A method for preparing deuterated cyclic compounds

Abstract

The present invention discloses a method for preparing a deuterated cyclic compound, which belongs to the technical field of electrolytic preparation of carbocyclic hydrocarbons. The method comprises mixing an aromatic ring or heteroaromatic ring compound, deuterated water, a first electrolyte, and a first solvent to obtain a solution and performing an electrolytic reaction to obtain a cyclic compound in which hydrogen on the ring is partially or completely replaced by deuterium. The present invention uses deuterated water as the main deuterium source, has a high deuterium atom utilization rate, good reaction substrate compatibility, and no strict requirements on raw materials. At the same time, the reaction does not require the addition of chemical oxidants or strong chemical reducing agents, the reaction conditions are mild, the reaction process is simple and easy to operate, and it is very suitable for preparing the corresponding deuterated compounds in laboratories and factories. The deuterated cyclic compound prepared by the invention has a high deuteration rate, high purity, simple preparation and separation operations, and low cost.

Description

Technical Field

[0001] The present invention relates to the technical field of electrolytic preparation of carbocyclic hydrocarbons, and in particular to a method for preparing deuterated cyclic compounds. Background Art

[0002] Deuterium is an inexpensive, non-radioactive hydrogen isotope. Because the bond energy of CD bonds is greater than that of CH bonds, and deuterium atoms have one more neutron than hydrogen atoms, introducing deuterium atoms into a compound to replace hydrogen atoms can alter the compound's properties to a certain extent. Isotope labeling has been widely used in chemistry, medicine, biology, and materials science. Its introduction into drug molecules may improve drug safety, reduce side effects, enhance drug tolerability, and mitigate first-pass effects.

[0003] Saturated (hetero)cyclic compounds are widely found in therapeutics, bioactive natural products, pharmaceutical molecules, and pesticides. Since most commercially available pharmaceuticals contain saturated (hetero)cyclic compounds, the synthesis of deuterated (hetero)cyclic molecules is of great importance. While direct hydrogen isotope exchange (HIE) is highly attractive, it typically only achieves deuteration at positions adjacent to the heteroatom or requires the presence of a directing group, preventing full ring deuteration of saturated (hetero)cyclic compounds and hindering high deuteration yields (>95%) per site. (Hetero)aromatic compounds are widespread in nature and readily available. The reduction of (hetero)aromatic rings to prepare saturated (hetero)cyclic compounds offers the advantages of inexpensive and readily available starting materials. However, the reduction of aromatic rings requires dearomatization, which requires high activation energies. Currently, only a few reports have used high-temperature and high-pressure deuterium gas or the strong reducing agent sodium deuterated borohydride to achieve this reduction. The use of high-pressure deuterium gas and sodium deuterated borohydride significantly increases production costs. This increases the difficulty of industrial production of saturated deuterated compounds.

[0004] Therefore, in order to reduce production costs and improve production safety, it is of great significance to study the use of cheap deuterated water as a deuterium source to achieve the reductive deuteration of aromatic rings to prepare saturated (hetero)cyclic compounds at room temperature and pressure. Summary of the Invention

[0005] The object of the present invention is to provide a simple, economical and safe method for preparing deuterated saturated cyclic and heterocyclic compounds.

[0006] In order to achieve the above object, the present invention provides a method for preparing a deuterated cyclic compound, comprising:

[0007] An aromatic ring or heteroaromatic ring compound, deuterated water, a first electrolyte, and a first solvent are mixed to obtain a solution and subjected to an electrolysis reaction to obtain a cyclic compound in which hydrogen on the ring is partially or completely replaced by deuterium.

[0008] Furthermore, the concentrations of the aromatic or heteroaromatic compound and the first electrolyte in the solution are 0.05-0.2 mol / L and 0.1-0.3 mol / L, respectively.

[0009] Furthermore, the first electrolyte includes at least one of sodium fluoride, sodium chloride, sodium bromide, sodium iodide, tetrabutylammonium tetrafluoroborate, tetrabutylammonium fluoride, tetrabutylammonium chloride, tetrabutylammonium bromide, and tetrabutylammonium iodide.

[0010] Furthermore, the first solvent includes at least one of deuterated methanol, deuterated ethanol, deuterated isopropanol, deuterated tert-butanol, tetrahydrofuran, and 1,4-dioxane.

[0011] Furthermore, the electrolysis reaction is carried out at a temperature of 20-80°C and a current density of 1-40 mA / cm 2 The condition lasts for 8-72 hours.

[0012] In the present invention, the anode material used in the electrolysis reaction does not need to be strictly limited and can be an inert material, such as a platinum sheet, a carbon sheet, a carbon cloth, a carbon felt, a carbon rod, a carbon paper, etc.; or it can be a sacrificial anode material, such as one of magnesium, aluminum, zinc, iron, copper, lead, etc.

[0013] Furthermore, the cathode material used in the electrolysis reaction is nitrogen-doped carbon felt loaded with metal, and its preparation method includes:

[0014] The carbon felt, melamine and ethanol are mixed and refluxed to obtain pretreated carbon felt;

[0015] The pretreated carbon felt is immersed in a mixed solution of melamine and paraformaldehyde to carry out a polymerization reaction to obtain a polymer-coated carbon felt;

[0016] calcining the polymer-coated carbon felt under a protective gas atmosphere to obtain nitrogen-doped carbon felt;

[0017] Immersing the nitrogen-doped carbon felt in a metal salt solution for adsorption reaction to obtain nitrogen-doped carbon felt adsorbing the metal salt;

[0018] The nitrogen-doped carbon felt adsorbed with metal salt is used as cathode to obtain the metal-loaded nitrogen-doped carbon felt through electrodeposition.

[0019] Furthermore, the mass ratio of the carbon felt, melamine and ethanol is 1:1-3:20;

[0020] Furthermore, the mass ratio of the pretreated carbon felt, melamine, paraformaldehyde and the solvent in the mixed solution is 1:1-15:1-15:10-50;

[0021] Furthermore, the mass ratio of the nitrogen-doped carbon felt, the metal salt, and the solvent in the metal salt solution is 1:0.05-0.5:40-60;

[0022] The metal element in the metal salt includes at least one of ruthenium, cerium, europium, gold, terbium, dysprosium, holmium, erbium, thulium, ytterbium, and lutetium.

[0023] Furthermore, the electrodeposition is carried out at a current density of 1-40 mA / cm 2 The electrolyte used in the cathode chamber and the anode chamber is prepared by the second electrolyte, the second organic solvent and water.

[0024] Wherein, the mass ratio of the second organic solvent to the water is 0-9:1;

[0025] The concentration of the second electrolyte is 0.05-0.2 mol / L;

[0026] The second electrolyte comprises at least one of sodium fluoride, tetrabutylammonium bromide, tetrabutylammonium chloride, and tetrabutylammonium iodide;

[0027] The second organic solvent includes at least one of tetrahydrofuran, 1,4-dioxane, methanol, ethanol, isopropanol, and tert-butanol;

[0028] The anode of the electrodeposition is made of an inert material.

[0029] The present invention also provides a perdeuterated piperazine compound, which is prepared by the above method.

[0030] The present invention also provides the use of the perdeuterated piperazine compound in the synthesis of deuterated drug molecules.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] The present invention uses deuterated water as the main deuterium source, has a high utilization rate of deuterium atoms, good reaction substrate compatibility, and no strict requirements on raw materials. At the same time, the reaction does not require the addition of chemical oxidants or strong chemical reducing agents. The reaction conditions are mild, the reaction process is simple and easy to operate, and it is very suitable for preparing corresponding deuterated compounds in laboratories and factories.

[0033] The deuterated cyclic compound prepared by the invention has high deuteration rate, high purity, simple preparation and separation operations and low cost. DETAILED DESCRIPTION

[0034] The endpoints of the ranges and any values ​​disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values ​​can be combined with each other to form one or more new numerical ranges, and these numerical ranges should be considered to be specifically disclosed in the present invention.

[0035] The following will be combined with specific embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0036] Example 1

[0037] A method for preparing a deuterated cyclic compound comprises the following steps:

[0038] S1. Add 0.4 mmol of benzamide, 0.8 mmol of sodium chloride, 2.5 mL of deuterated methanol, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution;

[0039] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at room temperature (25°C) and a current density (5 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0040] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0041] The preparation method of ruthenium-loaded nitrogen-doped carbon felt is as follows:

[0042] 1) Carbon felt was refluxed in a melamine ethanol dispersion at 80° C. and dried to prepare a melamine-adsorbed carbon felt, wherein the mass ratio of the carbon felt, melamine, and ethanol was 1:1:20.

[0043] 2) Melamine and paraformaldehyde were dissolved in dimethyl sulfoxide to obtain a mixed solution, and then the melamine-adsorbed carbon felt was immersed in the mixed solution, wherein the mass ratio of the melamine-adsorbed carbon felt, melamine, paraformaldehyde and dimethyl sulfoxide was 1:2:1:30. The mixture was heated at 110°C for 1 hour, and then raised to 160°C and heated for 24 hours to prepare the melamine and paraformaldehyde polymer-coated carbon felt.

[0044] 3) The carbon felt coated with melamine and paraformaldehyde was calcined at 800°C for 1 h under an argon atmosphere to prepare nitrogen-doped carbon felt.

[0045] 4) Immersing the nitrogen-doped carbon felt in a ruthenium trichloride aqueous solution, stirring at room temperature for 12 hours, and then removing and drying to obtain the nitrogen-doped carbon felt adsorbed with ruthenium salt, wherein the mass ratio of the nitrogen-doped carbon felt, ruthenium trichloride, and water is 1:0.05:50.

[0046] 5) Set up a separate electrolytic cell, where the electrolyte in the cathode chamber is prepared by 0.8 mmol tetrabutylammonium bromide, 5 mL tert-butyl alcohol and 5 mL water, and the electrolyte in the anode chamber is prepared by 0.8 mmol sodium fluoride and 10 mL water; insert the nitrogen-doped carbon felt adsorbed with ruthenium salt as the cathode into the cathode chamber, use a carbon rod as the anode, and connect the power supply at 5 mA / cm 2 The ruthenium-loaded nitrogen-doped carbon felt was obtained by deposition at a current density of 500 nm for 3 h.

[0047] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 5.49 (d, J = 23.2Hz, 2.00H), 2.16-2.10 (m, 0.11H), 1.91-1.87 (m, 0.19H), 1.81-1.76 (m, 1.22H), 1.64 (s, 0.21H), 1.39 (s, 1.32H), 1.31-1.22 (m, 0.92H), 1.19 (s, 0.64H); 13 CNMR (101 MHz, DMSO- d 6) δ 177.46, 43.16 (m, labeled), 28.55 (m, labeled), 24.79 (m, labeled).

[0048] Example 2

[0049] A method for preparing a deuterated cyclic compound comprises the following steps:

[0050] S1. Add 0.4 mmol N-methylbenzamide, 0.8 mmol sodium chloride, 2.5 mL deuterated methanol, and 2.5 mL deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution;

[0051] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at room temperature (25°C) and a current density (5 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0052] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0053] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0054] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 5.94 (s,1.00H), 2.75 (d, J = 4.8 Hz, 3.00H), 2.07-2.01 (m, 0.21H), 1.81-1.77 (m,0.30H), 1.74-1.70 (m, 1.09H), 1.63-1.59 (m, 0.26H), 1.36 (s, 1.46H), 1.18-1.13 (m, 0.97H); 13 C NMR (101 MHz, CDCl3) δ 176.01, 45.12 (m, labeled), 29.50 (m, labeled), 26.39, 25.31 (m, labeled).

[0055] Example 3

[0056] A method for preparing a deuterated cyclic compound comprises the following steps:

[0057] S1. Add 0.4 mmol of benzoic acid, 0.8 mmol of sodium bromide, 2.5 mL of deuterated methanol, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution.

[0058] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution below the liquid surface as cathode and anode, respectively, to construct a reaction system. The reaction system was heated at 60°C and a current density of 5 mA / cm 2 The electrolysis reaction was stirred for 72 h;

[0059] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0060] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0061] The NMR data of the product obtained in this example are: 1H NMR (400 MHz, CDCl3) δ 2.36-2.28 (m,0.06H), 1.94-1.89 (m, 0.08H), 1.76-1.68 (m, 1.07H), 1.65-1.55 (m, 1.08H), 1.42 (s, 0.98H), 1.19 (s, 0.53H); 13 C NMR (101 MHz, CDCl3) δ 183.11, 42.70 (m, labeled), 28.32 (m, labeled), 25.04 (m, labeled).

[0062] Example 4

[0063] A method for preparing a deuterated cyclic compound comprises the following steps:

[0064] S1. Add 0.4 mmol of phenol, 0.8 mmol of sodium bromide, 2.5 mL of deuterated methanol, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution.

[0065] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution below the liquid surface as cathode and anode, respectively, to construct a reaction system. The reaction system was heated at 60°C and a current density of 5 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0066] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0067] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0068] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 8.08-8.05 (m,1.99H), 7.57-7.52 (m, 1.00H), 7.44 (t, J = 7.6 Hz, 2.00H), 5.05-5.01 (m,0.01H), 1.90 (s, 0.50H), 1.76 (s, 0.90H), 1.56 (s, 0.63H), 1.53 (s, 0.34H), 1.41 (s, 0.78H), 1.31 (s, 0.48H); 13C NMR (101 MHz, CDCl3) δ 166.12, 132.80,131.11, 129.64, 128.43, 128.38, 72.60 (m, labeled), 31.10 (m, labeled), 24.93 (m, labeled), 23.07 (m, labeled).

[0069] To facilitate the determination of deuterated products, in step S3 of this embodiment, the organic phase was spin-dried, and then 0.04 mmol of 4-dimethylaminopyridine, 0.6 mmol of benzoyl chloride, 1.2 mmol of triethylamine, and 2 mL of dichloromethane were added. The mixture was stirred at room temperature (25°C) for 24 hours, and then the solution was spin-dried. The sample was dry-loaded using 200-300 mesh silica gel and eluted with a gradient of petroleum ether and ethyl acetate to separate the test sample.

[0070] Example 5

[0071] A method for preparing a deuterated cyclic compound comprises the following steps:

[0072] S1. Add 0.4 mmol of aniline, 0.8 mmol of tetrabutylammonium bromide, 2.5 mL of deuterated tert-butyl alcohol, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution.

[0073] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution below the liquid surface as cathode and anode, respectively, to construct a reaction system. The reaction system was heated at 60°C and a current density of 5 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0074] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0075] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0076] The NMR data of the product obtained in this example are: 1H NMR (400 MHz, CDCl3) δ 7.77-7.72 (m,1.98H), 7.49-7.45 (m, 1.00H), 7.40-7.37 (m, 2.01H), 6.55-6.16 (m, 0.99H), 3.56-3.47 (m, 0.02H), 3.28-3.19 (m, 0.02H), 2.26-2.00 (m, 0.53H), 1.90-1.85(m, 0.57H), 1.74-1.61 (m, 0.39H), 1.46-1.37 (m, 0.20H), 1.20-1.14 (m, 1.32H); 13 C NMR (101 MHz, CDCl3) δ 167.46, 167.10, 166.98, 135.12, 134.76, 134.64,131.66, 131.59, 131.45, 131.38, 128.68, 128.62, 128.60, 127.13, 127.12,127.00, 126.95, 125.91, 47.18 (m, labeled), 40.61 (m, labeled), 33.47 (m,labeled), 30.94 (m, labeled), 28.47 (m, labeled), 23.57 (m, labeled), 22.86(m, labeled), 19.11 (m, labeled).

[0077] To facilitate the determination of deuterated products, in step S3 of this embodiment, the organic phase was spin-dried, and then 0.04 mmol of 4-dimethylaminopyridine, 0.6 mmol of benzoyl chloride, 1.2 mmol of triethylamine, and 2 mL of dichloromethane were added. The mixture was stirred at room temperature (25°C) for 24 hours, and then the solution was spin-dried. The sample was dry-loaded using 200-300 mesh silica gel and eluted with a gradient of petroleum ether and ethyl acetate to separate the test sample.

[0078] Example 6

[0079] A method for preparing a deuterated cyclic compound comprises the following steps:

[0080] S1. Add 0.4 mmol of N-pentylaniline, 0.8 mmol of tetrabutylammonium bromide, 2.5 mL of deuterated tert-butyl alcohol, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution.

[0081] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution below the liquid surface as cathode and anode, respectively, to construct a reaction system. The reaction system was heated at 60°C and a current density of 5 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0082] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0083] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0084] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 7.35-7.34 (m,3.00H), 7.31-7.29 (m, 1.98H), 3.40 (s, 0.02H), 3.28 (s, 0.07H), 3.04 (s,0.03H), 2.20-2.14 (m, 0.25H), 1.77-1.65 (m, 2.60H), 1.46-1.34 (m, 4.49H), 1.07-0.72 (m, 5.05H); 13 C NMR (101 MHz, CDCl3) δ 171.48, 137.77, 128.98,128.75, 128.45, 126.07, 58.18 (m, labeled), 53.88 (m, labeled), 45.02 (m,labeled), 41.48 (m, labeled), 30.84 (m, labeled), 29.75, 29.64, 29.00, 24.96 (m, labeled), 22.57, 21.99, 14.17, 13.92.

[0085] To facilitate the determination of deuterated products, in step S3 of this embodiment, the organic phase was spin-dried, and then 0.04 mmol of 4-dimethylaminopyridine, 0.6 mmol of benzoyl chloride, 1.2 mmol of triethylamine, and 2 mL of dichloromethane were added. The mixture was stirred at room temperature (25°C) for 24 hours, and then the solution was spin-dried. The sample was dry-loaded using 200-300 mesh silica gel and eluted with a gradient of petroleum ether and ethyl acetate to separate the test sample.

[0086] Example 7

[0087] A method for preparing a deuterated cyclic compound comprises the following steps:

[0088] S1. Add 0.4 mmol of acetanilide, 0.8 mmol of tetrabutylammonium iodide, 2.5 mL of tetrahydrofuran, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution;

[0089] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution below the liquid surface as cathode and anode, respectively, to construct a reaction system. The reaction system was heated at 60°C and a current density of 5 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0090] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0091] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0092] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 5.60 (s,1.00H), 3.75-3.67 (m, 0.11H), 2.01 (s, 0.10H), 1.93 (s, 2.88H), 1.89-1.84 (m,0.33H), 1.69-1.64 (m, 1.05H), 1.59-1.55 (m, 0.31H), 1.35-1.23 (m, 0.55H), 1.14-1.06 (m, 1.69H); 13 C NMR (101 MHz, CDCl3) δ 169.27, 32.67 (m, labeled), 29.77 (m, labeled), 24.87 (m, labeled), 23.84.

[0093] Example 8

[0094] A method for preparing a deuterated cyclic compound comprises the following steps:

[0095] S1. In a dry 15 mL three-necked flask equipped with a magnet, add 0.4 mmol of tert-butyl N-phenylcarbamate, 0.8 mmol of tetrabutylammonium iodide, 2.5 mL of tetrahydrofuran, and 2.5 mL of deuterated water and stir to obtain a solution;

[0096] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at 50°C and a current density of 5 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0097] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0098] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0099] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 4.43 (s,0.98H), 3.39 (s, 0.05H), 1.91-1.84 (m, 0.34H), 1.64 (s, 1.09H), 1.53 (s,0.25H), 1.43 (s, 9.00H), 1.27 (s, 0.61H), 1.09 (s, 0.55H), 1.05 (s, 1.30H); 13 CNMR (101 MHz, CDCl3) δ 155.39, 79.10, 49.03 (m, labeled), 33.08 (m, labeled), 29.87, 28.61, 24.76 (m, labeled).

[0100] Example 9

[0101] A method for preparing a deuterated cyclic compound comprises the following steps:

[0102] S1. Add 0.4 mmol of 8-methylquinoline, 0.8 mmol of tetrabutylammonium tetrafluoroborate, 2.5 mL of 1,4-dioxane, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution;

[0103] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution below the liquid surface as cathode and anode, respectively, to construct a reaction system. The reaction system was heated at 80°C and a current density of 5 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0104] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0105] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0106] The NMR data of the product obtained in this example are: 1H NMR (400 MHz, CDCl3) δ 6.92-6.87 (m, 2.00H), 6.61-6.57 (m, 0.69H), 3.57-3.37 (m, 1.70H), 2.87-2.79 (m, 0.67H), 2.11-2.08 (m, 1.90H), 1.97-1.92 (m, 0.92H); 13 C NMR (101 MHz, CDCl3) δ 142.91,128.02, 127.91, 127.56, 127.45, 121.38, 121.29, 121.01, 120.95, 116.58, 42.08(m, labeled), 27.01 (m, labeled), 21.82 (m, labeled), 17.36, 17.08 (m, labeled).

[0107] Example 10

[0108] A method for preparing a deuterated cyclic compound comprises the following steps:

[0109] S1. Add 0.4 mmol of 2-hydroxypyridine, 0.8 mmol of tetrabutylammonium tetrafluoroborate, 2.5 mL of 1,4-dioxane, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution;

[0110] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution below the liquid surface as cathode and anode, respectively, to construct a reaction system. The reaction system was heated at 80°C and a current density of 5 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0111] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0112] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0113] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 6.88 (s,1.00H), 3.28-3.25 (m, 0.62H), 2.33-2.30 (m, 1.25H), 1.78-1.69 (m, 1.77H); 13CNMR (101 MHz, CDCl3) δ 172.94, 41.96 (m, labeled), 31.23 (m, labeled), 21.71 (m, labeled), 20.37 (m, labeled).

[0114] Example 11

[0115] A method for preparing a deuterated cyclic compound comprises the following steps:

[0116] S1. Add 0.4 mmol of 1-acetylindole, 0.8 mmol of sodium iodide, 2.5 mL of 1,4-dioxane, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution.

[0117] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at 50°C and a current density of 5 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0118] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0119] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0120] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 8.4Hz, 0.83H), 7.26-7.12 (m, 2.02H), 7.01 (t, J = 7.4 Hz, 1.00H), 4.11-3.96 (m,1.06H), 3.20-3.04 (m, 0.88H), 2.44-2.22 (m, 3.00H); 13 C NMR (101 MHz, CDCl3) δ168.88, 143.11, 131.20, 127.71, 126.07, 124.72, 123.73, 123.30, 117.11, 48.50(m, labeled), 27.80 (m, labeled), 24.83, 24.41.

[0121] Example 12

[0122] A method for preparing a deuterated cyclic compound comprises the following steps:

[0123] S1. Add 0.4 mmol of N-phenylcyclopentanolactam, 0.8 mmol of sodium bromide, 2.5 mL of 1,4-dioxane, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution;

[0124] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at 10°C and a current density of 5 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0125] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0126] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0127] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 3.90-3.83 (m,0.11H), 3.29 (t, J = 7.0 Hz, 2.00H), 2.33 (t, J = 8.0 Hz, 1.99H), 1.97-1.89 (m,1.99H), 1.69 (s, 0.92H), 1.64-1.57 (m, 0.62H), 1.28 (s, 2.02H), 1.01 (s,0.43H); 13 C NMR (101 MHz, CDCl3) δ 174.30, 50.07 (m, labeled), 42.90, 31.71, 29.75 (m, labeled), 24.87 (m, labeled), 18.23.

[0128] Example 13

[0129] A method for preparing a deuterated cyclic compound comprises the following steps:

[0130] S1. Add 0.4 mmol N-methylacetanilide, 0.8 mmol sodium bromide, 2.5 mL N,N-dimethylformamide, and 2.5 mL deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution;

[0131] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at room temperature of 25°C and a current density of 10 mA / cm 2 The electrolysis reaction was stirred for 6 h;

[0132] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0133] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0134] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 3.47-3.41 (m,0.05H), 2.78 (d, J = 12.8 Hz, 3.00H), 2.06 (d, J = 15.6 Hz, 2.98H), 1.78 (s,0.54H), 1.71 (s, 0.56H), 1.44 (s, 0.80H), 1.27 (s, 1.26H), 1.03-1.00 (m,0.52H); 13 C NMR (101 MHz, CDCl3) δ 170.21, 170.11, 57.27 (m, labeled), 51.60 (m, labeled), 30.31 (m, labeled), 30.29, 29.48 (m, labeled), 27.01, 24.99 (m, labeled), 22.66, 21.76.

[0135] Example 14

[0136] A method for preparing a deuterated cyclic compound comprises the following steps:

[0137] S1. Add 0.4 mmol of diphenylmethylphosphine oxide, 0.8 mmol of sodium chloride, 2.5 mL of deuterated methanol, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution.

[0138] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at room temperature of 25°C and a current density of 10 mA / cm 2 The electrolysis reaction was stirred for 12 h;

[0139] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0140] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0141] The title product was obtained with a 99% yield (99.2 mg, 0.4 mmol scale) as a white solid. 1 H NMR (400 MHz, CDCl3) δ 1.88-1.83 (m, 0.22H), 1.71-1.53 ​​(m, 2.05H), 1.25-1.10 (m, 7.73H); 13 C NMR (101 MHz, CDCl3) δ 35.07 (m, labeled), 31.19, 25.10 (m, labeled), 24.15 (m, labeled), 8.76, 8.14.

[0142] Example 15

[0143] A method for preparing a deuterated cyclic compound comprises the following steps:

[0144] S1. Add 0.4 mmol of 3-methylcyclopentylphenylphosphine oxide, 0.8 mmol of sodium iodide, 2.5 mL of deuterated tert-butyl alcohol, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution;

[0145] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution below the liquid surface as cathode and anode, respectively, to construct a reaction system. The reaction system was heated at 40°C and a current density of 8 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0146] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0147] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0148] The NMR data of the product obtained in this example are: 1H NMR (400 MHz, CDCl3) δ 2.31-2.18 (m,0.22H), 2.11-1.50 (m, 6.21H), 1.32-1.24 (m, 2.04H), 1.21-1.11 (m, 2.35H),1.07-1.02. (m, 3.00H); 13 C NMR (201 MHz, CDCl3) δ 38.28 (m, labeled), 34.08,34.00, 33.97, 33.42, 33.38, 33.35, 33.31, 32.67, 32.61, 32.52, 31.26, 26.67,26.07, 24.98 (m, labeled), 24.68, 21.25, 21.18, 21.12, 21.06.

[0149] Example 16

[0150] A method for preparing a deuterated cyclic compound comprises the following steps:

[0151] S1. Add 0.4 mmol of diphenyldimethylsilane, 0.8 mmol of sodium iodide, 2.5 mL of tetrahydrofuran, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution;

[0152] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution below the liquid surface as cathode and anode, respectively, to construct a reaction system. The reaction system was heated at room temperature of 25°C and a current density of 6 mA / cm 2 The electrolysis reaction was stirred for 18 h;

[0153] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0154] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0155] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 1.71-1.60 (m,2.49H), 1.17 (s, 1.27H), 1.05 (s, 2.53H), -0.15 (s, 4.81H); 13C NMR (101 MHz, CDCl3) δ 27.43 (m, labeled), 23.30 (m, labeled), -7.12.

[0156] Example 17

[0157] A method for preparing a deuterated cyclic compound comprises the following steps:

[0158] S1. Add 0.4 mmol of triethylphenylsilane, 0.8 mmol of tetrabutylammonium iodide, 2.5 mL of deuterated methanol, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution.

[0159] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution below the liquid surface as cathode and anode, respectively, to construct a reaction system. The reaction system was heated at 60°C and a current density of 5 mA / cm 2 The electrolysis reaction was stirred for 12 h;

[0160] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0161] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0162] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 1.72-1.63 (m,1.32H), 1.19-1.11 (m, 2.27H), 0.95 (t, J = 8.0 Hz, 9.00H), 0.52 (q, J = 8.0 Hz,5.98H); 13 C NMR (101 MHz, CDCl3) δ 27.69 (m, labeled), 26.70 (m, labeled), 22.96 (m, labeled), 7.94, 2.14.

[0163] Example 18

[0164] A method for preparing a deuterated cyclic compound comprises the following steps:

[0165] S1. In a dry 15 mL three-necked flask equipped with a magnet, 0.4 mmol of 4-trifluoromethylbiphenyl, 0.8 mmol of tetrabutylammonium iodide, 2.5 mL of 1,4-dioxane, and 2.5 mL of deuterated water were added and stirred to obtain a solution;

[0166] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at 30°C and a current density of 10 mA / cm 2 The electrolysis reaction was stirred for 15 h;

[0167] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0168] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0169] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 1.78-1.68 (m, 2.57H), 1.61-1.56 (m, 1.62H), 1.23-1.08 (m, 1.40H), 0.97-0.80 (m, 2.33H); 13 CNMR (101 MHz, CDCl3) δ 129.87, 127.10, 30.25 (m, labeled), 26.09 (m, labeled), 25.26 (m, labeled), 20.94 (m, labeled); 19 F NMR (377 MHz, CDCl3) -62.21, -71.52, -73.88.

[0170] Example 19

[0171] A method for preparing a deuterated cyclic compound comprises the following steps:

[0172] S1. In a dry 15 mL three-necked flask equipped with a magnet, add 0.4 mmol of n-decylphenyl ether, 0.8 mmol of tetrabutylammonium fluoride, 2.5 mL of tetrahydrofuran, and 2.5 mL of deuterated water, and stir to obtain a solution;

[0173] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at 10°C and a current density of 5 mA / cm 2 The electrolysis reaction was stirred for 20 h;

[0174] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0175] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0176] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 3.42 (t, J = 6.8Hz, 2.00H), 3.21-3.16 (m, 0.05H), 1.69 (s, 0.99H), 1.58-1.49 (m, 1.90H), 1.33-1.15 (m, 17.18H), 0.88 (t, J = 6.8 Hz, 3.00H); 13 C NMR (101 MHz, CDCl3) δ68.11, 32.11, 31.94 (m, labeled), 30.45, 29.84, 29.79, 29.73, 29.54, 26.45,25.28 (m, labeled), 23.89 (m, labeled), 22.90, 14.34.

[0177] Example 20

[0178] A method for preparing a deuterated cyclic compound comprises the following steps:

[0179] S1. Add 0.4 mmol of 2-hexylphenol, 0.8 mmol of tetrabutylammonium fluoride, 2.5 mL of 1,4-dioxane, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution;

[0180] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at 30°C and a current density of 10 mA / cm 2 The electrolysis reaction was stirred for 10 h;

[0181] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0182] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0183] The NMR data of the product obtained in this example are: 1H NMR (400 MHz, CDCl3) δ 3.87-3.86 (m,0.05H), 1.90 (s, 0.06H), 1.78-1.68 (m, 0.29H), 1.60 (s, 0.77H), 1.51 (s,0.59H), 1.43-1.03 (m, 9.98H), 0.88 (t, J = 6.6 Hz, 3.00H); 13 C NMR (101 MHz, CDCl3) δ 69.16 (m, labeled), 40.50 (m, labeled), 32.34 (m, labeled), 32.10, 29.97, 29.94, 29.91, 29.81, 29.79, 29.76, 27.20, 27.11, 27.01, 26.69, 26.60,26.49, 26.17 (m, labeled), 24.70 (m, labeled), 22.88, 20.07 (m, labeled),14.32.

[0184] Example 21

[0185] A method for preparing a deuterated cyclic compound comprises the following steps:

[0186] S1. Add 0.4 mmol of 1-naphthol, 0.8 mmol of sodium iodide, 2.5 mL of tetrahydrofuran, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution;

[0187] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at room temperature of 25°C and a current density of 3 mA / cm 2 The electrolysis reaction was stirred for 21 h;

[0188] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0189] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0190] The NMR data of the product obtained in this example are: 1H NMR (400 MHz, CDCl3) δ 1.76-1.68 (m,1.75H), 1.59-1.33 (m, 1.56H), 1.20 (s, 0.10H), 1.12-1.08 (m, 0.10H); 13 C NMR(101 MHz, CDCl3) δ 72.95 (m, labeled), 41.98 (m, labeled), 34.91 (m, labeled), 33.08 (m, labeled), 31.12 (m, labeled), 28.38 (m, labeled), 25.67(m, labeled), 23.75 (m, labeled), 21.02 (m, labeled), 20.04 (m, labeled), 18.32 (m, labeled).

[0191] Example 22

[0192] A method for preparing a deuterated cyclic compound comprises the following steps:

[0193] S1. Add 0.4 mmol of benzoic acid epoxybutyl-3-ester, 0.8 mmol of sodium chloride, 2.5 mL of deuterated methanol, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnetic stirrer and obtain a solution.

[0194] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at room temperature of 25°C and a current density of 5 mA / cm 2 The electrolysis reaction was stirred for 12 h;

[0195] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0196] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0197] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 5.45-5.39 (m,0.99H), 4.90 (t, J = 7.4 Hz, 2.00H), 4.62 (dd, J= 6.4, 8.4 Hz, 2.00H), 2.36-2.30(m, 0.17H), 1.93-1.89 (m, 0.27H), 1.78-1.72 (m, 1.49H), 1.67-1.63 (m, 0.71H), 1.42 (s, 1.77H), 1.20 (s, 0.88H); 13 C NMR (101 MHz, CDCl3) δ 175.69, 77.92, 67.75, 43.60 (m, labeled), 28.43 (m, labeled), 24.97 (m, labeled).

[0198] Example 23

[0199] A method for preparing a deuterated cyclic compound comprises the following steps:

[0200] S1. Add 0.4 mmol of trifluoropropyl benzoate, 0.8 mmol of sodium bromide, 2.5 mL of deuterated tert-butyl alcohol, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution.

[0201] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution below the liquid surface as cathode and anode, respectively, to construct a reaction system. The reaction system was heated at 40°C and a current density of 10 mA / cm 2 The electrolysis reaction was stirred for 7 h;

[0202] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0203] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0204] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 4.29 (t, J = 6.2Hz, 2.00H), 2.52-2.41 (m, 2.01H), 2.32-2.27 (m, 0.15H), 1.91-1.86 (m, 0.29H), 1.77-1.71 (m, 1.32H), 1.66-1.61 (m, 0.32H), 1.43-1.40 (m, 1.68H), 1.19 (s,1.21H); 13C NMR (101 MHz, CDCl3) δ 175.97, 126.05 (q, J = 277.8 Hz), 57.06 (q, J =3.7 Hz), 43.00 (m, labeled), 33.60 (q, J = 29.3 Hz), 28.22 (m, labeled), 24.73 (m, labeled).

[0205] Example 24

[0206] A method for preparing a deuterated cyclic compound comprises the following steps:

[0207] S1. Add 0.4 mmol of benzoylmorpholine, 0.8 mmol of tetrabutylammonium fluoride, 2.5 mL of deuterated methanol, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution.

[0208] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at 50°C and a current density of 7 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0209] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0210] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0211] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3)δ 3.66-3.47 (m,8.00H), 2.42-2.37 (m, 0.07H), 2.02-1.90 (m, 0.16H), 1.75 (s, 1.22H), 1.70-1.63 (m, 0.38H), 1.48 (s, 1.52H), 1.20 (s, 0.87H); 13 C NMR (101 MHz, CDCl3) δ174.92, 67.17, 67.04, 46.00, 42.00, 39.89 (m, labeled), 28.80 (m, labeled), 25.28 (m, labeled).

[0212] Example 25

[0213] A method for preparing a deuterated cyclic compound comprises the following steps:

[0214] S1. Add 0.4 mmol of benzoyl-4-trifluoromethylpyrrole, 0.8 mmol of tetrabutylammonium iodide, 2.5 mL of deuterated isopropanol, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution.

[0215] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at room temperature of 25°C and a current density of 3 mA / cm 2 The electrolysis reaction was stirred for 21 h;

[0216] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0217] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0218] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 4.75 (d, J = 13.2Hz, 1.00H), 4.01 (d, J = 13.6 Hz, 1.00H), 3.00 (t, J = 13.0 Hz, 1.00H), 2.52-2.40(m, 1.05H), 2.33-2.18 (m, 1.01H), 1.95-1.87 (m, 2.24H), 1.75 (s, 1.23H), 1.67-1.64 (m, 0.36H), 1.53-1.40 (m, 3.55H), 1.21 (s, 0.87H); 13 C NMR (101 MHz, CDCl3) δ 174.79, 127.14 (q, J = 279.30 Hz), 44.34, 41.28, 41.00, 40.73, 40.65,40.46, 40.01 (m, labeled), 28.98 (m, labeled), 25.64, 25.32 (m, labeled),24.48. 19 F NMR (377 MHz, CDCl3) δ -73.89.

[0219] Example 26

[0220] A method for preparing a deuterated cyclic compound comprises the following steps:

[0221] S1. Add 0.4 mmol of benzoylcyclopropylamine, 0.8 mmol of tetrabutylammonium tetrafluoroborate, 2.5 mL of deuterated methanol, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution.

[0222] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at 20°C and a current density of 10 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0223] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0224] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0225] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 4.13 (t, J = 7.6Hz, 2.00H), 3.97 (t, J = 7.6 Hz, 1.99H), 2.27-2.19 (m, 2.01H), 2.11-2.05 (m,0.08H), 2.02-1.96 (m, 0.03H), 1.72 (s, 1.32H), 1.66-1.60 (m, 0.45H), 1.41 (s,1.53H), 1.17 (s, 1.05H); 13 C NMR (201 MHz, CDCl3) δ 176.28, 50.16, 47.79, 28.08 (m, labeled), 25.16 (m, labeled), 15.24.

[0226] Example 27

[0227] A method for preparing a deuterated cyclic compound comprises the following steps:

[0228] S1. Add 0.4 mmol N,N-diethylbenzamide, 0.8 mmol tetrabutylammonium iodide, 2.5 mL 1,4-dioxane, and 2.5 mL deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution;

[0229] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution below the liquid surface as cathode and anode, respectively, to construct a reaction system. The reaction system was heated at 10°C and a current density of 15 mA / cm 2 The electrolysis reaction was stirred for 10 h;

[0230] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0231] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0232] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 3.37-3.28 (m,4.00H), 2.40-2.34 (m, 0.09H), 1.90 (s, 0.31H), 1.75 (s, 1.12H), 1.69-1.64 (m,0.48H), 1.51 (s, 1.52H), 1.26-1.16 (m, 4.09H), 1.10-1.06 (m, 3.00H); 13 C NMR (101 MHz, CDCl3) δ 175.74, 41.83, 40.18, 29.17 (m, labeled), 25.42 (m, labeled), 15.21, 13.33.

[0233] Example 28

[0234] A method for preparing a deuterated cyclic compound comprises the following steps:

[0235] S1. In a dry 15 mL three-necked flask equipped with a magnet, add 0.4 mmol N,N-dimethylbenzamide, 0.8 mmol tetrabutylammonium bromide, 2.5 mL tetrahydrofuran, and 2.5 mL deuterated water and stir to obtain a solution;

[0236] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at room temperature of 25°C and a current density of 20 mA / cm 2 The electrolysis reaction was stirred for 7 h;

[0237] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0238] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0239] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, CDCl3) δ 3.00 (s,2.74H), 2.88 (s, 2.63H), 2.42 (t, J = 12.0 H, 0.06H), 1.71 (s, 1.32H), 1.63-1.59 (m, 0.37H), 1.41 (s, 1.53H), 1.19-1.16 (m, 0.98H); 13 C NMR (201 MHz, CDCl3)δ 176.26, 40.10 (m, labeled), 37.12, 35.56, 28.62 (m, labeled), 25.30 (m, labeled).

[0240] Example 29

[0241] A method for preparing a deuterated cyclic compound comprises the following steps:

[0242] S1. Add 0.4 mmol of benzoyl 4,4-difluorocyclohexylamine, 0.8 mmol of sodium bromide, 2.5 mL of N,N-dimethylformamide, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution;

[0243] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution below the liquid surface as cathode and anode, respectively, to construct a reaction system. The reaction system was heated at room temperature of 25°C and a current density of 30 mA / cm 2 The electrolysis reaction was stirred for 4 h;

[0244] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0245] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0246] The NMR data of the product obtained in this example are: 1H NMR (400 MHz, CDCl3) δ 5.33 (d, J = 7.2Hz, 1.00H), 4.13 (q, J = 7.2 Hz, 0.11H), 3.94-3.85 (m, 0.88H), 2.23 (t, J = 7.4Hz, 0.06H), 2.12-1.75 (m, 6.52H), 1.67-1.64 (m, 0.79H), 1.54-1.44 (m, 1.80H), 1.38 (s, 1.23H), 1.28-1.21 (m, 1.18H); 13 C NMR (101 MHz, CDCl3) δ 175.86,125.11, 122.73, 120.32, 46.04, 32.70, 32.46, 32.21, 29.26 (m, labeled),28.99, 28.89, 25.26 (m, labeled). 19 F NMR (377 MHz, CDCl3) δ -94.48, -95.11, -101.08, -101.71.

[0247] Example 30

[0248] A method for preparing a deuterated cyclic compound comprises the following steps:

[0249] S1. Add 0.4 mmol of benzoyl-O-methylethanolamine, 0.8 mmol of sodium iodide, 2.5 mL of N,N-dimethylformamide, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution.

[0250] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at room temperature of 25°C and a current density of 10 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0251] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and the organic phase is then spin-dried. The product is separated by dry-loading on 200-300 mesh silica gel and gradient eluting with petroleum ether and ethyl acetate.

[0252] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0253] The NMR data of the product obtained in this example are: 1H NMR (400 MHz, CDCl3) δ 5.89 (s, 0.98H), 3.43-3.41 (m, 4.00H), 3.35-3.32 (m, 2.99H), 2.08-2.02 (m, 0.12H), 1.83-1.80 (m, 0.21H), 1.72 (s, 1.74H), 1.60 (s, 0.25H), 1.38 (s, 1.46H), 1.23-1.16 (m, 1.20H); 13 C NMR (201 MHz, CDCl3) δ 176.38, 71.51, 58.92, 45.02(m, labeled), 39.10, 29.19 (m, labeled), 25.25 (m, labeled).

[0254] Example 31

[0255] A method for preparing a deuterated cyclic compound comprises the following steps:

[0256] S1. Add 0.4 mmol of piperazine-d4, 0.8 mmol of sodium chloride, 2.5 mL of N,N-dimethylformamide, and 2.5 mL of deuterated water to a dry 15 mL three-necked flask equipped with a magnet and stir to obtain a solution;

[0257] S2: Nitrogen-doped carbon felt and aluminum sheet loaded with ruthenium were inserted into the solution as cathode and anode respectively to construct a reaction system. The reaction system was heated at room temperature of 25°C and a current density of 10 mA / cm 2 The electrolysis reaction was stirred for 14 h;

[0258] S3. After the electrolysis reaction is completed, the reaction solution is extracted with ethyl acetate, and then the organic phase is spin-dried and recrystallized to obtain the product.

[0259] The preparation method of the ruthenium-loaded nitrogen-doped carbon felt is the same as that in Example 1.

[0260] The NMR data of the product obtained in this example are: 1 H NMR (400 MHz, D O) δ 2.77; 13 C NMR (101MHz, D2O) δ 34.68.

[0261] The raw materials, deuterated products, yields and deuterated rates of the above examples are summarized in Table 1.

[0262] Table 1

[0263]

[0264]

[0265]

[0266] As can be seen from the results in Table 1, the present invention has no strict restrictions on the type of reactants. They can include functional groups such as arylamide, arylcarboxylic acid, arylamine, phenol, silicon, and trifluoromethyl, as well as heterocyclic aromatic compounds such as quinoline, indole, and piperazine. Using heavy water as a deuterium source, deuterated water can be reduced to form metal-deuterium species on nitrogen-doped carbon felt for preparing ruthenium-loaded materials during the electrolysis reaction. This species can reduce aromatic hydrocarbons to form deuterated saturated cyclic and heterocyclic compounds. The present invention has a high deuterium atom utilization rate, does not require the addition of chemical oxidants or strong chemical reducing agents for the electrolysis reaction, has mild reaction conditions, and is simple and easy to operate. It is very suitable for preparing corresponding deuterated compounds in laboratories and factories.

[0267] Example 32

[0268] The perdeuterated piperazine compound prepared in Example 31 It is applied to the synthesis of deuterated drug molecules, as shown in the following formulas 1 to 6.

[0269]

[0270] It can be seen that the perdeuterated piperidine compound obtained by this invention can be easily applied to the synthesis of deuterated drug molecules and can be converted into deuterium-labeled aripiprazole (Formula 1), brepirazole (Formula 2), buspirone (Formula 3), fepiprazole (Formula 4), trimetazidine (Formula 5), ​​and 2C-B-BZP (Formula 6). The deuterated drug molecules synthesized by this invention have a high deuteration rate and a large number of deuterium labels. This invention is of great significance for drug modification and innovation.

[0271] Finally, it should be noted that the above is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or make equivalent substitutions for some of the technical features therein. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for preparing a deuterated cyclic compound, characterized in that: include, An aromatic ring or heteroaromatic ring compound, deuterated water, a first electrolyte, and a first solvent are mixed to obtain a solution and subjected to an electrolysis reaction to obtain a cyclic compound in which hydrogen atoms on the ring are partially or completely replaced by deuterium; The cathode material used in the electrolysis reaction is nitrogen-doped carbon felt loaded with metal, and its preparation method includes: The carbon felt, melamine and ethanol are mixed and refluxed to obtain pretreated carbon felt; The pretreated carbon felt is immersed in a mixed solution of melamine and paraformaldehyde to carry out a polymerization reaction to obtain a polymer-coated carbon felt; calcining the polymer-coated carbon felt under a protective gas atmosphere to obtain nitrogen-doped carbon felt; Immersing the nitrogen-doped carbon felt in a metal salt solution for adsorption reaction to obtain nitrogen-doped carbon felt adsorbing the metal salt, wherein the metal salt is a ruthenium salt; The nitrogen-doped carbon felt adsorbed with metal salts is used as a cathode to obtain metal-loaded nitrogen-doped carbon felt by electrodeposition; The electrolysis reaction is carried out at a temperature of 20-80°C and a current density of 1-40 mA / cm 2 The condition lasts for 8-72 hours.

2. The method for preparing a deuterated cyclic compound according to claim 1, wherein The concentrations of the aromatic or heteroaromatic compound and the first electrolyte in the solution are 0.05-0.2 mol / L and 0.1-0.3 mol / L, respectively.

3. The method for preparing a deuterated cyclic compound according to claim 1, wherein The first electrolyte includes at least one of sodium fluoride, sodium chloride, sodium bromide, sodium iodide, tetrabutylammonium tetrafluoroborate, tetrabutylammonium fluoride, tetrabutylammonium chloride, tetrabutylammonium bromide, and tetrabutylammonium iodide.

4. The method for preparing a deuterated cyclic compound according to claim 1, wherein The first solvent includes at least one of deuterated methanol, deuterated ethanol, deuterated isopropanol, deuterated tert-butanol, tetrahydrofuran, and 1,4-dioxane.

5. The method for preparing a deuterated cyclic compound according to claim 1, wherein The mass ratio of the carbon felt, melamine and ethanol is 1:1-3:20; The mass ratio of the pretreated carbon felt, melamine, paraformaldehyde and the solvent in the mixed solution is 1:1-15:1-15:10-50; The mass ratio of the nitrogen-doped carbon felt, the metal salt, and the solvent in the metal salt solution is 1:0.05-0.5:40-60.

6. The method for preparing a deuterated cyclic compound according to claim 1, wherein The electrodeposition is carried out at a current density of 1-40 mA / cm 2 The electrolyte used in the cathode chamber is prepared by the second electrolyte, the second organic solvent and water, and the electrolyte used in the anode chamber is prepared by the second electrolyte and water; Wherein, the mass ratio of the second organic solvent to the water is 0-9:1; The concentration of the second electrolyte is 0.05-0.2 mol / L; The second electrolyte comprises at least one of sodium fluoride, tetrabutylammonium bromide, tetrabutylammonium chloride, and tetrabutylammonium iodide; The second organic solvent includes at least one of tetrahydrofuran, 1,4-dioxane, methanol, ethanol, isopropanol, and tert-butanol; The anode of the electrodeposition is made of an inert material.

Images