CN113979854A - Method for electrochemically preparing 2-phenylpropionic acid - Google Patents
Method for electrochemically preparing 2-phenylpropionic acid Download PDFInfo
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- phenylpropionic acid
- phenylchloroethane
- dimethyl carbonate
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- YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 title claims abstract description 29
- 238000006243 chemical reaction Methods 0.000 claims abstract description 34
- GTLWADFFABIGAE-UHFFFAOYSA-N 1-chloroethylbenzene Chemical compound CC(Cl)C1=CC=CC=C1 GTLWADFFABIGAE-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000003487 electrochemical reaction Methods 0.000 claims abstract description 24
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 21
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000002994 raw material Substances 0.000 claims abstract description 15
- XLLPLDFNCXWUOT-UHFFFAOYSA-N (2-methylphenyl) propanoate Chemical compound CCC(=O)OC1=CC=CC=C1C XLLPLDFNCXWUOT-UHFFFAOYSA-N 0.000 claims abstract description 12
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000011777 magnesium Substances 0.000 claims abstract description 12
- 229910052749 magnesium Inorganic materials 0.000 claims abstract description 12
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 12
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 12
- 238000002156 mixing Methods 0.000 claims abstract description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 150000003242 quaternary ammonium salts Chemical group 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000007810 chemical reaction solvent Substances 0.000 abstract description 3
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 238000005406 washing Methods 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 229960002373 loxoprofen Drugs 0.000 description 6
- YMBXTVYHTMGZDW-UHFFFAOYSA-N loxoprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1CC1C(=O)CCC1 YMBXTVYHTMGZDW-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 230000001276 controlling effect Effects 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000012295 chemical reaction liquid Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 3
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000012445 acidic reagent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 238000005034 decoration Methods 0.000 description 2
- CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 description 2
- DZIQUZJSNSZOCH-UHFFFAOYSA-N methyl 2-phenylpropanoate Chemical compound COC(=O)C(C)C1=CC=CC=C1 DZIQUZJSNSZOCH-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- CHQVQXZFZHACQQ-UHFFFAOYSA-M benzyl(triethyl)azanium;bromide Chemical compound [Br-].CC[N+](CC)(CC)CC1=CC=CC=C1 CHQVQXZFZHACQQ-UHFFFAOYSA-M 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000012022 methylating agents Substances 0.000 description 1
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000002341 toxic gas Substances 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0239—Quaternary ammonium compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/30—Catalysts, in general, characterised by their form or physical properties characterised by their physical properties
- B01J35/33—Electric or magnetic properties
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
- C07C51/44—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation by distillation
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/01—Products
- C25B3/07—Oxygen containing compounds
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Materials Engineering (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Electrochemistry (AREA)
- Metallurgy (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Electrolytic Production Of Non-Metals, Compounds, Apparatuses Therefor (AREA)
Abstract
The invention provides a method for electrochemically preparing 2-phenylpropionic acid, and belongs to the technical field of organic synthesis. The method comprises the following steps: (1) in the presence of a phase transfer catalyst, 1-phenylchloroethane and dimethyl carbonate are used as reaction raw materials, magnesium is used as a consumption electrode, and an electrochemical reaction is carried out to obtain 2-methyl phenylpropionate; (2) and mixing the 2-methyl phenylpropionate with inorganic acid, and carrying out hydrolysis reaction to obtain the 2-phenylpropionic acid. The invention takes 1-phenylchloroethane and dimethyl carbonate as reaction raw materials, has extremely low toxicity, and the dimethyl carbonate can be used as the reaction raw materials and also as a reaction solvent, thereby avoiding the use of other organic solvents and being more environment-friendly. The invention adopts an electrochemical reaction mode, has mild reaction conditions, avoids high-temperature and high-pressure reaction conditions, and has high industrial application value. Meanwhile, the 2-phenylpropionic acid obtained by the method provided by the invention has higher yield and purity.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for electrochemically preparing 2-phenylpropionic acid.
Background
The 2-phenylpropionic acid is a key intermediate for synthesizing the loxoprofen sodium. The loxoprofen sodium is a nonsteroidal anti-inflammatory analgesic drug which is developed and marketed by Sanshu corporation in 1986, has strong analgesic effect and small side effect on digestive tract. Since the medicine is on the market, the medicine is prepared into various types of preparations, and the medicine is gradually taken as the first-line medicine in the market of heat-clearing and pain-relieving medicines, and the market capacity is getting larger and larger.
2-Phenylpropionic acid of the formula
2-phenylpropionic acid is used as a key intermediate of loxoprofen sodium, and the quality and the price of the loxoprofen sodium have direct influence on the loxoprofen sodium. How to better synthesize the 2-phenylpropionic acid is the key for solving the problem of quality and quantity conservation of the loxoprofen sodium for market supply.
The synthesis process of the 2-phenylpropionic acid disclosed in the prior art is mainly as follows:
the first method uses benzyl cyanide as raw material, dimethyl carbonate as solvent and reaction raw material, potassium carbonate as catalyst, and reacts under high temperature and high pressure (180 deg.C, over 20 kg pressure) to produce 2-phenyl cyanide, which is hydrolyzed by sodium hydroxide, and then acid-regulated to pH value to obtain 2-phenyl propionic acid (Organic Syntheses, col. Vol.10, p.640 (2004); CN 200910052372). However, this method requires high temperature and high pressure, and the reaction conditions are severe, and it is also difficult to industrially implement the method. The prior art is improved with respect to the high temperature and high pressure reaction conditions used. One improvement is the use of dimethyl sulfate as the methylating agent instead of dimethyl carbonate, which, although it is possible to carry out the reaction at atmospheric pressure, is a highly toxic substance and requires an excess.
In the second method, styrene is used as a raw material and is subjected to carbonylation reaction with carbon monoxide under the catalysis of heavy metal to obtain 2-phenylpropionic acid (React.Kinet.Catal.Lett.,77,227,2002). However, this method uses toxic gases of carbon monoxide, which can cause damage to the human body.
Disclosure of Invention
In view of the above, the present invention aims to provide a method for electrochemically preparing 2-phenylpropionic acid. The method provided by the invention is green and environment-friendly, and avoids the use of virulent raw materials.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a method for electrochemically preparing 2-phenylpropionic acid, which comprises the following steps:
(1) in the presence of a phase transfer catalyst, 1-phenylchloroethane and dimethyl carbonate are used as reaction raw materials, magnesium is used as a consumption electrode, and an electrochemical reaction is carried out to obtain 2-methyl phenylpropionate;
(2) and mixing the 2-methyl phenylpropionate with inorganic acid, and carrying out hydrolysis reaction to obtain the 2-phenylpropionic acid.
Preferably, the mass ratio of the 1-phenylchloroethane to the dimethyl carbonate is 1: 1-6.
Preferably, the phase transfer catalyst is a quaternary ammonium salt.
Preferably, the molar ratio of the phase transfer catalyst to the 1-phenyl chloroethane is 0.05-0.2: 1.
Preferably, the current of the electrochemical reaction is direct current, and the current of the electrochemical reaction is 10 mA-2A.
Preferably, the temperature of the electrochemical reaction is 10-40 ℃, and the time is 3-8 h.
Preferably, the molar weight ratio of the magnesium to the 1-phenyl chloroethane is more than or equal to 1.
Preferably, the inorganic acid in the step (2) is hydrochloric acid and/or sulfuric acid, and the molar weight ratio of the inorganic acid to 1-phenyl chloroethane is more than or equal to 1.
Preferably, the temperature of the hydrolysis reaction is 60-80 ℃.
Preferably, the hydrolysis reaction further comprises distilling the hydrolysis reaction solution.
The invention provides a method for electrochemically preparing 2-phenylpropionic acid, which comprises the following steps: (1) in the presence of a phase transfer catalyst, 1-phenylchloroethane and dimethyl carbonate are used as reaction raw materials, magnesium is used as a consumption electrode, and an electrochemical reaction is carried out to obtain 2-methyl phenylpropionate; (2) and mixing the 2-methyl phenylpropionate with inorganic acid, and carrying out hydrolysis reaction to obtain the 2-phenylpropionic acid. The invention takes 1-phenylchloroethane and dimethyl carbonate as reaction raw materials, has extremely low toxicity, and the dimethyl carbonate can be used as the reaction raw materials and also as a reaction solvent, thereby avoiding the use of other organic solvents and being more environment-friendly. The invention adopts an electrochemical reaction mode, has mild reaction conditions, avoids high-temperature and high-pressure reaction conditions, and has high industrial application value. Meanwhile, the 2-phenylpropionic acid obtained by the method provided by the invention has higher yield and purity, and the example results show that the molar yield of the 2-phenylpropionic acid obtained by the method is 92% and the HPLC purity is more than 99%.
Detailed Description
The invention provides a method for electrochemically preparing 2-phenylpropionic acid, which comprises the following steps:
(1) in the presence of a phase transfer catalyst, 1-phenylchloroethane and dimethyl carbonate are used as reaction raw materials, magnesium is used as a consumption electrode, and an electrochemical reaction is carried out to obtain 2-methyl phenylpropionate;
(2) and mixing the 2-methyl phenylpropionate with inorganic acid, and carrying out hydrolysis reaction to obtain the 2-phenylpropionic acid.
In the presence of a phase transfer catalyst, 1-phenylchloroethane and dimethyl carbonate are used as reaction raw materials, magnesium is used as a consumption electrode, and an electrochemical reaction is carried out to obtain the 2-methyl phenylpropionate. In the invention, the phase transfer catalyst is preferably quaternary ammonium salt, and more preferably one or more of tetrabutylammonium bromide, benzyltriethylammonium bromide, tetrabutylammonium chloride and benzyltriethylammonium chloride.
In the present invention, the dimethyl carbonate serves as both a reaction raw material and a reaction solvent. In the present invention, the mass ratio of the 1-phenylchloroethane to the dimethyl carbonate is preferably 1:1 to 6, more preferably 1:2 to 5, and even more preferably 1:3 to 4.
In the present invention, the molar ratio of the phase transfer catalyst to 1-phenylchloroethane is preferably 0.05 to 0.2:1, more preferably 0.1 to 0.15: 1.
In the invention, the magnesium is used as a consumable electrode, and the ratio of the molar weight of the magnesium to the molar weight of the 1-phenyl chloroethane is preferably not less than 1, and preferably 1-2. In the present invention, methyl magnesium chloride is formed on the consumable electrode during the electrochemical reaction, and it is preferable to remove methyl magnesium chloride adhering to the surface of the consumable electrode by washing with dilute hydrochloric acid water.
In the present invention, in the electrochemical reaction, the anode is preferably made of carbon; in the present invention, the anode is further preferably a carbon rod.
In the present invention, the current of the electrochemical reaction is preferably direct current, and the current of the electrochemical reaction is preferably 10mA to 2A, more preferably 0.1 to 1A, and even more preferably 0.3 to 0.6A.
In the invention, the temperature of the electrochemical reaction is preferably 10-40 ℃, and more preferably 20-30 ℃; the time is preferably 3 to 8 hours, and more preferably 4 to 6 hours. In the present invention, the hydrolysis reaction is preferably carried out under normal pressure conditions.
After the electrochemical reaction, the present invention preferably performs a post-treatment on the obtained electrochemical reaction solution, and the post-treatment preferably comprises the following steps:
adjusting the pH value of the electrochemical reaction solution to 5-7, preferably 6, and layering to obtain an organic phase;
the organic phase was washed and used directly in the next hydrolysis reaction.
In the invention, the acidic reagent used for adjusting the pH value of the electrochemical reaction liquid is preferably hydrochloric acid and/or sulfuric acid, and the mass concentration of the acidic reagent is preferably 5-20%, and more preferably 10-15%.
In the invention, the washing mode is preferably water washing, and the volume of water in the water washing is preferably 0.5-2 times, more preferably 1-1.5 times of the volume of the organic phase; the frequency of the water washing is preferably 2-3 times, and magnesium salts in an organic phase and a byproduct methanol of an electrochemical reaction are removed by the water washing.
The 2-phenylpropionic acid methyl ester is mixed with inorganic acid to carry out hydrolysis reaction, and the 2-phenylpropionic acid is obtained. In the present invention, the inorganic acid is preferably hydrochloric acid and/or sulfuric acid; the mass concentration of the hydrochloric acid is preferably 10-30 wt%, and more preferably 20-25 wt%; in the present invention, the molar weight ratio of the acid to 1-phenylchloroethane is preferably not less than 1, and more preferably 1 to 2.
In the invention, the temperature of the hydrolysis reaction is preferably 60-80 ℃, and more preferably 70 ℃. In the present invention, the hydrolysis reaction is preferably carried out under reflux. In the present invention, the hydrolysis reaction further comprises distilling the hydrolysis reaction solution to remove methanol remaining as a byproduct in the methyl 2-phenylpropionate.
After the hydrolysis reaction, the invention preferably carries out post-treatment on the obtained hydrolysis reaction liquid; in the present invention, the post-treatment preferably comprises the steps of:
cooling the hydrolysis reaction liquid to room temperature, and layering to obtain an organic phase;
and washing, removing the solvent and distilling the organic phase in sequence to obtain a pure 2-phenylpropionic acid product.
In the present invention, the washing is preferably water washing; the pH value of the organic phase obtained after washing is preferably 4-6. According to the invention, the residual inorganic acid in the organic phase is removed by the water washing.
In the invention, the synthetic route of the 2-phenylpropionic acid is shown as a formula A.
The following examples are provided to illustrate the electrochemical preparation of 2-phenylpropionic acid according to the present invention, but they should not be construed as limiting the scope of the present invention.
Example 1
Placing 150 g of 1-phenylchloroethane and 630 g of dimethyl carbonate into an electrolytic cell provided with a magnesium electrode and a carbon electrode, adding 17.5 g of tetrabutylammonium bromide, controlling the temperature of the electrolytic cell at 35 ℃, starting a direct current power supply, adjusting the current value to be 100-200 mA, continuously carrying out electrolytic reaction for 3 hours, and controlling 1-phenylchloroethane to be completely converted in HPLC;
transferring the electrolyte into a reaction bottle, cooling the reaction solution to room temperature, adding 500 ml of 10% hydrochloric acid aqueous solution, stirring for 10 minutes, and standing for layering; the upper organic layer was washed three more times with 500 ml of water each;
placing the organic layer in a reaction bottle, adding 100 g of 10% hydrochloric acid aqueous solution, and heating to 60-80 ℃ for reaction; in the period, the azeotrope of methanol, dimethyl carbonate and water is continuously separated in the early stage until the reaction HPLC detection reaction is complete;
cooling the reaction solution to room temperature, standing and layering, washing the organic layer with 200 ml of water for three times respectively until the pH value of the reaction solution is 4;
the dimethyl carbonate is distilled out of the obtained organic layer at normal pressure, and then high vacuum distillation is carried out, and finally 147 g of 2-phenylpropionic acid is obtained, the molar yield is 92%, and the HPLC purity is more than 99%.
1H NMR(400MHz,CDCl3,TMS)δ:1.54(d,3H,J＝7.2,CH3),3.77(q,1H,J＝7.2,CH),7.32-7.35(m,4H,Ph),11.6-11.8(br s,1H,OH)；mass spectrum(70eV)m/z(relative intensity):150(M+,29),106(11),105(100),104(5),103(12),79(14),78(6),77(17),51(7).
Example 2
The feeding amount, the reaction temperature and the operation sequence of the embodiment 1 are the same, the current value is changed to be 500-600 milliamperes, the reaction is obviously accelerated, and the reaction can be completed within 2 hours; the subsequent reaction and workup were as in example 1, giving 132 g of 2-phenylpropionic acid with an HPLC purity of more than 99%.
1H NMR(400MHz,CDCl3,TMS)δ:1.54(d,3H,J＝7.2,CH3),3.77(q,1H,J＝7.2,CH),7.32-7.35(m,4H,Ph),11.6-11.8(br s,1H,OH)；mass spectrum(70eV)m/z(relative intensity):150(M+,29),106(11),105(100),104(5),103(12),79(14),78(6),77(17),51(7).
Example 3
Placing 150 g of 1-phenylchloroethane and 1050 g of dimethyl carbonate into an electrolytic cell provided with a magnesium electrode and a carbon electrode, adding 17.5 g of tetrabutylammonium bromide, controlling the temperature of the electrolytic cell to be 40 ℃, starting a direct-current power supply, adjusting the current value to be between 400 and 500 milliamperes, continuously carrying out electrolytic reaction for 3 hours, and controlling 1-phenylchloroethane to be completely converted in HPLC; the subsequent reaction was as in example 1, yielding 152 g of 2-phenylpropionic acid with an HPLC purity of greater than 99%.
1H NMR(400MHz,CDCl3,TMS)δ:1.54(d,3H,J＝7.2,CH3),3.77(q,1H,J＝7.2,CH),7.32-7.35(m,4H,Ph),11.6-11.8(br s,1H,OH)；mass spectrum(70eV)m/z(relative intensity):150(M+,29),106(11),105(100),104(5),103(12),79(14),78(6),77(17),51(7).
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (10)
1. A method of electrochemically preparing 2-phenylpropionic acid, comprising the steps of:
(1) in the presence of a phase transfer catalyst, 1-phenylchloroethane and dimethyl carbonate are used as reaction raw materials, magnesium is used as a consumption electrode, and an electrochemical reaction is carried out to obtain 2-methyl phenylpropionate;
(2) and mixing the 2-methyl phenylpropionate with inorganic acid, and carrying out hydrolysis reaction to obtain the 2-phenylpropionic acid.
2. The method according to claim 1, wherein the mass ratio of the 1-phenylchloroethane to the dimethyl carbonate is 1: 1-6.
3. The method of claim 1, wherein the phase transfer catalyst is a quaternary ammonium salt.
4. The process according to claim 1 or 3, wherein the molar ratio of the phase transfer catalyst to 1-phenylchloroethane is from 0.05 to 0.2: 1.
5. The method according to claim 1, wherein the current of the electrochemical reaction is direct current, and the current of the electrochemical reaction is 10 mA-2A.
6. The method according to claim 1, wherein the temperature of the electrochemical reaction is 10-40 ℃ and the time is 3-8 h.
7. The method according to claim 1, wherein the molar weight ratio of magnesium to 1-phenylchloroethane is not less than 1.
8. The method according to claim 1, wherein the inorganic acid in the step (2) is hydrochloric acid and/or sulfuric acid, and the molar weight ratio of the inorganic acid to 1-phenyl chloroethane is more than or equal to 1.
9. The method according to claim 1 or 8, wherein the temperature of the hydrolysis reaction is 60 to 80 ℃.
10. The method of claim 9, wherein the hydrolysis reaction further comprises distilling the hydrolysis reaction solution.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107573230A (en) * | 2017-08-11 | 2018-01-12 | 重庆沃肯精细化工有限公司 | A kind of synthetic method to bromomethyl benzenpropanoic acid |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107573230A (en) * | 2017-08-11 | 2018-01-12 | 重庆沃肯精细化工有限公司 | A kind of synthetic method to bromomethyl benzenpropanoic acid |
Non-Patent Citations (6)
| Title |
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| ABDIRISAK A. ISSE等: "Electrocatalytic carboxylation of benzyl chlorides at silver cathodes in acetonitrile", 《CHEMICAL COMMUNICATIONS (CAMBRIDGE, UNITED KINGDOM)》 * |
| DENG-TAO YANG等: "Direct Electrochemical Carboxylation of Benzylic C−N Bonds with Carbon Dioxide", 《ACS CATALYSIS》 * |
| HUI WANG等: "Amino-functionalized MIL Type Metal Organic Frameworks as Heterogeneous Catalysts for Asymmetric Electrocarboxylation of (1-chloroethyl)benzene with CO2", 《INTERNATIONAL JOURNAL OF ELECTROCHEMICAL SCIENCE》 * |
| LA-XIA WU等: "Nickel-catalyzed electrocarboxylation of allylic halides with CO2", 《NEW JOURNAL OF CHEMISTRY》 * |
| NATHAN CORBIN等: "Suppressing carboxylate nucleophilicity with inorganic salts enables selective electrocarboxylation without sacrificial anodes", 《CHEMICAL SCIENCE》 * |
| SILVIA MENA等: "Sustainable and efficient electrosynthesis of naproxen using carbon dioxide and ionic liquids", 《CHEMOSPHERE》 * |
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