CN107365307A - A kind of adjacent formamido benzamide compound of the substitution N- arylpyrazole structures containing trifluoromethyl and preparation method and application - Google Patents
A kind of adjacent formamido benzamide compound of the substitution N- arylpyrazole structures containing trifluoromethyl and preparation method and application Download PDFInfo
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- CN107365307A CN107365307A CN201710659664.2A CN201710659664A CN107365307A CN 107365307 A CN107365307 A CN 107365307A CN 201710659664 A CN201710659664 A CN 201710659664A CN 107365307 A CN107365307 A CN 107365307A
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- trifluoromethyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
- A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
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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
Abstract
The invention discloses a kind of adjacent formamido benzamide compound of the substitution N arylpyrazole structures containing trifluoromethyl and preparation method and application, shown in formula I, in formula, X is separately hydrogen, halogen, trifluoromethyl and cyano group to such compound；R1It is separately 2,6 dichloro-4,4 trifluoromethyls, the thiazolyl of 4 trifluoromethyl 2,3,5 two (trifluoromethyl) phenyl, the trifluoromethyl of 2 chlorine 6, the chlorphenyl of 2 trifluoromethyl 4, the fluorophenyl of 2 trifluoromethyl 4；R2It is separately methyl, ethyl, isopropyl, cyclopropyl, the tert-butyl group.Such compound have to Lepidoptera class pest it is excellent prevent effect, can be applicable to the pest and disease damage for preventing and treating various crops, there is the advantages of efficient, less toxic, environment-friendly.
Description
Technical field
The invention belongs to agricultural chemical insecticide field, a kind of adjacent formamido of the substitution N- arylpyrazole structures containing trifluoromethyl
Benzamide compound and preparation method and application.
Technical background
With the extensive use of insecticide, people are more and more deep to the understanding of insecticide.The continuous progressive and hair of society
Exhibition, promoting the concept of insecticide, there occurs deep change.Traditions of the past agricultural chemicals can not meet the development need of today's society
Ask, and find efficient, low toxicity, low-residual, the New-type wide-spectrum insecticide of environmentally friendly type is then placed in face of researcher
Problem urgently to be resolved hurrily.
Adjacent formamido benzamide compound is the effective insecticide for Lepidoptera class pest developed in recent years.
Du pont company is in a kind of new compound using ryanodine receptor as action target of exploitation in 2000.Such compound
There is efficient, less toxic, wide spectrum, safety, environment-friendly.Its representation compound Rynaxypyr (adopted name：
Chlorantraniliprole, trade name：Aliaco, Coragen, Rynaxypyr) various agricultural and gardening Lepidoptera are done harm to
Worm has good insecticidal activity.
Adjacent formamido benzamide compound has caused initiative field as efficient, low toxicity, the novel agrochemical of wide spectrum
The common concern of scientific research personnel, rapidly become one of newest focus of new pesticides innovative research.
It is to surround adjacent formamido in recent years that N- pyridines, which connect pyrazole group as the crucial pharmacophoric group of Rynaxypyr,
One of focus of benzamide insecticides structure of modification.The research method of main flow often retains N- pyridines and connects pyrazoles master at present
Body structure simultaneously carries out substantial amounts of structure replacement to the bromine on pyrazoles 3, such as：Ether-containing group, nitrogen heterocyclic ring, ester group, amide groups and
Ammonia substituted compound.Classification is illustrated below.
(1) structural modification of the ether-containing group to pyrazoles 3
It is that class pyrazoles 3 is methyl ether or the adjacent formamido benzoyl of trifluoroethyl ether that E.I.Du Pont Company in 2007, which reports,
Aminated compounds, which part compound have excellent prevention effect (Bioorganic＆ to diamondback moth at low concentrations
Medicinal Chemistry Letters, 2007,17 (22)：6274-6279.).Beyer Co., Ltd is then in 3 introducing oximes of pyrazoles
Ether, part of compounds have preferable prevention effect (WO 2006000336) to Lepidoptera class pest.2013, Nankai University
Li Zhengming academician seminar reports the series compound containing allyl ether series, and it has to mythimna separata and diamondback moth at low concentrations
100% fatal rate (Research on Chemical Intermediates, 2013,39 (7)：3071-3088.).2016
Year Huang et al. reports the compounds of 3 introducing propargyl ethers of pyrazoles, its cause to diamondback moth and mythimna separata at low concentrations
Dead rate is 100% (Journal of Heterocyclic Chemistry, 2016,53 (4)：1036-1045.).The same year, west
Pacify modern times chemistry institute Ning Bin seminar of section and dichloropropylene base ether is introduced into pyrazoles 3, if part of compounds is in 200mg
L-1Under concentration, after medicine 48h be 100% to the fatal rate of mythimna separata and diamondback moth (agricultural chemicals, 2016, (01)： 13-16.).2016
Xu Liangzhong seminars of Qingdao University of Science and Technology report the compound of the chloro- 5- thiazole methyls ether containing 2-, and it is at low concentrations to small
Diamond-back moth with 100% prevention effect (agricultural chemicals, 2016, (03)：170-173.).
(2) structural modification of the nitrogen heterocyclic ring to pyrazoles 3
2010-2011, Beyer Co., Ltd report series and contain trifluoromethyl pyrazol, and 4- trifluoromethylbenzenes connect triazole, contained
Trifluoromethyl triazole and tetrazotized zole compound containing trifluoromethyl, these compounds have to Lepidoptera class pest at low concentrations
Preferable prevention effect (WO 2010069502, WO 2011128329).
(3) structural modification of the ester group to pyrazoles 3
2010, rectification of name academician Nankai University Lee seminar reported the compounds that pyrazoles 3 is ester group substitution, its middle part
Break up compound in 10mg L-1There is 100% insecticidal activity (Journal of Agricultural and under concentration to mythimna separata
Food Chemistry, 2010,58 (23)：12327-12336.).2013, Li Zhengming academician seminar was by the ester of compound
Key reverses, and part of compounds is in 200mg L-1100% desinsection is respectively provided with concentration to oriental armyworm, diamondback moth and beet armyworm
Active (Chemical Research in Chinese Universities, 2013,29 (1)：51-56.).
(4) structural modification of amide groups and Ammonia substituted compound to pyrazoles 3
2010, it was amide groups and Ammonia substituted compound that rectification of name academician Nankai University Lee seminar, which reports pyrazoles 3,
Compound, which part compound is in 10mg L-1It is 100% to the fatal rate of mythimna separata under concentration, in 1mg L-1It is right under concentration
Diamondback moth has 100% and 80% insecticidal activity respectively, but when pyrazoles 3 be primary amine substituent, then almost without biological
Activity, but when for azide substitution base when, compound is 100% (Journal of to the fatal rate of mythimna separata under concentration
Agricultural and Food Chemistry, 2010,58 (23)：12327-12336.).
As seen from the above, the research method of main flow often retains N- pyridines and connects pyrazoles agent structure and to pyrazoles 3 at present
Bit substituent carries out substantial amounts of structure replacement, although having had now been found that some have the high-activity compound of DEVELOPMENT PROSPECT,
But still need to improve conventional method in the long term in the hope of obtaining the novel noval chemical compound of structure.
2014-2016 Li Zhengming academicians seminar substituted for 3- chloropyridines (Bioorganic using chloronitrobenzene
Medicinal Chemistry, 2014,22 (1)：186-193.Journal of Agricultural and Food
Chemistry, 2016,64 (18)：3697-3704.).Which part compound has to mythimna separata and diamondback moth at low concentrations
Excellent prevention effect.Such compound breaches the structural framework that N- pyridines in structure connect pyrazoles, and insecticidal effect is excellent.Can
Connecting pyrazoles with the N- pyridines found out in Rynaxypyr still has more wide development space.
Because trifluoromethyl has the characteristics such as strong electron-withdrawing, lipophilicity, less volume and stable C-F keys, by it
It is incorporated into the acidity that compound can be significantly changed in organic compound, dipole moment, polarity, lipophilicity and its chemistry and metabolism
Stability.Therefore the compound containing trifluoromethyl is used widely in fields such as medicine, agricultural chemicals and materials.Engage in trade at present
Also can also find its figure in many insecticides of product, as capillary, ethiprole, sulfoxaflor, lambda-cyhalothrin and
Indoxacarb.It can be seen that trifluoromethyl has potential application prospect in adjacent formamido benzamide compound.
Therefore, the 2- chloropyridine groups of the invention that N- pyridines in Rynaxypyr are connected to pyrazolyl are replaced with containing fluoroform
The phenyl or thiazolyl of base, and using the principle of activity splicing, in pyrazoles, 3 introduce trifluoromethyls, in the benzene containing trifluoromethyl
Halogen atom is introduced in base or thiazolyl, so as to breach the adjacent formamido benzene first that pyridine containing N- connects pyrrazole structure in structure
Amides compound and nitrobenzene containing N- connect the adjacent formamido benzamide compound of pyrrazole structure.In addition, by this
Class compound carries out biological activity test, it is found that such compound has very excellent insecticidal activity.
The content of the invention
It is an object of the invention to the substitution N- aryl containing trifluoromethyl for having synthesized a kind of brand new to connect pyrrazole structure
Adjacent formamido benzamide compound, it can be used for the insecticide for preparing preventing and treating agricultural insect pest.
The present invention relates to the adjacent formamido benzamide derivatives represented by leading to formula (I)：
A kind of adjacent formamido benzamide compound (I) of the substitution N- arylpyrazole structures containing trifluoromethyl, it is tied
Structure formula is：
Wherein, X is separately hydrogen, halogen, trifluoromethyl and cyano group；R1It is separately the chloro- 4- tri- of 2,6- bis-
Trifluoromethylphenyl, 4- trifluoromethyl -2- thiazolyls, 3,5- bis- (trifluoromethyl) phenyl, the chloro- 6- trifluoromethyls of 2-, 2- tri-
Methyl fluoride -4- chlorphenyls, 2- trifluoromethyl -4- fluorophenyls；R2It is separately methyl, ethyl, isopropyl, cyclopropyl and uncle
Butyl.Contain agricultural and horticultural insecticides of the above-claimed cpd as active component, and their application method.
Contain above-claimed cpd as the agricultural of active component and be suitable for preventing and treating Lepidoptera class pest with horticultural insecticides, such as
Agricultural and gardening lepidoptera pest, the cereal lepidoptera pest of storage, the lepidoptera pest etc. of health field.These insects are to water
Rice, fruit tree, vegetables other crops, flowers, ornamental plant etc. are harmful.
Preparation in accordance with the present invention is as follows, but it is never the model of the method limitation present invention in any form
Enclose.
Synthetic route is as follows：
1) by the compound V of 1 times of amount, the amount of material is unit, similarly hereinafter, in atent solvent, with the 1-2 times of oxalyl chloride measured
0.5-48 hours are stirred at room temperature under conditions of DMF makees catalyst, precipitation, are prepared into acyl chlorides IV；
2) above-claimed cpd IV is dissolved in atent solvent, with 1 times quantify compound III in condition existing for acid binding agent next time
Stream reaction 1-4 hours, precipitation, it is prepared into intermediate II；
3) above-claimed cpd II is dissolved in atent solvent, primary amine R is added dropwise2NH2, reacted under 0 DEG C to reflux temperature
0.5-48 hours obtain compound I.
Atent solvent for reaction is for example：DMF, DMA, acetone, acetonitrile, four
Hydrogen furans, chloroform, dichloromethane, ether, methyl tertiary butyl ether(MTBE), benzene, chlorobenzene, toluene or Isosorbide-5-Nitrae-dioxane etc.；
Acid binding agent for reaction is for example：Pyridine, triethylamine, N- ethyl diisopropylamines, sodium hydroxide, potassium hydroxide, carbon
Sour sodium or potassium carbonate etc..
After the completion of reaction, required compound is separated from the system containing required compound by conventional method, if
If necessary, purified by recrystallization, column chromatography etc., it is possible thereby to prepare required compound.
It is listed in Table 1 below as the typical compound of the adjacent formamido benzamide derivatives (I) of the present invention, but it determines
The scope not limiting the invention in any way.
Logical formula (I)
Table 1
The representative instance of the present invention is described below, but they are because being considered as limitation of the present invention.
Embodiment
Specific examples below is used for further illustrating the present invention
Organic synthesis example
Example 1：N- (4- chloro-2-methyls -6- (methyl-carbamoyl) phenyl) -1- (4- trifluoromethyl -2- thiazolyls) -3-
Trifluoromethyl-1 H- pyrazoles -5- formamides
3- Trifluoromethyl-1s-(4- trifluoromethyl -2- thiazolyls) -1H- pyrazoles -5- carboxylic acids (6mmol) are placed in 100 mL
In two mouthfuls of flasks, 50mL anhydrous methylene chlorides and 2 drop DMF are added.Reaction is placed in ice bath afterwards, oxalyl is slowly added dropwise at 0 DEG C
Chlorine (15mmol), finish after 20min, 2h is stirred under normal temperature condition.After the completion of TLC determines reaction, removal of solvent under reduced pressure, 3- is obtained
Trifluoromethyl-1-(4- trifluoromethyl-2- thiazolyls)-1H- pyrazoles-5- acyl chlorides, is sealed.
In 100mL three-necked flasks, the acyl chlorides (6mmol) of above-mentioned preparation is dissolved in the anhydrous N of 45mL, N- dimethyl formyls
In the mixed solution of amine and 15mL anhydrous pyridines, 30min is stirred at 70 DEG C.The chloro- 8- first of 2- phenyl -6- then is added portionwise
Base -4H-1,3- benzoxazinone (6mmol), there are in reaction solution a large amount of bubbles to release, 30min is finished, after stir under reflux conditions
Mix 4h.After the completion of TLC determines reaction, reaction solution is cooled to room temperature, solvent is sloughed in decompression, through column chromatography (tlc silica gel,
Petroleum ether and dichloromethane are eluant, eluent) obtain the chloro- 8- methyl -2- of compound 6- (3- Trifluoromethyl-1s-(4- trifluoromethyl -2- thiophenes
Oxazolyl) -1H- pyrazoles -5- bases) -4H-1,3- benzoxazinones, yield 53.2%.
By the chloro- 8- methyl -2- of above-mentioned preparation 6- (3- Trifluoromethyl-1s-(4- trifluoromethyl -2- thiazolyls) -1H- pyrazoles -
5- yls) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
The aqueous solution (6.0mmol) of methylamine, stirring at normal temperature 2h, filtering, dry cake obtain target product N- (4- chloro-2-methyls -6-
(methyl-carbamoyl) phenyl) -1- (4- trifluoromethyl -2- thiazolyls) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield
For 86.2%.
Example 2：N- (4- chloro-2-methyls -6- (isopropyl carbamoyl base) phenyl) -1- (4- trifluoromethyl -2- thiazolyls) -
3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By the chloro- 8- methyl -2- of above-mentioned preparation 6- (3- Trifluoromethyl-1s-(4- trifluoromethyl -2- thiazolyls) -1H- pyrazoles -
5- yls) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL N, N- dimethyl second
Acid amides, after be slowly added dropwise isopropylamine (6.0mmol), stirring at normal temperature 2h, filtering, dry cake obtains target product N- (the chloro- 2- of 4-
Methyl -6- (isopropyl carbamoyl base) phenyl) -1- (4- trifluoromethyl -2- thiazolyls) -3- Trifluoromethyl-1 H- pyrazoles -5- first
Acid amides, yield 89.1%.
Example 3：N- (4- chloro-2-methyls -6- (cyclopropylamino formoxyl) phenyl) -1- (4- trifluoromethyl -2- thiazolyls) -
3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By the chloro- 8- methyl -2- of above-mentioned preparation 6- (3- Trifluoromethyl-1s-(4- trifluoromethyl -2- thiazolyls) -1H- pyrazoles -
5- yls) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetone, after be slowly added dropwise
Cyclopropylamine (6.0mmol), stirring at normal temperature 2h, filtering, dry cake obtain the target product N- (4- chloro-2-methyls -6- (ammonia of ring third
Base formoxyl) phenyl) -1- (4- trifluoromethyl -2- thiazolyls) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield is
81.1%.
Example 4：N- (bromo- 2- methyl -6- (methyl-carbamoyl) phenyl of 4-) -1- (4- trifluoromethyl -2- thiazolyls) -3-
Trifluoromethyl-1 H- pyrazoles -5- formamides
In 100mL three-necked flasks, by 3- Trifluoromethyl-1s-(4- trifluoromethyl -2- thiazolyls) -1H- pyrazoles -5- acyls
Chlorine (6mmol) is dissolved in the mixed solution of 45mL anhydrous acetonitriles and 15mL anhydrous pyridines, and 30min is stirred at 70 DEG C.Then divide
Criticize and add bromo- 8- methyl -4H-1, the 3- benzoxazinones (6mmol) of 2- phenyl -6-, there are a large amount of bubbles to release in reaction solution,
30min is finished, after stir 4h under reflux conditions.After the completion of TLC determines reaction, reaction solution is cooled to room temperature, decompression is sloughed
Solvent, the bromo- 8- methyl -2- (3- of compound 6- are obtained through column chromatography (tlc silica gel, petroleum ether and dichloromethane are eluant, eluent)
Trifluoromethyl-1-(4- trifluoromethyl-2- thiazolyls)-1H- pyrazoles-5- bases)-4H-1,3- benzoxazinones, yield is
47.2%.
By the bromo- 8- methyl -2- of above-mentioned preparation 6- (3- Trifluoromethyl-1s-(4- trifluoromethyl -2- thiazolyls) -1H- pyrazoles -
5- yls) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL tetrahydrofurans, it is rear slowly
Be added dropwise methylamine the aqueous solution (6.0mmol), stirring at normal temperature 2h, filtering, dry cake obtain target product N- (the bromo- 2- methyl of 4--
6- (methyl-carbamoyl) phenyl) -1- (4- trifluoromethyl -2- thiazolyls) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, receive
Rate is 82.1%.
Example 5：N- (4- bromo- 2- methyl -6- (isopropyl carbamoyl base) phenyl) -1- (4- trifluoromethyl -2- thiazolyls) -
3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By the bromo- 8- methyl -2- of above-mentioned preparation 6- (3- Trifluoromethyl-1s-(4- trifluoromethyl -2- thiazolyls) -1H- pyrazoles -
5- yls) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
Isopropylamine (6.0mmol), stirring at normal temperature 2h, filtering, dry cake obtain target product N- (bromo- 2- methyl -6- (the isopropyl ammonia of 4-
Base formoxyl) phenyl) -1- (4- trifluoromethyl -2- thiazolyls) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield is
86.6%.
Example 6：N- (4- bromo- 2- methyl -6- (cyclopropylamino formoxyl) phenyl) -1- (4- trifluoromethyl -2- thiazolyls) -
3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By the bromo- 8- methyl -2- of above-mentioned preparation 6- (3- Trifluoromethyl-1s-(4- trifluoromethyl -2- thiazolyls) -1H- pyrazoles -
5- yls) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
Cyclopropylamine (6.0mmol), stirring at normal temperature 2h, filtering, dry cake obtain target product N- (the 4- bromo- 2- methyl -6- (ammonia of ring third
Base formoxyl) phenyl) -1- (4- trifluoromethyl -2- thiazolyls) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield is
84.9%.
Example 7：N- (4- chloro-2-methyls -6- (methyl-carbamoyl) phenyl) -1- (2,6- dichlor-4-trifluoromethyl benzene
Base) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- carboxylic acids (6mmol) are placed in
In two mouthfuls of flasks of 100mL, 50mL anhydrous methylene chlorides and 2 drop DMF are added.Reaction is placed in ice bath afterwards, is slowly added dropwise at 0 DEG C
Oxalyl chloride (15mmol), finish after 20min, 0.5h is stirred at 0 DEG C.After the completion of TLC determines reaction, removal of solvent under reduced pressure, obtain
1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- acyl chlorides, is sealed.
In 100mL three-necked flasks, the acyl chlorides (6mmol) of above-mentioned preparation is dissolved in 45mL anhydrous acetonitriles and 15mL is anhydrous
In the mixed solution of N- ethyl diisopropylamines, 30min is stirred at 70 DEG C.Then be added portionwise the chloro- 8- methyl of 2- phenyl -6- -
4H-1,3- benzoxazinone (6mmol), there are in reaction solution a large amount of bubbles to release, 30min is finished, after stir under reflux conditions
4h.After the completion of TLC determines reaction, reaction solution is cooled to room temperature, solvent is sloughed in decompression, through column chromatography (tlc silica gel, stone
Oily ether and dichloromethane are eluant, eluent) obtain the chloro- 8- methyl -2- of compound 6- (1- (2,6- dichlor-4-trifluoromethyl phenyl) -3-
Trifluoromethyl-1 H- pyrazoles -5- bases) -4H-1,3- benzoxazinones, yield 64.9%.
By the chloro- 8- methyl -2- of above-mentioned preparation 6- (1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrroles
Azoles -5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, it is rear slowly
The aqueous solution (6.0mmol) of methylamine is added dropwise, 10 DEG C of stirring 30h, rear removal of solvent under reduced pressure, residue is through column chromatography (silica gel 200-
300 mesh, petroleum ether and ethyl acetate are eluant, eluent) obtain target product N- (4- chloro-2-methyls -6- (methyl-carbamoyl) benzene
Base) -1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield 89.5%.
Example 8：N- (4- chloro-2-methyls -6- (isopropyl carbamoyl base) phenyl) -1- (2,6- dichlor-4-trifluoromethyl benzene
Base) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By the chloro- 8- methyl -2- of above-mentioned preparation 6- (1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrroles
Azoles -5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, it is rear slowly
Be added dropwise isopropylamine (6.0mmol), 20 DEG C stirring 10h, rear removal of solvent under reduced pressure, residue through column chromatography (silica gel 200-300 mesh,
Petroleum ether and ethyl acetate are eluant, eluent) obtain target product N- (4- chloro-2-methyls -6- (isopropyl carbamoyl base) phenyl) -
1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield 91.2%.
Example 9：N- (4- chloro-2-methyls -6- (cyclopropylamino formoxyl) phenyl) -1- (2,6- dichlor-4-trifluoromethyl benzene
Base) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By the chloro- 8- methyl -2- of above-mentioned preparation 6- (1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrroles
Azoles -5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL ether, it is rear slowly
Be added dropwise cyclopropylamine (6.0mmol), stirring at normal temperature 15h, rear removal of solvent under reduced pressure, residue through column chromatography (silica gel 200-300 mesh,
Petroleum ether and ethyl acetate are eluant, eluent) obtain target product N- (4- chloro-2-methyls -6- (cyclopropylamino formoxyl) phenyl) -
1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield 89.9%.
Example 10：N- (4- chloro-2-methyls -6- (methyl-carbamoyl) phenyl) -1- (2,6- dichlor-4-trifluoromethyl benzene
Base) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
In 100mL three-necked flasks, by 1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrazoles -
5- acyl chlorides (6mmol) is dissolved in the mixed solution of 45mL anhydrous acetonitriles and 15mL anhydrous triethylamines, and 30min is stirred at 70 DEG C.
Bromo- 8- methyl -4H-1, the 3- benzoxazinones (6 mmol) of 2- phenyl -6- then are added portionwise, there are a large amount of bubbles to put in reaction solution
Go out, 30min is finished, after stir 3h under reflux conditions.After the completion of TLC determines reaction, reaction solution is cooled to room temperature, depressurized
Slough solvent, through column chromatography (tlc silica gel, petroleum ether and dichloromethane are eluant, eluent) the bromo- 8- methyl of compound 6--
2- (1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- bases) -4H-1,3- benzoxazinones, receive
Rate is 59.9%.
By the bromo- 8- methyl -2- of above-mentioned preparation 6- (1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrroles
Azoles -5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL methyl tertbutyls
Ether, after the aqueous solution (6.0mmol) of methylamine is slowly added dropwise, stirring at normal temperature 2h, rear removal of solvent under reduced pressure, residue is through column chromatography
(silica gel 200-300 mesh, petroleum ether and ethyl acetate are eluant, eluent) obtains target product N- (the bromo- 2- methyl -6- (methylaminos of 4-
Formoxyl) phenyl) -1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield is
91.8%.
Example 11：N- (4- chloro-2-methyls -6- (isopropyl carbamoyl base) phenyl) -1- (2,6- dichlor-4-trifluoromethyls
Phenyl) -3- Trifluoromethyl-1 N- pyrazoles -5- formamides
By the bromo- 8- methyl -2- of above-mentioned preparation 6- (1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrroles
Azoles -5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, it is rear slowly
Be added dropwise isopropylamine (6.0mmol), stirring at normal temperature 18h, rear removal of solvent under reduced pressure, residue through column chromatography (silica gel 200-300 mesh,
Petroleum ether and ethyl acetate are eluant, eluent) obtain target product N- (4- bromo- 2- methyl -6- (isopropyl carbamoyl base) phenyl) -
1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield 95.1%.
Example 12：N- (4- chloro-2-methyls -6- (cyclopropylamino formoxyl) phenyl) -1- (2,6- dichlor-4-trifluoromethyls
Phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By the bromo- 8- methyl -2- of above-mentioned preparation 6- (1- (2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrroles
Azoles -5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, it is rear slowly
Cyclopropylamine (6.0mmol) is added dropwise, stirring at normal temperature 2h, rear removal of solvent under reduced pressure, residue is through column chromatography (silica gel 200-300 mesh, stone
Oily ether and ethyl acetate are eluant, eluent) obtain target product N- (4- bromo- 2- methyl -6- (cyclopropylamino formoxyl) phenyl) -1-
(2,6- dichlor-4-trifluoromethyl phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield 87.7%.
Example 13：N- (4- chloro-2-methyls -6- (methyl-carbamoyl) phenyl) -1- (3,5- bis- (trifluoromethyl) phenyl) -
3- Trifluoromethyl-1 H- pyrazoles -5- formamides
1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- carboxylic acids (6mmol) are placed in 100mL
In two mouthfuls of flasks, 50mL anhydrous methylene chlorides and 2 drop DMF are added.Reaction is placed in ice bath afterwards, oxalyl is slowly added dropwise at 0 DEG C
Chlorine (15mmol), finish after 20min, 48h is stirred under normal temperature condition.After the completion of TLC determines reaction, removal of solvent under reduced pressure, obtain
1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- acyl chlorides, is sealed.
In 100mL three-necked flasks, the acyl chlorides (6mmol) of above-mentioned preparation is dissolved in 45mL anhydrous acetonitriles and 15mL is anhydrous
In the mixed solution of pyridine, 30min is stirred at 70 DEG C.Chloro- 8- methyl -4H-1, the 3- benzene of 2- phenyl -6- then is added portionwise
Bing oxazinones (6mmol), there are in reaction solution a large amount of bubbles to release, 30min is finished, after stir 1h under reflux conditions.TLC is determined
After the completion of reaction, reaction solution is cooled to room temperature, solvent is sloughed in decompression, through column chromatography (tlc silica gel, petroleum ether and dichloro
Methane is eluant, eluent) obtain the chloro- 8- methyl -2- of compound 6- (1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrroles
Azoles -5- bases) -4H-1,3- benzoxazinones, yield 76.1%.
By the chloro- 8- methyl -2- of above-mentioned preparation 6- (1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles
- 5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
The aqueous solution (6.0mmol) of methylamine, stirring at normal temperature 48h, filtering, dry cake obtain target product N- (4- chloro-2-methyls -6-
(methyl-carbamoyl) phenyl) -1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, receive
Rate is 92.3%.
Example 14：N- (4- chloro-2-methyls -6- (isopropyl carbamoyl base) phenyl) -1- (3,5- bis- (trifluoromethyl) benzene
Base) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By the chloro- 8- methyl -2- of above-mentioned preparation 6- (1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles
- 5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
Isopropylamine (6.0mmol), stirring at normal temperature 2h, filtering, dry cake obtain target product N- (4- chloro-2-methyls -6- (isopropyl ammonia
Base formoxyl) phenyl) -1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield is
95.5%.
Example 15：N- (4- chloro-2-methyls -6- (cyclopropylamino formoxyl) phenyl) -1- (3,5- bis- (trifluoromethyl) benzene
Base) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By the chloro- 8- methyl -2- of above-mentioned preparation 6- (1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles
- 5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
Cyclopropylamine (6.0mmol), stirring at normal temperature 2h, filtering, dry cake obtain the target product N- (4- chloro-2-methyls -6- (ammonia of ring third
Base formoxyl) phenyl) -1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield is
91.5%.
Example 16：N- (4- chloro-2-methyls -6- (methyl-carbamoyl) phenyl) -1- (3,5- bis- (trifluoromethyl) phenyl) -
3- Trifluoromethyl-1 H- pyrazoles -5- formamides
In 100mL three-necked flasks, by 1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- acyls
Chlorine (6mmol) is dissolved in the mixed solution of 45mL anhydrous acetonitriles and 15mL anhydrous triethylamines, and 30min is stirred at 70 DEG C.Then
Bromo- 8- methyl -4H-1, the 3- benzoxazinones (6 mmol) of 2- phenyl -6- are added portionwise, there are a large amount of bubbles to release in reaction solution,
30min is finished, after stir 2h under reflux conditions.After the completion of TLC determines reaction, reaction solution is cooled to room temperature, decompression is sloughed
Solvent, the bromo- 8- methyl -2- (1- of compound 6- are obtained through column chromatography (tlc silica gel, petroleum ether and dichloromethane are eluant, eluent)
(3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- bases) -4H-1,3- benzoxazinones, yield is
76.4%.
By the bromo- 8- methyl -2- of above-mentioned preparation 6- (1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles
- 5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
The aqueous solution (6.0mmol) of methylamine, stirring at normal temperature 25h, filtering, dry cake obtain target product N- (the bromo- 2- methyl -6- of 4-
(methyl-carbamoyl) phenyl) -1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, receive
Rate is 89.1%.
Example 17：N- (4- chloro-2-methyls -6- (isopropyl carbamoyl base) phenyl) -1- (3,5- bis- (trifluoromethyl) benzene
Base) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By the bromo- 8- methyl -2- of above-mentioned preparation 6- (1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles
- 5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
Isopropylamine (6.0mmol), stirring at normal temperature 2h, filtering, dry cake obtain target product N- (bromo- 2- methyl -6- (the isopropyl ammonia of 4-
Base formoxyl) phenyl) -1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield is
96.7%.
Example 18：N- (4- chloro-2-methyls -6- (cyclopropylamino formoxyl) phenyl) -1- (3,5- bis- (trifluoromethyl) benzene
Base) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By the bromo- 8- methyl -2- of above-mentioned preparation 6- (1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles
- 5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
Cyclopropylamine (6.0mmol), stirring at normal temperature 2h, filtering, dry cake obtain target product N- (the 4- bromo- 2- methyl -6- (ammonia of ring third
Base formoxyl) phenyl) -1- (3,5- bis- (trifluoromethyl) phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield is
90.1%.
Example 19：N- (4- chloro-2-methyls -6- (methyl-carbamoyl) phenyl) -1- (the chloro- 6- trifluoromethyls of 2-) -
3- Trifluoromethyl-1 H- pyrazoles -5- formamides
1- (the chloro- 6- trifluoromethyls of 2-) -3- Trifluoromethyl-1 H- pyrazoles -5- carboxylic acids (6mmol) are placed in 100 mL
In two mouthfuls of flasks, 50mL anhydrous methylene chlorides and 2 drop DMF are added.Reaction is placed in ice bath afterwards, oxalyl is slowly added dropwise at 0 DEG C
Chlorine (15mmol), finish after 20min, 2h is stirred under normal temperature condition.After the completion of TLC determines reaction, removal of solvent under reduced pressure, 1- is obtained
(the chloro- 6- trifluoromethyls of 2-) -3- Trifluoromethyl-1 H- pyrazoles -5- acyl chlorides, is sealed.
In 100mL three-necked flasks, the acyl chlorides (6mmol) of above-mentioned preparation is dissolved in 45mL anhydrous acetonitriles and 15mL is anhydrous
In the mixed solution of pyridine, 30min is stirred at 70 DEG C.Chloro- 8- methyl -4H-1, the 3- benzene of 2- phenyl -6- then is added portionwise
Bing oxazinones (6mmol), there are in reaction solution a large amount of bubbles to release, 30min is finished, after stir 4h under reflux conditions.TLC is determined
After the completion of reaction, reaction solution is cooled to room temperature, solvent is sloughed in decompression, through column chromatography (tlc silica gel, petroleum ether and dichloro
Methane is eluant, eluent) obtain the chloro- 8- methyl -2- of compound 6- (1- (the chloro- 6- trifluoromethyls of 2-) -3- Trifluoromethyl-1 H- pyrroles
Azoles -5- bases) -4H-1,3- benzoxazinones, yield 48.7%.
By the chloro- 8- methyl -2- of above-mentioned preparation 6- (1- (the chloro- 6- trifluoromethyls of 2-) -3- Trifluoromethyl-1 H- pyrazoles -
5- yls) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
The aqueous solution (6.0mmol) of methylamine, stirring at normal temperature 2h, filtering, dry cake obtain target product N- (4- chloro-2-methyls -6-
(methyl-carbamoyl) phenyl) -1- (the chloro- 6- trifluoromethyls of 2-) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield
For 91.1%.
Example 20：N- (4- chloro-2-methyls -6- (t-Butylcarbamoyl) phenyl) -1- (chloro- 6- trifluoromethylbenzenes of 2-
Base) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By the chloro- 8- methyl -2- of above-mentioned preparation 6- (1- (the chloro- 6- trifluoromethyls of 2-) -3- Trifluoromethyl-1 H- pyrazoles -
5- yls) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
Tert-butylamine (6.0mmol), stirring at normal temperature 0.5h, filtering, dry cake obtain target product N- (4- chloro-2-methyls -6- (tertiary fourths
Base carbamoyl) phenyl) -1- (the chloro- 6- trifluoromethyls of 2-) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield is
94.6%.
Example 21：N- (4- cyano group -2- methyl -6- (methyl-carbamoyl) phenyl) -1- (chloro- 6- trifluoromethylbenzenes of 2-
Base) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
In 100mL three-necked flasks, by 1- (the chloro- 6- trifluoromethyls of 2-) -3- Trifluoromethyl-1 H- pyrazoles -5- acyls
Chlorine (6mmol) is dissolved in 45mL anhydrous acetonitriles, adds sodium hydroxide (12mmol), 30min is stirred at 70 DEG C.Then it is added portionwise
2- phenyl -6- cyano group -8- methyl -4H-1,3- benzoxazinones (6mmol), have in reaction solution a large amount of bubbles to release, and 30min adds
Finish, after stir 4h under reflux conditions.After the completion of TLC determines reaction, reaction solution is cooled to room temperature, solvent is sloughed in decompression, is passed through
Column chromatography (tlc silica gel, petroleum ether and dichloromethane are eluant, eluent) obtains compound 6- cyano group -8- methyl -2- (1- (2-
Chloro- 6- trifluoromethyls) -3- Trifluoromethyl-1 H- pyrazoles -5- bases) -4H-1,3- benzoxazinones, yield 46.1%.
By above-mentioned preparation 6- cyano group -8- methyl -2- (1- (the chloro- 6- trifluoromethyls of 2-) -3- Trifluoromethyl-1 H- pyrazoles
- 5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
The aqueous solution (6.0mmol) of methylamine, stirring at normal temperature 2h, filtering, dry cake obtain target product N- (4- cyano group -2- methyl -6-
(methyl-carbamoyl) phenyl) -1- (the chloro- 6- trifluoromethyls of 2-) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield
For 86.2%.
Example 22：N- (4- cyano group -2- methyl -6- (t-Butylcarbamoyl) phenyl) -1- (chloro- 6- trifluoromethyls of 2-
Phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By above-mentioned preparation 6- cyano group -8- methyl -2- (1- (the chloro- 6- trifluoromethyls of 2-) -3- Trifluoromethyl-1 H- pyrazoles
- 5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
Tert-butylamine (6.0mmol), stirring at normal temperature 2h, filtering, dry cake obtain target product N- (4- cyano group -2- methyl -6- (uncles
Butylcarbamoyl) phenyl) -1- (the chloro- 6- trifluoromethyls of 2-) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, receive
Rate is 82.7%.
Example 23：N- (4- chloro-2-methyls -6- (methyl-carbamoyl) phenyl) -1- (2- trifluoromethyl-4-chlorophenyls) -
3- Trifluoromethyl-1 H- pyrazoles -5- formamides
1- (2- trifluoromethyl-4-chlorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- carboxylic acids (6mmol) are placed in 100 mL
In two mouthfuls of flasks, 50mL anhydrous methylene chlorides and 2 drop DMF are added.Reaction is placed in ice bath afterwards, oxalyl is slowly added dropwise at 0 DEG C
Chlorine (15mmol), finish after 20min, 2h is stirred under normal temperature condition.After the completion of TLC determines reaction, removal of solvent under reduced pressure, 1- is obtained
(2- trifluoromethyl-4-chlorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- acyl chlorides, is sealed.
In 100mL three-necked flasks, the acyl chlorides (6mmol) of above-mentioned preparation is dissolved in 45mL anhydrous acetonitriles, adds hydroxide
Potassium (12mmol), 30min is stirred at 70 DEG C.Chloro- 8- methyl -4H-1, the 3- benzoxazines of 2- phenyl -6- then are added portionwise
Ketone (6mmol), there are in reaction solution a large amount of bubbles to release, 30min is finished, after stir 4h under reflux conditions.TLC determines to have reacted
Cheng Hou, reaction solution is cooled to room temperature, solvent is sloughed in decompression, and (tlc silica gel, petroleum ether and dichloromethane are through column chromatography
Eluant, eluent) obtain the chloro- 8- methyl -2- of compound 6- (1- (2- trifluoromethyl-4-chlorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5-
Base) -4H-1,3- benzoxazinones, yield 44.1%.
By the chloro- 8- methyl -2- of above-mentioned preparation 6- (1- (2- trifluoromethyl-4-chlorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -
5- yls) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL benzene, after first is slowly added dropwise
The aqueous solution (6.0mmol) of amine, stirring at normal temperature 2h, filtering, dry cake obtain target product N- (4- chloro-2-methyl -6- (first
Carbamoyl) phenyl) -1- (2- trifluoromethyl-4-chlorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield is
81.9%.
Example 24：N- (4- chloro-2-methyls -6- (t-Butylcarbamoyl) phenyl) -1- (2- trifluoromethyl -4- chlorobenzenes
Base) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By the chloro- 8- methyl -2- of above-mentioned preparation 6- (1- (2- trifluoromethyl-4-chlorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -
5- yls) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL chlorobenzenes, after be slowly added dropwise
Tert-butylamine (6.0mmol), stirring at normal temperature 2h, filtering, dry cake obtain target product N- (4- chloro-2-methyls -6- (tertiary fourths
Base carbamoyl) phenyl) -1- (2- trifluoromethyl-4-chlorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield is
88.0%.
Example 25：N- (4- cyano group -2- methyl -6- (methyl-carbamoyl) phenyl) -1- (2- trifluoromethyl -4- chlorobenzenes
Base) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
In 100mL three-necked flasks, by 1- (2- trifluoromethyl-4-chlorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- acyls
Chlorine (6mmol) is dissolved in 45mL anhydrous acetonitriles, adds sodium hydroxide (12mmol), 30min is stirred at 70 DEG C.Then it is added portionwise
2- phenyl -6- cyano group -8- methyl -4H-1,3- benzoxazinones (6mmol), have in reaction solution a large amount of bubbles to release, and 30min adds
Finish, after stir 4h under reflux conditions.After the completion of TLC determines reaction, reaction solution is cooled to room temperature, solvent is sloughed in decompression, is passed through
Column chromatography (tlc silica gel, petroleum ether and dichloromethane are eluant, eluent) obtains compound 6- cyano group -8- methyl -2- (1- (2- tri-
Methyl fluoride -4- chlorphenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- bases) -4H-1,3- benzoxazinones, yield 56.2%.
By above-mentioned preparation 6- cyano group -8- methyl -2- (1- (2- trifluoromethyl-4-chlorophenyls) -3- Trifluoromethyl-1 H- pyrazoles
- 5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL toluene, after be slowly added dropwise
The aqueous solution (6.0mmol) of methylamine, stirring at normal temperature 2h, filtering, dry cake obtain target product N- (4- cyano group -2- methyl -6-
(methyl-carbamoyl) phenyl) -1- (2- trifluoromethyl-4-chlorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield
For 85.0%.
Example 26：N- (4- cyano group -2- methyl -6- (t-Butylcarbamoyl) phenyl) -1- (2- trifluoromethyl -4- chlorine
Phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By above-mentioned preparation 6- cyano group -8- methyl -2- (1- (2- trifluoromethyl-4-chlorophenyls) -3- Trifluoromethyl-1 H- pyrazoles
- 5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
The tert-butyl group (6.0mmol), stirring at normal temperature 2h, filtering, dry cake obtain target product N- (4- cyano group -2- methyl -6- (tertiary fourths
Base carbamoyl) phenyl) -1- (2- trifluoromethyl-4-chlorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield is
89.7%.
Example 27：N- (4- chloro-2-methyls -6- (methyl-carbamoyl) phenyl) -1- (2- trifluoromethyl -4- fluorophenyls) -
3- Trifluoromethyl-1 H- pyrazoles -5- formamides
1- (2- trifluoromethyl -4- fluorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- carboxylic acids (6mmol) are placed in 100 mL
In two mouthfuls of flasks, 50mL anhydrous methylene chlorides and 2 drop DMF are added.Reaction is placed in ice bath afterwards, oxalyl is slowly added dropwise at 0 DEG C
Chlorine (15mmol), finish after 20min, 2h is stirred under normal temperature condition.After the completion of TLC determines reaction, removal of solvent under reduced pressure, 1- is obtained
(2- trifluoromethyl -4- fluorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- acyl chlorides, is sealed.
In 100mL three-necked flasks, the acyl chlorides (6mmol) of above-mentioned preparation is dissolved in 45mL anhydrous acetonitriles, adds sodium carbonate
(12mmol), 30min is stirred at 70 DEG C.Chloro- 8- methyl -4H-1, the 3- benzoxazinones of 2- phenyl -6- then are added portionwise
(6mmol), there are in reaction solution a large amount of bubbles to release, 30min is finished, after stir 4h under reflux conditions.TLC determines that reaction is completed
Afterwards, reaction solution is cooled to room temperature, solvent is sloughed in decompression, and (tlc silica gel, petroleum ether and dichloromethane are to wash through column chromatography
De- agent) obtain the chloro- 8- methyl -2- of compound 6- (1- (2- trifluoromethyl -4- fluorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5-
Base) -4H-1,3- benzoxazinones, yield 56.9%.
By the chloro- 8- methyl -2- of above-mentioned preparation 6- (1- (2- trifluoromethyl -4- fluorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -
5- yls) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL1,4- dioxane, after
The aqueous solution (6.0mmol) of methylamine is slowly added dropwise, stirring at normal temperature 2h is filtered, and dry cake obtains target product N- (the chloro- 2- of 4-
Methyl -6- (methyl-carbamoyl) phenyl) -1- (2- trifluoromethyl -4- fluorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- formyls
Amine, yield 94.1%.
Example 28：N- (4- chloro-2-methyls -6- (t-Butylcarbamoyl) phenyl) -1- (2- trifluoromethyl -4- fluorobenzene
Base) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By the chloro- 8- methyl -2- of above-mentioned preparation 6- (1- (2- trifluoromethyl -4- fluorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -
5- yls) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
Tert-butylamine (6.0mmol), stirring at normal temperature 2h, filtering, dry cake obtain target product N- (4- chloro-2-methyls -6- (tertiary fourths
Base carbamoyl) phenyl) -1- (2- trifluoromethyl -4- fluorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield is
92.9%.
Example 29：N- (4- cyano group -2- methyl -6- (methyl-carbamoyl) phenyl) -1- (2- trifluoromethyl -4- fluorobenzene
Base) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
In 100mL three-necked flasks, by 1- (2- trifluoromethyl -4- fluorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- acyls
Chlorine (6mmol) is dissolved in 45mL anhydrous acetonitriles, adds potassium carbonate (12mmol), 30min is stirred at 70 DEG C.Then it is added portionwise
2- phenyl -6- cyano group -8- methyl -4H-1,3- benzoxazinones (6mmol), have in reaction solution a large amount of bubbles to release, and 30min adds
Finish, after stir 4h under reflux conditions.After the completion of TLC determines reaction, reaction solution is cooled to room temperature, solvent is sloughed in decompression, is passed through
Column chromatography (tlc silica gel, petroleum ether and dichloromethane are eluant, eluent) obtains compound 6- cyano group -8- methyl -2- (1- (2- tri-
Methyl fluoride -4- fluorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- bases) -4H-1,3- benzoxazinones, yield 60.3%.
By above-mentioned preparation 6- cyano group -8- methyl -2- (1- (2- trifluoromethyl -4- fluorophenyls) -3- Trifluoromethyl-1 H- pyrazoles
- 5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
The aqueous solution (6.0mmol) of methylamine, stirring at normal temperature 2h, filtering, dry cake obtain target product N- (4- cyano group -2- methyl -6-
(methyl-carbamoyl) phenyl) -1- (2- trifluoromethyl -4- fluorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, yield
For 91.1%.
Example 30：N- (4- cyano group -2- methyl -6- (t-Butylcarbamoyl) phenyl) -1- (2- trifluoromethyl -4- fluorine
Phenyl) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides
By above-mentioned preparation 6- cyano group -8- methyl -2- (1- (2- trifluoromethyl -4- fluorophenyls) -3- Trifluoromethyl-1 H- pyrazoles
- 5- bases) -4H-1,3- benzoxazinones (2.0mmol) are placed in two mouthfuls of reaction bulbs of 50mL, add 25mL acetonitriles, after be slowly added dropwise
Tert-butylamine (6.0mmol), stirring at normal temperature 2h, filtering, dry cake obtain target product N- (4- cyano group -2- methyl -6- (uncles
Butylcarbamoyl) phenyl) -1- (2- trifluoromethyl -4- fluorophenyls) -3- Trifluoromethyl-1 H- pyrazoles -5- formamides, receive
Rate is 89.7%.
Biological activity test
Example 31：To the insecticidal effect of diamondback moth
3 instar larvaes are selected, insecticidal activity test is carried out using leaching leaf dish feeding method.The active compound acetone for weighing 20mg is molten
Solution, tween water are configured to 2000ppm mother liquor.Mother liquor obtains required concentration liquid with 0.05% tween water dilution.Each
Processing 3 repeats, if blank control.Ready-made fresh luxuriant dish leaf dish is impregnated 10 seconds in decoction, takes out naturally dry.Each training
Support and 3 leaf dish are put in ware, while access 7 third-instar larvaes, sealing.Investigation 3 days, life or death borer population is checked, and carry out statistical analysis.
Corrected mortality (%)=insect death toll ÷ insects sum × 100%
The results are shown below in Table 2
Table 2
Example 32：To the insecticidal effect of beet armyworm
3 instar larvaes are selected, insecticidal activity test is carried out using leaching leaf dish feeding method.Weigh 10mg active compound N, N- bis-
NMF dissolves, and the tween water constant volume 100ml with 0.05% is the mother liquor that 100ppm is made.Mother liquor with 0.05% tween
Water dilution obtains required concentration liquid.Each 1 processing of medicament, it is each to handle 24 cephalonts, if blank control.Using 24 holes
Plate, ready-made fresh luxuriant dish leaf dish is impregnated 10 seconds in decoction, take out naturally dry, place a piece of medicine dish in every hole, simultaneously
Access 1 third-instar larvae.Investigation 5 days, life or death borer population is checked, and carry out statistical analysis.
Corrected mortality (%)=insect death toll ÷ insects sum × 100%
The results are shown below in Table 3
Table 3
Any those skilled in the art, without departing from the spirit and scope of the present invention, it be able to should make
Various modifications and change.Therefore protection scope of the present invention should be considered as appended claims limited range.
Claims (4)
1. a kind of adjacent formamido benzamide compound (I) of the substitution N- arylpyrazole structures containing trifluoromethyl, its structure
Formula is：
Wherein X is separately hydrogen, halogen, trifluoromethyl and cyano group；R1It is separately 2,6- dichlor-4-trifluoromethyls
Phenyl, 4- trifluoromethyl -2- thiazolyls, 3,5- bis- (trifluoromethyl) phenyl, the chloro- 6- trifluoromethyls of 2-, 2- trifluoromethyls -
4- chlorphenyls, 2- trifluoromethyl -4- fluorophenyls；R2It is separately methyl, ethyl, isopropyl, cyclopropyl, the tert-butyl group.
A kind of 2. synthetic method of the compound I as described in any one in claim 1, it is characterised in that synthetic route is as follows
It is shown：
1) by the compound V of 1 times of amount, the amount of material is unit, similarly hereinafter, in atent solvent, with the 1-2 times of oxalyl chloride measured in N,
0.5-48 hours are stirred at room temperature under conditions of making catalyst in dinethylformamide, precipitation, are prepared into acyl chlorides IV；
2) above-claimed cpd IV is dissolved in atent solvent, quantify compound III with 1 times flows back instead under the conditions of existing for acid binding agent
1-4 hours are answered, precipitation, are prepared into intermediate II；
3) above-claimed cpd II is dissolved in atent solvent, primary amine R is added dropwise2NH2, react 0.5-48 under 0 DEG C to reflux temperature
Hour obtains compound I.
3. synthetic method according to claim 2, it is characterised in that：The reaction atent solvent is selected from N, N- dimethyl
Formamide, DMA, acetone, acetonitrile, tetrahydrofuran, chloroform, dichloromethane, ether, methyl tertiary butyl ether(MTBE),
One of benzene, chlorobenzene, toluene or Isosorbide-5-Nitrae-dioxane；Described acid binding agent is selected from pyridine, triethylamine, N- ethyl diisopropylamines, hydrogen
One of sodium oxide molybdena, potassium hydroxide, sodium carbonate or potassium carbonate.
4. a kind of agricultural and horticultural insecticides, it is characterised by substituting N- arylpyrazole knots containing trifluoromethyl containing claim 1
The adjacent formamido benzamide compound of structure is as active component.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108752330A (en) * | 2018-06-22 | 2018-11-06 | 南京工业大学 | A kind of pyridine of the oxadiazole rings containing 1,2,4- connects pyrazole-4-carboxamide class compound and the preparation method and application thereof |
| 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 |
| CN112939866A (en) * | 2019-12-10 | 2021-06-11 | 南开大学 | Fluorine-substituted phenyl pyrazole amide derivative and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1541063A (en) * | 2001-08-13 | 2004-10-27 | ��Ļ���Ű˾ | Method for controlling particular insects by applying anthranilamide compounds |
| CN100539840C (en) * | 2001-09-21 | 2009-09-16 | 杜邦公司 | The anthranilamide Arthropodicidal is handled |
-
2017
- 2017-07-31 CN CN201710659664.2A patent/CN107365307A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1541063A (en) * | 2001-08-13 | 2004-10-27 | ��Ļ���Ű˾ | Method for controlling particular insects by applying anthranilamide compounds |
| CN100539840C (en) * | 2001-09-21 | 2009-09-16 | 杜邦公司 | The anthranilamide Arthropodicidal is handled |
Non-Patent Citations (2)
| Title |
|---|
| ANDRÉK.ISAACS，等: ""Insect Ryanodine Receptor: Distinct but Coupled Insecticide Binding Sites for [N‑C3H3]Chlorantraniliprole, Flubendiamide, and [3H]Ryanodine"", 《CHEM. RES. TOXICOL.》 * |
| DAN-PING JIANG，等: ""Bioactive conformation analysis of anthranilic diamide insecticides:DFT-based potential energy surface scanning and 3D-QSAR investigations"", 《CHINESE CHEMICAL LETTERS》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN108752330A (en) * | 2018-06-22 | 2018-11-06 | 南京工业大学 | A kind of pyridine of the oxadiazole rings containing 1,2,4- connects pyrazole-4-carboxamide class compound and the preparation method and application thereof |
| CN112939866A (en) * | 2019-12-10 | 2021-06-11 | 南开大学 | Fluorine-substituted phenyl pyrazole amide derivative and preparation method and application thereof |
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