Method for preparing aryl deuterated methane compound by deoxidation and deuteration of hydrophilic carbon supported catalyst

Abstract

The invention discloses a method for preparing an aryl deuterated methane compound through deoxidation and deuteration of a hydrophilic carbon supported catalyst, and relates to the technical field of fine chemical synthesis. Comprising the following steps: by taking an aromatic aldehyde or aromatic ketone compound as a raw material, heavy water as a deuterium source, a hydrophilic carbon supported noble metal as a catalyst and a non-polar organic reagent as a solvent, carrying out deoxidation deuteration reaction in a hydrogen reaction atmosphere to prepare the aryl deuterated methane compound. Compared with a traditional deoxidation and deuteration technology, the method has the following advantages that the method belongs to heterogeneous catalysis reaction, reaction conditions are mild, reaction substrates and deuterium sources are cheap and easy to obtain, compared with a conventional activated carbon supported catalyst, the used hydrophilic carbon supported catalyst can remarkably improve the yield of a target product and the deuterium content in a methyl functional group, and the method is suitable for industrial production. And the polar surface of the carrier is beneficial to the removal of the non-polar aryl deuterated methane compound product, so that the catalytic efficiency and the product recovery can be improved.

Description

Technical Field

[0001] The invention belongs to the technical field of fine chemical synthesis, and relates to a method for preparing aromatic deuterated methane compounds by deoxygenation deuteration of a hydrophilic carbon-supported catalyst. Background Art

[0002] Deuterium-labeled chemicals are widely used in different research fields, such as new drug development, reaction mechanism exploration, nuclear magnetic resonance spectroscopy and mass spectrometry analysis (Nat. Chem. 2022, 14, 334–341). Compared with CH bonds, breaking CD bonds requires more energy. Therefore, deuterium labeling of common functional groups in drugs can regulate the metabolic rate of drugs in the body, thereby extending the half-life of drugs, reducing drug usage and reducing toxic metabolites. The U.S. Food and Drug Administration (FDA) approved the deuterated tetrabenazine drug for marketing in 2017. The introduction of deuterium-labeled methane functional groups effectively reduced the toxic side effects of non-deuterated tetrabenazine. The successful launch of the first deuterated drug has promoted the development of synthesis technology for deuterated drugs and deuterated drug intermediates.

[0003] According to statistics, about 80% of the best-selling drugs on the market contain methyl functional groups. Therefore, designing and developing intermediates containing deuterated methyl functional groups is crucial to promoting the research of deuterated drugs. Traditionally, the synthesis of deuterated methyl compounds relies on the use of deuterated alkylating agents such as CD 3 I. These deuterated alkylating agents are not only expensive, but may also produce toxic byproducts during the synthesis process. 4 、LiAlD 4 and D 2 Reducing aromatic esters, carboxylic acids or nitrile functional groups with reducing agents such as d-H-(2-nitropropene) is a viable alternative technology. However, this type of strong reducing deuterated reagents often have poor tolerance to a variety of functional groups, which limits its scope of application to a certain extent. In recent years, the method of synthesizing deuterated methane compounds by metal-catalyzed deoxydeuteration of aldehydes using the reaction characteristics of aldehyde compounds has shown potential. This technology not only simplifies the reaction steps, but also avoids the use of toxic deuterated reagents, and is therefore regarded as a promising deuteration technology. For example, Su et al. found that using D 2 Activated palladium-based molecular catalysts can selectively catalyze the deoxydeuteration reaction of aldehydes or ketones to achieve deuterium labeling of methyl sites in drug molecules (Angew. Chem. Int. Ed. 2021, 60, 6357–6361). At the same time, Min et al. developed a rhodium-based molecular catalyst that can selectively catalyze the deoxydeuteration reaction of aldehyde groups and achieve precise deuterium labeling on benzene rings (J. Am. Chem. Soc. 2022, 144, 11081-11087). Despite this, existing technologies still rely on expensive D 2Compared with homogeneous molecular catalysts, there are problems such as difficult catalyst recovery and high preparation cost, which to a certain extent restrict their industrial application. Summary of the invention

[0004] In order to solve the above technical problems, the applicant has developed a catalyst system and proposed a more economical, practical and high-deuterium content synthesis method for aromatic deuterated methane compounds. This method uses aromatic aldehydes or aromatic ketones as reaction raw materials, and uses a hydrophilic carbon-supported noble metal catalyst to catalyze the deoxydeuteration of aromatic aldehydes or ketones in a hydrogen, heavy water and non-polar organic reagent system to obtain the target deuterated product, providing a new synthesis technology for the synthesis of aromatic deuterated methane compounds.

[0005] In order to achieve the above object, the technical solution adopted by the present invention is:

[0006] A method for preparing aromatic deuterated methane compounds by deoxygenation deuteration of a hydrophilic carbon-supported catalyst, comprising: using aromatic aldehydes or aromatic ketones as raw materials, heavy water as a deuterium source, using a noble metal supported on hydrophilic carbon as a catalyst, and using a non-polar organic reagent as a solvent, and performing a deoxygenation deuteration reaction in a hydrogen reaction atmosphere to obtain aromatic deuterated methane compounds; wherein the hydrophilic carbon has a water vapor adsorption capacity of ≥10mmol·g at 298K and a relative humidity of ≤20RH%. -1 ; The precious metal is one or more of palladium, ruthenium, platinum and rhodium, and the mass percentage of the precious metal in the catalyst is 5 to 8wt.%;

[0007] The aromatic aldehyde compounds include one or more of the compounds represented by formula (1), the aromatic ketone compounds include one or more of the compounds represented by formula (2), and the aromatic deuterated methane compounds include one or more of the compounds represented by formula (3):

[0008]

[0009] Wherein, R represents one of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, nitro, hydroxyl, aldehyde, cyano and halogenated hydrocarbon; R' represents one of alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxyl and halogenated hydrocarbon.

[0010] The specific steps include:

[0011] S1: adding aromatic aldehydes or aromatic ketones, heavy water and a catalyst to a non-polar organic reagent, and ultrasonically treating the mixture until it is uniform;

[0012] After multiple replacements of the inert atmosphere, hydrogen is introduced into S2, and the temperature is raised and stirred to react; after the reaction is completed, the mixture is cooled to room temperature, and the catalyst is separated by filtration, and the filtrate is a mixed solution of a non-polar organic reagent and heavy water in which an aromatic deuterated methane compound is dissolved;

[0013] S3 adding an extractant to the mixed solution, standing the solution for stratification after the addition is complete, removing heavy water, and collecting the organic solution;

[0014] S4 removes the non-polar organic reagent and the extractant by vacuum rotary evaporation to obtain the target deuterated product.

[0015] The hydrophilic carbon is a porous carbon carrier doped with N / O heteroatoms, wherein the N atom doping content is 10-20%, the O atom doping content is 10-20%; the specific surface area is 300-1000m 2 g -1 The pore size distribution is in the range of 0.5 to 20 nm, and the water contact angle test is <35°.

[0016] The preparation method of the hydrophilic carbon comprises the following steps:

[0017] S01: copper salt and iron salt are dissolved in deionized water, and nitrogen-containing organic ligand is dissolved in organic solvent;

[0018] S02 sequentially adding the organic ligand solution and the copper salt aqueous solution to the iron salt aqueous solution, fully stirring and mixing to form a uniform solution, and obtaining a carbon precursor through standing, centrifugation and drying;

[0019] S03 pyrolyzes the precursor at a carbonization temperature of 400-600°C under an inert atmosphere, and then obtains a hydrophilic carbon material through acid washing, filtration and drying;

[0020] The mass ratio of the ligand to the copper salt in the homogeneous solution is 0.5 to 3:1; the mass ratio of the ligand to the iron salt is 0.5 to 3:1; and the volume ratio of water to the organic solvent is 5 to 20:1.

[0021] The molar amount of the noble metal in the catalyst is 2% to 5% of the molar amount of the aromatic aldehyde or aromatic ketone compound;

[0022] The molar amount of the aromatic aldehyde or aromatic ketone compound and the volume ratio of heavy water (mmol / mL) are 1:10-20.

[0023] The non-polar organic reagent is one of n-hexane, cyclohexane, toluene, xylene and dichloromethane, and the volume ratio of the non-polar organic reagent to heavy water is 1:2-5.

[0024] The number of inert gas replacements in S2 is greater than or equal to two times.

[0025] The reaction was carried out under a 0.1-0.5 MPa hydrogen atmosphere.

[0026] The reaction temperature is 90-130° C. and the reaction time is 1-12 hours.

[0027] The stirring rate in S2 is 600-1000 rpm.

[0028] The extraction reagent in S3 is 5 to 10 times the volume of heavy water. The extraction reagent is ethyl acetate.

[0029] The present invention has the same deoxygenation reaction principle for aromatic aldehyde compounds and aromatic ketone compounds. Taking aromatic aldehyde compounds as an example, the reaction principle is as follows: Figure 1 shown.

[0030] The beneficial effects of the present invention are as follows:

[0031] The present invention uses heavy water as a deuterium source, aromatic aldehydes or ketone compounds as reaction substrates, and uses a hydrophilic carbon-supported noble metal as a catalyst in a hydrogen atmosphere to generate aromatic deuterated methane compounds by catalyzing aldehydes or ketones for deoxygenation deuteration reaction. In this process, hydrogen acts as an auxiliary agent for activating metal sites to promote oxidation addition and reduction elimination reactions. Under the catalytic action of the metal active sites, hydrogen isotope exchange is first performed with heavy water to generate deuterium gas in situ, and then deoxygenation deuteration reaction is performed to generate aromatic deuterated methane compounds. The synthetic method of the aromatic deuterated methane compounds designed by the present invention is simple and efficient, the reaction operation is simple, the yield of the target product synthesized by deoxygenation deuteration is high, and the deuterium content in the methyl functional group is>95%. The hydrophilic carbon-supported catalyst is easy to prepare in large quantities, easy to separate from the deuterated product, and after five cycles of use, its deuterated performance has no significant decline, which is suitable for the needs of practical research and application. The present invention utilizes cheap heavy water as a deuterium source and synthesizes aryl deuterated methane compounds through heterogeneous catalysis, thus providing a new technical approach for the research and development or application of deuterium-labeled compounds.

[0032] Compared with the traditional technical route of using deuterated alkylating agents as deuterium sources and synthesizing through multiple steps of chemical synthesis, the present invention has the following advantages: simplified reaction steps, mild reaction conditions, no need to use toxic, highly volatile and expensive deuterated alkylating agents, and cheap and easily available reaction raw materials; the reaction product has high purity and has a high deuteration rate while ensuring a high yield. To a certain extent, it avoids the problems of catalyst deactivation, reduced product yield, and post-processing costs such as separation and purification caused by the difficulty in desorption of the product. In addition, the catalyst can be recycled after a simple reduction treatment, further reducing the catalyst cost of the deuterated reaction. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is the reaction principle diagram of aromatic aldehyde compounds.

[0034] Figure 2 This is the mass spectrum (MS) of deuterated 2-methylnaphthalene obtained in Example 1.

[0035] Figure 3 The hydrogen nuclear magnetic resonance spectrum of deuterated 2-methylnaphthalene obtained in Example 1 is ( 1 H NMR) spectrum.

[0036] Figure 4 The deuterium nuclear magnetic resonance spectrum of deuterated 2-methylnaphthalene obtained in Example 1 ( 2 H NMR) spectrum.

[0037] Figure 5 The figures show the existence state of the hydrophilic carbon-supported palladium-based catalyst in heavy water (a) and the actual picture of the deuterated 2-methylnaphthalene product obtained in Example 1 (b).

[0038] Figure 6 This is the catalytic cycle performance diagram of the catalyst in Example 1. DETAILED DESCRIPTION

[0039] The present invention is further described in detail below in conjunction with implementation examples, but the implementation examples are not intended to limit the protection scope of the present invention.

[0040] The steps for preparing the hydrophilic carbon in the embodiment are as follows: First, prepare 40 mL of 0.1 mol L -1 Cupric chloride aqueous solution, 700mL 0.005mol L -1 Ferric nitrate aqueous solution and 100 mL 0.05 mol L -1 Bipyridine ethanol solution. Subsequently, the bipyridine ethanol solution and the copper salt aqueous solution were added to the iron salt aqueous solution in turn, mixed evenly, and allowed to stand for 24 hours. After that, the carbon precursor was obtained by centrifugal separation and water washing, and dried in an oven at 50°C overnight. Then, under the protection of an argon atmosphere, it was heated to 500°C in a tube furnace and maintained for 1 hour, and naturally cooled to room temperature. Subsequently, the obtained black solid was soaked in nitric acid for 24 hours to remove the precipitated metallic copper, and then filtered, washed with water and dried to obtain a hydrophilic carbon material as a catalyst carrier. The N atom doping content in the obtained hydrophilic carbon material is 13.4%, and the O atom doping content is 16.2%; at 298K and relative humidity ≤20RH%, the water vapor adsorption amount is 10mmol·g -1 ; Specific surface area is 900m 2 ·g -1 The pore size range is between 0.5 and 1.5 nm, and the water contact angle test is in a completely wetting state.

[0041] The preparation steps of the hydrophilic carbon-supported noble metal catalyst are as follows: first, a certain concentration of noble metal aqueous solution is prepared, and the hydrophilic carbon material is used as a carrier, and the noble metal salt is loaded onto the hydrophilic carbon material by an impregnation method. The mass percentage of the noble metal (Ru / Pt / Pd) is 5-8wt.%; then, in 5% H 2 / 95% of the mixed gas atmosphere, the temperature was raised to 250°C, maintained for 2 hours, and naturally cooled to room temperature to obtain a hydrophilic carbon-supported precious metal catalyst.

[0042] Synthesis of deuterated 2-methylnaphthalene (4)

[0043]

[0044] Example 1

[0045] In 25mL Schlenk tube, add 0.2mmol (31.2mg) 2-naphthaldehyde, 1mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 10mg 5wt.% hydrophilic carbon-supported palladium catalyst, replace the residual air in the reaction system twice with argon (99.999%) after the reaction tube is evacuated under reduced pressure, finally feed 0.1MPa hydrogen (99.999%), then reaction tube is placed in 100 ℃ of preheated oil bath pots, react after 3h under 800rpm stirring speed (S.S.), reduce to room temperature, remove catalyst by filter tip, obtain heavy water, mixed solution of cyclohexane and crude product. Add ethyl acetate extraction product three times in the mixed solution, each 10mL, separate organic layer and heavy water layer, collect upper organic liquid. Subsequently, add 10mg anhydrous magnesium sulfate as desiccant to remove residual heavy water. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and organic solvent, and 24.6 mg of the target deuterated product was obtained with a yield of 78.8% and a methyl deuteration rate of 97%. The MS spectrum of deuterated 2-methylnaphthalene is shown in Figure 2 As shown, 1 HNMR spectrum Figure 3 As shown, 2 H NMR spectrum Figure 4 As shown. Figure 5 As shown in a, after the reaction stops, the catalyst is dispersed in the heavy water layer at the bottom, and the upper layer is the organic solvent layer; Figure 5 b shows a real shot of the deuterated product at the gram level. The catalyst was washed twice with ethanol and dried in a 60°C reduced pressure oven for 8 h. Then, the catalyst was heated to 40 ℃ in a mixed atmosphere (5% H 2 / 95%Ar), reduced at 250℃ for 2h and then reused. Its cycle stability is as follows Figure 6 shown.

[0046] Example 2

[0047] In 25mL Schlenk tube, add 0.2mmol (31.2mg) 2-naphthaldehyde, 1mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 10mg 5wt.% hydrophilic carbon-supported ruthenium catalyst, replace the residual air in the reaction system twice with argon (99.999%) after the reaction tube is evacuated and decompressed, finally pass into 0.1MPa hydrogen (99.999%), then the reaction tube is placed in a preheated 100 ℃ oil bath, react under 800rpm stirring speed after 3h and cool to room temperature, remove the catalyst through a filter tip, obtain a mixed solution of heavy water, cyclohexane and crude product. Add ethyl acetate extraction product three times in the mixed solution, each time 10mL, separate the organic layer and the heavy water layer, collect the upper organic liquid. Subsequently, add 10mg anhydrous magnesium sulfate as a desiccant to remove residual heavy water. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and the organic solvent, and 19.8 mg of the target deuterated product was obtained with a yield of 63.4% and a methyl deuterated rate of 81%.

[0048] Example 3

[0049] In 25mL Schlenk tube, add 0.2mmol (31.2mg) 2-naphthaldehyde, 1mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 15mg 5wt.% hydrophilic carbon-supported platinum catalyst, replace the residual air in the reaction system twice with argon (99.999%) after the reaction tube is evacuated under reduced pressure, finally pass into 0.1MPa hydrogen (99.999%), then the reaction tube is placed in 100 ℃ of preheated oil bath pots, react 3h after being cooled to room temperature at 800rpm stirring speed, remove catalyst by filter tip, obtain heavy water, mixed solution of cyclohexane and crude product. Add ethyl acetate extraction product three times in the mixed solution, each 10mL, separate organic layer and heavy water layer, collect upper organic liquid. Subsequently, add 10mg anhydrous magnesium sulfate as desiccant to remove residual heavy water. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and the organic solvent, and 21.7 mg of the target deuterated product was obtained with a yield of 69.6% and a methyl deuterated rate of 84%.

[0050] Example 4

[0051] In 25mL Schlenk tube, add 0.2mmol (31.2mg) 2-naphthaldehyde, 1mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 20mg 5wt.% hydrophilic carbon-supported palladium catalyst, replace residual air in the reaction system twice with argon (99.999%) after the reaction tube is evacuated under reduced pressure, finally feed 0.1MPa hydrogen (99.999%), then reaction tube is placed in 100 ℃ of preheated oil bath pots, react after 3h under 800rpm stirring speed (S.S.), reduce to room temperature, remove catalyst by filter tip, obtain heavy water, mixed solution of cyclohexane and crude product. Add ethyl acetate extraction product three times in the mixed solution, each 10mL, separate organic layer and heavy water layer, collect upper organic liquid. Subsequently, add 10mg anhydrous magnesium sulfate to remove residual heavy water as desiccant. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and the organic solvent, and 19.3 mg of the target deuterated product was obtained with a yield of 61.9% and a methyl deuterated rate of 98%.

[0052] Example 5

[0053] In 25mL Schlenk tube, add 0.2mmol (31.2mg) 2-naphthaldehyde, 1mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 10mg 8wt.% hydrophilic carbon-supported palladium catalyst, replace the residual air in the reaction system twice with argon (99.999%) after the reaction tube is evacuated under reduced pressure, finally feed 0.1MPa hydrogen (99.999%), then reaction tube is placed in 100 ℃ of preheated oil bath pots, react after 3h under 800rpm stirring speed (S.S.), reduce to room temperature, remove catalyst by filter tip, obtain heavy water, mixed solution of cyclohexane and crude product. Add ethyl acetate extraction product three times in the mixed solution, each 10mL, separate organic layer and heavy water layer, collect upper organic liquid. Subsequently, add 10mg anhydrous magnesium sulfate to remove residual heavy water as desiccant. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and the organic solvent, and 26.8 mg of the target deuterated product was obtained with a yield of 86.0% and a methyl deuterated rate of 95%.

[0054] Example 6

[0055] In 25mL Schlenk tube, add 0.2mmol (31.2mg) 2-naphthaldehyde, 2mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 10mg 5wt.% hydrophilic carbon-supported palladium catalyst, replace residual air in the reaction system twice with argon (99.999%) after the reaction tube is evacuated under reduced pressure, finally feed 0.1MPa hydrogen (99.999%), then reaction tube is placed in 100 ℃ of preheated oil bath pots, react after 3h under 800rpm stirring speed (S.S.), reduce to room temperature, remove catalyst by filter tip, obtain heavy water, mixed solution of cyclohexane and crude product. Add ethyl acetate extraction product three times in the mixed solution, each 10mL, separate organic layer and heavy water layer, collect upper organic liquid. Subsequently, add 10mg anhydrous magnesium sulfate to remove residual heavy water as desiccant. Finally, the organic solution was evaporated under reduced pressure at 40° C. to remove the extractant and the organic solvent, and 25.3 mg of the target deuterated product was obtained with a yield of 81.0% and a methyl deuterated rate of 97%.

[0056] Example 7

[0057] In 25mL Schlenk tube, add 0.2mmol (31.2mg) 2-naphthaldehyde, 1mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 10mg 5wt.% hydrophilic carbon-supported palladium catalyst, after the reaction tube is evacuated and decompressed, replace the residual air in the reaction system twice with argon (99.999%), finally feed 0.3MPa hydrogen (99.999%), then reaction tube is placed in 100 ℃ of preheated oil bath pots, react after 3h under 800rpm stirring speed (S.S.), reduce to room temperature, remove catalyst by filter tip, obtain heavy water, mixed solution of cyclohexane and crude product. Add ethyl acetate extraction product three times in the mixed solution, each 10mL, separate organic layer and heavy water layer, collect upper organic liquid. Subsequently, add 10mg anhydrous magnesium sulfate to remove residual heavy water as desiccant. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and the organic solvent, and 17.6 mg of the target deuterated product was obtained with a yield of 56.4% and a methyl deuterated rate of 72%.

[0058] Example 8

[0059] In 25mL Schlenk tube, add 0.2mmol (31.2mg) 2-naphthaldehyde, 1mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 10mg 5wt.% hydrophilic carbon-supported palladium catalyst, replace residual air in the reaction system twice with argon (99.999%) after the reaction tube is evacuated under reduced pressure, finally feed 0.1MPa hydrogen (99.999%), then reaction tube is placed in 120 ℃ of preheated oil bath pots, react after 3h under 800rpm stirring speed (S.S.), reduce to room temperature, remove catalyst by filter tip, obtain heavy water, mixed solution of cyclohexane and crude product. Add ethyl acetate extraction product three times in the mixed solution, each 10mL, separate organic layer and heavy water layer, collect upper organic liquid. Subsequently, add 10mg anhydrous magnesium sulfate to remove residual heavy water as desiccant. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and the organic solvent, and 24.1 mg of the target deuterated product was obtained with a yield of 77.2% and a methyl deuterated rate of 95%.

[0060] Example 9

[0061] In 25mL Schlenk tube, add 0.2mmol (31.2mg) 2-naphthaldehyde, 1mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 10mg 5wt.% hydrophilic carbon-supported palladium catalyst, replace residual air in the reaction system twice with argon (99.999%) after the reaction tube is evacuated under reduced pressure, finally feed 0.1MPa hydrogen (99.999%), then reaction tube is placed in 100 ℃ of preheated oil bath pots, react after 6h under 800rpm stirring speed (S.S.), reduce to room temperature, remove catalyst by filter tip, obtain heavy water, mixed solution of cyclohexane and crude product. Add ethyl acetate extraction product three times in the mixed solution, each 10mL, separate organic layer and heavy water layer, collect upper organic liquid. Subsequently, add 10mg anhydrous magnesium sulfate to remove residual heavy water as desiccant. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and the organic solvent, and 24.1 mg of the target deuterated product was obtained with a yield of 77.2% and a methyl deuterated rate of 95%.

[0062] Synthesis of deuterated 3-methoxytoluene (5)

[0063]

[0064] Example 10

[0065] In 25mL Schlenk tube, add 0.2mmol (27.2mg) 3-methoxybenzaldehyde, 1mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 10mg 5wt.% hydrophilic carbon-supported palladium catalyst, replace residual air in the reaction system twice with argon (99.999%) after the reaction tube is evacuated under reduced pressure, finally feed 0.1MPa hydrogen (99.999%), then reaction tube is placed in 100 ℃ of preheated oil bath pots, react after 3h under 800rpm stirring speed (S.S.), reduce to room temperature, remove catalyst by filter tip, obtain heavy water, mixed solution of cyclohexane and crude product. Add ethyl acetate extraction product three times in the mixed solution, each 10mL, separate organic layer and heavy water layer, collect upper organic liquid. Subsequently, add 10mg anhydrous magnesium sulfate to remove residual heavy water as desiccant. Finally, the organic solution was evaporated under reduced pressure at 40° C. to remove the extractant and the organic solvent, and 23.0 mg of the target deuterated product was obtained with a yield of 85.6% and a methyl deuterated rate of 95%.

[0066] Synthesis of deuterated p-chlorotoluene (6)

[0067]

[0068] Embodiment 11

[0069] In 25mL Schlenk tube, add 0.2mmol (28.1mg) p-chlorobenzaldehyde, 1mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 10mg 5wt.% hydrophilic carbon-supported palladium catalyst, replace the residual air in the reaction system twice with argon (99.999%) after the reaction tube is evacuated and decompressed, finally pass into 0.1MPa hydrogen (99.999%), then the reaction tube is placed in a preheated 100 ℃ oil bath, react under 800rpm stirring speed after 3h and cool to room temperature, remove the catalyst through a filter tip, obtain a mixed solution of heavy water, cyclohexane and crude product. Add ethyl acetate extraction product three times in the mixed solution, each time 10mL, separate the organic layer and the heavy water layer, collect the upper organic liquid. Subsequently, add 10mg anhydrous magnesium sulfate as a desiccant to remove residual heavy water. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and the organic solvent, and 17.6 mg of the target deuterated product was obtained with a yield of 63% and a methyl deuterated rate of 73%.

[0070] Synthesis of deuterated 3-methylindole (7)

[0071]

[0072] Example 12

[0073] In a 25mL Schlenk tube, 0.2mmol (29.0mg) of indole-3-carboxaldehyde, 1mL of heavy water (99.9%), 1mL of cyclohexane solution (99.9%), and 10mg of 5wt.% of a hydrophilic carbon-supported palladium catalyst were added. After the reaction tube was decompressed, the residual air in the reaction system was replaced twice with argon (99.999%). Finally, 0.1MPa of hydrogen (99.999%) was introduced. The reaction tube was then placed in a preheated 100°C oil bath. The reaction was cooled to room temperature after reacting for 3h at a stirring rate of 800rpm. The catalyst was removed by filtering to obtain a mixed solution of heavy water, cyclohexane, and a crude product. The mixed solution was divided into three times and 10mL of ethyl acetate was added to extract the product. The organic layer and the heavy water layer were separated and the upper organic liquid was collected. Subsequently, 10mg of anhydrous magnesium sulfate was added as a desiccant to remove the residual heavy water. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and the organic solvent, and 13.7 mg of the target deuterated product was obtained with a yield of 47.2% and a methyl deuterated rate of 92%.

[0074] Synthesis of deuterated 2,6-di-tert-butyltoluene (8)

[0075]

[0076] Example 13

[0077] 0.2mmol (43.7mg) 3,5-bis (tert-butyl) benzaldehyde, 1mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 20mg 5wt.% hydrophilic carbon-supported palladium catalyst were added to a 25mL Schlenk tube. After the reaction tube was evacuated and decompressed, the residual air in the reaction system was replaced twice with argon (99.999%). Finally, 0.1MPa hydrogen (99.999%) was introduced. Then the reaction tube was placed in a preheated 120°C oil bath pot. After reacting for 3h at a stirring rate of 800rpm, the temperature was lowered to room temperature. The catalyst was removed through a filter tip to obtain a mixed solution of heavy water, cyclohexane and crude product. The product was extracted with ethyl acetate three times, 10mL each time, and the organic layer and the heavy water layer were separated, and the upper organic liquid was collected. Subsequently, 10mg anhydrous magnesium sulfate was added as a desiccant to remove the residual heavy water. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and the organic solvent, and 31.0 mg of the target deuterated product was obtained with a yield of 72% and a methyl deuterated rate of 87%.

[0078] Synthesis of deuterated p-xylene (9)

[0079]

[0080] Embodiment 14

[0081] In a 25mL Schlenk tube, 0.2mmol (26.8mg) of terephthalaldehyde, 1mL of heavy water (99.9%), 1mL of cyclohexane solution (99.9%), 20mg of 5wt.% of hydrophilic carbon-supported palladium (4.7mol%) catalyst were added. After the reaction tube was decompressed, the residual air in the reaction system was replaced twice with argon (99.999%). Finally, 0.1MPa of hydrogen (99.999%) was introduced. Then the reaction tube was placed in a preheated 120°C oil bath. After reacting for 3h at a stirring rate of 800rpm, the temperature was lowered to room temperature. The catalyst was removed by filtering the catalyst to obtain a mixed solution of heavy water, cyclohexane and crude product. The mixed solution was divided into three times and 10mL of ethyl acetate was added to extract the product. The organic layer and the heavy water layer were separated and the upper organic liquid was collected. Subsequently, 10mg of anhydrous magnesium sulfate was added as a desiccant to remove the residual heavy water. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and the organic solvent, and 18.4 mg of the target deuterated product was obtained with a yield of 68% and a methyl deuterated rate of 75%.

[0082] Synthesis of deuterated p-methyldeuterated toluene (10)

[0083]

[0084] Embodiment 15

[0085] In 25mL Schlenk tube, add 0.2mmol (24.0mg) p-methylbenzaldehyde, 1mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 10mg 5wt.% hydrophilic carbon-supported palladium catalyst, replace residual air in the reaction system twice with argon (99.999%) after the reaction tube is evacuated under reduced pressure, finally feed 0.1MPa hydrogen (99.999%), then reaction tube is placed in 100 ℃ of preheated oil bath pots, react after 3h under 800rpm stirring speed (S.S.), reduce to room temperature, remove catalyst by filter tip, obtain heavy water, mixed solution of cyclohexane and crude product. Add ethyl acetate extraction product three times in the mixed solution, each 10mL, separate organic layer and heavy water layer, collect upper organic liquid. Subsequently, add 10mg anhydrous magnesium sulfate to remove residual heavy water as desiccant. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and the organic solvent, and 18.5 mg of the target deuterated product was obtained with a yield of 77% and a methyl deuterated rate of 80%.

[0086] Synthesis of deuterated diphenylmethane (11)

[0087]

[0088] Example 16

[0089] In a 25mL Schlenk tube, 0.2mmol (36.4mg) benzophenone, 1mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 10mg 5wt.% hydrophilic carbon-supported palladium catalyst were added, the reaction tube was decompressed and the residual air in the reaction system was replaced twice with argon (99.999%), and finally 0.1MPa of hydrogen (99.999%) was introduced, and then the reaction tube was placed in a preheated 100°C oil bath, and the reaction was cooled to room temperature after 2h of reaction at a stirring rate of 800rpm, and the catalyst was removed by a filter tip to obtain a mixed solution of heavy water, cyclohexane and crude product. The mixed solution was divided into three times and ethyl acetate was added to extract the product, each time 10mL, and the organic layer and the heavy water layer were separated, and the upper organic liquid was collected. Subsequently, 10mg anhydrous magnesium sulfate was added as a desiccant to remove the residual heavy water. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and the organic solvent, and 34.5 mg of the target deuterated product was obtained with a yield of 96% and a methyl deuterated rate of 90%.

[0090] Comparative Example 1

[0091] In 25mL Schlenk tube, add 0.2mmol (31.2mg) 2-naphthaldehyde, 2mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 10mg 5wt.% commercial carbon YP50 supported palladium catalyst, reaction tubes are evacuated to replace residual air in the reaction system twice with argon (99.999%) after decompression, finally feed 0.1MPa hydrogen (99.999%), then reaction tubes are placed in 100 ℃ of preheated oil baths, react after 3h under 800rpm stirring speed (S.S.), reduce to room temperature, remove catalyst by filter tip, obtain heavy water, mixture of cyclohexane and crude product. Add ethyl acetate extraction product three times in the mixed solution, each 10mL, separate organic layer and heavy water layer, collect upper organic liquid. Subsequently, add 10mg anhydrous magnesium sulfate to remove residual heavy water as desiccant. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and the organic solvent, and 24.1 mg of the target deuterated product was obtained with a yield of 83.5% and a methyl deuterated rate of 62%.

[0092] Comparative Example 2

[0093] In 25mL Schlenk tube, add 0.2mmol (31.2mg) 2-naphthaldehyde, 2mL heavy water (99.9%), 1mL cyclohexane solution (99.9%), 10mg 5wt.% hydrophilic carbon supported palladium catalyst, after the reaction tube is evacuated and decompressed, replace the residual air in the reaction system twice with argon (99.999%), finally pass into 0.1MPa argon (99.999%), then reaction tube is placed in 100 ℃ of preheated oil bath pots, react after 3h under 800rpm stirring speed (S.S.), reduce to room temperature, remove catalyst by filter tip, obtain heavy water, mixture of cyclohexane and crude product. Add ethyl acetate extraction product three times in the mixed solution, each 10mL, separate organic layer and heavy water layer, collect upper organic liquid. Subsequently, add 10mg anhydrous magnesium sulfate as desiccant to remove residual heavy water. Finally, the organic solution was evaporated under reduced pressure at 40°C to remove the extractant and organic solvent, but the target deuterated product could not be collected.

Claims

1. A method for preparing aromatic deuterated methane compounds by deoxygenation of a hydrophilic carbon-supported catalyst, characterized in that: The method comprises using aromatic aldehydes or aromatic ketones as raw materials, heavy water as a deuterium source, hydrophilic carbon loaded with noble metals as a catalyst, and a non-polar organic reagent as a solvent, and performing a deoxygenation deuteration reaction in a hydrogen reaction atmosphere to obtain aromatic deuterated methane compounds; the hydrophilic carbon has a water vapor adsorption capacity of ≥10mmol·g at 298K and a relative humidity of ≤20RH%. -1 ; The precious metal is one or more of palladium, ruthenium, platinum and rhodium, and the mass percentage of the precious metal in the catalyst is 5 to 8wt.%; The aromatic aldehyde compounds include one or more of the compounds represented by formula (1), the aromatic ketone compounds include one or more of the compounds represented by formula (2), and the aromatic deuterated methane compounds include one or more of the compounds represented by formula (3): Wherein, R represents one of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, nitro, hydroxyl, aldehyde, cyano and halogenated hydrocarbon; R' represents one of alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxyl and halogenated hydrocarbon.

2. The method for preparing aromatic deuterated methane compounds by deoxygenation of a hydrophilic carbon-supported catalyst as claimed in claim 1, characterized in that: Specifically include: S1: adding aromatic aldehydes or aromatic ketones, heavy water and a catalyst to a non-polar organic reagent, and ultrasonically treating the mixture until it is uniform; After multiple replacements of the inert atmosphere, hydrogen is introduced into S2, and the temperature is raised and stirred to react; after the reaction is completed, the mixture is cooled to room temperature, and the catalyst is separated by filtration, and the filtrate is a mixed solution of a non-polar organic reagent and heavy water in which an aromatic deuterated methane compound is dissolved; S3 adding an extractant to the mixed solution, standing the solution for stratification after the addition is complete, removing heavy water, and collecting the organic solution; S4 removes the non-polar organic reagent and the extractant by vacuum rotary evaporation to obtain the target deuterated product.

3. A method for preparing aromatic deuterated methane compounds by deoxygenation of a hydrophilic carbon-supported catalyst as claimed in claim 1 or 2, characterized in that: The hydrophilic carbon is a porous carbon carrier doped with N / O heteroatoms, wherein the N atom doping content is 10-20%, the O atom doping content is 10-20%; the specific surface area is 300-1000m 2 g -1 The pore size distribution is in the range of 0.5 to 20 nm, and the water contact angle test is <35°.

4. A method for preparing aromatic deuterated methane compounds by deoxygenation of a hydrophilic carbon-supported catalyst as claimed in claim 1 or 2, characterized in that: The preparation method of the hydrophilic carbon comprises the following steps: S01 prepares aqueous solutions of copper salt and iron salt, and an organic solution of nitrogen-containing organic ligand; S02 sequentially add the organic ligand solution and the copper salt aqueous solution to the iron salt aqueous solution, fully stir and mix to form a uniform solution, and obtain a carbon precursor after standing, centrifuging, washing with water, and drying; wherein, the mass ratio of the ligand and the copper salt in the uniform solution is 0.5 to 3:1; the mass ratio of the ligand and the iron salt is 0.5 to 3:1; and the volume ratio of water to the organic solvent is 5 to 20:

1. S03 is pyrolyzed as a precursor at a carbonization temperature of 400-600°C in an inert atmosphere, and then acid-washed, water-washed and dried to obtain a hydrophilic carbon material.

5. A method for preparing aromatic deuterated methane compounds by deoxygenation of a hydrophilic carbon-supported catalyst as claimed in claim 1 or 2, characterized in that: The molar amount of the noble metal in the catalyst is 2% to 5% of the molar amount of the aromatic aldehyde or aromatic ketone compound.

6. A method for preparing aromatic deuterated methane compounds by deoxygenation of a hydrophilic carbon-supported catalyst as claimed in claim 1 or 2, characterized in that: The molar amount ratio of the aromatic aldehyde or aromatic ketone compound to the volume amount of heavy water is 1:10-20.

7. A method for preparing aromatic deuterated methane compounds by deoxygenation of a hydrophilic carbon-supported catalyst as claimed in claim 1 or 2, characterized in that: The non-polar organic reagent is one of n-hexane, cyclohexane, toluene, xylene and dichloromethane, and the volume ratio of the non-polar organic reagent to heavy water is 1:2-5.

8. The method for preparing aromatic deuterated methane compounds by deoxygenation of a hydrophilic carbon-supported catalyst as claimed in claim 1 or 2, characterized in that: The reaction pressure is 0.1~0.5MP.

9. A method for preparing aromatic deuterated methane compounds by deoxygenation of a hydrophilic carbon-supported catalyst as claimed in claim 1 or 2, characterized in that: The reaction temperature is 90-130°C.

10. The method for preparing aromatic deuterated methane compounds by deoxygenation of a hydrophilic carbon-supported catalyst as claimed in claim 2, characterized in that: The stirring rate in S2 is 600-1000 rpm.

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