CN108069832A - The preparation method of 2,3,5,6- polytetrafluoroethylene phenols - Google Patents
The preparation method of 2,3,5,6- polytetrafluoroethylene phenols Download PDFInfo
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- CN108069832A CN108069832A CN201711320880.0A CN201711320880A CN108069832A CN 108069832 A CN108069832 A CN 108069832A CN 201711320880 A CN201711320880 A CN 201711320880A CN 108069832 A CN108069832 A CN 108069832A
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- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/367—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form
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- C07C37/50—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions decreasing the number of carbon atoms
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Abstract
The invention discloses a kind of preparation methods of 2,3,5,6 polytetrafluoroethylene phenol.The present invention, for raw material, in water by the reaction with inorganic base and phase transfer catalyst, is obtained 4 hydroxyl, 2,3,5,6 tetrafluorobenzoic aid, 2,3,5,6 polytetrafluoroethylene phenols is obtained using decarboxylation with 2,3,4,5,6 pentafluoro benzoic acids.The present invention uses 2,3,4,5,6 pentafluoro benzoic acids make raw material, cost of material can be substantially reduced, without special or harsh reaction condition, production equipment is required also not high, the special three wastes are not generated, intermediate is easily isolated, and is advantageously reduced the manufacture cost and cost of labor of production, is increased economic efficiency.
Description
Technical field
The present invention relates to a kind of preparation methods of 2,3,5,6- polytetrafluoroethylene phenols, belong to chemical production technology field.
Background technology
2,3,5,6- polytetrafluoroethylene phenols are important chemical raw materials and medicine intermediate, in pharmaceutical synthesis and new material preparation side
Mask is widely used.For the anti-inflammation drugs rofecoxib for the treatment of of arthritis；Inhibit the special cysteine egg of aspartic acid
Peptides of white enzyme etc..
There is method used by the synthesis usually of 2,3,5,6- polytetrafluoroethylene phenols：Such as document 1 (Dalian University of Technology, master's degree
Paper, 2008, He Guangwen, the study on the synthesis of four kinds of substitution phenyl tetrafluorides) in, raw material is made with phenyl-pentafluoride, 4-butyl ammonium hydrogen sulfate is made
Phase transfer catalyst generates 2,3,5,6- polytetrafluoroethylene phenols with sodium hydroxide hydrolysis.The by-product tri-n-butylamine of generation is not easy to remove, and
This method has isomers generation, is not easy to separate with product, and the method yield is low, and product purity is poor, unsuitable industrialization.
In Chinese patent CN104926617, with 1,2,4,5- phenyl tetrafluoride for starting material, reacted by low temperature butyl lithium,
Borate is obtained, boric acid is obtained after hydrolysis, reoxidizes to obtain 2,3,5,6- polytetrafluoroethylene phenol of product.It is very high that this method has used activity
Butyl lithium, reaction condition is harsher, it is necessary to low temperature, carries out under anhydrous and oxygen-free inert gas shielding, will to production equipment
Ask comparison high, production cost is very high, and uses substantial amounts of solvent, not easy to operate in industrialization.
The content of the invention
In view of the deficiency prepared in the prior art in 2,3,5,6- polytetrafluoroethylene phenols described above, the present invention provides a kind of new
2,3,5,6- polytetrafluoroethylene phenol of preparation method, this method raw material is easy to get, simple for process, and reaction condition is mild, and product content is high,
And it easily industrializes.
Technical scheme is as follows：
A kind of preparation method of 2,3,5,6- tetrafluorobenzoic aids, includes the following steps：
(1) 2, water, inorganic base and phase transfer catalyst, back flow reaction are added in 3,4,5,6- pentafluoro benzoic acids and obtains 4-
Hydroxyl -2,3,5,6- tetrafluorobenzoic aids, back flow reaction temperature are 90-200 DEG C, are preferably 90-120 DEG C；
(2) 4- hydroxyls -2,3,5,6- tetrafluorobenzoic aids are dissolved in solvent, carry out decarboxylic reaction, obtain 2,3,5,6- polytetrafluoroethylene phenols
Crude product, decarboxylic reaction temperature are 60-200 DEG C, are preferably 80-160 DEG C；
(3) 2,3,5,6- polytetrafluoroethylene phenol crude products obtain 2,3,5,6- polytetrafluoroethylene phenols through solvent extraction, concentration, rectifying.
In the above-mentioned technical solutions, in step (1), the inorganic base be inorganic base be sodium hydroxide, potassium hydroxide,
One kind in magnesium hydroxide, calcium hydroxide, ammonium hydroxide, barium hydroxide or two kinds are preferably potassium hydroxide.
In the above-mentioned technical solutions, in step (1), the phase transfer catalyst is quaternary ammonium compound, such as four
Ammonio methacrylate, 4 bromide, tetrabutylammonium chloride, tetrabutylammonium bromide, 4-butyl ammonium hydrogen sulfate, benzyl triethyl ammonium chlorine
Change one kind in ammonium, tri-n-octyl methyl ammonium chloride, dodecyl trimethyl ammonium chloride, tetradecyl trimethyl ammonium chloride, preferably
For benzyltriethylammoinium chloride.
In the above-mentioned technical solutions, in step (1), the inorganic base and 2, mole of 3,4,5,6- pentafluoro benzoic acids
Than for 1-100:1, it is preferably 2-5:1.
In the above-mentioned technical solutions, in step (1), the water and 2, the weight ratio of 3,4,5,6- pentafluoro benzoic acids is
2-10:1, it is preferably 2-5:1.
In the above-mentioned technical solutions, in step (1), the phase transfer catalyst and 2,3,4,5,6- pentafluoro benzoic acids
Molar ratio be 0.05-1:1, it is preferably 0.2-0.5:1.
In the above-mentioned technical solutions, in step (1), by the reacting liquid filtering after back flow reaction, filtrate is collected, filtrate is used
Acid adjusts pH to less than 2, and organic solvent extraction, extract liquor is concentrated to obtain 4- hydroxyls -2,3,5,6- tetrafluorobenzoic aids.Wherein, preferably
, using the pH value of the acid reagents tune filtrate such as sulfuric acid, hydrochloric acid, phosphoric acid or acetic acid, the preferred 1-2 of pH value, the acid is preferably sulphur
Acid or hydrochloric acid.
In the above-mentioned technical solutions, in step (2), the solvent is n,N-Dimethylformamide, N, N- dimethyl
Acetamide, n,N-Dimethylaniline, ethylene glycol, glycol monoethyl ether, 1,2-PD or 1,3-PD are preferably N, N- bis-
Methylaniline.
In the above-mentioned technical solutions, in step (3), by the crude product after decarboxylic reaction after solvent extraction, distillation is passed through
And rectifying obtains 2,3,5,6- tetrafluorobenzoic aids.Wherein, extraction with solvent be the more alkyl chlorides of C1-C2, ethyl acetate, ether, toluene,
Dimethylbenzene or chlorobenzene, the more alkyl chlorides of C1-C2 can be dichloromethane, chloroform, 1,2- dichloroethanes etc., be preferably two chloroethenes
Alkane.
The reaction equation of the preparation method of the 2,3,5,6- tetrafluorobenzoic aids of the present invention is as follows：
Beneficial effects of the present invention are as follows：
1st, compared with the prior art, the present invention makees raw material using 2,3,4,5,6- pentafluoro benzoic acids, overcomes the prior art
Middle raw material is not easy to obtain and the problem of higher price.Cost of material can be substantially reduced to increase economic efficiency.
2nd, compared with the prior art, the present invention is without special or harsh reaction condition, such as low temperature, high temperature, high pressure, reaction
Safety in the process is secure, is conducive to safety in production, clean manufacturing.It is also not high to production equipment requirement, advantageously reduce life
The manufacture cost and cost of labor of production, increase economic efficiency.
3rd, compared with the prior art, the present invention does not generate the special three wastes, and intermediate is easily isolated, and overcomes other technologies
Bottleneck, reduce waste processing cost, be conducive on a large scale commercialization promote.
Specific embodiment
The invention will now be further described with reference to specific embodiments, the advantages and features of the present invention will be with description and
It is apparent.But embodiment is only exemplary, does not form any restrictions to the scope of the present invention.Those skilled in the art should
It should be appreciated that the details and form of technical solution of the present invention can be repaiied without departing from the spirit and scope of the invention
Change or replace, but these modifications and replacement are each fallen in protection scope of the present invention.In following embodiments, unless otherwise specified,
Used experimental method is that conventional method, material therefor, reagent etc. can be bought from biological or chemical company.
Embodiment 1
2,3,4,5,6- pentafluoro benzoic acid 212g and 600g water are added in reaction kettle, stirring is opened, adds at normal temperatures
30% potassium hydroxide aqueous solution 367g, adds benzyltriethylammoinium chloride 65g and magnesium hydroxide 60g, is heated to 120
DEG C, when back flow reaction 3 is small, cool down, filtering, filter cake is washed with water 3 times, and filtrate is neutralized with hydrochloric acid to pH=2, and three are extracted with ether
Secondary, concentrated extract obtains 4- hydroxyls -2,3, and 5,6- tetrafluorobenzoic aid solid 189.3g, HPLC detection levels more than 98% are received
Rate：91%.
Embodiment 2
2,3,4,5,6- pentafluoro benzoic acid 212g and 400g water are added in reaction kettle, stirring is opened, adds at normal temperatures
30% sodium hydrate aqueous solution 340g, adds benzyltriethylammoinium chloride 58g and calcium hydroxide 90g, is heated to 120
DEG C, when back flow reaction 5 is small, cool down, filtering, filter cake is washed with water 3 times, and filtrate is neutralized with hydrochloric acid to pH=2, and three are extracted with ether
Secondary, concentrated extract obtains 4- hydroxyls -2,3, and 5,6- tetrafluorobenzoic aid solid 175g, HPLC detection levels more than 98% are received
Rate：84%.
Embodiment 3
Disubstituted-4-hydroxy -2,3,5,6- tetrafluorobenzoic aid dry product 208g are dissolved in 1000g n,N-Dimethylaniline, stirring
Under be to slowly warm up to flow back, when back flow reaction 5 is small at 160 DEG C after, sampling, HPLC analysis, raw material 4- hydroxyls -2,3,5,6- tetra-
Fluobenzoic acid conversion is complete, and cooling pours into reaction solution in 4L cold water, and with dichloromethane extraction three times, combining extraction liquid uses water
Three times, after anhydrous magnesium sulfate drying, concentration, distillation and then rectifying obtain 2,3,5,6- polytetrafluoroethylene phenols of 129.5g, yield for washing
78%, HPLC detection level are 99.3%.
Embodiment 4
Disubstituted-4-hydroxy -2,3,5,6- tetrafluorobenzoic aid dry product 210g are dissolved in 1050g n,N-Dimethylaniline, stirring
Under be to slowly warm up to flow back, when back flow reaction 5 is small at 160 DEG C after, sampling, HPLC analysis, raw material 4- hydroxyls -2,3,5,6- tetra-
Fluobenzoic acid conversion is complete, and cooling pours into reaction solution in 5L cold water, and with dichloromethane extraction three times, combining extraction liquid uses water
Three times, after anhydrous magnesium sulfate drying, concentration, distillation and then rectifying obtain 2,3,5,6- polytetrafluoroethylene phenols of 147g, yield for washing
88%, HPLC detection level are 99.1%.
Claims (10)
1. the preparation method of 2,3,5,6- polytetrafluoroethylene phenol of one kind, it is characterised in that include the following steps：
(1) 2, water, inorganic base and phase transfer catalyst, back flow reaction are added in 3,4,5,6- pentafluoro benzoic acids, obtain 4- hydroxyls-
2,3,5,6- tetrafluorobenzoic aids, back flow reaction temperature are 90-200 DEG C；
(2) 4- hydroxyls -2,3,5,6- tetrafluorobenzoic aids are dissolved in solvent, carry out decarboxylic reaction, it is thick to obtain 2,3,5,6- polytetrafluoroethylene phenols
Product, decarboxylic reaction temperature are 60-200 DEG C；
(3) 2,3,5,6- polytetrafluoroethylene phenol crude products obtain 2,3,5,6- polytetrafluoroethylene phenols through solvent extraction, concentration, rectifying.
2. preparation method according to claim 1, which is characterized in that in step (1), the inorganic base is hydroxide
One kind in lithium, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, ammonium hydroxide, barium hydroxide or two kinds.
3. preparation method according to claim 1, which is characterized in that in step (1), the phase transfer catalyst is
Tetramethyl ammonium chloride, 4 bromide, tetrabutylammonium chloride, tetrabutylammonium bromide, 4-butyl ammonium hydrogen sulfate, benzyl triethyl ammonium
One kind in ammonium chloride, tri-n-octyl methyl ammonium chloride, dodecyl trimethyl ammonium chloride, tetradecyl trimethyl ammonium chloride.
4. preparation method according to claim 1, which is characterized in that in step (1), the inorganic base and 2,3,4,
The molar ratio of 5,6- pentafluoro benzoic acids is 1-100:1.
5. preparation method according to claim 1, which is characterized in that in step (1), the water and 2,3,4,5,6-
The weight ratio of pentafluoro benzoic acid is 2-10:1.
6. preparation method according to claim 1, which is characterized in that in step (1), the phase transfer catalyst with
The molar ratio of 2,3,4,5,6- pentafluoro benzoic acids is 0.05-1:1.
7. preparation method according to claim 1, which is characterized in that in step (1), by the reaction solution after back flow reaction
Filtering, takes filtrate, and filtrate adjusts pH to less than 2 with acid, organic solvent extraction, extract liquor it is concentrated 4- hydroxyls -2,3,5,6- tetra-
Fluobenzoic acid.
8. preparation method according to claim 7, which is characterized in that the acid is sulfuric acid, hydrochloric acid, phosphoric acid or acetic acid.
9. preparation method according to claim 1, which is characterized in that in step (2), the solvent be N, N- diformazans
Base formamide, DMAC N,N' dimethyl acetamide, N, accelerine, ethylene glycol, glycol monoethyl ether, 1,2- propylene glycol or 1,3-
Propylene glycol.
10. preparation method according to claim 1, which is characterized in that in step (3), the solvent is more for C1-C2
Alkyl chloride, ethyl acetate, ether, toluene, dimethylbenzene or chlorobenzene.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201711320880.0A CN108069832B (en) | 2017-12-12 | 2017-12-12 | Preparation method of 2,3,5, 6-tetrafluorophenol |
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| CN201711320880.0A CN108069832B (en) | 2017-12-12 | 2017-12-12 | Preparation method of 2,3,5, 6-tetrafluorophenol |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112979424A (en) * | 2020-11-26 | 2021-06-18 | 浙江中欣氟材股份有限公司 | Synthetic method of compound containing fluorophenol structure |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03232833A (en) * | 1990-02-07 | 1991-10-16 | Nippon Carbide Ind Co Inc | Production of 4-hydroxy-2,3,5,6-tetrafluorobenzoic acid and 2,3,5,6-tetrafluorophenol |
-
2017
- 2017-12-12 CN CN201711320880.0A patent/CN108069832B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03232833A (en) * | 1990-02-07 | 1991-10-16 | Nippon Carbide Ind Co Inc | Production of 4-hydroxy-2,3,5,6-tetrafluorobenzoic acid and 2,3,5,6-tetrafluorophenol |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112979424A (en) * | 2020-11-26 | 2021-06-18 | 浙江中欣氟材股份有限公司 | Synthetic method of compound containing fluorophenol structure |
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Inventor after: Zhang Zhong Inventor after: Jiang Dianbao Inventor after: Zhang Hongxue Inventor after: Li Yongxiang Inventor before: Zhang Zhong Inventor before: Jiang Dianping Inventor before: Zhang Hongxue Inventor before: Li Yongxiang |
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