CN103664795A - Pyridazine ketone compound and use thereof - Google Patents

Pyridazine ketone compound and use thereof Download PDF

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CN103664795A
CN103664795A CN201210328143.6A CN201210328143A CN103664795A CN 103664795 A CN103664795 A CN 103664795A CN 201210328143 A CN201210328143 A CN 201210328143A CN 103664795 A CN103664795 A CN 103664795A
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compound
alkyl
alkoxyl group
cucumber
plant
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CN103664795B (en
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徐玉芳
赵振江
朱维平
韩景龙
李洪林
曹贤文
李宝聚
石延霞
钱旭红
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East China University of Science and Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
    • C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
    • C07D237/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/58—1,2-Diazines; Hydrogenated 1,2-diazines

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  • Agronomy & Crop Science (AREA)
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Abstract

The invention relates to a pyridazine ketone compound in a formula I and application thereof as a plant resistance activator. In a formula, R1-R5 are independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, halogen, halogenated C1-C6 alkyl, halogenated C1-C6 alkoxy, nitro, amino, CN, NCO, NCS, carboxyl, C1-C3 alkoxy formyl, and C1-C3 acylamino; X is selected from oxygen, sulphur and nitrogen; R6 is H, optionally substituted C1-C3 alkyl, optionally substituted phenyl substituent and 5-10-membered heteroaryl; R7 is selected from H, substituted C1-C3 alkyl, and optionally substituted phenyl.

Description

Pyridazinone compound and uses thereof
Technical field
The present invention relates to a kind of pyridazinone compound and uses thereof.
Background technology
Agricultural chemicals (Pesticides) mainly refers to for preventing the various diseases (insect, evil mite, nematode, pathogenic bacteria, weeds and muroid) of agriculture forest and husbandry in producing and the chemicals of coordinate plant growth.Before the eighties, " killing " of being mainly used in pest of agricultural chemicals, but since the eighties, the concept of agricultural chemicals has a very large change.Today, we do not focus on " killing ", but more pay attention to regulate.Therefore, the aim of modern agricultural chemicals is to insect pest germ high-efficiency prevention and control, to non-target organism and environmental safety.China Shi Yige large agricultural country, after liberation, China's pesticide industry is flourish, and pesticide species and output are doubled and redoubled, and China's agricultural chemicals output can meet agriculture needs, and has the outlet of some amount, but kind is still not enough.China is used pesticide preparation to reach 65 ~ 700,000 tons every year, and effective constituent amount reaches 22 ~ 250,000 tons.Really can prevent harmful organism seldom, approximately have more than 90% agricultural chemicals to be dissipated in contaminate environment in farmland, particularly highly toxic pesticide contaminate environment is more serious.
Agricultural chemicals has had the history of very long development in about 150 years in the world, 70, the eighties, the scientific research of chemical pesticide, exploitation and produce unprecedentedly active, efficiently, the agricultural chemicals novel type of low toxicity, mechanism of action novelty, as pyrethroid, pyrazoles, pyridines, nicotinoids, pyroles, process for preparation of benzoylurea compounds; Amino formate, beta-methoxy acrylic ester, benzimidazoles, triazole bactericidal agent; Imidazolone type, sulfonylurea herbicide etc. emerge in an endless stream, the motorway that impels chemical pesticide to step into develop rapidly.Yet the negative impact that the extensive use of traditional agricultural chemicals brings to environment and cause pathogenic micro-organism and the resistance of insect is had a greatly reduced quality its application power, if few, with agricultural chemicals, harmful organism can not effectively preventing, usually cause the agriculture underproduction, directly have influence on the development of national economy, the agricultural chemicals of 21 century progressively develops to the new ideas of biological regulation.
Since Chester K. in 1933 delivers about " the acquisition physiologic immunity of plant " literary composition first, more existing authors summarize it.Wherein the system about tobacco obtains disease resistance most study, to it, antiviral, antimycotic and resistance to bacteria has all carried out systematic study to different researchers, as Resistance In Tobacco tobacco mosaic virus (TMV) (TMV), anti-eye spot (Cercospora nicotianae), anti-balck shank (Phytophthora parasitica), downy mildew resistance (Peronospora tabacina), antibacterium wildfire (Pseudomonas syrtngae pv.tabaci) etc., and find pathogenesis-related proteins and system to obtain disease resistence gene proteins encoded.Eighties of last century beginning of the sixties, Ross research tobacco mosaic virus (TMV) has proposed systemic acquired resistance in plant (systemic acguired resistance, SAR), after the induction bacterium of necrotic type pathogen or screening is infected or the induction of some chemicals processes, what some plant can be to pathogen subsequently infects generation resistance.And these biological and chemical agents that can inducing plant produce SAR are just called plant disease resistance inductor or activator.
Plant activator (elicitor or plant activiator) refers to that compound itself and metabolite thereof are without direct fungicidal activity, but immunity system that can stimulating plant and plant generation system obtains the material of disease-resistant performance.This resistance has four characteristics, that is: systematicness, and SAR shows the non-inducible factor treatment sites of plant; Persistence, rear sustainable several weeks of SAR generation are some months even; Broad spectrum, SAR produces restraining effect to disease due to some fungies, bacterium, germ simultaneously; Security, these inductors itself do not produce toxic action to germ, but inducing plant body produces resistance, therefore environment is not had side effects.Therefore, the research and development of this series bactericidal agent have broad application prospects.
Pyridazine compound is the heterogeneous ring compound that a class has efficient weeding, Insecticiding-miticiding, plant growth regulating isoreactivity, and many kinds also have the feature of low toxicity, low residue.At present, pyridazine class derivative has become the important heteroaromatic compound of a class, and pyridazinone compound is a class of outbalance in pyridazine derivatives.1949, Schoene and Hoffmann reported first 4-hydroxyl pyridazinone had the characteristic of strongly inhibited plant cell division, and are applied in agriculture production as plant-growth regulator.Pyridazinone agricultural chemicals has the active feature such as high, environmentally friendly, aspect integrated pest control and reduction agricultural chemicals environmental pollution, playing an important role, it is one of focus of in recent years studying both at home and abroad, it has good biological activity, has become the heterogeneous ring compound of a class great exploitation potential for its and researching value.At present, existing many business-like pyridazinone agricultural chemicals, comprise plant-growth regulator, weedicide, sterilant, desinsection (killing mite) agent, insect growth regulator(IGR) etc.
The research of Systemic Acquired Resistance In Plants is started late in China, clone and the application of conduction mechanism, Mechanism of Physiological and Biochemical and relevant disease-resistant gene that mainly concentrates on disease-resistant signal about the research contents of plant inducing anti-disease mechanism of action is upper, and the development of the disease-resistant activator of new plant is slower.Only have so far the Plant activator of minority successfully to be developed, the more successful Plant activator of commercialization such as NCI, BTH, TDL wherein, can to bacterium, fungi and virus etc., produce the resistance (MichikoYasuda. of wide spectrum by inducing plant, J.Pestic.Sci.2004,29:46-49).
Given this, the exploitation of Plant activator is causing widely and is paying close attention to initiative.
Summary of the invention
The medicinal design of inventor's integrated use computer, pharmaceutical chemistry and molecular biology method and technology, a series of pyridazinone compounds have been designed and synthesized, it is compound shown in formula I, and these compounds produce disease-resistant activity and measuring method thereof at the biological activity and the inducing plant that suppress agricultural and gardening and forestry pathogenic fungi, provide the application of these compounds in agriculture field and gardening field and field of forestry simultaneously.
Pyridazinone compound of the present invention is compound shown in formula I:
Figure BDA00002106780100031
In formula I, R 1～R 5independently be selected from respectively: hydrogen, C1-C6 alkyl, C1-C6 alkoxyl group, halogen, halo C1-C6 alkyl, halo C1-C6 alkoxyl group, nitro, amino, CN, NCO, NCS, carboxyl, C1-C3 (alkoxymethyl)-2 acyl group, C1-C3 amide group; X is selected from oxygen, sulphur and nitrogen; R 6for H, the optional C1-C3 alkyl replacing and the optional phenyl replacing replace, 5-10 unit heteroaryl; R 7c1-C3 alkyl and the optional phenyl replacing for optional H, replacement.
In a specific embodiment, R 1and R 5independent is separately H, halogen, halo C1-C6 alkyl and halo C1-C6 alkoxyl group.
In a specific embodiment, R 3and R 4independent is separately H, halogen, halo C1-C6 alkyl and halo C1-C6 alkoxyl group.
In a specific embodiment, R 3be selected from H, halogen, C1-C6 alkoxyl group, halo C1-C6 alkyl, nitro, halo C1-C6 alkoxyl group and C1-C6 alkyl.
In a specific embodiment, R 6for H.
In a specific embodiment, R 7for H or C1-C6 alkyl.
In a specific embodiment, X is O.
In a specific embodiment, R 1, R 2, R 4, R 5and R 6for H, R 3be selected from H, halogen, C1-C6 alkoxyl group, halo C1-C6 alkyl, nitro, halo C1-C6 alkoxyl group and C1-C6 alkyl, X is O.
In a specific embodiment, R 1, R 3, R 5and R 6for H, R 2and R 4be selected from H, halogen and C 1-C6 alkoxyl group, X is O.
In a specific embodiment, the structure of the compound of general formula I is as shown in general formula I I:
Figure BDA00002106780100041
In formula, R 1-R 5independent certainly preferred respectively: hydrogen, C1-C6 alkoxyl group, halogen, nitro and halo C1-C6 alkoxyl group.
In a specific embodiment, the structure of the compound of general formula I is as shown in general formula I I:
Figure BDA00002106780100042
In formula, R 1-R 5independent certainly preferred respectively: hydrogen, C1-C6 alkoxyl group, halogen, nitro and halo C1-C6 alkoxyl group.
The invention still further relates to compound of Formula I as the application of Plant activator.
In one embodiment, the present invention relates to compound of Formula I and the upper acceptable carrier of agricultural or the purposes of auxiliary agent in preparing Plant activator, anti-plant virus agent, sterilant, sterilant, plant-growth regulator and weedicide.
In one embodiment, compound of Formula I of the present invention can suppress pathogenic fungi inducing plant anti-disease activity.The plant that available compound of Formula I of the present invention is prevented and treated comprises various agricultural plantss, gardening plant and forestry plant, includes but not limited to cucumber, tomato, paddy rice etc.
In one embodiment, the Plant diseases that available compound of Formula I of the present invention is prevented and treated includes but not limited to the climing rot of cucumber, Cucumber Target Leaf Spot, cucumber bacterial angular leaf spot, tomato late blight, rice sheath blight disease, gray mold of cucumber and cucumber fusarium axysporum etc.
In one embodiment, the Plant diseases that available compound of Formula I of the present invention is prevented and treated is tomato late blight, Cucumber Target Leaf Spot, the climing rot of cucumber and rice sheath blight disease.
In one embodiment, available compound of Formula I control of the present invention is by muskmelon ball chamber bacterium (Mycosphaerella melonis), the withered bacterium of stem (Corynespora cassiicola), pseudomonas syringae angular leaf spot of cucumber pathotype (Pseudomonas syringae pv.Lachrymans), phytophthora infestans (Phytophthora infestans (Mont.) De Bary), thanatephorus cucumeris(frank) donk (Thanatephorus cucumeris (Frank) Donk.), the germ Plant diseasess such as Botrytis cinerea (Botrytis cinerea Pers.ex Fr.) and sharp Fusariumsp cucumber specialized form (Fusarium oxysporum (Schl.) F.sp cucumerinum Owen).
The invention still further relates to the preparation of compound of Formula I.Particularly, preparation method of the present invention comprises: the substituted aniline (compound shown in formula A) of take is starting raw material, add hydrochloric acid and Sodium Nitrite to generate diazonium salt, then the diazonium salt of generation is added drop-wise to 1, in the aqueous ethanolic solution of 3-dimethyl acetone-1,3-dicarboxylate and sodium acetate, room temperature reaction (for example 20min), obtains intermediate phenylhydrazone (compound shown in formula B).Intermediate B is heating reflux reaction (for example about 2h) in orthodichlorobenzene, obtains Compound I I; Intermediate B is for example dissolved in, in aqueous sodium hydroxide solution (aqueous sodium hydroxide solution of 2M), drips concentrated hydrochloric acid and separates out solid, obtains compound III.
Figure BDA00002106780100051
In formula, R 1-R 5as mentioned before.
Embodiment
In the application, " alkyl " comprises side chain and straight chained alkyl, long 1-6 carbon atom, preferably 1-4 carbon atom, more preferably 1-3 the carbon atom of being generally.The example of alkyl includes but not limited to methyl, ethyl, propyl group, butyl, the tertiary butyl, isobutyl-etc.
" alkoxyl group " refers to " alkyl-O-" group, and wherein, alkyl can be C1-C6 straight or branched alkyl, preferably C1-C4 straight or branched alkyl.
In the present invention, the alkyl in alkyl or alkoxyl group is optionally by replacements such as halogen, hydroxyls.The example of haloalkyl or halogenated alkoxy includes but not limited to the C1-C6 alkyl or the C1-C6 alkoxyl group that by one or several F, Cl and/or Br, are replaced, and object lesson is as trifluoromethyl ,-O-CF 3deng.
" aryl " refers to the monocycle, dicyclo or the three ring aromatic groups that contain 6 to 14 carbon atoms, comprises phenyl, naphthyl, phenanthryl, anthryl, indenyl, Fluorene base, tetrahydro naphthyl, indanyl etc.
Aryl optionally for example, is selected from following substituting group by 1-5 (, 1,2,3,4 or 5) and replaces: halogen, C 1-4aldehyde radical, C 1-6alkoxyl group (for example trifluoromethoxy), carboxyl, C that the alkyl (for example trifluoromethyl) that straight or branched alkyl, cyano group, nitro, amino, hydroxyl, methylol, halogen replace, halogen replace 1-4alkoxyl group, ethoxycarbonyl, N (CH 3) and C 1-4acyl group.
For example, aryl can be selected from following group by 1-5 and replace: halogen ,-OH, C 1-4alkoxyl group, C 1-4alkyl chain ,-NO 2,-NH 2,-N (CH 3) 2, carboxyl, and ethoxycarbonyl etc.
" heteroaryl " used herein is in finger ring, to contain 5-10 atom, and has 6, and 10 or 14 electronics share in member ring systems.And contained annular atoms be carbon atom and from oxygen, nitrogen, sulphur optional 1-3 heteroatoms.
Useful heteroaryl comprises thienyl, furyl, pyranyl, pyrryl, imidazolyl, pyrazolyl, pyridyl, includes, but are not limited to 2-pyridyl, 3-pyridyl and 4-pyridyl, pyrazinyl, pyrimidyl etc.
Heteroaryl optionally for example, is selected from following substituting group by 1-5 (, 1,2,3,4 or 5) and replaces: halogen, C 1-4aldehyde radical, C 1-6alkoxyl group (for example trifluoromethoxy), carboxyl, C that the alkyl (for example trifluoromethyl) that straight or branched alkyl, cyano group, nitro, amino, hydroxyl, methylol, halogen replace, halogen replace 1-4alkoxyl group, ethoxycarbonyl, N (CH 3) and C 1-4acyl group.Optionally, except containing fluoro substituents, on aryl, can also contain other substituting group mentioned above, for example Cl, Br ,-OH, C 1-4alkoxyl group, C 1-4alkyl chain ,-NO 2,-NH 2,-N (CH 3) 2, carboxyl, and ethoxycarbonyl etc.
The present invention also comprises the pesticide composition that contains compound of the present invention.
In one embodiment, pesticide composition of the present invention also contains acceptable carrier in Pesticide Science.With acceptable carrier in Pesticide Science.
Described composition can contain by weight 0.01%～95% the formula I of the present invention as activeconstituents or the compound shown in II.
In described Pesticide Science, acceptable carrier comprises various solid carriers known in the art, liquid vehicle, carrier gas etc.Solid carrier can be that for example, clay material is as fine powder or the particle of kaolin, diatomite, synthetic hydrated silicon oxide, wilkinite, Fubasami clay and acid clay; All kinds of talcums, pottery and other inorganic materials are as the fine powder of sericite, quartz, sulphur, gac, calcium carbonate and hydrated SiO 2 or particle; And chemical fertilizer is as the fine powder of ammonium sulfate, ammonium phosphate, ammonium nitrate, urea and ammonium chloride or particle.
Liquid vehicle for example can comprise, water; Alcohols is as methyl alcohol and ethanol; Ketone is as acetone and methyl ethyl ketone; Hydro carbons is as hexane, hexanaphthene, kerosene and light oil; Ester class is as vinyl acetic monomer and N-BUTYL ACETATE; Nitrile is as acetonitrile and isopropyl cyanide; Ethers as Di Iso Propyl Ether with diox; Amides is as DMF and N,N-dimethylacetamide; Halohydrocarbon is as methylene dichloride, trichloroethane and tetracol phenixin; Dimethyl sulfoxide (DMSO); And vegetables oil is as soya-bean oil and Oleum Gossypii semen.
Carrier gas or propellent for example can comprise, Freon gas, butane gas, LPG (liquefied petroleum gas (LPG)), dme and carbonic acid gas.
In pesticide composition of the present invention, also can contain tensio-active agent, as alkyl-sulphate, alkylsulfonate, alkylaryl sulphonate, alkyl aryl ether and their polyethylene oxide derivant, polyglycol ether, polyol ester and sugar alcohol derivant.
Pesticide composition of the present invention can also contain auxiliary as fixing agent or dispersion agent, for example, casein, gelatin, polysaccharide (as starch, Sudan Gum-arabic, derivatived cellulose and Lalgine), lignin derivative, wilkinite, sugar and as synthetic polymers such as polyvinyl alcohol, polyvinylpyrrolidone and polyacrylic acid.
Pesticide composition of the present invention can also for example can comprise by stablizer, PAP (the acid phosphoric acid ester of sec.-propyl), BHT (2,6-, bis--tert-butyl-4-methylphenol), BHA (mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), vegetables oil, mineral oil, tensio-active agent, lipid acid and ester thereof.
Can be mixed with each other by the various components in pesticide composition of the present invention and prepare pesticide composition of the present invention.
So the pesticide composition of the present invention of preparation can directly use or dilute with water after use.In addition, it can use with other sterilant, nematocides, miticide, sterilant, mould inhibitor, weedicide, plant-growth regulator, synergistic agent, fertilizer, soil redeposition and/or animal-feed blending or not blending but simultaneously use.
Therefore, the present invention also comprises a kind of method of preventing and treating crop pest, and using method comprises such as spraying crop, grant the methods such as root of crop in soil.
When pesticide composition of the present invention is used for agricultural, can, according to comprising these conditions of preparation type, number of times, place and application process, pest species and degree of damage, set suitable amount of application and concentration.
The present invention is further elaborated by the following examples, and these embodiment are only for illustrating the present invention and understanding better content of the present invention, the protection domain that it does not limit the present invention in any way.
Embodiment 1
4-hydroxyl-6-oxo-1-(4-fluorophenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 1):
Figure BDA00002106780100081
Take 4-fluoroaniline (555mg, 0.5mmol) in 25mL single port eggplant-shape bottle, add 7.5mL4M aqueous hydrochloric acid, ice bath lower magnetic force stirs, and with constant pressure funnel, slowly drips sodium nitrite in aqueous solution (400mg Sodium Nitrite and 4mL water), drips and finishes, to reaction solution clarification, obtain reaction solution A.Get 870mg 1,3-dimethyl acetone-1,3-dicarboxylate and 3g sodium acetate, in 100mL eggplant-shape bottle, add 10mL water and 3mL ethanol, and room temperature magnetic agitation, obtains reaction solution B.Reaction solution A is slowly dropped in reaction solution B, have yellow mercury oxide to separate out, after 10min, react complete, suction filtration, washing, dry.Through silica gel column chromatography, (petrol ether/ethyl acetate=8/1, v/v) separation obtains orange/yellow solid 1.2g to crude product, productive rate 80%.
Take the above intermediate of 1.2g in 100mL eggplant-shape bottle, add the 22mL 2M NaOH aqueous solution, the clarification of question response liquid, slowly drips concentrated hydrochloric acid, regulates pH to 5, has Precipitation, suction filtration, and washing, dry.Crude product recrystallizing methanol, obtains 4-hydroxyl-6-oxo-1-(4-fluorophenyl)-1, the micro-yellow solid 750mg of 6-dihydrogen dazin-3-carboxylic acid, productive rate 75%.242 ~ 245 ° of C of fusing point. 1h NMR (400MHz, DMSO-d 6): δ 7.52 (dd, J 1=5.2Hz, J 2=8.8Hz, 2H), 7.27-7.32 (m, 2H), 5.76 (s, 1H) .HRMS (ESI) calculated value C 11h 7n 2o 4f[M+H] +251.0463, experimental value 251.0466.
Embodiment 2
4-hydroxyl-6-oxo-1-(4-fluorophenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylate methyl ester (Compound D 2):
Take 4-fluoroaniline (555mg, 0.5mmol) in 25mL single port eggplant-shape bottle, add 7.5mL4M aqueous hydrochloric acid, ice bath lower magnetic force stirs, and with constant pressure funnel, slowly drips sodium nitrite in aqueous solution (400mg Sodium Nitrite and 4mL water), drips and finishes, to reaction solution clarification, obtain reaction solution A.Get 870mg 1,3-dimethyl acetone-1,3-dicarboxylate and 3g sodium acetate, in 100mL eggplant-shape bottle, add 10mL water and 3mL ethanol, and room temperature magnetic agitation, obtains reaction solution B.Reaction solution A is slowly dropped in reaction solution B, have yellow mercury oxide to separate out, after 10min, react complete, suction filtration, washing, dry.Through silica gel column chromatography, (petrol ether/ethyl acetate=8/1, v/v) separation obtains orange/yellow solid 1.2g to crude product, productive rate 80%.
Take the above intermediate of 1.3g in 25mL eggplant-shape bottle, add 8mL orthodichlorobenzene, magnetic agitation, is heated to 180 ℃ of backflows, reacts 2 hours, and TLC tracks to raw material and transforms completely.Be down to room temperature, rotary evaporation, except desolventizing, obtains micro-yellow solid.Crude product is through silica gel column chromatography (petrol ether/ethyl acetate=1/1, v/v), separation obtains 4-hydroxyl-6-oxo-1-(4-fluorophenyl)-1,6-dihydrogen dazin-3-acid methyl esters white solid 92mg, productive rate 70%, 145 ~ 146 ° of C of fusing point. 1h NMR (400MHz, CDCl 3): δ 10.42 (s, 1H), 7.58 (dd, J 1=5.2Hz, J 2=8.8Hz, 2H), 7.17-7.22 (m, 2H), 6.41 (s, 1H), 4.05 (s, 3H) .HRMS (ESI) calculated value C 12h 9n 2o 4f[M+H] +265.0619, experimental value 265.0622.
Embodiment 3
4-hydroxyl-6-oxo-1-(4-p-methoxy-phenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (compound d3):
Outside para-fluoroaniline in P-nethoxyaniline alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains compound d3, yield 80%.Fusing point 232 ~ 234oC. 1h NMR (400MHz, DMSO-d 6): δ 7.41 (d, J=8.8Hz, 1H), 7.03 (d, J=8.8Hz, 1H), 6.18 (s, 1H), 3.81 (s, 3H) .HRMS (ESI) calculated value C 12h 7n 2o 5[M+H] +263.0662, experimental value 263.0666.
Embodiment 4
4-hydroxyl-6-oxo-1-(4-p-methoxy-phenyl)-1, the preparation of 6-dihydrogen dazin-3-acid methyl esters (Compound D 4):
Figure BDA00002106780100102
Outside para-fluoroaniline in P-nethoxyaniline alternative embodiment 2, other condition is identical with embodiment 2 with step, obtains Compound D 4), yield 67%, 184.1 ~ 184.5 ° of C of fusing point. 1h NMR (400MHz, CDCl 3): δ 10.40 (s, 1H), 7.50 (d, J=8.8Hz, 2H), 7.01 (d, J=8.8Hz, 2H), 6.40 (s, 1H), 4.04 (s, 3H), 3.87 (s, 3H) .HRMS (ESI) calculated value C 13h 12n 2o 5[M+H] +277.0819, experimental value 277.0822.
Embodiment 5
4-hydroxyl-6-oxo-1-phenyl-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 5):
Figure BDA00002106780100111
Outside para-fluoroaniline in aniline alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 5, yield 73%, 246.0 ~ 246.5 ° of C of fusing point. 1h NMR (400MHz, DMSO-d 6): δ 7.42-7.51 (m, 5H), 6.20 (s, 1H) .HRMS (ESI) calculated value C 11h 8n 2o 4[M+H] +233.0557, experimental value 233.0577.
Embodiment 6
4-hydroxyl-6-oxo-1-(4-chloro-phenyl-)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 6):
Figure BDA00002106780100112
Outside para-fluoroaniline in p-Chlorobenzoic acid amide alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 6, yield 80%, 248.1 ~ 248.5 ° of C of fusing point. 1h NMR (400MHz, DMSO-d 6): δ 7.57 (brs, 4H), 6.15 (s, 1H) .HRMS (ESI) calculated value C 11h 7n 2o 4cl[M+H] +267.0167, experimental value 267.0184.
Embodiment 7
4-hydroxyl-6-oxo-1-(3,5-dichlorophenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 7):
Outside para-fluoroaniline in 3,5-dichlorphenamide bulk powder alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 7, yield 74%, 263.4 ~ 263.6 ° of C of fusing point. 1h NMR (400MHz, DMSO-d 6): δ 7.71 (s, 1H), 7.7 (s, 2H), 6.14 (s, 1H) .HRMS (ESI) calculated value C 11h 6n 2o 4cl 2[M+H] +300.9777, experimental value 300.9778.
Embodiment 8
4-hydroxyl-6-oxo-1-(3,5-dichlorophenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylate methyl ester (Compound D 8):
Figure BDA00002106780100121
Outside para-fluoroaniline in 3,5-dichlorphenamide bulk powder alternative embodiment 2, other condition is identical with embodiment 2 with step, obtains Compound D 8, yield 71%. 1HNMR(400MHz,CDCl 3):δ10.45(s,1H),7.57(d,J=1.6Hz,2H),7.45(t,J=1.6Hz,1H),6.41(s,1H),4.08(s,3H)。
Embodiment 9
4-hydroxyl-6-oxo-1-(2,4 dichloro benzene base)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 9):
Figure BDA00002106780100122
Outside para-fluoroaniline in 2,4 dichloro aniline alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 9, yield 72%, 236 ~ 237 ° of C of fusing point. 1h NMR (400MHz, DMSO-d 6): δ 7.87(s, 1H), 7.61 (s, 2H), 6.13 (s, 1H) .HRMS (ESI) calculated value C 11h 6n 2o 4cl 2[M+H] +300.9777, experimental value 300.9773.
Embodiment 10
4-hydroxyl-6-oxo-1-(3,4-dichlorophenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 10):
Figure BDA00002106780100123
Outside para-fluoroaniline in 3,4-DCA alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 10, yield 77%, 268.1 ~ 268.3 ° of C of fusing point. 1h NMR (400MHz, DMSO-d 6): δ 7.89 (d, J=2.4Hz, 1H), 7.78 (d, J=8.8Hz, 1H), 7.59 (dd, J 1=2.4Hz, J 2=8.8Hz, 1H), 6.14 (s, 1H) .HRMS (ESI) calculated value C 11h 6n 2o 4cl 2[M+H] +300.9777, experimental value 300.9774.
Embodiment 11
4-hydroxyl-6-oxo-1-(3,4-dichlorophenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylate methyl ester (Compound D 11):
Outside para-fluoroaniline in 3,4-DCA alternative embodiment 2, other condition is identical with embodiment 2 with step, obtains Compound D 11, yield 81%, 179.1 ~ 179.3 ° of C of fusing point. 1h NMR (400MHz, CDCl 3): δ 10.41 (s, 1H), 7.76 (s, 1H), 7.57 (d, J=8.8Hz, 1H), 7.52 (d, J=8.8Hz, 1H), 6.39 (s, 1H) .HRMS (ESI) calculated value C 12h 8n 2o 4cl 2[M+H] +314.9934, experimental value 314.9940.
Embodiment 12
4-hydroxyl-6-oxo-1-(4-trifluoromethyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 12):
Figure BDA00002106780100132
Outside para-fluoroaniline in 4-5-trifluoromethylaniline alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 12, yield 71%, 255 ~ 256 ° of C of fusing point. 1h NMR (400MHz, DMSO-d 6): δ 7.88 (d, J=8.8Hz, 2H), 7.80 (d, J=8.8Hz, 2H), 6.16 (s, 1H) .HRMS (ESI) calculated value C 12h 7n 2o 4f 3[M+H] +301.0431, experimental value 301.0427.
Embodiment 13
4-hydroxyl-6-oxo-1-p-nitrophenyl-1, the preparation of 6-dihydrogen dazin-3-carboxylate methyl ester (Compound D 13):
Outside para-fluoroaniline in p-Nitroaniline alternative embodiment 2, other condition is identical with embodiment 2 with step, obtains Compound D 13, yield productive rate 72%, 200 ~ 212 ° of C of fusing point. 1h NMR (400MHz, CDCl 3): δ 10.47 (s, 1H), 8.38 (d, J=9.2Hz, 2H), 7.90 (d, J=9.2Hz, 2H), 6.44 (s, 1H), 4.08 (s, 3H) .HRMS (ESI) calculated value C 12h 9n 3o 6[M+H] +292.0564, experimental value 292.0564.
Embodiment 14
4-hydroxyl-6-oxo-1-(4-trifluoromethyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylate methyl ester (Compound D 14):
Figure BDA00002106780100142
Outside para-fluoroaniline in 4-5-trifluoromethylaniline alternative embodiment 2, other condition is identical with embodiment 2 with step, obtains Compound D 14, yield 69%. 1HNMR(400MHz,CDCl 3):δ7.57(dd,J 1=4.8Hz,J 2=8.8Hz,2H),7.19(m,2H),6.42(s,1H),4.05(s,3H)。
Embodiment 15
4-hydroxyl-6-oxo-1-is to bromophenyl-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 15):
Figure BDA00002106780100143
Outside para-fluoroaniline in 4-bromaniline alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 15, yield 83%. 1H?NMR(400MHz,DMSO-d 6):δ7.70(d,J=8.8Hz,2H),7.50(d,J=8.8Hz,2H),6.17(s,1H)。
Embodiment 16
4-hydroxyl-6-oxo-1-is to bromophenyl-1, the preparation of 6-dihydrogen dazin-3-carboxylate methyl ester (Compound D 16):
Figure BDA00002106780100151
Outside para-fluoroaniline in 4-bromaniline alternative embodiment 2, other condition is identical with embodiment 2 with step, obtains Compound D 16, yield 69%. 1HNMR(400MHz,CDCl 3):δ10.47(s,1H),8.38(d,J=9.2Hz,2H),7.90(d,J=9.2Hz,2H),6.44(s,1H),4.08(s,3H)。
Embodiment 17
4-hydroxyl-6-oxo-1-(3-trifluoromethyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 17):
Figure BDA00002106780100152
Outside para-fluoroaniline in 3-5-trifluoromethylaniline alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 17, yield 81%. 1H?NMR(400MHz,DMSO-d 6):δ7.95(s,1H),7.87(d,J=8.0Hz,1H),7.82(d,J=8.0Hz,1H),7.75(t,J=8.0Hz,1H),6.22(s,1H)。
Embodiment 18
4-hydroxyl-6-oxygen-1-(3-trifluoromethyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylate methyl ester (Compound D 18):
Figure BDA00002106780100161
Outside para-fluoroaniline in 3-5-trifluoromethylaniline alternative embodiment 2, other condition is identical with embodiment 2 with step, obtains Compound D 18, yield 71%. 1HNMR(400MHz,CDCl 3):δ10.47(s,1H),7.88(s,1H),7.85(d,J=8.0Hz,1H),7.72(d,J=7.6Hz,1H),7.62-7.67(m,1H),6.43(s,1H),4.08(s,3H)。
Embodiment 19
4-hydroxyl-6-oxo-1-(4-Trifluoromethoxyphen-l)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 19):
Figure BDA00002106780100162
Outside para-fluoroaniline in 4-trifluoro-methoxyaniline alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 19, yield 83%. 1H?NMR(400MHz,DMSO-d 6):δ7.67(d,J=8.8Hz,2H),7.51(d,J=8.8Hz,2H),6.17(s,1H)。
Embodiment 20
4-hydroxyl-6-oxo-1-(2-trifluoromethyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 20):
Figure BDA00002106780100163
Outside para-fluoroaniline in 2-5-trifluoromethylaniline alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 20, yield 85%. 1H?NMR(400MHz,DMSO-d 6):δ7.93(d,J=7.6Hz,1H),7.87(t,J=7.6Hz,1H),7.76(t,J=7.6Hz,1H),7.63(d,J=7.6Hz,1H),6.19(s,1H)。
Embodiment 21
4-hydroxyl-6-oxo-1-(3-p-methoxy-phenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 21):
Outside para-fluoroaniline in 3-anisidine alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 21, yield 82%. 1H?NMR(400MHz,DMSO-d 6):δ7.41(t,J=8.0Hz,1H),7.01-7.08(m,3H),6.17(s,1H),3.79(s,3H)。
Embodiment 22
4-hydroxyl-6-oxo-1-(2-p-methoxy-phenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 22):
Figure BDA00002106780100172
Outside para-fluoroaniline in 2-anisidine alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 22, yield 86%. 1H?NMR(400MHz,DMSO-d 6):δ7.46(t,J=7.6Hz,1H),7.30(d,J=7.6Hz,1H),7.20(d,J=7.6Hz,1H),7.07(t,J=7.6Hz,1H),6.14(s,1H),3.75(s,3H)。
Embodiment 23
4-hydroxyl-6-oxo-1-(2-p-methoxy-phenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylate methyl ester (Compound D 23):
Figure BDA00002106780100181
Outside para-fluoroaniline in 2-anisidine alternative embodiment 2, other condition is identical with embodiment 2 with step, obtains Compound D 23, yield 66%. 1HNMR(400MHz,CDCl 3):δ10.44(s,1H),7.46(t,J=7.6Hz,1H),7.31(d,J=7.6Hz,1H),7.05-7.11(m,2H),6.41(s,1H),4.02(s,3H),3.84(s,3H)。
Embodiment 24
4-hydroxyl-6-oxo-1-(3,5-Dimethoxyphenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 24):
Figure BDA00002106780100182
Outside para-fluoroaniline in 3,5-dimethoxyaniline alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 24, yield 77%. 1H?NMR(400MHz,DMSO-d 6):δ6.66(d,J=1.0Hz,2H),6.60(d,J=1.0Hz,1H),6.17(s,1H),3.78(s,6H)。
Embodiment 25
4-hydroxyl-6-oxo-1-(3,5-Dimethoxyphenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylate methyl ester (Compound D 25):
Figure BDA00002106780100183
Outside para-fluoroaniline in 3,5-dimethoxyaniline alternative embodiment 2, other condition is identical with embodiment 2 with step, obtains Compound D 25, yield 67%. 1HNMR(400MHz,CDCl 3):δ10.43(s,1H),6.69(d,J=2.4Hz,2H),6.54(d,J=2.4Hz,1H),6.40(s,1H),4.04(s,3H),3.83(s,6H)。
Embodiment 26
4-hydroxyl-6-oxo-1-(3,4-difluorophenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 26):
Figure BDA00002106780100191
Outside para-fluoroaniline in 3,4-difluoroaniline alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 26, yield 78%. 1H?NMR(400MHz,DMSO-d 6):δ7.39-7.46(m,3H),6.17(s,1H)。
Embodiment 27
4-hydroxyl-6-oxo-1-(the fluoro-4-aminomethyl phenyl of 3-)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (Compound D 27):
Figure BDA00002106780100192
Divided by 3-fluorine, to outside para-fluoroaniline in monomethylaniline alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 27, yield 77%. 1H?NMR(400MHz,DMSO-d 6):δ7.62(d,J=2.0Hz,1H),7.48(d,J=8.0Hz,1H),7.41(dd,J 1=2.0Hz,J 2=8.0Hz,1H),6.14(s,1H),2,39(s,3H)。
Embodiment 28
4-hydroxyl-6-oxo-1-(3-fluorophenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylate methyl ester (Compound D 28):
Figure BDA00002106780100201
Outside para-fluoroaniline in 3-fluoroaniline alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains Compound D 28, yield 79%. 1H?NMR(400MHz,DMSO-d 6):δ7.52-7.59(m,1H),7.46(d,J=2.0Hz,1H),7.40(d,J=8.0Hz,1H),7.31(dt,J 1=2.0Hz,J 2=8.0Hz,1H),6.16(s,1H)。
Embodiment 29
4-hydroxyl-6-oxo-1-(3-fluorophenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylate methyl ester (Compound D 29):
Figure BDA00002106780100202
Outside para-fluoroaniline in 4-5-trifluoromethylaniline alternative embodiment 2, other condition is identical with embodiment 2 with step, obtains Compound D 29, yield 66%. 1HNMR(400MHz,CDCl 3):δ10.43(s,1H),7.42-7.51(m,2H),7.36-7.39(m,1H),7.13-7.19(m,1H),6.41(s,1H),4.06(s,1H)。
Embodiment 30
4-hydroxyl-6-oxo-1-(2-fluorophenyl)-1, the preparation of 6-dihydrogen dazin-3-carboxylate methyl ester (compound d3 0):
Outside para-fluoroaniline in 2-fluoroaniline alternative embodiment 2, other condition is identical with embodiment 2 with step, obtains compound d3 0, yield 59%. 1HNMR(400MHz,CDCl 3):δ10.46(s,1H),7.42(m,2H),7.32(d,J=7.6Hz,1H),7.26(d,J=8.8Hz,1H),6.43(s,1H),4.05(s,1H)。
Embodiment 31
4-hydroxyl-6-oxo-1-(the fluoro-3-trifluoromethyl of 4-)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (compound d3 1):
Figure BDA00002106780100211
Outside para-fluoroaniline in the fluoro-3-5-trifluoromethylaniline of 4-alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains compound d3 1, yield 78%. 1H?NMR(400MHz,DMSO-d 6):δ7.65-8.02(m,3H),6.18(s,1H)。
Embodiment 32
4-hydroxyl-6-oxo-1-(the chloro-3-trifluoromethyl of 4-)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (compound d3 2):
Outside para-fluoroaniline in the chloro-3-5-trifluoromethylaniline of 4-alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains compound d3 2, yield 78%. 1H?NMR(400MHz,DMSO-d 6):δ8.09(d,J=2.0Hz,1H),7.87-7.93(m,2H),6.17(s,1H)。
Embodiment 33
4-hydroxyl-6-oxo-1-(the chloro-3-trifluoromethyl of 4-)-1, the preparation of 6-dihydrogen dazin-3-carboxylic acid (compound d3 3):
Figure BDA00002106780100221
Outside para-fluoroaniline in the bromo-3-5-trifluoromethylaniline of 4-alternative embodiment 1, other condition is identical with embodiment 1 with step, obtains compound d3 3, yield 81%. 1H?NMR(400MHz,DMSO-d 6):δ8.07(d,J=2.4Hz,1H),8.04(d,J=8.8Hz,1H),7.81(dd,J 1=2.4Hz,J 2=8.8Hz,1H),6.19(s,1H)。
Embodiment 34: active testing
Compound provided by the invention is the inhibition to germ as Plant activator:
1, experimental subjects: the climing rot of anti-yellowing melon, anti-Cucumber Target Leaf Spot, anti-cucumber bacterial angular leaf spot, anti-tomato late blight, rice sheath blight disease, gray mold of cucumber, cucumber fusarium axysporum.
2, test concentrations: this test all adopts 100mg/L test concentrations.
3, testing method: the good various crops of sowing in advance, and quantitatively take sample, and with DMF, dissolve and add proper amount of surfactant, be diluted with water to setting concentration.Adopt roll-back method inoculation first 7 days, 5 days, 3 days, 1 day, minute carry out drug treating four times, then disposablely inoculate pathogenic bacteria simultaneously.Experiment adopts pot-culture method to carry out, and repeats 3 times.The account form of disease index and protection effect is as follows: disease index=[∑ (the sick number of sheets * relative level numerical value at different levels) * 100]/(investigating the total number of sheets * highest level numerical value that represents of falling ill), prevention effect (%)=[(disease index-treatment zone, check plot disease index) * 100]/check plot disease index.
4, experimental result
The present invention is to 11 4-hydroxyl-6-oxo-1-phenyl-1, and 6-dihydrogen dazin-3-carboxylic acid derivative has adopted method mentioned above to test the inducing anti-disease activity of five kinds of diseases, shown in the following list 1 of compound test activity data in early stage:
Figure BDA00002106780100231
Preferred compound is active as shown in table 2 below to the live body of several germs and in vitro inhibition:
Note: on every row, column number is according to being isolated activity, and lower field live body is active.
Table 2
Figure BDA00002106780100241

Claims (10)

1. the compound shown in general formula:
Figure FDA00002106780000011
In formula,
R 1-R 5independently be selected from: hydrogen, C1-C6 alkyl, C1-C6 alkoxyl group, halogen, halo C1-C6 alkyl, halo C1-C6 alkoxyl group, nitro, amino, CN, NCO, NCS, carboxyl, C1-C3 (alkoxymethyl)-2 acyl group, C1-C3 amide group;
X is selected from oxygen, sulphur and nitrogen;
R 6for H, the optional C1-C3 alkyl replacing and the optional phenyl replacing replace, 5-10 unit heteroaryl; With
R 7c1-C3 alkyl and the optional phenyl replacing for optional H, replacement.
2. compound as claimed in claim 1, is characterized in that, described compound has the structure described in general formula I I or III:
Figure FDA00002106780000012
In formula, R 1-R 5independent certainly preferred: hydrogen, C1-C6 alkyl, C1-C6 alkoxyl group, halogen, nitro and halo C1-C6 alkoxyl group.
3. compound as claimed in claim 1 or 2, is characterized in that, R 1, R 2, R 4, R 5and R 6for H, R 3be selected from H, halogen, C1-C6 alkoxyl group, halo C1-C6 alkyl, nitro, halo C1-C6 alkoxyl group and C1-C6 alkyl, X is O.
4. compound as claimed in claim 1 or 2, is characterized in that, R 1, R 3, R 5and R 6for H, R 2and R 4be selected from H, halogen and C1-C6 alkoxyl group, X is O.
5. compound as claimed in claim 1 or 2, is characterized in that, described compound is selected from:
Figure FDA00002106780000021
Figure FDA00002106780000031
In claim 1-5 the compound described in any one as the application of anti-plant virus agent, sterilant, sterilant, plant-growth regulator or weedicide.
7. the application of the compound described in any one in claim 1-5, it is characterized in that, for preventing and treating by muskmelon ball chamber bacterium (Mycosphaerella melonis), the withered bacterium of stem (Corynespora cassiicola), pseudomonas syringae angular leaf spot of cucumber pathotype (Pseudomonas syringae pv.Lachrymans), phytophthora infestans (Phytophthora infestans (Mont.) De Bary), thanatephorus cucumeris(frank) donk (Thanatephorus cucumeris (Frank) Donk.), the germ Plant diseases of Botrytis cinerea (Botrytis cinerea Pers.ex Fr.) or sharp Fusariumsp cucumber specialized form (Fusarium oxysporum (Schl.) F.sp cucumerinum Owen).
8. application as claimed in claim 7, is characterized in that, described compound is used for preventing and treating the climing rot of cucumber, Cucumber Target Leaf Spot, cucumber bacterial angular leaf spot, tomato late blight, rice sheath blight disease, gray mold of cucumber or cucumber fusarium axysporum.
9. a pesticide composition, is characterized in that, described pesticide composition contains in claim 1-5 acceptable carrier on the compound described in any one and Pesticide Science.
10. a method for controlling plant diseases, is characterized in that, described method comprises: by the compound described in any one in claim 1-5 or pesticide composition claimed in claim 9, give described plant, thereby prevent and treat its disease.
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