CN108440516A - A kind of Chu Cao Ji Evil grass ether active compounds and preparation method thereof - Google Patents
A kind of Chu Cao Ji Evil grass ether active compounds and preparation method thereof Download PDFInfo
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- CN108440516A CN108440516A CN201810336172.4A CN201810336172A CN108440516A CN 108440516 A CN108440516 A CN 108440516A CN 201810336172 A CN201810336172 A CN 201810336172A CN 108440516 A CN108440516 A CN 108440516A
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- active compounds
- preparation
- grass ether
- evil grass
- reaction
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- TWIVWJUIYMPBDG-OQIURNAJSA-O CC(C(N1OCCC1)=O)OC(C=C1)=CCC=C1[OH+]/C(/C=C)=N/C=C(\C)/Cl Chemical compound CC(C(N1OCCC1)=O)OC(C=C1)=CCC=C1[OH+]/C(/C=C)=N/C=C(\C)/Cl TWIVWJUIYMPBDG-OQIURNAJSA-O 0.000 description 1
- UJKAOUZTKWLJGX-UHFFFAOYSA-N CC(C)CC(N1OCCCC1)=O Chemical compound CC(C)CC(N1OCCCC1)=O UJKAOUZTKWLJGX-UHFFFAOYSA-N 0.000 description 1
- YMPDCRWGMXAZFD-UHFFFAOYSA-N CC(CN1OCCC1)(C=O)Cl Chemical compound CC(CN1OCCC1)(C=O)Cl YMPDCRWGMXAZFD-UHFFFAOYSA-N 0.000 description 1
- YIVHOLJUADIONF-DWHDZERNSA-N ClC([C@H]12)=CCC1C(Cl)=CCN=C2Cl Chemical compound ClC([C@H]12)=CCC1C(Cl)=CCN=C2Cl YIVHOLJUADIONF-DWHDZERNSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
- C07D213/643—2-Phenoxypyridines; Derivatives thereof
Abstract
The present invention discloses a kind of Chu Cao Ji Evil grass ether active compounds and preparation method thereof, belongs to agricultural chemicals raw material technical field, preparation process is：With 2 (4 hydroxyphenoxy) propionic acid, 2,3,5 trichloropyridines are that raw material etherification reaction under the conditions of organic solvent A, alkali A and catalyst A synthesizes key intermediate (R, S) 2 (4 ((3,5 dichloropyridine, 2 base) oxygroup) phenoxy group) propionic acid, the intermediate is reacted with oxalyl chloride prepares (R, S) 2 (4 ((3,5 dichloropyridine, 2 base) oxygroup) phenoxy group) propionyl chloride, last Yu isoxazole alkyls hydrochloride carries out esterification Bei Evil grass ether active compounds under the conditions of alkali B, catalyst B and organic solvent B.In preparation method of the present invention, raw material is simple and easy to get, and synthesis is easily operated, and post-processing is easy, low for equipment requirements, the yield with high level sum.
Description
Technical field
The present invention relates to a kind of Chu Cao Ji Evil grass ether active compounds and preparation method thereof, and in particular to prepares virtue to through three-step reaction
The method of phenoxy phenoxy propionic acid Chu Cao Ji Evil grass ethers, belongs to agricultural chemicals raw material technical field.
Background technology
Evil grass ether (I) (isoxapyrifop), by the fragrant phenoxy third of Japanese Bei Xing chemical companies exploitation nineties listing
Acid herbicides, action target spot are acetyl-CoA carboxylase, can effectively prevent and kill off wheat, and rice Wang grass, is seen Alopecurus
A variety of grassy weeds such as wheat ma, hard grass, caput grass, wild oat, Itanlian rye, after dispenser 1-3 weeks it is with obvious effects, to crop
Compare safety.Dosage 60-100g/hm2。
The active compound synthetic route of Shenyang Chemical Engineering Inst's Dui Evil grass ethers has carried out system research, at present it has been reported that route
It is as follows：
Cong isoxazole alkyls hydrochloride is the first step of reaction, through chloride and two step etherification reaction get Evil grass ethers.The route
The shortcomings that be synthesis key intermediate 1 and 2 need column chromatography to purify, reduce yield, be unfavorable for industrialized production.
Invention content
A kind of at low cost present invention aims at providing, post-processing is easy, preparation side of the yield compared with Gao Evil grass ether active compounds
Method
Technical solution of the invention is the preparation method of a Evil grass ether active compounds, and feature includes following several steps
Suddenly：
(1) etherification reaction：It is raw material in organic solvent A, alkali using 2- (4- hydroxyphenoxies) propionic acid, 2,3,5- trichloropyridines
Key intermediate (R, S) -2- (4- ((3,5- dichloropyridine -2- bases) oxygroup) phenoxy group) third is synthesized under the conditions of A and catalyst A
Acid；
(2) acyl chloride reaction：Intermediate (R, S) -2- (4- ((3,5- dichloropyridine -2- bases) oxygroup) phenoxy group) propionic acid,
It is reacted with chlorination reagent and prepares (R, S) -2- (4- ((3,5- dichloropyridine -2- bases) oxygroup) phenoxy group) propionyl chloride；
(3) esterification：Yu Yi Evil after (R, S) -2- (4- ((3,5- dichloropyridine -2- bases) oxygroup) phenoxy group) propionyl chloride
Oxazolidine hydrochloride carries out esterification Bei Evil grass ether active compounds under the conditions of alkali B, catalyst B and organic solvent B.
Chemical equation is as follows：
The organic solvent A of the etherification reaction be dimethylformamide, acetonitrile, acetone, in glycol dimethyl ether extremely
Few one kind.
The alkali A is potassium carbonate, sodium carbonate, sodium hydride, at least one of sodium ethoxide, alkali A and 2- (4- hydroxy benzenes oxygen
Base) propionic acid molar feed ratio be 2.0-3.0:1, etherification reaction temperature is 50-200 DEG C.
Catalyst A used in the etherification reaction is tetrabutylammonium bromide, chlorinating benzyl triethylamine, polyethylene glycol-
400, at least one of polyethylene glycol -600,18 hats 6, mole throwing of catalyst A and raw material 2- (4- hydroxyphenoxies) propionic acid
Material is than being 0.05-0.1:1.
Chlorination reagent in the acyl chloride reaction is oxalyl chloride.
The esterification isoxazole alkyls hydrochloride and (R, S) -2- (4- ((3,5- dichloropyridine -2- bases) oxygroup) benzene
Oxygroup) propionyl chloride molar feed ratio be 1:1.2.
The alkali B of the esterification is at least one of triethylamine, pyridine, potassium carbonate.
The catalyst B of the esterification is 4-dimethylaminopyridine.
The organic solvent B of the esterification is at least one of dichloromethane, chloroform or tetrahydrofuran.
After the completion of the esterification, crude product is with ethyl alcohol, methanol or acetone recrystallization get Evil grass ether active compounds.
Compared with the existing technology, the present invention has the following advantages or beneficial outcomes：
1) compared with Japanese firm's synthetic route of existing report, the 2 of domestic industrialized production at present are made full use of
(- 4- hydroxyphenoxies) propionic acid, 2,3,5- trichloropyridines carry out etherification reaction and acylation reaction, both cost of material compare benzene
Diphenol is cheap, and totle drilling cost decreases, and is conducive to industrialized production.
2) compared with Japanese firm's synthetic route of existing report, which only has three-step reaction, in being prepared in reaction
Mesosome is purified without column chromatography, and post-processing is easy, improves yield, and three step total recoverys are 74.0% (with 2- (4- hydroxy benzenes oxygen
Base) propionic acid meter), be better than the route total recovery 50.2% of Bei Xing chemical companies of Japan, and avoid hydroquinone and N- [(R,
S bis ether by-product) is generated in -2- chloropropyls] isoxazole alkyl techniques, is conducive to industrialized production.
3) when preparing intermediate (II), thionyl chloride is replaced using oxalyl chloride, reaction condition is mild, avoids thionyl chloride
The pollution of exhaust gas and waste water, environmentally protective caused by the sulfur dioxide and hydrogen chloride generated when post-processing.
4) first step reaction of 2 (- 4- hydroxyphenoxies) propionic acid selected by this route, 2,3,5- trichloropyridines is etherificate
Reaction, is SN2Nucleophilic substitution obtains intermediate acid, and rear two step is acylation reaction, i.e. acyl chlorides He isoxazole alkyl hydrochloride occurs
Nucleophilic displacement of fluorine, and a molecule HCl is sloughed, finally post-process get Evil grass ether active compounds.
Specific implementation mode
Following embodiment is intended to illustrate invention rather than limitation of the invention further.
The process and method not being described in detail in the following embodiments are conventional methods well known in the art, institute in embodiment
It is to analyze pure or chemical pure and commercially available or prepared by method well known within the skill of those ordinarily skilled with reagent.
The present invention reaction equation be：
Embodiment 1
1.82g (0.01mol) 2- (4- hydroxyphenoxies) propionic acid and 60mL 2,3,5- trichlorine pyrroles are added in reaction bulb
After stirring 10min clocks 2.76g (0.02mol) potassium carbonate is added portionwise, 1.0mmol polyethylene glycol-400 is warming up to 75 DEG C in pyridine
4.5h is reacted, reaction is finished, is cooled to room temperature, and reaction solution is poured into 250mL ice water, is acidified to pH=2 with 10% hydrochloric acid, is stirred
Lower precipitation solid is mixed, stands, filters to obtain white solid (R, S) -2- (4- ((3,5- dichloropyridine -2- bases) oxygroup) phenoxy group) third
Sour 2.95g, purity 95.0%, yield 90.0%.
1.64g (0.005mol) (R, S) -2- (4- ((3,5- dichloropyridine -2- bases) oxygroup) benzene oxygen is added in reaction bulb
Base) propionic acid, 3.17g (0.025mol) oxalyl chloride is stirred overnight at room temperature, and reaction finishes, and removes remaining oxalyl chloride and obtains (R, S)-
2- (4- ((3,5- dichloropyridine -2- bases) oxygroup) phenoxy group) propionyl chloride is directly used in next step.
1.09g is added in reaction bulb, and (0.01mol) isoxazole alkyls hydrochlorides and 50mL dichloromethane, are added with stirring
4.16g (0.012mol) (R, S) -2- is added dropwise after stirring 0.5h in 0.01mol triethylamines and 0.001mol 4-dimethylaminopyridine
The 10mL dichloromethane solutions of (4- ((3,5- dichloropyridine -2- bases) oxygroup) phenoxy group) propionyl chloride react at room temperature 3.0h, reaction
Liquid is washed twice with dilute hydrochloric acid, and saturated salt solution washed once, dichloromethane extraction, merges organic layer, dry, precipitation, slightly
Product obtain colorless solid 3.15g with ethyl alcohol recrystallization, m.p.106-108 DEG C, purity 93.2%, yield：82.2%.
Embodiment 2
2g (0.01mol) 2- (4- hydroxyphenoxies) propionic acid and 2,3,5- trichloropyridines of 65mL are added in reaction bulb, stirs
After mixing 10min clocks, 3g (0.03mol) sodium hydride is added portionwise, 0.5mmol tetrabutylammonium bromide is warming up to 125 DEG C of reactions
4.5h, reaction finish, and are cooled to room temperature, and reaction solution is poured into 250mL ice water, pH=2 are acidified to 10% hydrochloric acid, under stirring
Solid is precipitated, stands, filters to obtain white solid (R, S) -2- (4- ((3,5- dichloropyridine -2- bases) oxygroup) phenoxy group) propionic acid
2.79g, purity 92.0%, yield 85.1%.
1.72g (0.005mol) (R, S) -2- (4- ((3,5- dichloropyridine -2- bases) oxygroup) benzene oxygen is added in reaction bulb
Base) propionic acid, 3.8g (0.025mol) oxalyl chloride is stirred overnight at room temperature, and reaction finishes, and removes remaining oxalyl chloride and obtains (R, S) -2-
(4- ((3,5- dichloropyridine -2- bases) oxygroup) phenoxy group) propionyl chloride is directly used in next step.
2.02g is added in reaction bulb, and (0.01mol) isoxazole alkyls hydrochlorides and 58mL tetrahydrofurans, are added with stirring
4.3g (0.012mol) (R, S) -2- (4- are added dropwise after stirring 0.5h in 0.01mol pyridines and 0.001mol 4-dimethylaminopyridine
((3,5- dichloropyridine -2- bases) oxygroup) phenoxy group) propionyl chloride 10mL tetrahydrofuran solutions, react at room temperature 5.0h, reaction solution
It is washed twice with dilute hydrochloric acid, saturated salt solution washed once, and tetrahydrofuran back extraction merges organic layer, dry, precipitation, crude product
Colorless solid 2.93g is obtained with recrystallizing methanol, m.p.106-108 DEG C, purity 93.2%, yield：76.5%.
Comparative example
N- (the synthesis of (scholar) -2- nitrogen propiono 〕 isoxazole alkyls
To in the mixture of 15.0g isoxazole alkyls hydrochloride and 220ml chloroforms in ice-cold lower addition 13.3g (scholar) 2- chlorine third
Acyl chlorides stirs lower dropwise addition 22.2g triethylamines, reacts 1h at room temperature.Then a large amount of water are added, are layered.After organic phase separation, successively
It is washed with 1N hydrochloric acid and 5% aqueous sodium carbonate, anhydrous sodium sulfate is used in combination to dry.Solvent is removed in vacuum distillation, obtains yellow oil
Shape object 20g colorless oils.
N- (the synthesis of (scholar) -2- (4- hydroxyphenoxies) propiono 〕 isoxazole alkyls
In above-mentioned product 17.2g, quinhydrones 14.2g, Anhydrous potassium carbonate 26g and dimethylformamide 11ml mixture in
120 DEG C of reaction 2h.After cooling, reaction mixture is filtered under diminished pressure, and removes solid matter.After filtrate decompression removes solvent, residue adds
Enter chloroform.Through 1N hydrochloric acid and water washing, after anhydrous sodium sulfate drying, removed under reduced pressure solvent obtains 22g light yellow oils.
The synthesis of Evil grass ethers
Above-mentioned product 23.7g, TCP20g, Anhydrous potassium carbonate 15g, dimethyl sulfoxide (DMSO) 22ml are mixed in 120 DEG C of reactions
4h.After reaction mixture cooling, water and benzene is added to be layered, organic phase is washed after separation with 1N sodium hydrate aqueous solutions, anhydrous sulphur
Sour sodium is dried, and light yellow crystalline solid is obtained after removed under reduced pressure solvent.It is solid that acquisition white crystals are recrystallized with n-hexane-ethyl acetate
Body, m.p.105.5-107 DEG C, this total recovery is 50.1%.
Preparation of the present invention is can be seen that from the technique and yield of embodiment and comparative example Suo Shu Evil grass ether active compounds
Method more easily operates, and post-processing is easy, and environmentally protective, yield higher.
Claims (10)
1. a kind of preparation method of Chu Cao Ji Evil grass ether active compounds, which is characterized in that including the following steps：
(1) etherification reaction：Using 2- (4- hydroxyphenoxies) propionic acid, 2,3,5- trichloropyridines as raw material organic solvent A, alkali A and
Under the conditions of catalyst A, key intermediate (R, S) -2- (4- ((3,5- dichloropyridine -2- bases) oxygroup) phenoxy group) propionic acid is synthesized；
(2) acyl chloride reaction：Intermediate (R, S) -2- (4- ((3,5- dichloropyridine -2- bases) oxygroup) phenoxy group) propionic acid and chlorination
Reagent reaction prepares (R, S) -2- (4- ((3,5- dichloropyridine -2- bases) oxygroup) phenoxy group) propionyl chloride；
(3) esterification：(R, S) -2- (4- ((3,5- dichloropyridine -2- bases) oxygroup) phenoxy group) propionyl chloride Yu isoxazole alkyl salt
Hydrochlorate carries out esterification Bei Evil grass ether active compounds under the conditions of alkali B, catalyst B and organic solvent B.
2. a kind of preparation method of Chu Cao Ji Evil grass ether active compounds according to claim 1, which is characterized in that the etherificate
In reaction, organic solvent A is at least one of dimethylformamide, acetonitrile, acetone, glycol dimethyl ether.
3. a kind of preparation method of Chu Cao Ji Evil grass ether active compounds according to claim 1, which is characterized in that the alkali A
For at least one of potassium carbonate, sodium carbonate, sodium hydride, sodium ethoxide, alkali A and 2- (4- hydroxyphenoxies) propionic acid mole feeds intake
Than for 2.0-3.0:1, etherification reaction temperature is 50-200 DEG C.
4. a kind of preparation method of Chu Cao Ji Evil grass ether active compounds according to claim 1, which is characterized in that the etherificate
Reaction catalyst A used is tetrabutylammonium bromide, chlorinating benzyl triethylamine, polyethylene glycol-400, polyethylene glycol -600,18 hats
The molar feed ratio of at least one of 6, catalyst A and raw material 2- (4- hydroxyphenoxies) propionic acid is 0.05-0.1:1.
5. a kind of preparation method of Chu Cao Ji Evil grass ether active compounds according to claim 1, which is characterized in that the acyl chlorides
Change in reaction, chlorination reagent is oxalyl chloride.
6. a kind of preparation method of Chu Cao Ji Evil grass ether active compounds according to claim 1, which is characterized in that the esterification is anti-
Answer mole of middle , isoxazole alkyls hydrochloride and (R, S) -2- (4- ((3,5- dichloropyridine -2- bases) oxygroup) phenoxy group) propionyl chloride
Rate of charge is 1:1.2.
7. a kind of preparation method of Chu Cao Ji Evil grass ether active compounds according to claim 1, which is characterized in that the esterification
In reaction, alkali B is at least one of triethylamine, pyridine, potassium carbonate.
8. a kind of preparation method of Chu Cao Ji Evil grass ether active compounds according to claim 1, which is characterized in that the esterification
In reaction, catalyst B is 4-dimethylaminopyridine；Organic solvent B is dichloromethane, in chloroform or tetrahydrofuran at least
It is a kind of.
9. a kind of preparation method of Chu Cao Ji Evil grass ether active compounds according to claim 1, which is characterized in that the esterification
After the completion of reaction, crude product is with ethyl alcohol, methanol or acetone recrystallization get Evil grass ether active compounds.
10. a kind of Chu Cao Ji Evil grass ether active compounds, which is characterized in that according to claim 1 to 9 any one of them preparation method system
Bei Evil grass ether active compounds and its any intermediate.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110894188A (en) * | 2018-09-13 | 2020-03-20 | 江苏丰山集团股份有限公司 | Preparation method of 2-substituted halogenated pyridine compound |
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| US4447259A (en) * | 1981-12-18 | 1984-05-08 | Hokko Chemical Industry Co., Ltd. | 2-(Substituted phenoxy)propionic acid derivatives and their uses for herbicidal purposes |
| CN101885703A (en) * | 2010-07-08 | 2010-11-17 | 湖南化工研究院 | N-oxyaryloxyphenoxy carboxylic acid amide compound with bioactivity and preparation method thereof |
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2018
- 2018-04-16 CN CN201810336172.4A patent/CN108440516A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4447259A (en) * | 1981-12-18 | 1984-05-08 | Hokko Chemical Industry Co., Ltd. | 2-(Substituted phenoxy)propionic acid derivatives and their uses for herbicidal purposes |
| CN101885703A (en) * | 2010-07-08 | 2010-11-17 | 湖南化工研究院 | N-oxyaryloxyphenoxy carboxylic acid amide compound with bioactivity and preparation method thereof |
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| 杨桂秋等: "异噁草醚的合成及其除草活性", 《现代农药》 * |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110894188A (en) * | 2018-09-13 | 2020-03-20 | 江苏丰山集团股份有限公司 | Preparation method of 2-substituted halogenated pyridine compound |
| CN110894188B (en) * | 2018-09-13 | 2023-07-07 | 江苏丰山生化科技有限公司 | Preparation method of 2-substituted halogenated pyridine compound |
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