CN104130128A - Synthetic method of phenoxyl acetate and intermediate thereof - Google Patents

Synthetic method of phenoxyl acetate and intermediate thereof Download PDF

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CN104130128A
CN104130128A CN201410347177.9A CN201410347177A CN104130128A CN 104130128 A CN104130128 A CN 104130128A CN 201410347177 A CN201410347177 A CN 201410347177A CN 104130128 A CN104130128 A CN 104130128A
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compound
alkyl
formula
phenyl
molar ratio
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CN104130128B (en
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江海
郭龑茹
王君良
黄铭辉
虞小华
蔡国平
陈邦池
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Inner Mongolia Shijie Chemical Co ltd
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Zhejiang Zhuji United Chemicals Co Ltd
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Abstract

The invention discloses a synthetic method of phenoxy acetate and an intermediate thereof. The method is as below: first reacting glycolic acid with organic amine to generate salt; then conducting nucleophilic substitution reaction with the product with aryl halides; and finally conducting esterification reaction to obtain the phenoxyl acetate compound (I). The method not only overcomes the shortcomings in the prior art for preparation of phenoxyl acetate intermediate, but also uses cheap and easily available raw materials, while largely inhibiting generation of hydrolysis byproduct nitrophenol in the aromatic nucleophilic substitution reaction, so as to improve the reaction yield, reduce the wastes, and benefit industrial production.

Description

The synthetic method of phenoxy acetic acid ester and intermediate thereof
Technical field: the invention belongs to the organic synthesis field of aromatic ester compound, particularly the synthetic method of phenoxy acetic acid ester and intermediate thereof.
Technical background: phenoxy acetic acid ester is the very important compound of a class, they are widely used in medicine and agricultural chemicals.For example, CN102718727 discloses the activator that both can be used as glucokinase containing the phenoxy acetic acid ester compound of urea groups, can be used as again the activated receptor activator of peroxidase vegetation.CN102532058 discloses containing the phenoxy acetic acid ester compound of benzo [1,2,3] thiadiazoles-7-carboxylic acid ester groups and can be used as Plant activator.In addition, 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic ester is also the important intermediate of synthetic N-phenyl phthalmide weedicide flumioxazin.
The method of synthetic phenoxy acetic acid ester compound has two kinds conventionally.The first is the nucleophilic substitution reaction based on phenol compound and halogenated acetic acids ester, and the second is the aromatic nucleophilic substitution reaction based on halogenated aryl hydrocarbon and oxyacetic acid ester compound.
There is nucleophilic substitution reaction in G.C.Finger report 3-fluorophenol and Mono Chloro Acetic Acid for example under sodium hydroxide effect, generates 3-fluorobenzene fluoroacetic acid, and yield is 73%.Then nitrated 2-(5-fluoro-2, the 4-2,4-dinitrophenoxy) acetic acid that obtains of 3-fluorobenzene fluoroacetic acid, yield is 30%.(J.Am.Chem.Soc,1959,81,1,94-101)。Although this method can be prepared 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid, raw material 3-fluorophenol used is more expensive, and overall yield is low.
EP0415641 discloses taking the fluoro-2-nitrophenols of 5-as starting raw material, and under the effect of salt of wormwood, with methyl bromoacetate generation nucleophilic substitution reaction, yield is 93%.Then the further nitrated generation 2-of the fluoro-2-nitrophenoxyacetic acid of 5-ester (5-fluoro-2,4-2,4-dinitrophenoxy) methyl acetate, yield is 98%.Although this method overall yield is higher, use the fluoro-2-nitrophenols of expensive 5-, therefore and be unfavorable for suitability for industrialized production another kind of raw material methyl bromoacetate has strong impulse effect to eyes, skin, mucous membrane and respiratory tract.
JP1989075452 and EP0237899 disclose the synthetic method of another kind of 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic ester.The method is chloro-2 with 1,5-bis-, and 4-dinitrobenzene is starting raw material, first with glycolic acid esters back flow reaction in salt of wormwood, crown ether and acetonitrile system, generates 2-(5-chloro-2,4-2,4-dinitrophenoxy) acetic ester, and yield is 73.9%.The 2-that obtains (5-chloro-2,4-2,4-dinitrophenoxy) acetic ester carries out fluoridation again in DMSO with Potassium monofluoride, generate 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic ester, and yield is 89.9%.The method has successfully been utilized the sucting electronic effect of dinitrobenzene on phenyl ring, and aromatic nucleophilic substitution reaction can be carried out.But the method is used expensive glycolic acid esters as raw material, simultaneously because chlorinated aromatic hydrocarbons activity is not high, so the first step productive rate is not ideal enough.In addition in order to obtain 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic ester, need further fluoridation.This fluoridation requires higher to conversion unit, produce the sulfur-bearing three wastes, is unfavorable for suitability for industrialized production.
JP1992305556 discloses with 1,5-bis-fluoro-2 simultaneously, and 4-dinitrobenzene is raw material, under the effect of the triethylamine of salt of wormwood and catalytic amount, there is aromatic nucleophilic substitution reaction with Butyl Glycolate, generate 2-(5-fluoro-2,4-2,4-dinitrophenoxy) butylacetate, yield is 92%.This method has solved chlorinated aromatic hydrocarbons and the not high problem of glycolic acid esters reaction yield, but the raw material Butyl Glycolate using is expensive.
EP0237899 also discloses with 1,5-bis-fluoro-2, and 4-dinitrobenzene and oxyacetic acid are raw material, under alkali effect, aromatic nucleophilic substitution reaction occur, and generates 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid.But concrete reactions steps and yield are not open.CN101948389 uses same processing method subsequently, and fluoro-2 with 1,5-bis-, 4-dinitrobenzene and oxyacetic acid are raw material, and under alkali effect, reaction generates 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid, and yield is between 28-81%.Fluoro-2 due to 1,5-bis-, 4-dinitrobenzene is quite active under alkaline condition, if there is any water in reaction system, water meeting and oxyacetic acid generation competing reaction, first hydrolysis produces nitrophenols by product, and this by product causes poisoning of catalyst in hydrogenation reaction subsequently.Therefore, this technique needs the strict moisture of controlling raw material, alkali and whole system.Raw material oxyacetic acid is easy deliquescence in air not only, and high temperature easily decomposes while dewatering.All of these factors taken together causes this method to be unfavorable for suitability for industrialized production.
Summary of the invention
One of object of the present invention is to overcome the existing deficiency of preparing phenoxy acetic acid intermediate technology, from the hydroxy acid solution and the organic amine that are cheaply easy to get, and dehydration salify, then react synthetic phenoxy acetic acid with halogenated aryl hydrocarbon.This invention has not only solved the high problem of anhydrous oxyacetic acid cost, has effectively controlled the moisture in reaction system simultaneously.Not only suppress so to a great extent to produce in aromatic nucleophilic substitution reaction hydrolysising by-product nitrophenols, improved reaction yield simultaneously.Another object of the present invention is on the novel process basis of preparing at phenoxy acetic acid, further to develop the more efficient synthesis of phenoxy acetic acid ester.
The synthetic method of a kind of phenoxy acetic acid ester (I), is characterized in that the general formula of compound (I) is as follows:
In formula:
R 1for C 1-C 12alkyl;
R 2for H, methyl or phenyl;
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
Described synthetic method comprises the steps:
Step (a): compound (II) reacts to obtain compound (IV) in organic solvent with compound (III);
The general formula of compound (II) is as follows:
In formula:
R 2for H, methyl or phenyl;
The general formula of compound (III) is as follows:
In formula:
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
The general formula of compound (IV) is as follows:
In formula:
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
Step (b): compound (IV) obtains compound (VI) under acid binding agent effect with compound (V),
The general formula of compound (V) is as follows:
In formula:
X is F, Cl, Br or I;
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
The general formula of compound (VI) is as follows:
In formula:
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
Step (c): compound (VI) is prepared into compound (I) with compound (VII) direct reaction;
The general formula of compound (VII) is as follows:
R 1-L(VII)
In formula:
R 1for C 1-C 12alkyl;
L is Cl, Br, I, MeSO 3 -, R 1oCO 2 -, TsSO 3 -or R 1oSO 3 -, wherein R 1definition as above.
In step (a), described solvent is to be selected from one or more in toluene, dimethylbenzene, methylene dichloride, trichloromethane, methyl alcohol, ethanol or Virahol; Compound (II) is 1:1-1:5 with the molar ratio of compound (III); Temperature of reaction is from-30 DEG C-50 DEG C; In step (b), described acid binding agent is mineral alkali or organic bases; Mineral alkali is selected from sodium carbonate, salt of wormwood, potassium hydroxide or sodium hydroxide; Organic bases is selected from triethylamine, tripropyl amine, Tributylamine, diethylamine, dicyclohexyl amine, piperidines, pyridine or compound (III) itself; Compound (V) is 1:0.9-1:5 with the molar ratio of compound (IV); The molar ratio of acid binding agent and compound (IV) is 1:1-5:1; Temperature of reaction is from-30 DEG C-25 DEG C; Compound (VI) is 1:0.9-1:5 with the molar ratio of compound (VII); Temperature of reaction is from-30 DEG C-50 DEG C.
In step (a), described solvent is preferably toluene and methylene dichloride; Compound (II) is preferably 1:1-1:2 with the molar ratio of compound (III); Temperature of reaction is preferably from 0-25 DEG C; In step (b), described acid binding agent is preferably triethylamine; Compound (V) is preferably 1:0.9-1:1.2 with the molar ratio of compound (IV); The molar ratio of acid binding agent and compound (IV) is preferably 1:1-1.2:1; Temperature of reaction is preferably from-5-10 DEG C.Compound (VI) is preferably 1:0.9-1:2 with the molar ratio of compound (VII); Temperature of reaction is preferably from-5 DEG C-25 DEG C.
The synthetic method of a kind of phenoxy acetic acid ester (I), is characterized in that the general formula of compound (I) is as follows:
In formula:
R 1for C 1-C 12alkyl;
R 2for H, methyl or phenyl;
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
Described synthetic method comprises:
Step (a): compound (II) reacts to obtain compound (IV) in organic solvent with compound (III),
The general formula of compound (II) is as follows:
In formula:
R 2for H, methyl or phenyl;
The general formula of compound (III) is as follows:
In formula:
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
The general formula of compound (IV) is as follows:
In formula:
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
Step (b): compound (IV) obtains compound (VI) under acid binding agent effect with compound (V),
The general formula of compound (V) is as follows:
In formula:
X is F, Cl, Br or I;
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
The general formula of compound (VI) is as follows:
In formula:
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
Step (c '): compound (VI) is free under mineral acid effect obtains compound (VIII), and the general formula of compound (VIII) is as follows:
In formula:
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
R 2for H, methyl or phenyl;
Step (d): compound (VIII) reacts and is prepared into compound (I) with compound (IX) under acid catalysis, or compound (VIII) reacts and is prepared into compound (I) with compound (VII) under alkali effect
The general formula of compound (IX) is as follows:
R 1OH(IX)
In formula:
R 1for C 1-C 12alkyl;
The general formula of compound (VII) is as follows:
R 1-L(VII)
In formula:
R 1for C 1-C 12alkyl;
L is Cl, Br, I, MeSO 3 -, R 1oCO 2 -, TsSO 3 -or R 1oSO 3 -, wherein R 1definition as above.
In step (a), described solvent is to be selected from one or more in toluene, dimethylbenzene, methylene dichloride, trichloromethane, methyl alcohol, ethanol or Virahol; Compound (II) is 1:1-1:5 with the molar ratio of compound (III); Temperature of reaction is from-30 DEG C-50 DEG C; In step (b), described acid binding agent is mineral alkali or organic bases; Mineral alkali is selected from sodium carbonate, salt of wormwood, potassium hydroxide or sodium hydroxide; Organic bases is selected from triethylamine, tripropyl amine, Tributylamine, diethylamine, dicyclohexyl amine, piperidines, pyridine or compound (III) itself; Compound (V) is 1:0.9-1:5 with the molar ratio of compound (IV); The molar ratio of acid binding agent and compound (IV) is 1:1-5:1; Temperature of reaction is from-30 DEG C-25 DEG C; In step (c '), described mineral acid is selected from sulfuric acid, hydrochloric acid or phosphoric acid; The molar ratio of mineral acid and compound (IV) is 1:1-15:1; Temperature of reaction is from-30 DEG C-25 DEG C; In step (d), described acid catalyst is selected from sulfuric acid, hydrochloric acid, acetic acid, phosphoric acid or tosic acid; Alkali is mineral alkali or organic bases; Mineral alkali is selected from sodium carbonate, salt of wormwood, potassium hydroxide or sodium hydroxide; Organic bases is selected from triethylamine, piperidines, DBU or pyridine; Compound (VIII) is 1:0.9-1:5 with the molar ratio of compound (IX) or compound (VII); The molar ratio of acid or alkali and compound (IV) is 1:1-5:1; Temperature of reaction is from-30 DEG C-130 DEG C.
In step (a), described solvent is preferably toluene or methylene dichloride; Compound (II) is preferably 1:1-1:2 with the molar ratio of compound (III); Temperature of reaction is preferably from 0-25 DEG C; In step (b), described acid binding agent is preferably triethylamine; Compound (V) is preferably 1:0.9-1:1.2 with the molar ratio of compound (IV); The molar ratio of acid binding agent and compound (IV) is preferably 1:1-1.2:1; Temperature of reaction is preferably from-5-10 DEG C; In step (c '), described mineral acid is preferably hydrochloric acid; The molar ratio of mineral acid and compound (IV) is preferably 1:1-2:1; Temperature of reaction is preferably from-5-25 DEG C; In step (d), described acid catalyst is preferably sulfuric acid; Alkali is mineral alkali or organic bases; Mineral alkali is preferably potassium hydroxide; Organic bases is preferably triethylamine; Compound (VIII) is preferably 1:0.9-1:2 with the molar ratio of compound (IX) or compound (VII); The molar ratio of acid or alkali and compound (IV) is preferably 1:0.9-1:2; Temperature of reaction is preferably from-5-130 DEG C.
A kind of phenoxy acetic acid ammonium salt (VI), is characterized in that the general formula of compound (VI) is as follows:
In formula:
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
The synthetic method of a kind of phenoxy acetic acid ammonium salt (VI), is characterized in that the general formula of compound (VI) is as follows:
In formula:
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
Described method comprises:
Step (a): compound (II) obtains compound (IV) in organic solvent with compound (III),
The general formula of compound (II) is as follows:
In formula:
R 2for H, methyl or phenyl;
The general formula of compound (III) is as follows:
In formula:
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
The general formula of compound (IV) is as follows:
In formula:
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
Step (b): compound (IV) obtains compound (VI) under acid binding agent effect with compound (V),
The general formula of compound (V) is as follows:
In formula:
X is F, Cl, Br or I;
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN.
In step (a), described solvent is to be selected from one or more in toluene, dimethylbenzene, methylene dichloride, trichloromethane, methyl alcohol, ethanol or Virahol; Compound (II) is 1:1-1:5 with the molar ratio of compound (III); Temperature of reaction is from-30 DEG C-50 DEG C; In step (b), described acid binding agent is mineral alkali or organic bases; Mineral alkali is selected from sodium carbonate, salt of wormwood, potassium hydroxide or sodium hydroxide; Organic bases is selected from triethylamine, tripropyl amine, Tributylamine, diethylamine, dicyclohexyl amine, piperidines, pyridine or compound (III) itself; Compound (V) is 1:0.9-1:5 with the molar ratio of compound (IV); The molar ratio of acid binding agent and compound (IV) is 1:1-5:1; Temperature of reaction is from-30 DEG C-25 DEG C.
In step (a), described solvent is preferably toluene or methylene dichloride; Compound (II) is preferably 1:1-1:2 with the molar ratio of compound (III); Temperature of reaction is preferably from 0-25 DEG C; In step (b), described acid binding agent is preferably triethylamine; Compound (V) is preferably 1:0.9-1:1.2 with the molar ratio of compound (IV); The molar ratio of acid binding agent and compound (IV) is preferably 1:1-1.2:1; Temperature of reaction is preferably from-5-10 DEG C.
The synthetic method of a kind of phenoxy acetic acid ammonium salt (VI), is characterized in that the general formula of compound (VI) is as follows:
In formula:
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
Described synthetic method is:
Compound (VIII) obtains compound (VI) in organic solvent with compound (III),
The general formula of compound (VIII) is as follows:
In formula:
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
R 2for H, methyl or phenyl;
The general formula of compound (III) is as follows:
In formula:
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical.
Embodiment
The object of following provided embodiment is to illustrate the present invention instead of limits the present invention.
The preparation of embodiment 1 compound (IV)
(1) preparation of oxyacetic acid triethylammonium salts
In 100ml there-necked flask, add 15.7g oxyacetic acid and 80ml toluene, add 22.9g triethylamine, stirring at room temperature 2 hours.Precipitation, obtains 30.2g oxyacetic acid triethylammonium salts.
(2) preparation of oxyacetic acid three positive fourth ammonium salts
In 100ml there-necked flask, add 3.9g oxyacetic acid and 20ml methylene dichloride, add 10.5g tri-n-butylamine at 0 DEG C, be incubated 2 hours.Precipitation, obtains the positive fourth ammonium salt of 11.2g oxyacetic acid three.
(3) preparation of oxyacetic acid two hexamethylene ammonium salts
In 100ml there-necked flask, add 7.8g oxyacetic acid and 90ml toluene, then add 19.6g dicyclohexyl amine, under room temperature, stir 2 hours.Suction filtration, uses 5ml toluene wash, and filter cake is dried, and obtains 24.8g oxyacetic acid two hexamethylene ammonium salts.
The preparation of embodiment 2 compound VI
(1) preparation of 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid triethylammonium salts
In 100ml there-necked flask, add 7g2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid and 50ml methylene dichloride, then add 2.7g triethylamine, under room temperature, stir 2 hours.Precipitation, obtains 9.5g oxyacetic acid triethylammonium salts.
1H?NMR(δ,D 2O):8.843-8.823(d,1H),7.098-7.066(d,1H),4.702(s,2H),3.118-3.063(m,6H),1.184-1.147(t,12H).
(2) preparation of 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid two hexamethylene ammoniums
In 100ml there-necked flask, add 7g2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid and 50ml toluene, then add 4.9g dicyclohexyl amine, under room temperature, stir 2 hours.Precipitation, obtains the positive fourth ammonium salt of 11.7g oxyacetic acid three.
1H?NMR(δ,D 2O):8.872-8.852(d,1H),7.086--7.055(d,1H),4.700(s,2H),3.133(m,2H),1.932(m,4H),1.704-1.667(m,4H),1.571-1.539(m,2H),1.257-1.165(m,8H),1.130-1.028(m,2H).
The preparation of embodiment 3 compound VI II
(1) preparation of 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid
In 500ml there-necked flask, add 19.4g1,5-bis-is fluoro-2,4-dinitrobenzene, and 250ml toluene and 24.8g oxyacetic acid two hexamethylene ammonium salts, stir and be cooled to 10 DEG C.Add 9.7g triethylamine, insulation reaction 8 hours.Add hydrochloric acid to adjust pH to 2, suction filtration, washing, dries and obtains 22.2g2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid.
(2) preparation of 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid
In 500ml there-necked flask, add 20.4g1,5-bis-is fluoro-2,4-dinitrobenzene, and 200ml toluene and 15.1g oxyacetic acid triethylammonium salts, stir and be cooled to-5 DEG C.Add 10.2g triethylamine, insulation reaction 8 hours.Add hydrochloric acid to adjust pH to 2, suction filtration, washing, dries and obtains 21.3g2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid.
The preparation of embodiment 4 Compound I
(1) preparation of 2-(5-fluoro-2,4-2,4-dinitrophenoxy) ethyl acetate
In 250ml there-necked flask, add 21.3g2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid and 120ml toluene, add the 0.2g vitriol oil, be warming up to 130 DEG C, drip 4.4g ethanol, reaction 2h, cooling, wash with water twice, precipitation obtains 21.6g2-(5-fluoro-2,4-2,4-dinitrophenoxy) ethyl acetate.
1H?NMR(δ,CDCl 3):8.830-8.815(d,1H),6.855-6.831(d,1H),4.894(s,2H),4.336-4.293(m,2H),1.344-1.315(t,3H).
(2) preparation of 2-(5-fluoro-2,4-2,4-dinitrophenoxy) methyl acetate
In 500ml there-necked flask, add 20.4g1,5-bis-is fluoro-2,4-dinitrobenzene, and 200ml toluene and 15.1g oxyacetic acid triethylammonium salts, stir and be cooled to-5 DEG C.Add 15.3g triethylamine, insulation reaction 8 hours.Add 25.2g methyl-sulfate, continue reaction 8 hours, wash twice with water, precipitation obtains 15.9g2-(5-fluoro-2,4-2,4-dinitrophenoxy) methyl acetate.
1H?NMR(δ,CDCl 3):8.822-8.806(d,1H),6.881-6.858(d,1H),4.929(s,2H),3.859(s,3H).

Claims (11)

1. a synthetic method for phenoxy acetic acid ester (I), is characterized in that the general formula of compound (I) is as follows:
In formula:
R 1for C 1-C 12alkyl;
R 2for H, methyl or phenyl;
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
Described synthetic method comprises the steps:
Step (a): compound (II) reacts to obtain compound (IV) in organic solvent with compound (III);
The general formula of compound (II) is as follows:
In formula:
R 2for H, methyl or phenyl;
The general formula of compound (III) is as follows:
In formula:
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
The general formula of compound (IV) is as follows:
In formula:
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
Step (b): compound (IV) obtains compound (VI) under acid binding agent effect with compound (V),
The general formula of compound (V) is as follows:
In formula:
X is F, Cl, Br or I;
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
The general formula of compound (VI) is as follows:
In formula:
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
Step (c): compound (VI) is prepared into compound (I) with compound (VII) direct reaction;
The general formula of compound (VII) is as follows:
R 1-L(VII)
In formula:
R 1for C 1-C 12alkyl;
L is Cl, Br, I, MeSO 3 -, R 1oCO 2 -, TsSO 3 -or R 1oSO 3 -, wherein R 1definition as above.
2. the synthetic method of phenoxy acetic acid ester (I) as claimed in claim 1, it is characterized in that, in step (a), described solvent is to be selected from one or more in toluene, dimethylbenzene, methylene dichloride, trichloromethane, methyl alcohol, ethanol or Virahol; Compound (II) is 1:1-1:5 with the molar ratio of compound (III); Temperature of reaction is from-30 DEG C-50 DEG C; In step (b), described acid binding agent is mineral alkali or organic bases; Mineral alkali is selected from sodium carbonate, salt of wormwood, potassium hydroxide or sodium hydroxide; Organic bases is selected from triethylamine, tripropyl amine, Tributylamine, diethylamine, dicyclohexyl amine, piperidines, pyridine or compound (III) itself; Compound (V) is 1:0.9-1:5 with the molar ratio of compound (IV); The molar ratio of acid binding agent and compound (IV) is 1:1-5:1; Temperature of reaction is from-30 DEG C-25 DEG C; Compound (VI) is 1:0.9-1:5 with the molar ratio of compound (VII); Temperature of reaction is from-30 DEG C-50 DEG C.
3. the synthetic method of phenoxy acetic acid ester (I) as claimed in claim 1 or 2, is characterized in that, in step (a), described solvent is preferably toluene and methylene dichloride; Compound (II) is preferably 1:1-1:2 with the molar ratio of compound (III); Temperature of reaction is preferably from 0-25 DEG C; In step (b), described acid binding agent is preferably triethylamine; Compound (V) is preferably 1:0.9-1:1.2 with the molar ratio of compound (IV); The molar ratio of acid binding agent and compound (IV) is preferably 1:1-1.2:1; Temperature of reaction is preferably from-5-10 DEG C; Compound (VI) is preferably 1:0.9-1:2 with the molar ratio of compound (VII); Temperature of reaction is preferably from-5 DEG C-25 DEG C.
4. a synthetic method for phenoxy acetic acid ester (I), is characterized in that the general formula of compound (I) is as follows:
In formula:
R 1for C 1-C 12alkyl;
R 2for H, methyl or phenyl;
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
Described synthetic method comprises:
Step (a): compound (II) reacts to obtain compound (IV) in organic solvent with compound (III),
The general formula of compound (II) is as follows:
In formula:
R 2for H, methyl or phenyl;
The general formula of compound (III) is as follows:
In formula:
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
The general formula of compound (IV) is as follows:
In formula:
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
Step (b): compound (IV) obtains compound (VI) under acid binding agent effect with compound (V),
The general formula of compound (V) is as follows:
In formula:
X is F, Cl, Br or I;
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
The general formula of compound (VI) is as follows:
In formula:
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
Step (c '): compound (VI) is free under mineral acid effect obtains compound (VIII), and the general formula of compound (VIII) is as follows:
In formula:
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
R 2for H, methyl or phenyl;
Step (d): compound (VIII) reacts and is prepared into compound (I) with compound (IX) under acid catalysis, or compound (VIII) reacts and is prepared into compound (I) with compound (VII) under alkali effect
The general formula of compound (IX) is as follows:
R 1OH(IX)
In formula:
R 1for C 1-C 12alkyl;
The general formula of compound (VII) is as follows:
R 1-L（VII)
In formula:
R 1for C 1-C 12alkyl;
L is Cl, Br, I, MeSO 3 -, R 1oCO 2 -, TsSO 3 -or R 1oSO 3 -, wherein R 1definition as above.
5. the synthetic method of a kind of phenoxy acetic acid ester (I) as claimed in claim 4, it is characterized in that, in step (a), described solvent is to be selected from one or more in toluene, dimethylbenzene, methylene dichloride, trichloromethane, methyl alcohol, ethanol or Virahol; Compound (II) is 1:1-1:5 with the molar ratio of compound (III); Temperature of reaction is from-30 DEG C-50 DEG C; In step (b), described acid binding agent is mineral alkali or organic bases; Mineral alkali is selected from sodium carbonate, salt of wormwood, potassium hydroxide or sodium hydroxide; Organic bases is selected from triethylamine, tripropyl amine, Tributylamine, diethylamine, dicyclohexyl amine, piperidines, pyridine or compound (III) itself; Compound (V) is 1:0.9-1:5 with the molar ratio of compound (IV); The molar ratio of acid binding agent and compound (IV) is 1:1-5:1; Temperature of reaction is from-30 DEG C-25 DEG C; In step (c '), described mineral acid is selected from sulfuric acid, hydrochloric acid or phosphoric acid; The molar ratio of mineral acid and compound (IV) is 1:1-15:1; Temperature of reaction is from-30 DEG C-25 DEG C; In step (d), described acid catalyst is selected from sulfuric acid, hydrochloric acid, acetic acid, phosphoric acid or tosic acid; Alkali is mineral alkali or organic bases; Mineral alkali is selected from sodium carbonate, salt of wormwood, potassium hydroxide or sodium hydroxide; Organic bases is selected from triethylamine, piperidines, DBU or pyridine; Compound (VIII) is 1:0.9-1:5 with the molar ratio of compound (IX) or compound (VII); The molar ratio of acid or alkali and compound (IV) is 1:1-5:1; Temperature of reaction is from-30 DEG C-130 DEG C.
6. the synthetic method of a kind of phenoxy acetic acid ester (I) as described in claim 4 or 5, is characterized in that, in step (a), described solvent is preferably toluene or methylene dichloride; Compound (II) is preferably 1:1-1:2 with the molar ratio of compound (III); Temperature of reaction is preferably from 0-25 DEG C; In step (b), described acid binding agent is preferably triethylamine; Compound (V) is preferably 1:0.9-1:1.2 with the molar ratio of compound (IV); The molar ratio of acid binding agent and compound (IV) is preferably 1:1-1.2:1; Temperature of reaction is preferably from-5-10 DEG C; In step (c '), described mineral acid is preferably hydrochloric acid; The molar ratio of mineral acid and compound (IV) is preferably 1:1-2:1; Temperature of reaction is preferably from-5-25 DEG C; In step (d), described acid catalyst is preferably sulfuric acid; Alkali is mineral alkali or organic bases; Mineral alkali is preferably potassium hydroxide; Organic bases is preferably triethylamine; Compound (VIII) is preferably 1:0.9-1:2 with the molar ratio of compound (IX) or compound (VII); The molar ratio of acid or alkali and compound (IV) is preferably 1:0.9-1:2; Temperature of reaction is preferably from-5-130 DEG C.
7. a phenoxy acetic acid ammonium salt (VI), is characterized in that the general formula of compound (VI) is as follows:
In formula:
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical.
8. a synthetic method for phenoxy acetic acid ammonium salt (VI), is characterized in that the general formula of compound (VI) is as follows:
In formula:
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
Described method comprises:
Step (a): compound (II) obtains compound (IV) in organic solvent with compound (III),
The general formula of compound (II) is as follows:
In formula:
R 2for H, methyl or phenyl;
The general formula of compound (III) is as follows:
In formula:
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
The general formula of compound (IV) is as follows:
In formula:
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
Step (b): compound (IV) obtains compound (VI) under acid binding agent effect with compound (V),
The general formula of compound (V) is as follows:
In formula:
X is F, Cl, Br or I;
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN.
9. the synthetic method of phenoxy acetic acid ammonium salt (VI) as claimed in claim 8, it is characterized in that, in step (a), described solvent is to be selected from one or more in toluene, dimethylbenzene, methylene dichloride, trichloromethane, methyl alcohol, ethanol or Virahol; Compound (II) is 1:1-1:5 with the molar ratio of compound (III); Temperature of reaction is from-30 DEG C-50 DEG C; In step (b), described acid binding agent is mineral alkali or organic bases; Mineral alkali is selected from sodium carbonate, salt of wormwood, potassium hydroxide or sodium hydroxide; Organic bases is selected from triethylamine, tripropyl amine, Tributylamine, diethylamine, dicyclohexyl amine, piperidines, pyridine or compound (III) itself; Compound (V) is 1:0.9-1:5 with the molar ratio of compound (IV); The molar ratio of acid binding agent and compound (IV) is 1:1-5:1; Temperature of reaction is from-30 DEG C-25 DEG C.
10. the synthetic method of phenoxy acetic acid ammonium salt (VI) as described in claim 8 or 9, is characterized in that, in step (a), described solvent is preferably toluene or methylene dichloride; Compound (II) is preferably 1:1-1:2 with the molar ratio of compound (III); Temperature of reaction is preferably from 0-25 DEG C; In step (b), described acid binding agent is preferably triethylamine; Compound (V) is preferably 1:0.9-1:1.2 with the molar ratio of compound (IV); The molar ratio of acid binding agent and compound (IV) is preferably 1:1-1.2:1; Temperature of reaction is preferably from-5-10 DEG C.
The synthetic method of 11. 1 kinds of phenoxy acetic acid ammonium salts (VI), is characterized in that the general formula of compound (VI) is as follows:
In formula:
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
R 2for H, methyl or phenyl;
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical;
Described synthetic method is:
Compound (VIII) obtains compound (VI) in organic solvent with compound (III),
The general formula of compound (VIII) is as follows:
In formula:
Y is H, C 1-C 4alkyl, phenyl, F, Cl, Br, NO 2, CF 3or CN;
EWG is NO 2, CF 3or CN;
R 2for H, methyl or phenyl;
The general formula of compound (III) is as follows:
In formula:
R 3, R 4and R 5for H, C 1-C 5alkyl or C 3-C 7cycloalkyl, R 3, R 4and R 5for identical or not identical.
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CN104628572A (en) * 2015-02-11 2015-05-20 利尔化学股份有限公司 Synthetic method of 2-(5-fluoro-2,4-dinitrophenoxy)acetate
CN108264449A (en) * 2016-12-30 2018-07-10 浙江省诸暨合力化学对外贸易有限公司 A kind of preparation method of 2,6- diethyl -4- methylphenols
CN109748799A (en) * 2018-12-18 2019-05-14 内蒙古世杰化工有限公司 A method of synthesis fluoro- 1,5 2,4-dinitrophenoxy of 2-(5-) acetic acid esters
CN110240545A (en) * 2018-03-08 2019-09-17 浙江省诸暨合力化学对外贸易有限公司 A kind of fluoro- 2,4- 2,4-dinitrophenoxy of 2-(5-) acetic acid preparation method

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CN102002013A (en) * 2010-08-16 2011-04-06 北京颖新泰康国际贸易有限公司 Preparation method of 6-amino-7-fluoro-1,4-benzoxazine-3(4H)-ketone
CN103380201A (en) * 2010-12-21 2013-10-30 路博润公司 Lubricating composition containing an antiwear agent

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CN101948389A (en) * 2010-08-16 2011-01-19 北京颖新泰康国际贸易有限公司 Method for preparing 2-(5-fluoro-2,4-dinitrophenoxy) acetic acid and ester thereof
CN102002013A (en) * 2010-08-16 2011-04-06 北京颖新泰康国际贸易有限公司 Preparation method of 6-amino-7-fluoro-1,4-benzoxazine-3(4H)-ketone
CN103380201A (en) * 2010-12-21 2013-10-30 路博润公司 Lubricating composition containing an antiwear agent

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104628572A (en) * 2015-02-11 2015-05-20 利尔化学股份有限公司 Synthetic method of 2-(5-fluoro-2,4-dinitrophenoxy)acetate
CN108264449A (en) * 2016-12-30 2018-07-10 浙江省诸暨合力化学对外贸易有限公司 A kind of preparation method of 2,6- diethyl -4- methylphenols
CN108264449B (en) * 2016-12-30 2022-04-26 浙江省诸暨合力化学对外贸易有限公司 Preparation method of 2, 6-diethyl-4-methylphenol
CN110240545A (en) * 2018-03-08 2019-09-17 浙江省诸暨合力化学对外贸易有限公司 A kind of fluoro- 2,4- 2,4-dinitrophenoxy of 2-(5-) acetic acid preparation method
CN109748799A (en) * 2018-12-18 2019-05-14 内蒙古世杰化工有限公司 A method of synthesis fluoro- 1,5 2,4-dinitrophenoxy of 2-(5-) acetic acid esters

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