CN103467380B - Substituted phenyl pyrazole amide derivative and preparation method and application thereof - Google Patents
Substituted phenyl pyrazole amide derivative and preparation method and application thereof Download PDFInfo
- Publication number
- CN103467380B CN103467380B CN201310456588.7A CN201310456588A CN103467380B CN 103467380 B CN103467380 B CN 103467380B CN 201310456588 A CN201310456588 A CN 201310456588A CN 103467380 B CN103467380 B CN 103467380B
- Authority
- CN
- China
- Prior art keywords
- substituted phenyl
- mmol
- pyrazole amide
- preparation
- derivative
- 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.)
- Active
Links
- 0 CC1=*C(C)=C(*)*C1 Chemical compound CC1=*C(C)=C(*)*C1 0.000 description 2
Classifications
-
- 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
- A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
- A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
- A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
- A01N47/34—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< containing the groups, e.g. biuret; Thio analogues thereof; Urea-aldehyde condensation products
-
- 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
-
- 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
- C07D231/16—Halogen atoms or nitro radicals
-
- 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
Abstract
The invention relates to a substituted phenyl pyrazole amide derivative which is represented in a general formula (1) and has insecticidal activity and preparation and application of the derivative. On the basis of existing pyrazole amide compounds, a benzene ring substituted by nitro and the like is guided into the first place of a pyrazole ring, and R<1>, R<2>, A, Z, R<4>, R<5>, R<6>, R<7>, R<8> and R<9> are limited according to an instruction book. The substituted phenyl pyrazole amide derivative and the preparation and the application of the substituted phenyl pyrazole amide derivative have the advantages that the drug resistance of the original compounds is improved, production cost is lowered, the insecticidal activity on certain injurious insects is improved, and the derivative is especially effective on lepidoptera pests, such as eastern armyworms, plutella xylostella and the like, and is insecticide with wide application prospects.
Description
Technical field
The present invention relates to the synthetic technology of agricultural chemical insecticide, particularly class substituted phenyl pyrazole amide derivatives and its preparation method and application.
Background technology
Since the mankind have agro-farming history, just continuous and Agricultural pests are struggled.Effective control Agricultural pests are the keys of boosting agricultural yield, simultaneously to woods, herd, secondary, fishing and public health also extremely important.The use of chemical insecticide is the means of effective pest control, but along with market continuous expansion and the resistance of insect, the work-ing life of medicine etc. problem and people to the pay attention to day by day of environment, need that constantly research and development are efficient, low toxicity, environmental protection, low cost and there is the novel insecticide variety of the mode of action.
Adjacent formamido-benzamides (ryanodine receptor class) derivative is the effective sterilant developing control lepidoptera pest in recent years.Du pont company, Bayer agriculture section and domestic a lot of research institutions have successively applied for a large amount of patents, report a large amount of compounds.See: WO2003016300, WO 2004067528, WO2007031213, WO 2008137970.
For design and synthesis has the novel derivative of insecticidal bioactivity, and improve insecticide resistance and reduce production cost, design and synthesis has no a class substituted phenyl pyrazole amide derivatives of bibliographical information, and biological activity test shows, this analog derivative has good insecticidal activity.
Summary of the invention
The object of the invention is to for above-mentioned technical Analysis, provide a kind of and can improve original compound resistance and the substituted phenyl pyrazole amide derivatives improving insecticidal activity and its preparation method and application.
Technical scheme of the present invention:
One class substituted phenyl pyrazole amide derivatives, has following general formula (I):
I
In formula:
Z is H, halogen, amino, cyano group, C
1-C
6alkyl, C
1-C
6alkoxyl group, C
1-C
6alkylamino or
or
; Y is O, S or NH; A is
or
;
U is H, C
1-C
6alkyl, halo C
1-C
6alkyl, C
2-C
6thiazolinyl, halo C
2-C
6thiazolinyl, C
2-C
6alkynyl, halo C
2-C
6alkynyl, C
3-C
6cycloalkyl or halo C
3-C
6cycloalkyl;
V is N or C; W is O, S or N;
R
1for H, halogen, nitro, C
1-C
6alkyl, halo C
1-C
6alkyl or C
1-C
6alkoxyl group;
R
2for H, halogen, cyano group, nitro, C
1-C
6alkyl or halo C
1-C
6alkyl;
R
3for C
1-C
6alkyl, halo C
1-C
6alkyl, methylthio group substituted alkyl, C
2-C
6thiazolinyl, halo C
2-C
6thiazolinyl, C
2-C
6alkynyl, halo C
2-C
6alkynyl, methylthio group replace unsaturated alkyl, C
3-C
6cycloalkyl or halo C
3-C
6cycloalkyl (does not comprise by least one C
3-C
4the alkyl of cycloalkyl substituted), substituted sulphonyl, substituted-amino formyl radical, replace N-cyano group sulfone (sulphur) imines or benzyl, the H wherein in benzyl rings can by halogen, C
1-C
6alkyl, halo C
1-C
6alkyl replaces further;
R
4for halogen, CF
3, CN, SOCF
3, SO
2cF
3, SOCHF
2, SO
2cHF
2, C
1-C
6alkoxyl group, halo C
1-C
6alkoxyl group, C
1-C
6alkylthio, halo C
1-C
6alkylthio, C
2-C
6alkene oxygen base, halo C
2-C
6alkene oxygen base, C
2-C
6alkynyloxy group, halo C
2-C
6alkynyloxy group, C
2-C
6alkanoyloxy or halo C
2-C
6alkanoyloxy;
R
5, R
6, R
7, R
8, R
9for H, halogen, NO
2, CN, NH
2, OH, C
1-C
6alkyl, halo C
1-C
6alkyl, C
2-C
6thiazolinyl, halo C
2-C
6thiazolinyl, C
2-C
6alkynyl, halo C
2-C
6alkynyl, C
3-C
6cycloalkyl or halo C
3-C
6cycloalkyl, C
1-C
4alkyl sulphinyl, halo C
1-C
4alkyl sulphinyl, C
1-C
4alkyl sulphonyl, halo C
1-C
4alkyl sulphonyl, C
1-C
4alkylamino radical, C
2-C
8dialkyl amino, C
3-C
6trialkyl silyl, C
1-C
4alkylthio or halo C
1-C
4alkylthio, simultaneously when A is NH, R
5, R
6, R
7, R
8, R
9can not be H simultaneously; R
5, R
6, R
7, R
8, R
9one can not be only had to be replaced by alkyl or haloalkyl, R
5, R
6, R
7, R
8, R
9in have one for halogen or CH
3time, other substituting group has one at least for non-halogen and non-CH
3;
R
10for amino, C
1-C
6alkyl, five yuan or hexa-member heterocycle, phenyl or pyridyl, wherein five yuan or hexa-member heterocycle, phenyl or pyridyl ring hydrogen can by halogen, C
1-C
6alkyl or halo C
1-C
6alkyl replaces further.
Halogen in described derivative is fluorine, chlorine, bromine or iodine; Alkyl is straight or branched alkyl; Haloalkyl is straight or branched alkyl, and the hydrogen atom on these alkyl can partly or entirely be replaced by halogen atom; " haloalkenyl group ", " halo alkynyl " are identical with definition and the term " haloalkyl " of " halogenated cycloalkyl "; Thiazolinyl is have the straight or branched of 2-6 carbon atom and can have double bond on any position; Alkynyl is have the straight or branched of 2-6 carbon atom and can have triple bond on any position; In five yuan or hexa-member heterocycle, heteroatoms is N, O or S.
The preparation method of substituted phenyl pyrazole amide derivatives described in one class, synthetic route is as follows:
Preparation process is as follows:
1) general formula II compound, organic solvent and water are mixed, oxygenant is added under stirring, then under temperature is 0 DEG C to solvent reflux temperature, 0.5-48 hour is reacted, after filtration, organic solvent is sloughed in decompression, with alkaline solution alkalization to pH 12, uses organic solvent extraction organic impurity, aqueous phase as acidified, to pH 1.5, obtains target compound III;
2) above-mentioned general formula III compound is dissolved in organic solvent, adds oxalyl chloride and DMF (DMF), at room temperature stirring reaction 3-12 hour obtained acyl chlorides IV;
3) when A is
time, above-mentioned acyl chlorides IV is dissolved in organic solvent, is then added drop-wise in the organic solvent of general formula VI compound and obtains mixed solution, in mixed solution, add alkali, under temperature is 0 DEG C to solvent reflux temperature, reacts 0.5-48 hour obtained target compound I; When A is
time, potassium sulfocyanate is dissolved in organic solvent, add phase-transfer catalyst PEG-4000, after stirring and dissolving, room temperature reaction 0.5-4 hour, the insolubles leached in reaction solution obtains compound V solution, in addition acyl chlorides IV is dissolved in organic solvent, be added drop-wise in compound V solution, finally by gained solution and general formula VI compound in molar ratio 1:1 under temperature is 0 DEG C to solvent reflux temperature, react 2-12 hour after mixing, obtained target compound generalformulaⅰcompound.
Described organic solvent is methylene dichloride, chloroform, tetracol phenixin, benzene,toluene,xylene, hexanaphthene, normal hexane, ethyl acetate, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane, DMF or dimethyl sulfoxide (DMSO).
Described oxygenant is potassium permanganate, MCPBA, NaClO
2, NaIO
4/ RuO
2, H
2o
2or ozone
Described alkali is triethylamine, pyridine, 1,8-diaza-dicyclo (5,4,0) 11 carbon-7-alkene, DMA, sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, sodium methylate, sodium tert-butoxide or potassium tert.-butoxide.
Described acid is methylsulphonic acid, Phenylsulfonic acid, p-methyl benzenesulfonic acid, acetic acid, phosphoric acid ester, hydrochloric acid, sulfuric acid or phosphoric acid.
The mass ratio of described step 1) formula of II compound, organic solvent and water is 1:2-50:2-50, and the mol ratio of general formula II compound and oxygenant is 1:3-11.
Described step 2) mol ratio of formula of III compound and oxalyl chloride is 1:1.5-4, the mol ratio of general formula III compound and DMF (DMF) is 1:0.05-0.15.
In described step 3), acyl chlorides IV is 1:2-50 with the mass ratio of organic solvent, the mass ratio of VI compound and organic solvent is 1:2-50, acyl chlorides IV is 1:1 with the mol ratio of general formula VI compound, acyl chlorides IV is 1:1.5 with the mol ratio of alkali, the mass ratio of potassium sulfocyanate and organic solvent is 1:10-80, the consumption of PEG-4000 is the 0.5-1wt% of organic solvent, and the mol ratio of acyl chlorides and potassium sulfocyanate is 1:2.5.
The application of substituted phenyl pyrazole amide derivatives described in one class, for the preparation of agricultural chemical insecticide, especially for the control of the insect such as oriental armyworm, small cabbage moth; Also can be used as activeconstituents and be equipped with the pesticide composition of agriculture acceptable auxiliary agent composition for preventing and treating the control of insect.
Technique effect of the present invention is: such substituted phenyl pyrazole amide derivatives not only improves original compound resistance, and improves the insecticidal activity to some insect; Preparation method is simple, easy to implement, production cost is low; Can be widely used in and prepare agricultural chemical insecticide, especially for the control of the insect such as oriental armyworm, small cabbage moth; Also can be used as activeconstituents and be equipped with the pesticide composition of agriculture acceptable auxiliary agent composition for preventing and treating the control of insect.
Embodiment
Further illustrate the present invention below in conjunction with embodiment, its objective is that can better understand content of the present invention is embody substantive distinguishing features of the present invention, therefore the cited case should not be considered as limiting the scope of the invention.
Embodiment 1:
A preparation method for substituted phenyl pyrazole amide derivatives, described substituted phenyl pyrazole amide derivatives is
3-Trifluoromethyl-1-(the chloro-6-nitrophenyl of 2-)-
n-[4-chloro-2-methyl-6-[(methyl) is amino)-carbonyl] phenyl]-1
h-pyrazoles-5-methane amide (derivative 01), synthesis step is as follows:
1) the fluoro-4-of 1,1,1-tri-(furans-2-base)-4-ketone-2-alkene-2-sodium alkoxide is prepared
In 100 mL single necked round bottom flask, add 30 mL dehydrated alcohols, lower point of ice bath adds 1.15 g (50 mmol) sodium Metal 99.5 for 5 times, and stirring reaction disappears to sodium sheet; Decompression is sloughed dehydrated alcohol and is obtained white solid, adds 50 mL anhydrous diethyl ethers in reaction flask, then stirs lower slowly dropping 7.10 g (50 mmol) Trifluoroacetic Acid Ethyl Ester, dissolves rear continuation stirring 5 min completely to solid; Slow dropping 5.5 g (50 mmol) 2-acetofuran, dropwises stirring at room temperature 8-12 hour; Collected by suction white solid, namely obtains the fluoro-4-of 1,1,1-tri-(furans-2-base)-4-ketone-2-alkene-2-sodium alkoxide with after anhydrous diethyl ether washing.
2) 3-trifluoromethyl-5-furans-2-base-1 is prepared
h-pyrazoles
In 100 mL single necked round bottom flask, by 9.12 g (40 mmol) 1,1, the fluoro-4-of 1-tri-(furans-2-base)-4-ketone-2-alkene-2-sodium alkoxide is dissolved in the ethanolic soln of 1 mol/L HCl, slowly add the hydrochloride of 4.11 g (60 mmol) hydrazine, back flow reaction 3-4 h, TLC detect to reacting completely; Reaction solution is cooled to room temperature, filters, after filtrate decompression precipitation, uses CH
2cl
2extraction, successively uses saturated NaHCO
3solution, saturated common salt water washing, dry, after finally filtering, namely precipitation obtains 3-trifluoromethyl-5-furans-2-base-1
h-pyrazoles.
3) 3-Trifluoromethyl-1-((the chloro-6-nitro of 2-) phenyl)-5-(furans-2-base)-1 is prepared
h-pyrazoles
In 100 mL tri-neck round-bottomed flasks, by 6.06 g (30 mmol) 3-trifluoromethyl-5-furans-2-base-1
h-pyrazoles, 6.22 g (45 mmol) K
2cO
3be dissolved in 30 mL DMF, add 2 mL water, be warming up to 50-60 DEG C, stirring reaction 1h; Slowly be added drop-wise in reaction solution by the mixed solution of 6.91 g (36 mmol) 2,3-dichloronitrobenzenes and 20 mL DMF, be warming up to 125 DEG C of reaction 3-4 h, TLC detects to reacting completely again; Reaction solution decompression precipitation, extraction into ethyl acetate, successively uses 1 molL
-1hydrochloric acid soln, saturated sodium bicarbonate solution, saturated common salt water washing, finally reduce pressure precipitation obtain product crude product, without the need to purifying directly carry out next step reaction.
4) 3-Trifluoromethyl-1-((the chloro-6-nitro of 2-) phenyl)-1 is prepared
h-pyrazoles-5-formic acid
In the 250 mL tri-neck round-bottomed flasks that alkali liquor absorption device is housed, by above-mentioned 10.73 g (30 mmol) 3-Trifluoromethyl-1-((the chloro-6-nitro of 2-) phenyl)-5-(furans-2-base)-1
h-pyrazoles crude product is dissolved in 50 mL acetonitriles, then adds 20.41 g (150 mmol) KH
2pO
4, water 50 mL, drips 330 mmol Textone (NaClO below 0 DEG C
2) the aqueous solution, continue stirring reaction 4 h under dropwising ice bath, TLC detect to reacting completely; Filter, filtrate decompression sloughs acetonitrile, be that 2 mol/L potassium hydroxide solutions fully alkalize to pH 12 by concentration, then organic impurity is extracted with ethyl acetate, aqueous phase concentration is that 2 mol/L hydrochloric acid solns are acidified to pH 1.5, separates out solid, suction filtration, drying, last column chromatography for separation obtains 3-Trifluoromethyl-1-((the chloro-6-nitro of 2-) phenyl)-1
h-pyrazoles-5-formic acid.
5) 2-amino-3-methyl-5-chloro phenylformic acid is prepared
By 9.98 g(66 mmol) 2-amino-3-tolyl acid is dissolved in 50 mL DMF, slowly add 8.81 g(66 mmol wherein) N-chlorosuccinimide (NCS), then be heated to 100 DEG C, react 2 h, pour in 200 mL frozen water after cooling, adularescent solid is separated out, filter, solid with ethyl acetate is dissolved, dry, precipitation obtains pale solid, obtains white solid 2-amino-3-methyl-5-chloro phenylformic acid after washed with diethylether.
6) prepare
n-methyl-2-amino-3-methyl-5-chloro benzamide
By 3.34 g(18 mmol) 2-amino-3-methyl-5-chloro phenylformic acid is dissolved in 30 mL thionyl chlorides, reflux 4 h, removed under reduced pressure thionyl chloride, resistates is dissolved in 20 mL tetrahydrofuran (THF)s, under cryosel bath, slow instillation 13.95 g(180 mmol) concentration is in the tetrahydrofuran solution of the aqueous methylamine solution of 40wt%, drips to finish at room temperature to stir 8 h, removes tetrahydrofuran (THF), acetic acid ethyl dissolution, washing, organic layer is dry, and after precipitation, column chromatography obtains
n-methyl-2-amino-3-methyl-5-chloro benzamide.
7) prepare 3-Trifluoromethyl-1-(the chloro-6-nitrophenyl of 2-)-
n-[4-chloro-2-methyl-6-[((methyl) is amino)-carbonyl] phenyl]-1
h-pyrazoles-5-methane amide
By 0.36 g (1.07 mmol) 3-Trifluoromethyl-1-((the chloro-6-nitro of 2-) phenyl)-1
h-pyrazoles-5-formic acid, is dissolved in 20 mL methylene dichloride, adds 0.20 g(1.6 mmol) oxalyl chloride and two DMF, mixed solution at room temperature reacts 3 h, and decompression is sloughed solvent and obtained crude acid chloride; Crude acid chloride is dissolved in 10 mL tetrahydrofuran (THF)s and is also slowly added dropwise to 0.20 g(1.0 mmol)
nin the mixed solution of 20 mL tetrahydrofuran (THF)s of-methyl-2-amino-3-methyl-5-chloro benzamide and 0.16 g (1.6 mmol) triethylamine, back flow reaction 4 h; Solvent is sloughed in decompression, adds 60 mL methylene dichloride, then use water, saturated common salt solution washing organic layer respectively, anhydrous Na in reaction flask
2sO
4drying, decompression precipitation, then obtain target compound through reduced pressure chromatography, faint yellow solid, m.p. 197-199 DEG C.
Embodiment 2:
A preparation method for substituted phenyl pyrazole amide derivatives, described substituted phenyl pyrazole amide derivatives be 3-Trifluoromethyl-1-(2-chloro-4 nitrophenyl)-
n-[4-chloro-2-methyl-6-[((n-propyl) is amino)-carbonyl] phenyl]-1
h-pyrazoles-5-methane amide (derivative 02), synthesis step is as follows:
1) prepare
n-n-propyl-2-amino-3-methyl-5-chloro benzamide
By 3.34 g(18 mmol) 2-amino-3-methyl-5-chloro phenylformic acid is dissolved in 30 mL thionyl chlorides, reflux 4 h, removed under reduced pressure thionyl chloride, resistates is dissolved in 20 mL tetrahydrofuran (THF)s, under cryosel bath, in the mixed solution of slow instillation 10.64 g (180 mmol) Tri N-Propyl Amine and 20 mL tetrahydrofuran (THF)s, drip to finish and at room temperature stir 8 h, remove tetrahydrofuran (THF), acetic acid ethyl dissolution, washing, organic layer is dry, and after precipitation, column chromatography obtains
n-n-propyl-2-amino-3-methyl-5-chloro benzamide.
2) 3-Trifluoromethyl-1-((the chloro-4-nitro of 2-) phenyl)-5-(furans-2-base)-1 is prepared
h-pyrazoles
In 100 mL tri-neck round-bottomed flasks, by 6.06 g (30 mmol) 3-trifluoromethyl-5-furans-2-base-1
h-pyrazoles, 6.22 g (45 mmol) K
2cO
3be dissolved in 30 mL DMF, add 2 mL water, be warming up to 50-60 DEG C, stirring reaction 1h; Slowly be added drop-wise in reaction solution by the mixed solution of the chloro-4-fluoronitrobenzene of 6.32 g (36 mmol) 3-and 20 mL DMF, be warming up to 125 DEG C of reaction 3-4 h, TLC detects to reacting completely again; Reaction solution decompression precipitation, extraction into ethyl acetate, successively uses 1 molL
-1hydrochloric acid soln, saturated sodium bicarbonate solution, saturated common salt water washing, finally reduce pressure precipitation obtain product crude product, without the need to purifying directly carry out next step reaction.
3) 3-Trifluoromethyl-1-((the chloro-4-nitro of 2-) phenyl)-1 is prepared
h-pyrazoles-5-formic acid
In the 250 mL tri-neck round-bottomed flasks that alkali liquor absorption device is housed, above-mentioned 10.73 g (30 mmol) 3-Trifluoromethyl-1-((the chloro-4-nitro of 2-) phenyl)-5-(furans-2-base)-1H-pyrazoles crude product is dissolved in 50 mL acetonitriles, then adds 20.41 g (150 mmol) KH
2pO
4, water 50 mL, drips the aqueous solution of 330 mmol Textones, continues stirring reaction 4 h under dropwising ice bath below 0 DEG C, and TLC detects to reacting completely; Filter, filtrate decompression sloughs acetonitrile, fully alkalize to pH 12 by the KOH solution that concentration is 2 mol/L, then organic impurity is extracted with ethyl acetate, aqueous phase concentration is that the hydrochloric acid soln of 2 mol/L is acidified to pH 1.5, separates out solid, suction filtration, drying, last column chromatography for separation obtains 3-Trifluoromethyl-1-((the chloro-4-nitro of 2-) phenyl)-1
h-pyrazoles-5-formic acid.
4) prepare 3-Trifluoromethyl-1-(2-chloro-4 nitrophenyl)-
n-[4-chloro-2-methyl-6-[((n-propyl) is amino)-carbonyl] phenyl]-1
h-pyrazoles-5-methane amide
By 0.36 g (1.07 mmol) 3-Trifluoromethyl-1-((the chloro-4-nitro of 2-) phenyl)-1
h-pyrazoles-5-formic acid, is dissolved in 20 mL methylene dichloride, adds 0.20 g(1.6 mmol) oxalyl chloride and two DMF, mixed solution at room temperature reacts 3 h, removes solvent under reduced pressure and obtains crude acid chloride; Gained acyl chlorides is dissolved in 10 mL tetrahydrofuran (THF)s, under ice bath, slowly instills 0.23 g (1.0 mmol)
n-n-propyl-2-amino-3-methyl-5-chloro benzamide and 0.16 g(1.6 mmol) triethylamine 20 mL tetrahydrofuran solutions in, back flow reaction 4 h; Solvent is sloughed in decompression, adds 60 mL methylene dichloride, then use water, saturated common salt solution washing organic layer respectively, anhydrous Na in reaction flask
2sO
4drying, decompression precipitation, then obtain target compound through reduced pressure chromatography, faint yellow solid, m.p. 210 ~ 212 DEG C.
Embodiment 3:
A preparation method for substituted phenyl pyrazole amide derivatives, described substituted phenyl pyrazole amide derivatives be 3-Trifluoromethyl-1-((2,4-dinitrobenzene) phenyl)-
n-[4-chloro-2-methyl-6-[((methyl) is amino)-carbonyl] phenyl]-1
h-pyrazoles-5-methane amide (derivative 03), synthesis step is as follows:
1) 3-Trifluoromethyl-1-((2,4-dinitrobenzene) phenyl)-5-(furans-2-base)-1 is prepared
h-pyrazoles
In 100 mL tri-neck round-bottomed flasks, by 6.06 g (30 mmol) 3-trifluoromethyl-5-furans-2-base-1
h-pyrazoles, 2.52 g (45 mmol) KOH are dissolved in 30 mL acetonitriles and 2 mL water, then add 0.10 g (0.30 mmol) tetrabutylammonium bromide, stirring at room temperature reaction 1h; Slowly be added drop-wise in reaction solution by the acetonitrile solution of 7.29 g (36 mmol) 2,4-nitro-chlorobenzenes, be warming up to 50-60 DEG C of reaction 3-4 h, TLC detects to reacting completely again; Reaction solution decompression precipitation, extraction into ethyl acetate, successively uses 1 molL
-1hydrochloric acid soln, saturated sodium bicarbonate solution, saturated common salt water washing, finally reduce pressure precipitation obtain product crude product, without the need to purifying directly carry out next step reaction.
2) 3-Trifluoromethyl-1-((2,4-dinitrobenzene) phenyl)-1 is prepared
h-pyrazoles-5-formic acid
In the 250 mL tri-neck round-bottomed flasks that alkali liquor absorption device is housed, by above-mentioned 11.05 g (30 mmol) 3-Trifluoromethyl-1-((2,4-dinitrobenzene) phenyl)-5-(furans-2-base)-1
h-pyrazoles crude product is dissolved in 50 mL acetonitriles, then adds 20.41 g (150 mmol) KH
2pO
4, water 50 mL, below 0 DEG C, drip the aqueous solution of 330 mmol Textones, continue stirring reaction 4 h under dropwising ice bath, TLC detects to reacting completely; Filter, filtrate decompression sloughs acetonitrile, fully alkalize to pH 12 by 2 mol/L KOH solution, then be extracted with ethyl acetate organic impurity, aqueous phase 2 mol/L hydrochloric acid solns are acidified to pH 1.5, separate out solid, suction filtration, drying, last column chromatography for separation obtains 3-Trifluoromethyl-1-((2,4-dinitrobenzene) phenyl)-1
h-pyrazoles-5-formic acid.
3) prepare 3-Trifluoromethyl-1-((2,4-dinitrobenzene) phenyl)-
n-[4-chloro-2-methyl-6-[((methyl) is amino)-carbonyl] phenyl]-1
h-pyrazoles-5-methane amide
By 0.37 g (1.07 mmol) 3-Trifluoromethyl-1-((2,4-dinitrobenzene) phenyl)-1
h-pyrazoles-5-formic acid, is dissolved in 20 mL methylene dichloride, and add 0.20 g (1.6 mmol) oxalyl chloride and two DMF, mixed solution at room temperature reacts 3 h, removes solvent under reduced pressure and obtains crude acid chloride; Gained crude acid chloride is dissolved in 10 mL tetrahydrofuran (THF)s, under ice bath, slowly instills 0.20 g (1.0 mmol)
nin 20 mL tetrahydrofuran solutions of-methyl-2-amino-3-methyl-5-chloro benzamide and 0.16 g (1.6 mmol) triethylamine, back flow reaction 4 h; Solvent is sloughed in decompression, adds 60 mL methylene dichloride, then use water, saturated common salt solution washing organic layer respectively, anhydrous Na in reaction flask
2sO
4drying, decompression precipitation, then obtain target compound through reduced pressure chromatography, faint yellow solid, m.p. 204 ~ 206 DEG C.
Now according to the preparation method of embodiment 1-3 but this analog derivative 01-488 adopting different raw materials to prepare, list table 1, table 2 in, partial derivatives
1h NMR(Bruker AV400 spectrometer using tetramethylsilane as the internal standard) data list table 3 in
Table 1 1-1
1-2
1-3
1-4
1-5
1-6
1-7
1-8
1-9
1-10
1-11
1-12
1-13
1-14
1-15
1-16
Table 2
2-1
2-2
2-3
2-4
2-5
Table 3
3-1
3-2
Embodiment 4:
Utilize derivative provided by the invention (01 ~ 488) to test, verify insect evaluated biological activity:
Any one derivative (01 ~ 488) provided by the invention is dissolved in solvent, water and tensio-active agent, is mixed into homogeneous aqueous phase, during use, be diluted with water to any required concentration, tested object and testing method as follows:
1) to the evaluated biological activity of oriental armyworm: for examination insect be oriental armyworm (
mythimna separatawalker), the normal population of indoor leaf of Semen Maydis raising; Adopt leaf dipping method, dipping Maize Seedling leaf is in the solution configured; Put into diameter 7 cm culture dish after drying, access 4 instar larvaes, each concentration repeats 3 times; Contrast acetone soln soaking maize leaf breeding grub, viewing test result after 24 hours, 48 hours, 72 hours.
2) to the evaluated biological activity of small cabbage moth: for examination insect be small cabbage moth 2 instar larvae (
plutella xylostella (L.)), be the normal population that indoor are normally raised; Adopt leaf dipping method, with tweezers dipping cabbage leaves in the solution configured, time 2-3 second, get rid of remaining liquid; Each 1, totally 3, each sample; After liquid is dry, put into the long straight type of 10cm in vitro, access 2 age diamondback moth larvae, build the mouth of pipe with gauze; Test process is placed in standard treatment chamber, viewing test result after 24 hours, 48 hours, 72 hours.
The test result of above-mentioned test is as shown in table 4, table 5.
Table 4
Mortality levels in table: A level is 100%-90%; B level is 90%-70%; C level is 70%-50%; D level is 50%-0%.
Part of compounds activity exceedes contrast medicine chlorantraniliprole (Chlorantraniliprole), is exemplified below table 5:
Table 5
Claims (2)
1. a class substituted phenyl pyrazole amide derivatives, is characterized in that having following general formula (I):
(I)
In formula:
Z is
y is NH; A is NH; R
1for methyl; R
2for Cl; R
3for ethyl or sec.-propyl; R
4for CF
3; R
7for nitro; R
9for Cl; R
5, R
6, R
8for H..
2. the application of class substituted phenyl pyrazole amide derivatives according to claim 1, is characterized in that: the pesticide composition being equipped with agriculture acceptable auxiliary agent composition as activeconstituents, for preventing and treating the purposes of insect.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310456588.7A CN103467380B (en) | 2013-09-29 | 2013-09-29 | Substituted phenyl pyrazole amide derivative and preparation method and application thereof |
PCT/CN2013/087579 WO2015051572A1 (en) | 2013-09-29 | 2013-11-21 | Class of substituted phenyl pyrazole amide derivatives and preparation method and use thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310456588.7A CN103467380B (en) | 2013-09-29 | 2013-09-29 | Substituted phenyl pyrazole amide derivative and preparation method and application thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN103467380A CN103467380A (en) | 2013-12-25 |
CN103467380B true CN103467380B (en) | 2015-06-24 |
Family
ID=49792461
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201310456588.7A Active CN103467380B (en) | 2013-09-29 | 2013-09-29 | Substituted phenyl pyrazole amide derivative and preparation method and application thereof |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN103467380B (en) |
WO (1) | WO2015051572A1 (en) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HUE060660T2 (en) | 2014-03-07 | 2023-04-28 | Biocryst Pharm Inc | Substituted pyrazoles as human plasma kallikrein inhibitors |
CN105712975B (en) * | 2016-01-26 | 2018-10-12 | 西安近代化学研究所 | A kind of pyrazole amide compound containing 1,2,3- triazole rings and application |
CN108530407A (en) * | 2017-03-04 | 2018-09-14 | 华南农业大学 | The preparation and its application of loop coil amides compound |
US10743535B2 (en) | 2017-08-18 | 2020-08-18 | H&K Solutions Llc | Insecticide for flight-capable pests |
CN109928928A (en) * | 2017-12-15 | 2019-06-25 | 南开大学 | Bisamide analog derivative of one kind Phenylpyrazole containing N- and its preparation method and application |
CN110041260A (en) * | 2019-05-17 | 2019-07-23 | 南开大学 | A kind of multi-substituted pyrazol amide derivatives and its preparation method and application |
CN112939866A (en) * | 2019-12-10 | 2021-06-11 | 南开大学 | Fluorine-substituted phenyl pyrazole amide derivative and preparation method and application thereof |
CN115572282A (en) * | 2021-07-05 | 2023-01-06 | 华东理工大学 | Pyrazole amide compound containing aromatic heterocyclic structure, and preparation method and application thereof |
CN114716408A (en) * | 2022-03-23 | 2022-07-08 | 南开大学 | Bisamide derivative containing aromatic amide and preparation method and application thereof |
CN114621144A (en) * | 2022-03-23 | 2022-06-14 | 南开大学 | Cyano-substituted phenyl pyrazole amide derivative and preparation method and application thereof |
CN115772132B (en) * | 2022-08-05 | 2024-03-15 | 山东大学 | Amidine/guanidyl modified fungal CYP51 inhibitor derivative, and preparation method and application thereof |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003016282A3 (en) * | 2001-08-13 | 2003-04-24 | Du Pont | Substituted 1h-dihydropyrazoles, their preparation and use |
CN101659655A (en) * | 2009-09-15 | 2010-03-03 | 南开大学 | Pyrazole amide derivative and application thereof |
CN101967139A (en) * | 2010-09-14 | 2011-02-09 | 中化蓝天集团有限公司 | Fluoro methoxylpyrazole-containing o-formylaminobenzamide compound, synthesis method and application thereof |
CN102276580A (en) * | 2011-06-02 | 2011-12-14 | 南开大学 | Pyrazole formylthiourea derivative and preparation method and application |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW200724033A (en) * | 2001-09-21 | 2007-07-01 | Du Pont | Anthranilamide arthropodicide treatment |
KR20060135881A (en) * | 2004-04-13 | 2006-12-29 | 이 아이 듀폰 디 네모아 앤드 캄파니 | Anthranilamide insecticides |
-
2013
- 2013-09-29 CN CN201310456588.7A patent/CN103467380B/en active Active
- 2013-11-21 WO PCT/CN2013/087579 patent/WO2015051572A1/en active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003016282A3 (en) * | 2001-08-13 | 2003-04-24 | Du Pont | Substituted 1h-dihydropyrazoles, their preparation and use |
CN101659655A (en) * | 2009-09-15 | 2010-03-03 | 南开大学 | Pyrazole amide derivative and application thereof |
CN101967139A (en) * | 2010-09-14 | 2011-02-09 | 中化蓝天集团有限公司 | Fluoro methoxylpyrazole-containing o-formylaminobenzamide compound, synthesis method and application thereof |
CN102276580A (en) * | 2011-06-02 | 2011-12-14 | 南开大学 | Pyrazole formylthiourea derivative and preparation method and application |
Non-Patent Citations (1)
Title |
---|
1-芳基-5-吡唑酰胺类化合物的合成与生物活性研究;郭丽琴 等;《农药研究与应用》;20080425;第12卷(第2期);15-18,第16页合成路线、实验部分,第17页-18页表1化合物V3、V4、V11、V12 * |
Also Published As
Publication number | Publication date |
---|---|
CN103467380A (en) | 2013-12-25 |
WO2015051572A1 (en) | 2015-04-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN103467380B (en) | Substituted phenyl pyrazole amide derivative and preparation method and application thereof | |
CN102015679B (en) | 1-substituted pyridyl-pyrazolyl amide compounds and uses thereof | |
CN101935291B (en) | Cyano phthalic diamide compounds, preparation method thereof and use thereof as agricultural chemical pesticide | |
KR101693375B1 (en) | Halogen-substituted compounds used as pesticides | |
CN101659655A (en) | Pyrazole amide derivative and application thereof | |
WO2008134969A1 (en) | Benzamide compounds and applications thereof | |
CN102276580B (en) | Pyrazole formylthiourea derivative and preparation method and application | |
CN112661665B (en) | Amide compound and preparation method and application thereof | |
CN110194726A (en) | A kind of benzamide compound and its application | |
CN105315199A (en) | N-pyridine aryloxyphenoxy carboxylic acid derivatives, preparation method and applications thereof | |
CN106608873A (en) | Pyrazole amide compound, and preparation method and application thereof | |
CN102503876A (en) | Bisamide derivative, preparation method for same and application thereof | |
CN105712975B (en) | A kind of pyrazole amide compound containing 1,2,3- triazole rings and application | |
CN112939866A (en) | Fluorine-substituted phenyl pyrazole amide derivative and preparation method and application thereof | |
CN109928928A (en) | Bisamide analog derivative of one kind Phenylpyrazole containing N- and its preparation method and application | |
CN101701016A (en) | N-methyl-N-o-benzoyl aminobenzene formamide compounds as well as preparation and application thereof | |
CN103570672B (en) | Benzoyl hydrazine compound containing thiophene ring, and preparation method and application of compound | |
CN103420975B (en) | Fluorine-contained o-amino thiobenzamide type compound and application thereof | |
CN102442960A (en) | Cyanuric chloride derivative as well as preparation method and application thereof | |
CN105541794A (en) | Heptafluoroisopropyl-containing pyridyl pyrazole amide derivative and application thereof | |
CN106234385B (en) | A kind of application of 1,2,4- triazole derivatives of the structure containing benzopyrazines as fungicide | |
US11390602B2 (en) | N-alkyl-N-cyanoalkylbenzamide compound and use thereof | |
CN110804019A (en) | Amide compound and preparation method and application thereof | |
WO2023284761A1 (en) | Pyrazole ether compound, and preparation method therefor and use thereof | |
CN105198859A (en) | Anthranilic diamide compound containing dichloropropene base 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 | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant |