CN106336379A - Phenyl bispyrazole carboxamide derivatives and preparation method and application thereof - Google Patents
Phenyl bispyrazole carboxamide derivatives and preparation method and application thereof Download PDFInfo
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- 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
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Abstract
The invention provides phenyl bispyrazole carboxamide derivatives and a preparation method and an application thereof; the compounds show relatively good inhibition performance on armyworm under the concentration of 500-100 ppm, a target compound I-6, a compound I-7 and a compound I-8 have the armyworm inhibitory rate of 80% under the concentration of 500 mg/L, and the target compound I-6, the compound I-7 and the compound I-8 have the armyworm inhibitory rate still of 80% under the concentration of 200 mg/L; the compounds are new compounds with insecticidal activity, and provide the basis for research and development of new pesticides.
Description
Technical field
The present invention relates to a kind of phenyl connect pyrazolecarboxamide analog derivative be 1- (2,6- dichlor-4-trifluoromethyl phenyl)-
N- (1- methyl -2- ethoxy) -3- Trifluoromethyl-1 h- pyrazoles -4- acid amides or 1- (2,6- dichlor-4-trifluoromethyl phenyl)-n-
(1- methyl -2- ethoxy) -3- difluoromethyl -1h- pyrazoles -4- amide derivatives and its preparation method and application.
Background technology
Pyrazole formylamine derivate has stronger biologically active, in 2005, Syngenta Co., Ltd finds that it has and efficiently kills
Bacterium activity, the furametpyr (furametpyr) of the product such as SUMITOMO CHEMICAL chemical company exploitation of commercialization is to rice banded sclerotial blight
Disease has excellent preventive effect, and the longevity of residure is long, and the dosage of control in field rice sheath blight disease is active ingredient 450～600g/hm2, and day
The pyrrole metsulfovax (penthiopyrad) that this Mitsui Chemicals, Inc. develops is in active ingredient 100～200g/hm2Under, white to cucumber
Powder disease has good bactericidal activity.
And commercialization agricultural chemicals ethiprole is Rhone-Poulenc Company developed in 1987～1989,1992 years
Registered in China, opened up application through for many years, had evolved into a very efficient insecticide.
The structure that the high activity based on pyrazolecarboxamide for the present invention connects pyrazoles with reference to ethiprole phenyl provides a kind of new
The phenyl with insecticidal activity connects preparation method and the application technology of pyrazolecarboxamide analog derivative.
Content of the invention
It is an object of the present invention to provide it is 1- (2,6- dichlor-4-trifluoromethyl that a kind of phenyl connects pyrazolecarboxamide analog derivative
Phenyl)-n- (1- methyl -2- ethoxy) -3- Trifluoromethyl-1 h- pyrazoles -4- acid amides or 1- (2,6- dichlor-4-trifluoromethyl benzene
Base)-n- (1- methyl -2- ethoxy) -3- difluoromethyl -1h- pyrazoles -4- amide derivatives and its preparation method and application,
And design and synthesized a series of noval chemical compounds, and these compounds have good insecticidal a bit, are that the synthesis of novel pesticide is visited
Rope method and technology of preparing.
A kind of described phenyl connects pyrazolecarboxamide analog derivative, is 1- (2,6- dichlor-4-trifluoromethyl phenyl)-n-
(1- methyl -2- ethoxy) -3- Trifluoromethyl-1 h- pyrazoles -4- amides compound or derivatives thereof is it is characterised in that it is tied
Shown in structure formula such as formula (i):
In formula (i): r1For trifluoromethyl or difluoromethyl, r2For c1～c4 alkyl, replace alkyl, halogen or cyano group.
A kind of described phenyl connects pyrazolecarboxamide analog derivative it is characterised in that r2For methyl, chlorine, bromine, fluorine, fluoroform
Base or itrile group.
Described phenyl connects the preparation method of pyrazolecarboxamide analog derivative it is characterised in that comprising the steps:
1) trifluoroacetic ethyl acetoacetate, triethyl orthoformate and acetic anhydride are mixed, back flow reaction reaction uses oil after terminating
Pump vacuum distillation collects 98～105 DEG C of cuts, obtains pale yellowish oil liquid, is the intermediate as shown in formula (), trifluoroacetyl
The ratio of the amount of the material of ethyl acetate, triethyl orthoformate and acetic anhydride is 1:1～2:2～3, preferably 1:1.5:3；
2) 2,6- dichlor-4-trifluoromethyl aniline is dissolved in glacial acetic acid, under mechanical agitation, instills concentrated hydrochloric acid, stirring half is little
When, instill the aqueous solution of natrium nitrosum under cold hydrazine, then reaction 85-95 minute obtains reactant liquor, cold hydrazine under the conditions of 5～10 DEG C
Under the conditions of this reactant liquor is added drop-wise in stannous chloride and the mixture of concentrated hydrochloric acid, completion of dropping is stirred at room temperature, filter, wash
Solid chemical compound as shown in formula ()；
3) by step 2) solid chemical compound as shown in formula () that obtains and sodium hydrate aqueous solution mix and blend 25-35
Minute, add ethanol stir 8-10 minute obtain mixed liquor, then by step 1 under ice bath) obtain as shown in formula ()
The ethanol solution of intermediate is slowly dropped in mixed liquor, is stirred at reflux 3.5-4.5 hour, and reaction uses two chloroethenes after terminating successively
Alkane extraction, anhydrous sodium sulfate drying, filtration, are spin-dried for solvent and obtain compound 1- (2,6- bis- as shown in formula () for the red brown solid
Chloro- 4- trifluoromethyl) -3- Trifluoromethyl-1 h- pyrazoles -4- Ethyl formate；
4) by step 3) compound as shown in formula () that obtains is dissolved in organic solvent c, adds 15% NaOH molten
Liquid, is heated to 50-55 DEG C of reaction 1.8-2.2 hour, and reaction is cooled to room temperature after terminating, and dropping watery hydrochloric acid to ph is in acidity, analysis
Go out solid, suction filtration, filter cake washes with water, dry compound 1- (2, the 6- dichlor-4-trifluoromethyl benzene obtaining as shown in formula ()
Base) -3- Trifluoromethyl-1 h- pyrazoles -4- formic acid；
5) by step 4) compound as shown in formula () that obtains is dissolved in dried tetrahydrofuran solvent, under ice bath
Dropping thionyl chloride, 0.4-0.6 hour drips off, back flow reaction 1.8-2.2 hour, and membrane pump is drained solvent and obtained as shown in formula ()
Compound 1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 h- pyrazoles -4- formyl chloride；
6) 1- methyl-2-amino propyl alcohol, triethylamine and dichloromethane are added in the single-necked flask being dried, slow under ice bath
Slow instill step 5) dichloromethane solution of the compound as shown in formula () that obtains, place after stirring 0.8-1.2h under room temperature
2.8-3.2h, is separated with tlc after precipitation, obtains compound 1- (2,6- dichlor-4-trifluoromethyl benzene as shown in formula () for the solid
Base)-n- (1- methyl -2- ethoxy) -3- Trifluoromethyl-1 h- pyrazole-4-carboxamide；
7) weighing step 6) intermediate that the obtains compound as shown in formula (), in single port bottle, adds organic solvent d
With substituted aryl isocyanates, instill 1 triethylamine, be stirred overnight under room temperature, concentrate, tlc separates, and obtains target product such as formula
1- (2,6- dichlor-4-trifluoromethyl phenyl)-n- (1- methyl -2- ethoxy) -3- Trifluoromethyl-1 h- pyrazoles shown in () -
4- Carbox amide；
The structural formula of each compound is as follows respectively:
Wherein r1=cf3Or chf2.
Described phenyl connects the preparation method of pyrazolecarboxamide analog derivative it is characterised in that step 2) in 2,6- bis- chloro-
The ratio of the amount of the material of 4- 5-trifluoromethylaniline, natrium nitrosum and stannous chloride is 1:1～2:1～1～2, preferably 1:1.2:
2；The volumetric usage of glacial acetic acid is calculated as 1～5ml/mmol, preferably 5ml/ with the amount of 2,6- dichlor-4-trifluoromethyl aniline material
mmol.
Described phenyl connects the preparation method of pyrazolecarboxamide analog derivative it is characterised in that step 3) shown in Chinese style ()
Solid chemical compound, NaOH and the amount of the material of intermediate shown in formula () ratio be 1:1-1.5:1-1.2 (1:1～
1.5～1:1.2), preferably 1:1.1:1；Stirring ethanol volumetric usage is with the amount of the solid chemical compound material shown in formula ()
It is calculated as 1～5ml/mmol, preferably 1.2ml/mmol.
Described phenyl connects the preparation method of pyrazolecarboxamide analog derivative it is characterised in that step 4) shown in Chinese style ()
Compound and NaOH the amount of material ratio be 1:1～2, preferably 1:1.5；Described organic solvent c is ethanol, methyl alcohol
Or oxolane, preferably ethanol；Described organic solvent c volumetric usage is calculated as 2 with the amount of the combinations of materials shown in formula ()
～5ml/mmol, preferably 2ml/mmol.
Described phenyl connects the preparation method of pyrazolecarboxamide analog derivative it is characterised in that step 5) described in as formula
The ratio of the amount of the material of the compound shown in () and thionyl chloride is 1:1～2, preferably 1:1.5；Oxolane volumetric usage
2～5ml/mmol, preferably 4ml/mmol are calculated as with the amount of the combinations of materials as shown in formula ().
Described phenyl connects the preparation method of pyrazolecarboxamide analog derivative it is characterised in that step 6) described in formula ()
1:1～1.2:1～1.5 of the shown amount of material of compound, 1- methyl-2-amino propyl alcohol and triethylamine, preferably 1:1:
1.2；Methylene chloride volume consumption is calculated as 2～5ml/mmol, preferably 2ml/ with the amount of the material of the compound shown in formula ()
mmol.
Described phenyl connects the preparation method of pyrazolecarboxamide analog derivative it is characterised in that step 7) shown in Chinese style ()
Compound and substituted aryl isocyanates the amount of material ratio be 1:1～1.5, preferably 1:1.1；Organic solvent d is four
One or more of hydrogen furans, dmf, dichloromethane, preferably oxolane；The volumetric usage of organic solvent d is with formula ()
The amount of the material of shown compound is calculated as 2～5ml/mmol, preferably 2ml/mmol.
Described phenyl connects application in preparing insecticide for the pyrazolecarboxamide analog derivative, 1- shown in formula (i) (2,6- bis-
Chloro- 4- trifluoromethyl)-n- (1- methyl -2- ethoxy) -3- Trifluoromethyl-1 h- pyrazole-4-carboxamide class compound exists
Preparing the concentration in insecticide is 500～100ppm.
Described phenyl connects application in preparing insecticide for the pyrazolecarboxamide analog derivative, and described insecticide is preventing and treating cinnabar
Tetranychid, aphis craccivora and mythimna separata.
Compared with prior art, the beneficial effects are mainly as follows: the invention provides a kind of 1- (2,6- bis-
Chloro- 4- trifluoromethyl)-n- (1- methyl -2- ethoxy) -3- Trifluoromethyl-1 h- pyrazole-4-carboxamide class compound and
Its preparation method and the application prepared in insecticide, compound of the present invention shows to mythimna separata under 500～100ppm concentration
Go out preferable inhibition, inhibiting rate is up to 80.0%, and compound of the present invention is the noval chemical compound with insecticidal activity, is
The research and development of novel pesticide provide the foundation.
Its reaction equation is as follows:
Specific embodiment
With reference to specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in
This:
Embodiment 1
(1) synthesis of Formula ():
By trifluoroacetic ethyl acetoacetate (0.036mol), triethyl orthoformate (0.059mol) and acetic anhydride (0.108mol)
It is added in 100ml there-necked flask, back flow reaction 6 hours, uses oil pump vacuum distillation after completion of the reaction, collect 98～105 DEG C and evaporate
Point, obtain pale yellowish oil liquid 7.4g, yield 92.6%.
(2) synthesis of chloro- 4 trifluoromethyls hydrazine formula () of 2,6- bis-:
2,6- dichlor-4-trifluoromethyl aniline (0.03mol) is dissolved in 20ml glacial acetic acid, stirring is lower to instill concentrated hydrochloric acid
(37ml), stir half an hour, under cold hydrazine, instill the aqueous solution of natrium nitrosum (0.036mol), then anti-under the conditions of 5～10 DEG C
Answer 90 minutes, under the conditions of cold hydrazine, above-mentioned reactant liquor be added drop-wise in stannous chloride (13.5g) and the mixture of concentrated hydrochloric acid (37ml),
Completion of dropping is stirred at room temperature, and filters, washes to obtain the chloro- 4 trifluoromethyl hydrazine 5.42g of 2,6- bis- shown in solid (), yield
73.7%.
(3) 1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 h- pyrazoles -4- Ethyl formate formula ()
Synthesis:
() 2 is added, the chloro- 4 trifluoromethyl hydrazines (0.01mol) of 6- bis-, by NaOH in 100ml flask
(0.01mol) aqueous solution is poured in flask, stirs half an hour, adds 50ml ethanol, stirs 10 minutes.() is dripped under ice bath
(0.01mol) ethanol solution (20ml), drips off back flow reaction 6 hours, extracts after completion of the reaction, is dried, is spin-dried for solvent and obtains final product
1- shown in formula () (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 h- pyrazoles -4- Ethyl formate 2.947g, produces
Rate 70%.
(4) synthesis of 1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 h- pyrazoles -4- formic acid formula ():
By () 1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 h- pyrazoles -4- Ethyl formate
(0.007mol) it is dissolved in 50ml ethanol, adds 15% sodium hydroxide solution (0.01mol), be heated to 50 DEG C, react 2 hours,
Then it is cooled to room temperature, dropping watery hydrochloric acid is in acidity to solution, has a large amount of solids to separate out, suction filtration, and filter cake washes with water, dries to obtain formula
1- shown in () (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 h- pyrazoles -4- formic acid 2.61g, yield 95%.
(5) conjunction of 1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 h- pyrazoles -4- formyl chloride formula ()
Become:
By formula () 1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 h- pyrazoles -4- formic acid
(0.02mol) it is dissolved in dry 50ml oxolane, be slowly added dropwise thionyl chloride (0.024mol), back flow reaction 2 hours, instead
Solvent should be evaporated after finishing and thionyl chloride obtains 1- shown in formula () (3- chloro-2-pyridyl) -3- Trifluoromethyl-1 h- pyrazoles -4-
Formyl chloride 5.766g, yield 93%.
(6) 1- (2,6- dichlor-4-trifluoromethyl phenyl)-n- (1- methyl -2- ethoxy) -3- Trifluoromethyl-1 h- pyrrole
The synthesis of azoles -4- formamide formula ():
0.75g (0.01mol) 2- amino -1- propyl alcohol, 1.26g (0.012mol) three second is added in the single-necked flask being dried
Amine and 15ml dichloromethane, are slowly dropped into the 10ml dichloromethane solution containing 0.01mol raw material (), under room temperature under ice bath
Place 3h after stirring 1h, use thin-layer chromatography (tlc) to separate (solvent is ethyl acetate) after precipitation, obtain white solid formula ()
Shown 1- (3- chloro-2-pyridyl)-n- (1- methyl -2- ethoxy) -3- Trifluoromethyl-1 h- pyrazole-4-carboxamide, yield
78.3%.
(7) synthesis of target compounds of formula ():
Weigh 10mmol intermediate () in single port bottle, add 20ml oxolane (thf) and 11mmol2- methyl -3-
Chlorine phenyl isocyanate, instills 1 triethylamine, is stirred overnight under room temperature, concentrates, and [solvent is v (ethyl acetate): v for tlc separation
(petroleum ether)=1:3], obtain target product (- 1), yield 30%.
(ⅰ-1)
2- (1- (2,6- chloro- 4- (trifluoromethyl) phenyl) -3- (trifluoromethyl) -1h- pyrazole-4-carboxamide) propyl group (3-
Chloro-2-methyl phenyl) .m.p.186-188 DEG C of carbamate；1h nmr(600mhz,cdcl3),δ8.08(s,1h),7.75
(s, 2h), 7.57 (s, 1h), 7.19 (d, j=7.9hz, 1h), 7.12 (t, j=8.1hz, 1h), 6.62 (s, 1h), 6.48 (d, j
=7.4hz, 1h), 4.54-4.50 (m, 1h), 4.34 (dd, j=11.6,7.2hz, 1h), 4.23 (dd, j=11.6,3.8hz,
1h), 2.29 (s, 3h), 1.32 (d, j=6.8hz, 3h) .esi-ms:617 [m+h]+；
Embodiment 2
Trifluoroacetic ethyl acetoacetate in embodiment 1 step (1) is changed into difluoro ethyl acetoacetate, other operations are with enforcement
Example 1, obtains (i-2), yield 80%.
(ⅰ-2)
2- (1- (2,6- chloro- 4- (trifluoromethyl) phenyl) -3- (difluoromethyl) -1h- pyrazole-4-carboxamide) propyl group (3-
Chloro-2-methyl phenyl) m.p.158-160 DEG C of carbamate；1h nmr(600mhz,cdcl3),δ8.04(s,1h),7.72(s,
2h), 7.51 (t, j=54hz, 1h), 7.19 (d, j=7.9hz, 1h), 7.10 (t, j=8.1hz, 1h), 6.94 (s, 1h),
6.82 (s, 1h), 4.52-4.47 (m, 1h), 4.38 (dd, j=11.3,7.9hz, 1h), 4.20 (dd, j=11.6,3.4hz,
1h), 2.26 (s, 3h), 1.31 (d, j=6.5hz, 3h) .esi-ms:599 [m+h]+；
Embodiment 3
Trifluoroacetic ethyl acetoacetate in embodiment 1 step (1) is changed into difluoro ethyl acetoacetate, 2- first in step (7)
Base -3- chlorine phenyl isocyanate changes 4- bromine phenyl isocyanate into, and other operations, with embodiment 1, obtain (i-3), yield 50%.
(ⅰ-3)
2- (1- (2,6- chloro- 4- (trifluoromethyl) phenyl) -3- (difluoromethyl) -1h- pyrazole-4-carboxamide) propyl group (4-
Bromophenyl) carbamate；1h nmr(600mhz,cdcl3) δ 8.14 (d, j=6.9hz, 1h), 8.10 (s, 1h), 7.73 (d, j
=2.8hz, 2h), 7.59 (d, j=7.1hz, 1h), 7.57 (d, j=6.5hz, 1h), 7.51 (t, j=18hz, 1h), 7.45
(s, 1h), 7.16 (t, j=7.6hz, 1h), 6.78 (d, j=7.7hz, 1h), 4.53-4.49 (m, 1h), 4.38 (dd, j=
11.5,6.1hz, 1h), 4.33 (dd, j=11.5,3.7hz, 1h), 1.36 (d, j=6.8hz, 3h) .esi-ms:565 [m+h
]+；
Embodiment 4
Trifluoroacetic ethyl acetoacetate in embodiment 1 step (1) is changed into difluoro ethyl acetoacetate, 2- first in step (7)
Base -3- chlorine phenyl isocyanate changes 2- itrile group phenyl isocyanate into, and other operations, with embodiment 1, obtain (i-4), yield 70%.
(ⅰ-4)
2- (1- (2,6- chloro- 4- (trifluoromethyl) phenyl) -3- (difluoromethyl) -1h- pyrazole-4-carboxamide) propyl group (2-
Cyanophenyl) m.p.107-109 DEG C of carbamate；1h nmr(600mhz,cdcl3)δ8.04(s,1h),7.73(s,2h),
7.49 (t, j=54hz, 1h), 7.41 (d, j=8.8hz, 2h), 7.27 (d, j=2.7hz, 1h), 7.06 (s, 1h), 6.80 (d,
J=7.6hz, 1h), 4.50-4.46 (m, 1h), 4.36 (dd, j=11.7,7.5hz, 1h), 4.22 (dd, j=11.5,2.9hz,
1h), 1.33 (d, j=6.8hz, 3h) .esi-ms:576 [m+h]+；
Embodiment 5
Trifluoroacetic ethyl acetoacetate in embodiment 1 step (1) is changed into difluoro ethyl acetoacetate, 2- first in step (7)
Base -3- chlorine phenyl isocyanate changes 2- itrile group -4- chlorine phenyl isocyanate into, and other operations, with embodiment 1, obtain (i-5), yield
70%.
(ⅰ-5)
2- (1- (2,6- chloro- 4- (trifluoromethyl) phenyl) -3- (difluoromethyl) -1h- pyrazole-4-carboxamide) propyl group (4-
Chloro- 2- cyanophenyl) carbamate；1h nmr(600mhz,cdcl3)δ8.25(s,1h),8.12(s,1h),7.74(s,
2h), 7.64 (s, 1h), 7.50 (d, j=6.0hz, 1h), 7.48 (t, j=36hz, 1h), 7.13 (d, j=10.2hz, 1h),
6.81 (d, j=7.7hz, 1h), 4.56-4.52 (m, 1h), 4.37 (dd, j=11.3,6.1hz, 1h), 4.32 (dd, j=
11.3,3.9hz, 1h), 1.36 (d, j=6.8hz, 3h) .esi-ms:610 [m+h]+；
Embodiment 6
Trifluoroacetic ethyl acetoacetate in embodiment 1 step (1) is changed into difluoro ethyl acetoacetate, 2- first in step (7)
Base -3- chlorine phenyl isocyanate changes 3- chloro- 4- fluorine phenyl isocyanate into, and other operations, with embodiment 1, obtain (i-6), yield
65%.
(ⅰ-6)
2- (1- (2,6- chloro- 4- (trifluoromethyl) phenyl) -3- (difluoromethyl) -1h- pyrazole-4-carboxamide) propyl group (3-
Chloro- 4- fluorophenyl) m.p.116-118 DEG C of carbamate；1h nmr(600mhz,cdcl3)δ8.15(s,1h),8.12(s,
1h), 7.74 (s, 2h), 7.64 (s, 1h), 7.50 (d, j=6.0hz, 1h), 7.48 (t, j=36hz, 1h), 7.13 (d, j=
10.2hz, 1h), 6.81 (d, j=7.7hz, 1h), 4.56-4.52 (m, 1h), 4.37 (dd, j=11.3,6.1hz, 1h), 4.32
(dd, j=11.3,3.9hz, 1h), 1.36 (d, j=6.8hz, 3h) .esi-ms:603 [m+h]+；
Embodiment 7
2- methyl -3- chlorine phenyl isocyanate in embodiment step (7) is changed into 3- chloro- 4- fluorine phenyl isocyanate, other behaviour
Make, with embodiment 1, to obtain (i-7), yield 65%.
(ⅰ-7)
2- (1- (2,6- chloro- 4- (trifluoromethyl) phenyl) -3- (trifluoromethyl) -1h- pyrazole-4-carboxamide) propyl group (3-
Chloro- 4- fluorophenyl) m.p.116-118 DEG C of carbamate；1h nmr(600mhz,dmso)δ9.93(s,1h),8.97(s,
2h), 8.64 (d, j=8.0hz, 1h), 8.43 (s, 1h), 7.79 (d, j=2.5hz, 1h), 7.80 (d, j=2.3hz, 1h),
4.35-4.27 (m, 1h), 4.15 (d, j=7.1hz, 2h), 1.23 (d, j=6.8hz, 3h) .esi-ms:621 [m+h]+；
Embodiment 8
Trifluoroacetic ethyl acetoacetate in embodiment 1 step (1) is changed into difluoro ethyl acetoacetate, 2- first in step (7)
Base -3- chlorine phenyl isocyanate changes 3- trifluoromethyl -4- chlorine phenyl isocyanate into, and other operations, with embodiment 1, obtain (i-8), produce
Rate 50%.
(ⅰ-8)
2- (1- (2,6- chloro- 4- (trifluoromethyl) phenyl) -3- (difluoromethyl) -1h- pyrazole-4-carboxamide) propyl group (4-
Chloro- 3- trifluoromethyl) carbamate 1h nmr (600mhz, cdcl3) δ 8.05 (s, 1h), 8.12 (s, 1h), 7.74
(s, 2h), 7.64 (s, 1h), 7.54 (d, j=6.0hz, 1h), 7.50 (t, j=36hz, 1h), 7.13 (d, j=10.2hz,
1h), 6.81 (d, j=7.7hz, 1h), 4.58-4.52 (m, 1h), 4.37 (dd, j=11.3,6.1hz, 1h), 4.32 (dd, j=
11.3,3.9hz, 1h), 1.25 (d, j=6.8hz, 3h) .esi-ms:653 [m+h]+；
Embodiment 9
2- methyl -3- chlorine phenyl isocyanate in embodiment step (7) is changed into 3- chlorine phenyl isocyanate, other operations are with real
Apply example 1, obtain (i-9), yield 80%.
(ⅰ-9)
2- (1- (2,6- chloro- 4- (trifluoromethyl) phenyl) -3- (trifluoromethyl) -1h- pyrazole-4-carboxamide) propyl group (3-
Chlorphenyl) m.p.176-178 DEG C of carbamate；1H nmr (600mhz, dmso) δ 10.12 (s, 1h), 8.65 (d, j=
8.0hz,1h),8.43(s,1h),8.36(s,2h),7.55–7.52(m,2h),7.20(s,1h),4.32-4.27(m,1h),
4.16 (dd, j=10.5,3.1hz, 2h), 1.22 (d, j=6.8hz, 3h) .esi-ms:603 [m+h]+；
Embodiment 10
2- methyl -3- chlorine phenyl isocyanate in embodiment step (7) is changed into 2- trifluoromethyl -4- chlorine phenyl isocyanate,
Other operations, with embodiment 1, obtain (i-10), yield 50%.
(ⅰ-10)
2- (1- (2,6- chloro- 4- (trifluoromethyl) phenyl) -3- (trifluoromethyl) -1h- pyrazole-4-carboxamide) propyl group (4-
Chloro- 2- trifluoromethyl) carbamate 1h nmr (600mhz, cdcl3) δ 8.10 (s, 1h), 7.75 (s, 2h), 7.73
(s, 1h), 7.55 (d, j=7.7hz, 1h), 7.41 (d, j=8.7hz, 1h), 7.29 (d, j=9.6hz, 1h), 6.45 6.41
(m, 1h), 4.56-4.52 (m, 1h), 4.33 (dd, j=11.5,7.3hz, 1h), 4.25 (dd, j=11.3,3.0hz, 1h),
1.33 (d, j=6.8hz, 3h) .esi-ms:671 [m+h]+；
Embodiment 11 insecticidal activity is tested
With reference to " country south pesticides discovery center give birth to mark quasi-ordering ", indoor living screening test target compound exists
Biologically active during 500～100mg/l, for examination target be: Tetranychus cinnabarinus, aphis craccivora and mythimna separata.
Test method: weigh a certain amount of active compound with assay balance (0.0001g), add containing 1% Tween-80 emulsifying agent
Dmf is dissolved, and is configured to 1.0%-5.0% mother liquor, then uses distilled water diluting standby.
When target is for mythimna separata, tested using leaf dipping method, the liquid preparing is put into maize leaves and fully soaks
Profit, naturally dries in the shade, is then placed in the culture dish be lined with filter paper, and mythimna separata 3 age mid-term larva is accessed training with the quantity of 10/ware
In foster ware, it is placed in 24～27 DEG C of observation interiors and is cultivated, observe result after 48h.Touch polypide with writing brush, if no anti-
Should, then it is considered as dead worm.
When target is for Tetranychus cinnabarinus or aphis craccivora, tested using spray-on process, Tetranychus cinnabarinus and lucerne will be connected to respectively
Then Tetranychus cinnabarinus is placed in 24～27 DEG C of observation interiors and enters by the Broad Bean Leaves seedling of Mu aphid spraying treatment under potter spray tower
Row culture, aphis craccivora is placed in 20～22 DEG C of observation interiors and is cultivated, and observes result after 48h.Touch polypide with writing brush, if no
Reaction, then be considered as dead worm.
Count the dead borer population of each process and borer population of living, calculate the death rate.
The death rate (%)=[(borer population of living after test worm number-medicine)/test worm number] * 100
Above-claimed cpd insecticidal activity screening test result shows, in 500mg/l, the Tetranychus cinnabarinus of process, aphis craccivora
Inhibiting rate is 0, and part of compounds has 80% inhibiting rate to mythimna separata.
Indoor living the selection result is shown in Table 1:
The insecticidal activity the selection result of table 1 compound ()
As it can be seen from table 1 target compound -6, compound -7 and -8 pairs of mythimna separatas of compound have under 500mg/l
80% inhibiting rate, under 200mg/l, target compound -6, compound -7 and -8 pairs of mythimna separatas of compound still have 80% suppression
Rate processed.
Claims (10)
1. a kind of phenyl connects pyrazolecarboxamide analog derivative, is 1- (2,6- dichlor-4-trifluoromethyl phenyl)-n- (1- methyl -2-
Ethoxy) -3- Trifluoromethyl-1 h- pyrazoles -4- amides compound or derivatives thereof is it is characterised in that its general structure such as formula
Shown in (i):
In formula (i): r1For trifluoromethyl or difluoromethyl, r2For c1～c4 alkyl, replace alkyl, halogen or cyano group.
2. a kind of phenyl according to claim 1 connects pyrazolecarboxamide analog derivative it is characterised in that r2For methyl, chlorine,
Bromine, fluorine, trifluoromethyl or itrile group.
3. a kind of phenyl according to claim 1 connects the preparation method of pyrazolecarboxamide analog derivative it is characterised in that wrapping
Include following steps:
1) trifluoroacetic ethyl acetoacetate, triethyl orthoformate and acetic anhydride are mixed, back flow reaction reaction is subtracted with oil pump after terminating
Pressure distillation 98～105 DEG C of cuts of collection, obtain pale yellowish oil liquid, are the intermediate as shown in formula (), trifluoroacetyl acetic acid
The ratio of the amount of the material of ethyl ester, triethyl orthoformate and acetic anhydride is 1:1～2:2～3, preferably 1:1.5:3；
2) 2,6- dichlor-4-trifluoromethyl aniline is dissolved in glacial acetic acid, under mechanical agitation, instills concentrated hydrochloric acid, stir half an hour,
The aqueous solution of natrium nitrosum is instilled, then reaction 85-95 minute obtains reactant liquor, cold hydrazine bar under the conditions of 5～10 DEG C under cold hydrazine
Under part, this reactant liquor is added drop-wise in stannous chloride and the mixture of concentrated hydrochloric acid, completion of dropping is stirred at room temperature, filter, wash as
Solid chemical compound shown in formula ()；
3) by step 2) solid chemical compound as shown in formula () and the sodium hydrate aqueous solution mix and blend 25-35 that obtain divide
Clock, add ethanol stir 8-10 minute obtain mixed liquor, then by step 1 under ice bath) obtain as shown in formula () in
The ethanol solution of mesosome is slowly dropped in mixed liquor, is stirred at reflux 3.5-4.5 hour, and reaction uses dichloroethanes after terminating successively
Extraction, anhydrous sodium sulfate drying, filtration, are spin-dried for solvent and obtain compound 1- as shown in formula () for the red brown solid (2,6- bis- is chloro-
4- trifluoromethyl) -3- Trifluoromethyl-1 h- pyrazoles -4- Ethyl formate；
4) by step 3) compound as shown in formula () that obtains is dissolved in organic solvent c, adds 15% sodium hydroxide solution, plus
Heat, to 50-55 DEG C of reaction 1.8-2.2 hour, is reacted and is cooled to room temperature after terminating, and dropping watery hydrochloric acid to ph is in acidity, separates out admittedly
Body, suction filtration, filter cake washes with water, dries compound 1- (2,6- dichlor-4-trifluoromethyl the phenyl) -3- obtaining as shown in formula ()
Trifluoromethyl-1 h- pyrazoles -4- formic acid；
5) by step 4) compound as shown in formula () that obtains is dissolved in dried tetrahydrofuran solvent, drips under ice bath
Thionyl chloride, 0.4-0.6 hour drips off, back flow reaction 1.8-2.2 hour, and membrane pump is drained solvent and obtained the change as shown in formula ()
Compound 1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 h- pyrazoles -4- formyl chloride；
6) add 1- methyl-2-amino propyl alcohol, triethylamine and dichloromethane in the single-necked flask being dried, slowly drip under ice bath
Enter step 5) dichloromethane solution of the compound as shown in formula () that obtains, place 2.8- after stirring 0.8-1.2h under room temperature
3.2h, after precipitation with tlc separate, obtain compound 1- (2,6- dichlor-4-trifluoromethyl phenyl) as shown in formula () for the solid-
N- (1- methyl -2- ethoxy) -3- Trifluoromethyl-1 h- pyrazole-4-carboxamide；
7) weighing step 6) intermediate that the obtains compound as shown in formula (), in single port bottle, adds organic solvent d and takes
For aromatic isocyanate, instill 1 triethylamine, be stirred overnight under room temperature, concentrate, tlc separates, and obtains target product such as formula ()
Shown 1- (2,6- dichlor-4-trifluoromethyl phenyl)-n- (1- methyl -2- ethoxy) -3- Trifluoromethyl-1 h- pyrazoles -4- first
Amides compound；
The structural formula of each compound is as follows respectively:
Wherein r1=cf3Or chf2.
4. phenyl according to claim 3 connects the preparation method of pyrazolecarboxamide analog derivative it is characterised in that step 2)
In 2,6- dichlor-4-trifluoromethyl aniline, natrium nitrosum and stannous chloride the amount of material ratio be 1:1～2:1～1～2, excellent
Elect 1:1.2:2 as；The volumetric usage of glacial acetic acid is calculated as 1～5ml/mmol with the amount of 2,6- dichlor-4-trifluoromethyl aniline material,
It is preferably 5ml/mmol.
5. phenyl according to claim 3 connects the preparation method of pyrazolecarboxamide analog derivative it is characterised in that step 3)
The ratio of the solid chemical compound shown in Chinese style (), NaOH and the amount of the material of intermediate shown in formula () is 1:1-1.5:
1-1.2 (1:1～1.5～1:1.2), preferably 1:1.1:1；Stirring ethanol volumetric usage is with the solid chemical combination shown in formula ()
The amount of thing material is calculated as 1～5ml/mmol, preferably 1.2ml/mmol.
6. phenyl according to claim 3 connects the preparation method of pyrazolecarboxamide analog derivative it is characterised in that step 4)
The ratio of the amount of the material of the compound shown in Chinese style () and NaOH is 1:1～2, preferably 1:1.5；Described organic solvent
C is ethanol, methyl alcohol or oxolane, preferably ethanol；Described organic solvent c volumetric usage is with the compound thing shown in formula ()
The amount of matter is calculated as 2～5ml/mmol, preferably 2ml/mmol.
7. phenyl according to claim 3 connects the preparation method of pyrazolecarboxamide analog derivative it is characterised in that step 5)
Described in the ratio of the amount of material of compound as shown in formula () and thionyl chloride be 1:1～2, preferably 1:1.5；Tetrahydrochysene furan
Volumetric usage of muttering is calculated as 2～5ml/mmol, preferably 4ml/mmol with the amount of the combinations of materials as shown in formula ().
8. phenyl according to claim 3 connects the preparation method of pyrazolecarboxamide analog derivative it is characterised in that step 6)
Described in the compound shown in formula (), 1- methyl-2-amino propyl alcohol and triethylamine the amount of material 1:1～1.2:1～
1.5, preferably 1:1:1.2；Methylene chloride volume consumption is calculated as 2～5ml/ with the amount of the material of the compound shown in formula ()
Mmol, preferably 2ml/mmol.
9. phenyl according to claim 3 connects the preparation method of pyrazolecarboxamide analog derivative it is characterised in that step 7)
The ratio of the amount of the material of the compound shown in Chinese style () and substituted aryl isocyanates is 1:1～1.5, preferably 1:1.1；Have
Machine solvent d is one or more of oxolane, dmf, dichloromethane, preferably oxolane；The volume of organic solvent d is used
Amount is calculated as 2～5ml/mmol, preferably 2ml/mmol with the amount of the material of the compound shown in formula ().
10. a kind of phenyl according to claim 1 connects application in preparing insecticide for the pyrazolecarboxamide analog derivative, formula
1- shown in (i) (2,6- dichlor-4-trifluoromethyl phenyl)-n- (1- methyl -2- ethoxy) -3- Trifluoromethyl-1 h- pyrazoles -4-
Concentration in preparing insecticide for the Carbox amide is 500～100ppm.
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