Method for preparing deuterated compound through electrochemical coupling and special catalyst thereof

Abstract

The invention belongs to the technical field of electrochemical synthesis and isotope labeling, and particularly discloses a method for preparing a deuterated compound through electrochemical coupling and a special catalyst thereof. According to the invention, a carbon-hydrogen bond halogenation-dehalogenation deuteration process is coupled, a specific noble metal nitrogen-doped carbon catalyst is screened and applied as a cathode and anode catalytic material, a brand new electrochemical system is constructed for the first time, and under the environment-friendly reaction conditions of completely no solvent and no supporting electrolyte, through electrochemical driving, the electrochemical performance of the electrochemical system is improved. The selective halogenation of carbon-hydrogen bonds of the anode and the dehalogenation deuteration reaction of the cathode are synchronously realized, the two half reactions are successfully and efficiently coupled in the same reactor, and the deuterated organic compound with high additional value is directly synthesized. According to the method, a large amount of organic solvents and electrolyte salts used in traditional organic synthesis are abandoned, the environmental load and post-treatment difficulty of the reaction are remarkably reduced, and the method has the outstanding advantages of being simple in process, environmentally friendly and high in atom economy.

Description

Technical Field

[0001] This invention belongs to the field of electrochemical synthesis and isotope labeling technology, specifically relating to an electrochemical coupling method for simultaneously achieving selective halogenation of anodic carbon-hydrogen bonds and dehalogenation of cathodic dehydrogenation in a solvent-free and electrolyte-free environment by constructing a three-channel membrane electrode electrolysis reactor with an anode chamber, an intermediate channel, and a cathode chamber. The invention also includes a noble metal nitrogen-doped carbon catalyst for this method. The halogenation reaction includes chlorination, bromination, or iodination. This invention is particularly suitable for the efficient and green deuteration of non-deuterated aromatic compounds containing electrochemically dehydrogen atoms, and can be widely applied to the synthesis of deuterated drug molecules, deuterated fine chemicals, and isotope-labeled compounds. Background Technology

[0002] Deuterated compounds are those in which one or more hydrogen atoms are replaced by their stable isotope deuterium (…). 2 Organic molecules substituted with H or D atoms play a crucial role in modern chemistry, medicine, and materials science. Because deuterium and hydrogen have the same electronic structure but different masses, the introduction of deuterium atoms can significantly alter the physicochemical properties of molecules, especially the kinetic isotope effect (KIE), which can effectively slow down the metabolic rate of drug molecules in vivo, thereby prolonging the drug's half-life, reducing toxicity, and improving bioavailability. Therefore, deuterated drugs have become an important strategy in new drug development, and several deuterated drugs have been successfully launched in recent years, demonstrating enormous market potential and application value.

[0003] Currently, the synthesis of deuterated compounds mainly relies on traditional organic synthesis methods, such as acid / base catalyzed H / D exchange reactions, transition metal catalyzed cross-coupling reactions, and transfer deuteration involving boron / silicon reagents. However, these methods generally have many limitations. First, most reactions require the use of large amounts of toxic and flammable organic solvents (such as tetrahydrofuran, dichloromethane, toluene, etc.) as reaction media, which not only increases production costs but also brings serious environmental burdens and safety risks. Second, in order to maintain charge balance and ion conduction, many reactions involving ionic intermediates must add supporting electrolytes (such as tetrabutylammonium salts, lithium salts, etc.), which not only increases the complexity of the system but also makes subsequent product separation and purification difficult, reducing the overall atom economy and greenness of the process. In addition, existing methods are often cumbersome, requiring the pre-preparation of specific halogen- or metal-containing precursors, and have limited compatibility with substrate functional groups, making it difficult to achieve efficient, one-step direct deuteration.

[0004] Electrochemical synthesis, as a green and sustainable synthetic strategy, has attracted widespread attention in recent years. It utilizes electrical energy to drive chemical reactions, avoiding the use of stoichiometric oxidants or reductants in traditional redox reactions, and offers advantages such as mild conditions, high selectivity, and ease of control. In the field of deuteration, electrochemical methods have also demonstrated unique advantages, such as the direct debromination of CX (X = Cl, Br, I) bonds via cathodic reduction. However, these reactions typically still require a homogeneous system composed of organic solvents and electrolytes, failing to fundamentally solve the problems associated with solvents and electrolytes. More importantly, existing electrochemical deuteration methods are mostly single reduction processes, lacking effective coupling with other oxidation processes, resulting in low system efficiency and low resource utilization.

[0005] To address the aforementioned challenges, it is urgent to develop a novel deuteration method that is efficient, green, and capable of reaction coupling without the need for external solvents and electrolytes. Summary of the Invention

[0006] This invention aims to address the problems of existing deuteration synthesis techniques, such as reliance on organic solvents, the need for supporting electrolytes, cumbersome procedures, heavy environmental burden, and low reaction efficiency. To overcome these shortcomings, this invention provides a novel method for the electrochemical coupling preparation of deuterated compounds and its dedicated catalyst.

[0007] The core of this invention lies in constructing a three-channel membrane electrode electrolysis reactor with an anode chamber, a middle channel, and a cathode chamber. The anode chamber and the middle channel are separated by an anion exchange membrane, and the cathode chamber and the middle channel are separated by a proton exchange membrane. Under conditions without added organic solvents or supporting electrolytes, the selective halogenation reaction of carbon-hydrogen bonds at the anode (including chlorination, bromination, or iodination) and the dehalogenation reaction at the cathode are spatially separated but electrochemically coupled simultaneously. A heavy water (D2O) solution containing a halogen source is introduced into the middle channel, serving simultaneously as a halide ion source and a deuterium source, enabling a one-pot direct conversion from aromatic compounds to deuterated products.

[0008] Meanwhile, the present invention provides a noble metal nitrogen-doped carbon catalyst suitable for this special reaction system. The catalyst can efficiently catalyze two key processes: anodic carbon-hydrogen bond activation halogenation and cathodic dehalogenation deuteration, significantly improving reaction efficiency and selectivity.

[0009] To achieve the above objectives, the specific technical solution adopted by the present invention is as follows:

[0010] In a first aspect, the present invention provides a method for preparing deuterated compounds by electrochemical coupling, wherein an electrolytic reaction is carried out using a membrane electrode electrolysis reactor with three parallel flow channels;

[0011] The reactor comprises, from left to right, an anode chamber, a central flow channel, and a cathode chamber, wherein the central flow channel is sandwiched between the anode chamber and the cathode chamber; an anion exchange membrane is provided between the anode chamber and the central flow channel, and a proton exchange membrane is provided between the cathode chamber and the central flow channel, for conducting halide anions and proton / deuterium ions, respectively;

[0012] The electrolysis process using the aforementioned reactor is as follows:

[0013] Aromatic compounds are introduced into the anode chamber without any added organic solvent. An oxidation potential is applied to the anode to induce a selective halogenation reaction of carbon-hydrogen bonds (including chlorination, bromination, or iodination) to generate the corresponding aromatic halogens. The halide ions used are derived from the intermediate flow channel.

[0014] The aromatic halogenated compound is introduced into the cathode chamber without the addition of an external organic solvent (i.e., no additional organic solvent is needed as a reaction medium). A reduction potential is applied to the cathode to induce an electrochemical reduction dehalogenation reaction, and deuterium atoms are obtained from the intermediate flow channel to carry out a deuteration reaction, generating the target deuterated aromatic compound. The aromatic halogenated compound introduced into the cathode can be a standard of the anode product that is purchased directly, or it can be derived from the anode separation product.

[0015] A heavy water (D2O) solution containing a halogen source is introduced into the middle channel. This solution serves as both a halide ion source for the anodic halogenation reaction and a deuterium source for the cathode deuteration reaction.

[0016] The method described in this invention is applicable to the deuteration of various aromatic compounds. In the electrochemical reaction, the aromatic compound undergoes a selective halogenation reaction (including chlorination, bromination, or iodination) of carbon-hydrogen bonds at the anode to generate the corresponding aromatic halide. This aromatic halide then undergoes a dehalogenation deuteration reaction at the cathode to generate the target deuterated aromatic compound. The entire reaction process is carried out without the addition of external organic solvents and without supporting electrolytes, achieving a one-pot electrochemical coupling conversion from aromatic compounds to deuterated products.

[0017] Furthermore, the aromatic compound introduced into the anode chamber is an aromatic compound containing at least one aromatic ring hydrogen atom that can be electrochemically halogenated, including but not limited to benzene, toluene, ethylbenzene, cumene, anisole, phenethyl ether, styrene and its derivatives, preferably anisole.

[0018] Furthermore, the halogen source includes, but is not limited to, one or more inorganic halide salts selected from sodium chloride, potassium chloride, sodium bromide, potassium bromide, sodium iodide, and potassium iodide, or one or more organic halide salts selected from tetrabutylammonium chloride, tetrabutylammonium bromide, and tetrabutylammonium iodide.

[0019] Furthermore, the electrolysis reaction is carried out in a constant current mode with a current density of 1-20 mA / cm² and a reaction time of 0.5-2 h.

[0020] Furthermore, to achieve the aforementioned highly efficient electrochemical coupling process, this invention also provides a dedicated noble metal nitrogen-doped carbon catalyst. This catalyst is suitable for three-channel membrane electrode electrolysis reaction systems without added organic solvents or supporting electrolytes. The catalyst comprises a nitrogen-doped carbon support and a noble metal supported on the nitrogen-doped carbon support. The catalyst is used as an anode catalyst to catalyze the selective halogenation reaction of aromatic compounds (including chlorination, bromination, or iodination) of carbon-hydrogen bonds, and / or as a cathode catalyst to catalyze the electrochemical reduction dehalogenation of aromatic halides and the introduction of deuterium atoms. The cathode catalyst and the anode catalyst can be the same or different.

[0021] Furthermore, the precious metals include, but are not limited to, platinum (Pt), palladium (Pd), ruthenium (Ru), rhodium (Rh), iridium (Ir), or gold (Au).

[0022] Furthermore, the nitrogen-doped carbon support can be prepared by nitrogen doping modification of various carbon materials, including but not limited to nitrogen-doped carbon materials synthesized using Ketjen black, acetylene black, activated carbon or carbon nanotubes as the parent material, with Ketjen black being preferred.

[0023] Secondly, the present invention provides the application of a dedicated catalyst in the above-mentioned electrochemical coupling method for preparing deuterated compounds. The dedicated catalyst is the above-mentioned noble metal nitrogen-doped carbon catalyst. The application includes using it as an anode catalyst for catalyzing the selective halogenation reaction of aromatic compounds involving carbon-hydrogen bonds, and / or as a cathode catalyst for catalyzing the electrochemical reduction and dehalogenation of aromatic halides and the introduction of deuterium atoms.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] This invention proposes and implements a novel electrochemical coupling strategy for the first time: by constructing a three-channel membrane electrode electrolysis reactor with an anode chamber, an intermediate channel, and a cathode chamber, wherein the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane, the C-H bond selective halogenation reaction at the anode (including chlorination, bromination, or iodination) and the dehalogenation deuteration reaction at the cathode are spatially separated but electrochemically coupled simultaneously. A heavy water (D2O) solution containing a halogen source is introduced into the intermediate channel, which simultaneously serves as a halide ion source in the anode halogenation reaction and as a deuterium source to provide deuterium atoms for the cathode deuteration reaction. Thus, a "one-pot" conversion from aromatic compounds to deuterated products is achieved. This method does not add organic solvents or supporting electrolytes to the entire reaction system, significantly improving the greenness of the process, and enhancing energy utilization efficiency and atom economy through reaction coupling; moreover, the reaction is carried out at room temperature and pressure, under mild conditions. Meanwhile, this invention develops a noble metal nitrogen-doped carbon catalyst suitable for this solvent-free, electrolyte-free three-channel system, which effectively promotes the synergistic process of two key steps: anodic carbon-hydrogen bond activation halogenation and cathodic dehalogenation deuteration. This provides a new technical route for the efficient and green synthesis of deuterated compounds, and the coupling process and catalyst system involved have broad application prospects and important industrial value. Attached Figure Description

[0026] Figure 1 This is a schematic diagram of a three-channel reactor (X = Cl, Br, I).

[0027] Figure 2 The image shows the gas chromatogram (GC) of the carbon-hydrogen selective halogenation reaction of anisole at the anode to produce p-bromoanisole in Example 1.

[0028] Figure 3 is a gas chromatogram (GC) of 4-D-ethylbenzene produced by the dehalogenation reaction of p-bromoethylbenzene at the cathode in Example 2.

[0029] Figure 4 The diagram shows the anode and cathode performance of Example 1. In the diagram, Anode represents the anode; Cathode represents the cathode; and FE% represents the Faraday efficiency. Detailed Implementation

[0030] This invention presents a novel electrochemical system that, under completely solvent-free and electrolyte-free green reaction conditions, simultaneously achieves selective halogenation (chlorination, bromination, iodination) of C-H bonds at the anode and dehalogenation at the cathode via electrochemical drive. This successfully couples two half-reactions efficiently within the same reactor, directly synthesizing high-value-added deuterated organic compounds. The reactor structure is as follows: Figure 1As shown, from left to right, the reactor includes an anode chamber, a central flow channel, and a cathode chamber, with the central flow channel sandwiched between the anode and cathode chambers. An anion exchange membrane is installed between the anode chamber and the central flow channel, and a proton exchange membrane is installed between the cathode chamber and the central flow channel, for conducting halide anions and proton / deuterium ions, respectively. The reaction process using the reactor is as follows:

[0031] Aromatic compounds are introduced into the anode chamber without added organic solvents. An oxidation potential is applied to the anode to induce a selective halogenation reaction of carbon-hydrogen bonds, generating the corresponding aromatic halogens. The halide ions used are derived from the intermediate flow channel.

[0032] The aromatic halogenated compound is introduced into the cathode chamber without the addition of an external organic solvent. A reduction potential is applied to the cathode to induce an electrochemical reduction dehalogenation reaction. Deuterium atoms are then obtained from the intermediate flow channel to carry out a deuteration reaction, generating the target deuterated aromatic compound.

[0033] A heavy water (D2O) solution containing a halogen source is introduced into the middle channel. This solution serves as both a halide ion source for the anodic halogenation reaction and a deuterium source to provide deuterium atoms for the cathode deuteration reaction.

[0034] The entire reaction process is carried out without the addition of external organic solvents and without supporting electrolytes, realizing a one-pot electrochemical coupling conversion from aromatic compounds to deuterated products.

[0035] The key to this invention lies in the coupling of a C-H bond halogenation-dehalogenation deuteration process, and the screening and application of specific noble metal nitrogen-doped carbon catalysts as anode and cathode catalysts. These catalysts exhibit excellent electrocatalytic activity and stability in solvent-free systems, effectively promoting the synergistic progression of key steps such as C-H bond activation, bromination, and deuteration. Examples of catalyst preparation are provided below:

[0036] Preparation method of noble metal nitrogen-doped carbon catalyst (taking PdNC catalyst with 5 wt.% noble metal loading as an example): 1 g of Ketjen black was dispersed in concentrated nitric acid solution and heated under reflux for 24 h to separate the treated Ketjen black. Then, 10 g of dicyandiamine was added as a nitrogen source, and the resulting solid was calcined at 800°C for 1 hour under a nitrogen atmosphere. After natural cooling, it was ground to obtain a nitrogen-doped carbon support.

[0037] 50 mg of nitrogen-doped carbon support was added to 50 mL of deionized water, followed by the addition of a chloropalladium acid solution (containing 2.5 mg of metallic Pd). The mixture was stirred for 2 hours, then 3 mL of 2 M sodium hydroxide and 120 mg of sodium borohydride were added, and the mixture was stirred for another 2 hours to obtain the PdNC catalyst. RuNC, PtNC, and other catalysts were prepared using a similar method, replacing the chloropalladium acid with the corresponding metal precursor.

[0038] The application method of the prepared noble metal nitrogen-doped carbon catalyst is as follows: 5 mg of the noble metal nitrogen-doped carbon catalyst is weighed and mixed with 700 μL of ethanol, 200 μL of deionized water, and 100 μL of Nafion solution to prepare a homogeneous slurry. 100 μL of the homogeneous slurry is uniformly coated onto one side of a carbon cloth, and the resulting dry carbon cloth loaded with the catalyst serves as the electrode. The side with the catalyst is assembled with an anion exchange membrane using a hot-pressing method to form an anode membrane electrode assembly. The side with the catalyst is assembled with a proton exchange membrane using a hot-pressing method to form a cathode membrane electrode assembly. The anode and cathode membrane electrode assemblies are placed between bipolar plates to form a complete assembly. Figure 1 The electrolytic reactor shown.

[0039] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. The anion exchange membrane used in all embodiments is Fumasep FAB-PK-130. The proton exchange membrane is DuPont Nafion N115 perfluorosulfonic acid ion exchange membrane.

[0040] Example 1

[0041] Pure anisole (4 mL) was introduced into the anode channel as a substrate for the C-H bond selective halogenation reaction. The anode catalyst was a palladium nitrogen-doped carbon catalyst (PdNC), and the cathode catalyst was a ruthenium nitrogen-doped carbon catalyst (RuNC). The catalyst was introduced into the intermediate channel through a coating process using a heavy aqueous solution containing 0.5 mol / L sodium bromide (D2O, 99.9% D) as a halogen source and a deuterium source. The anode chamber and the intermediate channel were separated by an anion exchange membrane, and the cathode chamber and the intermediate channel were separated by a proton exchange membrane.

[0042] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode chambers were collected separately.

[0043] Example 2

[0044] Pure ethylbenzene (4 mL) is introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is a palladium nitrogen-doped carbon catalyst (PdNC), and the cathode catalyst is a ruthenium nitrogen-doped carbon catalyst (RuNC); a heavy aqueous solution containing 0.5 mol / L sodium bromide (D2O, 99.9% D) is introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0045] Electrolysis was performed in constant current mode, with a current density of 20 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0046] Example 3

[0047] Pure toluene (4 mL) is introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is a platinum-nitrogen-doped carbon catalyst (PtNC), and the cathode catalyst is a rhodium-nitrogen-doped carbon catalyst (RhNC); a heavy aqueous solution containing 0.5 mol / L sodium chloride (D2O, 99.9% D) is introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0048] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0049] Example 4

[0050] Pure ethylbenzene (4 mL) is introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is a ruthenium nitrogen-doped carbon catalyst (RuNC), and the cathode catalyst is a palladium nitrogen-doped carbon catalyst (PdNC); a heavy aqueous solution containing 0.5 mol / L potassium iodide (D2O, 99.9% D) is introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0051] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0052] Example 5

[0053] Pure cumene (4 mL) was introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst was a palladium nitrogen-doped carbon catalyst (PdNC), and the cathode catalyst was an iridium nitrogen-doped carbon catalyst (IrNC); a heavy aqueous solution containing 0.5 mol / L tetrabutylammonium bromide (D2O, 99.9% D) was introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel were separated by an anion exchange membrane, and the cathode chamber and the intermediate channel were separated by a proton exchange membrane.

[0054] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0055] Example 6

[0056] The anode chamber is circulated with pure phenylethyl ether (4 mL) as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is a gold nitrogen-doped carbon catalyst (AuNC), and the cathode catalyst is a ruthenium nitrogen-doped carbon catalyst (RuNC); the intermediate channel is circulated with a heavy aqueous solution containing 0.1 mol / L potassium bromide (D2O, 99.9% D) as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0057] Electrolysis was performed in constant current mode, with a current density of 1 mA / cm² and a reaction time of 2 hours. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0058] Example 7

[0059] Pure styrene (4 mL) is introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is a platinum-nitrogen-doped carbon catalyst (PtNC), and the cathode catalyst is a palladium-nitrogen-doped carbon catalyst (PdNC); a heavy aqueous solution containing 1.0 mol / L potassium chloride (D2O, 99.9% D) is introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0060] Electrolysis was performed in constant current mode, with a current density of 5 mA / cm² and a reaction time of 0.5 hours. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0061] Example 8

[0062] Pure benzene (4 mL) is introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is a ruthenium nitrogen-doped carbon catalyst (RuNC), and the cathode catalyst is a rhodium nitrogen-doped carbon catalyst (RhNC); a heavy aqueous solution containing 0.5 mol / L sodium iodide (D2O, 99.9% D) is introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0063] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0064] Example 9

[0065] Pure toluene (4 mL) was introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst was a palladium-nitrogen-doped acetylene black support catalyst (Pd / NC-AB), and the cathode catalyst was a ruthenium-nitrogen-doped acetylene black support catalyst (Ru / NC-AB); a heavy aqueous solution containing 0.5 mol / L tetrabutylammonium chloride (D2O, 99.9% D) was introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel were separated by an anion exchange membrane, and the cathode chamber and the intermediate channel were separated by a proton exchange membrane.

[0066] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0067] Example 10

[0068] Pure anisole (4 mL) was introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst was a platinum-nitrogen-doped activated carbon catalyst (Pt / NC-AC), and the cathode catalyst was a palladium-nitrogen-doped activated carbon catalyst (Pd / NC-AC); a heavy aqueous solution containing 0.5 mol / L sodium bromide (D2O, 99.9% D) was introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel were separated by an anion exchange membrane, and the cathode chamber and the intermediate channel were separated by a proton exchange membrane.

[0069] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0070] Example 11

[0071] Pure ethylbenzene (4 mL) was introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst was a ruthenium nitrogen-doped carbon nanotube catalyst (Ru / NC-CNT), and the cathode catalyst was an iridium nitrogen-doped carbon nanotube catalyst (Ir / NC-CNT); a heavy aqueous solution containing 0.5 mol / L potassium iodide (D2O, 99.9% D) was introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel were separated by an anion exchange membrane, and the cathode chamber and the intermediate channel were separated by a proton exchange membrane.

[0072] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0073] Example 12

[0074] Pure cumene (4 mL) was introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst was a gold-nitrogen-doped carbon catalyst (AuNC), and the cathode catalyst was a rhodium-nitrogen-doped carbon catalyst (RhNC); a heavy aqueous solution containing 0.5 mol / L sodium chloride (D2O, 99.9% D) was introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel were separated by an anion exchange membrane, and the cathode chamber and the intermediate channel were separated by a proton exchange membrane.

[0075] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0076] Example 13

[0077] The anode chamber is purified with pure phenylethyl ether (4 mL) as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is a palladium nitrogen-doped carbon catalyst (PdNC), and the cathode catalyst is a platinum nitrogen-doped carbon catalyst (PtNC); the intermediate channel is purified with a heavy aqueous solution containing 0.5 mol / L tetrabutylammonium iodide (D2O, 99.9% D) as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0078] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0079] Example 14

[0080] Pure styrene (4 mL) is introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is a ruthenium nitrogen-doped carbon catalyst (RuNC), and the cathode catalyst is a palladium nitrogen-doped carbon catalyst (PdNC); a heavy aqueous solution containing 0.3 mol / L potassium bromide (D2O, 99.9% D) is introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0081] Electrolysis was performed in constant current mode, with a current density of 3 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0082] Example 15

[0083] Pure benzene (4 mL) is introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is a rhodium nitrogen-doped carbon catalyst (RhNC), and the cathode catalyst is an iridium nitrogen-doped carbon catalyst (IrNC); a heavy aqueous solution containing 0.5 mol / L potassium chloride (D2O, 99.9% D) is introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0084] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0085] Example 16

[0086] Pure toluene (4 mL) is introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is a palladium nitrogen-doped carbon catalyst (PdNC), and the cathode catalyst is a gold nitrogen-doped carbon catalyst (AuNC); a heavy aqueous solution containing 0.5 mol / L sodium iodide (D2O, 99.9% D) is introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0087] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0088] Example 17

[0089] Pure anisole (4 mL) was introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst was platinum-nitrogen-doped Ketjenblack catalyst (PtNC), and the cathode catalyst was ruthenium-nitrogen-doped Ketjenblack catalyst (RuNC); a heavy aqueous solution containing 0.7 mol / L sodium bromide (D2O, 99.9% D) was introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel were separated by an anion exchange membrane, and the cathode chamber and the intermediate channel were separated by a proton exchange membrane.

[0090] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0091] Example 18

[0092] Pure ethylbenzene (4 mL) is introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is an iridium nitrogen-doped carbon catalyst (IrNC), and the cathode catalyst is a palladium nitrogen-doped carbon catalyst (PdNC); a heavy aqueous solution containing 0.5 mol / L tetrabutylammonium bromide (D2O, 99.9% D) is introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0093] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0094] Example 19

[0095] Pure cumene (4 mL) was introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst was a ruthenium nitrogen-doped carbon catalyst (RuNC), and the cathode catalyst was a platinum nitrogen-doped carbon catalyst (PtNC); a heavy aqueous solution containing 0.5 mol / L sodium chloride (D2O, 99.9% D) was introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel were separated by an anion exchange membrane, and the cathode chamber and the intermediate channel were separated by a proton exchange membrane.

[0096] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0097] Example 20

[0098] The anode chamber is purified with pure phenylethyl ether (4 mL) as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is a palladium nitrogen-doped carbon catalyst (PdNC), and the cathode catalyst is a rhodium nitrogen-doped carbon catalyst (RhNC); the intermediate channel is purified with a heavy aqueous solution containing 0.5 mol / L potassium iodide (D2O, 99.9% D) as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0099] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0100] Example 21

[0101] Pure styrene (4 mL) is introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is a gold nitrogen-doped carbon catalyst (AuNC), and the cathode catalyst is an iridium nitrogen-doped carbon catalyst (IrNC); a heavy aqueous solution containing 0.5 mol / L sodium bromide (D2O, 99.9% D) is introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0102] Electrolysis was performed in constant current mode, with a current density of 20 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0103] Example 22

[0104] Pure benzene (4 mL) is introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is a palladium nitrogen-doped carbon catalyst (PdNC), and the cathode catalyst is a ruthenium nitrogen-doped carbon catalyst (RuNC); a heavy aqueous solution containing 0.5 mol / L tetrabutylammonium chloride (D2O, 99.9% D) is introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0105] Electrolysis was performed in constant current mode, with a current density of 12 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0106] Example 23

[0107] Pure toluene (4 mL) is introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is a platinum-nitrogen-doped carbon catalyst (PtNC), and the cathode catalyst is a palladium-nitrogen-doped carbon catalyst (PdNC); a heavy aqueous solution containing 0.5 mol / L sodium iodide (D2O, 99.9% D) is introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0108] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0109] Example 24

[0110] Pure anisole (4 mL) was introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst was a ruthenium nitrogen-doped carbon catalyst (RuNC), and the cathode catalyst was a gold nitrogen-doped carbon catalyst (AuNC); a heavy aqueous solution containing 0.2 mol / L potassium chloride (D2O, 99.9% D) was introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel were separated by an anion exchange membrane, and the cathode chamber and the intermediate channel were separated by a proton exchange membrane.

[0111] Electrolysis was carried out in constant current mode, with a current density of 15 mA / cm² and a reaction time of 1.5 hours. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0112] Example 25

[0113] Pure ethylbenzene (4 mL) is introduced into the anode chamber as a substrate for the C-H bond selective halogenation reaction; the anode catalyst is a rhodium nitrogen-doped carbon catalyst (RhNC), and the cathode catalyst is a palladium nitrogen-doped carbon catalyst (PdNC); a heavy aqueous solution containing 0.5 mol / L potassium bromide (D2O, 99.9% D) is introduced into the intermediate channel as a halogen source and a deuterium source; the anode chamber and the intermediate channel are separated by an anion exchange membrane, and the cathode chamber and the intermediate channel are separated by a proton exchange membrane.

[0114] Electrolysis was performed in constant current mode, with a current density of 2 mA / cm² and a reaction time of 1 hour. After the reaction was completed, the organic phase products in the anode and cathode channels were collected separately.

[0115] The following tests were performed on the products of the examples:

[0116] 1. Gas chromatography (GC) analysis was performed on the collected organic phase products in the anolyte and cathode channels. The results showed that the target products were successfully synthesized in all examples, and the products had high purity (no impurity peaks). Example figures are shown below. Figure 2-3 As shown.

[0117] II. Faraday efficiency (FE) tests were performed on the anode and cathode of each embodiment. The results showed that both the cathode and anode of each embodiment exhibited high Faraday efficiency. Figure 4 Taking the test results of Example 1 as an example, the Faraday efficiencies of both the cathode and anode are above 80%, indicating good reactivity and high electron selectivity. Furthermore, the anode Faraday efficiency is close to 100%, confirming that there are few byproducts.

[0118] This specific embodiment is merely an explanation of the present invention and is not intended to limit the present invention. Any changes made by those skilled in the art after reading the specification of the present invention, as long as they are within the scope of the claims of the present invention, will be protected by patent law.

Claims

1. A method for preparing deuterated compounds by electrochemical coupling, characterized in that, Electrolysis was carried out using a membrane electrode electrolysis reactor with three parallel flow channels; The reactor comprises, from left to right, an anode chamber, a central flow channel, and a cathode chamber, wherein the central flow channel is sandwiched between the anode chamber and the cathode chamber; an anion exchange membrane is provided between the anode chamber and the central flow channel, and a proton exchange membrane is provided between the cathode chamber and the central flow channel, for conducting halide anions and proton / deuterium ions, respectively; The electrolytic reaction process using the reactor is as follows: an aromatic compound is introduced into the anode chamber, where a selective halogenation reaction of carbon-hydrogen bonds occurs to generate the corresponding aromatic halide; the aromatic halide is introduced into the cathode chamber, where an electrochemical reduction dehalogenation reaction occurs, introducing deuterium atoms to generate the target deuterated aromatic compound; a heavy aqueous solution containing a halogen source is introduced into the intermediate channel, which serves both as a halide ion source participating in the anode halogenation reaction and as a deuterium source providing deuterium atoms for the cathode deuteration reaction; the entire reaction process is carried out without the addition of external organic solvents and without supporting electrolytes, realizing a one-pot electrochemical coupling conversion from aromatic compound to deuterated product.

2. The method according to claim 1, characterized in that, The aromatic compound introduced into the anode chamber is an aromatic compound containing at least one aromatic ring hydrogen atom that can be electrochemically halogenated, and is one of benzene, toluene, ethylbenzene, cumene, anisole, phenethyl ether, styrene and its derivatives.

3. The method according to claim 1, characterized in that, The halogen source is one or more inorganic halide salts selected from sodium chloride, potassium chloride, sodium bromide, potassium bromide, sodium iodide, and potassium iodide, or one or more organic halide salts selected from tetrabutylammonium chloride, tetrabutylammonium bromide, and tetrabutylammonium iodide.

4. The method according to claim 1, characterized in that, The catalyst used in the anode and / or cathode is a noble metal nitrogen-doped carbon catalyst, which includes a nitrogen-doped carbon support and a noble metal supported on the nitrogen-doped carbon support.

5. The method according to claim 4, characterized in that, The precious metal is platinum, palladium, ruthenium, rhodium, iridium, or gold.

6. The method according to claim 4, characterized in that, The nitrogen-doped carbon support is prepared by nitrogen doping modification of carbon materials, wherein the carbon materials are Ketjen black, acetylene black, activated carbon, or carbon nanotubes.

7. The use of a dedicated catalyst in the electrochemical coupling method for preparing deuterated compounds according to claim 1, characterized in that, The specific catalyst is a noble metal nitrogen-doped carbon catalyst, which includes a nitrogen-doped carbon support and a noble metal supported on the nitrogen-doped carbon support.

8. The application according to claim 7, characterized in that, The applications include serving as an anode catalyst for the selective halogenation of aromatic compounds via carbon-hydrogen bonds, and / or as a cathode catalyst for the electrochemical reduction and dehalogenation of aromatic halogens, introducing deuterium atoms into the reaction.

9. The application according to claim 7, characterized in that, The precious metal is platinum, palladium, ruthenium, rhodium, iridium, or gold.

10. The application according to claim 7, characterized in that, The nitrogen-doped carbon support is prepared by nitrogen doping modification of carbon materials, wherein the carbon materials are Ketjen black, acetylene black, activated carbon, or carbon nanotubes.

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