CN105175336B - A kind of carboxamides derivatives of 3 (3,3 2 chloroallyloxyamino) 1 Phenylpyrazole 5 and preparation method thereof - Google Patents
A kind of carboxamides derivatives of 3 (3,3 2 chloroallyloxyamino) 1 Phenylpyrazole 5 and preparation method thereof Download PDFInfo
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- CN105175336B CN105175336B CN201510495921.4A CN201510495921A CN105175336B CN 105175336 B CN105175336 B CN 105175336B CN 201510495921 A CN201510495921 A CN 201510495921A CN 105175336 B CN105175336 B CN 105175336B
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- 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
- C07D231/22—One oxygen atom attached in position 3 or 5 with aryl radicals attached to ring nitrogen atoms
- C07D231/26—1-Phenyl-3-methyl-5- pyrazolones, unsubstituted or substituted on the phenyl ring
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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
- A01N43/48—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
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 Phenylpyrazole 5 and preparation method thereof and the composition pesticide comprising said derivative.The carboxamides derivatives bacteriostatic activity of 3 (3,3 two chloroallyloxyamino) 1 Phenylpyrazole 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
Technical field
The invention belongs to technical field of pesticide, and in particular to a kind of 3- (3,3- bis- chloroallyloxyamino) -1- Phenylpyrazoles -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, pyrrole are prepared for as pyrazole ring is introduced carbamate, organophosphor by Geigy.s. A. companies in nineteen fifty-two
The agricultural insecticides such as azoles 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 reaching in the research and development later stage that BASF AG announces
Bactericide Sedaxane (Zhang Yibin, world pesticide, 2014,4 (36):31-33.), the common feature of these pesticide species is to contain
There is the amides compound of pyrazole heterocycle, with higher bactericidal activity.
The content of the invention
An object of the present invention is to provide a kind of 3- (chloroallyloxyaminos of 3,3- bis-) -1- Phenylpyrazole -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- Phenylpyrazole -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- Phenylpyrazole -5- benzoyl amine 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- Phenylpyrazole -5- carboxamides derivatives, chemical structure of general formula is as follows：
Wherein, R is isopropyl, cyclohexyl, 3- aminomethyl phenyls, 4- aminomethyl phenyls, 3- methoxyphenyls, 4- methoxybenzenes
Base, 2- fluorophenyls, 3- fluorophenyls, 4- bromophenyls, 4- trifluoromethyls, pyridine -2- bases or 2- p-fluorophenyl phenyl.
A kind of preparation method of above-mentioned 3- (3,3- bis- chloroallyloxyamino) -1- Phenylpyrazole -5- carboxamides derivatives, bag
Include following steps：
(1) preparation of 5- oxo pyrazoles alkane -2- phenyl -3- carboxylic acid, ethyl esters：
A. 35~45mL absolute ethyl alcohols are added into three neck round bottom flask, 25~35mmol metallic sodiums are added portionwise, are stirred
10~15min, forms alcohol sodium solution, is subsequently added into 28~32mmol phenylhydrazines formation yellow suspension, 60~70 DEG C of heating is extremely
28~32mmol diethyl maleates are added dropwise under backflow, reflux state, drop finishes, and continues the 0.8~1.2h that flows back；
B. after reaction terminates, reaction solution is cooled to 35~45 DEG C, adds 25~35mmol glacial acetic acids, and reaction solution is concentrated into
It is dry, produce 5- oxo pyrazoles alkane -2- phenyl -3- carboxylic acid, ethyl esters；
(2) preparation of 1- phenyl -3- hydroxy-pyrazoles -5- Ethyl formates：
Addition 40~45mmol 5- oxo pyrazoles alkane -2- phenyl -3- carboxylic acid, ethyl esters into single necked round bottom flask, 90~
110mL acetonitriles, 3~5mL 98wt% concentrated sulfuric acids stir 5~10min, and 45~52mmol K are added afterwards2S2O8, it is stirred at reflux
5~5.5h, is cooled to room temperature, obtains brown solution, concentration, gained residue column chromatography purifying, obtain yellow solid 1- phenyl-
3- hydroxy-pyrazole -5- Ethyl formates；
(3) preparation of 3- (3,3- dichloropropylenes epoxide) -1- Phenylpyrazole 5- Ethyl formates：
By 0.8~1.2mmol 1- phenyl -3- hydroxypyrazoles -5- Ethyl formates, 1.2~1.5mmol 1,1,3- trichlorines third
Room temperature 12~16h of condensation reaction under alkene, 3~5mL of acetone mixing, alkalescence condition, is filtered, concentration, gained residue column chromatography is pure
Change, obtain rufous grease 3- (3,3- dichloropropylene epoxide) -1- Phenylpyrazole 5- Ethyl formates；
(4) preparation of 3- (3,3- dichloropropylenes epoxide) -1- Phenylpyrazole -5- formic acid：
C. into 0.8~1.0mmol 3- (3,3- dichloropropylenes epoxide) -1- Phenylpyrazole 5- Ethyl formates add 2~
3mmol lithium hydroxides, are dissolved with 5~8mL methanol solution, 10~15h of backflow are stirred at room temperature；
D. after reaction terminates, concentration adds distilled water, is filtered under diminished pressure removing inorganic salts, aqueous phase is acidified to pH with hydrochloric acid
3.8~4.2, there is white precipitate generation, be filtered under diminished pressure, by filtration cakes torrefaction, i.e., product 3- (3,3- dichloropropylene epoxide) -1- benzene
Base pyrazoles -5- formic acid；
(5) preparation of 3- (3,3- dichloropropylenes epoxide) -1- phenyl-pyrazole -5- formyl chlorides：
0.5~0.7mmol3- (3,3- dichloropropylene epoxide) -1- Phenylpyrazole -5- formic acid is added in round-bottomed flask, plus
Enter 4~6 mL chloroforms, 0.15~0.25mL thionyl chlorides be added dropwise, 50~60 DEG C of 3~4h of stirring, reaction terminates rear vacuum distillation,
Obtain faint yellow solid 3- (3,3- dichloropropylenes epoxide) -1- phenyl-pyrazole -5- formyl chlorides；
(6) preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- Phenylpyrazole -5- carboxamides derivatives：
E. 0.8~1.2mmol 3- (3,3- dichloropropylenes epoxide) -1- phenyl-pyrazole -5- formyl chlorides are dissolved in 1.5
In~2.5mL tetrahydrofuran solutions, added in reaction bulb the corresponding organic amines of 1.1~1.3mmol, 4~6mL dichloromethane,
1.5~1.7mmol triethylamines, are cooled under -2~0 DEG C, inert gas shielding and above-mentioned tetrahydrofuran solution are added dropwise, completion of dropping
Room temperature is gradually increased to, 1~1.5h is stirred；
F. after reaction terminates, reaction solution 8~12mL dchloromethanes are washed, and are dried, concentration, gained residue glue
Column chromatography is purified, and obtains 3- (3,3- bis- chloroallyloxyamino) -1- Phenylpyrazole -5- carboxamides derivatives.
According to the preparation method of above-mentioned 3- (3,3- bis- chloroallyloxyamino) -1- Phenylpyrazole -5- carboxamides derivatives, step
Suddenly the alkalescence condition described in (3) is：1.5~2mmol K2CO3With 0.01~0.05mmol KI.
According to the preparation method of above-mentioned 3- (3,3- bis- chloroallyloxyamino) -1- Phenylpyrazole -5- carboxamides derivatives, step
Suddenly the column chromatography condition described in (2) is：200~300 mesh silicagel columns, eluant, eluent is the mixture of petroleum ether and ethyl acetate, two
The volume ratio of person is 3:1.
According to the preparation method of above-mentioned 3- (3,3- bis- chloroallyloxyamino) -1- Phenylpyrazole -5- carboxamides derivatives, step
Suddenly the column chromatography condition described in (3) is：200~300 mesh silicagel columns, eluant, eluent is the mixture of petroleum ether and ethyl acetate, two
The volume ratio of person is 5:1.
According to the preparation method of above-mentioned 3- (3,3- bis- chloroallyloxyamino) -1- Phenylpyrazole -5- carboxamides derivatives, step
Suddenly the column chromatography condition described in (6) is：200~300 mesh silica gel silicon, eluant, eluent is the mixture of petroleum ether and ethyl acetate, two
The volume ratio of person is 3:1~10:1.
According to the preparation method of above-mentioned 3- (3,3- bis- chloroallyloxyamino) -1- Phenylpyrazole -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- Phenylpyrazole -5- carboxamides derivatives, step
Suddenly the wash solution described in (6) is watery hydrochloric acid, saturated sodium bicarbonate solution and saturated aqueous common salt.
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- Phenylpyrazole -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 a kind of or several in Tolfenpyrad, tebufenpyrad, chlorfenapyr, pyrazinones, etoxazole, tebufenpyrad, rattle away young ketone, Nylar, emaricin
The mixing planted.
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
Go out prestige, carbofuran, vikane, dichloropropylene, dichloro-isonicotinic acid, allyl isothiazole etc. it is other known it is any can be as in bactericide
Any one or a few mixing.
The positive beneficial effect of the present invention：
3- (3,3- bis- chloroallyloxyamino) -1- Phenylpyrazole -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- Phenylpyrazole -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
Embodiment 1
A kind of 3- (3,3- bis- chloroallyloxyamino) -1- Phenylpyrazole -5- carboxamides derivatives, chemical structure of general formula I is as follows：
Wherein, R is isopropyl.
The preparation method of above-mentioned 3- (chloroallyloxyaminos of 3,3- bis-) -1- Phenylpyrazole -5- carboxamides derivatives include with
Lower step：
(1) preparation of 5- oxo pyrazoles alkane -2- phenyl -3- carboxylic acid, ethyl esters：
A. 40mL absolute ethyl alcohols are added into three-necked flask, 30mmol metallic sodiums are added portionwise, 10min is stirred, second is formed
Alcohol sodium solution, is subsequently added into 30mmol phenylhydrazines formation yellow suspension, and 70 DEG C of heating is added dropwise to flowing back under reflux state
30mmol diethyl maleates, drop finishes, and continues the 1h that flows back；
B. after reaction terminates, reaction solution is cooled to 40 DEG C, adds 30mmol glacial acetic acids, and reaction solution is concentrated to dryness, and produces 5-
Oxo pyrazoles alkane -2- phenyl -3- carboxylic acid, ethyl esters, yield 90%, purity >=93%；
(2) preparation of 1- phenyl -3- hydroxy-pyrazoles -5- Ethyl formates：
The addition 43mmol 5- oxo pyrazoles alkane -2- phenyl -3- carboxylic acid, ethyl esters into single necked round bottom flask, 100mL acetonitriles,
The 4mL 98wt% concentrated sulfuric acids, stir 5min, and 48mmol K are added afterwards2S2O8, 5h is stirred at reflux, room temperature is cooled to, brown is obtained
Solution, concentration, gained residue column chromatography purifying, elution obtains yellow solid 1- phenyl -3- hydroxy-pyrazole -5- formic acid second
Ester, yield 75%, purity >=95%,1H NMR(400MHz,CDCl3)：δ:7.47 (d, J=7.5Hz, 4H), 7.44-7.35
(m, 3H), 7.26 (s, 2H), 6.32 (s, 1H), 4.22 (d, J=7.1Hz, 2H), 1.22 (t, J=7.1Hz, 3H)；
(3) preparation of 3- (3,3- dichloropropylenes epoxide) -1- Phenylpyrazole 5- Ethyl formates：
By 1mmol 1- phenyl -3- hydroxypyrazoles -5- Ethyl formates, 1.2mmol 1,1,3- tri chloropropenes, acetone 4mL is mixed
Close, room temperature condensation reaction 15h under alkalescence condition is filtered, concentration, the purifying of gained residue column chromatography, elution obtains rufous oil
Shape thing 3- (3,3- dichloropropylene epoxide) -1- Phenylpyrazole 5- Ethyl formates, yield 80%, purity >=95%,1H NMR(400
MHz,CDCl3)：δ:7.98-7.32 (m, 9H), 7.26 (s, 1H), 6.42 (s, 1H), 6.24 (t, J=6.5Hz, 1H), 4.86
(d, J=6.5Hz, 3H), 4.23 (q, J=7.1Hz, 3H), 1.24 (t, J=8.9,5.4Hz, 3H)；
(4) preparation of 3- (3,3- dichloropropylenes epoxide) -1- Phenylpyrazole -5- formic acid：
C. 2.5mmol hydrogen is added into 0.9mmol 3- (3,3- dichloropropylenes epoxide) -1- Phenylpyrazole 5- Ethyl formates
Lithia, is dissolved with 5mL methanol solution, and backflow 12h is stirred at room temperature；
D. after reaction terminates, concentration removes most of solvent, adds distilled water, is filtered under diminished pressure removing inorganic salts, aqueous phase uses 1
It is 4 that mol/L hydrochloric acid, which is acidified to pH, has white precipitate generation, is filtered under diminished pressure, by filtration cakes torrefaction, i.e., product 3- (3,3- bis-
Chloropropene epoxide) -1- Phenylpyrazole -5- formic acid, yield 90%, purity >=95%,1H NMR(400MHz,CDCl3)：δ:
7.98-7.32 (m, 9H), 7.26 (s, 1H), 6.42 (s, 1H), 6.24 (t, J=6.5Hz, 1H), 4.86 (d, J=6.5Hz,
3H), 4.23 (q, J=7.1Hz, 3H), 1.24 (t, J=8.9,5.4Hz, 3H)；
(5) preparation of 3- (3,3- dichloropropylenes epoxide) -1- phenyl-pyrazole -5- formyl chlorides：
0.6mmol3- (3,3- dichloropropylene epoxide) -1- Phenylpyrazole -5- formic acid is added in round-bottomed flask, 5mL is added
Chloroform, is added dropwise 0.2mL thionyl chlorides, and 50 DEG C of stirring 3h, reaction terminates rear vacuum distillation, obtains faint yellow solid 3- (3,3- bis-
Chloropropene epoxide) -1- phenyl-pyrazole -5- formyl chlorides；
(6) preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- Phenylpyrazole -5- carboxamides derivatives：
E. 1.0mmol 3- (3,3- dichloropropylenes epoxide) -1- phenyl-pyrazole -5- formyl chlorides are dissolved in 2mL tetrahydrochysenes
In tetrahydrofuran solution, the corresponding organic amines of 1.2mmol, 5mL dichloromethane, 1.5mmol triethylamines are added in reaction bulb, is cooled to
0 DEG C, above-mentioned tetrahydrofuran solution is added dropwise under inert gas shielding, completion of dropping is gradually increased to room temperature, stirs 1h；
F. after reaction terminates, reaction solution 10mL dchloromethanes are washed, and are dried, concentration, gained residue column chromatography
Purifying, elution, obtains 3- (3,3- bis- chloroallyloxyamino) -1- Phenylpyrazole -5- carboxamides derivatives, product purity >=97%.
Alkalescence condition described in step (3) is：1.5mmol K2CO3With 0.05mmol KI.
Column chromatography condition described in step (2) is：200~300 mesh silicagel columns, eluant, eluent is petroleum ether and ethyl acetate
Mixture, both volume ratios are 3:1.
Column chromatography condition described in step (3) is：200~300 mesh silicagel columns, eluant, eluent is petroleum ether and ethyl acetate
Mixture, both volume ratios are 5:1.
Column chromatography condition described in step (6) is：200~300 mesh silicagel columns, eluant, eluent is petroleum ether and ethyl acetate
Mixture, both volume ratios are 5:1.
Described petroleum ether boiling point is 60~90 DEG C.
Wash solution described in step (6) is watery hydrochloric acid, saturated sodium bicarbonate solution and saturated aqueous common salt.
Embodiment 2~12 is similar with above-described embodiment general principle, does not repeat, and somewhat different is：R is respectively hexamethylene
Base, 3- aminomethyl phenyls, 4- aminomethyl phenyls, 3- methoxyphenyls, 4- methoxyphenyls, 2- fluorophenyls, 3- fluorophenyls, 4- bromobenzenes
Base, 4- trifluoromethyls, pyridine -2- bases, 2- p-fluorophenyl phenyl.
The preparation method of 3- (chloroallyloxyaminos of 3,3- bis-) -1- methylpyrazole -5- carboxamides derivatives of embodiment 2~12
Similar to Example 1, something in common is not repeated, somewhat different, the organic amine R-NH described in step (6)2Respectively with it is described
R groups it is corresponding.
3- (chloroallyloxyaminos of 3,3- bis-) -1- Phenylpyrazole -5- carboxamides derivatives prepared by above-described embodiment 1~12
Physical and chemical parameter is shown in Table 1.
3- (chloroallyloxyaminos of 3,3- bis-) -1- Phenylpyrazole -5- formamides prepared by the embodiment of the present invention 1~12 of table 1 spread out
Biological physical and chemical parameter
3- (chloroallyloxyaminos of 3,3- bis-) -1- Phenylpyrazole -5- formamides described in embodiments of the invention 1~12 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- phenyl pyrazolines of 5mg embodiments 1~12 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, averages, is compared with blank control, calculate relative bacteriostasis rate.
For examination strain：Represent the kind of most of pathogen that field occurs in agricultural production, AS：Tomato early blight bacterium
(Alternaria solani)；BC：Botrytis cinerea pers (Botrytis cinerea)；CA：Peanut Cercospora bacteria
(Cercospora arachidicola)；GZ：Fusarium graminearum (Gibberella zeae)；PI：Phytophthora infestans
(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 | BC | GZ | PP | SS | RC | PS |
| Mg-P-01 | 33 | 44 | 29 | 67 | 45 | 443 | 32 | 66 | 34 |
| Mg-P-02 | 22 | 57 | 28 | 69 | 12 | 37 | 10 | 23 | 13 |
| Mg-P-03 | 66 | 43 | 22 | 38 | 50 | 39 | 50 | 59 | 13 |
| Mg-P-04 | 17 | 71 | 61 | 38 | 23 | 30 | 0 | 45 | 19 |
| Mg-P-05 | 24 | 50 | 22 | 38 | 26 | 45 | 5 | 77 | 13 |
| Mg-P-06 | 32 | 71 | 39 | 58 | 38 | 46 | 15 | 41 | 19 |
| Mg-P-07 | 56 | 57 | 56 | 73 | 12 | 39 | 25 | 27 | 13 |
| Mg-P-08 | 7 | 36 | 11 | 19 | 53 | 33 | 25 | 32 | 13 |
| Mg-P-09 | 7 | 21 | 28 | 35 | 47 | 39 | 30 | 41 | 13 |
| Mg-P-10 | 15 | 43 | 11 | 19 | 47 | 46 | 55 | 82 | 25 |
| Mg-P-11 | 55 | 60 | 34 | 56 | 45 | 60 | 60 | 54 | 43 |
| Mg-P-12 | 47 | 63 | 50 | 63 | 23 | 34 | 50 | 37 | 30 |
Interpretation of result：As can be seen from Table 2,3- (3,3- bis- chloroallyloxyamino) -1- phenyl of the embodiment of the present invention 1~12
Pyrazoles -5- carboxamides derivatives good antimicrobial effects.
Claims (9)
1. a kind of 3- (3,3- bis- chloroallyloxyamino) -1- Phenylpyrazole -5- carboxamides derivatives, chemical structure of general formula is as follows：
R is isopropyl, cyclohexyl, 3- aminomethyl phenyls, 3- methoxyphenyls, 4- methoxyphenyls, 3- fluorophenyls, 4- trifluoromethyls
Phenyl, pyridine -2- bases or 2- p-fluorophenyl phenyl.
2. a kind of preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- Phenylpyrazole -5- carboxamides derivatives described in claim 1
Method, comprises the following steps：
(1) preparation of 5- oxo pyrazoles alkane -2- phenyl -3- carboxylic acid, ethyl esters：
A. 35~45mL absolute ethyl alcohols are added into three neck round bottom flask, 25~35mmol metallic sodiums are added portionwise, stirring 10~
15min, forms alcohol sodium solution, is subsequently added into 28~32mmol phenylhydrazines formation yellow suspension, and 60~70 DEG C of heating extremely flows back,
28~32mmol diethyl maleates are added dropwise under reflux state, drop finishes, and continues the 0.8~1.2h that flows back；
B. after reaction terminates, reaction solution is cooled to 35~45 DEG C, adds 25~35mmol glacial acetic acids, and reaction solution is concentrated to dryness, i.e.,
Obtain 5- oxo pyrazoles alkane -2- phenyl -3- carboxylic acid, ethyl esters；
(2) preparation of 1- phenyl -3- hydroxy-pyrazoles -5- Ethyl formates：
40~45mmol 5- oxo pyrazoles alkane -2- phenyl -3- carboxylic acid, ethyl esters, 90~110mL second are added into single necked round bottom flask
Nitrile, 3~5mL 98wt% concentrated sulfuric acids stir 5~10min, and 45~52mmol K are added afterwards2S2O8, 5~5.5h is stirred at reflux,
Be cooled to room temperature, obtain brown solution, concentrate, gained residue column chromatography purifying, obtain yellow solid 1- phenyl -3- hydroxyls -
Pyrazole-5-ethyl formate；
(3) preparation of 3- (3,3- dichloropropylenes epoxide) -1- Phenylpyrazole 5- Ethyl formates：
By 0.8~1.2mmol 1- phenyl -3- hydroxypyrazoles -5- Ethyl formates, 1.2~1.5mmol 1,1,3- tri chloropropenes,
3~5mL of acetone is mixed, room temperature 12~16h of condensation reaction under alkalescence condition, is filtered, concentration, the purifying of gained residue column chromatography,
Obtain rufous grease 3- (3,3- dichloropropylenes epoxide) -1- Phenylpyrazole 5- Ethyl formates；
(4) preparation of 3- (3,3- dichloropropylenes epoxide) -1- Phenylpyrazole -5- formic acid：
C. 2~3mmol is added into 0.8~1.0mmol 3- (3,3- dichloropropylenes epoxide) -1- Phenylpyrazole 5- Ethyl formates
Lithium hydroxide, is dissolved with 5~8mL methanol solution, 10~15h of backflow is stirred at room temperature；
D. after reaction terminates, concentration adds distilled water, is filtered under diminished pressure removing inorganic salts, aqueous phase be acidified to hydrochloric acid pH 3.8~
4.2, there is white precipitate generation, be filtered under diminished pressure, by filtration cakes torrefaction, produce product 3- (3,3- dichloropropylene epoxide) -1- phenyl pyrazolines
Azoles -5- formic acid；
(5) preparation of 3- (3,3- dichloropropylenes epoxide) -1- phenyl-pyrazole -5- formyl chlorides：
0.5~0.7mmol3- (3,3- dichloropropylene epoxide) -1- Phenylpyrazole -5- formic acid is added in round-bottomed flask, 4 are added
~6mL chloroforms, are added dropwise 0.15~0.25mL thionyl chlorides, and 50~60 DEG C of 3~4h of stirring, reaction terminates rear vacuum distillation, obtained
Faint yellow solid 3- (3,3- dichloropropylenes epoxide) -1- phenyl-pyrazole -5- formyl chlorides；
(6) preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- Phenylpyrazole -5- carboxamides derivatives：
E. by 0.8~1.2mmol 3- (3,3- dichloropropylenes epoxide) -1- phenyl-pyrazole -5- formyl chlorides be dissolved in 1.5~
In 2.5mL tetrahydrofuran solutions, the corresponding organic amines of 1.1~1.3mmol, 4~6mL dichloromethane, 1.5 are added in reaction bulb
~1.7mmol 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
It is warmed to room temperature, stirs 1~1.5h；
F. after reaction terminates, reaction solution 8~12mL dchloromethanes are washed, and are dried, concentration, gained residue column chromatography
Purifying, obtains 3- (3,3- bis- chloroallyloxyamino) -1- Phenylpyrazole -5- carboxamides derivatives.
3. the preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- Phenylpyrazole -5- carboxamides derivatives according to claim 2
Method, it is characterised in that the alkalescence condition described in step (3) is：1.5~2mmol K2CO3With 0.01~0.05mmol KI.
4. the preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- Phenylpyrazole -5- carboxamides derivatives according to claim 2
Method, it is characterised in that the column chromatography condition described in step (2) is：200~300 mesh silicagel columns, eluant, eluent is petroleum ether and second
The mixture of acetoacetic ester, both volume ratios are 3:1.
5. the preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- Phenylpyrazole -5- carboxamides derivatives according to claim 2
Method, it is characterised in that the column chromatography condition described in step (3) is：200~300 mesh silicagel columns, eluant, eluent is petroleum ether and second
The mixture of acetoacetic ester, both volume ratios are 5:1.
6. the preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- Phenylpyrazole -5- carboxamides derivatives according to claim 2
Method, it is characterised in that the column chromatography condition described in step (6) is：200~300 mesh silicagel columns, eluant, eluent is petroleum ether and second
The mixture of acetoacetic ester, both volume ratios are 3:1~10:1.
7. 3- (chloroallyloxyaminos of 3,3- bis-) -1- Phenylpyrazole -5- formamides according to any one of claim 4~6 spread out
Biological preparation method, it is characterised in that described petroleum ether boiling point is 60~90 DEG C.
8. the preparation of 3- (chloroallyloxyaminos of 3,3- bis-) -1- Phenylpyrazole -5- carboxamides derivatives according to claim 2
Method, it is characterised in that the wash solution described in step (6) is watery hydrochloric acid, saturated sodium bicarbonate solution and saturated aqueous common salt.
9. a kind of composition pesticide, it is characterised in that including 3- (3,3- bis- chloroallyloxyamino) -1- benzene described in claim 1
Base pyrazoles -5- carboxamides derivatives.
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| 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 |
| 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 |
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| 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 |
| 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 |
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