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CN104130128B - The synthetic method of phenoxy acetic acid ester and intermediate thereof - Google Patents

The synthetic method of phenoxy acetic acid ester and intermediate thereof Download PDF

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Publication number
CN104130128B
CN104130128B CN201410347177.9A CN201410347177A CN104130128B CN 104130128 B CN104130128 B CN 104130128B CN 201410347177 A CN201410347177 A CN 201410347177A CN 104130128 B CN104130128 B CN 104130128B
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formula
alkyl
phenyl
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CN104130128A (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 synthetic method and the intermediate thereof of a kind of phenoxy acetic acid ester.This method, from hydroxyacetic acid, is first reacted into salt, then is carried out nucleophilic substitution with halogenated aryl hydrocarbon with organic amine, after obtain phenoxy acetic acid ester compounds (I) through esterification.This method not only overcomes the existing deficiency preparing phenoxy acetic acid intermediate technology, raw material used is cheap and easily-available, inhibits the generation of hydrolysising by-product nitrophenol in aromatic nucleophilic substitution reaction to a great extent simultaneously, improves reaction yield, decrease the three wastes, beneficially industrialized 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 to the synthetic method of phenoxy acetic acid ester And intermediate.
Technical background: phenoxy acetic acid ester is a very important compound of class, they are widely used in medicine and pesticide.Example As, CN102718727 discloses the phenoxy acetic acid ester type compound containing urea groups and can not only be used for the activator of glucokinase, Again can be as the activated receptor activator of peroxidase paraphyte.CN102532058 discloses containing benzo [1,2,3] thiadiazoles-7- The phenoxy acetic acid ester type compound of carboxylic acid ester groups can be as Plant activator.It addition, 2-(5-fluoro-2,4-2,4-dinitrophenoxy) Acetas is also the important intermediate of synthesis N-phenyl phthalmide herbicide flumioxazin.
The method of synthesis phenoxy acetic acid ester type compound generally has two kinds.The first is based on phenol compound and halogenated acetic acids The nucleophilic substitution of ester, the second is aromatic nucleophilic substitution reaction based on halogenated aryl hydrocarbon Yu hydroxyacetic acid ester type compound.
There is nucleophilic substitution with monoxone in such as G.C.Finger report 3-fluorophenol under sodium hydroxide effect, generates 3- Fluorobenzene fluoroacetic acid, yield is 73%.Then 3-fluorobenzene fluoroacetic acid nitrification obtains 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid, yield It is 30%.(J.Am.Chem.Soc,1959,81,1,94-101).Although this method can prepare 2-(5-fluoro-2,4-2,4-dinitrophenoxy) Acetic acid, but raw material 3-fluorophenol used is costly, and gross production rate is low.
EP0415641 discloses with 5-fluoro-2-nitrophenol as initiation material, sends out with methyl bromoacetate under the effect of potassium carbonate Raw nucleophilic substitution, yield is 93%.Then the further nitrification of 5-fluoro-2-nitrophenoxyacetic acid ester generates 2-(the fluoro-2,4-of 5-bis- Nitrobenzol oxygen) methyl acetate, yield is 98%.Although this method overall yield is higher, but it is the use of the 5-fluoro-2-nitre of costliness Base phenol, another kind of raw material methyl bromoacetate has strong impulse effect to eyes, skin, mucosa and respiratory tract, the most also It is unfavorable for industrialized production.
JP1989075452 and EP0237899 discloses the synthetic method of another kind of 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetas. The method is with 1, and 5-bis-chloro-2,4-dinitro benzene is initiation material, first with glycolic acid esters in potassium carbonate, crown ether and acetonitrile system Back flow reaction, generates 2-(5-chloro-2,4-2,4-dinitrophenoxy) acetas, and yield is 73.9%.2-(the 5-chloro-2,4-dinitro obtained Benzene oxygen) acetas carries out fluorination reaction again in DMSO with potassium fluoride, generates 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetas, Yield is 89.9%.The method successfully make use of the sucting electronic effect of dinitro on phenyl ring, enables aromatic nucleophilic substitution reaction Carry out.But the glycolic acid esters of the method use costliness is as raw material, simultaneously because chlorinated aromatic hydrocarbons activity is the highest, so the first step Productivity is not ideal enough.In addition in order to obtain 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetas, further fluorination reaction is needed.This fluorine Change reaction and consersion unit is required higher, produce the sulfur-bearing three wastes, be unfavorable for industrialized production.
JP1992305556 also discloses with 1,5-bis-fluoro-2, and 4-dinitro benzene is raw material, with Butyl Glycolate at potassium carbonate and There is aromatic nucleophilic substitution reaction under the effect of the triethylamine of catalytic amount, generate 2-(5-fluoro-2,4-2,4-dinitrophenoxy) butyl acetate, Yield is 92%.This solves the problem that chlorinated aromatic hydrocarbons and glycolic acid esters reaction yield are the highest, but used Raw material hydroxyl butyl acetate is expensive.
EP0237899 also discloses with 1,5-bis-fluoro-2, and 4-dinitro benzene and hydroxyacetic acid are raw material, and fragrance occurs under alkali effect Nucleophilic substitution, generates 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid.But concrete reactions steps and yield are the openest. CN101948389 uses same process, with 1,5-bis-fluoro-2 subsequently, and 4-dinitro benzene and hydroxyacetic acid are raw material, Under alkali effect, reaction generates 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid, and yield is between 28-81%.Due to the fluoro-2,4-of 1,5-bis- Dinitro benzene is the most active, if there is any water in reaction system, water can occur competition anti-with hydroxyacetic acid Should, first hydrolysis produces nitrophenol by-product, and this by-product causes catalyst poisoning in hydrogenation reaction subsequently.Therefore, This technique needs strictly to control raw material, alkali and the moisture of whole system.Raw material hydroxyl acetic acid the easiest deliquescence, and And high temperature easily decomposes when removing water.All of these factors taken together causes the method to be unfavorable for industrialized production.
Summary of the invention
An object of the present invention is to overcome the existing deficiency preparing phenoxy acetic acid intermediate technology, from cheap and easily-available hydroxyl second Aqueous acid and organic amine set out, and are dehydrated into salt, then react with halogenated aryl hydrocarbon, synthesize phenoxy acetic acid.This invention not only solves The problem that anhydrous hydroxyacetic acid cost is high, is effectively controlled the moisture in reaction system simultaneously.The most not only Inhibit and produce in aromatic nucleophilic substitution reaction hydrolysising by-product nitrophenol, improve reaction yield simultaneously.The present invention's Another purpose is to develop the more effective synthetic method of phenoxy acetic acid ester on the basis of new technology prepared by phenoxy acetic acid further.
The synthetic method of a kind of phenoxy acetic acid ester (I), it is characterised in that the formula of compound (I) is as follows:
In formula:
R1For C1-C12Alkyl;
R2For H, methyl or phenyl;
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
Described synthetic method comprises the steps:
Step (a): compound (II) and compound (III) react to obtain compound (IV) in organic solvent;
The formula of compound (II) is as follows:
In formula:
R2For H, methyl or phenyl;
The formula of compound (III) is as follows:
In formula:
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
The formula of compound (IV) is as follows:
In formula:
R2For H, methyl or phenyl;
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
Step (b): compound (IV) and compound (V) obtain compound (VI) under acid binding agent effect,
The formula of compound (V) is as follows:
In formula:
X is F, Cl, Br or I;
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
The formula of compound (VI) is as follows:
In formula:
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
R2For H, methyl or phenyl;
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
Step (c): compound (VI) and compound (VII) direct reaction are prepared into compound (I);
The formula of compound (VII) is as follows:
R1-L(VII)
In formula:
R1For C1-C12Alkyl;
L is Cl, Br, I, MeSO3 -, R1OCO2 -, TsSO3 -Or R1OSO3 -, wherein R1It is as defined above.
In step (a), described solvent is selected from toluene, dimethylbenzene, dichloromethane, chloroform, methanol, ethanol or isopropyl One or more in alcohol;Compound (II) is 1:1-1:5 with the molar ratio of compound (III);Reaction temperature is from-30 DEG C-50 DEG C; In step (b), described acid binding agent is inorganic base or organic base;Inorganic base selected from sodium carbonate, potassium carbonate, potassium hydroxide or Sodium hydroxide;Organic base is selected from triethylamine, tripropyl amine (TPA), tri-n-butylamine, diethylamine, hexanamine, piperidines, pyridine or compound (III) own;Compound (V) is 1:0.9-1:5 with the molar ratio of compound (IV);Acid binding agent and the mol ratio of compound (IV) Example is 1:1-5:1;Reaction temperature is from-30 DEG C-25 DEG C;Compound (VI) is 1:0.9-1:5 with the molar ratio of compound (VII); Reaction temperature is from-30 DEG C-50 DEG C.
In step (a), described solvent is preferably toluene and dichloromethane;Compound (II) is preferred with the molar ratio of compound (III) For 1:1-1:2;Reaction temperature is preferably from 0-25 DEG C;In step (b), described acid binding agent is preferably triethylamine;Compound (V) molar ratio with compound (IV) is preferably 1:0.9-1:1.2;Acid binding agent is preferably with the molar ratio of compound (IV) 1:1-1.2:1;Reaction temperature is preferably from-5-10 DEG C.Compound (VI) is preferably 1:0.9-1:2 with the molar ratio of compound (VII); Reaction temperature is preferably from-5 DEG C-25 DEG C.
The synthetic method of a kind of phenoxy acetic acid ester (I), it is characterised in that the formula of compound (I) is as follows:
In formula:
R1For C1-C12Alkyl;
R2For H, methyl or phenyl;
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
Described synthetic method includes:
Step (a): compound (II) and compound (III) react to obtain compound (IV) in organic solvent,
The formula of compound (II) is as follows:
In formula:
R2For H, methyl or phenyl;
The formula of compound (III) is as follows:
In formula:
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
The formula of compound (IV) is as follows:
In formula:
R2For H, methyl or phenyl;
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
Step (b): compound (IV) and compound (V) obtain compound (VI) under acid binding agent effect,
The formula of compound (V) is as follows:
In formula:
X is F, Cl, Br or I;
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
The formula of compound (VI) is as follows:
In formula:
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
R2For H, methyl or phenyl;
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
Step (c '): compound (VI) is free under mineral acid effect obtains compound (VIII), and the formula of compound (VIII) is as follows:
In formula:
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
R2For H, methyl or phenyl;
Step (d): compound (VIII) and compound (IX) reacts under acid catalysis and be prepared into compound (I), or compound (VIII) and change Compound (VII) reacts under alkali effect and is prepared into compound (I),
The formula of compound (IX) is as follows:
R1OH(IX)
In formula:
R1For C1-C12Alkyl;
The formula of compound (VII) is as follows:
R1-L(VII)
In formula:
R1For C1-C12Alkyl;
L is Cl, Br, I, MeSO3 -, R1OCO2 -, TsSO3 -Or R1OSO3 -, wherein R1It is as defined above.
In step (a), described solvent is selected from toluene, dimethylbenzene, dichloromethane, chloroform, methanol, ethanol or isopropyl One or more in alcohol;Compound (II) is 1:1-1:5 with the molar ratio of compound (III);Reaction temperature is from-30 DEG C-50 DEG C; In step (b), described acid binding agent is inorganic base or organic base;Inorganic base selected from sodium carbonate, potassium carbonate, potassium hydroxide or Sodium hydroxide;Organic base is selected from triethylamine, tripropyl amine (TPA), tri-n-butylamine, diethylamine, hexanamine, piperidines, pyridine or compound (III) own;Compound (V) is 1:0.9-1:5 with the molar ratio of compound (IV);Acid binding agent and the mol ratio of compound (IV) Example is 1:1-5:1;Reaction temperature is from-30 DEG C-25 DEG C;In step (c '), described mineral acid is selected from sulphuric acid, hydrochloric acid or phosphorus Acid;Mineral acid is 1:1-15:1 with the molar ratio of compound (IV);Reaction temperature is from-30 DEG C-25 DEG C;In step (d), Described acid catalyst is selected from sulphuric acid, hydrochloric acid, acetic acid, phosphoric acid or p-methyl benzenesulfonic acid;Alkali is inorganic base or organic base;Inorganic base Selected from sodium carbonate, potassium carbonate, potassium hydroxide or sodium hydroxide;Organic base is selected from triethylamine, piperidines, DBU or pyridine;Change Compound (VIII) is 1:0.9-1:5 with the molar ratio of compound (IX) or compound (VII);Acid or alkali and compound (IV) rub Your ratio is 1:1-5:1;Reaction temperature is from-30 DEG C-130 DEG C.
In step (a), described solvent is preferably toluene or dichloromethane;Compound (II) is preferred with the molar ratio of compound (III) For 1:1-1:2;Reaction temperature is preferably from 0-25 DEG C;In step (b), described acid binding agent is preferably triethylamine;Compound (V) molar ratio with compound (IV) is preferably 1:0.9-1:1.2;Acid binding agent is preferably with the molar ratio of compound (IV) 1:1-1.2:1;Reaction temperature is preferably from-5-10 DEG C;In step (c '), described mineral acid is preferably hydrochloric acid;Mineral acid with The molar ratio of compound (IV) is preferably 1:1-2:1;Reaction temperature is preferably from-5-25 DEG C;In step (d), described Acid catalyst is preferably sulphuric acid;Alkali is inorganic base or organic base;Inorganic base is preferably potassium hydroxide;Organic base is preferably triethylamine; Compound (VIII) is preferably 1:0.9-1:2 with the molar ratio of compound (IX) or compound (VII);Acid or alkali and compound (IV) Molar ratio be preferably 1:0.9-1:2;Reaction temperature is preferably from-5-130 DEG C.
A kind of phenoxy acetic acid ammonium salt (VI), it is characterised in that the formula of compound (VI) is as follows:
In formula:
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
R2For H, methyl or phenyl;
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
The synthetic method of a kind of phenoxy acetic acid ammonium salt (VI), it is characterised in that the formula of compound (VI) is as follows:
In formula:
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
R2For H, methyl or phenyl;
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
Described method includes:
Step (a): compound (II) and compound (III) obtain compound (IV) in organic solvent,
The formula of compound (II) is as follows:
In formula:
R2For H, methyl or phenyl;
The formula of compound (III) is as follows:
In formula:
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
The formula of compound (IV) is as follows:
In formula:
R2For H, methyl or phenyl;
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
Step (b): compound (IV) and compound (V) obtain compound (VI) under acid binding agent effect,
The formula of compound (V) is as follows:
In formula:
X is F, Cl, Br or I;
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN.
In step (a), described solvent is selected from toluene, dimethylbenzene, dichloromethane, chloroform, methanol, ethanol or isopropyl One or more in alcohol;Compound (II) is 1:1-1:5 with the molar ratio of compound (III);Reaction temperature is from-30 DEG C-50 DEG C; In step (b), described acid binding agent is inorganic base or organic base;Inorganic base selected from sodium carbonate, potassium carbonate, potassium hydroxide or Sodium hydroxide;Organic base is selected from triethylamine, tripropyl amine (TPA), tri-n-butylamine, diethylamine, hexanamine, piperidines, pyridine or compound (III) own;Compound (V) is 1:0.9-1:5 with the molar ratio of compound (IV);Acid binding agent and the mol ratio of compound (IV) Example is 1:1-5:1;Reaction temperature is from-30 DEG C-25 DEG C.
In step (a), described solvent is preferably toluene or dichloromethane;Compound (II) is preferred with the molar ratio of compound (III) For 1:1-1:2;Reaction temperature is preferably from 0-25 DEG C;In step (b), described acid binding agent is preferably triethylamine;Compound (V) molar ratio with compound (IV) is preferably 1:0.9-1:1.2;Acid binding agent is preferably with the molar ratio of compound (IV) 1:1-1.2:1;Reaction temperature is preferably from-5-10 DEG C.
The synthetic method of a kind of phenoxy acetic acid ammonium salt (VI), it is characterised in that the formula of compound (VI) is as follows:
In formula:
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
R2For H, methyl or phenyl;
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
Described synthetic method is:
Compound (VIII) and compound (III) obtain compound (VI) in organic solvent,
The formula of compound (VIII) is as follows:
In formula:
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
R2For H, methyl or phenyl;
The formula of compound (III) is as follows:
In formula:
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ.
Detailed description of the invention
Embodiment provided below be intended to indicate that the present invention rather than limit the present invention.
The preparation of embodiment 1 compound (IV)
(1) preparation of hydroxyacetic acid triethylammonium salts
In 100ml there-necked flask, add 15.7g hydroxyacetic acid and 80ml toluene, add 22.9g triethylamine, be stirred at room temperature 2 little Time.Precipitation, obtains 30.2g hydroxyacetic acid triethylammonium salts.
(2) preparation of the positive fourth ammonium salt of hydroxyacetic acid three
In 100ml there-necked flask, add 3.9g hydroxyacetic acid and 20ml dichloromethane, add 10.5g tri-n-butylamine at 0 DEG C, protect Temperature 2 hours.Precipitation, obtains the positive fourth ammonium salt of 11.2g hydroxyacetic acid three.
(3) preparation of hydroxyacetic acid dicyclohexylamine salt
In 100ml there-necked flask, add 7.8g hydroxyacetic acid and 90ml toluene, be subsequently adding under 19.6g hexanamine, room temperature and stir Mix 2 hours.Sucking filtration, washs with 5ml toluene, and filter cake is dried, and obtains 24.8g hydroxyacetic acid dicyclohexylamine salt.
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 dichloromethane, be subsequently adding 2.7g triethylamine, stirs 2 hours under room temperature.Precipitation, obtains 9.5g hydroxyacetic acid triethylammonium salts.
1H NMR(δ,D2O):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 ammonium
In 100ml there-necked flask, add 7g2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid and 50ml toluene, be subsequently adding 4.9g bicyclo- Hexylamine, stirs 2 hours under room temperature.Precipitation, obtains the positive fourth ammonium salt of 11.7g hydroxyacetic acid three.
1H NMR(δ,D2O):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 VIII
(1) preparation of 2-(5-fluoro-2,4-2,4-dinitrophenoxy) acetic acid
19.4g1,5-bis-fluoro-2,4-dinitro benzene, 250ml toluene and 24.8g hydroxyacetic acid two hexamethylene is added in 500ml there-necked flask Ammonium salt, stirring is cooled to 10 DEG C.Add 9.7g triethylamine, insulation reaction 8 hours.Addition hydrochloric acid tune pH to 2, sucking 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
20.4g1,5-bis-fluoro-2,4-dinitro benzene, 200ml toluene and 15.1g hydroxyacetic acid three second ammonium is added in 500ml there-necked flask Salt, stirring is cooled to-5 DEG C.Add 10.2g triethylamine, insulation reaction 8 hours.Addition hydrochloric acid tune pH to 2, sucking 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 0.2g dense Sulphuric acid, is warming up to 130 DEG C, drips 4.4g ethanol, reacts 2h, cooling, is washed twice with water, and precipitation obtains 21.6g2-(5- Fluoro-2,4-2,4-dinitrophenoxy) ethyl acetate.
1H NMR(δ,CDCl3):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
20.4g1,5-bis-fluoro-2,4-dinitro benzene, 200ml toluene and 15.1g hydroxyacetic acid three second is added in 500ml there-necked flask Ammonium salt, stirring is cooled to-5 DEG C.Add 15.3g triethylamine, insulation reaction 8 hours.Add 25.2g dimethyl sulfate, continue Continuous reaction 8 hours, is washed twice with water, and precipitation obtains 15.9g2-(5-fluoro-2,4-2,4-dinitrophenoxy) methyl acetate.
1H NMR(δ,CDCl3):8.822-8.806(d,1H),6.881-6.858(d,1H),4.929(s,2H),3.859(s,3H).

Claims (8)

1. the synthetic method of a phenoxy acetic acid ester (I), it is characterised in that the formula of compound (I) is as follows:
In formula:
R1For C1-C12Alkyl;
R2For H, methyl or phenyl;
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
Described synthetic method comprises the steps:
Step (a): compound (II) and compound (III) react to obtain compound (IV) in organic solvent;
The formula of compound (II) is as follows:
In formula:
R2For H, methyl or phenyl;
The formula of compound (III) is as follows:
In formula:
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
The formula of compound (IV) is as follows:
In formula:
R2For H, methyl or phenyl;
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
Step (b): compound (IV) and compound (V) obtain compound (VI) under acid binding agent effect,
The formula of compound (V) is as follows:
In formula:
X is F, Cl, Br or I;
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
The formula of compound (VI) is as follows:
In formula:
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
R2For H, methyl or phenyl;
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
Step (c): compound (VI) and compound (VII) direct reaction are prepared into compound (I);
The formula of compound (VII) is as follows:
R1-L (VII)
In formula:
R1For C1-C12Alkyl;
L is Cl, Br, I, MeSO3 -, R1OCO2 -, TsSO3 -Or R1OSO3 -, wherein R1It is as defined above.
2. the synthetic method of phenoxy acetic acid ester (I) as claimed in claim 1, it is characterised in that in step (a), described solvent is One or more in toluene, dimethylbenzene, dichloromethane, chloroform, methanol, ethanol or isopropanol;Compound (II) It is 1:1-1:5 with the molar ratio of compound (III);Reaction temperature is from-30 DEG C-50 DEG C;In step (b), described acid binding agent is Inorganic base or organic base;Inorganic base is selected from sodium carbonate, potassium carbonate, potassium hydroxide or sodium hydroxide;Organic base selected from triethylamine, Tripropyl amine (TPA), tri-n-butylamine, diethylamine, hexanamine, piperidines, pyridine or compound (III) itself;Compound (V) and compound (IV) Molar ratio be 1:0.9-1:5;Acid binding agent is 1:1-5:1 with the molar ratio of compound (IV);Reaction temperature is from-30 DEG C -25℃;In step (c), compound (VI) is 1:0.9-1:5 with the molar ratio of compound (VII);Reaction temperature is from-30 DEG C -50℃。
3. the synthetic method of phenoxy acetic acid ester (I) as claimed in claim 1 or 2, it is characterised in that in step (a), described is molten Agent is preferably toluene and dichloromethane;Compound (II) is preferably 1:1-1:2 with the molar ratio of compound (III);Reaction temperature is excellent Elect as from 0-25 DEG C;In step (b), described acid binding agent is preferably triethylamine;Compound (V) and compound (IV) mole Ratio is preferably 1:0.9-1:1.2;Acid binding agent is preferably 1:1-1.2:1 with the molar ratio of compound (IV);Reaction temperature is preferred For from-5-10 DEG C;In step (c), compound (VI) is preferably 1:0.9-1:2 with the molar ratio of compound (VII);Reaction Temperature is preferably from-5 DEG C-25 DEG C.
4. the synthetic method of a phenoxy acetic acid ester (I), it is characterised in that the formula of compound (I) is as follows:
In formula:
R1For C1-C12Alkyl;
R2For H, methyl or phenyl;
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
Described synthetic method includes:
Step (a): compound (II) and compound (III) react to obtain compound (IV) in organic solvent,
The formula of compound (II) is as follows:
In formula:
R2For H, methyl or phenyl;
The formula of compound (III) is as follows:
In formula:
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
The formula of compound (IV) is as follows:
In formula:
R2For H, methyl or phenyl;
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
Step (b): compound (IV) and compound (V) obtain compound (VI) under acid binding agent effect,
The formula of compound (V) is as follows:
In formula:
X is F, Cl, Br or I;
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
The formula of compound (VI) is as follows:
In formula:
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
R2For H, methyl or phenyl;
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
Step (c '): compound (VI) is free under mineral acid effect obtains compound (VIII), and the formula of compound (VIII) is as follows:
In formula:
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
R2For H, methyl or phenyl;
Step (d): compound (VIII) and compound (IX) reacts under acid catalysis and be prepared into compound (I), or compound (VIII) and change Compound (VII) reacts under alkali effect and is prepared into compound (I),
The formula of compound (IX) is as follows:
R1OH (IX)
In formula:
R1For C1-C12Alkyl;
The formula of compound (VII) is as follows:
R1-L (VII)
In formula:
R1For C1-C12Alkyl;
L is Cl, Br, I, MeSO3 -, R1OCO2 -, TsSO3 -Or R1OSO3 -, wherein R1It is as defined above.
5. the synthetic method of a kind of phenoxy acetic acid ester (I), it is characterised in that in step (a), described is molten Agent is one or more in toluene, dimethylbenzene, dichloromethane, chloroform, methanol, ethanol or isopropanol;Chemical combination Thing (II) is 1:1-1:5 with the molar ratio of compound (III);Reaction temperature is from-30 DEG C-50 DEG C;In step (b), described ties up Acid agent is inorganic base or organic base;Inorganic base is selected from sodium carbonate, potassium carbonate, potassium hydroxide or sodium hydroxide;Organic base is selected from three Ethamine, tripropyl amine (TPA), tri-n-butylamine, diethylamine, hexanamine, piperidines, pyridine or compound (III) itself;Compound (V) with The molar ratio of compound (IV) is 1:0.9-1:5;Acid binding agent is 1:1-5:1 with the molar ratio of compound (IV);Reaction temperature For from-30 DEG C-25 DEG C;In step (c '), described mineral acid is selected from sulphuric acid, hydrochloric acid or phosphoric acid;Mineral acid and compound (IV) Molar ratio be 1:1-15:1;Reaction temperature is from-30 DEG C-25 DEG C;In step (d), described acid catalyst selected from sulphuric acid, Hydrochloric acid, acetic acid, phosphoric acid or p-methyl benzenesulfonic acid;Alkali is inorganic base or organic base;Inorganic base is selected from sodium carbonate, potassium carbonate, hydrogen-oxygen Change potassium or sodium hydroxide;Organic base is selected from triethylamine, piperidines, DBU or pyridine;Compound (VIII) and compound (IX) or change The molar ratio of compound (VII) is 1:0.9-1:5;The molar ratio of acid or alkali and compound (IV) is 1:1-5:1;Reaction temperature For from-30 DEG C-130 DEG C.
6. the synthetic method of a phenoxy acetic acid ammonium salt (VI), it is characterised in that the formula of compound (VI) is as follows:
In formula:
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN;
R2For H, methyl or phenyl;
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
Described method includes:
Step (a): compound (II) and compound (III) obtain compound (IV) in organic solvent,
The formula of compound (II) is as follows:
In formula:
R2For H, methyl or phenyl;
The formula of compound (III) is as follows:
In formula:
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
The formula of compound (IV) is as follows:
In formula:
R2For H, methyl or phenyl;
R3、R4And R5For H, C1-C5Alkyl or C3-C7Cycloalkyl, R3、R4And R5For identical or differ;
Step (b): compound (IV) and compound (V) obtain compound (VI) under acid binding agent effect,
The formula of compound (V) is as follows:
In formula:
X is F, Cl, Br or I;
Y is H, C1-C4Alkyl, phenyl, F, Cl, Br, NO2, CF3Or CN;
EWG is NO2, CF3Or CN.
7. the synthetic method of phenoxy acetic acid ammonium salt (VI) as claimed in claim 6, it is characterised in that in step (a), described is molten Agent is one or more in toluene, dimethylbenzene, dichloromethane, chloroform, methanol, ethanol or isopropanol;Chemical combination Thing (II) is 1:1-1:5 with the molar ratio of compound (III);Reaction temperature is from-30 DEG C-50 DEG C;In step (b), described ties up Acid agent is inorganic base or organic base;Inorganic base is selected from sodium carbonate, potassium carbonate, potassium hydroxide or sodium hydroxide;Organic base is selected from three Ethamine, tripropyl amine (TPA), tri-n-butylamine, diethylamine, hexanamine, piperidines, pyridine or compound (III) itself;Compound (V) with The molar ratio of compound (IV) is 1:0.9-1:5;Acid binding agent is 1:1-5:1 with the molar ratio of compound (IV);Reaction temperature For from-30 DEG C-25 DEG C.
The synthetic method of phenoxy acetic acid ammonium salt (VI) the most as claimed in claims 6 or 7, it is characterised in that in step (a), described Solvent be preferably toluene or dichloromethane;Compound (II) is preferably 1:1-1:2 with the molar ratio of compound (III);Reaction temperature Degree is preferably from 0-25 DEG C;In step (b), described acid binding agent is preferably triethylamine;Compound (V) and compound (IV) Molar ratio is preferably 1:0.9-1:1.2;Acid binding agent is preferably 1:1-1.2:1 with the molar ratio of compound (IV);Reaction temperature It is preferably from-5-10 DEG C.
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