CN116640092B - Benzyloxy substituted bispyridinyl ketone compounds and their application - Google Patents
Benzyloxy substituted bispyridinyl ketone compounds and their application Download PDFInfo
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen 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
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Abstract
The invention relates to benzyloxy substituted bipyridine methanone compounds and application thereof. Specifically, the invention provides a compound shown in a formula (I) or an agropharmaceutically acceptable salt thereof, wherein R 1、R2、R3、R4 and R 5 are respectively and independently hydrogen, halogen, cyano, hydroxyl and the like, X is halogen, Y is alkyl or halogenated alkyl, and Z is alkoxy or halogenated alkoxy. The compound has excellent bactericidal activity on powdery mildew of cucumber and gray mold of cucumber.
Description
Technical Field
The invention relates to benzyloxy substituted bipyridine methanone compounds and application thereof, which can be used for preventing and treating cucumber powdery mildew and cucumber gray mold, and also relates to preparation and composition of the compounds.
Background
One of the serious problems faced by agricultural production worldwide is crop disease caused by phytopathogenic fungi, which often rapidly infest many crops, resulting in reduced grain yield and the production of mycotoxins harmful to animal and human health. The continuous research and development of novel compounds with excellent bactericidal effect reduces the dosage, improves the drug effect, prolongs the duration of the drug effect, expands the bactericidal spectrum, avoids the phytotoxicity to crops and the like, and has important significance in ensuring the aspect of agricultural production.
The prior art CN1440389a discloses a class of benzoylpyridine derivatives or their salts, which have preventive and therapeutic effects on powdery mildew of barley, vegetables, fruits and flowering plants, but does not disclose the compounds of the present invention.
Disclosure of Invention
The invention aims to provide a novel benzyloxy substituted bipyridine methanone compound which has excellent bactericidal effect.
In one aspect, the present invention provides a compound having the formula (I):
Wherein:
R 1、R2、R3、R4 and R 5 are each independently hydrogen, halogen, cyano, hydroxy, nitro, amino, carboxyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, haloalkoxy, alkenyloxy, haloalkenyloxy, alkynyloxy, haloalkynyloxy, cycloalkyl or cycloalkyloxy;
x is halogen;
Y is alkyl or haloalkyl;
Z is alkoxy or haloalkoxy.
"Alkyl" as used herein means a saturated, straight or branched monovalent hydrocarbon group containing 1 to 20 carbon atoms, and in one embodiment, the alkyl group contains 1 to 20 carbon atoms. In one embodiment, the alkyl group contains 1 to 12 carbon atoms, in one embodiment the alkyl group contains 1 to 10 carbon atoms, in one embodiment the alkyl group contains 1 to 8 carbon atoms, in another embodiment the alkyl group contains 1 to 6 carbon atoms, in yet another embodiment the alkyl group contains 1 to 4 carbon atoms, and in yet another embodiment the alkyl group contains 1 to 3 carbon atoms.
"Alkenyl" as used herein means a straight or branched chain monovalent hydrocarbon radical containing 2 to 12 carbon atoms wherein there is at least one site of unsaturation, i.e., one carbon-carbon sp 2 double bond, wherein the alkenyl radical may be optionally substituted with one or more substituents as described herein, including the positioning of "cis" and "tans", or the positioning of "E" and "Z". In one embodiment, the alkenyl group comprises 2 to 10 carbon atoms, in one embodiment the alkenyl group comprises 2 to 8 carbon atoms, in another embodiment the alkenyl group comprises 2 to 6 carbon atoms, and in yet another embodiment the alkenyl group comprises 2 to 4 carbon atoms.
"Alkynyl" as used herein means a straight or branched chain monovalent hydrocarbon radical containing 2 to 12 carbon atoms, wherein there is at least one carbon-carbon sp triple bond, wherein the alkynyl radical may be optionally substituted with one or more substituents as described herein. In one embodiment, the alkynyl group comprises 2 to 10 carbon atoms, in one embodiment, the alkynyl group comprises 2 to 8 carbon atoms, in another embodiment, the alkynyl group comprises 2 to 6 carbon atoms, and in yet another embodiment, the alkynyl group comprises 2 to 4 carbon atoms.
"Haloalkyl" as used herein means an alkyl group substituted with one or more halogen atoms.
"Haloalkenyl" as used herein means alkenyl groups substituted with one or more halogen atoms.
"Haloalkynyl" as used herein means an alkynyl group substituted with one or more halogen atoms.
"Alkoxy" as used herein means an alkyl group attached to the remainder of the molecule through an oxygen atom, wherein the alkyl group has the meaning as described herein. In one embodiment, the alkoxy groups contain 1 to 12 carbon atoms, in one embodiment 1 to 10 carbon atoms, in one embodiment 1 to 8 carbon atoms, in one embodiment 1 to 6 carbon atoms, in another embodiment 1 to 4 carbon atoms, and in yet another embodiment 1 to 3 carbon atoms.
"Haloalkoxy" as used herein means an alkoxy group substituted with one or more halogen atoms.
"Alkenyloxy" as used herein means that the alkenyl group is attached to the remainder of the molecule through an oxygen atom, wherein the alkenyl group has the meaning as described herein.
"Haloalkenyloxy" as used herein means alkenyloxy substituted with one or more halogen atoms.
"Alkynyloxy" as used herein means an alkynyl group attached to the remainder of the molecule through an oxygen atom, wherein alkynyl has the meaning as described herein.
"Haloalkynyloxy" as used herein means that the alkynyloxy group is substituted with one or more halogen atoms.
"Cycloalkyl" as used herein means a monovalent or polyvalent saturated monocyclic, bicyclic or tricyclic ring system containing 3 to 15 carbon atoms. In one embodiment, cycloalkyl groups comprise 3 to 12 carbon atoms, in one embodiment cycloalkyl groups comprise 3 to 10 carbon atoms, in another embodiment cycloalkyl groups comprise 3 to 8 carbon atoms, and in yet another embodiment cycloalkyl groups comprise 3 to 6 carbon atoms. The cycloalkyl group is optionally substituted with one or more substituents described herein. Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.
"Cycloalkyloxy" as used herein means that the cycloalkyl group is attached to the remainder of the molecule through an oxygen atom, wherein the cycloalkyl group has the meaning as described herein.
"Halogen" as used herein refers to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).
As used herein, "room temperature" means a temperature of about 15 to 35 ℃, or about 20 to 30 ℃, or about 23 to 28 ℃, or about 25 ℃.
"Overnight" as used herein means a time of about 4 to 20 hours or about 6 to 15 hours or about 8 to 12 hours or about 8 hours or about 9 hours or about 10 hours or about 12 hours.
In the context of the present invention, all numbers disclosed herein are approximate, whether or not the word "about" or "about" is used. The numerical value of each number may vary by 1%,2%,3%,4% or 5%.
According to some embodiments of the invention, R 1、R2、R3、R4 and R 5 are each independently hydrogen, halogen, cyano, hydroxy, nitro, amino, carboxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogenated C 1-6 alkyl, halogenated C 2-6 alkenyl, halogenated C 2-6 alkynyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, C 2-6 alkenyloxy, halogenated C 2-6 alkenyloxy, C 2-6 alkynyloxy, halogenated C 2-6 alkynyloxy, C 3-8 cycloalkyl or C 3-8 cycloalkyloxy.
According to further embodiments of the invention, R 1、R2、R3、R4 and R 5 are each independently hydrogen, halogen, cyano, hydroxy, nitro, amino, carboxy, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halogenated C 1-4 alkyl, halogenated C 2-4 alkenyl, halogenated C 2-4 alkynyl, C 1-4 alkoxy, halogenated C 1-4 alkoxy, C 2-4 alkenyloxy, halogenated C 2-4 alkenyloxy, C 2-4 alkynyloxy, halogenated C 2-4 alkynyloxy, C 3-6 cycloalkyl or C 3-6 cycloalkyloxy.
According to further embodiments of the invention, R 1、R2、R3、R4 and R 5 are each independently hydrogen, fluoro, chloro, bromo, methyl, trifluoromethyl, methoxy, trifluoromethoxy, ethoxy, n-propoxy, isopropoxy, allyloxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy or cyclohexyloxy.
According to further embodiments of the invention, R 1 is hydrogen, fluorine or methyl, R 2 is fluorine, chlorine or bromine, R 3 is hydrogen or methoxy, R 4 is hydrogen, fluorine, chlorine or trifluoromethyl, R 5 is hydrogen, fluorine or methoxy.
According to some embodiments of the invention, X is halogen, Y is C 1-6 alkyl or halogenated C 1-6 alkyl, and Z is C 1-6 alkoxy or halogenated C 1-6 alkoxy.
According to further embodiments of the invention, X is halogen, Y is C 1-4 alkyl or halogenated C 1-4 alkyl, Z is C 1-4 alkoxy or halogenated C 1-4 alkoxy.
According to further embodiments of the invention, X is chlorine or bromine, Y is methyl, Z is methoxy.
Preferably, the compound of formula (I) according to the invention is selected from the following compounds or agropharmaceutically acceptable salts thereof:
Or alternatively
Compared with the compound disclosed by the prior art CN1440389A, the compound disclosed by the invention adopts a pyridine ring to replace a benzene ring, and optionally substituted benzyloxy is further introduced as a pyridine ring substituent, so that the benzyloxy substituted bipyridine ketone compound with a brand new structure is obtained.
The prior art CN1440389A is mainly aimed at powdery mildew of barley, vegetables, fruits and flowering plants, and the compound disclosed by the invention has good control effect on gray mold besides being effective on powdery mildew, and has more obvious broad-spectrum advantage.
The research shows that the compound has more excellent sterilization effect, for example, the disclosed compound No.27 (the structural formula is shown as follows, the specific synthesis is shown in synthesis example 6) in the prior art CN1440389A has the control effect on cucumber gray mold below 65% and the control effect of the compound is above 80% at the concentration of 500ppm by adopting the sterilization activity test method disclosed by the invention.
In another aspect, the present invention provides a pesticidal composition comprising at least one compound of the present invention or a pharmaceutically acceptable salt thereof, further optionally comprising a pharmaceutically acceptable adjuvant, including, but not limited to, solvents, liquid diluents, solid diluents, emulsifiers, dispersants, defoamers, thickeners, binders, penetrants, preservatives, antifreeze, fillers, and the like.
Where the compounds of the invention contain an acid moiety, pharmaceutically acceptable salts include, but are not limited to, inorganic and organic acid salts, such as acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, naphthalenesulfonic, benzenesulfonic or toluenesulfonic acid and the like, and where the compounds of the invention contain a base moiety, pharmaceutically acceptable salts include, but are not limited to, potassium, sodium, magnesium or ammonium salts and the like.
According to some of the embodiments of the invention, the pesticide composition is a fungicidal composition.
Preferably, the active ingredient is present in the bactericidal composition in an amount of 1 to 99.9 wt.%, more preferably 5 to 95 wt.%.
In a further aspect, the invention provides the use of a compound of the invention or a composition comprising a compound of the invention in agriculture.
In a further aspect, the present invention provides the use of a compound of the invention or a composition comprising a compound of the invention as a fungicide.
Preferably, the invention provides the use of the compounds of the invention or of a composition comprising the compounds of the invention for controlling powdery mildew of cucumber.
Preferably, the invention provides the use of the compounds according to the invention or of a composition comprising the compounds according to the invention for controlling cucumber gray mold.
The compounds of the present invention may also be prepared in conventional formulations for practical use. Examples of formulations include solutions, wettable powders, emulsions, emulsifiable concentrates, suspensions, powders, water dispersible granules, tablets, granules, microcapsules and the like. These formulations may be prepared by methods conventional in the art. For example, the active compound may be admixed with pharmaceutically acceptable adjuvants including, but not limited to, solvents, liquid diluents, solid diluents, emulsifiers, dispersants, defoamers, thickeners, binders, penetrants, preservatives, antifreeze, fillers, and the like.
When used, commercially available formulations are diluted in a usual manner if necessary, for example in wettable powders, emulsion concentrates, suspensions and particles suspended in water. The powder, granules for soil application or solutions for broadcast and spray application generally do not require further dilution with inert substances prior to use. The amount of active compound used varies with the external conditions, such as temperature, humidity, nature of the biocide used, and the like.
The compound can be used for preventing and treating oomycete diseases such as downy mildew, white rust, damping-off, cotton rot, epidemic disease, late blight and the like, half known fungus diseases such as fusarium wilt, root rot, damping-off, anthracnose, verticillium wilt, scab, gray mold, brown spot, black spot, spot blight, early blight, ring spot, leaf blight, stem basal rot and the like, basidiomycete diseases such as rust, smut and the like, ascomycete diseases such as powdery mildew, sclerotium disease, black star and the like.
The compounds of the invention can be used in crops of cereals (wheat, barley, rye, oats, rice, maize, sorghum and related species), sugar beets (sugar-beet and fodder beets), pome, stone fruits and soft fruits (apples, pears, plums, peas, almonds, cherries, strawberries, raspberries and blackberries), legumes (lentils, beans, peas, soybeans), oil crops (oilseed rape, mustard, olives, sunflowers, coconuts, castor oil plants, cocoa beans, peanuts or soybeans), melons (pumpkin, cucumber, melon), fiber plants (cotton, flax, jute), citrus fruits (oranges, lemon, grapefruit, citrus), vegetables (spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes, red peppers), laurel plants (avocados, camphor) or plants, such as tobacco, nuts, coffee, eggplant, sugarcane, tea, peppers, vines, hops, bananas and natural rubber plants, as well as flowers, ornamental and forest plants, such as flowers, ornamental and woody plants, such as leaves, and shrubs, such as for example, and pine and green plant and pine tree materials.
The compounds according to the invention may also be admixed with other active substances, such as insecticides, acaricides, herbicides and fungicides, and also with safeners, fertilizers and/or plant growth regulators, with the result that additional advantages and effects result.
The compound of the invention is preferably mixed with bactericides, wherein the bactericides comprise, but are not limited to, benomyl, carbendazim, corncob, thiabendazole, thiophanate-methyl and the like, dicarboxyimide comprises ethiprole, iprodione, procymidone, ethephon and the like, and the DMI-bactericides comprise imazalil, imidazole, fenoxanil, prochloraz, triflumuron, pyribenzoxim, chlorpyrimol, fluorobenzoyl, penconazole, bistriazolol, furazoles, cyproconazole, difenoconazole, diniconazole, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, Penconazole, propiconazole, prothioconazole, simeconazole, tebuconazole, fluoroether azole, triazolone, triadimenol, triticonazole, epoxiconazole, furtezole-cis and the like, phenylamide series such as benalaxyl, furalaxyl, metalaxyl, mefenoxam, furalamide and the like, amine series such as dodine, fenpropimorph, tridemorph, fenpropidin, triamcinolone and the like, thiophanate series such as EDDP, iprobenfos, pyrazophos and the like, dithiazol series such as isoprothiolane and the like, carboxamide such as mefenoxam, boscalid, carboxin, fenpropiconazole, flufenamide, furazalide, fenhexamid, carboxin, pyrifos-methyl, thizamide and the like, hydroxy- (2-amino) pyrimidine series such as bupirimate, Such as pyriminostrobin and bupirimate, AP bactericides (anilinopyrimidine) such as cyprodinil, cyprodinil and pyrimethanil, N-phenylcarbamate such as diethofencarb, qoI-bactericides (Qo inhibitor) such as azoxystrobin, picoxystrobin, pyraclostrobin, kresoxim-methyl, trifloxystrobin, fenhexamid, trifloxystrobin, pyraclostrobin, fluoxastrobin, imidazolone and phenoxyamine, PP bactericides (phenylpyrrole) such as fenpiclonil, fludioxonil, quinoline such as quinoxyfen, AH bactericides (aromatic hydrocarbon) such as biphenyl, anisole, chloronitrosamine, pentachloronitrobenzene, tetrachloronitrobenzene, tolclofos-methyl, MBI-R such as tetrachlorophthalide, the preparation method comprises the steps of preparing a compound, wherein the compound comprises the following components of fluquindone, tricyclazole and the like, MBI-D system, such as cyclopropylamide, dicyclopentadienyl amine, cyhalofop-butyl and the like, SBI agent, such as cyproconazole, pyributicarb and terbinafine and the like, phenylurea, such as pencycuron and the like, qiI-bactericide (Qi inhibitor), such as cyazofamid and the like, benzamide system, such as zoxamide and the like, enolpyruronic system, such as blasticidin, midomycin and the like, hexopyranosyl system, such as kasugamycin and valicarb, such as validamycin and the like, cyanoacetamide system, such as cymoxanil and the like, carbamate system, such as midocarb, propamocarb, carbofuran and the like, and the anticonfigurine, such as chlorpyrifos, chlorpyrifos and azoazophos, fluazinam and the like, organotin compounds such as triphenyltin acetate, triphenyltin chloride, triphenyltin hydroxide and the like, phosphate esters such as phosphorous acid, tolclofos-methyl, triethylphosphonic acid and the like, phthalamic acid systems such as leaf-cumyl phthalide and the like, benzotriazine systems such as imidazoxide and the like, benzenesulfonamide systems such as sulfenamide and the like, pyridazinone and the like, pyridalyl (carboxylic acid amide) systems such as dimethomorph, flumorph, benthiavalicarb, propineb, mandipropamid and the like, tetracyclines such as terramycin and the like, thiocarbamate systems such as thiodicarb and the like, and other compounds such as benomyl, polyoxin, quinate, hydroxyisoxazole, xin Sai ketone, silthiophanate, difluoroforest, alamic acid type benzene-S-methyl, Probenazole, tiadinil, ethaboxam, cyflufenamid, propiquindox, metrafenone, fluopicolide, copper hydroxide, organocopper, sulfur, thiram, mancozeb, maneb, metiram, thiuram, zineb, ziram, captan, folpet, chlorothalonil, benfomesafen, tolylfluanid, docusazin, biguanide salts, biguanide octopamide acetate, biguanide octopamide dodecyl benzene sulfonate, dichlormid, dithianon, chlorku, dazomet, mancozeb, esteramide, silthiopham, agrobacterium, zofura, and the like.
Detailed Description
The present invention will be described in detail by examples. In the following examples, the various starting materials used were either commercially available or may be prepared using methods conventional in the art, unless specifically indicated. The following examples are not all of the present invention and other examples are within the scope of the present invention as would be understood by one of ordinary skill in the art without undue burden.
Example 1 (5-chloro-2-methoxy-4-methylpyridin-3-yl) (6- ((3-chloro-5- (trifluoromethyl) benzyl) oxy) pyridin-2-yl) methanone
(A) 2- (6-hydroxypyridin-2-yl) acetonitrile (134 mg,1 mmol), 1- (bromomethyl) -3-chloro-5- (trifluoromethyl) benzene (273.5 mg,1 mmol), silver carbonate (27.6 mg,1 mmol) were added to toluene (30 mL), the mixture was stirred at 60 ℃ overnight, filtered off, concentrated under reduced pressure, and separated by column chromatography (eluent: petroleum ether/ethyl acetate (v/v) =20/1) to give 2- (6- ((3-chloro-5- (trifluoromethyl) benzyl) oxy) pyridin-2-yl) acetonitrile as a yellow solid (13 mg).
(B) To a solution of 2- (6- ((3-chloro-5- (trifluoromethyl) benzyl) oxy) pyridin-2-yl) acetonitrile (65.34 mg,0.2 mmol) in anhydrous DMF (5 mL) under nitrogen was added potassium tert-butoxide (246.8 mg,2.2 mmol), after stirring for 30 min, 3-bromo-5-chloro-2-methoxy-4-methylpyridine (47.3 mg,0.2 mmol) was added and the reaction was quenched at room temperature overnight, quenched at low temperature, extracted with ethyl acetate (10 mL), dried over anhydrous magnesium sulfate to give 2- (5-chloro-2-methoxy-4-methylpyridin-3-yl) -2- (6- ((3-chloro-5- (trifluoromethyl) benzyl) oxy) pyridin-2-yl) acetonitrile as a yellow solid (21 mg).
(C) To the flask was added a solution of 2- (5-chloro-2-methoxy-4-methylpyridin-3-yl) -2- (6- ((3-chloro-5- (trifluoromethyl) benzyl) oxy) pyridin-2-yl) acetonitrile (1447 mg,3 mmol) and dimethyl sulfoxide (30 mL), followed by the addition of potassium carbonate (1.00 g,7.2 mmol) in water (2 mL), stirring overnight at room temperature, the mixture was added to ice water (100 mL), extracted with diethyl ether (30 mL), the organic phase was washed with water (20 mL), dried over anhydrous magnesium sulfate, filtered, the solvent was removed under reduced pressure, and the column chromatography was performed (eluent: dichloromethane/hexane (v/v) =20/1) to give a pale yellow solid (471 mg).
MS-ESI:m/z 471.1[M+H]+;
1H NMR(500MHz,CDCl3)δ8.11(t,J＝15.0Hz,1H),7.87(s,1H),7.62(t,J＝3.0Hz,1H),7.46(t,J＝2.9Hz,1H),7.35(dd,J＝15.0,3.1Hz,1H),7.13(t,J＝3.0Hz,1H),7.09(dd,J＝15.0,3.1Hz,1H),5.21(s,2H),4.17(s,3H),2.43(s,3H).
Example 2 (5-chloro-2-methoxy-4-methylpyridin-3-yl) (6- ((3, 5-dichlorobenzyl) oxy) pyridin-2-yl) methanone
The preparation method of reference example 1 was except that 1- (bromomethyl) -3-chloro-5- (trifluoromethyl) benzene was replaced with 1- (bromomethyl) -3, 5-dichlorobenzene to give 2- (6- ((3, 5-dichlorobenzyl) oxy) pyridin-2-yl) acetonitrile, and thus the compound of example 2 was obtained as a yellow solid.
MS-ESI:m/z 437.1[M+H]+;
1H NMR(500MHz,CDCl3)δ8.06(t,J＝15.0Hz,1H),7.75(s,1H),7.56(t,J＝3.0Hz,1H),7.34(d,J＝3.0Hz,2H),7.28(dd,J＝15.0,3.1Hz,1H),7.04(dd,J＝15.0,3.1Hz,1H),5.20(s,2H),4.18(s,3H),2.45(s,3H).
Example 3 (6- ((3-bromo-6-methoxy-2-methylbenzyl) oxy) pyridin-2-yl) (5-chloro-2-methoxy-4-methylpyridin-3-yl) methanone
The preparation method of example 1 was referred to, except that 1- (bromomethyl) -3-chloro-5- (trifluoromethyl) benzene was replaced with 1-bromo-3- (bromomethyl) -4-methoxy-2-methylbenzene to give 2- (6- ((3-bromo-6-methoxy-2-methylbenzyl) oxy) pyridin-2-yl) acetonitrile, and the compound of example 3 was obtained as a yellow solid.
MS-ESI:m/z 491.1[M+H]+;
1H NMR(500MHz,CDCl3)δ8.03(t,J＝15.0Hz,1H),7.69(s,1H),7.47(d,J＝15.0Hz,1H),7.30(dd,J＝15.0,3.1Hz,1H),7.23(d,J＝14.8Hz,1H),7.04(dd,J＝15.0,3.1Hz,1H),5.16(s,2H),4.21(s,3H),3.72(s,3H),2.52(s,3H),2.45(s,3H).
Example 4 (5-chloro-2-methoxy-4-methylpyridin-3-yl) (6- ((2, 3,5, 6-tetrafluoro-4-methoxybenzyl) oxy) pyridin-2-yl) methanone
The preparation method of example 1 was referred to, except that 1- (bromomethyl) -3-chloro-5- (trifluoromethyl) benzene was replaced with 1- (bromomethyl) -2,3,5, 6-tetrafluoro-4-methoxybenzene to obtain 2- (6- ((2, 3,5, 6-tetrafluoro-4-methoxybenzyl) oxy) pyridin-2-yl) acetonitrile, and then the compound of example 4 was obtained as a yellow solid.
MS-ESI:m/z 471.1[M+H]+;
1H NMR(500MHz,CDCl3)δ8.05(t,J＝15.0Hz,1H),7.77(s,1H),7.30(dd,J＝15.0,3.1Hz,1H),7.04(dd,J＝15.0,3.1Hz,1H),5.17(s,2H),4.23(s,3H),3.92(s,3H),2.47(s,3H).
Test of bactericidal Activity
The compounds of examples 1-4 of the present invention were dissolved in DMF to 1% EC for use. The compounds of examples 1 to 4 of the present invention were evaluated for their bactericidal activity against powdery mildew (Sphaerotheca fuliginea) and Botrytis cinerea (Botrytis cinerea) at 500ppm by the living potting method.
The test method of the powdery mildew of cucumber comprises the steps of selecting a cucumber seedling with a true leaf period and consistent growth vigor, and drying in the shade for 24 hours after spray treatment. Washing fresh spores on the leaves of the cucumber grown with powdery mildew, filtering with double-layer gauze, preparing a suspension with the spore concentration of about 10 ten thousand/ml, and spraying and inoculating. The inoculated test material is moved into a climatic chamber, the relative humidity is kept between 60 and 70 percent, the temperature is kept between 21 and 23 ℃, and the grading investigation is carried out according to the disease condition of blank control for about 10 days, and the control effect is calculated according to the disease index.
Grading standard:
Grade 0, no disease;
Stage 1, the area of the disease spots accounts for less than 5% of the area of the whole leaf;
Stage 3, the area of the disease spots accounts for 5-15% of the area of the whole leaf;
stage 5, the area of the disease spots accounts for 15-25% of the area of the whole leaf;
Stage 7, the area of the disease spots accounts for 25-50% of the area of the whole leaf;
stage 9, the area of the disease spots accounts for 50-75% of the area of the whole leaf;
grade 11, the area of the disease spots accounts for more than 75% of the area of the whole leaf.
The calculation method comprises the following steps:
the test method of the botrytis cinerea comprises the steps of adopting a leaf inoculation method, selecting two pot cucumber seedlings with the same growth vigor in Zhang Zhenshe periods, and inoculating fungus cakes on the leaves after the pesticide is sprayed and dried. And after 24-26 ℃ in dark light for moisturizing for 24 hours, natural light moisturizing culture is restored for about 3 days. After the control was sufficiently sick, the spot diameter (mm) of each inoculation point was measured with a caliper, and the control effect was calculated.
The calculation method comprises the following steps:
Control effect = [ (control plaque diameter-treatment plaque diameter)/control plaque diameter ] ×100% of
The test results show that the bactericidal activity of the compounds in examples 1-4 of the invention is 100%, 95%, 90% and 100% for powdery mildew of cucumber at 500ppm and 85%, 80% and 90% for gray mildew of cucumber at 500ppm, respectively. And in the use process of the compound, no phytotoxicity is generated to crops. The compound has great popularization value.
The present invention is not limited to the above-mentioned embodiments, and any changes or substitutions that can be easily understood by those skilled in the art within the technical scope of the present invention are intended to be included in the scope of the present invention.
Claims (9)
1. A compound having the formula (I) or an agropharmaceutically acceptable salt thereof:
Wherein:
R 1、R2、R3、R4 and R 5 are each independently hydrogen, halogen, C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy;
x is halogen;
Y is C 1-6 alkyl or halogenated C 1-6 alkyl;
z is C 1-6 alkoxy or halogenated C 1-6 alkoxy.
2. A compound according to claim 1, wherein:
R 1、R2、R3、R4 and R 5 are each independently hydrogen, halogen, C 1-4 alkyl, halogenated C 1-4 alkyl, C 1-4 alkoxy, halogenated C 1-4 alkoxy.
3. The compound according to claim 2, wherein:
r 1、R2、R3、R4 and R 5 are each independently hydrogen, fluorine, chlorine, bromine, methyl, trifluoromethyl, methoxy, trifluoromethoxy, ethoxy, n-propoxy, isopropoxy.
4. A compound according to claim 3, wherein:
r 1 is hydrogen, fluorine or methyl;
R 2 is fluorine, chlorine or bromine;
R 3 is hydrogen or methoxy;
r 4 is hydrogen, fluorine, chlorine or trifluoromethyl;
R 5 is hydrogen, fluorine or methoxy.
5. A compound according to claim 1, wherein:
x is halogen;
Y is C 1-4 alkyl or halogenated C 1-4 alkyl;
Z is C 1-4 alkoxy or halogenated C 1-4 alkoxy.
6. A compound according to claim 5, wherein:
x is chlorine or bromine;
y is methyl;
z is methoxy.
7. The compound according to any one of claims 1-6, wherein the compound of formula (I) is selected from the following compounds or an agropharmaceutically acceptable salt thereof:
Or alternatively
8. A pesticidal composition comprising the compound of any one of claims 1 to 7 or an agropharmaceutically acceptable salt thereof, further optionally comprising an agropharmaceutically acceptable adjuvant, the pesticidal composition being a fungicidal composition.
9. Use of a compound according to any one of claims 1 to 7 or a pesticidal composition according to claim 8 for the preparation of a fungicide, wherein the fungicide is for the control of powdery mildew and/or botrytis cinerea in cucumbers.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04187675A (en) * | 1990-11-22 | 1992-07-06 | Hokko Chem Ind Co Ltd | 2-acylpyridine derivative |
| CN1440389A (en) * | 2000-07-05 | 2003-09-03 | 石原产业株式会社 | Benzoylpyridine derivative or salt thereof, fungicide containing it as an active ingredient, method for its production, and intermediate for production thereof |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04187675A (en) * | 1990-11-22 | 1992-07-06 | Hokko Chem Ind Co Ltd | 2-acylpyridine derivative |
| CN1440389A (en) * | 2000-07-05 | 2003-09-03 | 石原产业株式会社 | Benzoylpyridine derivative or salt thereof, fungicide containing it as an active ingredient, method for its production, and intermediate for production thereof |
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