Method for realizing coupling reaction of aryl halide and aryl boronic acid under electrochemical condition and application

Abstract

The application discloses a method for realizing coupling reaction of aryl halide and aryl boronic acid under electrochemical conditions and application thereof, and belongs to the technical field of organic synthesis and electrocatalysis. The method comprises the following steps: preparing an anode liquid and a cathode liquid, wherein the anode liquid is an alkali solution, and the cathode liquid comprises an alkali solution, a cosolvent and a palladium catalyst; then aryl halide substrates and aryl boronic acid substrates are added into the cathode liquid and uniformly dispersed to obtain a reaction liquid; the reaction liquid and the anode liquid are respectively transferred into a cathode chamber and an anode chamber of an electrochemical reaction device, the cathode chamber and the anode chamber are separated by an anion exchange membrane, a working electrode and a reference electrode are placed in the cathode chamber, and a counter electrode is placed in the anode chamber to form a three-electrode system, and under the action of an external potential, electrochemical reaction is carried out to make the aryl halide and the aryl boronic acid generate a biaryl product. The method successfully constructs a green electrochemical cross-coupling reaction system, and can improve the efficiency and selectivity of the carbon-carbon coupling reaction between the aryl halide and the aryl boronic acid.

Description

Technical Field

[0001] This invention relates to the fields of organic synthesis and electrocatalysis, specifically to a method and application for realizing the coupling reaction of aryl halides and arylboronic acids under electrochemical conditions. Background Technology

[0002] Constructing carbon-carbon bonds through efficient catalysis is an important research direction in organic synthesis and fine chemical production. Among the many carbon-carbon bond construction reactions, transition metal-catalyzed cross-coupling reactions have become one of the important strategies in modern organic synthesis due to their high reaction efficiency, good selectivity, and wide substrate applicability. The Suzuki-Miyaura coupling reaction is one of the most widely used cross-coupling reactions. This reaction constructs new aryl-aryl carbon-carbon bonds through the coupling reaction between aryl halides and arylboronic acids, thereby achieving the efficient synthesis of biaryl structures. This reaction is usually carried out in the presence of a palladium catalyst, and the reaction process is completed through a Pd(0) / Pd(II) catalytic cycle, specifically including three key steps: oxidative addition, transmetalation, and reductive elimination. The biaryl structures constructed through the Suzuki coupling reaction not only achieve efficient connection between aromatic rings but also allow for the control of molecular configuration and electronic properties, thus demonstrating significant application value in fields such as organic optoelectronic materials, polymer materials, and the synthesis of pharmaceutical intermediates. Therefore, developing efficient, stable, and green Suzuki-Miyaura coupling reaction systems is of great significance for promoting the construction of complex organic molecules and advancing the development of green chemistry.

[0003] Aryl halides and arylboronic acids can undergo Suzuki-Miyaura coupling under palladium catalysis to construct new aryl-aryl carbon-carbon bonds. However, in actual reactions, the oxidative addition step of aryl halides typically has a high energy barrier, and the active species of Pd(0) in the catalytic cycle are prone to oxidation or aggregation to form palladium black, leading to catalyst deactivation and reduced reaction efficiency. Therefore, effectively controlling the Pd catalytic cycle and maintaining the stable presence of Pd(0) active species is crucial for efficient Suzuki coupling reactions. Traditional Suzuki coupling reactions mainly rely on organic solvent systems and are carried out at high reaction temperatures, often requiring the addition of basic additives or additional chemical reducing agents to maintain the catalytic cycle. This results in a relatively complex reaction system and increases the environmental burden to some extent. Electrochemical organic synthesis technology, by controlling the reaction process with an applied potential, can achieve electron transfer reactions under mild conditions, providing a new reaction pathway for the construction of carbon-carbon bonds between aryl halides and arylboronic acids. However, the effectiveness of this technology largely depends on the electron transport efficiency at the catalyst-electrode interface. Currently, there are still two significant problems in the study of electrochemical Suzuki coupling reactions: First, some electrochemical coupling reaction systems still require additional chemical reducing agents or complex electrode materials to maintain the catalytic cycle; second, some electrochemical coupling reaction systems suffer from insufficient catalyst stability or limited reaction efficiency, making it difficult to achieve the synthesis of biaryl products in high yield under relatively mild conditions.

[0004] Chinese invention patent document CN107382734A discloses a Suzuki coupling reaction of nitrochlorobenzene catalyzed by dichlorodiaminepalladium catalysis. This invention, under solvent and alkaline conditions, uses dichlorodiaminepalladium catalyst to induce a Suzuki coupling reaction between nitrochlorobenzene and phenylboronic acid or diphenylboronic acid, thereby synthesizing biaryl compounds. This method primarily operates in organic solvent systems and relies on conventional thermocatalytic conditions to maintain the catalytic cycle; alkaline additives are still required during the reaction.

[0005] Chinese invention patent document CN113546652A discloses a photocatalytic Suzuki coupling reaction catalyst and its preparation method. The catalyst comprises cadmium sulfide and palladium phosphide supported on cadmium sulfide, which can promote the Suzuki coupling reaction under photocatalytic conditions, thereby achieving the construction of carbon-carbon bonds between aryl halides and organoboron reagents. This technology drives the catalytic reaction through photocatalysis, reducing to some extent the dependence of traditional thermocatalytic systems on high-temperature conditions.

[0006] In summary, the Suzuki coupling reaction between aryl halides and arylboronic acids currently relies mainly on traditional palladium catalytic systems under organic solvent conditions. Some novel catalytic systems promote the coupling reaction through photocatalysis and other methods. The reaction systems are complex and demanding, and there are still certain limitations in terms of catalytic cycle regulation. Summary of the Invention

[0007] To address the shortcomings of the existing technology, this invention provides a method for realizing the coupling reaction of aryl halides and arylboronic acids under electrochemical conditions, thereby improving the efficiency and selectivity of the carbon-carbon coupling reaction between aryl halides and arylboronic acids, and providing a reliable solution for achieving green and efficient aryl-aryl carbon-carbon bond construction under mild conditions.

[0008] The specific technical solution adopted is as follows: A method for realizing the coupling reaction of aryl halides with arylboronic acids under electrochemical conditions, comprising the following steps: S1 prepares anolyte and catholyte, the anolyte being an alkaline solution and the catholyte containing an alkaline solution, a co-solvent, and a palladium catalyst; S2. The aryl halide substrate and the arylboronic acid substrate are added to the catholyte and dispersed evenly to obtain the reaction solution; S3 The reaction solution and anolyte are transferred to the cathode chamber and anode chamber of the electrochemical reaction device, respectively. The cathode chamber and anode chamber are separated by anion exchange membrane. The working electrode and reference electrode are placed in the cathode chamber, and the counter electrode is placed in the anode chamber to form a three-electrode system. Under the action of an applied potential, the electrochemical reaction promotes the formation of biaryl products from aryl halides and arylboronic acids.

[0009] This invention provides a reaction system for Suzuki coupling catalyzed by palladium catalyst under electrochemical conditions. By driving a Pd(II) / Pd(0) catalytic cycle under electrochemical conditions, the palladium catalyst continuously regenerates active Pd(0) species at the electrode interface, thereby promoting the cross-coupling reaction between aryl halides and arylboronic acids. In the comparative system without electrochemical driving conditions, the active Pd(0) species are prone to oxidation or aggregation and deactivation during the reaction, resulting in low coupling reaction efficiency. Simultaneously, side reactions such as dehalogenation, reduction, or secondary coupling are easily generated in the system, thus reducing the selectivity of the target biaryl product. However, in the electrochemical reaction system of this invention, Pd(II) is reduced to Pd(0) at the electrode interface by an applied potential, thereby maintaining the catalytic cycle and significantly improving the reaction efficiency. This results in a higher conversion rate of the aryl halide substrate, while the selectivity and yield of the target biaryl coupling product are significantly improved. This invention achieves highly efficient Suzuki coupling reaction by controlling the Pd catalytic cycle in the electrochemical system.

[0010] Preferably, the alkaline solution is a potassium carbonate solution, the palladium catalyst is selected from Pd(PPh3)4, Pd(OAC)2 or Pd / C, and the co-solvent is methanol.

[0011] Preferably, the concentration of potassium carbonate in the anolyte or catholyte is 0.3-0.6 mol / L, more preferably 0.5 mol / L.

[0012] In the electrochemical Suzuki coupling reaction process of this invention, a palladium catalyst is used as the active reaction center. The electrochemical reaction is carried out under the action of an applied potential. The conversion of Pd(II) to Pd(0) is driven by the supply of electrons from the electrode, and the Pd(II) / Pd(0) catalytic cycle is completed at the electrode interface. The alkaline electrolyte potassium carbonate is used to promote the transmetallization reaction between arylboronic acid and Pd intermediate. The cathode in the electrochemical reaction system provides electrons to drive the catalytic cycle, while the anode achieves charge balance through oxidation reaction, thereby completing the entire electrochemical coupling reaction process.

[0013] Furthermore, aryl halides include, but are not limited to, bromobenzene, chlorobenzene, iodobenzene, 1,4-diiodobenzene, p-bromochlorobenzene, p-iodobromobenzene, etc., and arylboronic acids include, but are not limited to, 4-fluorophenylboronic acid, potassium phenyltrifluoroborate, 1,4-phenyldiboronic acid, etc.

[0014] Preferably, the molar ratio of aryl halide substrate to arylboronic acid substrate is 1:1~2, and the molar ratio of aryl halide substrate to palladium catalyst is 1:0.005~0.01.

[0015] Furthermore, in the three-electrode system, nickel foam is used as the working electrode, Hg / HgO is used as the reference electrode, and a platinum mesh electrode is used as the counter electrode.

[0016] Preferably, during the electrochemical reaction, the reaction potential is -0.9 ~ -1.2 V vs Hg / HgO, the reaction time is 4-12 h, and the reaction temperature is 30~50 ℃.

[0017] Specifically, after the electrochemical reaction is completed, the resulting reaction solution is extracted with dichloromethane, the organic phases are combined, dried, and the solvent is removed by vacuum distillation to obtain the crude product, which is then purified by column chromatography to obtain the target biaryl product.

[0018] The method for realizing the coupling reaction of aryl halides and arylboronic acids under electrochemical conditions provided by the present invention, taking the coupling reaction of 4-fluorophenylboronic acid and bromobenzene as an example, has a conversion rate of over 96% and a yield of over 95%, showing high reaction selectivity. No obvious byproducts were observed in the obtained product within the detection range.

[0019] This invention also provides the application of the method for realizing the coupling reaction of aryl halides and arylboronic acids under the electrochemical conditions described above in the field of organic synthesis.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) This invention achieves efficient Suzuki coupling reaction between aryl halides and arylboronic acids by introducing a palladium catalyst into an electrochemical system and driving a Pd(II) / Pd(0) catalytic cycle with an applied potential. Under electrochemical conditions, it enables the efficient construction of aryl-aryl carbon-carbon bonds. Under the corresponding reaction conditions of this invention, the aryl halide substrate achieves a high conversion rate. The target biaryl compound is the main product in the reaction system, and the product distribution is relatively concentrated, which is beneficial for subsequent separation and utilization. Compared with traditional reaction systems that do not use electrochemical driving, the electrochemical reaction system of this invention maintains the concentration of Pd(0) active species through electrode electron supply, making the reaction process more controllable and reducing side reactions such as dehalogenation and reduction, thereby significantly improving the selectivity and yield of the target biaryl product. Furthermore, this invention uses an electrochemical driving method for the reaction process, requiring no additional chemical oxidants or reductants. The system composition is relatively simple, the reaction conditions are mild, and it has good environmental adaptability, enabling a green and efficient Suzuki coupling reaction process.

[0021] (2) The electrochemical Suzuki coupling reaction system provided by the present invention has good stability and reusability. It can maintain high catalytic activity and product selectivity after multiple cycles of reaction, thereby reducing the reaction cost to a certain extent.

[0022] (3) The method of the present invention has low equipment requirements and simple operation. It realizes the efficient coupling reaction between aryl halides and arylboronic acid under mild electrochemical conditions. While obtaining a high substrate conversion rate, it achieves high selectivity for the generation of target biaryl products. It provides a new path for constructing a green electrochemical cross-coupling reaction system. The method of the present invention is suitable for laboratory research and large-scale production. It has good application prospects in the fields of organic synthesis and fine chemical preparation. Attached Figure Description

[0023] Figure 1 The image shows the total ion chromatogram of the product obtained from the electrochemical Suzuki coupling reaction system in Example 1 by GC-MS.

[0024] Figure 2 The diagram shows the different substrate yields in the electrochemical Suzuki coupling reaction systems in Examples 1-4.

[0025] Figure 3 The graph shows the yield of biaryl products in the Suzuki coupling reaction system of Comparative Example 1.

[0026] Figure 4The graph shows the yield of biaryl products after catalyst recycling in Example 1. Detailed Implementation

[0027] To make the objectives, features, and advantages of this invention more apparent and understandable, a detailed description is provided below through specific embodiments. Many specific details are set forth in the following description to provide a thorough understanding of the invention. However, the invention can be practiced in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below. Technical features in various embodiments of the invention can be combined appropriately without mutual conflict.

[0028] Unless otherwise specified, the operating methods in the following examples are generally performed under conventional conditions or as recommended by the manufacturer. Contents not described in detail in this specification are prior art known to those skilled in the art. Unless otherwise specified, the experimental materials used in the examples below can be purchased from conventional biochemical reagent companies.

[0029] Example 1 (1) Prepare 150 mL of K2CO3 electrolyte. Weigh out two portions of 5.18 g K2CO3 and dissolve them in two sets of solvents. One set is 75 mL of deionized water, and the other set is a mixture of 15 mL of methanol and 60 mL of deionized water to form a homogeneous electrolyte system. The electrolyte with added co-solvent is the catholy solution, and the other set is the anolyte. Add 5 mg of Pd(PPh3)4 catalyst to the catholy solution and sonicate for 15 min to disperse it fully.

[0030] (2) Dissolve 0.118 g of bromobenzene and 0.105 g of 4-fluorophenylboronic acid in the catholy liquid of step (1) and stir continuously for 30 min to fully disperse the catalyst and substrate in the solution to obtain the reaction solution.

[0031] (3) Take a clean nickel foam electrode (size 1 cm × 2 cm, effective area 1 cm × 1.4 cm), ultrasonically clean it in 3 mol / L hydrochloric acid solution for 30 min, ultrasonically clean the hydrochloric acid-treated nickel foam in water and ethanol for 30 min in sequence, dry it overnight, and set it aside.

[0032] (4) The obtained reaction solution and anolyte are transferred to the cathode chamber and anode chamber of the electrochemical reaction device, respectively. The cathode chamber and anode chamber are separated by an FAA anion exchange membrane. The working electrode (the foamed nickel electrode of step (3)) and the reference electrode Hg / HgO are placed in the cathode chamber, and the counter electrode platinum mesh electrode is placed in the anode chamber to form a three-electrode system. The electrochemical reaction is carried out under the action of the applied potential, so that the Pd(PPh3)4 catalyst completes the Pd(II) / Pd(0) catalytic cycle at the electrode interface, thereby promoting the Suzuki coupling reaction between aryl halides and arylboronic acid to generate biaryl products. The electrochemical reaction conditions are: reaction potential of -1.12 V (vs Hg / HgO), reaction time of 6 h, and reaction temperature of 40 ℃.

[0033] (5) After the reaction is complete, the reaction solution is extracted with dichloromethane, the organic phases are combined, dried, and the solvent is removed by vacuum distillation to obtain the crude product. The crude product is purified by column chromatography to obtain the target biaryl product and all products are analyzed.

[0034] The reaction system was characterized and the products were analyzed. The results are as follows: Figure 1 As shown, under the corresponding electrochemical reaction conditions in this embodiment, the Suzuki coupling reaction between aryl halides and arylboronic acids can proceed smoothly, with a bromobenzene conversion rate of 96.2% and a yield of 95.8% for the target biaryl product. This indicates that the electrochemical Suzuki coupling system established in this invention has high catalytic efficiency and good product selectivity.

[0035] Example 2 The only difference between this embodiment and Example 1 is that the aryl halide is replaced with chlorobenzene. All other experimental parameters and steps are the same as in Example 1, and the target biaryl product is obtained.

[0036] The results are as follows Figure 2 As shown, the conversion rate of chlorobenzene was 62.3%, and the yield of the target biaryl product was 62.3%.

[0037] Example 3 The only difference between this embodiment and Example 1 is that the aryl halide is replaced with iodobenzene. All other experimental parameters and steps are the same as in Example 1, and the target biaryl product is obtained.

[0038] The results are as follows Figure 2 As shown, the conversion rate of iodobenzene was 99.5%, and the yield of the target biaryl product was 99.5%.

[0039] Example 4 The only difference between this embodiment and Example 1 is that the electrochemical reaction time is 4 h. All other experimental parameters and steps are the same as in Example 1, and the target biaryl product is obtained.

[0040] The results are as follows Figure 2 As shown, the conversion rate of bromobenzene was 52.3%, and the yield of the target biaryl product was 52.3%.

[0041] Example 5 The only difference between this embodiment and Example 1 is that after the reaction is completed, the regenerated catalyst is obtained by centrifugation, washing and drying. The regenerated catalyst is used for the next electrocatalytic reaction. All other experimental parameters and steps are the same as in Example 1 to obtain the target biaryl product.

[0042] The results are as follows Figure 4 As shown, the yield of the target biaryl product was 82.3% after the catalyst was recycled four times.

[0043] Comparative Example 1 The only difference between this comparative example and Example 1 is that no electricity was applied to the system and the reaction time was extended to 12 h. All other experimental parameters and steps were the same as in Example 1, and the target biaryl product was obtained.

[0044] The results are as follows Figure 3 As shown, after 12 hours of reaction, the yield of the target biaryl product was 38.5%.

[0045] The embodiments described above provide a detailed explanation of the technical solutions of the present invention. It should be understood that the above descriptions are merely specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, additions, or similar substitutions made within the scope of the principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for realizing the coupling reaction of aryl halides with arylboronic acids under electrochemical conditions, characterized in that, Includes the following steps: S1 prepares anolyte and catholyte, the anolyte being an alkaline solution and the catholyte containing an alkaline solution, a co-solvent, and a palladium catalyst; S2. The aryl halide substrate and the arylboronic acid substrate are added to the catholyte and dispersed evenly to obtain the reaction solution; S3 The reaction solution and anolyte are transferred to the cathode chamber and anode chamber of the electrochemical reaction device, respectively. The cathode chamber and anode chamber are separated by anion exchange membrane. The working electrode and reference electrode are placed in the cathode chamber, and the counter electrode is placed in the anode chamber to form a three-electrode system. Under the action of an applied potential, the electrochemical reaction promotes the formation of biaryl products from aryl halides and arylboronic acids.

2. The method for realizing the coupling reaction of aryl halides and arylboronic acids under electrochemical conditions according to claim 1, characterized in that, The alkaline solution is a potassium carbonate solution, the palladium catalyst is Pd(PPh3)4, Pd(OAC)2 or Pd / C, and the co-solvent is methanol.

3. The method for realizing the coupling reaction of aryl halides and arylboronic acids under electrochemical conditions according to claim 1, characterized in that, The concentration of potassium carbonate in the anolyte or catholyte is 0.3-0.6 mol / L.

4. The method for realizing the coupling reaction of aryl halides with arylboronic acids under electrochemical conditions according to claim 1, characterized in that, Aromatic halides include bromobenzene, chlorobenzene, iodobenzene, 1,4-diiodobenzene, p-bromochlorobenzene, or p-iodobromobenzene; arylboronic acids include 4-fluorophenylboronic acid, potassium phenyltrifluoroborate, or 1,4-phenyldiboronic acid.

5. The method for realizing the coupling reaction of aryl halides with arylboronic acids under electrochemical conditions according to claim 1, characterized in that, The molar ratio of aryl halide substrate to arylboronic acid substrate is 1:1~2, and the molar ratio of aryl halide substrate to palladium catalyst is 1:0.005~0.

01.

6. The method for realizing the coupling reaction of aryl halides with arylboronic acids under electrochemical conditions according to claim 1, characterized in that, In the three-electrode system, nickel foam is used as the working electrode, Hg / HgO is used as the reference electrode, and platinum mesh electrode is used as the counter electrode.

7. The method for realizing the coupling reaction of aryl halides with arylboronic acids under electrochemical conditions according to claim 6, characterized in that, During the electrochemical reaction, the reaction potential is -0.9 ~ -1.2 V vs Hg / HgO, the reaction time is 4-12 h, and the reaction temperature is 30~50 ℃.

8. The method for realizing the coupling reaction of aryl halides with arylboronic acids under electrochemical conditions according to claim 1, characterized in that, After the electrochemical reaction was completed, the resulting reaction solution was extracted with dichloromethane, the organic phases were combined, dried, and the solvent was removed by vacuum distillation to obtain the crude product. The crude product was then purified by column chromatography to obtain the target biaryl product.

9. The application of the method for realizing the coupling reaction of aryl halides with arylboronic acids under electrochemical conditions according to any one of claims 1-8 in the field of organic synthesis.

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