Method for synthesizing ibuprofen and deuterated ibuprofen based on electrochemical strategy

Abstract

The invention provides a novel method for synthesizing ibuprofen and deuterated ibuprofen based on an electrochemical strategy, and relates to the technical field of medicine synthesis. The method comprises the following steps: carrying out Friedel-Crafts acylation reaction on isobutylbenzene and acetyl chloride to obtain 4-isobutyl acetophenone; then, water is used as a hydrogen source, and the 4-isobutyl acetophenone is converted into 1-(4-isobutyl phenyl) ethanol through electrochemical hydrogenation; then, carrying out electrochemical deoxidation halogenation reaction on the 1-(4-isobutylphenyl) ethanol and hydrogen halide to obtain a corresponding halogenated intermediate; finally, the halogenated intermediate and carbon dioxide are subjected to an electro-carboxylation reaction, and the target product ibuprofen can be prepared. In the electrochemical hydrogenation step of 4-isobutyl acetophenone, if deuterium water is used for replacing common water, novel deuterated ibuprofen can be finally obtained, and enhanced drugs are expected to be obtained. The method for electrocatalytic synthesis of ibuprofen and deuterated ibuprofen provided by the invention is a novel mild and efficient method taking water / heavy water as a hydrogen / deuterium source.

Description

Technical Field

[0001] This invention relates to the field of drug synthesis technology, and in particular to a method for synthesizing ibuprofen and deuterated ibuprofen via electrochemical hydrogenation, electrochemical deoxyhalogenation, and electrocarboxylation reactions. Background Technology

[0002] Ibuprofen is a highly effective, safe, best-selling, and inexpensive nonsteroidal anti-inflammatory drug (NSAID) widely used clinically for pain relief, anti-inflammation, and fever reduction. It exerts its analgesic and anti-inflammatory effects by inhibiting cyclooxygenase levels in the body, thus reducing prostaglandin synthesis; it also exerts its antipyretic effect through the hypothalamic thermoregulatory center. As a classic small-molecule organic drug, it was invented in the 1960s by Stewart Adams of Boots Pharmaceuticals in the UK and marketed under the trademark Brufen, and has been used for over half a century. It possesses stable and broad-spectrum efficacy, is listed in the World Health Organization's Essential Medicines List, and is one of the essential drugs in basic public health systems. Currently, its global annual production exceeds tens of thousands of tons. As the first over-the-counter drug announced by the State Drug Administration, it can usually be purchased directly from the market (Su Huaide, my country's first over-the-counter drug—Ibuprofen, China Medical Guide, 2001, 3, 233–234). It is worth noting that ibuprofen is the only fever reducer for children jointly recommended by the World Health Organization and the U.S. Food and Drug Administration, and is internationally recognized as a first-line anti-inflammatory drug for children. Ibuprofen can also relieve symptoms of COVID-19 infection and has a certain therapeutic effect on COVID-19 infection.

[0003] Ibuprofen comes in various dosage forms, has significant efficacy, few side effects, and a huge market demand. Currently, it is mainly obtained through chemical synthesis, and optimizing and upgrading its synthesis and purification processes is a hot topic in the pharmaceutical field.

[0004] Ibuprofen's chemical name is 2-(4-isobutylphenyl)propionic acid, CAS number 15687-27-1. It contains the isobutylbenzene substructure and can be synthesized in various ways, but primarily using the industrially abundant chemical isobutylbenzene (…). Figure 1 ) or its derivatives ( Figure 2Using Ibuprofen as a starting material (Yu Fengli, Zhao Yuliang, Jin Zilin, Progress in the Green Synthesis of Ibuprofen, Organic Chemistry, 2003, 23, 1198–1204.; M.-W. Ha, S.-M. Paek, Recent Advances in the Synthesis of Ibuprofen and Naproxen, Molecules 2021, 26, 4792.; RA Kjonaas, PE Williams, DACounce, LR Crawley, Synthesis of Ibuprofen in the Introductory Organic Laboratory, J. Chem. Educ. 2011, 88, 825–828.; Q. Li, M. Liu, Y. Zhang, L. Wan, F.-E. Chen, Scalable and Integrated Four-step Continuous-Flow Synthesis of Ibuprofen Using a Zinc-Catalyzed 1,2-Aryl Migration Strategy, ACSSustainable Chem.). Eng. 2024, 12, 8512–8520.).

[0005] Boots' earliest method for synthesizing ibuprofen is considered classic and practical. It uses isobutylbenzene, a bulk chemical, as a raw material. Through Friedel-Crafts acylation, 4-isobutylacetophenone is obtained, followed by a strong-base catalyzed Darsner condensation reaction to generate 1-(4-isobutylbenzene)propionaldehyde. Finally, it is directly oxidized (or through oximeization and hydrolysis) to obtain ibuprofen. This is the Boots method (see [link to documentation]). Figure 1 ).

[0006] Boots, in collaboration with Hoechst-Celanese, improved the aforementioned process, proposing a three-step reaction using isobutylbenzene as a raw material to produce ibuprofen: Friedel-Crafts acylation, reduction, and palladium-catalyzed carbonylation. This is known as the BHC method (see [link to BHC process]). Figure 1 ).

[0007] The above method has been used by Xinhua Pharmaceutical Factory and Changzhou Pharmaceutical Factory in my country for the mass production of ibuprofen.

[0008] Once a chemical reducing agent is selected, its reducing power is usually fixed and non-renewable and non-recyclable. Furthermore, its use often generates harmful solid waste, making it difficult to meet industry standards for green chemistry. Electrons, on the other hand, are clean, inexpensive, and renewable reducing agents. By simply adjusting the applied voltage, electrons can be endowed with different and continuously varying reducing powers. In recent years, electrochemical strategies have been successfully applied to various organic reactions, such as reduction, oxidation, coupling, halogenation, deuteration, and carboxylation, showing significant advantages over traditional transition metal catalysis. Therefore, organic electrosynthesis has received considerable attention from academia and industry and has achieved rapid development.

[0009] Replacing one or more hydrogen atoms on the carbon atoms of organic molecules with deuterium atoms creates deuterated compounds with higher economic value, which have wide applications in organic chemistry, medicinal chemistry, materials science, proteomics, and other fields. Drug metabolism in the human body often involves the activation and breaking of CH bonds. Replacing hydrogen atoms with deuterium at the active site of a drug can prolong its half-life, improve pharmacokinetics, reduce the frequency and dosage of medication for patients, and even reduce the toxic side effects of the parent drug, while maintaining its basic pharmacological activity. Therefore, deuteration of marketed drug molecules has become an important new drug design strategy. Currently, several deuterated drugs (also known as heavy hydrogen drugs or heavy drugs) have entered clinical trials both domestically and internationally.

[0010] To date, there is a lack of green synthetic methods for preparing (deuterated) ibuprofen based on electrochemical hydrogenation, electrocatalytic deoxyhalogenation, and electrocarboxylation strategies. Summary of the Invention

[0011] The purpose of this invention is to provide a method for the electrochemical synthesis of ibuprofen and deuterated ibuprofen. This invention is simple to operate, low in cost, and low in toxicity.

[0012] To address the above problems, the present invention proposes the following technical solution.

[0013] A method for electrocatalytic synthesis of (deuterated) ibuprofen, comprising the following steps.

[0014] S1. Isobutylbenzene reacts with acetyl chloride via a Friedel-Crafts acylation reaction to yield 4-isobutylacetophenone;

[0015] S2,4-Isobutylacetophenone undergoes electrochemical hydrogenation, with water as the hydrogen source, and the carbonyl group is reduced to 1-(4-isobutylphenyl)ethanol;

[0016] S3. Using hydrogen halide as the halogen source, 1-(4-isobutylphenyl)ethanol undergoes an electrocatalytic deoxyhalogenation reaction under the promotion of acid to obtain the corresponding halogenated intermediate.

[0017] S4. Under the action of an organic base, the product of S3 undergoes an electrocarboxylation reaction to obtain ibuprofen.

[0018] If deuterated water is used instead of ordinary water, and the S2, S3 and S4 processes are performed sequentially, deuterated ibuprofen will be obtained.

[0019] The structural formula of the 1-(4-isobutylphenyl)ethanol is:

[0020] ;

[0021] The structural formula of the halogenated intermediate is:

[0022] ;

[0023] The structural formula of the deuterated ibuprofen is:

[0024] ;

[0025] A further technical solution is as follows: In step S1 of the electrocatalytic synthesis of ibuprofen, the specific operation is as follows: dichloromethane, isobutylbenzene, and anhydrous aluminum trichloride are added to a flask, and a dichloromethane solution of acetyl chloride is added dropwise. After the reaction is completed, the reaction is quenched, and the product is extracted and purified to obtain 4-isobutylacetophenone.

[0026] A further technical solution is that, in step S2 of the electrocatalytic synthesis of ibuprofen, the specific operation is as follows: adding DMF, KOH solution, and... to the electrochemical cell. n Bu4NBF4, 4-isobutylacetophenone. A zinc sheet is used as the anode and a platinum sheet as the cathode, with direct current flowing through it. After the reaction is complete, the product is extracted and purified to obtain 1-(4-isobutylphenyl)ethanol.

[0027] A further technical solution is that, in step S3 of the electrocatalytic synthesis of ibuprofen, the specific operation is as follows: acetonitrile is added to the electrochemical cell... n A mixture of Bu4NBF4, hydrobromic acid solution, and 1-(4-isobutylphenyl)ethanol was reacted with a platinum sheet as the anode and a graphite felt as the cathode under direct current. After the reaction was complete, the product was extracted and purified to obtain a halogenated intermediate.

[0028] A further technical solution is that, in step S4 of the electrocatalytic synthesis of ibuprofen, the specific operation is as follows: DMF is added to the electrochemical cell. n Bu4NBF4, sodium carbonate solution, 4-dimethylaminopyridine, and 1-(1-bromoethyl)-4-isobutylbenzene were reacted with CO2 gas. A magnesium sheet was used as the anode and a platinum sheet as the cathode, and a direct current was applied. After the reaction was completed, the product was extracted and purified to obtain ibuprofen.

[0029] Compared with the prior art, the present invention can achieve the following technical effects:

[0030] The electrochemical synthesis method for ibuprofen and deuterated ibuprofen provided by this invention is a mild and efficient preparation method using isobutylbenzene as the starting material, water / deuterium water as the hydrogen / deuterium source, and electrons as the redox reagent. It has low production cost, eliminates the need for toxic deuterium gas, metal catalysts, and chemical oxidizing / reducing agents, and allows for precise deuteration at the benzylic position. At the same time, CO2 is used as the C1 resource, realizing the resource utilization of CO2. The synthesized deuterated ibuprofen is expected to enhance the efficacy and reduce the toxic side effects of the original drug. Attached Figure Description

[0031] Figure 1 This is a schematic diagram of the synthesis of ibuprofen using isobutylbenzene as the starting material.

[0032] Figure 2 A schematic diagram of the synthesis of ibuprofen using isobutylbenzene derivatives as starting materials. Detailed Implementation

[0033] The technical solutions in the implementation case will be described clearly and completely below.

[0034] The compounds mentioned in this invention can be prepared by the methods described herein. The following reaction schemes and examples are provided to further illustrate the content of this invention.

[0035] The specific operation process is as follows:

[0036] S1. Isobutylbenzene undergoes a Friedel-Crafts acylation reaction, with the acetyl group moving into the para position of the isobutyl group to yield 4-isobutylacetophenone. The reaction process is as follows.

[0037] In a round-bottom flask, a magnetic stir bar, 40 mL of anhydrous dichloromethane, isobutylbenzene (2.69 g, 20 mmol), and anhydrous aluminum trichloride (267 mg, 2 mmol, 0.1 equivalent) were added sequentially. While maintaining the reaction temperature at 5–8°C, a 0.5 M solution of acetyl chloride (24 mmol, 1.2 equivalent) in dichloromethane was slowly added dropwise through a constant-pressure dropping funnel in 48 mL. After 4 hours of reaction, sufficient ice water was slowly added to quench the reaction. The mixture was extracted twice with dichloromethane (2 × 30 mL), and the organic phases were separated and combined. The organic phase was washed with a 10% dilute sodium bicarbonate aqueous solution to remove acetic acid. The organic phase was separated, dried over anhydrous sodium sulfate, and filtered. The filtrate was evaporated under reduced pressure, and silica gel column chromatography was used to separate 3.28 g of 4-isobutylacetophenone, a yellow liquid, with a yield of 93%.

[0038] 1 ¹H NMR (400 MHz, CDCl₃, ppm): d7.900 (d, J = 8 Hz, 2H), 7.254 (d, J =8 Hz, 2H), 2.610 (s, 3H), 2.554 (d, J = 7.2 Hz, 2H), 1.971-1.869 (m, 1H), 0.930 (d, J = 6.8 Hz, 6H).

[0039] S2, using water as the hydrogen source, the product of S1 undergoes electrochemical hydrogenation, reducing the carbonyl group to give 1-(4-isobutylphenyl)ethanol. The reaction process is as follows:

[0040] Add magnetic particles, DMF (23 mL), and 1.0 M potassium hydroxide aqueous solution (2 mL) to a single-chamber electrochemical cell. n Bu4NBF4 (412 mg, 1.25 mmol), and 4-isobutylacetophenone (10 mmol, 1.76 g) obtained from the previous column chromatography step. A zinc electrode was used as the sacrificial anode, and a platinum electrode as the cathode, with a distance of approximately 1 cm between the two electrodes. The mixture was slowly stirred and subjected to a direct current of 20 mA for 6 hours, with the reaction progress monitored by thin-layer chromatography. After the reaction was complete, 70 mL of water was added to the reaction solution to fully dissolve the inorganic salts and DMF. Then, dichloromethane was added for extraction twice (2 × 40 mL), and the organic phases were separated and combined. After drying with anhydrous sodium sulfate, the solution was concentrated by rotary evaporation under reduced pressure. Silica gel column chromatography was performed using a petroleum ether solution with 5% ethyl acetate as the eluent. The separated product, 1-(4-isobutylphenyl)ethanol, was a colorless oil, 1.66 g, with a yield of 93%.

[0041] 1 ¹H NMR (400 MHz, CDCl₃, ppm): d 7.120 (d, J = 8.4 Hz, 2H), 7.046 (d, J= 8.4 Hz, 2H), 2.707 (s, 1H), 2.499 (d, J = 7.2 Hz, 2H), 1.945-1.861 (m, 1H), 1.520 (s, 3H), 0.945 (d, J = 6.4 Hz, 6H).

[0042] S3. Using hydrogen halide as the halogen source, the product of S2 undergoes an electrocatalytic deoxyhalogenation reaction under the promotion of acid to obtain the corresponding halogenated intermediate. The reaction process is as follows:

[0043] Add a magnetic wave and 20 mL of acetonitrile to a single-chamber electrolytic cell. nBu4NBF4 (329 mg, 1 mmol), a solution of hydrobromide and acetic acid (5 g, 33 wt.%), and 1-(4-isobutylphenyl)ethanol (0.72 g, 4 mmol) obtained from the previous column chromatography step were used. A platinum sheet was used as the anode, and a graphite felt as the cathode, with a distance of 1 cm between the electrodes. A direct current of 15 mA was applied, and the mixture was heated to 60°C for 5 hours. After cooling to room temperature, a suitable amount of saturated sodium bicarbonate solution was added to the reaction solution to neutralize excess hydrobromide and acetic acid. The mixture was extracted twice with dichloromethane (2 × 30 mL). The organic phases were separated, combined, dried over anhydrous sodium sulfate, and concentrated by rotary evaporation under reduced pressure. Silica gel column chromatography was performed using a petroleum ether solution with 5% ethyl acetate as eluent. The separated product was 1-(1-bromoethyl)-4-isobutylbenzene, a pale yellow oil, 0.88 g, with a yield of 91%.

[0044] 1 ¹H NMR (400 MHz, CDCl₃, ppm): d 7.235 (d, J = 8.0 Hz, 2H), 7.148 (d, J= 8.0 Hz, 2H), 4.297 (q, J = 6.4 Hz, 1H), 2.491 (d, J = 7.2 Hz, 2H), 1.935-1.833 (m, 1H), 1.459 (d, J = 6.4 Hz, 3H), 0.930 (d, J = 6.8 Hz, 6H).

[0045] S4. Using CO2 as a synthon, the product of S3 is electrocarboxylated under the promotion of a base to obtain ibuprofen. The reaction process is as follows:

[0046] Add a magnetic particle and 20 mL of DMF to a single-chamber electrolytic cell. n Bu4NBF4 (1 mmol, 329 mg), sodium carbonate aqueous solution (1 mL, 1.0 M), 4-dimethylaminopyridine (10 mmol, 1.22 g), and 1-(1-bromoethyl)-4-isobutylbenzene (2.5 mmol, 603 mg) obtained from the previous column chromatography step were reacted with CO2 gas slowly introduced through a long needle, using a magnesium sheet as the sacrificial anode and a platinum sheet as the cathode, and a direct current of 20 mA was applied at room temperature for 6 h. After the reaction was completed, 10% dilute hydrochloric acid was added to adjust the pH of the reaction solution to 5. Then, 60 mL of water was added to fully dissolve the inorganic salts, DMF, and dimethylaminopyridine hydrochloride. Dichloromethane was added for extraction twice (2 × 30 mL), the organic phases were separated and combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure by rotary evaporation, and recrystallized. A white solid precipitated, which was the target product ibuprofen, weighing 0.44 g, with a yield of 85%.

[0047] 1 ¹H NMR (400 MHz, CDCl₃, ppm): d 7.245 (d, J = 8 Hz, 2H), 7.127 (d, J =8 Hz, 2H), 3.733 (q, J = 7.2 Hz, 1H), 2.469 (d, J = 7.2 Hz, 2H), 1.917-1.815(m, 1H), 1.522 (d, J = 7.2 Hz, 3H), 0.920 (d, J = 6.8 Hz, 6H).

[0048] If deuterated water is used instead of ordinary water, and steps S2, S3 and S4 are performed sequentially, deuterated ibuprofen will be obtained in the end, with a total yield of 70% for the three steps.

[0049] 1 ¹H NMR (400 MHz, CDCl₃, ppm): d 7.515 (d, J = 8 Hz, 2H), 7.057 (d, J =8 Hz, 2H), 2.469 (d, J = 7.2 Hz, 2H), 1.917-1.815 (m, 1H), 1.562 (s, 3H), 0.920 (d, J = 6.8 Hz, 6H).

[0050] The above describes the specific embodiments of the present invention.

[0051] In summary, the electrocatalytic synthesis method for ibuprofen and deuterated ibuprofen provided by this invention is a mild and efficient method using the bulk chemical isobutylbenzene as a starting material, inexpensive water / deuterium water as the hydrogen / deuterium source, and CO2 as the carboxyl source, without the need for toxic deuterium gas or high-pressure operation. The entire synthesis process is mild, green, and safe, with precise deuteration sites. The synthesized deuterated ibuprofen is expected to prolong the metabolic half-life of the original drug, enhance efficacy, reduce dosage, and even reduce toxic side effects.

Claims

1. A method for the electrocatalytic synthesis of ibuprofen and deuterated ibuprofen, characterized in that, Includes the following steps: S1. Isobutylbenzene reacts with acetyl chloride via a Friedel-Crafts acylation reaction to yield 4-isobutylacetophenone; S2. Using water as a hydrogen source, 4-isobutylacetophenone undergoes an electrochemical hydrogenation reaction to yield 1-(4-isobutylphenyl)ethanol; S3. Using hydrogen halide as the halogen source, 1-(4-isobutylphenyl)ethanol is subjected to an electrochemical deoxyhalogenation reaction to obtain 1-(1-haloethyl)-4-isobutylbenzene. S4, 1-(1-haloethyl)-4-isobutylbenzene undergoes an electrocarboxylation reaction with CO2 to yield ibuprofen.

2. If 4-isobutylacetophenone is subjected to an S2 electrochemical reduction and deuteration reaction, an S3 electrochemical deoxyhalogenation reaction, and an S4 electrocarboxylation reaction using deuterated water as the deuterium source, deuterated ibuprofen will be obtained, with the following structural formula: The reaction process in step S1 is as follows: In a round-bottom flask, a magnetic spool, 40 mL of anhydrous dichloromethane, 2.68 g of isobutylbenzene (20 mmol), and 267 mg of anhydrous aluminum trichloride (2 mmol) were added sequentially. While maintaining the reaction temperature at 5–8 °C, 48 mL of a 0.5 M solution of acetyl chloride in dichloromethane (acetyl chloride concentration of 24 mmol) was slowly added dropwise through a constant-pressure dropping funnel. After reacting for 4 hours, the reaction was quenched slowly with ice water. The mixture was extracted twice with dichloromethane (2 × 30 mL), and the organic phases were separated and combined. The organic phases were washed with a 10% dilute sodium bicarbonate aqueous solution to neutralize the acetic acid. The organic phases were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated under reduced pressure. 4-Isobutylacetophenone was obtained by silica gel column chromatography.

3. The reaction process in step S2 is as follows: A magnetic wave was added to a single-chamber electrochemical cell, along with 23 mL of N,N-dimethylformamide (DMF), 2 mL of 1.0 M potassium hydroxide aqueous solution, and 412 mg of tetrabutylammonium tetrafluoroborate. n Bu4NBF4 (1.25 mmol), 1.76 g 4-isobutylacetophenone (10 mmol); a commercial zinc sheet was used as the sacrificial anode and a platinum sheet as the cathode, with a distance of about 1 cm between the two electrodes; the reaction was carried out by slow stirring to promote mass transfer, and a direct current of 20 mA was applied for 6 hours, and the reaction progress was monitored by thin-layer chromatography; after the reaction was completed, 70 mL of water was added to the reaction solution to fully dissolve the inorganic salt and DMF, and then dichloromethane was added for extraction twice (2 x 40 mL), the organic phases were separated and combined, dried over anhydrous sodium sulfate and concentrated by rotary evaporation under reduced pressure; silica gel column chromatography was performed using a petroleum ether solution with 5% ethyl acetate as the eluent, and the separated product was 1-(4-isobutylphenyl)ethanol.

4. The reaction process in step S3 is as follows: Add magnetic flux, 20 mL acetonitrile, and 329 mg of [unspecified substance] to a single-chamber electrolytic cell. n Bu4NBF4 (1 mmol), 5 g of hydrobromoacetic acid solution (33 wt.%), 0.72 g of 1-(4-isobutylphenyl)ethanol (4 mmol), with an acid-resistant platinum sheet as the anode and graphite felt as the cathode, maintaining a distance of 1 cm between the two electrodes; a direct current of 15 mA was applied and the temperature was raised to 60°C for 5 hours; after cooling to room temperature, an appropriate amount of saturated sodium bicarbonate solution was added to the reaction solution to neutralize excess hydrobromoacetic acid; dichloromethane was added for extraction twice (2 × 30 mL), the organic phases were separated and combined, dried over anhydrous sodium sulfate, and concentrated by rotary evaporation under reduced pressure; silica gel column chromatography was performed using a petroleum ether solution with 5% ethyl acetate as the eluent, and the separated product was 1-(1-bromoethyl)-4-isobutylbenzene.

5. The reaction process in step S4 is as follows: Add magnetic flux, 20 mL DMF, and 329 mg of [unspecified substance] to a single-chamber electrolytic cell. n Bu4NBF4 (1 mmol), 1 mL of 1.0 M sodium carbonate aqueous solution, 1.22 g of 4-dimethylaminopyridine (10 mmol), and 603 mg of 1-(1-bromoethyl)-4-isobutylbenzene (2.5 mmol) were reacted by slowly introducing CO2 gas through a long needle, using a commercial magnesium sheet as the sacrificial anode and a platinum sheet as the cathode, and maintaining a direct current of 20 mA at room temperature for 6 h. After the reaction was completed, 10% dilute hydrochloric acid was added to adjust the pH of the reaction solution to 5. Then, 60 mL of water was added to fully dissolve the inorganic salts, DMF, and dimethylaminopyridine hydrochloride. The mixture was extracted twice with ethyl acetate (2 × 30 mL), and the combined organic phases were separated, dried over anhydrous sodium sulfate, concentrated under reduced pressure by rotary evaporation, and recrystallized. A white solid precipitated, which was ibuprofen.

6. The method for electrocatalytic synthesis of ibuprofen as described in claim 1, characterized in that, In step S1, the catalyst for Friedel-Crafts acylation is anhydrous aluminum chloride, hydrogen fluoride, or other Lewis acids, and the solvent is anhydrous dichloromethane.

7. The method for electrocatalytic synthesis of ibuprofen as described in claim 1, characterized in that, In step S2, the hydrogen / deuterium source for electrochemical hydrogenation is water / deuterium water; the catalytic electrode is divided into two types: sacrificial and stable, including copper foam, nickel foam, iron foam, platinum sheet, copper sheet, zinc sheet, iron sheet, magnesium sheet, carbon felt, carbon cloth, graphite felt, and graphite rod; the electrolyte is lithium perchlorate, tetrabutylammonium tetrafluoroborate, lithium hexafluorophosphate, etc.; the DC current is 5.0~30.0 mA; the selected electrolytic cell is a single-chamber or diaphragm cell; the reaction solvent is a polar aprotic solvent such as DMF, DMSO, acetonitrile, and THF.

8. The method for electrocatalytic synthesis of ibuprofen as described in claim 1, characterized in that, In step S3, the hydrogen halide is the halogen source and the halogen atom is Cl, Br or I; the electrode is an acid-resistant material such as platinum sheet, graphite felt, carbon felt, carbon rod, or carbon cloth; the electrolyte is lithium perchlorate, tetrabutylammonium tetrafluoroborate, lithium hexafluorophosphate, etc.; the DC current is 5.0~30.0 mA; and the reaction solvent is a proton or aprotic polar solvent such as acetonitrile, methanol, THF, or DMF.

9. The method for electrocatalytic synthesis of ibuprofen as described in claim 1, characterized in that, In step S4, the electrodes are platinum sheets, zinc sheets, magnesium sheets, nickel foam, graphite rods, etc., and copper materials such as copper sheets and copper foam, which have good reduction activity for CO2, should not be used as cathodes; the electrolyte is carbonates such as sodium carbonate, cesium carbonate, lithium carbonate, potassium carbonate, etc., which have a certain buffering capacity for CO2; the DC current is 5.0~30.0 mA.

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