CN106608873B - Pyrazol acid amide compounds and the preparation method and application thereof - Google Patents
Pyrazol acid amide compounds and the preparation method and application thereof Download PDFInfo
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- CN106608873B CN106608873B CN201510704893.2A CN201510704893A CN106608873B CN 106608873 B CN106608873 B CN 106608873B CN 201510704893 A CN201510704893 A CN 201510704893A CN 106608873 B CN106608873 B CN 106608873B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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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
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
- A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
Abstract
The invention discloses pyrazol acid amide compounds shown in formula (I) and the preparation method and application thereof.R, R in formula1、R2, W have specification given in define.Formula (I) compound of the present invention has sterilization, desinsection or mite killing bioactivity, especially has very high activity to pathogen such as Powdery Mildew, ash arrhizus bacteria and rust etc..
Description
Technical field
The invention belongs to kill insects mites, fungicide field, and in particular to have the pyrazole amide for killing insects mites, sterilizing bioactivity
Class compound and preparation method thereof kills insects mites, microbicide compositions and with these compound controls containing the compound
Make evil insects mites, the purposes of disinfect pathogen and method.
Background technique
Pyrazol acid amide compounds, which have, kills insects mites and bactericidal activity, and has acaricide-tebufenpyrad shown in D1
(tebufenpyrad) and shown in D2 insects mites agent-Tolfenpyrad (tolfenpyrad) etc. is killed to be desinsection, killed by successive exploitation
Mite agent.
Tebufenpyrad (EP289879) is used as Mitochondria In Developing Flight Muscle of Insects respiration inhibitor, has to the development full period of various mite class and mite
Quick-acting and efficient effect.Analog of the Tolfenpyrad (EP365925) as tebufenpyrad, activity profile is wider, it to Lepidoptera,
Semiptera, beetle mesh, Hymenoptera, Diptera and mite class are effective.
High efficiency, highly selective, high Environmental compatibility and economy are the characteristics of modern should have.To be lived
Property spectrum is wider, activity is higher and/or more economical pyrazol acid amide compounds, the minor structures such as thiazole introduce pyrazoles acyl by inventor
In amine structure, a series of pyrroles for having no document report and there are the broad spectrum of activity such as excellent insecticidal/mite and/or sterilization are designed and synthesized
Azoles amides compound.Compared with D1 and D2, the compounds of this invention has more wide spectrum and efficient bioactivity, such as compound 7
It is far superior to D2 Deng the bactericidal activity to powdery mildew, gray mold etc., can be mutually equal to commercialization fungicide Fluoxastrobin, Boscalid
Beauty；Compound 10 then has and the comparable insecticidal activity of D2.
Summary of the invention
The present invention provides have the pyrazol acid amide for murdering the bioactivity such as insects mites, disinfect pathogen shown in formula (I)
Close object:
Wherein:
R represents C1-C12Alkyl, C2-C12Alkenyl, C2-C12Alkynyl group, C3-C8Naphthenic base or phenyl；
R1Represent C1-C12Alkyl, C2-C12Alkenyl, C2-C12Alkynyl group, C3-C8Naphthenic base or phenyl；
R2Represent hydrogen, halogen, C1-C12Alkyl, C2-C12Alkenyl, C2-C12Alkynyl group or C3-C8Naphthenic base；
R、R1And R2Some or all of middle hydrogen atom can be replaced by identical or different substituent group in following: halogen
Element, C1-C6Alkyl, C1-C6Alkoxy, C1-C6Alkylthio group, C1-C6Alkyl amine group, C2-C6Alkenyl, C2-C6Alkenyl oxy,
C2-C6Alkenyl thio, C2-C6Alkenyl amido, C2-C6Alkynyl group, C2-C6Alkynyl group oxygroup, C2-C6Alkynyl group sulfenyl, C2-C6
Alkynyl group amido, C3-C8Naphthenic base, C3-C8Cycloalkyl oxy, C3-C8Cycloalkylsulfanyl, C3-C8Naphthenic base amido, C6-C12Aryl
Or heteroaryl, the C of up to 10 carbon atoms of band6-C12The heteroaryl oxygroup of up to 10 carbon atoms of aryloxy or band, C6-C12
Heteroarylthio, the C of up to 10 carbon atoms of artyl sulfo or band6-C12The heteroaryl of up to 10 carbon atoms of arylamine group or band
Base amido, C6-C12Heteroarylaryl, the C of up to 10 carbon atoms of aryl or band6-C12Aryl heteroaryl or band up to 10
The heteroarylheteroaryl of a carbon atom；
R1And R2It can be connected to each other, form C with two carbon of pyrazole ring4-C8Cycloalkane structure；
W represents oxygen or sulphur；
And R=R1=CH3, when W=O, R2Do not represent H；
In the definition of compound (I) given above, no matter term used exclusive use is also used in compound word, represent
Following substituent group:
Halogen: refer to fluorine, chlorine, bromine, iodine；
Alkyl: refer to linear or branched alkyl group；
Halogenated alkyl: referring to linear or branched alkyl group, hydrogen moiety on these alkyl or is all replaced by halogen atom；
Naphthenic base: refer to saturation or unsaturated ring alkyl；
Heterocyclylalkyl: refer to saturation or unsaturated heterocycle alkyl, at least 1 N, O and/or S in formula；
Halogenated cycloalkyl: referring to saturation or unsaturated ring alkyl, and hydrogen moiety therein or is all replaced by halogen atom；
Alkenyl；Refer to linear or branched alkyl group, and can in any position on there are double bonds；
Halogenated alkenyl: referring to linear or branched alkyl group, and can in any position on there are double bond, and hydrogen atom therein
Partly or entirely replaced by halogen atom；
Alkynyl group；Refer to linear or branched alkyl group, and can in any position on there are three keys；
Halo alkynyl: referring to linear or branched alkyl group, and can in any position on there are three keys, and hydrogen atom portion therein
Divide or is all replaced by halogen atom；
C6-C12Aryl means phenyl and by its derivative ring aryl phenyl or polyaromatic naphthalene, xenyl, anthryl,
Phenanthryl；
The heteroaryl of up to 10 carbon atoms of band refers to a ring heteroaryl or polyheteroaromatic, at least 1 N in formula, O and/
Or S, such as thiazolyl, pyrazolyl, thiadiazolyl group, pyridyl group, thienyl, benzothienyl, furyl, benzofuranyl, pyrroles
Base, benzopyrrole base, indyl, benzindole base, imidazole radicals, benzimidazolyl, quinolyl, pyranose, pyrazinyl, pyrimidine
Base, pyridazinyl, benzopyranyl, benzopyrazines base, benzo pyrimidine radicals, benzo pyridazinyl, oxazolyl, isoxazolyl, benzo are disliked
Oxazolyl, benzo isoxazolyl, benzothiazolyl, isothiazolyl, benzisothia oxazolyl, pyrimido triazolyl.
Currently preferred compound is compound shown in formula (I), in which: R represents C1-C12Alkyl or phenyl；R1It represents
C1-C12Alkyl；R2Represent hydrogen, halogen or C1-C12Alkyl；And R, R1And R2Some or all of middle hydrogen atom can be selected from down
Identical or different substituent group replaces in column: halogen, C1-C6Alkyl, C1-C6Alkoxy；R1And R2It can be connected to each other, with pyrazoles
Two carbon of ring form C5-C6Cycloalkane structure；W represents oxygen or sulphur.
The further preferred compound of the present invention is compound shown in formula (I), in which: R represents C1-C6Alkyl；R1It represents
C1-C6Alkyl；R2Represent hydrogen, halogen, C1-C6Alkyl；And R, R1And R2Some or all of middle hydrogen atom can be by selected from following
In identical or different substituent group replace: halogen, C1-C3Alkyl, C1-C3Alkoxy；W represents oxygen.
Compound specifically preferred according to the invention is compound shown in formula (I), in which: R represents methyl or ethyl；R1Represent C1-
C6Alkyl；R2Represent hydrogen, halogen, C1-C3Alkyl；And R, R1And R2Some or all of middle hydrogen atom can be by selected from following middle phase
Same or different substituent group replaces: halogen, methyl, ethyl, methoxyl group；W represents oxygen.
Specifically preferred formula (I) compound is following compounds to the present invention:
1,3,4- trimethyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (4)；
The chloro- 1,3- dimethyl-N-of 4- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (6)；
3- ethyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (7)；
3- ethyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- carbothioic acid amide (8)；
3- ethyl -1,4- dimethyl-N-[(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (9)；
The chloro- 3- ethyl -1- methyl-N- of 4- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (10)；
The bromo- 3- ethyl -1- methyl-N- of 4- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (11)；
1- methyl -3- propyl -- N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (12)；
3- isopropyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (13)；
3- cyclopropyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (14)；
3- butyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (20)；
2- methyl-N- [(2- phenyl thiazole -4- base) methyl] -2,4,5,6- tetrahydro cyclopentyl alkane simultaneously [c] pyrazoles -3- formic acid acyl
Amine (23)；
2- methyl-N- [(2- phenyl thiazole -4- base) methyl] -4,5,6,7- tetrahydro -2H- Yin rattles away azoles -3- benzoic acid amides
(24)
1- ethyl -3- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (25)；
The chloro- 1- ethyl -3- methyl-N- of 4- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (27)；
The chloro- 1,3- diethyl-N- of 4- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (30)；
3- methyl-1-phenyl-N- [(2- phenyl thiazole-4- base) methyl]-1H- pyrazoles-5- benzoic acid amides (31)；
3- methyl-1-(4- chlorphenyl)-N- [(2- phenyl thiazole-4- base) methyl]-1H- pyrazoles-5- benzoic acid amides (35)；
1- methyl -5- propyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -3- benzoic acid amides (50)；
5- isopropyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -3- benzoic acid amides (52).
The invention further relates to a kind of pest control/mites, formula (I) compound containing biologic effective dose of disinfect pathogen and extremely
A kind of few other composition selected from surfactant, solid diluent and liquid diluent.
The invention further relates to a kind of pest control/mite, disinfect pathogen formula (I) compound containing biologic effective dose and have
The composition of at least one other bioactive compound or preparation of effect amount.
The invention further relates to a kind of pest control/mites, the method for disinfect pathogen, including changing the formula (I) of biologic effective dose
It closes object and contacts evil insects mites, disinfect pathogen or its environment.Such a harmful insects mites, disinfect pathogen control method are also related to,
It does harm to formula (I) compound of insects mites, disinfect pathogen or its environment biologic effective dose or contains formula (I) compound and biologically effective
The mixture of at least one other compound or preparation of amount, which is contacted, comes pest control/mite, disinfect pathogen.
Formula (I) compound of the invention has broad spectrum of activity: the compound having can be used for pest control/mite, it may also be used for
Prevent and treat disinfect pathogen.And the compound having has very high bioactivity to certain harmful insects mites and/or disinfect pathogen, so that
It is obtained with good effect at very low concentrations.
Currently preferred composition is the composition containing above-mentioned preferred compound.It is preferable that with above-mentioned excellent
The method for selecting compound.
The present invention is further illustrated with the part formula (I) compound listed in 1~table of table 2 below, but does not limit this
Invention.Fusing point given in the present invention is not calibrated；When (I) compound of formula synthesized by the present invention is viscous liquid, some are viscous
Property liquid refrigerator place after can solidify, when to invent synthesized formula (I) compound be viscous solid, some viscous solid refrigerators are put
Non-tacky solids can be cured as by postponing；All compounds are in LC-MS (APCI, Pos) (Agilent1100Series LC/ in table 1
MSD its molecular ion peak) or in GC-MS (Agilent 7890-5975C) can be observed；Compound in table 11H NMR
(Varian INOVA-300spectrometer) makees internal standard, deuterated chloroform (CDCl with tetramethylsilane (TMS)3)
Or deuterated dimethyl sulfoxide (DMSO) makees solvent.
Table 1
Table 2
Formula (I) compound represented of the invention can be obtained by reaction equation 1 shown below；In reaction equation 1
(II) it can be obtained by reaction equation 2 shown below；(III) in reaction equation 1 can be obtained by reaction equation 3；Reaction equation 2
In (IV) can by purchase or reaction equation 4-1 or 4-2 obtain；Z of the reaction equation 1 into reaction equation 3 is leaving group, such as
Chlorine, bromine etc., other substituent groups are outer unless specified otherwise to be limited as preceding.
Reaction equation 1:
Reaction equation 2:
Reaction equation 3:
Reaction equation 4:
The compound of formula (I) can prepare in this way (reaction equation 1): in suitable solvent such as tetrahydrofuran, acetonitrile, dichloro
In methane, dichloroethanes, toluene or dimethylbenzene, in -10 DEG C~system reflux temperature, in no alkali or in appropriate base such as three second
In the presence of amine, pyridine, sodium hydride, sodium hydroxide or potassium hydroxide, with formula (II W=O) compound represented and formula (III) institute
The compound reaction shown, obtains formula (I W=O) compound, be added catalyst such as 4- dimethylamino pyridine etc. can accelerate to react into
Row；Formula (I W=O) compound represented is through suitable sulfide such as P2S5Handle to obtain formula (I W=S) compound.
The compound of formula (II) can prepare in this way (reaction equation 2): solvent-free or suitable solvent such as dichloroethanes,
In methylene chloride or toluene, in 15 DEG C~system reflux temperature, with formula (IV W=O) compound represented and with suitable halogenation
Reagent such as thionyl chloride, phosgene or oxalyl chloride etc. react to obtain formula (II W=O) compound.
The compound of formula (III) can be prepared via a method which (reaction equation 3): in suitable solvent such as ethyl alcohol, tetrahydro
In the mixture of furans, ethyl alcohol and tetrahydrofuran, in 25 DEG C~system reflux temperature, 1.3 dihalo-s (chlorine or bromine) acetone and thio
Benzamide reacts to obtain 4- chloromethyl -2- phenyl thiazole；4- chloromethyl -2- phenyl thiazole AMMONIA TREATMENT or 4- chloromethyl -2-
Phenyl thiazole reacts the compound that the solid object product of gained handles formula (III) to obtain the final product with hydrazine hydrate with potassium phthalimide.
The compound of formula (IV W=O) can prepare (reaction equation 4) by purchase or following method: suitable solvent such as
In ethyl alcohol, methanol, propyl alcohol, butanol or water, in the presence of suitable alkali such as sodium ethoxide, sodium methoxide or sodium hydroxide, in -15 DEG C~
System reflux temperature is reacted with formula (V) or (V ') compound represented with oxalate diester such as diethy-aceto oxalate, obtain formula (VI) or
(VI ') compound represented；After the compound of formula (VI) or (VI ') are routinely post-processed, then with hydrazine hydrate cyclization, obtain formula
(VII) or the compound of (VII ')；In suitable solvent such as n,N-Dimethylformamide, under the conditions of 30 DEG C~100 DEG C, formula
(VII) or the compound of (VII ') with alkylating reagent such as dimethyl suflfate, dithyl sulfate or iodomethane etc. reacts to obtain formula
(VIII) or (VIII ') compound；Or the compound of formula (VI) or (VI ') is after routinely post-processing, and replaces hydrazine cyclization, obtains
Formula (VIII) or (VIII ') compound；(VIII ') compound represented obtains formula through the respective reactions such as halogenating reaction or alkylation
(VIII) compound represented；In suitable solvent such as water, ethyl alcohol, the single solvent of methanol or water and ethyl alcohol, water and methanol
In the mixed solvent, in the presence of appropriate base such as sodium hydroxide or potassium hydroxide, under 50 DEG C~system reflux temperature, (VIII) changes
Close object after conventional hydrolysis, with dilute hydrochloric acid solution handle formula (IV) compound.
Specific synthetic method has more detailed elaboration in the following embodiments.
The invention will be further described with reference to embodiments, and however, the present invention is by no means limited to these examples, implements
Yield in example is not optimized.
Formula (I) compound provided by the invention has broad-spectrum biological living under 15~2250 grams of effective components/hectare dosage
Property, can be not only used for pest control/mite, it may also be used for prevention and treatment disinfect pathogen, some compounds have well evil insects mites and/or
Disinfect pathogen preventive and therapeutic effect is obtained with good effect at very low concentrations.
Formula (I) compound provided by the invention, with bioactivity and the compound that has has good bioactivity.It is special
Be not agricultural, gardening, flowers and sanitary insect pest, germ prevention and treatment in terms of show activity.Harmful organism packet described here
It includes, but is not limited only to this, also never limit the present invention.
Evil insects mites:
Homoptera such as leafhopper, plant hopper, aphid, Lepidoptera such as oriental armyworm, snout moth's larva, prodenia litura, diamondback moth, beet night
Moth, cabbage looper, cabbage caterpillar etc., Hymenoptera such as sawfly larva etc., Diptera such as yellow-fever mosquito, culex, fly etc., Acarina such as cotton leaf
Mite, Zhu noisy tetranychid, the full melon mite of citrus, Shenmu-Yanan railway, apple tetranychus, citrus rust mite, Rhizoglyphus hyacinthi, T.urticae Koch etc..
Particularly, lead to formula (I) compound to homoptera pest such as aphid and lepidoptera pest such as mythimna separata etc., in low concentration
Under still have well activity.
Harmful disease:
Oomycetes diseases, such as downy mildew, white rust, samping off, pythium rot, epidemic disease, late blight；
Fungi Imperfecti disease, as wilt disease, root rot, damping-off, anthracnose, verticillium wilt, scab, gray mold, brown spot,
Black spot, spot blight, early blight, ring spot, leaf blight, base rot disease etc.；
Load fungus diseases, such as rust, smut；
Sac fungus disease, such as powdery mildew, sclerotiniose (flax sclerotiniose, sclerotinia sclerotiorum, soybean sclerotinia crown rot, peanut sclerotium
Disease, tobacco sclerotiniose, capsicum sclerotiniose, eggplant sclerotiniose, bean sclerotinia rot, pea sclerotiniose, cucumber timberrot, balsam pear sclerotium
Disease, wax gourd sclerotinia, watermelon sclerotiniose, celery sclerotiniose), scab etc.；
Particularly, the compounds of this invention still has powdery mildew, gray mold, rust etc. living well under low concentration
Property.
Due to its positive characteristic, above compound is advantageously used for protection agricultural and the important crop of horticulture, family
Injury of the environment that poultry and breeding stock and the mankind often go from pest, germ.
To obtain ideal effect, the dosage of compound changes because of various factors, for example, compound used therefor, pre- protection,
Type, gradient of infection, weather conditions, application method, the dosage form of use of harmful organism.
The invention also includes to lead to desinsection, bactericidal composition of the formula (I) compound as active component.The desinsection, sterilization
The weight percentage of active component is between 0.5-99% in composition.It further include agricultural, woods in the desinsection, bactericidal composition
Acceptable carrier in industry, health.
It is effectively that they can also be with it to control pest, germ when formula of the invention (I) compound is used alone
Allogene chemical substance is used together, these biochemicals include other insecticides, fungicide, herbicide, plant growth
Regulator, acaricide or fertilizer etc., and thus can produce additional advantage and effect.
Using formula provided by the invention (I) compound as the preparation of effective ingredient, desired any one can be made
Dosage form, such as dry compressed particle, Yi Liudong intermixture, granula, wettable powder, water dispersible granules, emulsifiable concentrate, powder
Agent, powdery concentrate, microemulsion, suspending agent, missible oil, aqueous emulsion, soluble liquid, aqua, dispersible agent, suitable auxiliary agent
Including carrier (diluent) and other adjuvants such as spreader-sticker, emulsifier, wetting agent, dispersing agent, sticker and distintegrant.These
Contain in preparation and is mixed with the compound of the present invention with the acceptable solid of inert, pharmacology or liquid diluent.
Desired any dosage form, such as dry compressed particle, Yi Liu can also be made in composition example of the invention
Dynamic intermixture, wettable powder, water dispersible granules, emulsifiable concentrate, pulvis, powdery concentrate, microemulsion, hangs at granula
Floating agent, missible oil, aqueous emulsion, soluble liquid, aqua, dispersible agent, suitable auxiliary agent include carrier (diluent) and other
Adjuvant such as spreader-sticker, emulsifier, wetting agent, dispersing agent, sticker and distintegrant.Containing with inert, medicine in these preparations
Acceptable solid or liquid diluent of science are mixed with the compound of the present invention.
It should be appreciated that various transformation and change can be carried out in scope defined by the claims of the present invention.
The invention will be further described with reference to embodiments, and the yield in embodiment is not optimized.
Specific embodiment
Embodiment 1 this example demonstrates that in table 1 compound 4 preparation
3- methylpyrazole -5- Ethyl formate is under -15~-5 DEG C and stirring condition, by acetone (0.30mol) and oxalic acid two
The mixed solution of ethyl ester (0.32mol) is added drop-wise in ethyl alcohol (300mL) solution of 96% sodium ethoxide (0.45mol).It is added dropwise
Afterwards, after the reaction was continued 2-4 hours, reaction solution is poured into ice water, adjusts its PH=4, ethyl acetate extraction, gained with dilute hydrochloric acid
After washing, anhydrous sodium sulfate is dry for organic phase, and acetopyruvic acid ethylester 46.5g is obtained after reduced pressure.In -10~-5 DEG C and stir
Under the conditions of mixing, in 1-2 hours, 80% hydrazine hydrate (0.38mol) is added drop-wise to the ethyl alcohol of above-mentioned acetopyruvic acid ethylester
In (300mL) solution.After being added dropwise, continue insulation reaction 1-2hr.After removed under reduced pressure major part solvent, ethyl acetate extraction,
After washing, anhydrous sodium sulfate is dry for gained organic phase, is concentrated under reduced pressure, obtains title compound 31.5g.
1,3- dimethyl pyrazole -5- Ethyl formate 3- methylpyrazole -5- Ethyl formate (65mmol) and dimethyl suflfate
(78mmol) is stirred to react 2-4 hours in n,N-Dimethylformamide (DMF, 120mL) in 60-70 DEG C.After reaction solution is cooling
It is extracted with ethyl acetate, for gained organic phase through washing, anhydrous sodium sulfate is dry, is concentrated under reduced pressure, obtains title compound 9.0g.
1,3,4- trimethylpyrazol -5- Ethyl formate is under room temperature and stirring condition, by 1,3- dimethyl pyrazole -5- formic acid
Ethyl ester (50mmol) adds to paraformaldehyde (100mmol) in batches, the Isosorbide-5-Nitrae-two of concentrated hydrochloric acid (100mmol) and the concentrated sulfuric acid (5mmol)
In six ring of oxygen (100mL) solution.It is reacted 4-6 hours under counterflow condition, it is cooling, ice water is poured into after removed under reduced pressure partial solvent
In, ethyl acetate extraction, for gained organic phase through washing, anhydrous sodium sulfate is dry, and 1,3- dimethyl -4- chloromethyl is concentrated under reduced pressure to obtain
Pyrazole-5-ethyl formate 9.0g.Under nitrogen protection, 1,3- dimethyl -4- chloromethyl pyrazole-5-ethyl formate (40mmol) is turned
It moves in pressure bottle, and methanol (50mL) is added, water (10mL) and 5%Pd/C catalyst (50% moisture, 0.4g).It stirs evenly
Afterwards, it is passed through hydrogen to replace 5 times, react 8-10 hours at room temperature.Water (100mL) is added in filtrate, ethyl acetate in filtering reacting liquid
Extraction, for gained organic phase through washing, anhydrous sodium sulfate is dry, and title object 4.6g is concentrated under reduced pressure to obtain.
1,3,4- trimethylpyrazol -5- formic acid 1,3,4- trimethylpyrazol -5- Ethyl formate (25mmol), sodium hydroxide
(75mmol), water (60mL) and ethyl alcohol (10mL) react 3-5 hours under reflux and stirring condition.After reaction solution is cooling, acetic acid
Ethyl ester extraction, gained water phase are acidified to faintly acid (PH=5-6) with dilute hydrochloric acid, are stood, are filtered the solid of precipitation, obtain title compound
Object 2.6g.
1,3,4- trimethylpyrazol -5- formic acid acyl chlorides, 1,3,4- trimethylpyrazol -5- formic acid (15mmol), thionyl chloride
(35mmol) and 1,2- dichloroethanes (25mL) react 3-5 hours under reflux and stirring condition.After cooling, removed under reduced pressure solvent
And excessive thionyl chloride, obtain title compound 2.2g.
1.3 dichloroacetone (170mmol) of 4- chloromethyl -2- phenyl thiazole, thiobenzamide (150mmol), ethyl alcohol
After (150mL) and THF (75mL) react 5-8 hours under reflux and stirring condition.Remove most of solvent, cooling, reaction solution
It pours into ice water, organic phase is washed in ethyl acetate extraction, and anhydrous sodium sulfate is dry, and decompression sloughs solvent and obtains yellow liquid title
Object 28g.
4- aminomethyl -2- phenyl thiazole (III) 4- chloromethyl -2- phenyl thiazole (45mmol), phthalimide
It is cold after potassium (50mmol) and n,N-Dimethylformamide (DMF, 100mL) are reacted 2-5 hours under 60-80 DEG C and stirring condition
But to room temperature, reaction solution is poured into ice water, and solid is precipitated.Filter solid and hydrazine hydrate (100mmol) be precipitated, ethyl alcohol
It is cooling after (200mL) reacts 3-5 hours under reflux and stirring condition, filtering.After filtrate removes most of ethyl alcohol, acetic acid second
Ester extraction, organic phase obtain title compound 6.0g through washing, anhydrous sodium sulfate drying, removed under reduced pressure solvent.
1,3,4- trimethyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (compound in table 1
4) under the cooling simultaneously stirring condition of ice-water bath, by the tetrahydro furan of 1,3,4- trimethylpyrazol -5- formic acid acyl chlorides (10mmol) in 1 hour
(THF, 5mL) solution of muttering is added dropwise to 4- aminomethyl -2- phenyl thiazole (10mmol), triethylamine (20mmol) and 4- dimethylamino
In THF (25mL) mixture of pyridine (catalytic amount).After being added dropwise, the reaction was continued overnight.Reaction mixture acetic acid second
Ester extraction, organic phase chromatograph (petroleum ether/second through column through washing, anhydrous sodium sulfate drying, removed under reduced pressure solvent, gained crude product
Acetoacetic ester=10:1~5:1) purifying, obtain the title object 2.1g of off-white powder.
Embodiment 2 this example demonstrates that in table 1 compound 7 preparation
Under -10~-5 DEG C of 3- ethylpyrazol -5- Ethyl formate and stirring condition, 1-2 hour it is interior by butanone (0.30mol) and
The mixed solution of diethy-aceto oxalate (0.32mol) is added drop-wise in ethyl alcohol (300mL) solution of 96% sodium ethoxide (0.45mol).Drop
After adding, continue to be stirred to react 2-4 hours.It controls under temperature -5~0 DEG C and stirring condition, successively by acetic acid (0.30mol)
Above-mentioned reaction mixture is added dropwise to 80% hydrazine hydrate (0.38mol).After being added dropwise, the reaction was continued 1-2 hours.Gained reaction
Water (200mL) is added after being concentrated under reduced pressure in object, ethyl acetate extraction, and after washing, anhydrous sodium sulfate is dry for gained organic phase, decompression
Concentration, obtains title compound 29.6g.
3- ethyl -1- methylpyrazole -5- Ethyl formate 3- ethylpyrazol -5- Ethyl formate (100mmol) and dimethyl sulfate
Ester (120mmol) reacts 3-4 hours under 60-70 DEG C and stirring condition in DMF (150mL).Acetic acid is used after reaction solution is cooling
Ethyl ester extraction, for gained organic phase through washing, anhydrous sodium sulfate is dry, is concentrated under reduced pressure, obtains title compound 15.0g.
3- ethyl -1- methylpyrazole -5- formic acid 3- ethyl -1- methylpyrazole -5- Ethyl formate (50mmol), sodium hydroxide
(150mmol), water (120mL) and ethyl alcohol (20mL) react 4-5 hours under reflux and stirring condition.After reaction solution is cooling, second
Acetoacetic ester extraction, gained water phase are acidified to faintly acid (PH=5-6) with dilute hydrochloric acid, are stood, are filtered the solid of precipitation, obtain titled
Close object 4.8g.
3- ethyl -1- methylpyrazole -5- formic acid acyl chlorides 3- ethyl -1- methyl pyrazole formic acid (10mmol), thionyl chloride
(25mmol) and 1,2- dichloroethanes (15mL) react 3-4 hours under reflux and stirring condition.After cooling, taken off under reduced pressure
Except solvent and excessive thionyl chloride, title compound 1.3g is obtained.
3- ethyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (chemical combination in table 1
Object 7) under the cooling simultaneously stirring condition of ice-water bath, by the tetrahydro furan of 1- methyl -3- ethylpyrazol -5- formic acid acyl chlorides (7.5mmol)
(THF, 5mL) solution of muttering is added dropwise to 4- aminomethyl -2- phenyl thiazole (7.5mmol), triethylamine (15mmol) and 4- dimethylamine
In THF (15mL) mixture of yl pyridines (catalytic amount).After being added dropwise, the reaction was continued overnight.Reaction mixture acetic acid
Ethyl ester extraction, for organic phase through removing solvent under washing, anhydrous sodium sulfate drying, reduced pressure, gained crude product chromatographs (stone through column
Oily ether/ethyl acetate=10:1~5:1) purifying, obtain off-white powder title object 1.5g.
Embodiment 3 this example demonstrates that in table 1 compound 8 preparation
3- ethyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- carbothioic acid amide is (in table 1
Compound 8) 3- ethyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (2.5mmol) and
After back flow reaction 2-3 hours, second batch phosphorus pentasulfide is added in tetrahydrofuran (50mL) in phosphorus pentasulfide (7.5mmol)
(7.5mmol) after continuing back flow reaction 2-3 hours, is added third batch phosphorus pentasulfide (7.5mmol), is further continued for back flow reaction
2-3 hours.Reaction mixture is concentrated through cooling under reduced pressure.Saturated salt solution is added in concentrate, ethyl acetate extracts,
Organic phase is through washing, anhydrous sodium sulfate is dry, removed under reduced pressure solvent, gained crude product chromatograph through column (petrol ether/ethyl acetate=
10:1~5:1) purifying, obtain the title object 0.7g of yellow solid.
Embodiment 4 this example demonstrates that in table 1 compound 10 preparation
The chloro- 3- ethyl -1- methylpyrazole -5- Ethyl formate of 4- is under the cooling simultaneously stirring condition of ice-water bath, by chlorination sulfone
(55mmol) is added drop-wise to 1,2- dichloroethanes (100mL) solution of 3- ethyl -1- methylpyrazole -5- Ethyl formate (50mmol)
In.It reacts 3-4 hours under counterflow condition after being added dropwise, is extracted with ethyl acetate after reaction solution is cooling, gained organic phase warp
Washing, anhydrous sodium sulfate is dry, is concentrated under reduced pressure, obtains title compound 7.9g.
The chloro- 3- ethyl -1- methylpyrazole -5- formic acid of 4- is referring to 3- ethyl -1- methylpyrazole -5- formic acid in embodiment 2
Preparation method replaces 3- ethyl -1- methylpyrazole -5- Ethyl formate with 4- chlorine 3- ethyl -1- methylpyrazole -5- Ethyl formate,
The chloro- 3- ethyl -1- methylpyrazole -5- formic acid of 4- can be prepared.
The chloro- 3- ethyl -1- methylpyrazole -5- formic acid acyl chlorides of 4- is referring to 3- ethyl -1- methylpyrazole -5- first in embodiment 2
The preparation method of isoxazolecarboxylic acid replaces 3- ethyl -1- methylpyrazole -5- formic acid with 4- chlorine 3- ethyl -1- methylpyrazole -5- formic acid,
The chloro- 3- ethyl -1- methylpyrazole -5- formic acid acyl chlorides of 4- can be prepared.
The chloro- 3- ethyl -1- methyl-N- of 4- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides are (in table 1
Compound 10) referring to the preparation method of 3- ethyl -1- methylpyrazole -5- benzoic acid amides in embodiment 2, with 4- chlorine 3- ethyl -1-
Methylpyrazole -5- formic acid acyl chlorides replaces 3- ethyl -1- methylpyrazole -5- formic acid acyl chlorides, can prepare the chloro- 3- ethyl -1- first of 4-
Base-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides.
Embodiment 5 this example demonstrates that in table 1 compound 13 and 52 preparation
3- isopropyl -1- methylpyrazole -5- formic acid and 5- isopropyl -1- methylpyrazole -3- formic acid are referring in embodiment 2
The preparation method of 3- ethyl -1- methylpyrazole -5- formic acid, replaces butanone with 3- methyl -2- butanone, 3- isopropyl -1- can be made
The mixture of methylpyrazole -5- formic acid and 5- isopropyl -1- methylpyrazole -3- formic acid.
3- isopropyl -1- methylpyrazole -5- formic acid acyl chlorides and 5- isopropyl -1- methylpyrazole -3- formic acid acyl chlorides are referring to real
The preparation method of 3- ethyl -1- methylpyrazole -5- formic acid acyl chlorides in example 2 is applied, with above-mentioned 3- isopropyl -1- methylpyrazole -5- first
The mixture of acid and 5- isopropyl -1- methylpyrazole -3- formic acid replaces 3- ethyl -1- methylpyrazole -5- formic acid, can prepare 3-
The mixture of isopropyl -1- methylpyrazole -5- formic acid acyl chlorides and 5- isopropyl -1- methylpyrazole -3- formic acid acyl chlorides.
3- isopropyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (are changed in table 1
Close object 13) and 5- isopropyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -3- benzoic acid amides (change in table 1
Close object 52) referring to the preparation method of 3- ethyl -1- methylpyrazole -5- benzoic acid amides in embodiment 2, with 3- isopropyl -1- methyl
The mixture of pyrazoles -5- formic acid acyl chlorides and 5- isopropyl -1- methylpyrazole -3- formic acid acyl chlorides replaces 3- ethyl -1- methylpyrazole -
5- formic acid acyl chlorides can prepare 3- isopropyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- formic acid acyl
Amine (compound 13 in table 1) and 5- isopropyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -3- formic acid acyl
The mixture of amine (compound 52 in table 1) is isolated and purified through column chromatography (petrol ether/ethyl acetate=10:1~5:1), respectively
To off-white powder title object 13 and 52.
Embodiment 6 this example demonstrates that in table 1 compound 24 preparation
Butanone is replaced with cyclohexanone, referring to the correlation method in embodiment 2,2- methyl-N- [(2- phenyl thiophene can be prepared
Azoles -4- base) methyl] -4,5,6,7- tetrahydro -2H- Yin rattles away azoles -3- benzoic acid amides (compound 24 in table 1).
The other compounds of the present invention are referred to embodiment 1 to embodiment 6 and relevant references method and prepare.
The preparation of 7 missible oil of embodiment
Appropriate formula (I) compound of the invention is proportionally weighed, pesticide auxiliaries and solvent etc. are put into reaction kettle.First plus
Enter a certain amount of solvent and defoaming agent and stir 10~30min, add the components such as stabilizer, synergist, continue stirring 10~
30min, then a effective amount of solvent is put into kettle, blowing after mixing evenly.
8 3- ethyl -1- methyl-N- of embodiment [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides (table
Compound 7 in 1) missible oil preparation: weigh formula provided by the invention (I) compound of appropriate (percentage according to the required weight): 3-
Ethyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides, suitable solvent such as N, N- diformazan
Base formamide, acetone, ethyl acetate or dimethylbenzene, suitable pesticide use emulsifier such as Tween80 and other pesticide are with helping
Agent is put into reaction kettle, and a certain amount of defoaming agent is first added and stirs 10~30min, adds suitable stabilizer, synergist, penetrate
The components such as agent continue 10~30min of stirring, adjust pH value, then a effective amount of solvent is put into kettle, blowing is after mixing evenly
The cream of weight percent needed for obtaining 3- ethyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides
Oil.
Biological activity determination embodiment
The compounds of this invention is carried out to sterilize and kill insects mites activity test, the results showed that the compound of the present invention has
Insects mites activity is sterilized and/or kills well, part of test results is as follows:
Bactericidal activity (pot-culture method) of the embodiment 9 to wheat powdery mildew (Erisiphe griminis)
Method is as follows: untested compound is dissolved in suitable solvent such as n,N-Dimethylformamide (DMF), then with containing 0.2%
The sterile water of Tween80 emulsifier is diluted to required concentration；The basin alms bowl of cut-off stem 15cm or so, every alms bowl sow the full stalwartness of wheat
20, seed, wait grow two leaves wholeheartedly afterwards be for experiment；Ready wheat seedling plant is taken to spray through certain density medicament
Mist processing, carries out germ inoculation after one day.3 repetitions of every processing, set the blank without untested compound separately as blank control, quotient
Product fungicide Fluoxastrobin is commercial References；After the onset of moisturizing thermophilic culture to blank control, lesion area is checked, calculate medicament
Preventive effect.Activity in percentage, is divided into A, B, C, D level Four relative to blank control, and 100%≤Fang Xiao≤90% is A grades, and 90%
> Fang Xiao≤70% is B grades, and 70% > Fang Xiao≤50% is C grades, and 50% > Fang Xiao≤0% is D grades.The result shows that of the invention
Compound has control efficiency to wheat powdery mildew, and the compound having still has very high activity at very low concentrations.For
Compare the compounds of this invention and D2 to the activity height of wheat powdery mildew, selects the compounds of this invention 7 for representative, be pair with D2
It shines into and has gone test, the results showed that the compounds of this invention 7 is much better than D2 to wheat powdery mildew to the activity of wheat powdery mildew
Activity.Partial results are as follows:
Under 500mg/L concentration, the compounds of this invention 1,4,7,8,13,14,23 etc. and Fluoxastrobin have A to wheat powdery mildew
Grade prevention and treatment activity；
Under 100mg/L concentration, the compounds of this invention 1,7,13 etc. and Fluoxastrobin there are A grades of prevention and treatments to live wheat powdery mildew
Property；4,14 etc. have B grades of prevention and treatment activity to wheat powdery mildew；9 and 11 etc. have C grades of prevention and treatment activity to wheat powdery mildew；
Under 25mg/L concentration, the compounds of this invention 7 and Fluoxastrobin etc. still have A grades of prevention and treatment activity to wheat powdery mildew；1 He
13 etc. still have B grades of prevention and treatments activity to wheat powdery mildew；D2 is B grades to the activity of wheat powdery mildew；
Further to compare the compounds of this invention and D2 to the activity height of wheat powdery mildew, the compounds of this invention is selected
7 be representative, is that control has carried out deep screening, partial results such as table 3. with D2
The control efficiency (%) of 3 the compounds of this invention 7 of table and D2 to wheat powdery mildew
Control efficiency of the embodiment 10 to powdery mildew of cucumber (Sphaerotheca fuliginea)
Further to verify the compounds of this invention to the activity of Powdery Mildew, select the compounds of this invention 7 for representative, with Huang
Melon powdery mildew is target, and Fluoxastrobin is comparison medicament, has carried out the pharmacodynamic test that the compounds of this invention 7 prevents and treats powdery mildew of cucumber.
Test result shows that the compounds of this invention 7 has excellent control efficiency to powdery mildew of cucumber, and preventive effect is better than under Isodose
The preventive effect of comparison medicament Fluoxastrobin.Partial results are as follows:
7 days after 2 medicines, in 225g a.i./hm2、281.25g a.i./hm2、337.5g a.i./hm2Under dosage, this hair
Bright compound 718%EC is respectively 82.30%, 85.84% and 87.35% to the control efficiency of powdery mildew of cucumber；Comparison medicament
Fluoxastrobin 250g/L SC is in 281.25g a.i./hm2Under dosage, the control efficiency to powdery mildew of cucumber is 83.15%.
Bactericidal activity (pot-culture method) of the embodiment 11 to botrytis cinerea pers (Botrytis cinerea)
Method: untested compound is dissolved in suitable solvent such as n,N-Dimethylformamide (DMF), then with containing 0.2%
The sterile water of Tween80 emulsifier is diluted to required concentration；4 repetitions of every processing, separately set the blank without untested compound as
Blank control, commercialization fungicide Boscalid are commercial References；After gray mold of cucumber opportunistic pathogen is gone to PDA plate activation culture
It goes in PD culture medium, water bath with thermostatic control culture 4 days；Cultured mycelium pellet is crushed with refiner and is deployed with clear water to certain
The bacteria suspension of concentration；When the cucumber long two panels true leaf to flattening, the medical fluid of untested compound is sprayed, bacteria suspension is sprayed after 1 day extremely
Seedling surface, moisturizing culture simultaneously observe seedling incidence；When control treatment morbidity is obvious, start the morbidity feelings for recording each processing
Condition calculates pharmacy control efficacy.Activity in percentage, is divided into A, B, C, D level Four relative to blank control, and 100%≤Fang Xiao≤
90% is A grades, and 90% > Fang Xiao≤70% is B grades, and 70% > Fang Xiao≤50% is C grades, and 50% > Fang Xiao≤0% is D grades.Knot
Fruit shows that the compound of the present invention has control efficiency to gray mold of cucumber, and the compound having still has at very low concentrations
Very high activity.To compare the compounds of this invention and D2 to the activity height of gray mold of cucumber, select the compounds of this invention 7 for generation
Table is that control is tested with D2, the results showed that the compounds of this invention 7 is much better than D2 to cucumber to the activity of gray mold of cucumber
The activity of gray mold.Partial results are as follows:
Under 500mg/L concentration, the compounds of this invention 1,4,7,20,52 etc. and Boscalid have A grades to gray mold of cucumber
Prevention and treatment activity, 12,14,30 etc. have B grades of prevention and treatment activity to gray mold of cucumber；
Under 100mg/L concentration, the compounds of this invention 1,4,7,20 etc. and Boscalid have A grades of prevention and treatments to gray mold of cucumber
Activity；
Under 25mg/L concentration, still there are A grades to be prevented to gray mold of cucumber for the compounds of this invention 1,4,7,20 etc. and Boscalid
Control activity；
To compare the compounds of this invention and D2 to the activity height of botrytis cinerea pers, select the compounds of this invention 7 for generation
Table is that control has carried out deep screening with D2, the results showed that the compounds of this invention 7 is much better than D2 to the activity of botrytis cinerea pers
To the activity of botrytis cinerea pers, partial results such as table 4.
The control efficiency (%) of 4 the compounds of this invention 7 of table and D2 to gray mold of cucumber
Bactericidal activity (pot-culture method) of the embodiment 12 to corn rust (Puccinia Polysora)
Untested compound is dissolved in suitable solvent such as n,N-Dimethylformamide (DMF), then with containing 0.2%Tween80 cream
The sterile water of agent is diluted to required concentration；4 repetitions of every processing, if the blank without untested compound is with D2 to compare
Control；Morbidity maize leaf is cut, washes lower spore with 0.05%Tween80 or other suitable surfactant aqueous solutions, and with 2
~4 layers of filtered through gauze, it is 1 × 10 that concentration, which is made,5The suspension of a spore/mL；Test compounds are sprayed to corn length to 2 leaf, 1 heart
The medical fluid of object, spore suspension spray inoculation after 1 day, inoculation move back to moisturizing cabinet (95% or more relative humidity, 20 DEG C of temperature~
22 DEG C), (intensity of illumination 5000Lux~10000Lux) is cultivated 15~24 hours under low light condition；It is reached to blank control disease leaf rate
When 50% or more, the incidence of each processing is investigated, calculates pharmacy control efficacy.Activity in percentage, is divided relative to blank control
For A, B, C, D level Four, 100%≤Fang Xiao≤90% is A grades, and 90% > Fang Xiao≤70% is B grades, and 70% > Fang Xiao≤50% is
C grades, 50% > Fang Xiao≤0% is D grades.The result shows that the compounds of this invention has control efficiency, and the change having to corn rust
Close object still has control efficiency at very low concentrations, and partial results are listed below:
Under 500mg/L concentration, the compounds of this invention 1,7,9,12,13,20,30,31 and 52 etc. has A grades to corn rust
Prevention and treatment activity；6,11 and 50 etc. have B grades of prevention and treatment activity to corn rust；
Under 100mg/L concentration, the compounds of this invention 1 and 13 etc. has A grades of activity to corn rust, and 9 and 11 etc. to corn
Rust has B grades of activity, and 30 wait to corn rust with C grades of activity, and D2 is to the activity of corn rust less than C grades；
Under 50mg/L concentration, the compounds of this invention 13 etc. still has A grades of activity to corn rust, and D2 does not have corn rust
Show activity.
Bactericidal activity of the embodiment 13 to Sclerotinia sclerotiorum (Sclerotonia sclerotiorum)
Method: untested compound is dissolved in suitable solvent such as n,N-Dimethylformamide (DMF), then with containing 0.2%
The sterile water of Tween80 emulsifier is diluted to required concentration；The 27mL Ma Ling for taking the addition of 3mL medical fluid to be cooled to 45 DEG C with pipette
Culture dish is poured into after shaking up in potato agar medium (PDA) and sufficiently；Use transfer needle from the sclerotinia sclerotiorum of culture 7 days after cooling
Bacterium colony edge takes 6mm diameter mycelia block, moves to culture dish center, mycelia is face-down, while setting the sky without untested compound
White is control, 4 repetitions of every processing；Culture dish is placed in 28 DEG C of constant temperature biochemical cultivation cases after being disposed and is cultivated, is surveyed after 4 days
Mycelia growth diameter is measured, is analyzed using EXCEL statistical software and calculates mycelial growth inhibition rate (%).It is simultaneously pair with D2
According to.Activity in percentage, is divided into A, B, C, D level Four relative to blank control, and 100%≤Fang Xiao≤90% is A grades, 90% >
Fang Xiao≤70% is B grades, and 70% > Fang Xiao≤50% is C grades, and 50% > Fang Xiao≤0% is D grades.The result shows that chemical combination of the present invention
Object has obvious activity to Sclerotinia sclerotiorum.Partial results are listed below:
Under 25mg/L concentration, the compounds of this invention 4,13,31 and 52 etc. to Sclerotinia sclerotiorum have A grade it is active, 9,10,
27 and 35 etc. have B grades of activity to Sclerotinia sclerotiorum, and D2 is to the active less than 20% of Sclerotinia sclerotiorum.
Biological evaluation of the embodiment 14 to mythimna separata (Mythimna separata)
Potter spray-on process: untested compound is dissolved in suitable solvent such as n,N-Dimethylformamide (DMF), then with containing
The clear water of 0.2%Tween80 emulsifier is diluted to required concentration, if the blank without untested compound is control.It takes fresh and tender
Maize leaves are cut into the almost the same segment of size, are put into and are lined in the culture dish (Ф 90mm) of filter paper in advance.Then it is connect in ware
Enter 3 instar larvae of mythimna separata 10, be put under Potter spray tower and carry out metered dose, spray liquid measure 1ml, 3 repetitions of every concentration.Place
Reason finishes, and covers ware lid, is placed in culture, routine observation in recovery room and test worm death condition is checked and recorded after 72 hours, count
The death rate is calculated, results are averaged.The result shows that the compounds of this invention has remarkable activity to mythimna separata, such as in 500mg/L concentration
Under, the compounds of this invention 7 and 10 etc. has 100% activity to mythimna separata.
Insecticidal Activity of the embodiment 15 to aphid (Aphis fabae)
It is evaluation the compounds of this invention to the activity of homoptera pest, selects aphid for object, use infusion process indoors
The compounds of this invention is determined to the activity of aphid.
Infusion process: untested compound is dissolved in suitable solvent such as n,N-Dimethylformamide (DMF), then with containing 0.2%
The clear water of Tween80 emulsifier is diluted to required concentration, if the blank without untested compound is control, 3 repetitions of every processing.
Black bean aphid is connected on just unearthed bean seedlings, every plant connects 20 or more, and bean seedlings are then dipped in the present invention together with test worm and are mentioned
In formula (I) medical fluid of confession, is taken out after 5 seconds, suck extra medical fluid, be inserted into the sponge of water suction, covered with glass-tube, after 24 hours
Check survival and dead borer population, results are averaged.Active (death rate) relative to blank control in percentage, be divided into A, B,
C, D level Four, 100%≤Fang Xiao≤90% are A grades, and 90% > Fang Xiao≤70% is B grades, and 70% > Fang Xiao≤50% is C grades,
50% > Fang Xiao≤0% is D grades.The result shows that the compounds of this invention is active to aphid, and the compound having is very low
Still there is high activity under concentration, partial results are listed below:
Under 500mg/L concentration, the compounds of this invention 1,4,6,7,9,10,11,12,13,20,24 and 50 etc. has aphid
A grades of activity；8,14,23 and 25 etc. have B grades of activity to aphid；
Under 50mg/L concentration, the compounds of this invention 4,6,7,9,10 and 11 etc. all has A grades of activity to aphid；
Under 12.5mg/L concentration, the compounds of this invention 10 etc. still has A grades of activity to aphid.
Embodiment 16 evaluates the acaricidal activity of two-spotted spider mite (Tetranychus urticae)
Method: untested compound is dissolved in suitable solvent such as n,N-Dimethylformamide (DMF), then with containing 0.2%
The water of Tween80 emulsifier is diluted to required concentration, if the blank without untested compound is blank control, 3 weights of every processing
It is multiple；The bean seedlings to grow fine inoculation red spider is selected, has 100-200 mite on every plant of bean seedlings, it, will be with mite after red spider colonizes
Bean seedlings are cut to be impregnated 10 seconds in the medical fluid of prepared formula (I) compound provided by the invention, and it is extra that taking-up is sucked with filter paper
Medical fluid, insert in and be filled with water in beaker, survival and dead mite number are checked in cultivating in observation ward, after 48 hours, results are averaged.
The result shows that the compound of the present invention has remarkable activity to red spider, under 500mg/L concentration, the compounds of this invention 6,7,
14,24 and 52 etc. have A grades of activity to red spider, and 1,12,13,35 and 50 etc. have B grades of activity to red spider.
Claims (10)
1. pyrazol acid amide compounds, it is characterised in that indicate pyrazol acid amide compounds with logical formula (I):
Wherein:
R represents C1-C12Alkyl, C2-C12Alkenyl, C2-C12Alkynyl group, C3-C8Naphthenic base or phenyl；
R1Represent C1-C12Alkyl, C2-C12Alkenyl, C2-C12Alkynyl group, C3-C8Naphthenic base or phenyl；
R2Represent hydrogen, halogen, C1-C12Alkyl, C2-C12Alkenyl, C2-C12Alkynyl group or C3-C8Naphthenic base；
R、R1And R2Some or all of middle hydrogen atom can be replaced by identical or different substituent group in following: halogen,
C1-C6Alkyl, C1-C6Alkoxy, C1-C6Alkylthio group, C1-C6Alkyl amine group, C2-C6Alkenyl, C2-C6Alkenyl oxy, C2-C6
Alkenyl thio, C2-C6Alkenyl amido, C2-C6Alkynyl group, C2-C6Alkynyl group oxygroup, C2-C6Alkynyl group sulfenyl, C2-C6Alkyne
Base amido, C3-C8Naphthenic base, C3-C8Cycloalkyl oxy, C3-C8Cycloalkylsulfanyl, C3-C8Naphthenic base amido, C6-C12Aryl or band
Heteroaryl, the C of up to 10 carbon atoms6-C12The heteroaryl oxygroup of up to 10 carbon atoms of aryloxy or band, C6-C12Aryl
Heteroarylthio, the C of up to 10 carbon atoms of sulfenyl or band6-C12The heteroaryl amine of up to 10 carbon atoms of arylamine group or band
Base, C6-C12Heteroarylaryl, the C of up to 10 carbon atoms of aryl or band6-C12Aryl heteroaryl or band up to 10 carbon
The heteroarylheteroaryl of atom；
R1And R2It can be connected to each other, form C with two carbon of pyrazole ring4-C8Cycloalkanes；
W represents oxygen or sulphur；
And R=R1=CH3, when W=O, R2Do not represent H；
In the definition of compound (I) given above, no matter term used exclusive use is also used in compound word, represent as follows
Substituent group:
Halogen: refer to fluorine, chlorine, bromine, iodine；
Alkyl: refer to linear or branched alkyl group；
Halogenated alkyl: referring to linear or branched alkyl group, hydrogen moiety on these alkyl or is all replaced by halogen atom；
Naphthenic base: refer to saturation or unsaturated ring alkyl；
Heterocyclylalkyl: refer to saturation or unsaturated heterocycle alkyl, at least 1 N, O and/or S in formula；
Halogenated cycloalkyl: referring to saturation or unsaturated ring alkyl, and hydrogen moiety therein or is all replaced by halogen atom；
Alkenyl；Refer to linear or branched alkyl group, and can in any position on there are double bonds；
Halogenated alkenyl: referring to linear or branched alkyl group, and can in any position on there are double bond, and hydrogen moiety therein
Or all replaced by halogen atom；
Alkynyl group；Refer to linear or branched alkyl group, and can in any position on there are three keys；
Halo alkynyl: referring to linear or branched alkyl group, and can in any position on there are three keys, and hydrogen moiety therein or
All replaced by halogen atom；
C6-C12Aryl means phenyl and by its derivative naphthalene, xenyl, anthryl or phenanthryl；
The heteroaryl of up to 10 carbon atoms of band refers to thiazolyl, pyrazolyl, thiadiazolyl group, pyridyl group, thienyl, benzothiophene
Base, furyl, benzofuranyl, pyrrole radicals, benzopyrrole base, indyl, benzindole base, imidazole radicals, benzimidazolyl, quinoline
Quinoline base, pyranose, pyrazinyl, pyrimidine radicals, pyridazinyl, benzopyranyl, benzopyrazines base, benzo pyrimidine radicals, benzo pyridazinyl,
Oxazolyl, isoxazolyl, benzoxazolyl, benzo isoxazolyl, benzothiazolyl, isothiazolyl, benzisothia oxazolyl or phonetic
Pyridine and triazolyl.
2. pyrazol acid amide compounds according to claim 1, it is characterised in that in compound shown in logical formula (I):
R represents C1-C12Alkyl or phenyl；R1Represent C1-C12Alkyl；R2Represent hydrogen, halogen or C1-C12Alkyl；And R, R1And R2In
Some or all of hydrogen atom can be replaced by identical or different substituent group in following: halogen, C1-C6Alkyl, C1-C6
Alkoxy；R1And R2It can be connected to each other, form C with two carbon of pyrazole ring5-C6Cycloalkane structure；W represents oxygen or sulphur.
3. pyrazol acid amide compounds according to claim 1, it is characterised in that in compound shown in logical formula (I):
R represents C1-C6Alkyl；R1Represent C1-C6Alkyl；R2Represent hydrogen, halogen, C1-C6Alkyl；And R, R1And R2The portion of middle hydrogen atom
Point or can all be replaced by identical or different substituent group in following: halogen, C1-C3Alkyl, C1-C3Alkoxy；W generation
Epoxy.
4. pyrazol acid amide compounds according to claim 1, it is characterised in that in compound shown in logical formula (I):
R represents methyl or ethyl；R1Represent C1-C6Alkyl；R2Represent hydrogen, halogen, C1-C3Alkyl；And R, R1And R2Middle hydrogen atom
It can partly or entirely be replaced by identical or different substituent group in following: halogen, methyl, ethyl, methoxyl group；W is represented
Oxygen.
5. pyrazol acid amide compounds according to claim 1, it is characterised in that compound shown in logical formula (I) is:
1,3- dimethyl-N-[(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides；
1,3,4- trimethyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides；
The chloro- 1,3- dimethyl-N-of 4- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides；
3- ethyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides；
3- ethyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- carbothioic acid amide；
3- ethyl -1,4- dimethyl-N-[(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides；
The chloro- 3- ethyl -1- methyl-N- of 4- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides；
The bromo- 3- ethyl -1- methyl-N- of 4- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides；
1- methyl -3- propyl -- N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides；
3- isopropyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides；
3- cyclopropyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides；
3- butyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides；
2- methyl-N- [(2- phenyl thiazole -4- base) methyl] -2,4,5,6- tetrahydro cyclopentyl alkane simultaneously [c] pyrazoles -3- benzoic acid amides；
2- methyl-N- [(2- phenyl thiazole -4- base) methyl] -4,5,6,7- tetrahydro -2H- Yin rattles away azoles -3- benzoic acid amides；
1- ethyl -3- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides；
The chloro- 1- ethyl -3- methyl-N- of 4- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides；
The chloro- 1,3- diethyl-N- of 4- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -5- benzoic acid amides；
3- methyl-1-phenyl-N- [(2- phenyl thiazole-4- base) methyl]-1H- pyrazoles-5- benzoic acid amides；
3- methyl-1-(4- chlorphenyl)-N- [(2- phenyl thiazole-4- base) methyl]-1H- pyrazoles-5- benzoic acid amides；
1- methyl -5- propyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -3- benzoic acid amides；
5- isopropyl -1- methyl-N- [(2- phenyl thiazole -4- base) methyl] -1H- pyrazoles -3- benzoic acid amides.
6. the preparation method of pyrazol acid amide compounds according to claim 1, it is characterised in that chemical combination shown in formula (I)
Object is prepared by reaction shown below,
Reaction equation 1:
Reaction equation 2:
Reaction equation 3:
Reaction equation 4:
In solvents tetrahydrofurane, acetonitrile, methylene chloride, dichloroethanes, toluene or dimethylbenzene, flow back in -10 DEG C~system warm
Degree, in no alkali or in the presence of triethylamine, pyridine, sodium hydride, sodium hydroxide, potassium hydroxide, shown in formula (II W=O)
Compound and the reaction of formula (III) compound represented, obtain formula (I W=O) compound, catalyst 4- dimethylamino pyridine is added can
To accelerate reaction to carry out；Formula (I W=O) compound represented is through sulfide P2S5Handle to obtain formula (I W=S) compound；
Solvent-free or in solvent dichloroethanes, methylene chloride or toluene, in 15 DEG C~system reflux temperature, with formula (IV W
=O) compound represented and formula (II W=O) compound is reacted to obtain with halide reagent thionyl chloride, phosgene or oxalyl chloride；
In the mixture of etoh solvent, tetrahydrofuran or ethyl alcohol and tetrahydrofuran, in 25 DEG C~system reflux temperature, 1.3 2
Chlroacetone and thiobenzamide react to obtain 4- chloromethyl -2- phenyl thiazole；4- chloromethyl -2- phenyl thiazole AMMONIA TREATMENT or
4- chloromethyl -2- phenyl thiazole reacts the solid object product of gained with potassium phthalimide and is handled with hydrazine hydrate up to formula (III)
Compound；
In etoh solvent, methanol, propyl alcohol, butanol or water, in the presence of alkali sodium ethoxide, sodium methoxide or sodium hydroxide, in -15 DEG C
~system reflux temperature is reacted with formula (V) or (V ') compound represented with diethy-aceto oxalate, is obtained shown in formula (VI) or (VI ')
Compound；After the compound of formula (VI) or (VI ') are routinely post-processed, then with hydrazine hydrate cyclization, obtain formula (VII) or (VII ')
Compound；In solvent n,N-Dimethylformamide, under the conditions of 30 DEG C~100 DEG C, the compound of formula (VII) or (VII ')
Formula (VIII) or (VIII ') compound are obtained with alkylating reagent dimethyl suflfate, dithyl sulfate or iodomethane reaction；Or formula
(VI) or the compound of (VI ') is after routinely post-processing, and with substitution hydrazine cyclization, obtains formula (VIII) or (VIII ') compound；
(VIII ') compound represented obtains formula (VIII) compound represented through respective reaction；Aqueous solvent, ethyl alcohol, methanol it is single
The in the mixed solvent of solvent or water and ethyl alcohol, water and methanol, in the presence of alkali sodium hydroxide or potassium hydroxide, in 50 DEG C~system
Under reflux temperature, (VIII) compound after conventional hydrolysis, with dilute hydrochloric acid solution handle formula (IV) compound；
R, R in formula1、R2, W have claim 1 given in define, Z is leaving group chlorine.
7. the purposes of described in any item pyrazol acid amide compounds according to claim 1~5, it is characterised in that 15~5000
There is sterilization, desinsection or mite killing bioactivity under gram effective component/hectare dosage.
8. described in any item pyrazol acid amide compounds are used to prepare with sterilization, desinsection or mite killing according to claim 1~5
The purposes of active drug.
9. a kind of sterilization, desinsection or miticide composition, it is characterised in that: containing appointing as active component such as Claims 1 to 5
Pyrazol acid amide compounds described in one, the weight percentage of active component is 0.5-99% in composition.
10. a kind of Clinics and Practices method of the non-disease of prevention and treatment pathogen, pest or harmful mite, it is characterised in that: by effective quantity
Pyrazol acid amide compounds as claimed in any one of claims 1 to 5 impose on the pathogen, pest, harmful mite or its growth
On medium.
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| CN109081810A (en) * | 2018-09-20 | 2018-12-25 | 沈阳药科大学 | The synthetic method of 1- methyl-3-((methylamino) methyl)-1H- pyrazoles-5- nitrile |
| CN109535154B (en) * | 2018-12-14 | 2021-09-10 | 南通大学 | Pyrazole amide compound containing 4-arylthiazole structure and preparation method and application thereof |
| CN109535143B (en) * | 2018-12-19 | 2021-12-10 | 南通大学 | Pyrazole amide derivative containing 5-aryl oxazole structure and preparation method and application thereof |
| CN113512002A (en) * | 2020-04-10 | 2021-10-19 | 华东理工大学 | Pyrazole amide compound containing azo structure and preparation and application thereof |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1222506A (en) * | 1997-11-25 | 1999-07-14 | 日本农药株式会社 | Phthalic acid diamide derivatives, agricultural and horticultural insecticides, and method for application of insecticides |
| CN103183669A (en) * | 2011-12-27 | 2013-07-03 | 湖南化工研究院 | Thiazole methylaminopyridine compounds and preparation method for same |
| CN104163791A (en) * | 2013-05-20 | 2014-11-26 | 湖南化工研究院 | N-pyridine (hetero) aryl amide compound and preparation method and application thereof |
| CN104277033A (en) * | 2013-07-02 | 2015-01-14 | 湖南化工研究院 | N-(arylalkyl)aryloxy phenoxy carboxylic acid amide compounds, and preparation method and application thereof |
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| CN103183669A (en) * | 2011-12-27 | 2013-07-03 | 湖南化工研究院 | Thiazole methylaminopyridine compounds and preparation method for same |
| CN104163791A (en) * | 2013-05-20 | 2014-11-26 | 湖南化工研究院 | N-pyridine (hetero) aryl amide compound and preparation method and application thereof |
| CN104277033A (en) * | 2013-07-02 | 2015-01-14 | 湖南化工研究院 | N-(arylalkyl)aryloxy phenoxy carboxylic acid amide compounds, and preparation method and application thereof |
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