CN113979854A - Method for electrochemically preparing 2-phenylpropionic acid - Google Patents

Method for electrochemically preparing 2-phenylpropionic acid Download PDF

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CN113979854A
CN113979854A CN202111345098.0A CN202111345098A CN113979854A CN 113979854 A CN113979854 A CN 113979854A CN 202111345098 A CN202111345098 A CN 202111345098A CN 113979854 A CN113979854 A CN 113979854A
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reaction
phenylpropionic acid
phenylchloroethane
dimethyl carbonate
acid
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CN113979854B (en
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胡开波
汪令节
杨冰
吴伟
朱甄珍
魏孝强
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Chongqing Woken New Material Technology Co ltd
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/09Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235Nitrogen containing compounds
    • B01J31/0239Quaternary ammonium compounds
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J35/00Catalysts, in general, characterised by their form or physical properties
    • B01J35/30Catalysts, in general, characterised by their form or physical properties characterised by their physical properties
    • B01J35/33Electric or magnetic properties
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42Separation; Purification; Stabilisation; Use of additives
    • C07C51/43Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
    • C07C51/44Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation by distillation
    • CCHEMISTRY; METALLURGY
    • C25ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25BELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
    • C25B3/00Electrolytic production of organic compounds
    • C25B3/01Products
    • C25B3/07Oxygen containing compounds

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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

Method for electrochemically preparing 2-phenylpropionic acid
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.
Figure BDA0003353753160000011
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:
Figure BDA0003353753160000012
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.
Figure BDA0003353753160000051
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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Citations (1)

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Patent Citations (1)

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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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