retains the biological efficacy of the free acid and free base of the specified compound, and has no adverse effects in biology or other aspects, which can be achieved by removing the acid groups in the parent compound The group is converted into a salt form.
  • Agrochemical acceptable salts include, but are not limited to, inorganic or organic base salts of acid groups such as carboxyl groups.
  • the agrochemicals acceptable salt in this application can be synthesized from the parent compound, that is, the acidic group in the parent compound reacts with 1-4 equivalents of base in a solvent system to form alkali metals (such as sodium, potassium) Salt, alkaline earth metal (such as calcium, magnesium) salt, transition metal (such as zinc) salt, ammonium salt, amine (such as diethanolamine, triethanolamine, octylamine, dioctylmethylamine, morpholine) salt, preferably formed by the parent compound Sodium, potassium, calcium, zinc or ammonium salt.
  • alkali metals such as sodium, potassium
  • alkaline earth metal such as calcium, magnesium
  • transition metal such as zinc
  • ammonium salt such as diethanolamine, triethanolamine, octylamine, dioctylmethylamine, morpholine
  • the compound represented by the formula (I) of the present invention shows good activity against a variety of bacterial pathogens in the agricultural field. Moreover, these compounds can obtain good control effects at very low doses, so they can be used to prepare bactericides, especially fungicides for crops or plants. In addition, the compound has been proved to have good activity for improving crop growth and development.
  • the compound of the present invention has simple preparation steps and high yield, so it has better application prospects.
  • the compound obtained in the above embodiment is used to prepare a wettable powder, which is specifically prepared with the following raw material composition:
  • Compound 1 60.0%, dodecylphenol polyethoxy glycol ether 4.0%, sodium lignosulfonate 5.0%, sodium aluminosilicate 6.0%, montmorillonite (calcined) 25.0%.
  • the compound obtained in the above embodiment is used to prepare granules, which are prepared with the following raw material composition:
  • Compound 2 10.0%, the other components are sodium lauryl sulfate 2%, calcium lignosulfonate 6%, potassium chloride 10%, polydimethylsiloxane 1%, and soluble starch supplement to 100%.
  • the compound obtained in the above embodiment is used to prepare the extruded pellets, which are prepared with the following raw material composition:
  • Compound 7 25.0%, anhydrous calcium sulfate 10.0%, crude calcium lignosulfonate 5.0%, sodium alkyl naphthalene sulfonate 1.0%, calcium/magnesium bentonite 59.0%.
  • Compound 8 25.0%, solvent 150 60%, PEG400 5%, Rhodacal 70/B 3%, Rhodameen RAM/7 7%.
  • the compound obtained in the above embodiment is used to prepare an aqueous suspension concentrate, which is specifically prepared with the following raw material composition:
  • Compound 9 30.0%, POE polystyrene phenyl ether sulfate 5.0%, xanthan gum 0.5%, polyethylene glycol 5%, triethanolamine 1%, sorbitol 0.5%, and water to 100.0%.
  • the compound of the present invention shows good activity against a variety of bacterial pathogens in the agricultural field.
  • Example 12 Determination of bactericidal activity
  • the compound of the present invention has carried out in vitro antibacterial activity or in vivo protective effect tests on various bacterial diseases of plants, and has carried out an effect test on improving crop growth and development.
  • the results of the bactericidal activity determination and the effect of improving the growth and development of crops are shown in the following examples.
  • the test method is as follows: Dilute the drug with a suitable solvent (the type of solvent such as acetone, methanol, N,N dimethylformamide and dimethyl sulfoxide, etc., and is selected according to its ability to dissolve the sample). Series concentration. Under aseptic operation conditions, the NB culture medium was divided into test tubes in equal amounts, and the drug solution was drawn quantitatively from low concentration to high concentration, respectively added to the above test tubes, shaken well, and then added equal amounts respectively in logarithmic growth For the bacterial suspension of the first stage, each treatment is repeated 4 times. After mixing, culture in the dark in a shaking incubator at 25°C, and measure the OD value in the logarithmic growth phase.
  • a suitable solvent the type of solvent such as acetone, methanol, N,N dimethylformamide and dimethyl sulfoxide, etc.
  • the compounds with an inhibition rate of more than 90% against the pathogen of cucumber bacterial angular leaf spot are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of cucumber bacterial angular leaf spot were 2% and 48%, respectively.
  • the compounds with an inhibition rate of more than 90% against cucumber bacterial angular leaf spot pathogens are: 1, 2, 3, 4, 6, 7, 8, 11, 12, 13, 14, 15, 17, 18, 19, 20, 24;
  • the compounds with inhibition rate above 80% are: 5, 9, 10, 16, 21, 22, and 23.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of cucumber bacterial angular leaf spot were 0 and 21%, respectively.
  • the compounds with an inhibition rate of more than 90% against the pathogen of tobacco bacterial wilt are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of tobacco bacterial wilt were 5% and 51%, respectively.
  • the compounds with an inhibition rate of more than 90% against tobacco bacterial wilt pathogens are: 1, 2, 3, 4, 6, 7, 8, 11, 12, 13, 14, 15, 17, 18, 19, 20, 24;
  • the compounds with inhibition rate above 80% are: 5, 9, 10, 16, 21, 22, and 23.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of tobacco bacterial wilt were 0 and 28%, respectively.
  • the compounds with an inhibition rate of more than 90% against the pathogen of potato black shank are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of potato black shank were 3% and 55%, respectively.
  • the compounds with an inhibition rate of more than 90% against the pathogen of potato black shank are: 1, 2, 3, 4, 5, 6, 7, 8, 13, 14, 15, 16, 17, 18, 19, 20;
  • the compounds with inhibition rate above 80% are: 9, 10, 11, 12, 21, 22, 23, 24.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of potato black shank were 0 and 38%, respectively.
  • the compounds with an inhibition rate of more than 90% against the pathogen of sweet potato stalk rot are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of sweet potato stem rot were 7% and 46%, respectively.
  • the compounds with an inhibitory rate of more than 90% against sweet potato stem rot pathogens are: 1, 2, 3, 4, 5, 6, 7, 8, 13, 14, 15, 16, 17, 18, 19, 20;
  • the compounds with inhibition rate above 80% are: 9, 10, 11, 12, 21, 22, 23, 24.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of sweet potato stem rot were 2% and 25%, respectively.
  • the compounds with an inhibition rate of more than 90% against the pathogen of rice bacterial blight are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 , 15, 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of rice bacterial blight were 16% and 48%, respectively.
  • the compounds with an inhibition rate of more than 90% against the pathogen of rice bacterial blight are: 1, 2, 3, 4, 5, 6, 7, 8, 13, 14, 15, 16, 17, 18 , 19, 20;
  • the compounds with inhibition rate above 80% are: 9, 10, 11, 12, 21, 22, 23, 24.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of rice bacterial blight were 9% and 30%, respectively.
  • the compounds with an inhibition rate of more than 90% against the pathogen of watermelon fruit spot disease are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 , 15, 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of watermelon fruit spot disease were 3% and 52%, respectively.
  • the compounds with an inhibition rate of more than 90% against watermelon fruit spot pathogens are: 1, 2, 3, 4, 5, 6, 7, 8, 13, 14, 15, 16, 17, 18 , 19, 20;
  • the compounds with inhibition rate above 80% are: 9, 10, 11, 12, 21, 22, 23, 24.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of watermelon fruit spot disease were 0 and 29%, respectively.
  • the compounds with an inhibition rate of more than 90% against the pathogenic bacteria of Chinese cabbage black rot are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 , 15, 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogenic bacteria of Chinese cabbage black rot were 5% and 46%, respectively.
  • the compounds with an inhibition rate of more than 90% against the pathogenic bacteria of Chinese cabbage black rot are: 1, 2, 3, 4, 5, 6, 7, 8, 13, 14, 15, 16, 17, 18 , 19, 20;
  • the compounds with inhibition rate above 80% are: 9, 10, 11, 12, 21, 22, 23, 24.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogenic bacteria of Chinese cabbage black rot were 0 and 19%, respectively.
  • the compounds with an inhibition rate of more than 90% against the pathogen of cassava bacterial fusarium wilt are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 , 15, 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of cassava bacterial fusarium wilt were 15% and 51%, respectively.
  • the compounds with an inhibition rate of more than 90% against the pathogen of cassava bacterial wilt are: 1, 2, 3, 4, 6, 7, 8, 11, 12, 13, 14, 15, 17, 18 , 19, 20, 24;
  • the compounds with inhibition rate above 80% are: 5, 9, 10, 16, 21, 22, and 23.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of cassava bacterial fusarium wilt were 7% and 32%, respectively.
  • the compounds with an inhibition rate of more than 90% against the pathogen of pear fire blight are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 , 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of pear fire blight were 3% and 43%, respectively.
  • the compounds with an inhibition rate of more than 90% against the pathogen of pear fire blight are: 1, 2, 3, 4, 5, 6, 7, 8, 13, 14, 15, 16, 17, 18, 19 , 20;
  • the compounds with inhibition rate above 80% are: 9, 10, 11, 12, 21, 22, 23, 24.
  • the inhibitory rates of the control agents copper quinoline and Zhongshengmycin on the pathogen of pear fire blight were 0 and 23%, respectively.
  • solvents for the test compound solvent types such as acetone, methanol, N,N dimethylformamide and dimethyl sulfoxide, etc.
  • solvents such as acetone, methanol, N,N dimethylformamide and dimethyl sulfoxide, etc.
  • the pathogenic bacteria cultured to the stable growth period are mixed with the quantitative compound solution uniformly, and the melon seeds, tomato seeds, tobacco seeds and potato seed potatoes that have been germinated are soaked in the mixture of the bacterial solution and the compound for half an hour, and then the seeds are sown Put it in an earthworm soil culture cup and place it in a greenhouse for moisturizing culture. After the control is fully onset, the control effect will be investigated.
  • the soft rot disease of Chinese cabbage cut 2 cm square cabbage leaves and put them in a glass petri dish with double filter paper.
  • the compound to be tested is dissolved in a small amount of suitable solvent (the type of solvent is acetone, methanol, N,N dimethylformamide and dimethyl sulfoxide, etc., and is selected according to its ability to dissolve the sample), and then diluted with water to Spray on the surface of the cabbage leaves at the required concentration.
  • a fume hood After drying the liquid on the surface of the cabbage leaves in a fume hood, use an inoculation needle to acupuncture the surface of the cabbage leaves to cause wounds, and take 5 micrometers of the soft rot fungi cultivated to the stable growth period. Li is added to the wound for vaccination.
  • the test materials were placed in an incubator for 48 hours in the dark, and the control effect was investigated after the control had fully developed disease.
  • suitable solvents for the test compound solvent types such as acetone, methanol, N,N dimethylformamide and dimethyl sulfoxide, etc.
  • suitable solvents for the test compound solvent types such as acetone, methanol, N,N dimethylformamide and dimethyl sulfoxide, etc.
  • Select for the dissolving ability of the sample After dissolving, dilute with water to the desired concentration.
  • the compound aqueous solution is sprayed on the surface of the plant test material, and after the surface drug solution is air-dried in a cool place, the pathogenic bacteria liquid cultured to a stable growth stage is sprayed on the surface of the plant test material, and then the plant test material is placed in a greenhouse for moisturizing culture.
  • test compound For potato black shank disease, use a small amount of suitable solvent for the test compound (the type of solvent is acetone, methanol, N,N dimethylformamide, dimethyl sulfoxide, etc., and is selected according to its ability to dissolve the sample) After dissolving, dilute with water to the desired concentration.
  • the test potatoes were irrigated according to the designed drug concentration, and the dosage of each plant was 200 mL, and the dosage of each plant was kept consistent (including the control treatment). Inoculation of Black Shank pathogen was carried out on the second day after application. According to the results of the investigation.
  • the compounds that have a control effect of more than 90% on cucumber bacterial angular leaf spot are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 , 15, 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the control effects of the control agents copper quinoline and Zhongshengmycin on cucumber bacterial keratoderma were 15% and 20%, respectively.
  • the compounds that have a control effect of more than 90% on cucumber bacterial angular leaf spot are: 1, 2, 3, 4, 5, 6, 7, 8, 13, 14, 15, 16, 17, 18, 19, 20; Compounds with a control effect of more than 80% are: 9, 10, 11, 12, 21, 22, 23, 24.
  • the inhibitory rates of the control agents of copper quinoline and Zhongshengmycin on cucumber bacterial keratoderma were 10% and 12%, respectively.
  • the compounds with a control effect of more than 90% against tobacco bacterial wilt are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 , 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the control effects of the control agents copper quinoline and Zhongshengmycin on tobacco bacterial wilt were 11% and 35%, respectively.
  • the compounds with a control effect of more than 90% against tobacco bacterial wilt are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 , 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the control effects of the control drugs Cuquinoline and Zhongshengmycin against tobacco bacterial wilt are 5% and 24%, respectively.
  • the compounds that have an efficacy of more than 90% against potato black shank are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 , 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the inhibitory rates of the control agents of copper quinoline and Zhongshengmycin against potato black shank were 22% and 25%, respectively.
  • the compounds that have an efficacy of more than 90% against potato black shank are: 1, 2, 3, 4, 5, 6, 7, 8, 13, 14, 15, 16, 17, 18, 19 , 20; Compounds with a control effect of more than 80% are: 9, 10, 11, 12, 21, 22, 23, 24.
  • the control effects of the control agents copper quinoline and Zhongshengmycin on potato black shank were 11% and 17%, respectively.
  • the compounds with a control effect of more than 90% against sweet potato stem rot are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 , 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the control effects of the control agents copper quinoline and Zhongshengmycin on sweet potato stem rot were 20% and 38%, respectively.
  • the compounds with a control effect of more than 90% against sweet potato stem rot are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 , 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the control effects of the control agents copper quinoline and Zhongshengmycin against sweet potato stem rot were 13% and 23%, respectively.
  • the compounds with a control effect of more than 90% against rice bacterial blight are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the control effects of the control agents copper quinoline and Zhongshengmycin against rice bacterial blight were 10% and 35%, respectively.
  • the compounds with a control effect of more than 90% against rice bacterial blight are: 1, 2, 3, 4, 5, 6, 7, 8, 13, 14, 15, 16, 17, 18, 19, 20;
  • the compounds with a control effect of more than 80% are: 9, 10, 11, 12, 21, 22, 23, and 24.
  • the control effects of the control agents copper quinoline and Zhongshengmycin against rice bacterial blight were 6% and 24%, respectively.
  • the compounds with a control effect of more than 90% against watermelon fruit spot disease are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the control effects of the control agents copper quinoline and Zhongshengmycin on watermelon fruit spot disease were 22% and 33%, respectively.
  • the compounds that have an efficacy of more than 90% against watermelon fruit spot disease are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the control effects of the control agents copper quinoline and Zhongshengmycin on watermelon fruit spot disease were 15% and 19%, respectively.
  • the compounds with a control effect of more than 90% against soft rot of Chinese cabbage are: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24.
  • the control effects of the control agents copper quinoline and Zhongshengmycin on soft rot of Chinese cabbage were 16% and 39%, respectively.
  • the compounds that have a control effect of more than 90% against soft rot of Chinese cabbage are: 1, 2, 3, 4, 5, 6, 7, 8, 13, 14, 15, 16, 17, 18, 19, 20;
  • the compounds with a control effect of more than 80% are: 9, 10, 11, 12, 21, 22, 23, and 24.
  • the control effects of the control agents copper quinoline and Zhongshengmycin on soft rot of Chinese cabbage were 6% and 23%, respectively.
  • the plant heights of the plants were measured before and 14 days after the application.
  • RI-growth rate increase rate the unit is percentage (%)
  • R2 The growth rate of chemical treatment.
  • leaf length is the distance from the base of the leaf to the tip
  • leaf width is the measured value of the shoulder width of the upper leaf
  • SI-leaf area growth rate the unit is percentage (%)
  • ⁇ S1 the increase in leaf area of blank control
  • ⁇ S2 the increase in leaf area treated by the medicament.
  • SPI-chlorophyll increase rate the unit is percentage (%)
  • ⁇ SP1 the increase in chlorophyll content of blank control
  • ⁇ SP2 the increase of chlorophyll content in chemical treatment.
  • the positive physiological effects of the compound of the present invention on crops are specifically manifested in: Compared with the blank control, it promotes plant height growth, stimulates chlorophyll synthesis and increases plant leaf area, making crop leaves greener and thicker, improving photosynthetic efficiency, and indirectly improving Plant immunity and the ability to resist the bad environment make the plant stronger.

Abstract

本发明属于杀细菌剂技术领域，具体涉及一种下式(I)所示的喹啉羧酸类化合物或其农药学上可接受的盐，式(I)化合物对农业领域中的多种细菌都表现出很好的活性。而且，由于这些化合物具有很高的生物活性，使得在很低的剂量下就可以获得很好的效果，在农业领域中可用于制备杀细菌剂。

Description

一种喹啉羧酸类化合物及其制备方法与用途
本申请要求2019年4月4日向中国国家知识产权局提交的，专利申请号为201910273280.6，发明名称为“一种喹啉羧酸类化合物及其制备方法与用途”在先申请的优先权。该申请的全文通过引用的方式结合于本申请中。
技术领域
本发明属于农用杀细菌剂技术领域，具体涉及一种喹啉羧酸类化合物及其制备方法与用途。
背景技术
近年来随着气候变化，作物品种的改变以及设施农业的快速发展等因素的共同影响，农作物细菌性病害造成的损失逐年加重，同时缺乏有效的化学防治药剂，导致农作物病害一旦大规模发生就很难在短时间内得到有效控制。
目前农业生产中防治细菌性病害的药剂主要是两大类产品，用量最大的是铜制剂，包括有机或无机铜制剂。另一类是抗生素类产品。铜制剂的防效较低，大量的重金属喷施到环境中，对土壤、水体和食品形成污染，引发环境及食品的安全风险；抗生素的大量使用，可能引起人体病原菌对医用抗生素产生抗药性。其他能用于农业细菌治疗的仅有少量品种，实际生产中受到抗性及防效的双重限制，推广面积较小。因此，开发新型低毒、低残留、安全的绿色化学农药是一种迫切的需求。
发明内容
为进一步开发性能优良的杀细菌剂，本发明提供一种如下式(I)所示的喹啉羧酸类化合物或其农药学上可接受的盐，
Figure PCTCN2020080890-appb-000001
其中，R 1选自卤素；
R 2选自C 1-C 16烷基、C 3-C 12环烷基或C 1-C 16卤代烷基。
根据本发明的实施方案，式(I)中，
R 1选自氟、氯、溴或碘；
R 2选自C 1-C 6烷基、C 3-C 6环烷基或C 1-C 6卤代烷基。
作为实例，R 1选自卤素；
R 2选自C 2-C 4烷基、C 3-C 6环烷基或C 2-C 4卤代烷基。
根据本发明的实施方案，式(I)中，
R 1选自氟、氯、溴或碘；
R 2选自C 2-C 4烷基、C 3-C 6环烷基或C 2-C 4卤代烷基。
优选地，式(I)中，
R 1选自F、Cl、Br或I；
R 2选自CH 2CH 3、CH 2CH 2CH 3、CH(CH 3) 2、CH 2CH 2CH 2CH 3、CH 2CH(CH 3) 2、CH(CH 3)(CH 2CH 3)、C(CH 3) 3、CH 2CH 2Cl、CH 2CHF 2、CH 2CF 3、CH 2CH 2CCl 3、
Figure PCTCN2020080890-appb-000002
Figure PCTCN2020080890-appb-000003
优选地，通式(I)所示化合物的盐选自钠盐、钾盐、铵盐、钙盐或锌盐。
进一步优选地，式(I)中，
R 1选自F或Cl；
R 2选自CH 2CH 3、CH 2CH 2CH 3、CH(CH 3) 2、CH 2CH 2CH 2CH 3、CH 2CH(CH 3) 2、CH(CH 3)(CH 2CH 3)、C(CH 3) 3、CH 2CF 3、
Figure PCTCN2020080890-appb-000004
优选地，通式(I)所示化合物的盐选自钠盐、钾盐或铵盐。
作为实例，所述式(I)化合物选自如下化合物，
Figure PCTCN2020080890-appb-000005
Figure PCTCN2020080890-appb-000006
Figure PCTCN2020080890-appb-000007
为降低说明书篇幅之目的，采用上述表格的形式对本发明的示例性基团和/或化合物进行描述。换言之，上述列出的定义应当被理解为包括分别对所述基团进行定义，以及将所述基团结合进行定义。
本发明还提供如上所述式(I)化合物的制备方法，包括将式(II)所示的化合物与式(III)所示的化合物反应得到式(I)所示的化合物，
Figure PCTCN2020080890-appb-000008
其中R 1、R 2具有如上所述的定义；L选自离去基团，例如卤原子，如氟、氯、溴或碘。
根据本发明的实施方案，所述反应可以在碱的存在下进行；所述碱选自有机碱或无机碱；所述有机碱可选自三乙胺、吡啶等中的一种、两种或更多种，所述无机碱可选自碳酸钠、碳酸钾、氢氧化钠、氢氧化钾、甲醇钠、乙醇钠、叔丁醇钾、氢化钠、钠或钾等中的一种、两种或者更多种。
根据本发明的制备方法，所述反应可以在溶剂中进行；所述溶剂可选自芳烃类溶剂、酰胺类溶剂、砜类溶剂等中的一种、两种或者更多种，例如选自甲苯、N-甲基吡咯烷酮、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺或二甲基亚砜等中的一种、两种或者更多种。
根据本发明的实施方案，所述反应的温度优选为50℃～130℃。
或者，也可将式(II)所示的化合物与式(III)所示化合物的金属盐(III-1)反应得到式(I)所示的化合物，
Figure PCTCN2020080890-appb-000009
其中R 1、R 2具有如上所述的定义；L选自离去基团，例如卤原子，如氟、氯、溴或碘；M选自碱金属，例如钠或钾。
根据本发明的实施方案，所述反应可以在溶剂中进行；所述溶剂可选自芳烃类溶剂、酰胺类溶剂、砜类溶剂等中的一种、两种或者更多种，例如选自甲苯、N-甲基吡咯烷酮、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺或二甲基亚砜等中的一种、两种或者更多种。
根据本发明的实施方案，所述反应的温度优选为50℃～150℃。
根据本发明的实施方案，式(II)所示化合物可市售获得或可用已知方法制备。例如，
Figure PCTCN2020080890-appb-000010
其中R 1具有上文所述的定义；L选自离去基团，例如卤原子，如氟、氯、溴或碘。
由起始原料取代苯乙酮(VIII)与碳酸二甲酯或乙酯反应制备相应的苯甲酰乙酸酯(VII)，再由(VII)与原甲酸三烷基酯反应制备相应的丙烯酸酯(VI)，(VI)与环丙胺反应制备胺基丙烯酸酯(IV)，(IV)在碱性条件下合环制备喹啉羧酸酯(V)，(V)水解制备喹啉羧酸(II)。
根据本发明的实施方案，所述反应可参考现有技术文献或类似方法进行。
类似地，式(III)、(III-1)所示化合物也可市售获得或可用已知方法制备。
本发明的制备方法可根据各情况下适合的反应条件和原料的选择，可以例如在一步反应中用根据本发明的另一取代基仅替换一个取代基，或可在相同反应步骤中用根据本发明的其他取代基替换多个取代基。
如果各化合物不可经由上述路线得到，则它们可通过衍生其他式(I)所示化合物或通过将所述合成路线常规变化而制备。
反应混合物以常规方式后处理，如通过与水混合、相分离以及通过色谱法例如在氧化铝或硅胶上提纯粗产物。
本发明还提供式(I)所示化合物农药学上可接受的盐的制备方法，所述农药学上可接受的盐可以通过已知的方法来制备。羧酸的碱盐可通过适宜的碱处理得到式(I)所示化合物的农药学上可接受的盐。其制备方法如下：将式(I)所示化合物与碱(如氢氧化钠、氢氧化钾、氢氧化钙、氢氧化锌、碳酸钾、碳酸钠或氨水等)在水或甲醇等溶剂中反应，可以很方便地得到通式(I)所示化合物农药学上可接受的盐。
以上制备方法可以获得式(I)所示化合物的异构体混合物，如需得到纯异构体，可采用常规方法如结晶或色谱法进行分离。
除非另外指明，上述所有反应可便利地在大气压力下或特定反应的自身压力下进行。
本发明还提供式(I)所示的化合物或其农药学上可接受的盐中的至少一种用于制备杀细菌剂的用途，所述杀细菌剂用于农业领域中。
本发明还提供式(I)所示的化合物或其农药学上可接受的盐中的至少一种作为杀细菌剂的用途，所述杀细菌剂用于农业领域中。
本发明还提供一种组合物，其包含作为活性成分的式(I)所示的化合物或其农药学上可接受的盐中的至少一种。
本发明还提供所述组合物作为杀细菌剂的用途，其可用于农业领域中。
优选地，所述组合物为杀细菌组合物。
根据本发明，所述杀细菌剂优选为杀作物细菌剂或杀植物细菌剂。
本发明还提供一种防治细菌(如植物原病菌)或其导致的病害的方法，包括将有效量的式(I)所示的化合物或其农药学上可接受的盐中的至少一种或将所述组合物施于细菌或病害的生长介质上。
下面提及的细菌病害的例子仅用来说明本发明，但绝不限定本发明。
式(I)所示的化合物可用于防治下列细菌或其导致的病害：
革兰氏阴性菌：欧文氏菌属(引起梨火疫病等)；果胶杆菌属(引起十字花科蔬菜的软腐病，马铃薯黑胫病等)；迪基氏菌属(引起甘薯茎腐病、玉米细菌性茎腐病、水稻细菌性基腐病、马铃薯黑胫病、梨锈水病等)；泛菌属(引起玉米细菌性枯萎病、玉米泛菌叶斑病、红小豆细菌性叶枯病、核果树溃疡病菌等)；假单胞杆菌(引起桃树溃疡病菌、豌豆细菌性疫病菌、十字花科细菌性黑斑病菌、番茄细菌性叶斑病菌、番茄细菌性斑点病、油菜细菌性黑斑病、芝麻细菌性角斑病、黄瓜细菌性角斑病、烟草野火病、玉米细菌性褐斑病、玉米细菌性褐斑病、蚕豆细菌性茎疫病、大豆细菌性斑点病、甜菜细菌性斑枯病、番茄细菌性髓部坏死病、人参铜绿假单胞菌软腐病等)；雷尔氏菌属(引起多种青枯病等)；伯克氏菌属(引起香石竹细菌性萎蔫病、洋葱腐烂病、水稻细菌性穗枯病等)；噬酸菌属(引起瓜类果斑病、兰花褐斑病、燕麦褐条病、魔芋细菌性叶斑病等)；黄单胞菌属(引起水稻白叶枯病、水稻细菌性条斑病、辣椒和番茄斑点病、辣椒和番茄疮痂病、芒果细菌性黑斑病菌、胡椒细菌性叶斑病菌、一品红细菌性疫病、棉花角斑病、大豆细菌性斑疹病、十字花科黑腐病、木薯细菌性枯萎病、甘蔗流胶病、红掌细菌性疫病、柑橘溃疡病菌、风信子黄腐病、桃细菌性穿孔病、草莓角斑病菌、杨树细菌性溃疡病等)；土壤杆菌属(引起蔷薇科植物的根癌病等)；木质部小菌属(引起葡萄皮尔斯病和柑橘的杂色萎黄病等)；韧皮部杆菌属(引起柑橘黄龙病等)；肠杆菌属(引起杨树枯萎病菌等)；嗜木质菌属(引起葡萄细菌性 疫病等)。
革兰氏阳性菌：棒形杆菌属(引起马铃薯环腐、番茄细菌溃疡病、苜蓿细菌萎蔫病、玉米内州萎蔫病、小麦细菌花叶病等)；链丝(霉)菌属(引起马铃薯疮痂病等)；短小杆菌属(引起菜豆细菌性萎蔫病、郁金香黄色疱斑病、菜豆萎蔫病等)；节杆菌属(引起美国冬青叶疫病等)；红球菌属(引起香豌豆带化病等)；芽孢杆菌属(引起玉米芽孢杆菌叶斑病、小麦白叶条斑病等)；拉塞氏杆菌属(引起鸭茅蜜穗病等)。
由于其积极的特性，上述化合物可有利地用于保护农业和园艺业重要的作物或植物，以使其免于遭受细菌病菌的伤害。
为获得理想效果，化合物的用量因各种因素而改变，例如所用化合物、预保护的作物、有害生物的类型、感染程度、气候条件、施药方法、采用的剂型。
本文中所述剂型或组合物成分的选择应与有效成分的物理性质，应用方式和环境因素例如土壤类型，湿度与温度相一致。
所述剂型包括液剂如溶液(包括乳油)，悬浮剂，乳液(包括微乳剂和/或悬浮剂)等等，它们可任选被粘稠成胶状物。所述剂型还包括固体的如粉剂，粉末，颗粒剂，片剂，丸剂，薄膜等，它们可以是水分散性的(“可湿的”)或水溶性的。有效成分可被微囊化再制成悬浮剂或固体剂型；另外有效成分的整个剂型也可以成胶囊化。成胶囊可以控制或延缓释放有效成分。可喷雾剂型可在适当的介质中冲稀，使用的喷雾体积为每公顷大约一百至几百升。高浓度的组合物主要用作进一步加工的中间体。
典型的固体稀释剂在Watkins等人，Handbook of Insecticide Dust Diluents and Carriers，2nd Ed.，Dorland Books，Caldwell，New Jersey中作了介绍。典型的液体稀释剂在Marsden，SolventsGuide，2nd Ed.，Interscience，New York，1950中作了介绍。McCutcheon′s Detergents and Emulsifiers Annual，Allured Publ.Corp.，Ridgewood，New Jersey，以及Sisely and Wood，Encyclopedia of Surface Active Agents，Chemical Publ.Co.，Inc.，New York，1964，列出了表面活性剂和推荐应用。所有剂型都可含有少量的添加剂，以减少泡沫，防结块，防腐蚀，防止微生物的生长等，或加增稠剂以增加粘度。
表面活性剂包括，例如，聚乙氧基化醇，聚乙氧基化烷基酚，聚乙氧基化脱水山梨醇脂肪酸酯，磺化丁二酸二烷基酯，硫酸烷基酯，烷基苯磺酸盐，有机硅烷，N,N-二烷基牛磺酸酯，木质素磺酸盐，萘磺酸盐用醛缩合物，聚羧酸酯和聚氧乙烯/聚氧丙烯嵌段共聚物。
固体稀释剂包括，例如，粘土，如膨润土，蒙脱石，硅镁土和高岭土，淀粉，糖，二氧化硅，滑石，硅藻土，尿素，碳酸钙，碳酸钠，碳酸氢钠，硫酸钠；液体稀释剂包括，例如，水，N,N-二甲基甲酰胺，二甲砜，N-烷基吡咯啉酮，乙二醇，聚丙二醇，石腊，烷基苯，烷基萘，橄榄油，蓖麻油，亚麻籽油，桐油，芝麻油，玉米油，花生油，棉籽油，大豆油，菜籽油和可可油，脂肪酸酯，酮类如环己酮，2-庚酮，异佛尔酮和4-羟基-4-甲基-2-戊酮，和醇类如甲醇，环己醇，十二烷醇和四氢呋喃醇。
溶液，包括乳油，可以通过简单地混合各组分来制备。粉剂和细粉可通过混合或通常在锤磨或液能磨中通过研磨来制备。悬浮剂一般通过湿磨来制备，例如US 3060084中所述方法。颗粒剂和丸剂通过将有效物质喷到刚制成的颗粒载体上或通过造粒技术来制备。可参见Browning，“Agglomeration”，Chemical Engineering，December 4，1967，147-48；Perry′s Chemical Engineer′s Handbook，4TH Ed.，McGraw-Hill，NewYork，1963，8-57；以及WO 9113546。丸剂的制备如US 4172714中介绍，水分散性和水溶性粒剂如US 4144050，US 3920442和DE 3246493中所述的方法来制备，片剂如在US 5180587，US 5232701和US 5208030中所述的方法来制备。薄膜可通过在GB2095558和US 3299566中所述的方法来制备。
有关加工的更多信息可见US 3235361，6栏16行至7栏19行，及实施例10-41；US 3309192，5栏43行至7栏62行及实施例8，12，15，39，41，52，53，58，132，138-140，162-164，166，167和169-182；US 2891855，3栏66行至5栏17行及实施例1-4；Klingman，Weed Control as a Science，John Wiley and Sons，Inc.，New York 1961，81-96；以及Hance等，Weed Control Handbook，8th Ed.，Blackwell Scientific Publications，Oxford，1989。
本文中，对于所述组合物的某些应用，例如在农业上，可在本发明所述的组合物中加入一种、两种或多种其它的杀菌剂、杀虫杀螨剂、除草剂、植物生长调节剂或肥料等，由此可产生附加的优点和效果。
术语定义和说明
除非另有定义，否则本文所有科技术语具有的涵义与权利要求主题所属领域技术人员通常理解的涵义相同。除非另有说明，本文全文引用的所有专利、专利申请、公开材料通过引用方式整体并入本文。如果本文对术语有多个定义，以本章的定义为准。
在本说明书中，可由本领域技术人员选择基团及其取代基以提供稳定的结构部分和化合物。当通过从左向右书写的常规化学式描述取代基时，该取代基也同样包括从右向左书写结构式时所得到的在化学上等同的取代基。举例而言，CH 2O等同于OCH 2。
本申请说明书和权利要求书记载的数值范围，当该数值范围仅可为“整数”时，应当理解为记载了该范围的两个端点以及该范围内的每一个整数。例如，为“1-5”应当理解为记载了1、2、3、4、5的每一个整数。
术语“卤素”指氟、氯、溴或碘。
术语“C 1-C 16烷基”应理解为表示具有1～16个碳原子的直链或支链饱和一价烃基，优选为C 1-C 10烷基。“C 1-C 10烷基”应理解为优选表示具有1、2、3、4、5、6、7、8、9或10个碳原子的直链或支链饱和一价烃基。所述烷基是例如甲基、乙基、丙基、丁基、戊基、己基、异丙基、异丁基、仲丁基、叔丁基、异戊基、2-甲基丁基、1-甲基丁基、1-乙基丙基、1,2-二甲基丙基、新戊基、1,1-二甲基丙基、4-甲基戊基、3-甲基戊基、2-甲基戊基、1-甲基戊基、2-乙基丁基、1-乙基丁基、3,3-二甲基丁基、2,2-二甲基丁基、1,1-二甲基丁基、2,3-二 甲基丁基、1,3-二甲基丁基或1,2-二甲基丁基等或它们的异构体。特别地，所述基团具有1、2、3、4、5、6个碳原子(“C 1-C 6烷基”)，例如甲基、乙基、丙基、丁基、异丙基、异丁基、仲丁基、叔丁基、戊基、己基，更特别地，所述基团具有2、3或4个碳原子的直链或支链饱和一价烃基，例如甲基、乙基、丙基、丁基、异丙基、异丁基、仲丁基、叔丁基或它们的异构体。
上述对术语“烷基”，如“C 1-C 16烷基”的定义同样适用于含有“C 1-C 16烷基”的其他术语，例如术语“C 1-C 16卤代烷基”等。
术语“C 3-C 12环烷基”应理解为表示饱和的一价单环或双环烃环，其具有3～12个碳原子，优选“C 3-C 10环烷基”。术语“C 3-C 10环烷基”应理解为表示饱和的一价单环或双环烃环，其具有3、4、5、6、7、8、9或10个碳原子。所述C 3-C 10环烷基可以是单环烃基，如环丙基、环丁基、环戊基、环己基、环庚基、环辛基、环壬基或环癸基，或者是双环烃基如十氢化萘环。特别地，所述基团具有3、4、5、6个碳原子，例如环丙基、环丁基、环戊基、环己基。
术语“卤代烷基”，应理解为直链或支链烷基，在这些烷基上的氢原子部分或全部被卤原子所取代，例如CF 3CH 2-。
术语“农药学上可接受的盐”是指保留了指定化合物的游离酸和游离碱的生物效力，并且在生物学或其它方面上没有不良作用的盐，其可通过把母体化合物中的酸基基团转换成盐的形式获得。农药学上可接受的盐包括，但不仅限于，酸基基团例如羧基的无机或有机碱盐类。本申请中所述农药学上可接受的盐可以由母体化合物合成，即母体化合物中的酸性基团与1-4当量的碱在一个溶剂系统中反应，形成的碱金属(如钠、钾)盐、碱土金属(如钙、镁)盐、过渡金属(如锌)盐、铵盐、胺(如二乙醇胺、三乙醇胺、辛胺、二辛甲胺、吗啉)盐，优选母体化合物形成的钠盐、钾盐、钙盐、锌盐或铵盐。
有益效果
本发明所述式(I)所示的化合物对农业领域中的多种细菌病菌都表现出很好的活性。并且，这些化合物在很低的剂量下就可以获得很好的防治效果，因此可用于制备杀细菌剂，特别是用于作物或植物的杀菌剂。并且，所述化合物还被证明具有改善作物生长发育的良好活性。
此外，本发明化合物制备步骤简单，收率较高，因此具有较好的应用前景。
具体实施方式
下文将结合具体实施例对本发明的技术方案做更进一步的详细说明。下列实施例仅为示例性地说明和解释本发明，而不应被解释为对本发明保护范围的限制。凡基于本发明上 述内容所实现的技术均涵盖在本发明旨在保护的范围内。
除非另有说明，以下实施例中使用的原料和试剂均为市售商品，或者可以通过已知方法制备。
下述方法用于LC-MS分析：
色谱柱：Agilent ZORBAX SB-C18 150mm×4.6mm，5μm(内径)；
检测波长：254nm；
流速：0.8mL/min；
柱温：30℃；
梯度洗脱条件：
时间(min) 乙腈(％) 0.1％甲酸水溶液(％)
0.00 50 50
5.00 50 50
15.00 90 10
20.00 90 10
合成实施例
实施例1：1-环丙基-7-乙氧基-6-氟-4-氧-1,4-二氢喹啉-3-羧酸(化合物1)
Figure PCTCN2020080890-appb-000011
室温下，向2.30g(50mmol)乙醇中分批加入钠丝0.46g(20mmol)，加热，回流3h。向上述溶液中依次加入15mL N,N-二甲基甲酰胺、2.82g(10mmol)7-氯-1-环丙基-6-氟-4-氧-1,4-二氢喹啉-3-羧酸，逐渐加热至90℃，反应5h。降至室温，向上述反应体系中加入20mL水，乙酸乙酯(3×15mL)萃取。合并有机层，有机层依次用15mL水洗、15mL饱和食盐水洗，无水硫酸镁干燥。减压脱溶，柱层析(洗脱剂：乙酸乙酯、石油醚和甲酸的混合液(1:1:0.01))得产品1.86g，收率64％。
LC/MS[M+H] +＝292.1、[M+Na] +＝314.08、[M+K] +＝330.05。
实施例2：1-环丙基-6-氟-4-氧-7-丙氧基-1,4-二氢喹啉-3-羧酸(化合物2)
Figure PCTCN2020080890-appb-000012
室温下，向3.00g(50mmol)丙醇中分批加入钠丝0.46g(20mmol)，加热，回流4h。向上 述溶液中依次加入15mL N,N-二甲基甲酰胺、2.82g(10mmol)7-氯-1-环丙基-6-氟-4-氧-1,4-二氢喹啉-3-羧酸，逐渐加热至90℃，反应5h。降至室温，向上述反应体系中加入20mL水，乙酸乙酯(3×15mL)萃取。合并有机层，有机层依次用15mL水洗、15mL饱和食盐水洗，无水硫酸镁干燥。减压脱溶，柱层析(洗脱剂：乙酸乙酯、石油醚和甲酸的混合液(1:1:0.01))得产品2.01g，收率66％。
LC/MS[M+H] +＝306.12、[M+Na] +＝328.1、[M+K] +＝344.07。
实施例3：7-叔丁氧基-1-环丙基-6-氟-4-氧-1,4-二氢喹啉-3-羧酸(化合物7)
Figure PCTCN2020080890-appb-000013
室温下，依次将2.24g(20mmol)叔丁醇钾、2.82g(10mmol)7-氯-1-环丙基-6-氟-4-氧-1,4-二氢喹啉-3-羧酸溶于15mL N,N-二甲基甲酰胺中，逐渐加热至110℃，反应6h。降至室温，向上述反应体系中加入20mL水，乙酸乙酯(3×15mL)萃取。合并有机层，有机层依次用15mL水洗、15mL饱和食盐水洗，无水硫酸镁干燥。减压脱溶，柱层析(洗脱剂：乙酸乙酯、石油醚和甲酸的混合液(1:1:0.01))得产品1.78g，收率56％。
LC/MS[M+H] +＝320.13、[M+Na] +＝342.11、[M+K] +＝358.08。
实施例4：1-环丙基-6-氟-4-氧-7-(2,2,2-三氟乙氧基)-1,4-二氢喹啉-3-羧酸(化合物8)
Figure PCTCN2020080890-appb-000014
室温下，向4.00g(40mmol)三氟乙醇中分批加入钠丝0.46g(20mmol)，加热，回流5h。向上述溶液中依次加入15mL N,N-二甲基甲酰胺、2.82g(10mmol)7-氯-1-环丙基-6-氟-4-氧-1,4-二氢喹啉-3-羧酸，逐渐加热至90℃，反应5h。降至室温，向上述反应体系中加入20mL水，乙酸乙酯(3×15mL)萃取。合并有机层，有机层依次用15mL水洗、15mL饱和食盐水洗，无水硫酸镁干燥。减压脱溶，柱层析(洗脱剂：乙酸乙酯、石油醚和甲酸的混合液(1:1:0.01))得产品2.13g，收率62％。
LC/MS[M+H] +＝346.07、[M+Na] +＝368.05、[M+K] +＝384.02。
实施例5：7-环丙氧基-1-环丙基-6-氟-4-氧-1,4-二氢喹啉-3-羧酸(化合物9)
Figure PCTCN2020080890-appb-000015
室温下，向2.32g(40mmol)环丙醇中分批加入钠丝0.46g(20mmol)，加热，回流6h。向上述溶液中依次加入15mL N,N-二甲基甲酰胺、2.82g(10mmol)7-氯-1-环丙基-6-氟-4-氧-1,4-二氢喹啉-3-羧酸，逐渐加热至100℃，反应6h。降至室温，向上述反应体系中加入20mL水，乙酸乙酯(3×15mL)萃取。合并有机层，有机层依次用15mL水洗、15mL饱和食盐水洗，无水硫酸镁干燥。减压脱溶，柱层析(洗脱剂：乙酸乙酯、石油醚和甲酸的混合液(1:1:0.01))得产品1.57g，收率52％。
LC/MS[M+H] +＝304.1、[M+Na] +＝326.08、[M+K] +＝342.05。
实施例6：6-氯-1-环丙基-7-乙氧基-4-氧-1,4-二氢喹啉-3-羧酸(化合物13)
Figure PCTCN2020080890-appb-000016
室温下，向2.76g(60mmol)乙醇中分批加入钠丝0.46g(20mmol)，加热，回流3h。向上述溶液中依次加入15mL N,N-二甲基甲酰胺、2.98g(10mmol)6,7-二氯-1-环丙基-4-氧-1,4-二氢喹啉-3-羧酸，逐渐加热至80℃，反应5h。降至室温，向上述反应体系中加入20mL水，乙酸乙酯(3×15mL)萃取。合并有机层，有机层依次用15mL水洗、15mL饱和食盐水洗，无水硫酸镁干燥。减压脱溶，柱层析(洗脱剂：乙酸乙酯、石油醚和甲酸的混合液(1:1:0.01))得产品1.72g，收率56％。
LC/MS[M+H] +＝308.07、[M+Na] +＝330.05、[M+K] +＝346.02。
本发明的其他化合物参照上述方法合成。
其他部分式(I)化合物的结构表征数据如下：
Figure PCTCN2020080890-appb-000017
Figure PCTCN2020080890-appb-000018
Figure PCTCN2020080890-appb-000019
Figure PCTCN2020080890-appb-000020
制剂实施例
在以下实施例中，所有百分数均以重量计，所有剂型都用常规方法制备。
实施例7：
本实施例使用如上实施例中得到的化合物制备可湿性粉剂，具体采用如下配比的原料组成进行制备：
化合物1 60.0％、十二烷基酚聚乙氧基乙二醇醚4.0％、木质素磺酸钠5.0％、硅铝酸钠6.0％、蒙脱石(煅烧的)25.0％。
实施例8：
本实施例使用如上实施例中得到的化合物制备颗粒剂，具体采用如下配比的原料组成进行制备：
化合物2 10.0％，其他组分为十二烷基硫酸钠2％、木质素磺酸钙6％、氯化钾10％、聚二甲基硅氧烷1％、可溶性淀粉补齐至100％。
实施例9：
本实施例使用如上实施例中得到的化合物制备挤压丸，具体采用如下配比的原料组成进行制备：
化合物7 25.0％、无水硫酸钙10.0％、粗木质素磺酸钙5.0％、烷基萘磺酸钠1.0％、钙/镁膨润土59.0％。
实施例10：
本实施例使用如上实施例中得到的化合物制备乳油，具体采用如下配比的原料组成进行制备：
化合物8 25.0％、溶剂150 60％、PEG400 5％、Rhodacal 70/B 3％、Rhodameen RAM/7 7％。
实施例11：
本实施例使用如上实施例中得到的化合物制备水悬浮剂，具体采用如下配比的原料组成进行制备：
化合物9 30.0％、POE聚苯乙烯苯基醚硫酸盐5.0％、黄原胶0.5％、聚乙二醇5％、三乙 醇胺1％、山梨糖醇0.5％、水补至100.0％。
生物活性测定
本发明化合物对农业领域中的多种细菌性病菌都表现出很好的活性。
实施例12：杀菌活性测定
本发明化合物对植物的多种细菌病害进行了离体抑菌活性或活体保护效果试验，并进行了改善农作物生长发育效果试验。杀菌活性测定结果与改善农作物生长发育效果见以下各实施例。
1.离体杀菌活性测定
测试方法如下：将药剂用合适的溶剂(溶剂的种类如丙酮、甲醇、N,N二甲基甲酰胺和二甲基亚砜等，并且依据其对样品的溶解能力而选择)配制稀释至一系列浓度。在无菌操作条件下，将NB培养液等量分装至试管中，从低浓度到高浓度依次定量吸取药液，分别加入上述试管中，充分摇匀，然后分别等量加入处于对数生长期的菌悬液，每处理重复4次。混匀后，放于25℃振荡培养箱黑暗培养，待对数生长期测量OD值。
(1)部分化合物对黄瓜细菌性角斑病病原菌的离体抑菌活性(以抑制率表示)测试结果如下：
在5ppm剂量下，对黄瓜细菌性角斑病病原菌的抑制率在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对黄瓜细菌性角斑病病原菌的抑制率分别为2％、48％。
在1ppm剂量下，对黄瓜细菌性角斑病病原菌的抑制率在90％以上的化合物有：1、2、3、4、6、7、8、11、12、13、14、15、17、18、19、20、24；抑制率在80％以上的化合物有：5、9、10、16、21、22、23。在该剂量下，对照药剂喹啉铜、中生菌素对黄瓜细菌性角斑病病原菌的抑制率分别为0、21％。
(2)部分化合物对烟草青枯病病原菌的离体抑菌活性(以抑制率表示)测试结果如下：
在5ppm剂量下，对烟草青枯病病原菌的抑制率在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对烟草青枯病病原菌的抑制率分别为5％、51％。
在1ppm剂量下，对烟草青枯病病原菌的抑制率在90％以上的化合物有：1、2、3、4、6、7、8、11、12、13、14、15、17、18、19、20、24；抑制率在80％以上的化合物有：5、9、10、16、21、22、23。在该剂量下，对照药剂喹啉铜、中生菌素对烟草青枯病病原菌的抑制率分别为0、28％。
(3)部分化合物对马铃薯黑胫病病原菌的离体抑菌活性(以抑制率表示)测试结果如下：
在5ppm剂量下，对马铃薯黑胫病病原菌的抑制率在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对马铃薯黑胫病病原菌的抑制率分别为3％、55％。
在1ppm剂量下，对马铃薯黑胫病病原菌的抑制率在90％以上的化合物有：1、2、3、4、5、6、7、8、13、14、15、16、17、18、19、20；抑制率在80％以上的化合物有：9、10、11、12、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对马铃薯黑胫病病原菌的抑制率分别为0、38％。
(4)部分化合物对甘薯茎腐病病原菌的离体抑菌活性(以抑制率表示)测试结果如下：
在5ppm剂量下，对甘薯茎腐病病原菌的抑制率在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对甘薯茎腐病病原菌的抑制率分别为7％、46％。
在1ppm剂量下，对甘薯茎腐病病原菌的抑制率在90％以上的化合物有：1、2、3、4、5、6、7、8、13、14、15、16、17、18、19、20；抑制率在80％以上的化合物有：9、10、11、12、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对甘薯茎腐病病原菌的抑制率分别为2％、25％。
(5)部分化合物对水稻白叶枯病病原菌的离体抑菌活性(以抑制率表示)测试结果如下：
在5ppm剂量下，对水稻白叶枯病病原菌的抑制率在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对水稻白叶枯病病原菌的抑制率分别为16％、48％。
在1ppm剂量下，对水稻白叶枯病病原菌的抑制率在90％以上的化合物有：1、2、3、4、5、6、7、8、13、14、15、16、17、18、19、20；抑制率在80％以上的化合物有：9、10、11、12、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对水稻白叶枯病病原菌的抑制率分别为9％、30％。
(6)部分化合物对西瓜果斑病病原菌的离体抑菌活性(以抑制率表示)测试结果如下：
在5ppm剂量下，对西瓜果斑病病原菌的抑制率在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对西瓜果斑病病原菌的抑制率分别为3％、52％。
在1ppm剂量下，对西瓜果斑病病原菌的抑制率在90％以上的化合物有：1、2、3、4、5、6、7、8、13、14、15、16、17、18、19、20；抑制率在80％以上的化合物有：9、10、11、12、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对西瓜果斑病病原菌的抑制率分别为0、29％。
(7)部分化合物对大白菜黑腐病病原菌的离体抑菌活性(以抑制率表示)测试结果如下：
在5ppm剂量下，对大白菜黑腐病病原菌的抑制率在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对大白菜黑腐病病原菌的抑制率分别为5％、46％。
在1ppm剂量下，对大白菜黑腐病病原菌的抑制率在90％以上的化合物有：1、2、3、4、5、6、7、8、13、14、15、16、17、18、19、20；抑制率在80％以上的化合物有：9、10、11、12、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对大白菜黑腐病病原菌的抑制率分别为0、19％。
(8)部分化合物对木薯细菌性枯萎病病原菌的离体抑菌活性(以抑制率表示)测试结果如下：
在5ppm剂量下，对木薯细菌性枯萎病病原菌的抑制率在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对木薯细菌性枯萎病病原菌的抑制率分别为15％、51％。
在1ppm剂量下，对木薯细菌性枯萎病病原菌的抑制率在90％以上的化合物有：1、2、3、4、6、7、8、11、12、13、14、15、17、18、19、20、24；抑制率在80％以上的化合物有：5、9、10、16、21、22、23。在该剂量下，对照药剂喹啉铜、中生菌素对木薯细菌性枯萎病病原菌的抑制率分别为7％、32％。
(9)部分化合物对梨火疫病病原菌的离体抑菌活性(以抑制率表示)测试结果如下：
在5ppm剂量下，对梨火疫病病原菌的抑制率在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对梨火疫病病原菌的抑制率分别为3％、43％。
在1ppm剂量下，对梨火疫病病原菌的抑制率在90％以上的化合物有：1、2、3、4、5、6、7、8、13、14、15、16、17、18、19、20；抑制率在80％以上的化合物有：9、10、11、12、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对梨火疫病病原菌的抑制率分别为0、23％。
2.活体保护活性测定
针对西瓜果斑病、烟草青枯病、甘薯茎腐病，将待测化合物用少量合适溶剂(溶剂的种类如丙酮、甲醇、N,N二甲基甲酰胺和二甲基亚砜等，并且依据其对样品的溶解能力而选择)溶解后用0.1％吐温80稀释至试验浓度。将培养至稳定生长期的病原细菌与定量化合物溶液混合均匀，将经过催芽的甜瓜种子、番茄种子、烟草种子和马铃薯种薯放入菌液与化合物的混合液中浸泡半小时，再将种子播种于蚯蚓土培养杯中，放入温室中保湿培养，待 对照充分发病后进行防效调查。
针对大白菜软腐病，切取2厘米见方的白菜叶片，放入垫有双层滤纸的玻璃培养皿中。将待测化合物用少量合适溶剂(溶剂的种类如丙酮、甲醇、N,N二甲基甲酰胺和二甲基亚砜等，并且依据其对样品的溶解能力而选择)溶解后，用水稀释至所需浓度，喷雾于白菜叶片表面，于通风橱内晾干白菜叶片表面药液后，使用接种针在白菜叶片表面针刺造成伤口，将培养至稳定生长期的大白菜软腐病菌取5微升加入伤口内，进行接种。最后将试材放入培养箱中避光培养48小时，待对照充分发病后进行防效调查。
针对黄瓜细菌性角斑病、水稻白叶枯病，将待测化合物用少量合适溶剂(溶剂的种类如丙酮、甲醇、N,N二甲基甲酰胺和二甲基亚砜等，并且依据其对样品的溶解能力而选择)溶解后，用水稀释至所需浓度。将化合物水溶液喷雾于植物试材表面，于阴凉处风干表面药液后，将培养至稳定生长期的病原细菌菌液喷雾接种于植物试材表面，然后将植物试材放入温室中保湿培养。通常培养十天左右，待对照充分发病后，进行防效调查。
针对马铃薯黑胫病，将待测化合物用少量合适溶剂(溶剂的种类如丙酮、甲醇、N,N二甲基甲酰胺和二甲基亚砜等，并且依据其对样品的溶解能力而选择)溶解后，用水稀释至所需浓度。按设计药剂浓度对试验马铃薯进行灌根，每株用量200mL，保持每株马铃薯用药量一致(含对照处理)。接种黑胫病菌，于施药后第2天进行。根据发病情况调查结果。
(1)部分化合物对黄瓜细菌性角斑病的防效测试结果如下：
在10ppm剂量下，对黄瓜细菌性角斑病的防效在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对黄瓜细菌性角斑病的防效分别为15％、20％。
在5ppm剂量下，对对黄瓜细菌性角斑病的防效在90％以上的化合物有：1、2、3、4、5、6、7、8、13、14、15、16、17、18、19、20；防效在80％以上的化合物有：9、10、11、12、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对黄瓜细菌性角斑病的防效的抑制率分别为10％、12％。
(2)部分化合物对烟草青枯病的防效测试结果如下：
在10ppm剂量下，对烟草青枯病的防效在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对烟草青枯病的防效分别为11％、35％。
在5ppm剂量下，对烟草青枯病的防效在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对烟草青枯病的防效分别为5％、24％。
(3)部分化合物对马铃薯黑胫病的防效测试结果如下：
在10ppm剂量下，对马铃薯黑胫病的防效在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对马铃薯黑胫病的防效的抑制率分别为22％、25％。
在5ppm剂量下，对马铃薯黑胫病的防效在90％以上的化合物有：1、2、3、4、5、6、7、8、13、14、15、16、17、18、19、20；防效在80％以上的化合物有：9、10、11、12、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对马铃薯黑胫病的防效分别为11％、17％。
(4)部分化合物对甘薯茎腐病的防效测试结果如下：
在10ppm剂量下，对甘薯茎腐病的防效在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对甘薯茎腐病的防效分别为20％、38％。
在5ppm剂量下，对甘薯茎腐病的防效在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对甘薯茎腐病的防效分别为13％、23％。
(5)部分化合物对水稻白叶枯病的防效测试结果如下：
在10ppm剂量下，对水稻白叶枯病的防效在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对水稻白叶枯病的防效分别为10％、35％。
在5ppm剂量下，对水稻白叶枯病的防效在90％以上的化合物有：1、2、3、4、5、6、7、8、13、14、15、16、17、18、19、20；防效在80％以上的化合物有：9、10、11、12、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对水稻白叶枯病的防效分别为6％、24％。
(6)部分化合物对西瓜果斑病的防效测试结果如下：
在10ppm剂量下，对西瓜果斑病的防效在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对西瓜果斑病的防效分别为22％、33％。
在5ppm剂量下，对西瓜果斑病的防效在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对西瓜果斑病的防效分别为15％、19％。
(7)部分化合物对大白菜软腐病的防效测试结果如下：
在10ppm剂量下，对大白菜软腐病的防效在90％以上的化合物有：1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对大白菜软腐病的防效分别为16％、39％。
在5ppm剂量下，对大白菜软腐病的防效在90％以上的化合物有：1、2、3、4、5、6、7、8、13、14、15、16、17、18、19、20；防效在80％以上的化合物有：9、10、11、12、21、22、23、24。在该剂量下，对照药剂喹啉铜、中生菌素对大白菜软腐病的防效分别为6％、23％。
3.改善农作物生长发育作用
以室内盆栽黄瓜苗为例，主要评价本发明化合物对作物株高生长速率、叶绿素含量、叶面积等。
(1)生长速率
分别测量施药前和施药后14天植株的株高。
按公式①计算生长速率
Figure PCTCN2020080890-appb-000021
式中：R—生长速率(mm/d)；
L—植株新生高度或长度(mm)；
D—时间天(d)。
按公式②计算生长速率增加率(％)
Figure PCTCN2020080890-appb-000022
式中：RI—生长速率增加率，单位为百分率(％)；
R1—空白对照生长速率；
R2—药剂处理生长速率。
(2)叶面积
分别测量施药前和施药14天后植株第二个叶片的纵、横径(即叶长、叶宽，叶长为叶片基部至叶尖的距离，叶宽为叶片上部肩宽测值)。
按公式③计算叶面积
S＝0.7430×ab  ③，
式中：S—叶面积(cm 2)；
a—叶片长度(cm)；
b—叶片宽度(cm)。
按公式④计算叶面积增长量
△S＝S2-S1  ④，
式中：
S1—施药前叶面积；
S2—施药14天后的叶面积。
按公式⑤计算叶面积生长增加率(％)
Figure PCTCN2020080890-appb-000023
式中：SI—叶面积生长增加率，单位为百分率(％)；
△S1—空白对照叶面积增长量；
△S2—药剂处理叶面积增长量。
(3)叶绿素含量
用叶绿素测定仪，型号SPAD-520Plus，测定叶片叶绿素含量。
按公式⑥计算叶绿素含量增长量
△SP＝SP2-SP1  ⑥，
式中：
SP1—施药前叶绿素含量；
SP2—施药14天后的叶绿素含量。
按公式⑦计算叶绿素含量增加率(％)
Figure PCTCN2020080890-appb-000024
式中：SPI—叶绿素增加率，单位为百分率(％)；
△SP1—空白对照叶绿素含量增长量；
△SP2—药剂处理叶绿素含量增长量。
本发明化合物对黄瓜苗的安全性和保健作用结果如下表1所示：
表1本发明化合物对黄瓜苗的安全性和保健作用结果
Figure PCTCN2020080890-appb-000025
Figure PCTCN2020080890-appb-000026
在200ppm剂量下，化合物1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24，对植株生长安全，施药后无变色、坏死、萎蔫、畸形等现象出现。即本发明化合物对试验作物均无不良影响，安全性好，符合绿色农药的安全性要求。
本发明化合物对作物正面生理效应具体表现在：与空白对照相比，促进植株株高生长，刺激叶绿素的合成并且增加植株叶面积，使得作物叶片更绿、更厚实、提高光合效率，间接提高了植株免疫力和抵御外界不良环境的能力，使植株更健壮。
以上，对本发明的实施方式进行了说明。但是，本发明不限定于上述实施方式。凡在本发明的精神和原则之内，所做的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。

Claims (10)

  1. 一种式(I)所示的喹啉羧酸类化合物或其农药学上可接受的盐，
    Figure PCTCN2020080890-appb-100001
    其中，R 1选自卤素；
    R 2选自C 1-C 16烷基、C 3-C 12环烷基或C 1-C 16卤代烷基。
  2. 根据权利要求1所述化合物或其农药学上可接受的盐，其特征在于，式(I)中，
    R 1选自氟、氯、溴或碘；
    R 2选自C 1-C 6烷基、C 3-C 6环烷基或C 1-C 6卤代烷基。
  3. 根据权利要求2所述化合物或其农药学上可接受的盐，其特征在于，式(I)中，
    R 1选自F、Cl、Br或I；
    R 2选自CH 2CH 3、CH 2CH 2CH 3、CH(CH 3) 2、CH 2CH 2CH 2CH 3、CH 2CH(CH 3) 2、CH(CH 3)(CH 2CH 3)、C(CH 3) 3、CH 2CH 2Cl、CH 2CHF 2、CH 2CF 3、CH 2CH 2CCl 3、
    Figure PCTCN2020080890-appb-100002
    Figure PCTCN2020080890-appb-100003
    通式(I)所示化合物的盐选自钠盐、钾盐、铵盐、钙盐或锌盐。
  4. 根据权利要求3所述化合物或其农学上可接受的盐，其特征在于，式(I)中，
    R 1选自F或Cl；
    R 2选自CH 2CH 3、CH 2CH 2CH 3、CH(CH 3) 2、CH 2CH 2CH 2CH 3、CH 2CH(CH 3) 2、CH(CH 3)(CH 2CH 3)、C(CH 3) 3、CH 2CF 3、
    Figure PCTCN2020080890-appb-100004
    通式(I)所示化合物的盐选自钠盐、钾盐或铵盐。
  5. 权利要求1-4任一项所述化合物或其农药学上可接受的盐的制备方法，其特征在于，包括如下步骤：
    将式(II)所示的化合物与式(III)所示的化合物反应得到所述式(I)所示的化合物，
    Figure PCTCN2020080890-appb-100005
    或者，将式(II)所示的化合物与式(III)所示化合物的金属盐(III-1)反应得到所述式(I)所示的化合物，
    Figure PCTCN2020080890-appb-100006
    其中R 1、R 2具有权利要求1-4任一项所述的定义；L选自离去基团，例如卤原子，如氟、氯、溴或碘；M选自碱金属，例如钠或钾。
  6. 权利要求1-4任一项所述化合物或其农药学上可接受的盐中的至少一种用于制备杀细菌剂的用途，所述杀细菌剂用于农业领域中。
  7. 一种组合物，其特征在于，所述组合物包含作为活性成分的权利要求1-4任一项所述化合物或其农药学上可接受的盐中的至少一种。
  8. 根据权利要求7所述的组合物，其特征在于，所述组合物为杀细菌剂，例如杀作物细菌剂或杀植物细菌剂。
  9. 权利要求7或8所述组合物作为杀细菌剂的用途，所述杀细菌剂用于农业领域中。
  10. 一种防治细菌或其导致的病害的方法，包括将有效量的权利要求1-4任一项所述化合物或其农药学上可接受的盐中的至少一种施于细菌或病害的生长介质上。
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