An aqueous phase micelle-assisted electrochemical pd catalyzed aryl halide and olefin coupling method

Abstract

This invention discloses an aqueous micelle-assisted electrochemical Pd-catalyzed coupling method for aryl halides and olefins, belonging to the field of electrocatalytic organic synthesis technology. The method includes: S1 preparing an alkaline electrolyte, adding a surfactant, and stirring to form a micelle structure in the aqueous system to obtain a catholy; using the alkaline solution as the anolyte; S2 adding an aryl halide substrate, an olefin substrate, and a palladium catalyst to the catholy, and mixing them evenly to obtain a reaction solution; S3 transferring the reaction solution and the anolyte to the cathode chamber and anode chamber of an electrochemical reaction apparatus, respectively, placing a working electrode and a reference electrode in the cathode chamber, and a counter electrode in the anode chamber to form a three-electrode system, and carrying out an electrochemical reaction under an applied potential, causing the aryl halide to undergo a coupling reaction with the olefin to generate a substituted olefin product. This invention offers high selectivity, high yield of the target substituted olefin product, mild reaction conditions, and is environmentally friendly.

Description

Technical Field

[0001] This invention belongs to the field of electrocatalytic organic synthesis technology, specifically relating to an aqueous micelle-assisted electrochemical Pd-catalyzed coupling method for aryl halides and olefins. Background Technology

[0002] Developing efficient coupling methods for aryl halides and alkenes is crucial, as the construction of aryl-alkenyl C-C bonds is a core technique for synthesizing complex π-conjugated molecules, natural products, and drug skeletons. Compared to traditional methods, modern catalytic systems can improve step economy and functional group tolerance, providing efficient and green synthetic pathways for functional materials and bioactive molecules. Palladium-catalyzed coupling reactions of aryl halides and alkenes (Heck reactions) are a classic class of transition metal-catalyzed coupling reactions that can efficiently construct various functionalized alkene structures, providing a powerful tool for the synthesis of drug molecules, natural products, and organic optoelectronic materials. Currently, researchers are continuously optimizing processes and improving systems to drive the development of green catalytic systems, thereby achieving the efficient synthesis of complex molecules.

[0003] In practical reactions, aryl halides and olefin substrates often exhibit strong hydrophobicity and low solubility in aqueous systems. Under catalytic conditions, they are easily affected by mass transfer efficiency and substrate dispersion, leading to a decrease in reaction efficiency. Furthermore, in palladium-catalyzed coupling reactions, catalyst cycling and reaction selectivity are also easily affected by the reaction environment, making the achievement of highly efficient and selective coupling reactions still challenging. Traditional aryl halide-olefin coupling reactions are mainly carried out in organic solvent systems, such as polar solvents like N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), or dimethyl sulfoxide (DMSO), and the reaction process is completed at relatively high temperatures. Basic additives or oxidants are usually required to maintain the catalytic cycle, resulting in complex reaction systems and the potential generation of byproducts.

[0004] Electrochemical organic synthesis technology, by controlling the reaction process with an applied potential, can utilize electrons as clean redox reagents to achieve catalytic cycling under mild conditions, thus providing a new reaction pathway for transition metal-catalyzed coupling reactions. However, the effectiveness of this technology largely depends on the reaction system and microenvironment structure. Currently, two significant problems remain in the research of electrochemical aryl halide-olefin coupling reactions: first, most electrochemical coupling reactions still rely on organic solvent systems, making it difficult to achieve a green aqueous reaction environment; second, in aqueous systems, the low solubility of organic substrates and limited mass transfer efficiency at the reaction interface often result in a trade-off between reaction efficiency and selectivity.

[0005] Chinese patent document CN112892596A discloses a palladium catalyst and its application in the Heck reaction. This palladium catalyst is obtained by reacting 2,6-diphenylaniline and a diketone to yield a diimine ligand, which is then coordinated with PdCl2. This palladium catalyst is further used to promote the coupling reaction between aryl halides and olefins, thereby synthesizing substituted olefin compounds. Chinese patent document CN111715262A discloses a palladium-supported nitrogen-rich carbon nitride photocatalyst. The catalyst is prepared by: thermally polymerizing carbon nitride using melamine as a precursor; then heat-treating the prepared carbon nitride in ammonia water to prepare N-rich carbon nitrides; loading palladium using an impregnation method; and preparing a palladium-supported nitrogen-rich carbon nitride photocatalyst using sodium borohydride as a reducing agent. Further, using aryl halides and olefins as raw materials, Z-type Heck coupling occurs under the action of a certain amount of photocatalyst, base, and visible light to obtain C-C bond products. All of the above methods involve reactions in organic solvent systems, and the efficiency of the Heck reaction is improved by modifying the catalyst.

[0006] In summary, developing a method to achieve efficient coupling reactions between aryl halides and olefins under aqueous conditions is of great significance for constructing green and efficient electrochemical organic synthesis systems. Summary of the Invention

[0007] To address the shortcomings of existing technologies, this invention provides an aqueous micelle-assisted electrochemical Pd-catalyzed coupling method for aryl halides and olefins. This method constructs a micelle microenvironment in the aqueous phase to achieve effective enrichment of hydrophobic substrates and drives Pd catalytic cycling under electrochemical conditions, thereby realizing a highly efficient coupling reaction between aryl halides and olefins under mild conditions and constructing a green electrochemical coupling reaction system.

[0008] The specific technical solution adopted is as follows: An aqueous micelle-assisted electrochemical Pd-catalyzed coupling method for aryl halides and olefins includes the following steps: S1 Prepare an alkaline electrolyte, add a surfactant to it, and stir to form a micelle structure in the aqueous system to obtain the catholy solution; use the alkaline solution as the anolyte; S2 Add aryl halide substrate, olefin substrate and palladium catalyst to catholy solution and mix well to obtain reaction solution; S3 The reaction solution and anolyte are transferred to the cathode chamber and anode chamber of the electrochemical reaction device, respectively. 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, an electrochemical reaction is carried out, causing the aryl halide to undergo a coupling reaction with the olefin to generate substituted olefin products.

[0009] This invention achieves highly efficient coupling reactions between aryl halides and olefins by introducing surfactants into an alkaline aqueous system to form a micellar microenvironment and combining this with an electrochemical method to drive a Pd catalytic cycle. Substituted olefin products are successfully prepared under mild conditions. Compared to traditional organic solvent reaction systems, the aqueous micellar-assisted system of this invention effectively improves the dispersibility and local concentration of hydrophobic substrates, enhances mass transfer in the reaction system, promotes reaction progress, reduces side reactions, and improves reaction selectivity. Under comparative conditions without the introduction of micelles, the substrate dispersibility in the reaction system is poor, the reaction efficiency is low, and side reactions are easily generated. However, with the introduction of the micellar system and combined with electrochemical conditions, the coupling reaction between aryl halides and olefins can proceed efficiently under aqueous conditions, achieving highly selective generation of the target coupling product in a green and environmentally friendly manner.

[0010] Furthermore, the solute in the alkaline electrolyte is potassium carbonate, the solvent is water and methanol (where methanol is a co-solvent, and the volume ratio of water to methanol is 3-5:1, preferably 4:1), the surfactant is hexadecyltrimethylammonium bromide (CTAB), and the alkaline solution is an aqueous solution of potassium carbonate.

[0011] Preferably, the concentration of potassium carbonate in the catholyte and anolyte is 0.1-0.7 M, more preferably 0.5 M; and the concentration of surfactant in the catholyte is 0.1-2 mM, more preferably 1-2 mM.

[0012] An alkaline environment can provide a stable ion conduction environment and reaction conditions during electrochemical reactions, which is conducive to maintaining the continuous progress of electrode reactions and provides a suitable reaction medium for the electrochemical coupling reaction between aryl halides and alkenes.

[0013] The micelle structure formed by surfactants can enrich hydrophobic aryl halides and olefin substrates and improve the mass transfer process at the reaction interface.

[0014] By constructing micelle structures in the aqueous phase, hydrophobic aryl halides and olefin substrates can be effectively enriched, thereby increasing the substrate concentration at the reaction interface, promoting the coupling reaction, and reducing side reactions.

[0015] Optionally, the aryl halides include, but are not limited to, chlorobenzene, bromobenzene, iodobenzene, 1,4-diiodobenzene, 1,4-dibromobenzene, 4-iodoanisole, 4-acetyliodobenzene, and 2-iodotoluene; the alkenes include, but are not limited to, styrene, 4-fluorostyrene, 4-cyanostyrene, 4-methoxystyrene, and 4-vinylpyridine; the molar ratio of the aryl halide substrate to the alkene substrate is 1:0.5-2, preferably 1:1.

[0016] Preferably, the palladium catalyst is Pd(PPh3)4, and the molar ratio of the aryl halide substrate to the palladium catalyst is 1:0.005-0.05.

[0017] Preferably, the concentration of the aryl halide in the reaction solution is 0.005-0.06 M, more preferably 0.010 M.

[0018] Furthermore, the cathode chamber and anode chamber of the electrochemical reaction device are separated by an ion exchange membrane.

[0019] Preferably, a hydrophilic carbon paper electrode is used as the working electrode, an Hg / HgO electrode as the reference electrode, and a platinum mesh electrode as the counter electrode.

[0020] Under the influence of an applied potential, the cathode chamber provides the necessary electrons to the reaction system, enabling the palladium catalyst to complete the Pd reaction. (II) / Pd (0) The catalytic cycle promotes the coupling reaction between aryl halides and olefins. Simultaneously, the ion-exchange membrane conducts ions generated on the anode side, facilitating their migration to the cathode chamber, thereby maintaining the charge balance and stability of the reaction environment in the electrochemical system.

[0021] Preferably, the electrochemical reaction conditions are: a potential of -0.1 V to -1.2 V (vs. RHE), more preferably -0.6 V (vs. RHE); a current of 2-12 mA; and a current density of 1-6 mA / cm². 2 More preferably 5 mA / cm 2 The reaction is carried out at 30-70 °C for 5-10 h, more preferably at 70 °C for 10 h. Under these conditions, aryl halides and olefins can undergo efficient coupling reactions in an aqueous micelle-assisted system to generate the target substituted olefin products.

[0022] Specifically, after the electrochemical reaction is completed, 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, which is then further purified by column chromatography to obtain the substituted olefin product.

[0023] This invention also provides the application of the aqueous micelle-assisted electrochemical Pd-catalyzed coupling method for aryl halides and olefins in the field of organic synthesis.

[0024] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) Currently, the coupling reaction between aryl halides and alkenes mainly relies on organic solvent systems. Under aqueous conditions, due to the low solubility of the substrate and the limited mass transfer efficiency at the reaction interface, it is often difficult to achieve both high reaction efficiency and selectivity. This invention solves the above-mentioned technical problems by introducing a micellar structure into the aqueous system and combining it with an electrochemical method to drive a palladium catalytic cycle. It realizes a highly efficient coupling reaction between aryl halides and alkenes with high substrate conversion and high product yield, and it does not require the use of organic solvents, making it green and environmentally friendly.

[0025] (2) The reaction conditions of the method of the present invention are mild, the reaction system is simple, there are few side reactions, the equipment requirements are low, it is easy to operate, and it has good prospects for industrial application.

[0026] (3) The method of the present invention continuously regenerates Pd by applying an external cathode potential. (0) Active species are obtained, and hydrophobic substrates are enriched at the electrode-electrolyte interface using CTAB micelles, which can effectively suppress side reactions such as dehalogenation, homocoupling and over-reduction, and improve the selectivity of the target substituted olefin products. Attached Figure Description

[0027] Figure 1 This is a schematic diagram of the aqueous micelle-assisted electrochemical Pd-catalyzed coupling of aryl halides and olefins in Example 1.

[0028] Figure 2 The image shows the total ion chromatogram of the product obtained by the method in Example 1 using GC-MS. Detailed Implementation

[0029] 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.

[0030] 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.

[0031] Example 1 In this embodiment, a schematic diagram of aqueous micelle-assisted electrochemical Pd-catalyzed coupling of aryl halides and olefins is shown below. Figure 1 As shown, the specific steps are as follows: (1) A certain amount of deionized water was added to a beaker, followed by 5.18 g of potassium carbonate, which was then dissolved by sonication to obtain 60 mL of potassium carbonate solution. 15 mL of methanol was then added to prepare an alkaline electrolyte. The surfactant cetyltrimethylammonium bromide (CTAB) was added to the alkaline electrolyte to prepare the catholyte. The surfactant concentration in the catholyte was 1 mM, and the potassium carbonate concentration was 0.5 M. The mixture was stirred to form a micelle structure, yielding 75 mL of catholyte. Simultaneously, 75 mL of a 0.5 M potassium carbonate aqueous solution was used as the anolyte. The micelle structure in the catholyte can enrich hydrophobic aryl halides and olefin substrates, thereby increasing the local concentration of the substrate at the reaction interface and promoting the coupling reaction.

[0032] (2) Add 0.153 g of iodobenzene substrate and 0.078 g of styrene substrate to the catholy solution, and add 45 mg of palladium catalyst Pd(PPh3) to form a homogeneous reaction solution under stirring conditions. The concentrations of iodobenzene and styrene in the reaction solution are both 0.010 M.

[0033] (3) The above reaction solution and anolyte were transferred to the cathode chamber and anode chamber of the electrochemical reaction apparatus, respectively. The anolyte was 75 mL of 0.5 M potassium carbonate aqueous solution. The cathode chamber and anode chamber were separated by an ion exchange membrane. A working electrode (hydrophilic carbon paper electrode) and a reference electrode (Hg / HgO electrode) were placed in the cathode chamber, and a counter electrode (platinum mesh electrode) was placed in the anode chamber to form a three-electrode system. An electrochemical reaction was carried out under the action of an applied potential. During the reaction, a potential of -0.6 V (vs. RHE) and a current density of 5 mA / cm² were applied. 2 An electrochemical reaction was carried out at 70 °C for 10 h to induce an electrochemical catalytic coupling reaction between aryl halides and olefins. After the reaction, the reaction solution was extracted with dichloromethane, the organic phases were combined, and anhydrous sodium sulfate was added for drying. The organic solvent was then removed by vacuum distillation to obtain the crude product. The crude product was further purified by silica gel column chromatography to obtain the final product.

[0034] The product was analyzed by gas chromatography-mass spectrometry (GC-MS) to confirm the yield of the target conjugated product (GC-MS total ion chromatogram as shown in the figure). Figure 2 (As shown). The results indicate that under the above electrochemical reaction conditions, aryl halides and olefins can undergo efficient coupling reactions to generate the target substituted olefin product, with a GC-MS yield of 99.5%.

[0035] The above results indicate that, under the combined action of an aqueous micelle system and electrochemical conditions, aryl halides and alkenes can achieve efficient coupling reactions under mild conditions, thereby generating the target substituted olefin products.

[0036] Example 2 The only difference between this embodiment and Example 1 is that the aryl halide is replaced with bromobenzene. All other experimental parameters and steps are the same as in Example 1. The GC-MS yield of the target substituted olefin product trans-stilbene is 53.0%.

[0037] Example 3 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. The GC-MS yield of the target substituted olefin product trans-stilbene is 13.4%.

[0038] Example 4 The only difference between this embodiment and Example 1 is that the electrochemical reaction conditions are adjusted to: potential -0.9 V (vs. RHE) and current density 5 mA / cm². 2 The reaction was carried out at 70 °C for 10 h, and the remaining experimental parameters and steps were the same as in Example 1. The GC-MS yield of the target substituted olefin product trans-stilbene was 50.3%.

[0039] Example 5 This example illustrates the electrochemical continuous regeneration of Pd. (0) The reaction was promoted. Intermittent electrolysis was conducted on the reaction system of Example 1. During the first 0-4 hours of electrolysis, the yield increased from 0% to ~37%. During the 4-8 hours without electrolysis, the yield remained relatively stable at ~37%. During the 8-11 hours, the yield increased from ~40% to ~80% with electrolysis, while the yield remained stable at ~80% without electrolysis. That is, the product yield increased significantly during the electrolysis phase, and the product formation rate decreased during the electrolysis phase. After electrolysis was restarted, the coupling product continued to form. These results indicate that the applied cathode potential can continuously regenerate active Pd. (0) Species and maintain catalytic cycles.

[0040] Comparative Example 1 To investigate the effect of the cosolvent system on the reaction, a control experiment was conducted without methanol.

[0041] 0.153 g of iodobenzene, 0.078 g of styrene, and 5 mg of Pd(PPh3)4 were weighed and added to 60 mL of 0.5 M potassium carbonate solution. 15 mL of acetonitrile was used as a co-solvent, and 1 mM CTAB was used as a surfactant to prepare a 75 mL reaction solution. The reaction solution was transferred to the cathode chamber of an electrochemical reactor, while only 75 mL of 0.5 M potassium carbonate aqueous solution was added to the anode chamber. The cathode and anode chambers were separated by an ion-exchange membrane. A hydrophilic carbon paper working electrode and an Hg / HgO reference electrode were placed in the cathode chamber, and a platinum mesh counter electrode was placed in the anode chamber. A potential of -0.6 V (vs. RHE) was applied, and the reaction was carried out at 70 °C for 10 h. After the reaction, post-processing and product analysis were performed according to the method in Example 1.

[0042] Experimental results show that the GC-MS yield of the target coupling product, trans-stilbene, was 23.5%, significantly lower than that of Example 1. This indicates that methanol, as a co-solubilizer, can effectively promote substrate contact and interfacial mass transfer, thereby improving the efficiency of the electrochemical coupling reaction.

[0043] Comparative Example 2 The difference between this comparative example and Example 1 is that the surfactant CTAB was not added; all other experimental parameters and procedures were the same as in Example 1. Experimental results show that the yield of the target coupling product, trans-stilbene, was only 2.3%, indicating that CTAB micelles play a crucial role in the enrichment of hydrophobic substrates, interfacial mass transfer, and coupling reactions.

[0044] 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 aqueous micelle-assisted electrochemical Pd-catalyzed coupling of aryl halides and olefins, characterized in that, Includes the following steps: S1 Prepare an alkaline electrolyte, add a surfactant to it, and stir to form a micelle structure in the aqueous system to obtain a cathodic liquid; An alkaline solution is used as the anolyte; S2 Add aryl halide substrate, olefin substrate and palladium catalyst to catholy solution and mix well to obtain reaction solution; S3 The reaction solution and anolyte are transferred to the cathode chamber and anode chamber of the electrochemical reaction device, respectively. 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, an electrochemical reaction is carried out, causing the aryl halide to undergo a coupling reaction with the olefin to generate substituted olefin products.

2. The aqueous micelle-assisted electrochemical Pd-catalyzed coupling method for aryl halides and olefins according to claim 1, characterized in that, The solute in the alkaline electrolyte is potassium carbonate, the solvents are water and methanol, the surfactant is hexadecyltrimethylammonium bromide, and the alkaline solution is an aqueous solution of potassium carbonate.

3. The aqueous micelle-assisted electrochemical Pd-catalyzed coupling method for aryl halides and olefins according to claim 2, characterized in that, The concentration of potassium carbonate in the catholyte and anolyte is 0.1-0.7 M; The concentration of surfactant in the catholyte is 0.1-2 mM.

4. The aqueous micelle-assisted electrochemical Pd-catalyzed coupling method for aryl halides and olefins according to claim 1, characterized in that, The aryl halides include chlorobenzene, bromobenzene, iodobenzene, 1,4-diiodobenzene, 1,4-dibromobenzene, 4-iodoanisole, 4-acetyliodobenzene, or 2-iodotoluene; the alkenes include styrene, 4-fluorostyrene, 4-cyanostyrene, 4-methoxystyrene, or 4-vinylpyridine; the molar ratio of the aryl halide substrate to the alkene substrate is 1:0.5-2.

5. The aqueous micelle-assisted electrochemical Pd-catalyzed coupling method for aryl halides and olefins according to claim 1, characterized in that, The palladium catalyst used is Pd(PPh3)4, and the molar ratio of aryl halide substrate to palladium catalyst is 1:0.005-0.

05.

6. The aqueous micelle-assisted electrochemical Pd-catalyzed coupling method for aryl halides and olefins according to claim 1, characterized in that, The concentration of aryl halides in the reaction solution is 0.005-0.06 M.

7. The aqueous micelle-assisted electrochemical Pd-catalyzed coupling method for aryl halides and olefins according to claim 1, characterized in that, A carbon paper electrode was used as the working electrode, an Hg / HgO electrode as the reference electrode, and a platinum mesh electrode as the counter electrode.

8. The aqueous micelle-assisted electrochemical Pd-catalyzed coupling method for aryl halides and olefins according to claim 1, characterized in that, The electrochemical reaction conditions were: potential of -0.1 V to -1.2 V vs. RHE, and current density of 1-6 mA / cm². 2 The reaction is carried out at 30-70 ℃ for 5-10 h.

9. The aqueous micelle-assisted electrochemical Pd-catalyzed coupling method for aryl halides and olefins according to claim 1, characterized in that, After the electrochemical reaction was completed, the 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, which was further purified by column chromatography to obtain the substituted olefin product.

10. The application of the aqueous micelle-assisted electrochemical Pd-catalyzed coupling method for aryl halides and olefins according to any one of claims 1-9 in the field of organic synthesis.

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