CN105175335B - A kind of carboxamides derivatives of 3 (3,3 2 chloroallyloxyamino) 1 methylpyrazole 5 and preparation method thereof - Google Patents

A kind of carboxamides derivatives of 3 (3,3 2 chloroallyloxyamino) 1 methylpyrazole 5 and preparation method thereof Download PDF

Info

Publication number
CN105175335B
CN105175335B CN201510498215.5A CN201510498215A CN105175335B CN 105175335 B CN105175335 B CN 105175335B CN 201510498215 A CN201510498215 A CN 201510498215A CN 105175335 B CN105175335 B CN 105175335B
Authority
CN
China
Prior art keywords
methylpyrazole
bis
chloroallyloxyaminos
preparation
carboxamides derivatives
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN201510498215.5A
Other languages
Chinese (zh)
Other versions
CN105175335A (en
Inventor
毛武涛
鲍克燕
王志强
李政道
刘光印
曹凤璞
郭瑞婷
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nanyang Normal University
Original Assignee
Nanyang Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nanyang Normal University filed Critical Nanyang Normal University
Priority to CN201510498215.5A priority Critical patent/CN105175335B/en
Publication of CN105175335A publication Critical patent/CN105175335A/en
Application granted granted Critical
Publication of CN105175335B publication Critical patent/CN105175335B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or 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
    • C07D231/18—One oxygen or sulfur atom
    • C07D231/20—One oxygen atom attached in position 3 or 5
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—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
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/84—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

The invention belongs to technical field of pesticide, and in particular to a kind of carboxamides derivatives of 3 (3,3 two chloroallyloxyamino) 1 methylpyrazole 5 and preparation method thereof and the composition pesticide including said derivative.The carboxamides derivatives bacteriostatic activity of 3 (3,3 two chloroallyloxyamino) 1 methylpyrazole 5 of the invention is high, it is adaptable to the preventing and treating of agriculture field, the plant disease of field of forestry and horticultural field and virus disease, effectively preventing diseases and pests of agronomic crop.

Description

A kind of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- carboxamides derivatives and Its preparation method
Technical field
The invention belongs to technical field of pesticide, and in particular to a kind of 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazoles -5- Carboxamides derivatives and preparation method thereof and the composition pesticide including said derivative.
Background technology
Nitrogen-containing hetero cyclics have higher physiology and pharmacological activity, have important value in the exploitation of agricultural chemicals, Wherein pyrazoles is the 1,2- ribavirin five-ring heterocycles containing two nitrogen-atoms.Compound containing pyrazole ring has higher biology living Property, from nineteen forty-six Thmaposon, biological growth and U.S. Rubber in 1949 can be suppressed by reporting 2- pyrazoles -5- ketone for the first time Company has been synthesized after the foliage spray bactericide of pyrazoles, and pyrazole compound is achieved in pesticide field and developed rapidly, example Pyrolan, isolan, pyrazoles are prepared for as pyrazole ring is introduced carbamate, organophosphor by Geigy.s.A. companies in nineteen fifty-two The agricultural insecticides such as sulphur phosphorus, pyrazoles oxygen phosphorus and dimetilan.
And in recent years, commercialization or i.e. that the pesticide species containing pyrazole heterocycle of commercialization are more numerous is particularly in recent years fast Suddenly the pyrazole amide series bactericidal agent grown up, the pyrazole amide bactericide Bixafen of Bayer department exploitation first just reaches and finds and open The Isopyrazam of hair, compound fluxapyroxad and first just reach killing in the research and development later stage that BASF AG announces Microbial inoculum Sedaxane (Zhang Yibin, world pesticide, 2014,4 (36):31-33.), the common feature of these pesticide species be containing The amides compound of pyrazole heterocycle, with higher bactericidal activity, but be due to for a long time use, plant gradually generate compared with The high resistance to the action of a drug.
The content of the invention
An object of the present invention is to provide a kind of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- formamides Derivative, bioactivity is high.
The second object of the present invention is to provide above-mentioned 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- formyls The preparation method of amine derivative.
The third object of the present invention also resides in a kind of composition pesticide of offer, including above-mentioned 3- (3,3- dichloro allyl oxygen Base) -1- methylpyrazole -5- carboxamides derivatives.
To achieve the above object, the present invention is adopted the following technical scheme that：
A kind of 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- carboxamides derivatives, chemical structure of general formula is as follows：
Wherein, R is methyl, isopropyl, cyclopropyl, cyclopenta, cyclohexyl, morpholine, phenyl, 2- aminomethyl phenyls, 3- methyl Phenyl, 4- aminomethyl phenyls, 2- methoxyphenyls, 3- methoxyphenyls, 4- methoxyphenyls, 4- Trifluoromethoxyphen-ls, 2- fluorine Phenyl, 3- fluorophenyls, 4- fluorophenyls, 2- chlorphenyls, 3- chlorphenyls, 4- chlorphenyls, 2- bromophenyls, 3- bromophenyls, 4- bromophenyls, 2- trifluoromethyls, 3- trifluoromethyls, 4- trifluoromethyls, 2- cyano-phenyls, 3- cyano-phenyls, 4- cyano group benzene Base, 2-N, N- dimethylaminophenyls, 3-N, N- dimethylaminophenyls, 4-N, N- dimethylaminophenyls, 2- nitrobenzophenones, 3- nitrobenzophenones, 4- nitrobenzophenones, pyridine -2- bases, pyridin-3-yl, pyridin-4-yl, 3- picoline -2- bases, 4- methyl pyrroles Pyridine -2- bases, 5- picoline -2- bases, 2- phenyls, 2- p-fluorophenyls phenyl, 2- rubigan phenyl or 5- methyl thiazoliums Azoles -2- bases.
A kind of preparation method of 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- carboxamides derivatives, including it is following Step：
(1) preparation of intermediate 3- hydroxyls -1- methylpyrazoles -5- methyl formates：
A. 90~110mmol methylhydrazinium sulphates are added in three neck round bottom flask, dissolved with 180~220mL methanol, Dissociate followed by 180~220mmol triethylamines are added, be eventually adding 90~110mmol butine dimethyl phthalates, be heated to 40~60 DEG C, magnetic agitation, flow back 10~15h；
B. after the completion of reacting, stopping is heated, and is cooled to 5~10 DEG C, is stood, until white crystal is separated out, filter, wash, Dry, that is, obtain 3- hydroxyl -1- methylpyrazole -5- methyl formates；
(2) preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- methyl formates：
15~25mL of acetone, 3- hydroxyl -1- methylpyrazole -5- methyl formates 4.8 are sequentially added in three neck round bottom flask Room temperature 8~15h of condensation reaction under~5.2mmol, 1,1,3- 5~6mmol of tri chloropropene, alkalescence condition, is filtered, and is washed, concentration, Obtain 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- methyl formates；
(3) preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- formic acid：
C. by 1.8~2.2mmol of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- methyl formates, methanol 15~ 20mL, 3~5mL of distilled water, 3.5~4.5mmol of lithium hydroxide mixing, are stirred at room temperature 8~15h；
D. after reaction terminates, concentration adds distilled water, filtering, and hydrochloric acid adjusts pH to be 2.8~3.2, separates out white precipitate, mistake Filter, dries, produces 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- formic acid；
(4) preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- formyl chlorides：
0.8~1.2mmol of 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- formic acid is added in reaction bulb, according to 4~6mL of secondary addition chloroforms, 0.18~0.22mL thionyl chlorides, 45~55 DEG C of 1.5~2.5h of stirring reaction are concentrated under reduced pressure Obtain 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- formyl chlorides；
(5) preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- carboxamides derivatives：
E. 0.8~1.2mmol of 3- (3,3- dichloropropylenes epoxide) -1- methyl pyrazole -5- formyl chlorides is dissolved in 1.5~ In 2.5mL tetrahydrofuran solutions, added in reaction bulb 1.0~1.5mmol organic amine, 4~6mL dichloromethane, 1~ 2mmol triethylamines, are cooled under -2~0 DEG C, inert gas shielding and above-mentioned tetrahydrofuran solution are added dropwise, and completion of dropping is gradually increased to Room temperature, stirs 1~1.5h；
F. after reaction terminates, 10~12mL of dichloromethane is added, above-mentioned reaction solution is diluted, washed, is dried, concentration, institute The purifying of residue column chromatography is obtained, product is obtained.
According to the preparation method of above-mentioned 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- carboxamides derivatives, step Suddenly the alkalescence condition described in (2) is：6~8mmol of potassium carbonate, 0.05~0.25mmol of KI.
According to the preparation method of above-mentioned 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- carboxamides derivatives, step Suddenly the column chromatography condition described in (5) is：200~300 mesh silicagel columns, elution is petroleum ether and ethyl acetate with eluant, eluent, both Volume ratio is 3:1~10:1.
According to the preparation method of above-mentioned 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- carboxamides derivatives, institute The petroleum ether boiling point stated is 60~90 DEG C.
According to the preparation method of above-mentioned 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- carboxamides derivatives, step Suddenly the washing methods described in (5) is that watery hydrochloric acid, saturated sodium bicarbonate solution and saturated aqueous common salt are washed successively.
The reaction expression of above-mentioned preparation method is expressed as follows：
A kind of composition pesticide, including above-mentioned 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- formamides derive Thing.
According to above-mentioned composition pesticide, in addition to agricultural chemical insecticide, described agricultural chemical insecticide is chlopyrifos, it is sub- Nong, Acetamiprid, emamectin benzoate, milbemectin, AVM, pleocidin, fenvalerate, esfenvalerate, chlorine Cyano chrysanthemate, effective cypermethrin, Cyhalothrin, decis, Fenpropathrin, Beta- cyfloxylates, cyfluthrin chrysanthemum Ester, Lambda- Cyhalothrins, Permanone, permethrin, allethrin, cyhalothrin, Biphenthrin, chlorine chrysanthemum Ester, ethofenprox, flumethrin, fluvalinate, imidacloprid, Acetamiprid, Nitenpyram, imidaclothiz, thiacloprid, thiophene worm Piperazine, clothianidin, MTI-446, clothianadin, Da Tenan, diflubenzuron, d ichlorbenzuron, Teflubenzuron, grand deinsectization, HEXAFLUMURON, flufenoxuron, pyridine worm Grand, lufenuron, poisonous insect urea, penfluron, Noviflumuron are noviflumuron, flucycloxuron, Novaluron i.e. Rimon, fluorine pyridine Urea, Bay sir 6874 are { 1- [(3.5- bis- chloro- 4) 4-nitrophenoxy phenyl 3-3- (2- chlorobenzenes)-urea }, Bay SIR- 8514 i.e. [1- (4- Trifluoromethoxyphen-ls) -3- (2- chlorobenzenes)-urea], piperazine worm urea, Bistrifluron is bistrifluron, furan Mutter tebufenozide, tebufenozide, chlorine tebufenozide, methoxyfenozide, ring tebufenozide, Rogor, flolimat, DDVP, orthene, Hostathion, quinalphos, pyridaphethione, isazofos, isoprocarb, sevin, Aphox, MTMC, Mobucin, cartap, Zhong Ding Prestige, leaf disperse, carbaryl, Benfuracard micro, carbosulfan, cartap, fenisobromolate, Hexythiazox, fenpyroximate, pyridaben, four Mite piperazine, propargite, diafenthiuron, Benfuracard micro, pymetrozine, Envidor, spiral shell worm ester, spiral shell worm ethyl ester, butene-fipronil, triazole Tin, Buprofezin, phonamiphos, ethiprole, Cupric sulfate, dimehypo, chlorantraniliprole, Flubendiamide, fluorine cyanogen insect amide, cyanogen insect amide, It is any one in Tolfenpyrad, tebufenpyrad, chlorfenapyr, pyrazinones, etoxazole, tebufenpyrad, rattle away young ketone, Nylar, emaricin Plant or several combinations.
According to above-mentioned composition pesticide, in addition to agriculture chemicals fungicide, described agriculture chemicals fungicide is diazosulfide, thiophene Acyl bacterium amine, tisocromide, first thiophene lure amine, 4- methyl isophthalic acids, 2,3- thiadiazoles -5- formic acid, 4- methyl isophthalic acids, 2,3- thiadiazoles -5- formic acid Sodium, 4- methyl isophthalic acids, 2,3- thiadiazoles -5- Ethyl formates, DL- beta-aminobutyric acids, isotianil, virazole, antofine, Ningnan are mould Element or salicylic acid, cymoxanil, thiram, ziram, Mancozeb, aliette, thiophanate-methyl, Bravo, enemy can pines, rotten mould Profit, fenpropidin, thiophanate methyl, thiophanate, Metalaxyl-M, salicylic acid, flumorph, dimethomorph, mefenoxam, efficient benzene White spirit, double chlorine zarilamid, flusulfamide, first flusulfamide, thiophene fluorine bacterium amine, flutolanil, tecloftalam, ring propionyl bacterium amine, cyflufenamid, ring Acyl bacterium amine, zarilamid, Silthiopham, furametpyr, pyrrole metsulfovax, mandipropamid, zoxamide, fenfuram, carboxin, Chlozolinate, iprodione, Fluoxastrobin, dimoxystrobin, fluoxastrobin, kresoxim-methyl, SSF 126, orysastrobin, ZEN 90160, azoles bacterium amine Ester, trifloxystrobin, Enestroburin, alkene oxime amine, oxygen ring azoles, bromuconazole, Cyproconazole, Difenoconazole, olefin conversion, efficient alkene azoles Alcohol, epoxiconazole, RH-7592, Fluquinconazole, Flusilazole, Flutriafol, hexaconazole, glyoxalin, kind bacterium azoles, metconazole, nitrile bacterium azoles, penta bacterium Azoles, propiconazole, prothioconazoles, simeconazoles, Tebuconazole, tetraconazole, Triadimenol, triticonazole, bitertanol, probenazole, wheat Fringe is peaceful, imazalil, efficient imazalil, Prochloraz, fluorine bacterium azoles, cyazofamid, Fenamidone, Evil imidazoles, pefurazoate, famoxadones, The spirit of SYP-Z048, hymexazo, Evil frosts, Guardian, Grandox fumigant, octhilinone, benthiozole, dodemorph, butadiene morpholine, ten Morpholine, fenpiclonil, fludioxonil, fluazinam, pyrifenox, ring pyridine bacterium amine, Boscalid, fluopicolide, pyridine bacterium amine, phonetic collarium Amine, fluorine mepanipyrim, ferimzone, mepanipyrim, pyrimethanil, Fenarimol, nuarimol, chinomethionat, dithianon, ethoxyquin Quinoline, oxyquinoline, the third oxygen quinoline, quinoxyfen, diethofencarb, iprovalicarb, benzene metsulfovax, Propamocarb, methasulfocarb, edifenphos, Different rice blast net, pyrazophos, tolelofos-methyl, blasticidin-S, kasugarnycin, polyoxin, Polyoxin, valida, well ridge are mould Element, streptomysin, metalaxyl, furalaxyl, M 9834, ofurace, mebenil, carbendazim, benomyl, thiophanate-methyl, triazolone, Bupirimate, dimethirimol, ethirimol, difoltan, captan, folpet, vinclozolin, fluoromide, sclerotium Only, Bravo, Isoprothiolane, kitazine, Yekuzuo, pentachloronitrobenzene, Mancozeb, Propineb, phosethyl-Al, sulphur, ripple Your many liquid, copper sulphate, copper oxychloride, cuprous oxide, Kocide SD, metrafenone, Pencycuron, diclomezin, Rabcide, cough up quinoline Ketone, volution bacterium amine, tricyclazole, triforine, many fruit pyridines, the pungent salt of biguanides, iminoctadine, botran, benzene flusulfamide, toluene sulphur bacterium Amine, K-281, fenaminosulf, oxolinic acide, probenazole, bronopol, iodomethane, metham-sodium, enemy's line ester, dazomet, dichloro isopropyl Ether, lythidathion, cadusafos, fensulfothion, thionazin, fenamiphos, phonamiphos, dichlofenthion, isazofos, fosthietan, oxamyl, tears Any one or a few the combination gone out in prestige, carbofuran, vikane, dichloropropylene, dichloro-isonicotinic acid, allyl isothiazole.
The positive beneficial effect of the present invention：
3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- carboxamides derivatives bacteriostatic activity of the present invention is high, it is adaptable to The preventing and treating of agriculture field, the plant disease of field of forestry and horticultural field and virus disease, effectively preventing crop diseases and pest Evil.
3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- carboxamides derivatives chemical yield of the present invention is high, purity Height, preparation method is simple, and production cost is low, it is easy to operate.
Embodiment
With reference to some specific embodiments, the present invention is further described.
Embodiment 1
A kind of 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- carboxamides derivatives, chemical structure of general formula is as follows：
Wherein, R is methyl.
The preparation method of above-mentioned 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- carboxamides derivatives include with Lower step：
(1) preparation of intermediate 3- hydroxyls -1- methylpyrazoles -5- methyl formates：
A. 100mmol methylhydrazinium sulphates are added in three neck round bottom flask, dissolved with 200mL methanol, followed by adding Enter 200mmol triethylamines to dissociate, be eventually adding 100mmol butine dimethyl phthalates, be heated to 60 DEG C, magnetic agitation, backflow 15h；
B. after the completion of reacting, stop heating, be cooled to 5 DEG C, stand 2 days, until white crystal is separated out, filtering, ethanol are washed Wash, dry, that is, obtain 3- hydroxyl -1- methylpyrazole -5- methyl formates, yield is 60%, purity >=95%,1H NMR (400MHz,DMSO-d6):δ=3.79 (s, 3H), 3.88 (s, 3H), 6.01 (s, 1H), 10.05 (s, 1H)；
(2) preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- methyl formates：
Acetone 20mL, 3- hydroxyl -1- methylpyrazole -5- methyl formates 5mmol, 1 are sequentially added in three neck round bottom flask, Room temperature condensation reaction 12h under 1,3- tri chloropropene 5.5mmol alkalescence conditions, filtering, acetone washing, concentration obtains white solid 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- methyl formates, yield 95%, purity >=95%,1H NMR(400MHz, CDCl3) δ 6.39 (s, 1H), 6.22 (t, J=6.2Hz, 1H), 4.71 (d, J=6.1Hz, 2H), 4.01 (s, 3H), 3.82 (s, 3H)；
(3) preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- formic acid：
C. by 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- methyl formates 2mmol, methanol 16mL, distilled water 4mL, lithium hydroxide 4mmol are mixed, and 12h is stirred at room temperature；
D. after reaction terminates, concentration removes most of solvent, adds distilled water, filters a small amount of not tolerant, aqueous phase hydrochloric acid It is 3 to adjust pH, separates out white precipitate, is filtered, and dries, produces 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- formic acid, is received Rate 96%, purity >=95%；
(4) preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- formyl chlorides：
3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- formic acid 1.0mmol is added in reaction bulb, added successively Enter 5mL chloroforms, 0.2mL thionyl chlorides, 50 DEG C of stirring reaction 2h are concentrated under reduced pressure to give but yellow solid 3- (3,3- dichloros Allyloxy) -1- methylpyrazole -5- formyl chlorides；
(5) preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- carboxamides derivatives：
E. 3- (3,3- dichloropropylenes epoxide) -1- methyl pyrazole -5- formyl chlorides 1.0mmol is dissolved in 2mL tetrahydrofurans In solution, 1.2mmol methylamine, 5mL dichloromethane, 1.5mmol triethylamines is added in reaction bulb, 0 DEG C, nitrogen is cooled to Protection is lower to be added dropwise above-mentioned tetrahydrofuran solution, and completion of dropping is gradually increased to room temperature, stirs 1h；
F. after reaction terminates, dichloromethane 10mL is added, above-mentioned reaction solution is diluted, washed, is dried, concentration, gained is residual Excess column chromatography is purified, elution, obtains product, product purity >=97%.
Alkalescence condition described in step (2) is：Potassium carbonate 7.5mmol, KI 0.1mmol.
Column chromatography condition described in step (5) is：200~300 mesh silicagel columns, eluant, eluent be petroleum ether and ethyl acetate, Both volume ratios are 5:1.
Described petroleum ether boiling point is 60~90 DEG C.
Washing methods described in step (5) is washed successively for watery hydrochloric acid, saturated sodium bicarbonate solution and saturated aqueous common salt.
Embodiment 2~45 is similar with above-described embodiment general principle, does not repeat, and is a difference in that：R be respectively isopropyl, Cyclopropyl, cyclopenta, cyclohexyl, morpholine, phenyl, 2- aminomethyl phenyls, 3- aminomethyl phenyls, 4- aminomethyl phenyls, 2- methoxyphenyls, 3- methoxyphenyls, 4- methoxyphenyls, 4- Trifluoromethoxyphen-ls, 2- fluorophenyls, 3- fluorophenyls, 4- fluorophenyls, 2- chlorobenzenes Base, 3- chlorphenyls, 4- chlorphenyls, 2- bromophenyls, 3- bromophenyls, 4- bromophenyls, 2- trifluoromethyls, 3- trifluoromethylbenzenes Base, 4- trifluoromethyls, 2- cyano-phenyls, 3- cyano-phenyls, 4- cyano-phenyls, 2-N, N- dimethylaminophenyls, 3-N, N- dimethylaminophenyls, 4-N, N- dimethylaminophenyls, 2- nitrobenzophenones, 3- nitrobenzophenones, 4- nitrobenzophenones, pyridine- 2- bases, pyridin-3-yl, pyridin-4-yl, 3- picoline -2- bases, 4- picoline -2- bases, 5- picoline -2- bases, 2- benzene Base phenyl, 2- p-fluorophenyls phenyl, 2- rubigan phenyl, 5- methylthiazol -2- bases..
The preparation method of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- carboxamides derivatives of embodiment 2~45 Similar to Example 1, something in common is not repeated, and is a difference in that：Organic amine R-NH described in step (5)2Respectively with described R Group is corresponding.
3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- carboxamides derivatives prepared by above-described embodiment 1~45 Physical and chemical parameter be shown in Table 1.
3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- formamides prepared by the embodiment of the present invention 1~45 of table 1 spread out Biological physical and chemical parameter
3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- formamides described in embodiments of the invention 1~45 derive Thing suppresses the determination experiment of disease fungus growth activity：
Method of testing：Thalli growth rate determination method.
Detailed process is：(1) any described 3- (chloroallyloxyaminos of the 3,3- bis-) -1- methyl pyrroles of 5mg embodiments 1~45 are taken Azoles -5- carboxamides derivatives are dissolved in appropriate dimethylformamide, are then used and are contained a certain amount of polysorbas20 emulsifier aqueous solution 500 μ g/mL medicament is diluted to, reagent agent is aseptically respectively drawn in 1mL injection culture dishes, then be separately added into 9 Milliliter culture medium, is made 50 μ g/mL pastille flat boards, blank control is done with the flat board for adding 1mL aqua sterilisas after shaking up.
(2) bacterium disk is cut along mycelia outer rim with diameter 4mm card punch, moves on pastille flat board, put in equilateral triangle To put, often processing is repeated 3 times, culture dish is placed on culture in 24 ± 1 DEG C of constant incubators, colony diameter to be compareed expands to 2~ After 3cm, each processing bacterium disk extension diameter is investigated, is averaged, the relative bacteriostasis rate of calculating is compared with blank control.
For examination strain：For the kind of a variety of representative most of phytopathogens that field is actually occurred in China's agricultural production Category, AS：Tomato early blight bacterium (Alternaria solani)；BC：Botrytis cinerea pers (Botrytis cinerea)；CA：Flower Raw brown patch germ (Cercospora arachidicola)；GZ：Fusarium graminearum (Gibberella zeae)；PI：Ma Ling Potato late disease bacteria (Phytophthora infestans (Mont.) de Bary)；PP：Botryosphaeria berengeriana f. sp (Physalospora piricola)；PS：Rhizoctonia solani Kuhn (Pellicularia sasakii)；RC：Rhizoctonia cerealis (Rhizoctonia cerealis)；SS：Sclerotinia sclerotiorum (Sclerotinia sclerotiorum).
Experimental result is shown in Table 2.
Bacteriostasis rate testing result/the % of the 3- of table 2 (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- carboxamides derivatives
Compound PI CA AS GZ PP BC SS RC PS
Mg-M-01 41.4 45.8 14.2 40.8 56.6 79.2 47.9 74.9 20.6
Mg-M-02 36.8 40.1 16.6 60.0 71.2 40.7 46.1 71.2 24.7
Mg-M-03 36.8 40.1 10.6 45.9 43.8 45.0 49.7 82.1 12.3
Mg-M-04 32.2 28.6 7.1 47.2 80.3 62.1 51.4 71.2 24.7
Mg-M-05 32.2 45.8 10.6 56.1 62.1 30.0 46.1 78.5 28.8
Mg-M-06 36.8 22.9 17.7 39.5 65.7 47.1 55.0 93.5 24.7
Mg-M-07 23.0 22.9 9.0 37.0 82.2 49.3 37.2 82.0 16.4
Mg-M-08 22.0 50 33.3 65.4 61.8 36.9 60 90.9 43.7
Mg-M-09 7.3 42.9 22.2 50 47.1 39.1 55 36.4 12.5
Mg-M-10 65.8 42.9 22.2 38.5 50.0 39.1 50.0 59.1 12.5
Mg-M-11 36.6 57.1 55.6 73.1 47.1 43.5 30 72.7 37.5
Mg-M-12 41.5 64.3 50 65.4 32.4 36.9 30 36.4 18.8
Mg-M-13 17.1 50 33.3 42.3 55.9 39.1 55 86.4 25.0
Mg-M-14 23.0 17.2 0.0 38.3 62.1 45.0 37.2 30.2 12.3
Mg-M-15 65.9 64.3 50 61.5 67.6 43.5 35 95.5 31.3
Mg-M-16 56.1 64.3 50 65.4 58.8 52.2 70 100 43.8
Mg-M-17 2.4 21.4 27.8 38.5 23.5 39.1 30 31.8 12.5
Mg-M-18 27.6 11.4 13.1 28.1 69.4 47.1 33.7 82.2 20.6
Mg-M-19 27.6 28.6 3.5 30.6 43.8 0.0 28.4 65.2 16.4
Mg-M-20 32.2 34.3 7.8 38.3 63.9 30.0 39.0 70.9 12.3
Mg-M-21 46.0 62.9 45.7 85.5 47.5 92.1 69.2 70.9 82.2
Mg-M-22 21.2 19.1 38.8 56.1 60.8 48.6 53.2 66.2 29.9
Mg-M-23 27.2 22.9 23.9 32.9 80.5 29.4 49.4 71.9 12.8
Mg-M-24 12.1 11.4 12.0 34.2 78.7 33.3 41.8 64.7 17.1
Mg-M-25 27.2 7.6 47.8 41.1 48.3 14.1 38.0 96.4 8.5
Mg-M-26 65.9 64.3 44.4 69.2 55.8 47.8 65 90.9 50.0
Mg-M-27 24.2 22.9 6.0 39.7 73.3 44.8 38.0 79.1 21.3
Mg-M-28 27.2 15.3 26.9 49.3 60.8 32.0 39.9 94.9 17.1
Mg-M-29 24.2 26.7 3.0 43.8 76.9 42.2 39.9 97.8 25.6
Mg-M-30 30.2 19.1 0.0 37.0 71.6 34.5 43.7 97.8 21.3
Mg-M-31 60.4 22.9 3.0 47.9 80.5 29.4 45.6 78.0 34.2
Mg-M-32 15.1 64.9 56.8 84.9 84.1 90.8 49.4 92.1 47.0
Mg-M-33 45.3 15.3 38.8 32.9 64.4 19.2 41.8 68.0 17.1
Mg-M-34 60.8 57.2 71.7 84.9 62.6 92.1 70.3 82.2 89.7
Mg-M-35 47.0 73.6 47.4 86.4 83.1 13.2 61.7 96.4 67.6
Mg-M-36 26.8 12.9 19.3 47.2 9.7 29.0 35.4 84.7 82.6
Mg-M-37 15.0 27.9 0.0 38.6 18.2 44.0 63.3 82.2 46.1
Mg-M-38 16.1 34.3 6.4 44.0 3.2 42.9 70.8 73.7 38.6
Mg-M-39 37.6 27.9 0.0 36.5 7.5 42.9 67.6 96.9 59.0
Mg-M-40 20.4 44.0 6.4 46.1 7.5 32.2 71.9 90.4 68.7
Mg-M-41 15.0 33.3 35.4 32.2 16.1 22.5 23.6 82.5 95.5
Mg-M-42 15.0 29.0 46.1 38.6 26.8 11.8 0.0 94.0 30.0
Mg-M-43 15.0 33.3 30.0 37.6 20.4 25.8 36.5 80.0 89.1
Mg-M-44 24.7 37.6 18.2 33.3 18.2 40.8 47.2 75.5 37.6
Mg-M-45 7.5 41.8 40.8 31.1 9.7 8.6 66.5 89.4 62.2
Interpretation of result：From table 2 it can be seen that 3- (3,3- bis- chloroallyloxyamino) -1- methyl of the embodiment of the present invention 1~45 Pyrazoles -5- carboxamides derivatives good antimicrobial effects.

Claims (7)

1. a kind of 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- carboxamides derivatives, chemical structure of general formula is as follows：
R be methyl, isopropyl, cyclopropyl, cyclopenta, cyclohexyl, 3- aminomethyl phenyls, 3- methoxyphenyls, 4- methoxyphenyls, 4- Trifluoromethoxyphen-ls, 3- fluorophenyls, 3- chlorphenyls, 3- bromophenyls, 2- trifluoromethyls, 3- trifluoromethyls, 4- Trifluoromethyl, 2- cyano-phenyls, 3- cyano-phenyls, 2-N, N- dimethylaminophenyls, 3-N, N- dimethylaminophenyls, 4-N, N- dimethylaminophenyl, 2- nitrobenzophenones, 3- nitrobenzophenones, pyridine -2- bases, pyridin-3-yl, pyridin-4-yl, 3- first Yl pyridines -2- bases, 4- picoline -2- bases, 5- picoline -2- bases, 2- phenyls, 2- p-fluorophenyls phenyl, 2- are to chlorine Phenyl or 5- methylthiazol -2- bases.
2. a kind of preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- carboxamides derivatives described in claim 1 Method, comprises the following steps：
(1) preparation of intermediate 3- hydroxyls -1- methylpyrazoles -5- methyl formates：
A. 90~110mmol methylhydrazinium sulphates are added in three neck round bottom flask, dissolved with 180~220mL methanol, then connect 180~220mmol of addition triethylamines to dissociate, be eventually adding 90~110mmol butine dimethyl phthalates, be heated to 40~60 DEG C, Magnetic agitation, flow back 10~15h；
B. after the completion of reacting, stopping is heated, and is cooled to 5~10 DEG C, standing, until white crystal is separated out, is filtered, washs, dried, Obtain 3- hydroxyl -1- methylpyrazole -5- methyl formates；
(2) preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- methyl formates：
Sequentially added in three neck round bottom flask 15~25mL of acetone, 3- hydroxyl -1- methylpyrazole -5- methyl formates 4.8~ Room temperature 8~15h of condensation reaction under 5.2mmol, 1,1,3- 5~6mmol of tri chloropropene, alkalescence condition, is filtered, and is washed, and concentration is obtained To 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- methyl formates；
(3) preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- formic acid：
C. by 1.8~2.2mmol of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- methyl formates, 15~20mL of methanol, 3~5mL of distilled water, 3.5~4.5mmol of lithium hydroxide are mixed, and 8~15h is stirred at room temperature；
D. after reaction terminates, concentration adds distilled water, filtering, and hydrochloric acid adjusts pH to be 2.8~3.2, separates out white precipitate, filter, does It is dry, produce 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- formic acid；
(4) preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- formyl chlorides：
0.8~1.2mmol of 3- (3,3- bis- chloroallyloxyamino) -1- methylpyrazole -5- formic acid is added in reaction bulb, added successively Enter 4~6mL chloroforms, 0.18~0.22mL thionyl chlorides, 45~55 DEG C of 1.5~2.5h of stirring reaction are concentrated under reduced pressure to give 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- formyl chlorides；
(5) preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- carboxamides derivatives：
E. 0.8~1.2mmol of 3- (3,3- dichloropropylenes epoxide) -1- methyl pyrazole -5- formyl chlorides is dissolved in 1.5~2.5mL In tetrahydrofuran solution, 1.0~1.5mmol organic amine, 4~6mL dichloromethane, the second of 1~2mmol tri- is added in reaction bulb Amine, is cooled under -2~0 DEG C, inert gas shielding and above-mentioned tetrahydrofuran solution is added dropwise, and completion of dropping is gradually increased to room temperature, stirring 1~1.5h；
F. after reaction terminates, 10~12mL of dichloromethane is added, above-mentioned reaction solution is diluted, washed, is dried, concentration, gained is residual Excess column chromatography is purified, elution, obtains product.
3. the preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- carboxamides derivatives according to claim 2 Method, it is characterised in that the alkalescence condition described in step (2) is：6~8mmol of potassium carbonate, 0.05~0.25mmol of KI.
4. the preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- carboxamides derivatives according to claim 2 Method, it is characterised in that the column chromatography condition described in step (5) is：200~300 mesh silicagel columns, elution is oil with eluant, eluent Ether and ethyl acetate, both volume ratios are 3:1~10:1.
5. the preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- carboxamides derivatives according to claim 4 Method, it is characterised in that described petroleum ether boiling point is 60~90 DEG C.
6. the preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- carboxamides derivatives according to claim 2 Method, it is characterised in that washing methods described in step (5) for watery hydrochloric acid, saturated sodium bicarbonate solution and saturated aqueous common salt according to Secondary washing.
7. a kind of composition pesticide, it is characterised in that including 3- (3,3- bis- chloroallyloxyamino) -1- first described in claim 1 Base pyrazoles -5- carboxamides derivatives.
CN201510498215.5A 2015-08-13 2015-08-13 A kind of carboxamides derivatives of 3 (3,3 2 chloroallyloxyamino) 1 methylpyrazole 5 and preparation method thereof Expired - Fee Related CN105175335B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510498215.5A CN105175335B (en) 2015-08-13 2015-08-13 A kind of carboxamides derivatives of 3 (3,3 2 chloroallyloxyamino) 1 methylpyrazole 5 and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510498215.5A CN105175335B (en) 2015-08-13 2015-08-13 A kind of carboxamides derivatives of 3 (3,3 2 chloroallyloxyamino) 1 methylpyrazole 5 and preparation method thereof

Publications (2)

Publication Number Publication Date
CN105175335A CN105175335A (en) 2015-12-23
CN105175335B true CN105175335B (en) 2017-11-03

Family

ID=54897856

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510498215.5A Expired - Fee Related CN105175335B (en) 2015-08-13 2015-08-13 A kind of carboxamides derivatives of 3 (3,3 2 chloroallyloxyamino) 1 methylpyrazole 5 and preparation method thereof

Country Status (1)

Country Link
CN (1) CN105175335B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111620850B (en) * 2020-05-27 2021-06-29 江苏七洲绿色化工股份有限公司 Preparation method of 1- (3-chloropyridine-2-yl) -3-bromo-1H-pyrazole-5-formic ether
CN114685448A (en) * 2020-12-25 2022-07-01 江苏天士力帝益药业有限公司 Synthesis method of zopiclone impurity pyrazine-2-carboxylic acid (5-chloro-pyridin-2-yl) -amide

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1711255A (en) * 2002-11-15 2005-12-21 杜邦公司 Novel anthranilamide insecticides
WO2010003350A1 (en) * 2008-07-07 2010-01-14 中国中化集团公司 1-substituted pyridyl-pyrazolyl amide compounds and uses thereof
CN101659655A (en) * 2009-09-15 2010-03-03 南开大学 Pyrazole amide derivative and application thereof
CN104203237A (en) * 2012-01-24 2014-12-10 艾库里斯有限及两合公司 Amidine substituted beta - lactam compounds, their preparation and use as antibacterial agents
CN104725348A (en) * 2013-05-20 2015-06-24 江苏省农药研究所股份有限公司 Anthraniloyl alkyl iso (thio) urea compound and synthesis method and application thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1711255A (en) * 2002-11-15 2005-12-21 杜邦公司 Novel anthranilamide insecticides
WO2010003350A1 (en) * 2008-07-07 2010-01-14 中国中化集团公司 1-substituted pyridyl-pyrazolyl amide compounds and uses thereof
CN101659655A (en) * 2009-09-15 2010-03-03 南开大学 Pyrazole amide derivative and application thereof
CN104203237A (en) * 2012-01-24 2014-12-10 艾库里斯有限及两合公司 Amidine substituted beta - lactam compounds, their preparation and use as antibacterial agents
CN104725348A (en) * 2013-05-20 2015-06-24 江苏省农药研究所股份有限公司 Anthraniloyl alkyl iso (thio) urea compound and synthesis method and application thereof

Also Published As

Publication number Publication date
CN105175335A (en) 2015-12-23

Similar Documents

Publication Publication Date Title
CN105061396B (en) A kind of amide derivatives and preparation method thereof
CN107531700A (en) Meso-ionic compound
CN105622422B (en) A kind of bromo hexahydro indanone compounds and its production and use
CN109970650A (en) Pyrazole phenyl formamide analog derivative and its preparation method and application
CN105175335B (en) A kind of carboxamides derivatives of 3 (3,3 2 chloroallyloxyamino) 1 methylpyrazole 5 and preparation method thereof
CN105175336B (en) A kind of carboxamides derivatives of 3 (3,3 2 chloroallyloxyamino) 1 Phenylpyrazole 5 and preparation method thereof
CN105828614A (en) Co-crystal production method
CN110128419A (en) A kind of difluoro pyrazole heterocycle carboxamides derivatives and its preparation method and application
CN109970653A (en) Methoxy acrylate derivative and its preparation method and application of the one kind containing difluoromethyl pyrazole
CN110041260A (en) A kind of multi-substituted pyrazol amide derivatives and its preparation method and application
CN116891466A (en) Pyrazole-containing dithiazole carboxamide derivative and preparation method and application thereof
CN107602515A (en) One kind 5A5B6CTricyclic spiro lactone derivatives and its production and use
CN113929696B (en) Acyl thiourea psoralen derivatives, and preparation method and application thereof
CN104496980B (en) Novel thiazole heterocyclic compounds and its preparation method and application
CN107226812A (en) One class piperidines thiazole oxime ether methoxy base acrylate derivative and its production and use
CN113929695B (en) Sulfimide psoralen derivatives, and preparation method and application thereof
CN110128346A (en) A kind of biaryl amide pyrazole derivatives and its preparation method and application
US10906880B2 (en) Kind of isothiazole oxime ether-containing strobilurin derivatives and its preparation methods and application
CN113880863B (en) 1,2, 4-triazole [3,4-b ] -1,3, 4-thiadiazine derivatives, and preparation method and application thereof
CN107602547A (en) Heterocycle triazole derivative and its production and use
CN112480103A (en) Coumarin derivatives containing 3, 4-dichloroisothiazole and preparation method and application thereof
CN107459509A (en) A kind of nitrogenous sulfur-bearing sulfimide derivative and its production and use
CN112358474A (en) Difluoropyrazole thiazole methanamide derivatives and preparation method and application thereof
CN108191787A (en) A kind of isothiazole imdazole derivatives and its preparation method and application
CN106995420B (en) A kind of thiadiazoles oxime ether methoxy base acrylate derivative and its preparation method and application

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20171103

Termination date: 20180813