A method for synthesizing deuterated olefins by using D2O as deuterium source and palladium membrane catalysis

Abstract

The application discloses a synthesis method of deuterium-substituted olefin by using D2O as a deuterium source and a palladium membrane for catalysis, and belongs to the technical field of synthesis of deuterium-substituted olefin blocks. The application uses a three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane as a reactor, uses the palladium membrane as a working electrode, uses a deuterium water solution as an electrolyte, electrolyzes the deuterium water by using a constant potential electrolysis method, transmits active deuterium formed to an organic reaction side using anhydrous ethanol or cyclohexane as an organic solvent, and then synthesizes deuterium-substituted olefin compounds by using a palladium membrane modified by sodium benzene thiol for catalyzing reduction and deuterization of acetylene compounds with high selectivity, so as to further synthesize corresponding deuterium-substituted drugs. The application provides a green, efficient, high-universality and low-cost amplification synthesis method for synthesizing deuterium-substituted olefin blocks containing easily-reduced and easily-hydrolyzed functional groups, and has a wide application prospect.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of synthesis of deuterated olefin building blocks, and particularly relates to a synthesis method of deuterated olefin catalyzed by a palladium membrane with D2O as a deuterium source. BACKGROUND

[0002] By taking advantage of the fact that C-D is more stable than C-H, selective deuteration of compounds with physiological activity can prolong their half-life to improve sustainability, and can also inhibit the generation of toxic metabolites to improve their safety. In 2017, the world's first deuterated drug (deuterated tetrabenazine) was approved by the US Food and Drug Administration (FDA) for the treatment of Huntington's disease, and is considered to be a specific drug with better treatment effect than tetrabenazine. In 2021, Donafenib developed by Suzhou Zijing Pharmaceutical was approved for listing as the world's first deuterated tumor drug. In recent years, more and more deuterium-containing drugs have entered clinical trials, and deuterium-labeled compounds are widely used as metabolic or pharmacokinetic probes. Terminal olefins, as useful synthetic building blocks, exist in a large number of drugs, agrochemicals and natural products.

[0003] So far, the methods for synthesizing deuterated olefins have developed from direct H / D exchange to water-phase electrocatalytic deuterium addition to alkyne, the latter of which does not require the harsh reaction conditions, expensive organic deuterium source or deuterium gas usually required by the former, and can effectively control the selectivity of the product by adjusting the voltage or current, providing an important means with mild conditions, environmental friendliness, high economy and high synthesis efficiency, but still has many deficiencies, limiting its wide application. For example, the solubility of alkyne and olefin in water is usually low, so it is difficult to carry out large-scale synthesis, and the separation step is complicated, increasing the separation cost; for alkyne containing easily reduced functional groups, the functional groups are difficult to preserve; for alkyne containing easily hydrolyzed functional groups, they cannot exist under water-phase electrocatalytic conditions; in addition, most drug synthesis processes are in anhydrous conditions, and the olefin synthesized in water phase must be dried before use. As can be seen, deuterated olefins are currently mainly obtained by olefin H / D exchange or alkyne reduction deuterization in water phase, which has problems such as environmental unfriendliness, low universality, difficulty in scaling up and high separation cost, especially for alkyne containing easily reduced and easily hydrolyzed functional groups, which has greater difficulties and challenges. Therefore, it is urgent to develop a green, economical and efficient method to realize the wide synthesis of deuterated olefins with high functional group compatibility and facilitate the subsequent synthesis of deuterated drugs.

[0004] In recent research and development, palladium membrane is used in electrocatalytic organic synthesis reactor due to its transmission of active deuterium, which solves the problems of low solubility of alkyne in water, difficult large-scale synthesis, and high cost of water phase separation by separating aqueous electrolyte and organic phase deuterium reaction, and is expected to solve the problem that alkyne containing easily hydrolyzed functional groups cannot exist in water phase, and has wide application potential, but the selectivity of olefin is difficult to control, which greatly limits the application of the method. Therefore, it is a challenge to modify the palladium membrane reactor to improve the selectivity of deuterated olefin. SUMMARY

[0005] To solve the above problems in the prior art, the present application provides a synthesis method of palladium membrane catalytic deuterated olefin with D2O as deuterium source, which uses economical D2O as deuterium source, sodium benzene sulfide modified palladium membrane to catalyze alkyne reduction deuterization to synthesize deuterated olefin building block and deuterated drug containing easily reduced and easily hydrolyzed functional groups. In a wide range of potential and current, high selectivity synthesis of deuterated olefin compounds can be realized, the reaction conditions are mild, the operation is simple, the palladium membrane catalyst can be reused, which provides a safe, green and efficient method for the synthesis of deuterated olefin, and the synthesized deuterated olefin solution can be directly used for subsequent drug synthesis without separation, which provides a lower cost and more convenient method for the application of deuterated olefin building block.

[0006] To achieve the above purpose, the present application provides the following technical scheme:

[0007] One of the technical schemes of the present application: a synthesis method of palladium membrane catalytic deuterated olefin with D2O as deuterium source, comprising the following steps: in a three-chamber reactor separated by palladium membrane and ion exchange membrane, electrolyte deuterium water solution is added in two reaction chambers separated by ion exchange membrane for electrolysis deuterium water reaction, organic solvent, sodium benzene sulfide and alkyne reactant are added in another reaction chamber for alkyne deuterization organic reaction, palladium membrane is used as working electrode, deuterium water is used as deuterium source, deuterium water is electrolyzed by constant potential electrolysis method, active deuterium generated from electrolysis reaction side is transmitted to organic reaction side, and then deuterated olefin compound is obtained by reducing deuterization of alkyne compound through sodium benzene sulfide modified palladium membrane.

[0008] Further, one side of the palladium membrane is deposited with palladium nanotaper, and the side deposited with palladium nanotaper faces the reaction chamber for organic reaction.

[0009] Further, the concentration of the sodium benzene sulfide is 0.3-0.5M.

[0010] Further, the concentration of the sodium benzene sulfide is 0.4M.

[0011] Further, the preparation method of the palladium membrane comprises the following steps: taking the palladium membrane as the working electrode, and constant potential electrolysis of the electrolyte containing palladium.

[0012] The palladium nanotips are deposited to increase the active area and improve the deuterium rate of alkynes.

[0013] Deuterium rate of alkynes: without palladium nanotips, palladium membrane modified by sodium benzene thiol = 4:9.

[0014] Further, the palladium membrane is cleaned, calcined in inert atmosphere and acidized in advance; the electrolysis uses Hg / HgO as reference electrode and carbon rod as counter electrode; the constant potential is -0.2V, and the electrolysis of the palladium-containing electrolyte is carried out until the coulombic quantity reaches at least 13C.

[0015] Further, the palladium membrane is cleaned, calcined in inert atmosphere and acidized in advance; the electrolysis uses Hg / HgO as reference electrode and carbon rod as counter electrode; the constant potential is -0.2V, and the electrolysis of the palladium-containing electrolyte is carried out until the coulombic quantity reaches at least 13C. -1 Further, the palladium membrane is cleaned, calcined in inert atmosphere and acidized in advance; the electrolysis uses Hg / HgO as reference electrode and carbon rod as counter electrode; the constant potential is -0.2V, and the electrolysis of the palladium-containing electrolyte is carried out until the coulombic quantity reaches at least 13C.

[0016] Further, the palladium membrane is cleaned, calcined in inert atmosphere and acidized in advance; the electrolysis uses Hg / HgO as reference electrode and carbon rod as counter electrode; the constant potential is -0.2V, and the electrolysis of the palladium-containing electrolyte is carried out until the coulombic quantity reaches at least 13C.

[0017] Further, the palladium membrane is cleaned, calcined in inert atmosphere and acidized in advance; the electrolysis uses Hg / HgO as reference electrode and carbon rod as counter electrode; the constant potential is -0.2V, and the electrolysis of the palladium-containing electrolyte is carried out until the coulombic quantity reaches at least 13C.

[0018] Further, the palladium membrane is cleaned, calcined in inert atmosphere and acidized in advance; the electrolysis uses Hg / HgO as reference electrode and carbon rod as counter electrode; the constant potential is -0.2V, and the electrolysis of the palladium-containing electrolyte is carried out until the coulombic quantity reaches at least 13C.

[0019]

[0020] Wherein, R is selected from halogen, nitro, acyl, cyano or borate.

[0021] Further, R is selected from bromine, chlorine, iodine, nitro, formyl, cyanomethyl or borate.

[0022] Further, the alkyne reactant includes any one of 3-bromopropyne, 4-bromophenylacetylene, 3-bromophenylacetylene, 2-bromophenylacetylene, 4-chlorophenylacetylene, 4-iodophenylacetylene, 4-nitrophenylacetylene, 4-ethynylbenzaldehyde, 4-ethynylbenzonitrile, 2-(4-ethynylphenyl)-4,4,5,5-tetramethyl-[1,3 2]-dioxaborolane and 2-[(prop-2-ynoxy)methyl]oxirane; the R substituent can be substituted at any position on the benzene ring. The corresponding deuterated alkene compound is 3-bromoprop-1-ene-1,2-d2, 1-bromo-4-(vinyl-d2)benzene, 1-bromo-3-(vinyl-d2)benzene, 1-bromo-2-(vinyl-d2)benzene, 1-chloro-4-(vinyl-d2)benzene, 1-iodo-4-(vinyl-d2)benzene, 1-nitro-4-(vinyl-d2)benzene, 4-(vinyl-d2)benzaldehyde, 1-(4-(vinyl-d2)phenyl)carbonitrile, 2-(4-(vinyl-d2)-4,4,5,5-tetramethyl-[1,3 2]-dioxaborolane, 2-(((allyl-2,3-d2)oxy)methyl)oxirane.

[0023] Further, the alkali salt includes potassium carbonate, and the concentration of the deuterium oxide solution of potassium carbonate is 0.5M; the organic solvent includes anhydrous ethanol or cyclohexane; the temperature of the electrolytic deuterium oxide reaction and the organic reaction is 20-25℃, and the time is 4-8h; the constant potential is-1.5--4V.

[0024] The second technical scheme of the present application is the application of the synthesis method in the synthesis of deuterated drugs.

[0025] Further, the deuterated drugs include naphthol, cinnarizine, artemisinin derivatives and estradiol derivatives.

[0026] The third technical scheme of the present application is a sodium thiophenol modified palladium membrane, one side of the palladium membrane is modified with sodium thiophenol.

[0027] Further, the side modified with sodium thiophenol is previously deposited with palladium nanotapers. The palladium membrane on the side facing the electrochemical chamber is not specially treated, that is, no palladium nanotapers are deposited, and no sodium thiophenol modification is performed.

[0028] The fourth technical scheme of the present application is a preparation method of the sodium thiophenol modified palladium membrane as described above, the sodium thiophenol modified palladium membrane is generated in situ in the synthesis process of the palladium membrane catalyzed deuterated alkene with D2O as the deuterium source.

[0029] The fifth technical solution of the present application: the application of the sodium benzene thiol modified palladium membrane in the synthesis of deuterated olefins catalyzed by the palladium membrane with D2O as the deuterium source.

[0030] The reaction principle of the synthesis of deuterated olefins is as follows:

[0031]

[0032] The method for synthesizing deuterated olefins by using the sodium benzene thiol modified palladium membrane to catalyze the reduction deuterization of alkynes in a palladium membrane reactor with D2O as the deuterium source, and then synthesizing deuterated drugs, comprises the following contents: in a three-chamber reactor separated by a palladium membrane and an ion exchange membrane, electrolyte is added in two chambers separated by an ion exchange membrane to carry out electrolysis of deuterium water reaction, and organic solvent is added in the other chamber to carry out organic reaction of deuterization of alkynes, the palladium membrane is used as the working electrode, deuterium water is used as the deuterium source, the constant potential electrolysis method is used to electrolyze the deuterium water, the active deuterium generated is transmitted from the side of the electrolysis reaction to the side of the organic reaction, and then the sodium benzene thiol modified palladium membrane is used to reduce and deuterize the alkynyl compound to obtain the deuterated olefin compound, and the related deuterated drugs are obtained through a simple synthesis process.

[0033] The reaction mechanism of the present application is characterized in that the active deuterium generated by the electrolysis of water on one side of the palladium membrane is transmitted to the other side of the palladium membrane to participate in the deuterization reaction of alkynes, the palladium membrane is modified by sodium benzene thiol, and the selectivity of deuterated olefins is improved.

[0034] Compared with the prior art, the present application has the following beneficial effects:

[0035] (1) The present application can realize efficient and high-selectivity synthesis of deuterated olefins in a wide range of potentials and currents, and the reaction conversion rate can reach 92% and the selectivity can reach 95% in the potential range of-1.5 to-4 V or the current range of 10 to 300 mA.

[0036] (2) The present application has good tolerance to easily reduced and easily hydrolyzed functional groups and good substrate applicability.

[0037] (3) The present application uses low-cost deuterium water as the deuterium source, has mild reaction conditions, and is simple to operate, reduces the complicated extraction steps, has high utilization rate of deuterium water, does not need to replace deuterium water due to changes in the type of alkynyl compound, and effectively avoids the problems of using expensive deuterium gas, organic deuterated reagents, complex operation, long reaction time, and low utilization rate of deuterium water in other synthesis methods.

[0038] (4) The present application solves the problem that alkynyl compounds cannot be used to synthesize olefins in large quantities due to low solubility in water.

[0039] (6) The palladium membrane catalyst of the present application has good stability and can be used for a long time. BRIEF DESCRIPTION OF DRAWINGS

[0040] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed in the embodiments will be briefly introduced below. Obviously, the drawings in the following description only constitute some embodiments of the present application, and for those skilled in the art, other drawings can also be obtained from these drawings without creative effort.

[0041] Figure 1 Schematic diagram of catalytic semi-deuteration reaction of alkyne in the palladium membrane reactor of the present application;

[0042] Figure 2 NMR spectrum of the product 3-bromoprop-1-ene-1,2-d2 (2a) prepared in Example 1, wherein (a) is 1 H NMR spectrum;

[0043] Figure 3 NMR spectrum of the product 1-bromo-4-(vinyl-d2)benzene (2b) prepared in Example 2, wherein (a) is 1 H NMR spectrum, (b) is 13 C NMR spectrum;

[0044] Figure 4 NMR spectrum of the product 1-bromo-3-(vinyl-d2)benzene (2c) prepared in Example 3, wherein (a) is 1 H NMR spectrum, (b) is 13 C NMR spectrum;

[0045] Figure 5 NMR spectrum of the product 1-bromo-2-(vinyl-d2)benzene (2d) prepared in Example 4, wherein (a) is 1 H NMR spectrum, (b) is 13 C NMR spectrum;

[0046] Figure 6 NMR spectrum of the product 4-(vinyl-d2)benzaldehyde (2e) prepared in Example 5, wherein (a) is 1 H NMR spectrum, (b) is 13 C NMR spectrum;

[0047] Figure 7 NMR spectrum of the product 1-nitro-4-(vinyl-d2)benzene (2f) prepared in Example 6, wherein (a) is 1 H NMR spectrum, (b) is 13 C NMR spectrum;

[0048] Figure 8The NMR spectrum of the product 1-iodo-4-(vinyl-d2)benzene (2g) prepared in Example 7 is shown, wherein (a) is 1 The H NMR spectrum, (b) is 13 C NMR spectrum;

[0049] Figure 9 The NMR spectrum of the product 2-(4-(vinyl-d2)-4,4,5,5-tetramethyl-[1,32]-dioxoborane (2h) prepared in Example 8 is shown, wherein (a) is 1 The H NMR spectrum, (b) is 13 C NMR spectrum;

[0050] Figure 10 The NMR spectrum of the product 2-(((allyl-2,3-d2)oxy)methyl)ethylene oxide (2i) prepared in Example 9 is shown, where (a) is... 1 The H NMR spectrum, (b) is 13 C NMR spectrum;

[0051] Figure 11 The NMR spectrum of product 1-(4-(vinyl-d2)phenyl)formonitrile (2j) prepared in Example 10 is shown, wherein (a) is 1 The H NMR spectrum, (b) is 13 C NMR spectrum;

[0052] Figure 12 The NMR spectrum of the product naftifine-d2(2k) prepared in Example 11 is shown in (a). 1 The H NMR spectrum, (b) is 13 C NMR spectrum;

[0053] Figure 13 The NMR spectrum of the product cinnarizine-d2(2l) prepared in Example 12 is shown, where (a) is... 1 The H NMR spectrum, (b) is 13 C NMR spectrum;

[0054] Figure 14 The image shows the NMR spectrum of the artemisinin derivative-d2(2m) prepared in Example 13, where (a) is... 1 HNMR spectrum, (b) is 13 C NMR spectrum;

[0055] Figure 15 The NMR spectrum of the estradiol derivative-d2(2n) prepared in Example 14 is shown in (a). 1 HNMR spectrum, (b) is 13 C NMR spectrum;

[0056] Figure 16 Substrate expansion chart for reduction of functionalized alkyne compounds to functionalized deuterated olefin compounds using PhS-Pd prepared in Example 15 as catalyst and synthesis chart of naphthol, cinnarizine, artemisinin derivatives, estradiol derivatives using deuterated olefin as starting material;

[0057] Figure 17 Scanning electron microscope (SEM) image of PhS-Pd prepared in Example 15;

[0058] Figure 18 In (a) and (b) are high angle annular dark field scanning transmission electron microscope (HADDF-STEM) and energy dispersive X-ray spectroscopy (EDS) elemental mapping images of PhS-Pd prepared in Example 15, (b) is high resolution transmission electron microscope (HRTEM) image;

[0059] Figure 19 X-ray diffraction (XRD) image of PhS-Pd prepared in Example 15;

[0060] Figure 20 In (a) and (b) are Pd 3d and S2p X-ray photoelectron spectroscopy (XPS) images of PhS-Pd prepared in Example 15, respectively;

[0061] Figure 21 Conversion of starting material and selectivity of product comparison chart of Example 2 and Comparative Example 2;

[0062] Figure 22 Long time catalytic reduction deuterization stability test chart of PhS-Pd prepared in Example 15, reaction is modeled on Example 2.

[0063] Figure 23 High selectivity electrocatalytic semi-hydrogenation of alkyne to olefin chart of PhS-Pd prepared in Example 15 in wide potential (-1.5 to -4 V) and wide current (10 to 300 mA) range, reaction is modeled on 2b formation. DETAILED DESCRIPTION

[0064] Various illustrative embodiments of the present application are now described in detail below. The applications described herein, however, can be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and fully convey the scope of the application to those skilled in the art. In the drawings, like reference numerals refer to like elements throughout the several views. As used herein, the term "or" as used herein, without additional context, can be used to indicate alternative examples or non-mutually exclusive examples.

[0065] Also, for ranges of values, the disclosure herein also contemplates each and every value and sub-range within the range. The disclosure herein also contemplates that, in some embodiments, the ranges should be greater than or equal to the minimum value and less than or equal to the maximum value. In this document, the terms "comprise", "comprising", "include", "including", "contain", "containing", "have", "having", "engage", "engaging", "connect", "connecting" or "provide", "providing" or the like are open-ended licensing terms. The phrase "consisting of" is a closed-ended licensing term and means that the named elements are the only ones that are present in the composition. The phrase "consisting essentially of" is a closed-ended licensing term and means that the named elements are the only ones that are present in the composition, with the exception of impurities that are present in the composition. The term "comprising" means "including, but not limited to".

[0066] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, preferred methods and materials are described. All documents mentioned herein are incorporated by reference to disclose and describe the methods and / or materials in connection with which the documents are cited. In case of conflict between the content of the specification and that of any document incorporated herein by reference, the content of the specification prevails.

[0067] Various modifications and changes can be made to the specific embodiments described herein without departing from the scope or spirit of the application. Other embodiments will be apparent to those of ordinary skill in the art from consideration of the description and practice of the application. The description and examples are illustrative only.

[0068] With respect to the use of "comprising", "including", "containing", "having" and "encompassing" herein, these terms are used in their open-ended, conventional sense, i.e., to mean including, but not limited to.

[0069] The raw materials used in the following examples are all commercially available conventional raw materials, which are not particularly limited. In the following examples, the palladium membrane used is a palladium block with a purity of 99.99wt% and a size of 25*25*0.025mm, and the ion exchange membrane used is Nafion 117. The following examples are all carried out at room temperature (20-25°C), and a magnetic stirrer is added in the chemical room for magnetic stirring at a speed of 950rpm. In the following examples, the preparation method of the palladium membrane with one side of palladium nano-cones is as follows:

[0070] Step 1: Clean the newly purchased palladium membrane (a palladium block with a purity of 99.99% and a size of 25*25*0.025mm) with acetone and deionized water to remove surface impurities;

[0071] Step 2: Calcine under argon atmosphere at 850°C for 90min, with a heating rate of 5°C / min -1 ;

[0072] Step 3: Soak in a mixture of HNO3: 30% H2O2: H2O (v:v:v = 1:1:2) for 15min;

[0073] Step 4: Prepare the palladium electrodeposition solution: Add PdCl2 to 1M hydrochloric acid solution and dissolve by sonication. The concentration of PdCl2 is 15.9mM.

[0074] Step 5: The treated palladium film is loaded into the reactor. Palladium solution is added to the electrochemical chamber to electrodeposit palladium nanocones. The palladium film is used as the working electrode, Hg / HgO as the reference electrode, and a carbon rod as the counter electrode. Constant potential electrolysis is performed by applying -0.2V until the coulombic charge reaches 13C, at which point the electrolysis is stopped, resulting in a palladium film with one side of electrodeposited palladium nanocones. This will not be described again below.

[0075] Example 1

[0076] Synthesis of 3-bromoprop-1-ene-1,2-d2(2a):

[0077] A three-chamber electrolytic cell, separated by a palladium membrane and an ion-exchange membrane, was used as the reaction vessel. Palladium nanocones were electrodeposited on one side of the palladium membrane before the reduction and deuteration of alkynes, and were placed facing the chemical chamber upon loading into the reactor. 14 mL of a deuterated aqueous solution of 0.5 Mk₂CO₃ was added to the electrochemical chamber, and 6 mL of cyclohexane, 0.1 mmol of sodium thiophene, and 1 mmol of 3-bromopropyne (1a) were added to the chemical chamber. The mixture was continuously stirred with a magnetic stirrer. The palladium membrane was used as the working electrode, a carbon rod as the counter electrode, and Hg / HgO as the reference electrode. The system was connected to an electrochemical workstation, and electrolysis was performed at a constant voltage of -2V. After 6 hours of reaction, the reaction solution was collected, and quantitative analysis by gas chromatography revealed a conversion rate of 96% for 1a and a selectivity of 97% for 2a. Subsequently, the fraction was collected by vacuum distillation, and qualitative analysis was performed by NMR. The product was dissolved in CDCl₃ and analyzed by proton NMR, yielding deuteration rates of α-: 99% and β1-: 99%.

[0078] A schematic diagram of the catalytic semi-deuteration reaction of alkynes in the palladium membrane reactor of this invention is shown below. Figure 1 As shown.

[0079] The product 3-bromoprop-1-ene-1,2-d2(2a) prepared in this embodiment 1 H NMR spectrum as shown Figure 2 As shown.

[0080] Example 2

[0081] Synthesis of 1-bromo-4-(vinyl-d2)benzene (2b):

[0082] A three-compartment electrochemical cell separated by palladium membrane and ion exchange membrane was used as the reaction vessel. Palladium nanotips were electrodeposited on one side of the palladium membrane before the reduction and deuteration of the alkyne and faced the chemical compartment when the cell was assembled. A solution of 14 mL of 0.5 M K2CO3 in deuterium water was added to the electrochemical compartment, 6 mL of anhydrous ethanol, 0.1 mmol of sodium benzenethiol and 0.2 mmol of 4-bromo-phenylacetylene (1b) were added to the chemical compartment and stirred constantly with a magnetic stirrer. The palladium membrane was used as the working electrode, a carbon rod as the counter electrode and Hg / HgO as the reference electrode. The cell was connected to an electrochemical workstation and a constant voltage of -2 V was selected for the electrolysis. After 2 h of reaction, the reaction solution was collected and analyzed quantitatively by gas chromatography. The conversion of 1b was 93% and the selectivity of 2b was 96%. Subsequently, the reaction solution was distilled under reduced pressure to 0.5 mL, the product was purified by thin layer chromatography and qualitatively analyzed by nuclear magnetic resonance. The product was dissolved in DMSO-d6 for testing the hydrogen spectrum and carbon spectrum. The deuteration rate was: a-: 99%, b1-: 99%, as shown in Figure 3 (a) is the H NMR spectrum, (b) is the 1 H NMR spectrum, (c) is the 13 C NMR spectrum.

[0083] Comparative Example 1

[0084] The same as Example 2, except that the palladium nanotips were not deposited on one side of the palladium membrane in advance.

[0085] In Example 2, the rate of deuteration of the alkyne was 0.09 mmol h -1 In this comparative example, the rate of deuteration of the alkyne was 0.04 mmol h -1 .

[0086] Note: The calculation method of the rate of deuteration of the alkyne is: the amount of substance of the converted alkyne / the reaction time.

[0087] Example 3

[0088] Synthesis of 1-bromo-3-(vinyl-d2)benzene (2c):

[0089] A three-compartment electrolysis cell separated by palladium membrane and ion exchange membrane was used as the reactor, palladium nanotips were electrodeposited on one side of the palladium membrane before the reduction-deuteriation of the alkyne, and faced the chemical compartment when the reactor was assembled, 14 mL of 0.5M K2CO3 solution in deuterium water was added into the electrochemical compartment, 6 mL of anhydrous ethanol, 0.1 mmol of sodium thiophenolate and 0.2 mmol of 3-bromo-phenylacetylene (1c) were added into the chemical compartment and stirred constantly by a magnetic stirrer, the palladium membrane was used as the working electrode, a carbon rod as the counter electrode, and Hg / HgO as the reference electrode, which were connected to an electrochemical workstation, and a constant voltage of -2 V was selected for electrolysis, after 2.5 h of reaction, the reaction solution was collected and analyzed quantitatively by gas chromatography, and the conversion rate of 1c was 94% and the selectivity of 2c was 95%. Subsequently, it was distilled under reduced pressure to 0.5 mL, and the product was purified by thin layer chromatography, and then qualitatively analyzed by nuclear magnetic resonance, and the product was dissolved in DMSO-d6 for testing of hydrogen spectrum and carbon spectrum, and the deuterium substitution rate was: a-: 95%, b1-: 95%, as shown in Figure 4 (a) is the H NMR spectrum, (b) is the 1 H NMR spectrum, (c) is the 13 C NMR spectrum.

[0090] Example 4

[0091] Synthesis of 1-bromo-2-(vinyl-d2)benzene (2d):

[0092] A three-compartment electrolysis cell separated by palladium membrane and ion exchange membrane was used as the reactor, palladium nanotips were electrodeposited on one side of the palladium membrane before the reduction-deuteriation of the alkyne, and faced the chemical compartment when the reactor was assembled, 14 mL of 0.5M K2CO3 solution in deuterium water was added into the electrochemical compartment, 6 mL of anhydrous ethanol, 0.1 mmol of sodium thiophenolate and 0.2 mmol of 3-bromo-phenylacetylene (1c) were added into the chemical compartment and stirred constantly by a magnetic stirrer, the palladium membrane was used as the working electrode, a carbon rod as the counter electrode, and Hg / HgO as the reference electrode, which were connected to an electrochemical workstation, and a constant voltage of -2 V was selected for electrolysis, after 2.5 h of reaction, the reaction solution was collected and analyzed quantitatively by gas chromatography, and the conversion rate of 1c was 94% and the selectivity of 2c was 95%. Subsequently, it was distilled under reduced pressure to 0.5 mL, and the product was purified by thin layer chromatography, and then qualitatively analyzed by nuclear magnetic resonance, and the product was dissolved in DMSO-d6 for testing of hydrogen spectrum and carbon spectrum, and the deuterium substitution rate was: a-: 95%, b1-: 95%, as shown in Figure 5 (a) is the H NMR spectrum, (b) is the 1 H NMR spectrum, (c) is the 13 C NMR spectrum.

[0093] Example 5

[0094] Synthesis of 4-(vinyl-d2)benzaldehyde (2e):

[0095] A three-compartment electrolysis cell separated by palladium membrane and ion exchange membrane was used as the reaction vessel. Palladium nanotips were electrodeposited on one side of the palladium membrane before the reduction-deuteriation of the alkyne and faced the chemical compartment when the cell was assembled. 14 mL of 0.5 M K2CO3 solution in deuterium water was added to the electrochemical compartment, 6 mL of anhydrous ethanol, 0.1 mmol of sodium benzenethiolate and 0.2 mmol of 4-ethynylbenzaldehyde (1e) were added to the chemical compartment and stirred constantly with a magnetic stirrer. The palladium membrane was used as the working electrode, a carbon rod as the counter electrode and Hg / HgO as the reference electrode. The cell was connected to an electrochemical workstation and a constant voltage of -2 V was selected for electrolysis. After 2 h of reaction, the reaction solution was collected and analyzed quantitatively by gas chromatography. The conversion of 1e was 95% and the selectivity of 2e was 92%. Subsequently, the solution was distilled under reduced pressure to 0.5 mL. The product was purified by thin layer chromatography and qualitatively analyzed by nuclear magnetic resonance. The product was dissolved in CD3CN for testing hydrogen spectrum and carbon spectrum. The deuterium substitution rate was: a-: 99%, b1-: 99%, as shown in Figure 6 (a) is the H NMR spectrum, 1 (b) is the C NMR spectrum. 13

[0096] Example 6

[0097] Synthesis of 4-(vinyl-d2)nitrobenzene (2f):

[0098] A three-compartment electrolysis cell separated by palladium membrane and ion exchange membrane was used as the reaction vessel. Palladium nanotips were electrodeposited on one side of the palladium membrane before the reduction-deuteriation of the alkyne and faced the chemical compartment when the cell was assembled. 14 mL of 0.5 M K2CO3 solution in deuterium water was added to the electrochemical compartment, 6 mL of anhydrous ethanol, 0.1 mmol of sodium benzenethiolate and 0.2 mmol of 4-nitrophenylacetylene (1f) were added to the chemical compartment and stirred constantly with a magnetic stirrer. The palladium membrane was used as the working electrode, a carbon rod as the counter electrode and Hg / HgO as the reference electrode. The cell was connected to an electrochemical workstation and a constant voltage of -2 V was selected for electrolysis. After 2 h of reaction, the reaction solution was collected and analyzed quantitatively by gas chromatography. The conversion of 1f was 94% and the selectivity of 2f was 96%. Subsequently, the solution was distilled under reduced pressure to 0.5 mL. The product was purified by thin layer chromatography and qualitatively analyzed by nuclear magnetic resonance. The product was dissolved in CD3OH for testing hydrogen spectrum and carbon spectrum. The deuterium substitution rate was: a-: 99%, b1-: 93%, as shown in Figure 7 (a) is the H NMR spectrum, 1 (b) is the C NMR spectrum. 13

[0099] Example 7

[0100] Synthesis of 1-iodo-4-(vinyl-d2)benzene (2g):

[0101] ​​A three-compartment electrolysis cell separated by palladium membrane and ion exchange membrane was used as the reaction vessel. Palladium nanotips were electrodeposited on one side of the palladium membrane before the reduction-deuteriation of the alkyne and faced the chemical compartment when the cell was assembled. 14 mL of 0.5 M K2CO3 solution in deuterium water was added to the electrochemical compartment, 6 mL of anhydrous ethanol, 0.1 mmol of sodium benzenethiolate and 0.2 mmol of 4-iodophenylacetylene (1g) were added to the chemical compartment and stirred constantly with a magnetic stirrer. The palladium membrane was used as the working electrode, a carbon rod as the counter electrode and Hg / HgO as the reference electrode. The cell was connected to an electrochemical workstation and a constant voltage of -2 V was selected for electrolysis. After 2 h of reaction, the reaction solution was collected and analyzed quantitatively by gas chromatography. The conversion of 1g was 93% and the selectivity of 2g was 95%. Subsequently, the product was purified by thin layer chromatography and analyzed qualitatively by nuclear magnetic resonance. The product was dissolved in DMSO-d6 for testing hydrogen spectrum and the deuterium substitution rate was: a-: 99%, b1-: 92%, as shown in Figure 8 (a) is the H NMR spectrum, 1 (b) is the C NMR spectrum. 13

[0102] Example 8

[0103] Synthesis of 2-(4-(vinyl-d2)-4,4,5,5-tetramethyl-[1,3 2]-dioxaborolane (2h):

[0104] A three-compartment electrolysis cell separated by palladium membrane and ion exchange membrane was used as the reaction vessel. Palladium nanotips were electrodeposited on one side of the palladium membrane before the reduction-deuteriation of the alkyne and faced the chemical compartment when the cell was assembled. 14 mL of 0.5 M K2CO3 solution in deuterium water was added to the electrochemical compartment, 6 mL of anhydrous ethanol, 0.1 mmol of sodium benzenethiolate and 0.2 mmol of 4-iodophenylacetylene (1g) were added to the chemical compartment and stirred constantly with a magnetic stirrer. The palladium membrane was used as the working electrode, a carbon rod as the counter electrode and Hg / HgO as the reference electrode. The cell was connected to an electrochemical workstation and a constant voltage of -2 V was selected for electrolysis. After 2 h of reaction, the reaction solution was collected and analyzed quantitatively by gas chromatography. The conversion of 1g was 93% and the selectivity of 2g was 95%. Subsequently, the product was purified by thin layer chromatography and analyzed qualitatively by nuclear magnetic resonance. The product was dissolved in DMSO-d6 for testing hydrogen spectrum and the deuterium substitution rate was: a-: 99%, b1-: 92%, as shown in Figure 9 (a) is the H NMR spectrum, 1 (b) is the C NMR spectrum. 13

[0105] Example 9

[0106] ​​Synthesis of 2-(((allyl-2,3-d2)oxy)methyl)oxirane (2i):

[0107] A three-compartment electrolysis cell separated by palladium membrane and ion exchange membrane was used as the reaction vessel, palladium nanotips were electrodeposited on one side of the palladium membrane before the reduction deuteriation of the alkyne, and faced the chemical compartment when loaded into the reactor, 14 mL of 0.5M K2CO3 solution in deuterium water was added into the electrochemical compartment, 6 mL of anhydrous ethanol, 0.1 mmol of sodium benzenethiol and 0.2 mmol of 2-[(prop-2-ynyloxy)methyl]oxirane (1i) were added into the chemical compartment and constantly stirred by a magnetic stirrer, the palladium membrane was used as the working electrode, a carbon rod as the counter electrode, and Hg / HgO as the reference electrode, which were connected to an electrochemical workstation, and a constant voltage of -2 V was selected for electrolysis, after 3 h of reaction, the reaction solution was collected and quantitatively analyzed by gas chromatography, and the conversion rate of 1i was 95% and the selectivity of 2i was 94%. Then, the fraction was collected by distillation under reduced pressure, and qualitative analysis was performed by nuclear magnetic resonance, and the product was dissolved in CDCl3 for testing of hydrogen spectrum and carbon spectrum, and the deuterium substitution rate was: a-: 99%, b1-: 99%, as shown in Figure 10 (a) is the H NMR spectrum, (b) is the 1 H NMR spectrum, (c) is the 13 C NMR spectrum.

[0108] Example 10

[0109] Synthesis of 1-(4-(vinyl-d2)phenyl)carbonitrile (2j):

[0110] A three-compartment electrolysis cell separated by palladium membrane and ion exchange membrane was used as the reaction vessel, palladium nanotips were electrodeposited on one side of the palladium membrane before the reduction deuteriation of the alkyne, and faced the chemical compartment when loaded into the reactor, 14 mL of 0.5M K2CO3 solution in deuterium water was added into the electrochemical compartment, 6 mL of anhydrous ethanol, 0.1 mmol of sodium benzenethiol and 0.2 mmol of 2-[(prop-2-ynyloxy)methyl]oxirane (1i) were added into the chemical compartment and constantly stirred by a magnetic stirrer, the palladium membrane was used as the working electrode, a carbon rod as the counter electrode, and Hg / HgO as the reference electrode, which were connected to an electrochemical workstation, and a constant voltage of -2 V was selected for electrolysis, after 3 h of reaction, the reaction solution was collected and quantitatively analyzed by gas chromatography, and the conversion rate of 1i was 95% and the selectivity of 2i was 94%. Then, the fraction was collected by distillation under reduced pressure, and qualitative analysis was performed by nuclear magnetic resonance, and the product was dissolved in CDCl3 for testing of hydrogen spectrum and carbon spectrum, and the deuterium substitution rate was: a-: 99%, b1-: 99%, as shown in Figure 11 (a) is the H NMR spectrum, (b) is the 1 H NMR spectrum, (c) is the 13 C NMR spectrum.

[0111] Example 11

[0112] Synthesis of naphthol-d2 (2k):

[0113] Take 0.2 mmol of N-methyl-1-naphthylamine and 0.6 mmol of K2CO3, respectively, and disperse them in 5 mL of anhydrous ethanol, add 0.4 mmol of 3-bromopropyne, stir at room temperature for 3 h, and detect whether the reaction is complete by gas chromatography-mass spectrometry. After the reaction is complete, extract with ethyl acetate and deionized water, wash the organic layer with salt water, remove water with anhydrous sodium sulfate, and remove ethyl acetate by rotary evaporation to obtain the crude product.

[0114] Take a three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane as the reaction vessel, and use the palladium membrane to electrodeposit palladium nanotips on one side before performing the reduction deuteriation, and face the chemical chamber when loading the reactor. Add 14 mL of a 0.5M K2CO3 solution in deuterium water to the electrochemical chamber, add 5 mL of anhydrous ethanol, 0.1 mmol of sodium phenylthiol, and the obtained crude product to the chemical chamber, and continuously stir with a magnetic stirrer. Take the palladium membrane as the working electrode, a carbon rod as the counter electrode, and Hg / HgO as the reference electrode, connect to an electrochemical workstation, select a constant voltage of -2 V, and perform electrolysis. After 4 h of reaction, collect the reaction solution and concentrate to obtain the crude product.

[0115] Under an argon atmosphere, add a solution of Pd(dba)2 (0.02 mmol) and benzo[h]phenanthroline (0.024 mmol) in anhydrous N,N-dimethylformamide (DMF) to a round-bottom flask, and stir at room temperature for 30 min. Then add the benzene diazonium salt (0.4 mmol) and the above-mentioned crude product, and stir at room temperature for 12 h. Subsequently, extract the reaction solution with ethyl acetate and deionized water, distill the organic phase under reduced pressure to 0.5 mL, and purify the product by thin-layer chromatography. Weigh the dried sample to obtain a separation yield of 72%. Qualitative analysis is performed by nuclear magnetic resonance, and the product is dissolved in CDCl3 for testing of the hydrogen spectrum and carbon spectrum, as shown in Figure 12 Fig. 1, where (a) is 1 the H NMR spectrum, and (b) is 13 the C NMR spectrum.

[0116] Example 12

[0117] Synthesis of cinnarizine-d2 (2l):

[0118] Take 0.2 mmol of 1-(diphenylmethyl)-piperazine and 0.6 mmol of K2CO3, respectively, and disperse them in 5 mL of anhydrous ethanol, add 0.4 mmol of 3-bromopropyne, stir at room temperature for 3 h, and detect whether the reaction is complete by gas chromatography-mass spectrometry. After the reaction is complete, extract with ethyl acetate and deionized water, wash the organic layer with salt water, remove water with anhydrous sodium sulfate, and remove ethyl acetate by rotary evaporation to obtain the crude product.

[0119] A three-compartment electrochemical cell separated by palladium membrane and ion exchange membrane was used as the reaction vessel. Palladium nanotips were electrodeposited on one side of the palladium membrane before reduction deuteriation and faced the chemical compartment when the reactor was assembled. A solution of 14 mL 0.5 M K2CO3 in deuterium water was added to the electrochemical compartment, 5 mL anhydrous ethanol, 0.1 mmol sodium thiophenol and the obtained crude product were added to the chemical compartment and constantly stirred by a magnetic stirrer. The palladium membrane was used as the working electrode, a carbon rod as the counter electrode and Hg / HgO as the reference electrode, which were connected to an electrochemical workstation. A constant voltage of -2 V was selected for electrolysis. After 4 h of reaction, the reaction solution was collected and concentrated to obtain the crude product.

[0120] Anhydrous DMF solution containing Pd(dba)2(0.02 mmol), Pd / C (0.02 mmol) and benzo[h]phenalene (0.024 mmol) was added to a round-bottom flask under argon atmosphere and stirred at room temperature for 30 min. Then, phenyldiazonium salt (0.2 mmol) and the above-mentioned crude product were added and stirred at room temperature for 12 h. Subsequently, the reaction solution was extracted with ethyl acetate and deionized water, and the organic phase was distilled under reduced pressure to 0.5 mL. The product was purified by thin-layer chromatography. After drying, the sample was weighed to obtain an isolated yield of 61%. The product was qualitatively analyzed by nuclear magnetic resonance, and the hydrogen spectrum and carbon spectrum of the product were tested by dissolving it in CDCl3, as shown in Figure 13 (a) is the H NMR spectrum, and (b) is the 1 H NMR spectrum, (b) is the 13 C NMR spectrum.

[0121] Example 13

[0122] Synthesis of artemisinin derivative-d2(2m):

[0123] 0.2 mmol dihydroartemisinin and 0.4 mmol 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) were weighed separately and dissolved in 5 mL of anhydrous DCM, 0.4 mmol 3-bromopropynyl was added, and stirred at room temperature for 3 h. The reaction was detected by gas chromatography-mass spectrometry. After the reaction was completed, the reaction solution was extracted with ethyl acetate and deionized water, the organic layer was washed with brine and anhydrous sodium sulfate, and the ethyl acetate was removed by rotary evaporation to obtain the crude product.

[0124] A three-compartment electrolysis cell separated by palladium membrane and ion exchange membrane was used as the reaction vessel. Palladium nanotips were electrodeposited on one side of the palladium membrane before reduction deuteriation. The palladium membrane faced the chemical compartment when loaded into the reactor. A solution of 14 mL of 0.5 M K2CO3 in deuterium water was added to the electrochemical compartment. 5 mL of anhydrous ethanol, 0.1 mmol of sodium benzenethiolate and the obtained crude product were added to the chemical compartment and constantly stirred with a magnetic stirrer. The palladium membrane was used as the working electrode, a carbon rod as the counter electrode and Hg / HgO as the reference electrode, which were connected to an electrochemical workstation. A constant voltage of -2 V was selected for electrolysis. After 3 h of reaction, the reaction solution was collected. Subsequently, the product was purified by thin layer chromatography after distillation under reduced pressure to 0.5 mL. The dried sample was weighed to obtain a separation yield of 62%. The product was qualitatively analyzed by nuclear magnetic resonance, and the product was dissolved in CDCl3 to test the hydrogen spectrum and carbon spectrum, as shown in FIGS. 1A and 1B, respectively. Figure 14 FIG. 1A is a1H NMR spectrum, and FIG. 1B is a13C NMR spectrum. 1 FIG. 1A is a1H NMR spectrum, and FIG. 1B is a13C NMR spectrum. 13 FIG. 1A is a1H NMR spectrum, and FIG. 1B is a13C NMR spectrum.

[0125] Example 14

[0126] Synthesis of estradiol derivative-d2 (2n):

[0127] 0.2 mmol of estradiol and 0.6 mmol of NaH were weighed and dissolved in 5 mL of anhydrous DMF, 0.4 mmol of 3-bromopropynyl was added, and stirred at room temperature for 3 h. The reaction was detected by gas chromatography-mass spectrometry. After the reaction was completed, the product was extracted with ethyl acetate and deionized water. The organic layer was washed with brine, dehydrated with anhydrous sodium sulfate, and the ethyl acetate was removed by rotary evaporation to obtain the crude product.

[0128] A three-compartment electrolysis cell separated by palladium membrane and ion exchange membrane was used as the reaction vessel. Palladium nanotips were electrodeposited on one side of the palladium membrane before reduction deuteriation. The palladium membrane faced the chemical compartment when loaded into the reactor. A solution of 14 mL of 0.5 M K2CO3 in deuterium water was added to the electrochemical compartment. 5 mL of anhydrous ethanol, 0.1 mmol of sodium benzenethiolate and the obtained crude product were added to the chemical compartment and constantly stirred with a magnetic stirrer. The palladium membrane was used as the working electrode, a carbon rod as the counter electrode and Hg / HgO as the reference electrode, which were connected to an electrochemical workstation. A constant voltage of -2 V was selected for electrolysis. After 3 h of reaction, the reaction solution was collected. Subsequently, the product was purified by thin layer chromatography after distillation under reduced pressure to 0.5 mL. The dried sample was weighed to obtain a separation yield of 62%. The product was qualitatively analyzed by nuclear magnetic resonance, and the product was dissolved in CDCl3 to test the hydrogen spectrum and carbon spectrum, as shown in FIGS. 1A and 1B, respectively. Figure 15 FIG. 1A is a1H NMR spectrum, and FIG. 1B is a13C NMR spectrum. 1 FIG. 1A is a1H NMR spectrum, and FIG. 1B is a13C NMR spectrum. 13 FIG. 1A is a1H NMR spectrum, and FIG. 1B is a13C NMR spectrum.

[0129] The substrate expansion chart for preparing deuterated olefin compounds containing easily reducible and easily hydrolyzable functional groups by catalytic reduction and deuterization of alkyne compounds by PhS-Pd, and the synthetic route of deuterated naphthalofin, guairesin, artemisinin derivatives and estradiol derivatives are shown in Figure 16 .

[0130] Example 15: Modification of catalyst to form in-situ sodium phenyl sulfide modified palladium film (PhS-Pd)

[0131] Step 1: Clean the newly purchased palladium film with acetone and deionized water to remove surface impurities;

[0132] Step 2: Calcine at 850°C for 90 min under argon atmosphere, with a heating rate of 5°C / min -1 .

[0133] Step 3: Soak in a mixture of HNO3: 30% H2O2: H2O (v:v:v = 1:1:2) for 15 min;

[0134] Step 4: Prepare the electrodeposition palladium solution: add PdCl2 to 1M hydrochloric acid solution, ultrasonic dissolution, the concentration of PdCl2 is 15.9mM;

[0135] Step 5: Put the treated palladium film into the reactor, add palladium solution in the electrochemical chamber for electrodeposition of palladium nanotips, use palladium film as working electrode, Hg / HgO as reference electrode, carbon rod as counter electrode, apply -0.2V for constant potential electrolysis until the coulombic quantity reaches 13C;

[0136] Step 6: Take out the palladium film, rinse the palladium film, reactor and electrodes with deionized water and ethanol, dry, then put the side of the palladium film containing the electrodeposited palladium nanotips into the reactor again, facing the chemical chamber, for standby;

[0137] Step 7: Add 14mL 0.5M K2CO3 solution in deuterium water in the electrochemical chamber, add 5mL anhydrous ethanol, 0.1mmol sodium phenyl sulfide in the chemical chamber and continuously stir with a magnetic stirrer, use palladium film as working electrode, carbon rod as counter electrode, Hg / HgO as reference electrode, connect to the electrochemical workstation, select constant voltage -2V for electrolysis, the catalyst adsorbed on the palladium nanotips wrapped by amorphous palladium sulfide from sodium phenyl sulfide in-situ forms during electrolysis.

[0138] After the reaction is completed, the palladium film is taken out and washed to obtain the in-situ formed sodium phenyl sulfide modified palladium film (catalyst PhS-Pd), the scanning electron microscope image thereof is shown in Figure 17 , the high-angle annular dark-field scanning transmission electron microscope (HADDF-STEM) and the corresponding STEM energy dispersive X-ray spectrum (EDS) element mapping image are shown in Figure 18The high-resolution transmission electron microscopy (HRTEM) image is shown in Figure (a), the X-ray diffraction (XRD) image is shown in Figure (b), the Pd 3d and S 2p X-ray photoelectron spectroscopy (XPS) images of PhS-Pd are shown in Figures (a) and (b) respectively. Figure 18 The high-resolution transmission electron microscopy (HRTEM) image is shown in Figure (a), the X-ray diffraction (XRD) image is shown in Figure (b), the Pd 3d and S 2p X-ray photoelectron spectroscopy (XPS) images of PhS-Pd are shown in Figures (a) and (b) respectively. Figure 19 The high-resolution transmission electron microscopy (HRTEM) image is shown in Figure (a), the X-ray diffraction (XRD) image is shown in Figure (b), the Pd 3d and S 2p X-ray photoelectron spectroscopy (XPS) images of PhS-Pd are shown in Figures (a) and (b) respectively. Figure 20 The high-resolution transmission electron microscopy (HRTEM) image is shown in Figure (a), the X-ray diffraction (XRD) image is shown in Figure (b), the Pd 3d and S 2p X-ray photoelectron spectroscopy (XPS) images of PhS-Pd are shown in Figures (a) and (b) respectively.

[0139] Comparative Example 2

[0140] Based on Example 2, the present comparative example was set up to verify the necessity of sodium phenylthiol modification. A three-chamber electrolysis cell separated by a palladium membrane and an ion exchange membrane was used as the reaction vessel, palladium nanotips were electrodeposited on one side of the palladium membrane before the reduction deuterization of the alkyne, and the palladium membrane faced the chemical chamber when loaded into the reactor, 14 mL of a 0.5 M K2CO3 solution in deuterium water was added to the electrochemical chamber, 6 mL of anhydrous ethanol and 0.2 mmol of 4-bromophenylacetylene (1b) were added to the chemical chamber and constantly stirred with a magnetic stirrer, the palladium membrane was used as the working electrode, a carbon rod as the counter electrode, and Hg / HgO as the reference electrode, which were connected to an electrochemical workstation, and a constant voltage of -2 V was selected for electrolysis, after 2 h of reaction, the reaction solution was collected and quantitatively analyzed by gas chromatography, and the conversion rate of 1b was 97% and the selectivity of 2b was 10%. The results of this comparative example fully demonstrate the importance of sodium phenylthiol modified palladium membrane for the high selectivity synthesis of deuterated alkenes, and the results are shown in Figure 21

[0141] Example 16

[0142] Stability test of PhS-Pd for long-term catalysis of alkyne reduction deuterization

[0143] The stability of PhS-Pd for long-term catalysis of alkyne reduction deuterization was also tested, based on Example 2, 20 g of 4-bromophenylacetylene was subjected to reduction deuterization in a clean electrolysis cell, and the stability of the catalyst was determined by detecting the selectivity of the product every 18 h. The experimental results are shown in Figure 22

[0144] Example 17

[0145] ​​The application also tests the potential current applicable range of the PhS-Pd catalyzed reduction deuterization of alkyne. The experimental steps are the same as those in Example 2, only the applied potential is changed. The application applies a potential of-1.5 to-4.5 V or a current of 10 to 400 mA. After 2 h of reaction, the reaction solution is collected and subjected to quantitative analysis by gas chromatography to obtain the conversion rate of 1b and the selectivity of 2b, as shown in Table 2. Figure 23 As shown in Table 2, in the potential range of-1.5 to-4 V or the current range of 10 to 300 mA, the selectivity of 2b can reach a selectivity higher than 90% and a faradic efficiency of 70%, indicating that the catalytic system of the application can be applicable to a wide potential and current range.

[0146] The above description is only the preferred specific implementation of the application, and the protection scope of the application is not limited thereto. Any person skilled in the art can make equivalent replacements or changes to the technical solution and the inventive concept of the application within the technical range disclosed by the application, which should be covered in the protection scope of the application.

Claims

1. A method for synthesizing deuterated olefins using D2O as a deuterium source and palladium membrane catalysis, characterized in that, The process includes the following steps: In a three-chamber reactor separated by a palladium membrane and an ion-exchange membrane, an electrolyte deuterium aqueous solution is added to two reaction chambers separated by an ion-exchange membrane to carry out an electrolysis reaction of deuterium water. In another reaction chamber, an organic solvent, sodium thiophene, and alkyne reactants are added to carry out an organic reaction of alkyne deuteration. The palladium membrane is used as the working electrode, and deuterium water is used as the deuterium source. Deuterium water is electrolyzed by a constant potential electrolysis method. The generated active deuterium is transferred from the electrolysis reaction side to the organic reaction side. The deuterated alkyne compound is then reduced by a palladium membrane modified with sodium thiophene to obtain a deuterated olefin compound. Palladium nanocones are electrodeposited on one side of the palladium film, and the side with the electrodeposited palladium nanocones faces the reaction chamber where the organic reaction takes place; the constant potential is -1.5 to -4 V.

2. The synthesis method according to claim 1, characterized in that, It also includes the steps of removing the organic solvent from the reaction solution containing deuterated olefins using a rotary evaporator to obtain a crude product of deuterated olefins; and purifying the crude product of deuterated olefins using thin-layer chromatography or column chromatography to obtain a pure product of deuterated olefins.

3. The synthesis method according to claim 1, characterized in that, The electrolyte is an alkaline salt, and the concentration of the deuterium aqueous solution of the electrolyte is 0.1–1.5 M; the organic solvent includes alcohols or alkanes; the alkyne reactant has the structure shown in Formula I, Formula II, or Formula III: ； R is selected from halogen, nitro, acyl, cyano or borate ester groups.

4. The synthesis method according to claim 3, characterized in that, The alkaline salt includes potassium carbonate, and the concentration of the potassium carbonate deuterium aqueous solution is 0.5 M; the organic solvent includes anhydrous ethanol or cyclohexane; the temperature of the electrolysis of deuterium water and the organic reaction are both 20-25 °C, and the time is 4-8 h.

5. The application of the synthesis method according to claim 1 in the synthesis of deuterated drugs.

6. A palladium film modified with sodium thiophene, characterized in that, Palladium nanocones are first electrodeposited on one side of the palladium film, and then modified with sodium thiophenolate. The sodium thiophene modified palladium membrane is generated in situ in the method for synthesizing deuterated olefins using a palladium membrane catalyzed by D2O as a deuterium source, as described in claim 1.

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