Method for selective deuteration of benzene and derivatives thereof

Abstract

The invention discloses a selective deuteration method of benzene and derivatives thereof, in a reaction system containing a catalyst, the benzene and the derivatives thereof are contacted and reacted with deuterium gas to generate deuterated compounds, and the deuterated compounds comprise benzyl methyl single deuterated products and / or benzene ring perdeuterated products; the catalyst is at least one of bulk-phase barium hydride and a supported catalyst; in the process, BaH2 loaded by a carrier with a large specific surface area is taken as a catalyst, and BaH2 is taken as a catalytic active center. The catalyst can catalyze hydrogen-deuterium exchange between deuterium gas and benzene and derivatives thereof under mild conditions, deuterium / hydrogen exchange sites can be selectively controlled at benzyl methyl sites, or a perdeuteration process of benzyl methyl and benzene ring sites is realized. The highest methyl deuteration rate can reach 95%, and the benzene ring deuteration rate can reach 92% or above.

Description

Technical Field

[0001] This application relates to a method for the selective deuteration of benzene and its derivatives, belonging to the field of organic synthesis. Background Technology

[0002] Deuterated organic compounds are compounds in which hydrogen atoms are replaced by their isotope deuterium. Compared to CH bonds, CD bonds have higher activation energies. This is because the atomic mass of D is heavier than that of H, resulting in a lower vibrational frequency and thus a lower zero-point energy for CD bonds. The significant differences in physicochemical properties between CD and CH bonds in organic compounds make deuterated organic compounds extremely important in fields such as organic reaction kinetics analysis, mechanism research, materials science, analytical testing, and life sciences. Deuterated chemicals can be used as deuteration reagents in NMR spectroscopy and as isotopic internal standards in liquid chromatography-mass spectrometry. In medicinal chemistry, deuterated drugs can effectively alter the ADME properties of existing candidate drugs and improve drug metabolism kinetics. Therefore, achieving full or site-selective deuteration of organic compounds under mild conditions is of great significance.

[0003] Direct hydrogen-deuterium exchange using organic molecules and deuterium sources is one of the more mature technologies in deuteration research. A classic method involves homogeneous catalysis with transition metals, such as rhodium, palladium, and iridium, utilizing the directing effect of guiding groups to achieve ortho-deuteration of the benzene ring. However, precious metals are expensive, the reaction products are difficult to separate from the catalyst in homogeneous systems, the deuteration process is complex, and energy consumption is high. On the other hand, using bases to mediate the deuteration of organic substrates is one of the more widely studied approaches in this field. However, traditional processes still have many insurmountable problems, such as strict reaction conditions, poor site selectivity, low deuteration efficiency, and the fact that they are usually stoichiometric processes. Therefore, the development of efficient organic substrate deuteration technologies and novel deuteration catalysts to improve the deuteration rate, moderate reaction conditions, and achieve site-selective deuteration has gradually attracted more attention. Summary of the Invention

[0004] This invention provides a novel, milder deuteration process for benzene and its derivatives based on a heterogeneous catalyst. This technique uses supported barium hydride and / or bulk barium hydride as catalysts, and under mild conditions with deuterium gas as the deuterium source, achieves highly efficient deuteration of the benzylmethyl and benzene ring sites in benzene and its derivatives. This method does not require transition metals, operates under mild conditions at room temperature, and the catalyst is easily separable, simplifying the complex separation and purification process of homogeneous systems. Simultaneously, it exhibits high catalytic efficiency, enabling selective deuteration of benzylmethyl and full deuteration of both the benzene ring and benzylmethyl groups.

[0005] One aspect of this application provides a method for the selective deuteration of benzene and its derivatives. This method is a novel process for the efficient deuteration of benzene and its derivatives under mild conditions using barium hydride catalyst to selectively deuterate benzene and its derivatives at different sites.

[0006] The method includes:

[0007] In a reaction system containing a catalyst, benzene and its derivatives come into contact with deuterium gas and react to generate deuterated compounds, including benzylmethyl monodeuterated products and / or benzene ring fully deuterated products;

[0008] Wherein, benzene and its derivatives are selected from at least one of toluene and its derivatives, and benzene and its derivative I;

[0009] The toluene and its derivatives have the structure shown in Formula 1;

[0010] The benzene and its derivative I have the structure shown in Formula 2;

[0011] The benzylmethyl monodeuterated product has the structure shown in Formula 3;

[0012] The fully deuterated benzene ring product has at least one of the structures shown in Formula 4 and Formula 5.

[0013] When benzene and its derivatives are toluene and its derivatives, the fully deuterated benzene ring products have the structure shown in Formula 4.

[0014] When benzene and its derivatives are benzene and its derivative I, the fully deuterated benzene ring products have at least one of the structures shown in Formula 4 and Formula 5;

[0015] The catalyst is at least one of bulk barium hydride and supported catalyst;

[0016] The supported catalyst includes an active component and a support, wherein the active component is barium hydride.

[0017]

[0018]

[0019] Wherein, R1 is selected from at least one of hydrogen substituents, alkyl substituents having 1 to 10 carbon atoms, and methoxy groups;

[0020] R2 is selected from at least one of hydrogen substituents, alkyl substituents having 1 to 10 carbon atoms, methoxy groups, amino groups, N,N-dimethyl groups, and phenyl groups.

[0021] Optionally, the catalyst is BaH2 or BaH2 supported on a support.

[0022] Optionally, the support is selected from at least one of MgO, SiO2, BN, carbon materials, and metal-organic frameworks (MOFs).

[0023] Optionally, the mass ratio of barium hydride to the support is 1:0 to 1:2000.

[0024] Optionally, the toluene and its derivatives are selected from at least one of toluene, o-xylene, m-xylene, p-xylene, disubstituted benzene with 2 to 10 carbon atoms, trisubstituted benzene with 1 to 10 carbon atoms, tetrasubstituted benzene with 1 to 10 carbon atoms, pentasubstituted benzene with 1 to 10 carbon atoms, hexasubstituted benzene with 1 to 10 carbon atoms, methoxy-substituted toluene, amino-substituted toluene, N,N-dimethyl-substituted toluene, halogen-substituted toluene, naphthalene, 2-methylnaphthalene, biphenyl, 2-methylbiphenyl, 3-methylbiphenyl, and 4-methylbiphenyl.

[0025] The benzene and its derivative I are selected from at least one of benzene and alkylbenzenes with substituents having 2 to 10 carbon atoms;

[0026] The halogen atom is selected from at least one of F, Cl, Br, and I.

[0027] Optionally, the molar ratio of the catalyst to the benzene and its derivatives is 10:1 to 1:2000, wherein the molar amount of the catalyst is expressed as the molar amount of barium hydride.

[0028] Optionally, the molar ratio of the catalyst to the benzene and its derivatives is independently selected from any value of 10:1, 1:1, 1:10, 1:100, 1:500, 1:1000, 1:1500, 1:2000 or a range between any two of the above.

[0029] Optionally, the reaction temperature is 0℃ to 250℃;

[0030] The reaction time ranges from 5 minutes to 48 hours.

[0031] Optionally, the temperature of the reaction is independently selected from any value of 0°C, 25°C, 50°C, 60°C, 80°C, 100°C, 120°C, 150°C, 200°C, 250°C, or a range between any two of the above.

[0032] Optionally, the reaction time is independently selected from any value of 5 minutes, 1 hour, 6 hours, 12 hours, 18 hours, 24 hours, 36 hours, 48 ​​hours, or a range between any two of the above.

[0033] Optionally, when the molar ratio of the bulk barium hydride to the benzene and its derivatives is 10:1 to 1:10, the reaction temperature is 0℃ to 120℃, and the reaction time is 6 hours to 48 hours, the deuterated compound is a single deuterated product of benzylmethyl having the structure shown in Formula 3.

[0034] Optionally, when the molar ratio of barium hydride to benzene and its derivatives in the supported catalyst is 1:1 to 1:1000, the reaction temperature is 0℃ to 60℃, and the reaction time is ≤12 hours, the deuterated compound is a single deuterated product of benzylmethyl having the structure shown in Formula 3.

[0035] Optionally, when the molar ratio of barium hydride to benzene and its derivatives in the supported catalyst is 1:1 to 1:100, the reaction temperature is 25℃ to 250℃, and the reaction time is ≥6 hours, the deuterated compound is a fully deuterated benzene ring product having at least one of the structures shown in Formula 4 and Formula 5.

[0036] Optionally, the pressure of the deuterium gas is 0.1 to 200 bar.

[0037] Optionally, the reaction system further includes an organic solvent;

[0038] The organic solvent is selected from one of n-pentane, n-hexane, cyclohexane, tetrahydrofuran, benzene, 2-methyltetrahydrofuran, and 1,4-dioxane.

[0039] Optionally, the method for preparing the supported catalyst includes:

[0040] Method 1: BaH2 and carrier are ball-milled and mixed;

[0041] or,

[0042] Method 2: Barium metal and a support are impregnated in liquid ammonia and reduced under a hydrogen atmosphere.

[0043] As a specific implementation method, the catalyst is a barium hydride catalyst supported on a multiphase high specific surface area support. The catalyst preparation process includes two routes: one is preparation by ball milling barium hydride material with a high specific surface area support at 150 rpm for 3 hours; the other synthesis route starts with metallic barium, impregnating barium with a high specific surface area support in liquid ammonia solution, then removing excess ammonia, and reducing the resulting solid under hydrogen pressure to obtain the target catalyst. As a specific implementation method, the method for efficiently preparing deuterated organic chemicals from benzene and its derivatives under mild conditions includes:

[0044] The catalyst and reaction substrate are placed in a stainless steel reactor, with or without the addition of organic solvent. The reaction system is then filled with deuterium gas at a certain pressure, and magnetic stirring is used to promote the contact between the substrate, deuterium gas, and catalyst.

[0045] Using a supported barium hydride catalyst, toluene and its derivatives can react with deuterium gas in the presence of the catalyst to generate benzylmethyl monodeuterated products and benzylmethyl fully deuterated products with a benzene ring at a relatively rapid rate. The deuteration sites and deuteration rates of the deuterated products were analyzed using liquid nuclear magnetic resonance (LMR).

[0046] The method of this application involves toluene and its derivatives undergoing a hydrogen-deuterium exchange reaction with deuterium gas in the presence of supported barium hydride in an organic solvent or solvent-free system under mild conditions. This reaction selectively replaces hydrogen at different sites on toluene and its derivatives with deuterium, generating deuterated compounds.

[0047] In the method of this application, after deuteration of toluene and its derivatives, the deuteration site can be selectively regulated. By controlling the reaction conditions, single deuteration of the benzylmethyl site of the benzene ring can be achieved, as well as full deuteration of both the benzene ring and the benzylmethyl site.

[0048] The beneficial effects that this application can produce include:

[0049] 1) The preparation method of this catalyst is simple, does not require the participation of transition metals, is a heterogeneous catalytic process, and the catalyst is easy to separate and can be removed by means of filtration. Compared with the separation and purification methods of homogeneous systems, the process is simple and easy to operate.

[0050] 2) It can prepare deuterated organic chemicals under mild conditions. Using deuterium gas as the deuterium source, the activation of deuterium gas and the hydrogen-deuterium exchange on organic compounds can be achieved at room temperature. The deuteration rate is fast, the deuteration yield is high, the conditions are mild, and energy consumption is saved.

[0051] 3) In this process, BaH2 supported on a large specific surface area carrier is used as the catalyst, with BaH2 as the catalytic active center. This catalyst can catalyze the hydrogen-deuterium exchange between deuterium and toluene and its derivatives under mild conditions. The deuterium / hydrogen exchange site can be selectively controlled at the benzylmethyl site, or a full deuteration process can be achieved at both the benzylmethyl and benzene ring sites. The methyl deuteration rate can reach up to 95%, and the benzene ring deuteration rate can reach over 90%.

[0052] 4) This method can achieve deuteration selectivity at different sites in toluene and its derivatives. By adjusting the reaction conditions, specific site-specific deuteration of the benzylmethyl site can be achieved, or full deuteration of the benzene ring and the benzylmethyl site can be achieved. Furthermore, it has broad substrate applicability, allowing the production of various organic deuterated chemicals according to actual needs, creating extremely high catalyst value. Attached Figure Description

[0053] Figure 1 XRD characterization of the supported barium hydride obtained in Example 1 of this application;

[0054] Figure 2This is the 1H NMR spectrum of the fully deuterated toluene product of Example 2 of this application;

[0055] Figure 3 This is the 1H NMR spectrum of the fully deuterated benzene product of Example 3 of this application. Detailed Implementation

[0056] The present application is described in detail below with reference to the embodiments, but the present application is not limited to these embodiments.

[0057] Unless otherwise specified, all raw materials used in the embodiments of this application were purchased through commercial channels.

[0058] In the embodiments of this application, the yield of the deuterated product after reaction is confirmed by gas chromatography and gas chromatography-mass spectrometry, and the deuteration sites and deuteration rates of the deuterated product are analyzed by liquid nuclear magnetic resonance (NMR).

[0059] Preparation Example 1

[0060] Preparation of magnesium oxide-supported barium hydride catalyst by impregnation method: In a glove box, barium metal and magnesium oxide were placed in a specially made stainless steel impregnation tube at a mass ratio of 1:4. First, the stainless steel impregnation tube was cooled to approximately 0°C using liquid nitrogen. Ammonia gas was then introduced until a liquid ammonia surface was formed. The reaction tube was placed on a shaker and shaken for 5 hours until the liquid ammonia turned colorless. Excess ammonia was then removed, yielding a white powder, which was the magnesium oxide-supported barium hydride sample. This sample was then reduced under hydrogen pressure for 6 hours using a fixed-bed apparatus to obtain the magnesium oxide-supported barium hydride sample. XRD characterization of the supported barium hydride was as follows: Figure 1 As shown, by Figure 1 It can be seen that the XRD diffraction peaks of BaH2 are extremely weak, indicating that BaH2 may be in a highly dispersed state.

[0061] Preparation Example 2

[0062] Preparation of magnesium oxide-supported barium hydride catalyst by ball milling: Barium hydride and magnesium oxide were mixed at a mass ratio of 1:4 in a specially designed stainless steel ball mill jar within a glove box. The milling speed was set to 150 rpm, and the milling time was 3 hours. After milling, the sample was scraped off to obtain the magnesium oxide-supported barium hydride sample.

[0063] Example 1

[0064] In an argon-filled glove box, 2.8 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 42 μL of toluene (Comio, >99%) (BaH2 to toluene molar ratio 1:100) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the quartz liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 2 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain Sample 1. 500 μL of the liquid phase product and 300 μL of deuterated chloroform were collected in an NMR tube for proton NMR analysis. The relaxation delay time of the proton NMR spectrum was set to 32 seconds, and 64 scans were performed. Data were collected to analyze the deuteration sites and deuteration rate. The selective deuteration rate of benzylmethyl was calculated based on the undeuterated sites. The total deuteration rate of benzylmethyl and the benzene ring was calculated using 1,3,5-trimethoxybenzene as an internal standard. The deuteration rate of the reaction was obtained by calculating the ratio of the decrease in the actual measured integrated intensity to the integrated intensity of the standard substance. The calculation formula is as follows. The test results are as follows.

[0065]

[0066] The NMR data for sample 1 are as follows:

[0067]

[0068] Toluene-d3: 1 ¹H NMR (400MHz, Chloroform-d) δ 2.18–2.68 (m, 0.09H, 97% deuteration), 6.67–7.16 (m, 3H), 7.16–7.65 (m, 2H).

[0069] 13 C NMR(101MHz,Chloroform-d)δ20.53-20.93(m),125.13-126.03,127.70-128.86,128.86-129.91,137.42-138.19.

[0070] Example 2

[0071] In an argon-filled glove box, 27.8 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 42 μL of toluene (Comio, >99%) (BaH2 to toluene molar ratio 1:10) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the quartz liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 12 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain Sample 2. 500 μL of the liquid phase product and 300 μL of deuterated chloroform were placed in an NMR tube for proton NMR spectroscopy analysis. The relaxation delay time of the proton NMR spectrum was set to 32 seconds, and 64 scans were performed. Data were collected and analyzed to determine the deuteration sites and deuteration rate. The test results are as follows: Figure 2 As shown.

[0072] like Figure 2 As shown, deuteration occurs on both the benzylmethyl group and the benzene ring of toluene. The deuteration yield of benzylmethyl group can reach 95%, the deuteration yield of meta-toluene can reach 92%, and the deuteration yield of ortho-para-toluene can reach 80%.

[0073] Example 3

[0074] In an argon-filled glove box, 27.8 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 35 μL of benzene (Aladdin, >99%) (BaH2 to benzene molar ratio 1:10) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the quartz liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas. The argon gas in the reactor was replaced three times with deuterium-containing gas, and then the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 15 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 3. 500 μL of the liquid phase product and 300 μL of deuterated chloroform were placed in an NMR tube for proton NMR spectroscopy analysis. The relaxation delay time of the proton NMR spectrum was set to 32 seconds, and 64 scans were performed. Data were collected and analyzed to determine the deuteration sites and deuteration rate. The test results are as follows: Figure 3 As shown.

[0075] like Figure 3 As shown, after 15 hours of reaction, the H on the benzene ring was significantly replaced by D, and the calculated deuteration rate was 96%.

[0076] Comparative Example 1

[0077] For Comparative Example 1, unsupported BaH2 MgO was used as the catalyst. In an argon glove box, 27.8 mg of MgO and 42 μL of toluene (Commeo, >99%) were accurately weighed (MgO to toluene molar ratio 1:0.6), placed in a quartz liner, and a PTFE magnetic stir bar was added. The liner was then placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed under a heating device, and magnetically stirred at 500 rpm. The pipeline was evacuated and filled with deuterium, replacing the argon gas in the reactor three times. The deuterium was then pressurized to 6 bar. After reacting at 25°C for 15 hours, the deuterium was depressurized, and the resulting suspension of catalyst and substrate was filtered using a syringe and a PTFE filter membrane. The catalyst was removed, and the liquid product was collected. 500 μL of the liquid phase product and 300 μL of deuterated chloroform were collected in an NMR tube for proton NMR spectroscopy analysis. The relaxation delay time of the proton NMR spectrum was set to 32 seconds, and 64 scans were performed. Data were collected and analyzed to determine the deuteration sites and deuteration rate. In the comparative example, no deuterated products were detected.

[0078] Example 4

[0079] In an argon-filled glove box, 5.6 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 49 μL of p-xylene (BaH2 to p-xylene molar ratio of 1:50) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the quartz liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 6 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 4. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0080] The NMR data for sample 4 are as follows:

[0081]

[0082] p-Xylene-d6: 1 ¹H NMR (400MHz, Chloroform-d) δ 2.1–2.7 (s, 0.24H, 96% deuteration), 6.9–7.2 (s, 4H).

[0083] 13C NMR(101MHz,Chloroform-d)δ19.6-22.7(m),27.1-27.4,76.4-77.3.

[0084] Example 5

[0085] In an argon-filled glove box, 5.6 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 49 μL of m-xylene (Annex, 99%) (BaH2 to m-xylene molar ratio of 1:50) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 6 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 4. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0086] The NMR data for sample 5 are as follows:

[0087]

[0088] m-xylene-d6: 1 ¹H NMR (400MHz, Chloroform-d) δ 2.1–2.5 (s, 0.26H, 96% deuteration), 6.7–7.0 (m, 3H), 7.0–7.6 (t, J = 7.5Hz, 1H).

[0089] 13 C NMR(101MHz,Chloroform-d)δ124.0-127.2,127.2-128.8,128.8-133.0,135.0-142.4.

[0090] Example 6

[0091] In an argon-filled glove box, 5.6 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 55 μL of mesitylene (Aladdin, >98%) (BaH2 to mesitylene molar ratio of 1:50) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 6 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 6. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0092] The NMR data for sample 6 are as follows:

[0093]

[0094] Trimethylbenzene-d9: 1 ¹H NMR (400MHz, Chloroform-d) δ 2.1–2.7 (m, 0.21H, 98% deuteration), 6.4–7.0 (s, 3H).

[0095] 13 C NMR (101MHz, Chloroform-d) δ12.2-23.2 (d, J=19.3Hz), 120.0-131.3, 131.5-143.3.

[0096] Example 7

[0097] In an argon-filled glove box, 5.6 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 49 μL of ethylbenzene (Aladdin, AR) (BaH2 to ethylbenzene molar ratio of 1:50) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 6 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 7. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0098] The NMR data for sample 7 are as follows:

[0099]

[0100] Ethylbenzene-d2: 1 ¹H NMR (400MHz, Chloroform-d) δ 2.5–3.1 (dt, J = 2.1, 7.7 Hz, 0.02H, 99% deuteration), 6.7–7.2 (m, 3H), 7.2–7.7 (t, J = 7.5 Hz, 2H).

[0101] 13 C NMR(101MHz,Chloroform-d)δ13.8-17.1,28.0-30.0,124.2-127.3,127.7-128.3,128.3-129.4,138.9-150.3.

[0102] Example 8

[0103] In an argon-filled glove box, 5.6 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 62 μL of sec-butylbenzene (Maclean, >99%) (BaH2 to sec-butylbenzene molar ratio of 1:50) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 6 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 8. Take 500 μL of the liquid phase product and 200 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0104] The NMR data for sample 8 are as follows:

[0105]

[0106] sec-butylbenzene-d1: 1 ¹H NMR (400MHz, Chloroform-d) δ 0.6–0.8 (t, J = 7.4 Hz, 3H), 1.1–1.4 (m, 2H), 1.5–1.6 (d, J = 6.7 Hz, 2H), 2.4–2.8 (h, J = 7.2 Hz, 0.07H, 93% deuteration), 6.7–7.2 (dq, J = 4.0, 6.9 Hz, 3H), 7.1–7.7 (m, 1.57H, 22% deuteration).

[0107] 13 C NMR(101MHz,Chloroform-d)δ9.2-14.5,19.2-23.1,29.7-34.6,38.4-53.9(m),124.1-126.3(d,J=11.4Hz),126.0-127.5(m),127.5-

[0108] 140.4(d,J=11.3Hz),142.4-154.6.

[0109] Example 9

[0110] In an argon-filled glove box, 5.6 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 56 μL of p-ethyltoluene (Mairyl, 98%) (BaH2 to p-ethyltoluene molar ratio of 1:50) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 6 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 9. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0111] The NMR data for sample 9 are as follows:

[0112]

[0113] p-Ethyltoluene-d5: 1 ¹H NMR (400MHz, Chloroform-d) δ 1.1–1.2 (m, 3H), 2.2–2.4 (pent, J = 2.2 Hz, 0.1H, 97% deuteration), 2.4–2.9 (dddd, J = 2.2, 4.9, 7.5, 9.8 Hz, 0.06H, 97% deuteration), 6.9–7.1 (s, 4H).

[0114] 13 C NMR(101MHz,Chloroform-d)δ14.6-17.9,18.7-21.6(m),124.5-128.4,128.4-130.9,132.5-137.8,138.8-148.8.

[0115] Example 10

[0116] In an argon-filled glove box, 5.6 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 67.5 μL of cyclohexylbenzene (Maclean, 98%) (BaH2 to cyclohexylbenzene molar ratio of 1:50) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 6 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 10. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0117] The NMR data for sample 10 are as follows:

[0118]

[0119] Cyclohexylbenzene-d1: 1 ¹H NMR (400MHz, Chloroform-d) 1.8–2.0 (m, 2H), 2.3–2.9 (m, 0.14H, 86% deuteration), 6.8–7.2 (m, 3H), 7.2–7.7 (m, 1.72H, 14% deuteration).

[0120] 13 C NMR (101MHz, Chloroform-d) δ23.9-26.7,32.5-45.6,124.8-126.6,126.6-127.7,128.0-134.1,142.4-153.1.

[0121] Example 11

[0122] In an argon-filled glove box, 11.2 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 67 μL of diphenylmethane (BaH2 to diphenylmethane molar ratio of 1:25) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 12 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 11. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0123] The NMR data for sample 11 are as follows:

[0124]

[0125] Diphenylmethane-d2: 1 ¹H NMR (400MHz, Chloroform-d) δ 3.8–4.5 (m, 0.02H, 99% deuteration), 6.7–7.2 (m, 6H), 7.2–7.7 (m, 4H).

[0126] 13 C NMR(101MHz,Chloroform-d)δ41.1-41.7(m),123.9-127.5,128.0-128.8,128.8-133.9,137.1-146.2.

[0127] Example 12

[0128] In an argon-filled glove box, 11.2 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 66 μL of 4-methylbiphenyl (Maclean, 98%) (BaH2 to 4-methylbiphenyl molar ratio of 1:25) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 6 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 12. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0129] The NMR data for sample 12 are as follows:

[0130]

[0131] 4-Methylbiphenyl-d3: 1 ¹H NMR (400MHz, Chloroform-d) δ 2.3–2.6 (s, 0.1H, 97% deuteration), 7.2–7.2 (d, J = 8.1 Hz, 2H), 7.2–7.3 (m, 1H), 7.3–7.4 (t, J = 7.7 Hz, 2H), 7.4–7.5 (d, J = 8.2 Hz, 2H), 7.5–8.0 (m, 2H).

[0132] 13 C NMR(101MHz,Chloroform-d)δ19.50-21.50,126.78-127.20,127.20-127.72(d,J=3.017 Hz),128.53-129.15,129.37-130.19,136.17-137.82,138.55-139.53,141.28-142.44.

[0133] Example 13

[0134] In an argon-filled glove box, 27.8 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 56 mg of 2-methylnaphthalene (Bohr, 97%) (BaH2 to 2-methylnaphthalene molar ratio of 1:10) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 12 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 13. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0135] The NMR data for sample 13 are as follows:

[0136]

[0137] 2-Methylnaphthalene-d3: 1 ¹H NMR (400MHz, Chloroform-d) δ 2.3–2.6 (d, J = 3.7 Hz, 0.13H, 96% deuteration), 7.2–7.3 (dd, J = 1.8, 8.3 Hz, 1H), 7.3–7.5 (pd, J = 1.4, 6.9 Hz, 2H), 7.5–7.6 (d, J = 1.7 Hz, 1H), 7.6–8.1 (m, 3H).

[0138] 13 C NMR(101MHz,Chloroform-d)δ21.2-22.9(d,J=37.3Hz),124.3-125.5,125.5-126.4,126.4-127.2, 127.3-127.5,127.6-127.8,127.8-128.1,128.1-130.2,131.2-132.6,133.5-134.8,135.2-137.3.

[0139] Example 14

[0140] In an argon-filled glove box, 11.2 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 50 μL of 2-methylanisole (Meryl, 99%) (BaH2 to 2-methylanisole molar ratio of 1:25) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 6 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 14. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0141] The NMR data for sample 14 are as follows:

[0142]

[0143] 2-methylanisole-d3: 1 ¹H NMR (400MHz, Chloroform-d) δ 2.0–2.3 (s, 0.13H, 96% deuteration), 3.7–4.2 (s, 3H), 6.4–6.9 (m, 1.31H, 69% labeled), 6.9–7.4 (m, 2H).

[0144] 13 C NMR (101MHz, Chloroform-d) δ13.1-20.6, 98.3-116.0, 116.4-123.6, 124.7-128.7 (d, J = 10.8Hz), 128.7-135.3, 155.9-161.0.

[0145] Example 15

[0146] In an argon-filled glove box, 11.2 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 50.4 μL of p-methyl anisole (Maclean, 99%) (BaH2 to p-methyl anisole molar ratio of 1:25) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 6 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 15. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0147] The NMR data for sample 15 are as follows:

[0148]

[0149] p-Methyl anisole-d3: 1 H NMR (400MHz, Chloroform-d) δ2.2-2.7 (dd, J=2.2, 4.3Hz, 0.46H, 85% deuteration rate), 3.5-4.0 (d, J=7.6Hz, 3H), 6.4-6.9 (d, J=8.9Hz, 0.11H, 95% labeled), 6.9-7.3 (s, 2H).

[0150] 13 C NMR(101MHz,Chloroform-d)δ17.8-20.6,47.2-61.5,109.9-

[0151] 115.6(m),126.9-132.4,156.0-160.1.

[0152] Example 16

[0153] In an argon-filled glove box, 11.2 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 52 μL of m-methyl anisole (Anage, 97%) (BaH2 to m-methyl anisole molar ratio of 1:25) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 6 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 16. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0154] The NMR data for sample 16 are as follows:

[0155]

[0156] 1 H NMR (400MHz, Chloroform-d) δ2.1-2.6 (d, J=9.9Hz, 0.92H, 69% deuteration rate), 3.6-3.7 (d, J=2.0Hz, 3H), 6.4-6.9 (m, 1.86H, 38% labeled), 6.9-7.3 (dd, J=3.3, 7.8Hz, 1H).

[0157] 13 C NMR(101MHz,Chloroform-d)δ19.1-23.2(m),54.4-54.8,110.0-114.1,113.3- 117.5,119.3-123.9,124.5-132.0(d,J=10.9Hz),134.6-141.0,157.8-161.1.

[0158] Example 17

[0159] In an argon glove box, 11.2 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 49.5 μL of benzyl methyl ether (BaH2 to benzyl methyl ether molar ratio of 1:25) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced with deuterium gas three times. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 6 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 17. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0160] The NMR data for sample 17 are as follows:

[0161]

[0162] Benzyl methyl ether-d2: 1 H NMR (400MHz, Chloroform-d) δ3.0-3.5 (s, 3H), 4.2-4.7 (d, J = 9.1Hz, 0.49H, 76% labeled), 6.8-7.7 (m, 5H).

[0163] 13 C NMR (101MHz, Chloroform-d) δ 56.2-59.3, 70.1-75.4 (dd, J = 18.7, 40.3Hz), 126.3-127.5, 127.5-127.8, 127.8-129.4, 132.0-146.4. Example 18

[0164] In an argon-filled glove box, 27.4 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 60 μL of N,N-dimethyl-p-toluidine (Aladdin, >98%) were accurately weighed (BaH2 to N,N-dimethyl-p-toluidine molar ratio of 1:10), placed in a quartz liner, a polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 12 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 18. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0165] The NMR data for sample 18 are as follows:

[0166]

[0167] N,N-Dimethyl-p-toluidine-d3: 1 H NMR(400MHz,Chloroform-d)δ2.16-

[0168] 2.51 (dd, J = 2.052, 4.119 Hz, 0.28 H, 91% deuteration), 6.39-6.89 (d, J = 8.700 Hz, 1.43 H, 29% deuteration), 6.89-7.19 (m, 2 H).

[0169] 13 C NMR (101MHz,) δ13.38-24.53, 37.31-45.29, 107.40-118.04, 122.76-127.93, 128.16-134.58 (d, J = 10.894Hz), 144.70-153.79 (d, J = 5.461Hz).

[0170] Example 19

[0171] In an argon-filled glove box, 27.4 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 60 μL of N,N-dimethyl-m-toluidine (Gilead, 98%) were accurately weighed (BaH2 to N,N-dimethyl-m-toluidine molar ratio of 1:10), placed in a quartz liner, a polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 12 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 19. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0172] The NMR data for sample 19 are as follows:

[0173]

[0174] N,N-Dimethyl-m-Toluidine-d3: 1 ¹H NMR (400MHz, Chloroform-d) δ 2.13–2.50 (d, J = 16.180 Hz, 0.1H, 97% deuteration), 2.67–3.28 (s, 6H), 6.25–6.76 (m, 3H), 6.86–7.30 (td, J = 1.746, 7.244 Hz, 1H).

[0175] 13 C NMR(101MHz,Chloroform-d)δ17.95-23.46(m),36.78-45.79,105.48-112.27,11 2.27-117.15,117.67-124.31,126.01-134.43,136.50-144.70,147.14-154.82.

[0176] Example 20

[0177] In an argon-filled glove box, 27.4 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 60 μL of N,N-dimethyl-o-toluidine (Gilead, 99%) were accurately weighed (BaH2 to N,N-dimethyl-o-toluidine molar ratio of 1:10), placed in a quartz liner, a polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 12 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 20. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0178] The NMR data for sample 20 are as follows:

[0179]

[0180] N,N-Dimethyl-o-toluidine-d3: 1 H NMR(400MHz,Chloroform-d)δ2.17-

[0181] 2.39 (s, 0.08H, 97% deuteration rate), 2.48-2.99 (s, 6H), 6.80-6.92 (td, J = 1.177, 7.452Hz, 1H), 6.93-7.02 (d, J = 7.659Hz, 1H), 7.02-7.51 (t, J = 7.411Hz, 2H).

[0182] 13 C NMR (101MHz, Chloroform-d) δ16.5-25.9(m),36.7-58.7,116.6-121.8,119.6-125.3,125.2-128.3,130.2-131.8,131.9-142.1,148.5-158.3.

[0183] Example 21

[0184] In an argon-filled glove box, 55.6 mg of the supported barium hydride catalyst obtained in Preparation Example 1 and 44 μL of p-fluorotoluene (Aladdin, 98%) (BaH2 to p-fluorotoluene molar ratio of 1:5) were accurately weighed and placed in a quartz liner. A polytetrafluoroethylene (PTFE) magnetic stir bar was added, and the liner was placed in a stainless steel high-pressure reactor. After sealing the reactor, it was removed from the glove box, placed in a heating device, and magnetically stirred at a stirring rate of 500 rpm. The pipeline was evacuated and filled with deuterium gas, and the argon gas in the reactor was replaced three times with deuterium gas. Then, the deuterium gas was pressurized to 6 bar. After reacting at 25°C for 6 hours, the deuterium gas was depressurized, and the suspension of catalyst and substrate after the reaction was filtered using a syringe and a PTFE filter membrane. The catalyst was filtered off, and the liquid product was collected to obtain sample 21. Take 500 μL of the liquid phase product and 300 μL of deuterated chloroform into an NMR tube for 1H NMR spectroscopy analysis. Set the relaxation delay time of the 1H NMR spectrum to 32 seconds and scan 64 times. Collect data to analyze the deuteration sites and deuteration rate.

[0185] The NMR data for sample 21 are as follows:

[0186]

[0187] p-Fluorotoluene-d3: 1 ¹H NMR (400MHz, Chloroform-d) δ 2.04–2.59 (d, J = 7.941 Hz, 1.61H, 46% deuteration), 6.55–6.98 (t, J = 8.874 Hz, 0.17H, 92% deuteration), 6.98–7.48 (d, J = 5.193 Hz, 2H).

[0188] The above description is merely a few embodiments of this application and is not intended to limit this application in any way. Although this application discloses preferred embodiments as described above, it is not intended to limit this application. Any changes or modifications made by those skilled in the art without departing from the scope of the technical solution of this application using the disclosed technical content are equivalent to equivalent implementation cases and fall within the scope of the technical solution.

Claims

1. A method for selective deuteration of benzene and its derivatives, characterized in that, In a reaction system containing a catalyst, benzene and its derivatives come into contact with deuterium gas and react to generate deuterated compounds, including benzylmethyl monodeuterated products and / or benzene ring fully deuterated products; Wherein, benzene and its derivatives are selected from at least one of toluene and its derivatives, and benzene and its derivative I; The toluene and its derivatives have the structure shown in Formula 1; The benzene and its derivative I have the structure shown in Formula 2; The benzylmethyl monodeuterated product has the structure shown in Formula 3; The fully deuterated benzene ring product has at least one of the structures shown in Formula 4 and Formula 5. When benzene and its derivatives are toluene and its derivatives, the fully deuterated benzene ring products have the structure shown in Formula 4. When benzene and its derivatives are benzene and its derivative I, the fully deuterated benzene ring products have at least one of the structures shown in Formula 4 and Formula 5; The catalyst is at least one of bulk barium hydride and supported catalyst; The supported catalyst includes an active component and a support, wherein the active component is barium hydride. Wherein, R1 is selected from at least one of hydrogen substituents, alkyl substituents having 1 to 10 carbon atoms, and methoxy groups; R2 is selected from at least one of hydrogen substituents, alkyl substituents having 1 to 10 carbon atoms, methoxy groups, amino groups, N,N-dimethyl groups, and phenyl groups.

2. The method according to claim 1, characterized in that, The carrier is selected from at least one of MgO, SiO2, BN, carbon materials, and metal-organic framework materials; Preferably, the mass ratio of barium hydride to the carrier is 1:0 to 1:2000.

3. The method according to claim 1, characterized in that, The toluene and its derivatives are selected from at least one of toluene, o-xylene, m-xylene, p-xylene, disubstituted benzene with 2 to 10 carbon atoms, trisubstituted benzene with 1 to 10 carbon atoms, tetrasubstituted benzene with 1 to 10 carbon atoms, pentasubstituted benzene with 1 to 10 carbon atoms, hexasubstituted benzene with 1 to 10 carbon atoms, methoxy-substituted toluene, amino-substituted toluene, N,N-dimethyl-substituted toluene, halogen-substituted toluene, naphthalene, 2-methylnaphthalene, biphenyl, 2-methylbiphenyl, 3-methylbiphenyl, and 4-methylbiphenyl. The benzene and its derivative I are selected from at least one of benzene and alkylbenzenes with substituents having 2 to 10 carbon atoms; The halogen atom is selected from at least one of F, Cl, Br, and I.

4. The method according to claim 1, characterized in that, The molar ratio of the catalyst to the benzene and its derivatives is from 10:1 to 1:2000, wherein the molar amount of the catalyst is expressed as the molar amount of barium hydride.

5. The method according to claim 4, characterized in that, The reaction temperature is 0℃~250℃; The reaction time ranges from 5 minutes to 48 hours.

6. The method according to claim 5, characterized in that, When the molar ratio of the bulk barium hydride to the benzene and its derivatives is 10:1 to 1:10, the reaction temperature is 0℃ to 120℃, and the reaction time is 6 hours to 48 hours, the deuterated compound is a single deuterated product of benzylmethyl having the structure shown in Formula 3.

7. The method according to claim 5, characterized in that, When the molar ratio of barium hydride to benzene and its derivatives in the supported catalyst is 1:1 to 1:1000, the reaction temperature is 0℃ to 60℃, and the reaction time is ≤12 hours, the deuterated compound is a single deuterated product of benzylmethyl having the structure shown in Formula 3.

8. The method according to claim 5, characterized in that, When the molar ratio of barium hydride to benzene and its derivatives in the supported catalyst is 1:1 to 1:100, the reaction temperature is 25℃ to 250℃, and the reaction time is ≥6 hours, the deuterated compound is a fully deuterated benzene ring product having at least one of the structures shown in Formula 4 and Formula 5.

9. The method according to claim 1, characterized in that, The pressure of the deuterium gas is 0.1–200 bar; Preferably, the reaction system further includes an organic solvent; The organic solvent is selected from one of n-pentane, n-hexane, cyclohexane, tetrahydrofuran, benzene, 2-methyltetrahydrofuran, and 1,4-dioxane.

10. The method according to claim 1, characterized in that, The preparation method of the supported catalyst includes: Method 1: BaH2 and carrier are ball-milled and mixed; or, Method 2: Barium metal and a support are impregnated in liquid ammonia and reduced under a hydrogen atmosphere.

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