CN113278996A - Preparation method of 2, 4, 5-trifluorophenylacetic acid - Google Patents
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Abstract
The invention discloses a preparation method of 2, 4, 5-trifluoro-phenylacetic acid, belonging to the field of pharmaceutical chemicals, and the invention uses 1, 2, 4-trifluoro-benzene, paraformaldehyde and chlorinating agent to react to obtain 2, 4, 5-trifluoro-benzyl chloride; dissolving 2, 4, 5-trifluorobenzyl chloride in electrolyte solution, taking inert metal or other electrodes as a cathode, taking active metal as an anode, and reacting with CO under the electrified condition2Reacting, acidifying, and purifying to obtain 2, 4, 5-trifluoro phenylacetic acid. The invention has the advantages of cheap and easily obtained raw materials, mild reaction conditions, less three wastes, good safety, easy realization of industrialization, high product purity and stable quality, completely meets the use requirement of the product as a drug intermediate, and is suitable for industrialized production.
Description
Technical Field
The invention relates to the field of pharmaceutical chemicals, and particularly relates to a preparation method of 2, 4, 5-trifluorophenylacetic acid.
Background
2, 4, 5-trifluoro-phenylacetic acid is a key intermediate for synthesizing a medicament Sitagliptinphosate/Januvia (trade name) for treating II type diabetes mellitus, the medicament is the first DPP-IV inhibitor newly marketed by Merck company, and the medicament has good curative effect, small side effect, good safety and tolerance for treating II type diabetes mellitus and wide market prospect.
Various methods for preparing 2, 4, 5-trifluorophenylacetic acid have been disclosed. Such as:
U.S. Pat. No. 4,068,141 reports 2, 4, 5-trifluorobromobenzene and diethyl malonate reacted under basic conditions to obtain 2, 4, 5-trifluorophenylacetic acid after hydrolysis. However, the reaction condition of the route is high, the atom economy is poor, and the method is not suitable for industrial production.
U.S. Pat. No. 4, 6,870,067 reports that 2, 4, 5-trifluorobromobenzene is prepared into a Grignard reagent, then reacted with allyl bromide, and oxidized with periodic acid under the catalysis of ruthenium trichloride to obtain 2, 4, 5-trifluorophenylacetic acid. However, the grignard reaction in the method usually adopts low-boiling-point volatile solvents such as diethyl ether and the like, so the method is easy to explode, has poor production safety, and the grignard reagent is unstable, the product yield is low, and the used catalysts, namely ruthenium trichloride and periodic acid as oxidant, are expensive, so the method is not suitable for industrial production.
Chinese patent 200510030162.0 reports that 1, 2, 4-trifluorobenzene is used as raw material, chlorosulfonic acid and zinc chloride are used as chlorinating agent, and reacts with paraformaldehyde through Blanc reaction to prepare 2, 4, 5-trifluorobenzyl chloride, then phase transfer catalyst is added into acetonitrile to make cyanidation reaction, and finally hydrolysis is carried out to obtain 2, 4, 5-trifluorophenylacetic acid. However, chlorosulfonic acid in the route has extremely strong pungent odor and poor safety, and the phase transfer catalyst is difficult to recycle, so that the method is poor in atom economy, greatly improves the production cost, and is poor in environmental friendliness, and therefore, the method is not suitable for industrial production. In addition, the 2, 4, 5-trifluoro-phenylacetonitrile obtained after the cyanidation reaction can be subjected to hydrolysis reaction only after separation and purification, the separation and purification of products are always difficult problems of synthetic chemistry, water extraction and separation are only suitable for hydrophilic products, the distillation technology is not suitable for products with poor volatility, and the use of organic solvents can cause cross contamination. Organic solvents are consumed in 50 billion dollars every year worldwide, and pose a great threat to the environment and human health. With the increasing awareness of environmental protection, green chemistry is more and more highly called worldwide, and the traditional solvent extraction technology is in urgent need of improvement.
Chinese patent 200810187895.9 reports that benzyl trifluorohalide reacts with magnesium in organic solvent to prepare Grignard reagent, and then reacts with carbon dioxide to obtain 2, 4, 5-trifluorophenylacetic acid, and the method has high requirement on anhydrous condition, great operation difficulty, poor safety and is not suitable for industrialization.
Therefore, the preparation method of 2, 4, 5-trifluorophenylacetic acid with low requirement on reaction conditions, convenient operation, good production safety, good environmental friendliness, low cost and high product yield is needed to be developed.
Disclosure of Invention
1. Technical problem to be solved
The technical problem to be solved by the invention is to provide a preparation method of 2, 4, 5-trifluorophenylacetic acid, which has the advantages of low requirement on reaction conditions, convenient operation, good production safety, good environmental friendliness, low cost and high product yield, so as to overcome the defects of the prior art.
2. Technical scheme
In order to solve the problems, the invention adopts the following technical scheme:
the invention takes 1, 2, 4-trifluorobenzene as raw material, after chloromethylation, the raw material reacts with CO in electrolyte solution2The electro-carboxylation reaction is directly carried out to directly synthesize the 2, 4, 5-trifluoro-phenylacetic acid, which is reasonable from the perspective of production safety and production cost reduction.
The invention provides a preparation method of 2, 4, 5-trifluorophenylacetic acid, which is realized by the following route:
the method comprises the following specific steps:
(1) firstly, adding a chlorinating agent (the chlorinating agent comprises concentrated sulfuric acid and NaCl) and paraformaldehyde into a container, then adding 1, 2, 4-trifluorobenzene, and carrying out heat preservation reaction at the temperature of 30-50 ℃, wherein the molar ratio of the 1, 2, 4-trifluorobenzene to the chlorinating agent to the paraformaldehyde is 1 (1-2) to 1-3; pouring the reaction solution into ice water, separating an organic layer, washing with water, drying and purifying to obtain 2, 4, 5-trifluorobenzyl chloride;
(2) firstly, filling CO in a sealed electrolytic cell2Adding electrolyte solution and the 2, 4, 5-trifluorobenzyl chloride obtained in the step (1) into the gas, stirring the mixture until the electrolyte solution is dissolved, and continuously introducing CO2A gas; after 1 hour, inert metal or other electrodes are taken as a cathode, active metal or metal platinum is taken as an anode, and 1-5000 mA/cm of metal is introduced2Continuously electrolyzing the current on the surface area of the cathode at the temperature of-50-100 ℃ to obtain a 2, 4, 5-trifluoro-phenylacetate solution; then obtaining the 2, 4, 5-trifluoro-phenylacetic acid after acidification and purification.
Specifically, the cathode in the step (2) is metal copper, metal nickel, metal platinum, metal tungsten, metal silver, metal titanium, a platinum mesh electrode, a carbon electrode, a graphite electrode or a glassy carbon electrode.
Specifically, the anode in the step (2) is metal zinc, metal aluminum, metal magnesium, metal manganese, metal iron or metal platinum.
Specifically, the electrolyte solution in step (2) is a solution prepared from N, N-dimethylformamide and any one electrolyte selected from tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium perchlorate, tetrabutyltetrafluoroboric acid, tetrabutylammonium hexafluorophosphate, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetraethylammonium perchlorate and tetraethyltetrafluoroboric acid.
Specifically, the electrolyte solution in step (2) is a solution prepared from acetonitrile and any one electrolyte selected from tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium perchlorate, tetrabutyltetrafluoroboric acid, tetrabutylammonium hexafluorophosphate, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetraethylammonium perchlorate, and tetraethyltetrafluoroboric acid.
Specifically, the electrolyte solution in step (2) is a solution prepared from N, N-dimethylacetamide and any one electrolyte selected from tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium perchlorate, tetrabutyltetrafluoroboric acid, tetrabutylammonium hexafluorophosphate, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetraethylammonium perchlorate and tetraethyltetrafluoroboric acid.
Specifically, the concentration of the electrolyte solution in the step (2) is 0.01M to 5M, preferably 0.05M to 1M, and more preferably 0.1M to 0.5M.
Specifically, the concentration of the 2, 4, 5-trifluorobenzyl chloride in the electrolyte solution in the step (2) is 0.01M to 5M, preferably 0.05M to 1M, and more preferably 0.1M to 0.5M.
Specifically, the reaction temperature of the electrolytic reaction in the step (2) is preferably-20 to 50 ℃, and more preferably 20 to 40 ℃.
Specifically, the acid used in the acidification process in the step (2) is selected from any one of hydrochloric acid, sulfuric acid, phosphoric acid and acetic acid.
Specifically, the purification in the steps (1) and (2) adopts a method of distillation and rectification.
3. Advantageous effects
(1) The invention takes 1, 2, 4-trifluorobenzene as raw material, after chloromethylation, the raw material reacts with CO in electrolyte solution2The electro-carboxylation reaction is directly carried out to directly synthesize the 2, 4, 5-trifluoro-phenylacetic acid, the process is simple, the reaction is not required to be carried out under anhydrous condition, the reaction condition is mild, and the operability is strong.
(2) The preparation method of 2, 4, 5-trifluoro-phenylacetic acid provided by the invention does not adopt volatile solvent with low boiling point, so that the explosion is not easy to occur, and the production safety is good; the adopted raw materials have no pungent smell, do not generate substances with pungent smell, and have good environmental friendliness.
(3) The raw materials adopted in the preparation method of the 2, 4, 5-trifluorophenylacetic acid provided by the invention are all cheap and easily available materials, and the production cost is low.
(4) The products of 2, 4, 5-trifluorobenzene chloride and 2, 4, 5-trifluorobenzene acetic acid in the preparation method of 2, 4, 5-trifluorobenzene acetic acid provided by the invention have stable properties, the product yield can reach more than 85 percent, and can reach 98.2 percent at most, and the product yield is high; and the product is efficiently purified by adopting a method of distilling firstly and then rectifying, the content of the product can reach more than 98 percent, the highest content can reach 99.8 percent, and the product purity is high.
In conclusion, the method has the advantages of mild reaction conditions, simple process, strong operability, good production safety and good environmental friendliness; the raw materials are cheap and easy to obtain, and the cost is low; and the product has high purity, high yield and stable quality, completely meets the use requirement of being used as a drug intermediate, and is suitable for industrial production.
Drawings
FIG. 1 is a hydrogen spectrum of 2, 4, 5-trifluorobenzyl chloride according to the present invention;
FIG. 2 is a hydrogen spectrum of 2, 4, 5-trifluorophenylacetic acid according to the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The technical scheme of the invention is further explained by the specific implementation mode in combination with the attached drawings.
The raw materials used are as follows: 1, 2, 4-trifluorobenzene, paraformaldehyde, sodium chloride, 98% sulfuric acid, 30% hydrochloric acid, acetic acid, metallic silver, metallic platinum, a graphite electrode, a carbon electrode, metallic aluminum, metallic magnesium, tetrabutylammonium iodide, tetraethylammonium chloride, N-dimethylformamide, acetonitrile, N-dimethylacetamide (DMAc), CO with a purity of 99.99%2A gas.
The equipment used was: constant current electrolysis instrument
Instrument model and analysis conditions of nuclear magnetic resonance: adopting a Bruker superconducting nuclear magnetic resonance spectrometer; the resonance frequency is 500 MHz; with CDCl3As solvent, TMS as internal standard.
Example 1
(1) Preparation of 2, 4, 5-trifluorobenzyl chloride: firstly, 100ml of 98 percent sulfuric acid is added into a 250ml four-mouth reaction bottle, after the temperature is reduced to 20 ℃, 21.3g of paraformaldehyde (equivalent to 0.71mol of monomer formaldehyde) and 44.8g of sodium chloride (0.766mol) are added, 50.8g (0.385mol) of 1, 2, 4-trifluorobenzene are added, and the heat preservation reaction is carried out for 10 hours at the temperature of 40 ℃; and pouring the reaction solution into ice water, separating an organic layer, washing the organic layer to be neutral, drying, distilling under reduced pressure and rectifying to obtain the 2, 4, 5-trifluorobenzyl chloride.
The weight of the obtained 2, 4, 5-trifluorobenzyl chloride is 58.8g, the content is 99.8 percent and the yield reaches 84.7 percent. And the obtained 2, 4, 5-trifluorobenzyl chloride is subjected to nuclear magnetic resonance treatment and detection, and the hydrogen spectrogram of the obtained 2, 45-trifluorobenzyl chloride is shown in figure 1. As can be seen from fig. 1:
1H-NMR(CDCl3，500Hz)δppm：4.56(s，2H)，6.95(m，1H)，7.26(m，1H)。
δ 4.56 ppm: benzyl position CH2The number of hydrogen in Cl is 2; 6.95 ppm: the number of hydrogen beside C3 carbon atom in benzene ring is 1; 7.26 ppm: the number of hydrogen beside C6 carbon atom in benzene ring is 1. Therefore, the peaks of impurities in the spectrogram are extremely few except the peaks of the solvent and TMS, which indicates that the product has very high purity and can be put into subsequent production without an additional purification process.
(2) Preparation of 2, 4, 5-trifluorophenylacetic acid: first, a 100ml sealed electrolytic cell was filled with CO2Adding tetrabutylammonium iodide 3.69g (10mmol), 2, 4, 5-trifluorobenzyl chloride 1.80g (10mmol) and N, N-dimethylformamide 70mL into the mixture, stirring to dissolve, and introducing CO2A gas; after 1 hour, the surface area is 10cm2The pure silver sheet is taken as a cathode, the magnesium ingot is taken as an anode, 0.5A of current is introduced, and the electrolysis is continuously carried out for 1.5 hours at the temperature of 30 ℃; then cooled to room temperature, added with 100mL (1M) of diluted hydrochloric acid, extracted twice with 70mL of ethyl acetate, and finally distilled and rectified after drying to obtain the trifluoro-phenylacetic acid.
The weight of the obtained trifluoro-phenylacetic acid is 1.87g, the content is 99.8 percent, and the yield reaches 98.2 percent. And performing nuclear magnetic resonance treatment detection on the obtained 2, 4, 5-trifluorophenylacetic acid, and obtaining a hydrogen spectrum of the 2, 4, 5-trifluorophenylacetic acid as shown in figure 2. As can be seen from fig. 2:
1H-NMR(CDCl3，500Hz)δ：3.74(s，2H)，7.01(m，1H)，7.30(m，1H)。
δ 3.74 ppm: benzyl position CH2The number of hydrogen in CO is 2; 7.01 ppm: the number of hydrogen beside C3 carbon atom in benzene ring is 1; 7.30 ppm: the number of hydrogen beside C6 carbon atom in benzene ring is 1. Therefore, the peaks of impurities in the spectrogram are extremely few except the peaks of the solvent and TMS, which indicates that the product has very high purity and can be put into subsequent production without an additional purification process.
Example 2
(1) 2, 4, 5-trifluorobenzyl chloride was obtained in the same manner as in example 1.
(2) Using a graphite electrode as a cathode instead of a pure silver plate and an aluminum ingot as an anode instead of a magnesium ingot, trifluoro phenylacetic acid was prepared under the same conditions and in the same operation as in example 1.
The detection shows that the weight of the obtained trifluoro-phenylacetic acid is 1.75g, the content is 99.2 percent, and the yield reaches 92.0 percent.
Example 3
(1) 2, 4, 5-trifluorobenzyl chloride was obtained in the same manner as in example 1.
(2) Using a pure platinum sheet as a cathode instead of a pure silver sheet and using platinum metal as an anode instead of a magnesium ingot, trifluorophenylacetic acid was prepared under the same conditions and in the same operation as in example 1.
The detection shows that the weight of the obtained trifluoro-phenylacetic acid is 1.85g, the content is 99.6 percent, and the yield reaches 97.3 percent.
Example 4
(1) 2, 4, 5-trifluorobenzyl chloride was obtained in the same manner as in example 1.
(2) Using a carbon electrode as a cathode instead of a pure silver plate and using platinum as an anode instead of a magnesium ingot, trifluorophenylacetic acid was prepared under the same conditions and in the same operation as in example 1.
The detection shows that the weight of the obtained trifluoro-phenylacetic acid is 1.80g, the content is 99.4 percent, and the yield reaches 94.8 percent.
Example 5
(1) 2, 4, 5-trifluorobenzyl chloride was obtained in the same manner as in example 1.
(2) Trifluorophenylacetic acid was obtained by substituting acetonitrile for N, N-dimethylformamide under the same conditions and in the same operation as in example 1.
The detection shows that the weight of the obtained trifluoro-phenylacetic acid is 1.62g, the content is 98.2 percent, and the yield reaches 85.2 percent.
Example 6
(1) 2, 4, 5-trifluorobenzyl chloride was obtained in the same manner as in example 1.
(2) Trifluorophenylacetic acid was obtained by substituting N, N-dimethylformamide with N, N-dimethylacetamide (DMAc) under the same conditions and in the same operation as in example 1.
The detection shows that the weight of the obtained trifluoro-phenylacetic acid is 1.74g, the content is 99.1 percent, and the yield reaches 91.8 percent.
Example 7
(1) 2, 4, 5-trifluorobenzyl chloride was obtained in the same manner as in example 1.
(2) Trifluorophenylacetic acid was prepared under the same conditions and in the same manner as in example 1, except that tetraethylammonium chloride (10mmol) was used in place of tetrabutylammonium iodide in an amount of 3.22 g.
The detection shows that the weight of the obtained trifluoro-phenylacetic acid is 1.68g, the content is 99.7 percent, and the yield reaches 87.8 percent.
Example 8
(1) Adding 34.65g of paraformaldehyde (equivalent to 1.155mol of monomer formaldehyde) and 45.03g of sodium chloride (0.77mol), then adding 50.8g (0.385mol) of 1, 2, 4-trifluorobenzene, and carrying out heat preservation reaction at the temperature of 30 ℃ for 12 hours; under the same conditions and in the same manner as in example 1, 2, 4, 5-trifluorobenzyl chloride was obtained.
(2) Trifluoroaniline was obtained in the same manner as in example 1 except that 2mmol of tetrabutylammonium iodide was used in place of 10mmol of tetrabutylammonium iodide, 2mmol of 2, 4, 5-trifluorobenzyl chloride was used in place of 10mmol of 2, 4, 5-trifluorobenzyl chloride, the current was applied at 10mA, the temperature of the electrolysis reaction was-50 ℃ and the time of the electrolysis reaction was 2 hours, acetic acid was used in place of dilute hydrochloric acid, and other conditions and operations were changed to those in example 1.
The detection shows that the weight of the obtained trifluoro-phenylacetic acid is 1.60g, the content is 98.1 percent, and the yield reaches 85.1 percent.
Example 9
(1) Adding 11.55g of paraformaldehyde (equivalent to 0.385mol of monomer formaldehyde) and 22.52g of sodium chloride (0.385mol), then adding 50.8g (0.385mol) of 1, 2, 4-trifluorobenzene, and carrying out heat preservation reaction at the temperature of 50 ℃ for 8 hours; under the same conditions and in the same manner as in example 1, 2, 4, 5-trifluorobenzyl chloride was obtained.
(2) Trifluoroaniline was obtained in the same manner as in example 1 except that 50mmol of tetrabutylammonium iodide was used in place of 10mmol of tetrabutylammonium iodide and 50mmol of 2, 4, 5-trifluorobenzyl chloride was used in place of 10mmol of 2, 4, 5-trifluorobenzyl chloride, a current was applied thereto at 50A, the temperature of the electrolysis reaction was 100 ℃ and the time of the electrolysis reaction was 1 hour.
The detection shows that the weight of the obtained trifluoro-phenylacetic acid is 1.82g, the content is 99.3 percent, and the yield reaches 97.5 percent.
According to the invention, the reaction condition is mild, the process is simple, the operability is strong, the production safety is good, and the environment friendliness is good; the raw materials are cheap and easy to obtain, and the cost is low; and the product has high purity, high yield and stable quality, completely meets the use requirement of being used as a drug intermediate, and is suitable for industrial production.
The above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (9)
1. The preparation method of 2, 4, 5-trifluoro-phenylacetic acid is characterized by comprising the following steps:
the method comprises the following specific steps:
(1) firstly, adding a chlorinating agent and paraformaldehyde into a container, then adding 1, 2, 4-trifluorobenzene, and carrying out heat preservation reaction at the temperature of 30-50 ℃, wherein the molar ratio of the 1, 2, 4-trifluorobenzene to the chlorinating agent to the paraformaldehyde is 1 (1-2) to 1-3; pouring the reaction solution into ice water, separating an organic layer, washing with water, drying and purifying to obtain 2, 4, 5-trifluorobenzyl chloride;
(2) firstly, filling CO in a sealed electrolytic cell2Adding the electrolyte solution and the 2, 4, 5-trifluorobenzyl chloride obtained in the step (1) into the gas, stirring the mixture until the electrolyte solution and the 2, 4, 5-trifluorobenzyl chloride are dissolved, and continuously introducing CO into the mixture2A gas; after 1 hour, taking any one of an inert metal or platinum mesh electrode, a carbon electrode, a graphite electrode and a glassy carbon electrode as a cathode, taking an active metal or metal platinum as an anode, and introducing 1-5000 mA/cm2Continuously electrolyzing the current on the surface area of the cathode at the temperature of-50-100 ℃ to obtain a 2, 4, 5-trifluoro-phenylacetate solution; then obtaining the 2, 4, 5-trifluoro-phenylacetic acid after acidification and purification.
2. The method of claim 1, wherein the inert metal in step (2) is selected from the group consisting of copper, nickel, platinum, tungsten, silver, and titanium.
3. The method for preparing 2, 4, 5-trifluorophenylacetic acid according to claim 1, wherein the active metal in step (2) is zinc, aluminum, magnesium, manganese, or iron.
4. The method according to claim 1, wherein the electrolyte solution in step (2) is a solution prepared from N, N-dimethylformamide and any one electrolyte selected from tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium perchlorate, tetrabutyltetrafluoroborate, tetrabutylammonium hexafluorophosphate, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetraethylammonium perchlorate and tetraethyltetrafluoroborate.
5. The method according to claim 1, wherein the electrolyte solution in step (2) is a solution prepared from acetonitrile and any one electrolyte selected from tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium perchlorate, tetrabutyltetrafluoroborate, tetrabutylammonium hexafluorophosphate, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetraethylammonium perchlorate, and tetraethyltetrafluoroborate.
6. The method according to claim 1, wherein the electrolyte solution in step (2) is a solution prepared from N, N-dimethylacetamide and any one electrolyte selected from tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium perchlorate, tetrabutyltetrafluoroborate, tetrabutylammonium hexafluorophosphate, tetraethylammonium chloride, tetraethylammonium bromide, tetraethylammonium iodide, tetraethylammonium perchlorate, and tetraethyltetrafluoroborate.
7. The method of claim 1, wherein the electrolyte solution of step (2) has a concentration of 0.01-5M; the concentration of the 2, 4, 5-trifluorobenzyl chloride in the electrolyte solution is 0.01M-5M.
8. The method for preparing 2, 4, 5-trifluorophenylacetic acid according to claim 1, wherein the acid used in the acidification in step (2) is selected from any one of hydrochloric acid, sulfuric acid, phosphoric acid and acetic acid.
9. The method for preparing 2, 4, 5-trifluorophenylacetic acid according to claim 1, wherein the purification in steps (1) and (2) is performed by distillation followed by rectification.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4686018A (en) * | 1985-09-05 | 1987-08-11 | Societe Nationale Des Poudres Et Explosifs | Organic electrolysis cell with sacrificial electrode |
| CN1749232A (en) * | 2005-09-29 | 2006-03-22 | 上海康鹏化学有限公司 | Process for preparing 2,4,5-triflorophenylacetic acid |
| CN101260532A (en) * | 2008-04-15 | 2008-09-10 | 华东师范大学 | One-room type electrochemical synthesis method for alpha-phenylacetpropionic acid |
| CN101659611A (en) * | 2009-09-28 | 2010-03-03 | 浙江永太科技股份有限公司 | Method for preparing 2, 4, 5-trifluoro-phenylacetic-acid |
| CN102659634A (en) * | 2012-05-15 | 2012-09-12 | 华东师范大学 | Synthetic method for 2-(N-4-fluorobenzyl) methoxy-acetyl-amino methyl isobutyrate |
-
2021
- 2021-04-01 CN CN202110353845.9A patent/CN113278996A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4686018A (en) * | 1985-09-05 | 1987-08-11 | Societe Nationale Des Poudres Et Explosifs | Organic electrolysis cell with sacrificial electrode |
| CN1749232A (en) * | 2005-09-29 | 2006-03-22 | 上海康鹏化学有限公司 | Process for preparing 2,4,5-triflorophenylacetic acid |
| CN101260532A (en) * | 2008-04-15 | 2008-09-10 | 华东师范大学 | One-room type electrochemical synthesis method for alpha-phenylacetpropionic acid |
| CN101659611A (en) * | 2009-09-28 | 2010-03-03 | 浙江永太科技股份有限公司 | Method for preparing 2, 4, 5-trifluoro-phenylacetic-acid |
| CN102659634A (en) * | 2012-05-15 | 2012-09-12 | 华东师范大学 | Synthetic method for 2-(N-4-fluorobenzyl) methoxy-acetyl-amino methyl isobutyrate |
Non-Patent Citations (3)
| Title |
|---|
| ABDIRISAK A. ISSE等: "Electrocatalytic carboxylation of benzyl chlorides at silver cathodes in acetonitrile", 《CHEM. COMMUN.》, pages 2798 - 2799 * |
| 何人宝等: "2, 4, 5-三氟苯乙酸的合成", 化工生产与技术, no. 03, pages 4 - 6 * |
| 杜敬星等: "采用牺牲阳极法电解还原氯苄制苯乙酸", 《化学世界》, no. 12, pages 535 - 538 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115246762A (en) * | 2022-08-25 | 2022-10-28 | 上海朴颐化学科技有限公司 | Preparation method of 2,4,5-trifluorophenylacetic acid |
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