Method for synthesizing deuterated olefin under catalysis of palladium membrane by taking D2O as deuterium source

Abstract

The invention discloses a method for synthesizing deuterated olefin under catalysis of a palladium membrane by taking D2O as a deuterium source, and belongs to the technical field of synthesis of deuterated olefin building blocks. According to the method, a three-chamber electrolytic tank separated by a palladium membrane and an ion exchange membrane is used as a reactor, the palladium membrane is used as a working electrode, an electrolyte deuterium aqueous solution is used as an electrolyte, deuterium water is electrolyzed through a constant-potential electrolysis method, and formed active deuterium is transmitted to one side of an organic reaction taking absolute ethyl alcohol or cyclohexane as an organic solvent; and catalyzing an alkyne compound by using a palladium membrane modified by sodium thiophenol to perform reduction deuterization so as to synthesize a deuterated olefin compound with high selectivity, and further synthesizing a corresponding deuterated drug. The invention provides a green, efficient, high-universality and low-cost amplification synthesis method for synthesizing a deuterated olefin building block containing a functional group easy to reduce and hydrolyze, and the method has a wide application prospect.

Description

Technical Field

[0001] The invention belongs to the technical field of synthesis of deuterated olefin building blocks, and in particular relates to a method for synthesizing deuterated olefins by using D2O as a deuterium source and palladium film catalysis. Background Art

[0002] Taking advantage of the fact that CD is more stable than CH, selective deuteration of physiologically active compounds can extend their half-life to improve sustainability, and can also inhibit the production of toxic metabolites to improve their safety. In 2017, the world's first deuterated drug (deuterated tetrabenazine) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of Huntington's disease, and is considered to be a specific drug with better therapeutic effects than tetrabenazine. In 2021, Donafenib, developed by Suzhou Zejing Pharmaceutical, was approved for marketing as the world's first deuterated anti-cancer 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 are useful synthetic building blocks and exist in a large number of drugs, agrochemicals and natural products.

[0003] So far, the method of synthesizing deuterated olefins has developed from the direct H / D exchange method to the electrocatalytic addition of deuterium to alkynes in water. The latter does not require the harsh reaction conditions and expensive organic deuterium sources or deuterium gas usually required by the former, and can effectively control the product selectivity by regulating the voltage or current, providing an important means of mild conditions, environmental friendliness, high economy, and efficient synthesis. However, there are still many shortcomings that limit its wide application. For example, the solubility of alkynes and alkenes in water is usually low, so it is difficult to synthesize them in large quantities. At the same time, the separation steps are complicated, which increases the separation cost; for alkynes containing easily reducible functional groups, the functional groups are difficult to retain; for alkynes containing easily hydrolyzed functional groups, they cannot exist under aqueous electrocatalytic conditions; in addition, most drug synthesis processes are anhydrous conditions, and alkenes synthesized in water must be separated and dried before being put into use. It can be seen that at present, deuterated alkenes are mainly obtained through two strategies: olefin H / D exchange or alkyne reductive deuteration in water phase, which have problems such as environmental unfriendliness, low universality, difficulty in scale-up and high separation cost. Especially for alkynes containing easily reducible and easily hydrolyzed functional groups, there are greater difficulties and challenges. Therefore, it is urgent to develop a green, economical and efficient method to achieve the extensive synthesis of deuterated alkenes with high functional group compatibility and facilitate the subsequent synthesis of deuterated drugs.

[0004] In recent research and development, palladium membranes are used in electrocatalytic organic synthesis reactors due to their ability to transport active deuterium. By separating the aqueous electrolyte and the organic deuteration reaction, the low solubility of alkynes in water makes them difficult to synthesize in large quantities and the high cost of aqueous separation is solved. It is also expected to solve the problem that alkynes containing easily hydrolyzed functional groups cannot exist in the aqueous phase. It has a wide range of application potential, but the difficulty in controlling the selectivity of olefins has greatly limited the application of this method. Therefore, modifying the palladium membrane reactor to improve the selectivity of deuterated olefins is a challenge that needs to be overcome. Summary of the invention

[0005] In order to solve the above problems in the prior art, the present invention provides a method for synthesizing deuterated olefins by using palladium membrane catalysis with D2O as a deuterium source. The synthesis method uses economical D2O as a deuterium source and a sodium benzenethiophenol-modified palladium membrane to catalyze the reduction deuteration of alkynes to synthesize deuterated olefin building blocks and deuterated drugs containing easily reducible and easily hydrolyzed functional groups under normal temperature and pressure conditions. The method can achieve high-selective synthesis of deuterated olefin compounds within a wide range of potential and current. The reaction conditions are mild, the operation is simple, and the palladium membrane catalyst can be reused. A safe, green and efficient method is provided for the synthesis of deuterated olefins. The synthesized deuterated olefin solution can be directly used for subsequent drug synthesis without separation, and a lower-cost and more convenient method is provided for the application of deuterated olefin building blocks.

[0006] To achieve the above object, the present invention provides the following technical solutions:

[0007] One of the technical solutions of the present invention is a method for synthesizing deuterated olefins by using a palladium membrane to catalyze the deuterium source, comprising 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 the ion exchange membrane to perform an electrolytic deuterium water reaction, an organic solvent, sodium thiophenolate and an alkyne reactant are added to the other reaction chamber to perform an organic reaction of alkyne deuteration, a palladium membrane is used as a working electrode, deuterium water is used as a deuterium source, deuterium water is electrolyzed by a constant potential electrolysis method, the generated active deuterium is transferred from one side of the electrolysis reaction to the one side of the organic reaction, and then the deuterated alkyne compound is reduced by a palladium membrane modified with sodium thiophenolate to obtain a deuterated olefin compound.

[0008] Furthermore, palladium nanocones are deposited on one side of the palladium film, and the side on which the palladium nanocones are deposited faces a reaction chamber where an organic reaction is performed.

[0009] Furthermore, the concentration of the sodium thiophenolate is 0.3-0.5M.

[0010] Furthermore, the concentration of the sodium thiophenolate is 0.4M.

[0011] Furthermore, the method for preparing the palladium film comprises the following steps: using the palladium film as a working electrode and electrolyzing a palladium-containing electrolyte at a constant potential.

[0012] The purpose of electrodeposition of palladium nanocones is to increase their active area and improve the rate of deuteration of alkynes.

[0013] The deuteration rate of alkyne: without depositing palladium nanocones, directly modifying the palladium film with sodium benzenethiophenolate: depositing palladium nanocones, modifying the palladium film with sodium benzenethiophenolate = 4:9.

[0014] Furthermore, the palladium membrane is cleaned, calcined in an inert atmosphere, and acidified in advance; the electrolysis uses Hg / HgO as a reference electrode and a carbon rod as a counter electrode; the constant potential is -0.2V, and the palladium-containing electrolyte is electrolyzed until the coulomb content reaches at least 13C.

[0015] Furthermore, the cleaning is to use acetone and deionized water to clean the palladium membrane to remove surface impurities; the calcination temperature is 800-900°C, and the heating rate is 5°C min -1 , time is 60 to 120 minutes; the acidification liquid is a mixture of concentrated nitric acid, 30% hydrogen peroxide and water, and the volume ratio is 1:1:1, soaking for 10 to 20 minutes; the preparation method of the palladium-containing electrolyte is: adding PdCl2 to 0.8 to 1M hydrochloric acid, ultrasonically dissolving, and obtaining a palladium-containing electrolyte with a PdCl2 concentration of 15 to 16.5mM; after the electrolysis is completed, the obtained palladium film is removed, rinsed with deionized water and ethanol, and blown dry, and a saturated KCl deuterium aqueous solution is added to the reference electrode.

[0016] Furthermore, the method also includes the steps of removing the organic solvent in the reaction solution containing deuterated olefin compounds by a rotary evaporator to obtain a crude product of deuterated olefin; and purifying the crude product of deuterated olefin by thin layer chromatography or column chromatography to obtain a pure deuterated olefin.

[0017] Furthermore, the thickness of the palladium membrane is 20 to 30 μm; the ion exchange membrane separates the positive and negative electrodes of the deuterium water electrolysis reaction. The palladium membrane serves as both a working electrode and a diaphragm to separate the electrochemical chamber and the chemical chamber. The palladium membrane facing the electrochemical chamber performs water electrolysis to produce active deuterium, and the palladium membrane facing the chemical chamber performs alkyne deuteration reaction after modification with sodium benzenethiophenol.

[0018] Furthermore, the electrolyte is an alkali salt, and the concentration of the electrolyte deuterium aqueous solution is 0.1-1.5M; the organic solvent includes alcohols or alkanes, and different solvents are selected due to the properties of different alkyne reactants; the electrolyte deuterium aqueous solution and the organic solvent are respectively installed in different chambers, and the volume is not limited, and each can be sufficient in the chamber; the alkyne reactant has a structure shown in Formula I, Formula II or Formula III:

[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] Furthermore, 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-ynylphenyl)-4,4,5,5-tetramethyl-[1,3 2]-dioxaborane and 2-[(prop-2-ynyloxy)methyl]oxirane; and the R substituent can be substituted at any position on the benzene ring. The corresponding deuterated olefin compounds are 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]-dioxaborane, and 2-(((allyl-2,3-d2)oxy)methyl)oxirane.

[0023] Furthermore, the alkali salt includes potassium carbonate, and the concentration of potassium carbonate deuterium aqueous solution is 0..5M; the organic solvent includes anhydrous ethanol or cyclohexane; the temperature of the deuterium water electrolysis reaction and the organic reaction are both 20-25°C, and the time is 4-8h; the constant potential is -1.5--4V.

[0024] The second technical solution of the present invention: application of the synthesis method in the synthesis of deuterated drugs.

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

[0026] The third technical solution of the present invention: a sodium thiophenolate-modified palladium membrane, wherein one side of the palladium membrane is modified with sodium thiophenolate.

[0027] Furthermore, the side modified with sodium thiophenolate is pre-deposited with palladium nanocones. The palladium membrane facing the electrochemical chamber is not specially treated, that is, no palladium nanocones are deposited, and no sodium thiophenolate modification is performed.

[0028] Technical solution four of the present invention: a method for preparing a palladium membrane modified with sodium thiophenolate as described above, wherein the palladium membrane modified with sodium thiophenolate is generated in situ during the synthesis of deuterated olefins catalyzed by the palladium membrane using D2O as a deuterium source.

[0029] The fifth technical solution of the present invention: an application of the palladium membrane modified with sodium benzenethiophenol as described above in the synthesis of deuterated olefins catalyzed by palladium membrane using D2O as a deuterium source.

[0030] The reaction principle of the deuterated olefin synthesis of the present invention is as follows:

[0031]

[0032] The invention discloses a method for synthesizing deuterated olefin building blocks containing easily reducible and easily hydrolyzed functional groups by reducing deuteration of alkynes catalyzed by a sodium benzenethiophenol modified palladium membrane in a palladium membrane reactor, and further synthesizing deuterated drugs. The method comprises the following contents: in a three-chamber reactor separated by a palladium membrane and an ion exchange membrane, an electrolyte is added to two chambers separated by an ion exchange membrane to perform an electrolysis of deuterated water, an organic solvent is added to another chamber to perform an organic reaction of deuteration of alkynes, deuterated water is electrolyzed by a constant potential electrolysis method using a palladium membrane as a working electrode and deuterated water as a deuterium source, and the generated active deuterium is transferred from one side of the electrolysis reaction to the one side of the organic reaction, and then the deuterated alkyne compound is reduced by a sodium benzenethiophenol modified palladium membrane to obtain a deuterated olefin compound, and the related deuterated drugs are obtained through a simple synthesis process.

[0033] The reaction mechanism of the present invention is characterized in that active deuterium generated by the water electrolysis reaction on one side of the palladium membrane is transferred to the other side of the palladium membrane to participate in the deuteration reaction of alkynes, and the palladium membrane is modified by sodium thiophenol to improve the selectivity of deuterated olefins.

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

[0035] (1) The present invention can achieve efficient and highly selective synthesis of deuterated olefins within a wide range of potential and current. In the range of potential of -1.5 to -4 V or current of 10 to 300 mA, the reaction conversion rate can reach 92% and the selectivity can reach 95%.

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

[0037] (3) The present invention uses low-cost deuterium water as a deuterium source, has mild reaction conditions, is simple to operate, reduces tedious extraction steps, and has a high utilization rate of deuterium water. There is no need to replace deuterium water due to changes in the type of alkyne compounds, effectively avoiding the problems of using expensive deuterium gas, organic deuterated reagents, complex operations, long reaction times, and low utilization rate of deuterium water in other synthesis methods.

[0038] (4) The present invention solves the problem that alkyne compounds have low solubility in water and cannot be used to synthesize olefins in large quantities.

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

[0040] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0041] Figure 1 It is a schematic diagram of the catalytic semideuteration reaction of alkynes in the palladium membrane reactor of the present invention;

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

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

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

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

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

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

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

[0049] Fig. 9 The NMR spectrum of the product 2-(4-(vinyl-d2)-4,4,5,5-tetramethyl-[1,3 2]-dioxaborane (2h) prepared in Example 8, wherein (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum;

[0050] Fig.10 This is the NMR spectrum of the product 2-(((allyl-2,3-d2)oxy)methyl)oxirane (2i) prepared in Example 9, wherein (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum;

[0051] Fig.11 This is the NMR spectrum of the product 1-(4-(vinyl-d2)phenyl)carbonitrile (2j) prepared in Example 10, wherein (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum;

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

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

[0054] Fig.14 This is the nuclear magnetic spectrum of the product artemisinin derivative-d2 (2m) prepared in Example 13, wherein (a) is 1 HNMR spectrum, (b) 13 C NMR spectrum;

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

[0056] Fig.16 The substrate expansion diagram for preparing functionalized deuterated olefin compounds by reducing functionalized alkyne compounds using PhS-Pd prepared in Example 15 as a catalyst, and the synthesis diagram for synthesizing naphthol, cinnarizine, artemisinin derivatives, and estradiol derivatives using deuterated olefins as raw materials;

[0057] Fig.17 This is a scanning electron microscope (SEM) image of PhS-Pd prepared in Example 15;

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

[0059] Fig.19 This is the X-ray diffraction (XRD) image of PhS-Pd prepared in Example 15;

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

[0061] Fig.21 It is a comparison diagram of the raw material conversion rate and product selectivity of Example 2 and Comparative Example 2;

[0062] Fig. 22 This is a stability test diagram of the long-term catalytic reduction deuteration of alkynes by PhS-Pd prepared in Example 15. The reaction is modeled after Example 2.

[0063] Fig.23 The PhS-Pd prepared in Example 15 highly selectively electrocatalyzes the semi-hydrogenation of alkynes to form alkenes in a wide potential (-1.5 to -4 V) and current (10 to 300 mA) range, and the reaction follows the formation model 2b. DETAILED DESCRIPTION

[0064] Now, various exemplary embodiments of the present invention are described in detail, and this detailed description should not be considered as a limitation of the present invention, but should be understood as a more detailed description of certain aspects, characteristics and embodiments of the present invention. It should be understood that the terms described in the present invention are only for describing specific embodiments and are not used to limit the present invention.

[0065] In addition, for the numerical range in the present invention, it is understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0066] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0067] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present invention description and examples are exemplary only.

[0068] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0069] The raw materials used in the following examples are all commercially available conventional raw materials, without special restrictions; in the following examples, the palladium membrane used is a palladium block with a purity of 99.99wt% pressed, with a specific 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), a magnet is added to the chemical chamber, and magnetic stirring is used at a speed of 950rpm; in the following examples, the preparation method of the palladium membrane with palladium nanocones electrodeposited on one side is:

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

[0071] Step 2: Calcination at 850 °C for 90 min in an argon atmosphere 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 15 min;

[0073] Step 4: Prepare the electroplated palladium solution: add PdCl2 into 1M hydrochloric acid solution and dissolve it by ultrasonication. The concentration of PdCl2 is 15.9mM.

[0074] Step 5: Load the treated palladium film into the reactor, add palladium solution into the electrochemical chamber to electro-deposit palladium nanocones, use the palladium film as the working electrode, Hg / HgO as the reference electrode, and the carbon rod as the counter electrode, apply -0.2V for constant potential electrolysis until the coulomb volume reaches 13C, and then obtain a palladium film with palladium nanocones electro-deposited on one side. The following description will not be repeated.

[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 a reaction vessel. Before the alkyne reduction deuteration, palladium nanocones were electrodeposited on one side of the palladium membrane, and the membrane was placed facing the chemical chamber when loaded into the reactor. A 14 mL 0.5 M K2CO3 solution of deuterated water was added to the electrochemical chamber. 6 mL cyclohexane, 0.1 mmol sodium benzenethiophenol and 1 mmol 3-bromopropyne (1a) were added to the chemical chamber and stirred continuously with a magnet. The palladium membrane was used as the working electrode, the carbon rod was used as the counter electrode, and Hg / HgO was used as the reference electrode. The electrolysis was performed at a constant voltage of -2 V. After 6 hours of reaction, the reaction solution was collected and quantitatively analyzed by gas chromatography, and the conversion rate of 1a was 96%, and the selectivity of 2a was 97%. Subsequently, the fractions were collected by vacuum distillation, and then qualitatively analyzed by nuclear magnetic resonance. The product was dissolved in CDCl3 to test the hydrogen spectrum, and the deuteration rate was obtained: α-: 99%, β1-: 99%.

[0078] The schematic diagram of the catalytic half-deuteration reaction of alkynes in the palladium membrane reactor of the present invention is as follows Figure 1 shown.

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

[0080] Example 2

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

[0082] A three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane was used as a reaction container. Palladium nanocones were electrodeposited on one side of the palladium membrane before reduction and deuteration of alkynes, and faced the chemical chamber when loaded into the reactor. 14 mL of a 0.5 M K2CO3 deuterated water solution was added to the electrochemical chamber. 6 mL of anhydrous ethanol, 0.1 mmol sodium thiophenol and 0.2 mmol 4-bromophenylacetylene (1b) were added to the chemical chamber and stirred continuously with a magnet. The palladium membrane was used as the working electrode, the carbon rod was used as the counter electrode, and Hg / HgO was used as the reference electrode. The reaction was connected to an electrochemical workstation and a constant voltage of -2 V was selected for electrolysis. After reacting for 2 hours, the reaction solution was collected and quantitatively analyzed by gas chromatography, and the conversion rate of 1b was 93% and the selectivity of 2b was 96%. Then, the product was distilled under reduced pressure to 0.5 mL, purified by thin layer chromatography, and qualitatively analyzed by nuclear magnetic resonance. The product was dissolved in DMSO-d6 to test the hydrogen and carbon spectra, and the deuterated rates were: α-: 99%, β1-: 99%, as shown in Figure 3 As shown, (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum.

[0083] Comparative Example 1

[0084] The same as Example 2, except that no palladium nanocones are deposited on one side of the palladium film.

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

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

[0087] Example 3

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

[0089] A three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane was used as a reaction container. Palladium nanocones were electrodeposited on one side of the palladium membrane before reduction and deuteration of alkynes, and faced the chemical chamber when loaded into the reactor. 14 mL of a 0.5 M K2CO3 deuterated water solution was added to the electrochemical chamber. 6 mL of anhydrous ethanol, 0.1 mmol sodium thiophenol and 0.2 mmol 3-bromophenylacetylene (1c) were added to the chemical chamber and stirred continuously with a magnet. The palladium membrane was used as the working electrode, the carbon rod was used as the counter electrode, and Hg / HgO was used as the reference electrode. The electrochemical workstation was connected and a constant voltage of -2 V was selected for electrolysis. After reacting for 2.5 h, the reaction solution was collected and quantitatively analyzed by gas chromatography, and the conversion rate of 1c was 94% and the selectivity of 2c was 95%. Then, the product was distilled under reduced pressure to 0.5 mL, purified by thin layer chromatography, and qualitatively analyzed by nuclear magnetic resonance. The product was dissolved in DMSO-d6 to test the hydrogen and carbon spectra, and the deuterated rates were: α-: 95%, β1-: 95%, such as Figure 4 As shown, (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum.

[0090] Example 4

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

[0092] A three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane was used as the reaction container. Palladium nanocones were electrodeposited on one side of the palladium membrane before reduction and deuteration of alkynes, and faced the chemical chamber when loaded into the reactor. 14 mL of a 0.5 M K2CO3 deuterated water solution was added to the electrochemical chamber. 6 mL of anhydrous ethanol, 0.1 mmol sodium thiophenol and 0.2 mmol 2-bromophenylacetylene (1d) were added to the chemical chamber and stirred continuously with a magnet. The palladium membrane was used as the working electrode, the carbon rod was used as the counter electrode, and Hg / HgO was used as the reference electrode. The electrochemical workstation was connected and a constant voltage of -2 V was selected for electrolysis. After reacting for 4 hours, the reaction solution was collected and quantitatively analyzed by gas chromatography, and the conversion rate of 1d was 91% and the selectivity of 2d was 94%. Then, the product was distilled under reduced pressure to 0.5 mL, purified by thin layer chromatography, and qualitatively analyzed by nuclear magnetic resonance. The product was dissolved in DMSO-d6 to test the hydrogen and carbon spectra, and the deuterated rates were: α-: 99%, β1-: 93%, as shown in Figure 5 As shown, (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum.

[0093] Example 5

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

[0095] A three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane was used as a reaction container. Palladium nanocones were electrodeposited on one side of the palladium membrane before reduction and deuteration of alkynes, and faced the chemical chamber when loaded into the reactor. 14 mL of a 0.5 M K2CO3 deuterated water solution was added to the electrochemical chamber. 6 mL of anhydrous ethanol, 0.1 mmol sodium thiophenol and 0.2 mmol 4-ethynylbenzaldehyde (1e) were added to the chemical chamber and stirred continuously with a magnet. The palladium membrane was used as the working electrode, the carbon rod was used as the counter electrode, and Hg / HgO was used as the reference electrode. The electrochemical workstation was connected and a constant voltage of -2 V was selected for electrolysis. After reacting for 2 hours, the reaction solution was collected and quantitatively analyzed by gas chromatography, and the conversion rate of 1e was 95% and the selectivity of 2e was 92%. Then, the product was distilled under reduced pressure to 0.5 mL, purified by thin layer chromatography, and qualitatively analyzed by nuclear magnetic resonance. The product was dissolved in CD3CN to test the hydrogen and carbon spectra, and the deuterium substitution rate was obtained: α-: 99%, β1-: 99%, such as Figure 6 As shown, (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum.

[0096] Example 6

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

[0098] A three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane was used as the reaction container. Palladium nanocones were electrodeposited on one side of the palladium membrane before reduction and deuteration of alkynes, and faced the chemical chamber when loaded into the reactor. 14 mL of a 0.5 M K2CO3 deuterated water solution was added to the electrochemical chamber. 6 mL of anhydrous ethanol, 0.1 mmol sodium thiophenol and 0.2 mmol 4-nitrophenylacetylene (1f) were added to the chemical chamber and stirred continuously with a magnet. The palladium membrane was used as the working electrode, the carbon rod was used as the counter electrode, and Hg / HgO was used as the reference electrode. The reaction was connected to an electrochemical workstation and a constant voltage of -2 V was selected for electrolysis. After reacting for 2 hours, the reaction solution was collected and quantitatively analyzed by gas chromatography, and the conversion rate of 1f and the selectivity of 2f were obtained to be 94% and 96%. Then, the product was distilled under reduced pressure to 0.5 mL, purified by thin layer chromatography, and qualitatively analyzed by nuclear magnetic resonance. The product was dissolved in CD3OH to test the hydrogen and carbon spectra, and the deuteration rates were: α-: 99%, β1-: 93%, as shown in Figure 7 As shown, (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum.

[0099] Example 7

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

[0101] A three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane is used as a reaction vessel. Before the alkyne reduction deuteration, palladium nanocones are electrodeposited on one side of the palladium membrane, and when loaded into the reactor, it faces the chemical chamber. A 14mL 0.5MK2CO3 deuterated water solution is added to the electrochemical chamber. 6mL anhydrous ethanol, 0.1mmol sodium benzenethiophenol and 0.2mmol 4-iodophenylacetylene (1g) are added to the chemical chamber and stirred continuously with a magnetic bar. The palladium membrane is used as the working electrode, the carbon rod is used as the counter electrode, and Hg / HgO is used as the reference electrode. It is connected to an electrochemical workstation and a constant voltage of -2V is selected for electrolysis. After 2h of reaction, the reaction liquid is collected and quantitatively analyzed by gas chromatography, and the conversion rate of 1g is 93% and the selectivity of 2g is 95%. Subsequently, it is distilled under reduced pressure to 0.5mL, and the product is purified by thin layer chromatography, and then qualitatively analyzed by nuclear magnetic resonance. The product is dissolved in DMSO-d6 to test the hydrogen spectrum, and the deuteration rate is obtained: α-: 99%, β1-: 92%, such as Figure 8 As shown, (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum.

[0102] Example 8

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

[0104] A three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane was used as a reaction container. Palladium nanocones were electrodeposited on one side of the palladium membrane before reduction and deuteration of alkynes, and faced the chemical chamber when loaded into the reactor. 14 mL of a 0.5 M K2CO3 deuterated water solution was added to the electrochemical chamber, and 6 mL of anhydrous ethanol, 0.1 mmol sodium thiophenol and 0.2 mmol 2-(4-alkynylphenyl)-4,4,5,5-tetramethyl-[1,3 2]-dioxaborane (1 h) were added to the chemical chamber and stirred continuously with a magnet. The palladium membrane was used as the working electrode, the carbon rod was used as the counter electrode, and Hg / HgO was used as the reference electrode. The electrochemical workstation was connected and a constant voltage of -2 V was selected for electrolysis. After reacting for 3 h, the reaction solution was collected and quantitatively analyzed by gas chromatography, and the conversion rate for 1 h and the selectivity for 2 h were obtained to be 95% and 94%. Then, the product was distilled under reduced pressure to 0.5 mL, purified by thin layer chromatography, and qualitatively analyzed by nuclear magnetic resonance. The product was dissolved in DMSO-d6 to test the hydrogen and carbon spectra, and the deuterated rates were: α-: 99%, β1-: 99%, as shown in Fig. 9 As shown, (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum.

[0105] Example 9

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

[0107] A three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane is used as a reaction vessel. Before the alkyne reduction deuteration, palladium nanocones are electrodeposited on one side of the palladium membrane, and the membrane faces the chemical chamber when loaded into the reactor. A 14 mL 0.5 M K2CO3 solution of deuterated water is added to the electrochemical chamber. 6 mL of anhydrous ethanol, 0.1 mmol sodium benzenethiophenol and 0.2 mmol 2-[(prop-2-ynyloxy)methyl]ethylene oxide (1i) are added to the chemical chamber and stirred continuously with a magnetic bar. The palladium membrane is used as the working electrode, the carbon rod is used as the counter electrode, and Hg / HgO is used as the reference electrode. The electrolysis is performed at a constant voltage of -2 V. After the reaction for 3 hours, the reaction solution is collected and quantitatively analyzed by gas chromatography, and the conversion rate of 1i is 95%, and the selectivity of 2i is 94%. Subsequently, the fractions are collected by vacuum distillation, and then qualitatively analyzed by nuclear magnetic resonance. The product is dissolved in CDCl3 to test the hydrogen spectrum and carbon spectrum, and the deuteration rate is obtained: α-: 99%, β1-: 99%, such as Fig.10 As shown, (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum.

[0108] Example 10

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

[0110] A three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane was used as a reaction container. Palladium nanocones were electrodeposited on one side of the palladium membrane before reduction and deuteration of alkynes, and faced the chemical chamber when loaded into the reactor. 14 mL of a 0.5 M K2CO3 deuterated water solution was added to the electrochemical chamber. 6 mL of anhydrous ethanol, 0.1 mmol sodium thiophenol and 0.2 mmol 4-ethynylbenzonitrile (1j) were added to the chemical chamber and stirred continuously with a magnet. The palladium membrane was used as the working electrode, the carbon rod was used as the counter electrode, and Hg / HgO was used as the reference electrode. The electrochemical workstation was connected and a constant voltage of -2 V was selected for electrolysis. After reacting for 3 hours, the reaction solution was collected and quantitatively analyzed by gas chromatography, and the conversion rate of 1j was 94% and the selectivity of 2j was 95%. Then, the product was distilled under reduced pressure to 0.5 mL, purified by thin layer chromatography, and qualitatively analyzed by nuclear magnetic resonance. The product was dissolved in DMSO-d6 to test the hydrogen and carbon spectra, and the deuterated rates were: α-: 99%, β1-: 99%, as shown in Fig.11 As shown, (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum.

[0111] Embodiment 11

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

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

[0114] A three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane was used as a reaction container. Palladium nanocones were electrodeposited on one side of the palladium membrane before reduction deuteration, and faced the chemical chamber when loaded into the reactor. 14 mL of a 0.5 M K2CO3 deuterated water solution was added to the electrochemical chamber. 5 mL of anhydrous ethanol, 0.1 mmol sodium thiophenol and the obtained crude product were added to the chemical chamber and stirred continuously with a magnet. The palladium membrane was used as the working electrode, the carbon rod was used as the counter electrode, and Hg / HgO was used as the reference electrode. The electrochemical workstation was connected and a constant voltage of -2 V was selected for electrolysis. After reacting for 4 hours, the reaction solution was collected and concentrated to obtain a crude product.

[0115] Under an argon atmosphere, an anhydrous N,N-dimethylformamide (DMF) solution containing Pd(dba)2 (0.02mmol) and benzophenanthroline (0.024mmol) was added to a round-bottom flask and stirred at room temperature for 30 minutes. Then, benzene diazonium salt (0.4mmol) and the above crude product were added and stirred at room temperature for 12 hours. The reaction solution was then extracted with ethyl acetate and deionized water, the organic phase was distilled under reduced pressure to 0.5mL, and the product was purified by thin layer chromatography. The dried sample was weighed and the separation yield was 72%. Qualitative analysis was then performed by nuclear magnetic resonance, and the product was dissolved in CDCl3 to test the hydrogen spectrum and carbon spectrum, as shown in FIG. Fig.12 As shown, (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum.

[0116] Example 12

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

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

[0119] A three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane was used as a reaction container. Palladium nanocones were electrodeposited on one side of the palladium membrane before reduction deuteration, and faced the chemical chamber when loaded into the reactor. 14 mL of a 0.5 M K2CO3 deuterated water solution was added to the electrochemical chamber. 5 mL of anhydrous ethanol, 0.1 mmol sodium thiophenol and the obtained crude product were added to the chemical chamber and stirred continuously with a magnet. The palladium membrane was used as the working electrode, the carbon rod was used as the counter electrode, and Hg / HgO was used as the reference electrode. The electrochemical workstation was connected and a constant voltage of -2 V was selected for electrolysis. After reacting for 4 hours, the reaction solution was collected and concentrated to obtain a crude product.

[0120] Under argon atmosphere, an anhydrous DMF solution containing Pd(dba)2 (0.02mmol), Pd / C (0.02mmol) and benzophenanthroline (0.024mmol) was added to a round-bottom flask and stirred at room temperature for 30 minutes. Then benzene diazonium salt (0.2mmol) and the above crude product were added and stirred at room temperature for 12 hours. The reaction solution was then extracted with ethyl acetate and deionized water, the organic phase was distilled under reduced pressure to 0.5mL, and the product was purified by thin layer chromatography. The dried sample was weighed to obtain a separation yield of 61%. Qualitative analysis was then performed using nuclear magnetic resonance, and the product was dissolved in CDCl3 to test the hydrogen spectrum and carbon spectrum, as shown in FIG. Fig.13 As shown, (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum.

[0121] Embodiment 13

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

[0123] Weigh 0.2mmol dihydroartemisinin and 0.4mmol 1,8-diazacyclo[5,4,0]undecene-7 (DBU) respectively and dissolve them in 5mL anhydrous DCM, add 0.4mmol 3-bromopropyne, stir at room temperature for 3h, and check whether the reaction is complete by gas chromatography-mass spectrometry. After the reaction is completed, extract with ethyl acetate and deionized water, wash the organic layer with brine in turn, remove water with anhydrous sodium sulfate, and remove ethyl acetate by rotary evaporation to obtain a crude product.

[0124] 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 reduction and deuteration, and faced the chemical chamber when loaded into the reactor. 14 mL of 0.5 M K2CO3 deuterated water solution was added to the electrochemical chamber, and 5 mL of anhydrous ethanol, 0.1 mmol sodium benzenethiophenol and the obtained crude product were added to the chemical chamber and stirred continuously with a magnet. The palladium membrane was used as the working electrode, the carbon rod was used as the counter electrode, and Hg / HgO was used as the reference electrode. It was connected to an electrochemical workstation and a constant voltage of -2 V was selected for electrolysis. After reacting for 3 hours, the reaction solution was collected. It was then distilled under reduced pressure to 0.5 mL, and the product was purified by thin layer chromatography. The dried sample was weighed, and the separation yield was 62%. Qualitative analysis was then performed using nuclear magnetic resonance, and the product was dissolved in CDCl3 to test the hydrogen spectrum and carbon spectrum, as shown in FIG. Fig.14 As shown, (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum.

[0125] Embodiment 14

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

[0127] Weigh 0.2mmol estradiol and 0.6mmol NaH respectively and dissolve them in 5mL anhydrous DMF, add 0.4mmol 3-bromopropyne, stir at room temperature for 3h, and check whether the reaction is complete by gas chromatography-mass spectrometry. After the reaction is completed, extract with ethyl acetate and deionized water, wash the organic layer with brine in turn, remove water with anhydrous sodium sulfate, and remove ethyl acetate by rotary evaporation to obtain a crude product.

[0128] A three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane is used as the reaction container. Palladium nanocones are electrodeposited on one side of the palladium membrane before reduction and deuteration, and the membrane faces the chemical chamber when loaded into the reactor. 14mL of 0.5MK2CO3 deuterated water solution is added to the electrochemical chamber, and 5mL of anhydrous ethanol, 0.1mmol sodium benzenethiophenol and the obtained crude product are added to the chemical chamber and stirred continuously with a magnet. The palladium membrane is used as the working electrode, the carbon rod is used as the counter electrode, and Hg / HgO is used as the reference electrode. It is connected to an electrochemical workstation and a constant voltage of -2V is selected for electrolysis. After reacting for 2h, the reaction solution is collected. It is then distilled under reduced pressure to 0.5mL, and the product is purified by thin layer chromatography. The dried sample is weighed, and the separation yield is 77%. Qualitative analysis is then performed using nuclear magnetic resonance, and the product is dissolved in DMSO-d6 to test the hydrogen spectrum and carbon spectrum, such as Fig.15 As shown, (a) is 1 H NMR spectrum, (b) 13 C NMR spectrum.

[0129] The present invention provides a substrate expansion diagram for preparing deuterated olefin compounds containing easily reducible and easily hydrolyzed functional groups by catalytic reduction of deuterated alkyne compounds by PhS-Pd, and a synthetic route for synthesizing deuterated naftifine, cinnarizine, artemisinin derivatives and estradiol derivatives. Fig.16 shown.

[0130] Example 15: Modified catalyst in situ formation of sodium thiophenolate modified palladium film (PhS-Pd)

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

[0132] Step 2: Calcination at 850 °C for 90 min in an 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 electroplated palladium solution: add PdCl2 into 1M hydrochloric acid solution and dissolve it by ultrasonication. The concentration of PdCl2 is 15.9mM.

[0135] Step 5: Load the treated palladium film into the reactor, add palladium solution into the electrochemical chamber to electro-deposit palladium nanocones, use the palladium film as the working electrode, Hg / HgO as the reference electrode, and the carbon rod as the counter electrode, apply -0.2V for constant potential electrolysis until the coulomb value reaches 13C;

[0136] Step 6: Remove the palladium membrane, rinse the palladium membrane, reactor and electrodes with deionized water and ethanol, blow dry, and then re-install the palladium membrane containing the electrodeposited palladium nanocones into the reactor with the side facing the chemical chamber for standby use;

[0137] Step 7: Add 14 mL of 0.5 M K2CO3 deuterated water solution into the electrochemical chamber, add 5 mL of anhydrous ethanol and 0.1 mmol of sodium thiophenolate into the chemical chamber and stir continuously with a magnet, use palladium film as the working electrode, carbon rod as the counter electrode, Hg / HgO as the reference electrode, connect to the electrochemical workstation, select a constant voltage of -2 V for electrolysis, and the catalyst composed of sodium thiophenolate adsorbed on the palladium nanocones wrapped by amorphous palladium sulfide is formed in situ during the electrolysis process.

[0138] After the reaction is completed, the palladium film is taken out and washed to obtain the in-situ formed sodium benzenethiophenol modified palladium film (catalyst PhS-Pd), the scanning electron microscope image of which is as follows: Fig.17 As shown in the figure, high-angle annular dark field scanning transmission electron microscopy (HADDF-STEM) and the corresponding STEM energy dispersive X-ray spectroscopy (EDS) elemental mapping images are shown in the figure. Fig.18As shown in Figure (a), the high-resolution transmission electron microscopy (HRTEM) image is as follows Fig.18 As shown in Figure (b); X-ray diffraction (XRD) image is as shown Fig.19 As shown; the Pd3d and S2p X-ray photoelectron spectroscopy (XPS) images of PhS-Pd are shown as Fig. 20 As shown in (a) and (b), it can be seen that the in-situ formed catalyst composition structure is that sodium thiophenolate molecules are adsorbed on the surface of palladium nanocones wrapped by amorphous palladium sulfide layer.

[0139] Comparative Example 2

[0140] Using Example 2 as a model, this comparative example was set up to verify the necessity of sodium benzenethiol modification. A three-chamber electrolytic cell separated by a palladium membrane and an ion exchange membrane was used as a reaction vessel. Palladium nanocones were electrodeposited on one side of the palladium membrane before alkyne reduction and deuteration, and faced the chemical chamber when loaded into the reactor. 14mL of 0.5M K2CO3 deuterated water solution was added to the electrochemical chamber, 6mL of anhydrous ethanol and 0.2mmol 4-bromophenylacetylene (1b) were added to the chemical chamber and stirred continuously with a magnet. The palladium membrane was used as the working electrode, the carbon rod was used as the counter electrode, and Hg / HgO was used as the reference electrode. It was connected to an electrochemical workstation, and a constant voltage of -2V was selected for electrolysis. After reacting for 2h, 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%. This comparative result fully illustrates the importance of sodium benzenethiol modification of the palladium membrane for the highly selective synthesis of deuterated olefins. The results are shown in FIG. Fig.21 As shown, sodium thiophenolate-Pd (palladium film modified with sodium thiophenolate) represents Example 2, and Pd (palladium film) represents Comparative Example 2.

[0141] Example 16

[0142] Stability test of PhS-Pd catalytic deuteration reduction of alkynes over a long period of time

[0143] The present invention also tests the stability of PhS-Pd in ​​the long-term catalytic reduction deuteration of alkynes. Using Example 2 as a model, 20g of 4-bromophenylacetylene reduction deuteration reaction was carried out in a clean electrolytic cell, and the stability of the catalyst was determined by selective detection of the product every 18 hours. The experimental results are shown in FIG. Fig. 22 As shown, the conversion rate of 1b reaches 95% after 216 hours, and the selectivity of 2b reaches 98%. After the reaction is continued for 10 hours, the selectivity of 2b only slightly decreases by less than <5%. Therefore, it can be seen that the catalyst of the present invention has good stability.

[0144] Embodiment 17

[0145] The present invention also tests the applicable range of potential and current for PhS-Pd catalyzed alkyne deuteration reduction. The experimental steps are the same as those in Example 2, except that the applied potential is changed. The present invention applies a potential of -1.5 to -4.5 V or a current of 10 to 400 mA. After reacting for 2 h, the reaction solution is collected and quantitatively analyzed by gas chromatography to obtain the conversion rate of 1b and the selectivity of 2b. Fig.23 As shown, 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 Faraday efficiency of 70%, indicating that the catalytic system of the present invention is applicable to a wide potential and current range.

[0146] The above description is only a preferred specific implementation manner of the present invention, and the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, and they should be covered by the protection scope of the present invention.

Claims

1. A method for synthesizing deuterated olefins by using D2O as a deuterium source and catalyzing palladium film, characterized in that: The method comprises 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 the ion exchange membrane to carry out an electrolytic deuterated water reaction, an organic solvent, sodium thiophenolate and an alkyne reactant are added to another reaction chamber to carry out an organic reaction of alkyne deuteration, the palladium membrane is used as a working electrode, deuterated water is used as a deuterium source, deuterated water is electrolyzed by a constant potential electrolysis method, the generated active deuterium is transferred from one side of the electrolytic reaction to the other side of the organic reaction, and then the deuterated alkyne compound is reduced by the palladium membrane modified by the sodium thiophenolate to obtain a deuterated olefin compound.

2. The synthesis method according to claim 1, characterized in that Palladium nanocones are deposited on one side of the palladium film, and the side on which the palladium nanocones are deposited faces a reaction chamber where an organic reaction is performed.

3. The synthesis method according to claim 1, characterized in that The method also includes the steps of removing the organic solvent in the reaction solution containing deuterated olefin compounds by a rotary evaporator to obtain a crude product of deuterated olefin; and purifying the crude product of deuterated olefin by thin layer chromatography or column chromatography to obtain a pure deuterated olefin.

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

5. The synthesis method according to claim 1, characterized in that The alkaline salt includes potassium carbonate, and the concentration of potassium carbonate deuterium aqueous solution is 0.5M; the organic solvent includes anhydrous ethanol or cyclohexane; the temperature of the deuterium water electrolysis reaction and the organic reaction are both 20-25°C, and the time is 4-8h; the constant potential is -1.5--4V.

6. Use of the synthesis method according to claim 1 in the synthesis of deuterated drugs.

7. A sodium thiophenolate-modified palladium membrane, characterized in that: One side of the palladium membrane is modified with sodium thiophenolate.

8. The sodium thiophenolate-modified palladium membrane according to claim 7, characterized in that: The side modified with sodium thiophenolate is previously deposited with palladium nanocones.

9. A method for preparing a sodium thiophenolate-modified palladium film according to claim 7 or 8, characterized in that: The sodium benzenethiophenol modified palladium membrane is generated in situ during the synthesis of deuterated olefins catalyzed by palladium membrane using D2O as a deuterium source as claimed in claim 1.

10. Use of the sodium benzenethiolate-modified palladium membrane according to claim 7 or 8 in the synthesis of deuterated olefins catalyzed by palladium membrane using D2O as a deuterium source.

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