A method for double cheap metal catalyzed hydrogen-deuterium exchange of heterocyclic aromatic hydrocarbons

Abstract

This invention provides a method for hydrogen-deuterium substitution in heterocyclic aromatic hydrocarbons using a binary, inexpensive metal catalyst, belonging to the field of organic synthesis technology. The method uses heterocyclic aromatic hydrocarbons as raw materials, adding heavy water and a binary, inexpensive metal catalyst with or without solvent. Under inert gas protection, the hydrogen-deuterium substitution reaction is carried out at elevated temperature. After the reaction, the product is separated and purified to obtain the deuterated heterocyclic aromatic hydrocarbon compound. The preparation method provided by this invention uses inexpensive heavy water as the deuterium source and an inexpensive binary metal as the catalyst, resulting in low cost, high operability, wide applicability, and high deuteration rate. It achieves a low-cost and efficient deuteration technology for heterocyclic aromatic hydrocarbons, overcoming the limitations of current heterocyclic aromatic hydrocarbon deuteration technologies.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for hydrogen-deuterium substitution in heterocyclic aromatic hydrocarbons using a binary low-cost metal catalysis. Background Technology

[0002] Deuterium shares similar chemical properties with hydrogen. Because deuterium has one more neutron than hydrogen, its CD bond has a lower zero-point vibrational energy than its CH bond, resulting in better stability in deuterated compounds. Based on this characteristic, deuterated compounds have been widely used in various fields, including reaction mechanisms, drug research, analytical chemistry, and organic optoelectronic materials. With the increasing market and research demand, the need for different deuterated raw materials (such as deuterated aromatics, deuterated alkanes, and deuterated heterocyclic aromatics) is also growing, placing higher demands on the broad adaptability, environmental friendliness, and economic efficiency of deuteration technology. Especially in the field of organic optoelectronic materials, deuterated compounds, with their high luminous efficiency and thermal stability, have become an indispensable raw material for next-generation deuterated OLED materials. Since over 90% of OLED materials contain heterocyclic aromatic structures, research on deuterated heterocyclic aromatic organic materials has significant application potential.

[0003] The synthesis of deuterated aromatics and deuterated alkanes without heteroatoms mostly has mature industrialized technical routes, but there are few reports on deuteration technology for heterocyclic aromatics. Chinese patent application CN112876406A discloses a process for deuterating carbazole compounds using fluorine-containing catalysts, heavy water as the deuterium source, and dioxane as the solvent. This technology directly prepares deuterated carbazoles through a hydrogen-deuterium exchange reaction on carbazole compounds, reducing the number of synthetic steps. However, this method uses strong organic acids such as trifluoromethanesulfonic acid, which poses certain risks; and it generates large amounts of wastewater containing organic acids, causing serious environmental pollution. Chinese patent application CN113620866A discloses a method for preparing deuterated nitrogen-containing heterocyclic compounds, using an inorganic base such as potassium tert-butoxide as a catalyst, deuterated dimethyl sulfoxide as the deuterium source reagent, and conducting a pressurized reaction at 100°C. This method uses expensive deuterium source deuterated dimethyl sulfoxide, the reaction requires pressurization, and it is only applicable to carbazole-structured compounds. The high cost of the deuterium source, the demanding reaction conditions, and the limited substrates make it unsuitable for industrial scale-up.

[0004] In the technology of deuterated aromatics, noble metal catalysts, such as Pt, Pd, Ir, Ru, and Rh, are frequently used for high-temperature and high-pressure reactions. Some literature also discloses the use of metal catalysts such as Fe, Ag, and Mo for deuteration reactions of benzene, anthracene, and carbazole, but these are limited to laboratory-scale applications and have not been widely used in industrial applications. For example, SynOpen 2024, 8, 328-359; J.Am.Chem.Soc., 1972, 94, 5913. Furthermore, the hydrogen-deuterium exchange reaction catalyzed by noble metals has certain limitations, such as high catalyst prices, harsh reaction conditions, the need for hydrogen or deuterium to activate the catalyst in some reactions, and high requirements for the materials of the reaction equipment, thus resulting in a low rate of industrial application.

[0005] In summary, existing technologies have obvious technical shortcomings, and developing a highly efficient and inexpensive metal catalyst for the deuteration of heterocyclic aromatic hydrocarbons is of great significance. Summary of the Invention

[0006] This invention addresses the shortcomings of existing technologies by providing a method for hydrogen-deuterium substitution in heterocyclic aromatic hydrocarbons using a binary, inexpensive metal catalyst. This method employs inexpensive heavy water as the deuterium source and an inexpensive binary metal as the catalyst, resulting in low cost, high operability, wide applicability, and high deuteration rate. It achieves an inexpensive and efficient deuteration technology for heterocyclic aromatic hydrocarbons, overcoming the limitations of current deuteration technologies for heterocyclic aromatic hydrocarbons.

[0007] The technical solution of the present invention to solve the above-mentioned technical problems is as follows: a method for hydrogen-deuterium substitution of heterocyclic aromatic hydrocarbons by binary inexpensive metal catalyst, the method being: using a heterocyclic aromatic hydrocarbon compound as raw material, with or without the addition of solvent, heavy water and a binary inexpensive metal catalyst are added, and under the protection of inert gas, the hydrogen-deuterium substitution reaction is carried out by heating. After the reaction is completed, the product is separated and purified to obtain a heterocyclic aromatic deuterated compound.

[0008] Furthermore, when heterocyclic aromatic compounds are in a liquid state, no solvent is added.

[0009] Furthermore, when the heterocyclic aromatic compounds are in a solid state, a solvent needs to be added, and the mass ratio of the solvent to heavy water is (1~5):1.

[0010] Furthermore, the solvent is any one of cyclohexane, decahydronaphthalene, and mesitylene.

[0011] Furthermore, the molar ratio of heterocyclic aromatic compounds to heavy water is 1:(20~200).

[0012] Furthermore, the binary inexpensive metal catalyst comprises 1% to 30% of the weight of the heterocyclic aromatic compound.

[0013] Furthermore, heterocyclic aromatic compounds may be free of substituents or contain one or more substituents.

[0014] Furthermore, the substituent is selected from at least one of fluorine, chlorine, bromine, iodine, alkyl, alkoxy, amino, and hydroxyl groups.

[0015] Furthermore, the heterocyclic aromatic compounds are selected from one of the following: carbazole compounds, indole compounds, pyrrole compounds, furan compounds, and thiophene compounds.

[0016] Furthermore, carbazole compounds are one of carbazole, 4-phenylcarbazole, and 4-chlorocarbazole.

[0017] Furthermore, the furan compound is 4-bromodibenzofuran.

[0018] Furthermore, thiophene compounds are thiophenes.

[0019] Furthermore, the temperature for the hydrogen-deuterium replacement reaction is 80~150℃, and the reaction time is 12~48 hours.

[0020] Furthermore, the preparation method of the binary low-cost metal catalyst includes the following steps:

[0021] S1. Dissolve two inexpensive metal salts in deionized water to prepare a mixed solution. Then, spray the mixed solution evenly onto the molecular sieve support. After spraying, dry it with hot air for 2 hours. Then, transfer it to a muffle furnace and calcine it at 600℃~800℃ for 6~10 hours under inert conditions to obtain the precursor of the binary inexpensive metal catalyst.

[0022] S2. The precursor of the binary low-cost metal catalyst is placed in a hydrogen atmosphere or reduced using other reducing agents to obtain a supported binary low-cost metal catalyst.

[0023] Furthermore, in step S1, the two inexpensive metal salts are selected from any two of copper (Cu) salts, iron (Fe) salts, cobalt (Co) salts, molybdenum (Mo) salts, silver (Ag) salts, and nickel (Ni) salts.

[0024] Furthermore, the molecular sieve support is a mesoporous molecular sieve support, preferably SBA-15.

[0025] Furthermore, in step S1, the total concentration of the two ions in the mixed solution is 0.5 mol / L to 2.0 mol / L, and the molar ratio of the two ions is 1:(1 to 5).

[0026] Furthermore, in step S2, the total loading of the binary low-cost metal catalyst is 5% to 30%.

[0027] Furthermore, the copper salt is CuCl.

[0028] Furthermore, the iron salt is one of Fe(NO3)3 and FeCl3.

[0029] Furthermore, the cobalt salt is one of CoSO4 and CoCl2.

[0030] Furthermore, the molybdenum salt is one of (NH4)2MoSO4 or NaMoSO4.

[0031] Furthermore, the silver salt is AgNO3.

[0032] Furthermore, the nickel salt is one of NiCl2, NiSO4, Ni(NO3)3, and Ni(CH3COO)2.

[0033] Furthermore, in step S2, the hydrogen reduction temperature is 150~200℃, and the reduction time is 3~5 hours.

[0034] The beneficial effects of this invention are:

[0035] (1) The method described in this invention uses inexpensive heavy water as a deuterium source and substituted or unsubstituted heterocyclic aromatic compounds as raw materials. Under the action of a binary inexpensive metal catalyst, the deuteration reaction of heterocyclic aromatics is completed. It is mainly applied to the preparation of organic optoelectronic intermediate materials, providing a wider range of deuterated basic raw materials for deuterated OLED monomer materials.

[0036] (2) A self-made binary low-cost metal catalyst is carried out using a mesoporous molecular sieve support. Its two-dimensional hexagonal ordered pore structure has a large pore size and thick pore wall, which can enhance the dispersion of metal and reduce sintering; it can also improve the catalyst's tolerance to high-temperature hydrothermal systems and ensure the catalyst's high catalytic activity in the reaction system.

[0037] (3) The active component of the catalyst is a binary inexpensive metal, which not only solves the problem of expensive precious metal catalysts, but also makes full use of the different catalytic properties of different metal elements through the combination of different metal elements, thereby improving the CH activation ability of the catalyst and its tolerance to heterocyclic substrates, and realizing the hydrogen-deuterium replacement of heterocyclic aromatic hydrocarbons.

[0038] (4) The deuteration technology described in this invention has wide applicability to heterocyclic aromatic substrates containing N, O and S elements. The reaction conditions are mild, the catalyst has high activity and strong stability, and the reaction is easy to scale up for industrial production, thus having potential commercial value. Attached Figure Description

[0039] Figure 1 The image shows the 1H NMR spectrum of deuterated 4-chlorocarbazole in Example 10. Detailed Implementation

[0040] The specific embodiments of the present invention will be described in detail below. The present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed.

[0041] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used is for describing particular embodiments only and is not intended to limit the invention.

[0042] Unless otherwise stated, all raw materials and compounds involved in this invention are commercially available.

[0043] This invention provides a method for hydrogen-deuterium substitution in heterocyclic aromatic hydrocarbons using a binary inexpensive metal catalyst. The method involves using a heterocyclic aromatic hydrocarbon compound as a raw material, adding heavy water and a binary inexpensive metal catalyst with or without the addition of a solvent, and carrying out the hydrogen-deuterium substitution reaction under inert gas protection. After the reaction is completed, the product is separated and purified to obtain a deuterated heterocyclic aromatic hydrocarbon compound.

[0044] Specifically, when the heterocyclic aromatic hydrocarbon compound is in a liquid state, no solvent is added. When the heterocyclic aromatic hydrocarbon compound is in a solid state, a solvent must be added, with a solvent-to-heavy water mass ratio of (1~5):1; the solvent can be any one of cyclohexane, decahydronaphthalene, or mesitylene.

[0045] Specifically, the molar ratio of heterocyclic aromatic compounds to heavy water is 1:(20~200).

[0046] Specifically, the binary low-cost metal catalyst is 1% to 30% of the weight of the heterocyclic aromatic compound.

[0047] Specifically, heterocyclic aromatic compounds either do not contain substituents or contain one or more substituents.

[0048] Specifically, the substituent is selected from at least one of fluorine, chlorine, bromine, iodine, alkyl, alkoxy, amino, and hydroxyl groups.

[0049] Specifically, the heterocyclic aromatic compounds are selected from one of the following: carbazole compounds, indole compounds, pyrrole compounds, furan compounds, and thiophene compounds.

[0050] More specifically, carbazole compounds are one of carbazole, 4-phenylcarbazole, and 4-chlorocarbazole.

[0051] More specifically, the furan compound is 4-bromodibenzofuran.

[0052] More specifically, thiophene compounds are thiophenes.

[0053] Specifically, the temperature for the hydrogen-deuterium replacement reaction is 80~150℃, and the reaction time is 12~48 hours.

[0054] More specifically, the preparation method of the binary low-cost metal catalyst includes the following steps:

[0055] S1. Dissolve two inexpensive metal salts in deionized water to prepare a mixed solution. Then, spray the mixed solution evenly onto the molecular sieve support. After spraying, dry it with hot air for 2 hours. Then, transfer it to a muffle furnace and calcine it at 600℃~800℃ for 6~10 hours under inert conditions to obtain the precursor of the binary inexpensive metal catalyst.

[0056] S2. The precursor of the binary low-cost metal catalyst is placed in a hydrogen atmosphere or reduced using other reducing agents to obtain a supported binary low-cost metal catalyst.

[0057] Specifically, in step S1, the two inexpensive metal salts are selected from any two of copper (Cu) salt, iron (Fe) salt, cobalt (Co) salt, molybdenum (Mo) salt, silver (Ag) salt, and nickel (Ni) salt.

[0058] Specifically, the molecular sieve support is a mesoporous molecular sieve support. In this specific embodiment of the invention, SBA-15 is preferred, but this does not limit the technology; it is merely for clearer description. The SBA-15 support selected in this specific embodiment has a two-dimensional hexagonal ordered pore structure with large pore size and thick pore walls, which can enhance the dispersibility of metals, reduce sintering, and is suitable for loading large molecular active components such as Ni and Co, ensuring good reactivity of the active components in the hydrogen-deuterium exchange reaction. This support has good hydrothermal stability and strong thermal stability in systems using heavy water as a deuterium source, able to withstand high-temperature systems containing water and maintain high catalyst activity.

[0059] The active components of the catalyst are selected from transition metal elements such as Cu, Fe, Co, Mo, Ag, and Ni. Through an oxidative addition mechanism, the CH bonds of the substrate undergo oxidative addition with the low-valence transition metal catalyst, leading to the cleavage and activation of the CH bonds to generate CMH. This CMH further undergoes a hydrogen-deuterium exchange reaction with heavy water, followed by its reverse reaction to achieve substrate deuteration. By co-impregnating, two different active component elements are uniformly loaded onto the support surface. The interaction between the two different elements enhances the stability of the catalyst's active components. Simultaneously, different metals possess different catalytic activities, further achieving full deuteration of the substrate. For example, in traditional Cu catalysts, during CH activation, Cu(II) readily disproportionates to Cu(III), making reverse CD bond reconstruction difficult and resulting in a low deuteration rate. By introducing another metal element and its interaction with molecular sieve ligands, Cu(II) species are stabilized and disproportionation is suppressed, promoting the hydrogen-deuterium exchange reaction of the substrate. Fe catalysts, by introducing a dual-element metal, endow the Fe center with good stability and electronic properties, and realize the meta- and para-CH activation of the substrate based on its unique steric effect, further achieving deuteration. Co catalysts, low-valent Co species activate the CH bond of the substrate through oxidative addition or σ bond metathesis mechanism, forming Co-hydrides and Co-C intermediates, thereby achieving deuteration. The introduction of Mo element is mainly applied to S-containing heterocyclic aromatic structures. The introduction of Mo can change the surface acidity, reducing properties of the support and the interaction between the metal and the support, and improve the catalyst's resistance to poisoning. Ag can efficiently catalyze the CH bond activation of heterocyclic aromatic halides to achieve hydrogen-deuterium exchange reaction. Ni is suitable for the deuteration reaction of electron-deficient and electron-rich substrates. The core of Ni-catalyzed hydrogen-deuterium exchange is to promote CH bond activation, oxidative addition, and σ bond metathesis. It has a unique ability to activate inert CH bonds, and is especially suitable for hydrogen-deuterium exchange of nitrogen-containing heterocycles.

[0060] Specifically, in step S1, the total concentration of the two ions in the mixed solution is 0.5 mol / L to 2.0 mol / L, and the molar ratio of the two ions is 1:(1~5).

[0061] Specifically, in step S2, the total loading of the binary low-cost metal catalyst is 5% to 30%.

[0062] Specifically, the copper salt is CuCl; the iron salt is one of Fe(NO3)3 and FeCl3; the cobalt salt is one of CoSO4 and CoCl2; the molybdenum salt is one of (NH4)2MoSO4 and NaMoSO4; the silver salt is AgNO3; and the nickel salt is one of NiCl2, NiSO4, Ni(NO3)3, and Ni(CH3COO)2.

[0063] Specifically, in step S2, the hydrogen reduction temperature is 150~200℃ and the reduction time is 3~5 hours.

[0064] Example 1

[0065] Preparation of Fe-Co (Fe / Co=1 / 1.25) binary catalyst:

[0066] S1. Dissolve 0.02 mol of ferric nitrate and 0.025 mol of cobalt chloride in 50 mL of deionized water, heat to dissolve, and stir until homogeneous to obtain Fe. 3+ and Co 2+ A mixed solution with a total concentration of 0.9 mol / L, wherein Fe 3+ and Co 2+ The molar ratio was 1:1.25. The mixture was then sprayed evenly onto 45g of SBA-15 molecular sieve support. After spraying, it was dried for 2 hours at 80~100℃ with hot air. Then it was transferred to a muffle furnace and calcined at 700℃ for 8 hours under inert conditions to obtain the precursor of Fe-Co binary low-cost metal catalyst.

[0067] S2. The precursor of the binary inexpensive metal catalyst was placed in a hydrogen atmosphere and reduced at 200℃ for 4 hours. After reduction, the catalyst was pressed into tablets, and 20-50 mesh catalyst powder was collected for use. Finally, a Fe-Co (Fe / Co=1 / 1.25) binary catalyst with a loading of 5.4% was obtained.

[0068] Example 2

[0069] Preparation of Ag-Mo (Ag / Mo=1 / 1.3) binary catalyst:

[0070] S1. Dissolve silver nitrate (0.02 mol) and ammonium molybdate (0.026 mol) in 50 mL of deionized water, heat to dissolve, and stir until homogeneous to obtain Ag. + and Mo 2+ A mixed solution with a total concentration of 0.92 mol / L, wherein Ag + and Mo 2+ The molar ratio was 1:1.3. The mixture was then sprayed evenly onto 45g of SBA-15 molecular sieve support. After spraying, it was dried for 2 hours at 80~100℃ with hot air. Then it was transferred to a muffle furnace and calcined at 650℃ for 7 hours under inert conditions to obtain the precursor of Ag-Mo binary low-cost metal catalyst.

[0071] S2. The precursor of the binary inexpensive metal catalyst was placed in a hydrogen atmosphere and reduced at 200℃ for 6 hours. After reduction, the catalyst was pressed into tablets, and 20-50 mesh catalyst powder was collected for use. Finally, an Ag-Mo (Ag / Mo=1 / 1.3) binary catalyst with a loading of 11.7% was obtained.

[0072] Example 3

[0073] Preparation of Cu-Ni (Cu / Ni=1 / 3) binary catalyst:

[0074] S1. Dissolve 0.015 mol of cuprous chloride and 0.045 mol of nickel chloride in 50 mL of deionized water. Heat the solution and stir until homogeneous to obtain Cu. + and Ni 2+ A mixed solution with a total concentration of 1.2 mol / L, wherein Cu + and Ni 2+ The molar ratio was 1:3. The mixture was then sprayed evenly onto 14.5g of SBA-15 molecular sieve support. After spraying, it was dried for 2 hours at 80~100℃ with hot air. Then it was transferred to a muffle furnace and calcined at 600℃ for 10 hours under inert conditions to obtain the precursor of Fe-Co binary low-cost metal catalyst.

[0075] S2. The precursor of the binary inexpensive metal catalyst was placed in a hydrogen atmosphere and reduced at 200℃ for 3 hours. After reduction, the catalyst was pressed into tablets, and 20-50 mesh catalyst powder was collected for use. Finally, a Cu-Ni (Cu / Ni=1 / 3) binary catalyst with a loading of 19.9% ​​was obtained.

[0076] Example 4

[0077] Preparation of Ag-Ni (Ag / Ni=1 / 5) binary catalyst:

[0078] S1. Dissolve silver nitrate (0.01 mol) and nickel nitrate (0.05 mol) in 50 mL of deionized water, heat to dissolve, and stir until homogeneous to obtain Fe. 3+ and Co 2+ A mixed solution with a total concentration of 1.2 mol / L, wherein Fe 3+ and Co 2+ The molar ratio of the two components was 1:5. The mixture was then evenly sprayed onto 10.1g of SBA-15 molecular sieve support. After spraying, the mixture was dried for 2 hours at 80~100℃ with hot air. Then it was transferred to a muffle furnace and calcined at 800℃ for 6 hours under inert conditions to obtain the precursor of Fe-Co binary low-cost metal catalyst.

[0079] S2. The precursor of the binary low-cost metal catalyst was placed in a hydrogen atmosphere and reduced at 200℃ for 5 hours. After reduction, the catalyst was pressed into tablets, and 20-50 mesh catalyst powder was collected for use. Finally, an Ag-Ni (Ag / Ni=1 / 4.2) binary catalyst with a loading of 28.3% was obtained.

[0080] Example 5

[0081] Preparation of Co-Mo (Co / Mo=1 / 1.17) binary catalyst: Example 5 uses the same method as Example 2, except that: cobalt nitrate (0.03 mol) and sodium molybdate (0.035 mol) are dissolved in 50 mL of deionized water, heated to dissolve, and stirred until homogeneous to obtain Co. 2+ and Mo 2+ A mixed solution with a total concentration of 1.3 mol / L, wherein Co 2+ and Mo 2+ The molar ratio is 1:1.17.

[0082] The final result was a Co-Mo (Co-Mo=1 / 1.17) binary catalyst with a loading of 12.7%.

[0083] Example 6

[0084] Synthesis of deuterated carbazole:

[0085] ;

[0086] (1) After nitrogen purging, add 16.7g carbazole (0.1mol), 200g heavy water (10.0mol), 800g mesitylene and 4.18g of Fe-Co (Fe / Co=1 / 1.32) binary catalyst prepared in Example 1 to the reaction flask in sequence, and heat to 130℃ under nitrogen atmosphere and stir for 36h.

[0087] (2) After the reaction was deemed satisfactory, the temperature was lowered to 20-30℃, and 400g of mesitylene was added. The mixture was then directly filtered to separate the organic phase, dried, passed through a silica gel column, and slurried with petroleum ether to obtain 15.1g of the product deuterated carbazole, with a yield of 90.4% and a deuteration rate of 95%. The NMR spectroscopy data are as follows: 1 H NMR (400Hz, CDCl3): δ=11.06 (m, 1H), 8.09 (m, 0.03H), 7.49 (m, 0.03H), 7.15 (m, 0.03H) ppm.

[0088] Example 7

[0089] Synthesis of deuterated thiophene:

[0090] ;

[0091] (1) After nitrogen purging, add 84.1 g thiophene (1.0 mol), 50 g heavy water (25.0 mol) and 16.8 g Ag-Mo (Ag / Mo=1 / 1.16) binary catalyst prepared in Example 2 to the reaction flask in sequence, and heat to 80 °C under nitrogen atmosphere and stir for 48 h.

[0092] (2) After the reaction was successful, the catalyst was first filtered out, then the solvent was removed, and the product, deuterated thiophene, was recrystallized from methanol to obtain 53.4 g, with a yield of 63.5% and a deuteration rate of 89.2%. The NMR spectroscopy data are as follows: 1 H NMR (400Hz, CDCl3): δ=7.30(t, J = 4.5 Hz, 0.21H), 7.03 (t, J = 4.5 Hz, 0.222H)ppm.

[0093] Example 8:

[0094] Synthesis of deuterated 4-bromodibenzofuran:

[0095] ;

[0096] (1) After nitrogen purging, 247.1 g of 4-bromodibenzofuran (1.0 mol), 800 g of heavy water (40.0 mol) and 800 g of decahydronaphthalene were added to the reaction flask in sequence. Then, 10.1 g of Cu-Ni (Cu / Ni=1 / 3) binary catalyst prepared in Example 3 was added. The mixture was heated to 90 °C under a nitrogen atmosphere and stirred for 38 h.

[0097] (2) After the reaction was deemed satisfactory, the temperature was lowered to 20–30 °C, and the mixture was directly filtered. The filter cake was extracted with dichloromethane to separate the organic phase. The organic phase was dried, passed through a silica gel column, and after solvent removal, 217.5 g of the product, deuterated 4-bromodibenzofuran, was obtained, with a yield of 85.6% and a deuteration rate of 86.3%. The NMR spectral data were as follows: 1 H NMR (400Hz, CDCl3): δ=8.02(dd, 0.12H), 7.97(dd, 0.25H), 7.56(dt, 0.31H), 7.45(td, 0.11H), 7.41-7.33(m, 0.17H)ppm.

[0098] Example 9

[0099] Synthesis of deuterated 4-phenylcarbazole:

[0100] ;

[0101] Example 9 uses the same method as Example 6, except that the substrate is replaced with 24.3 g of 4-phenylcarbazole (0.1 mol), and 4.2 g of the Ag-Ni (Ag / Ni = 1 / 5) binary catalyst prepared in Example 4 is used. After post-reaction processing, 19.8 g of deuterated 4-phenylcarbazole is obtained, with a yield of 84.5% and a deuteration rate of 85.0%. The NMR spectroscopy data are as follows: 1H NMR (400Hz, CDCl3): δ=10.69(s, 1H), 7.91(s, 0.21H), 7.35(s, 0.27H), 7.63–7.57(m, 0.33H), 7.47(s, 0.42H), 7.44 –7.39(m, 0.08H), 7.40(s, 0.22H), 7.41–7.33(m, 0.18H), 7.29(d, 0.05H), 7.16(d, 0.04H)ppm.

[0102] Example 10

[0103] Synthesis of deuterated 4-chlorocarbazole:

[0104] ;

[0105] Example 10 uses the same method as Example 6, except that the substrate was replaced with 20.2 g of 4-chlorocarbazole (0.1 mol) under the same reaction conditions. After post-reaction processing, 17.4 g of deuterated 4-chlorocarbazole was obtained, with a yield of 86.0% and a deuteration rate of 97.0%. The NMR spectroscopy data are as follows: 1 H NMR (400Hz, DMSO-) d 6 1H NMR spectrum: 11.60 (s, 1H), 8.39 (s, 0.03H), 7.53 (d, 0.03H), 7.46 (d, 0.03H), 7.43 (d, 0.03H), 7.34 (d, 0.03H), 7.19 (d, 0.03H), 7.17 (d, 0.03H) ppm. The 1H NMR spectrum is shown below. Figure 1 .

[0106] Comparative Example 1

[0107] Synthesis of deuterated carbazole:

[0108] Comparative Example 1 used the same method as Example 6, except that 6.68 g of the Fe-Co (Fe / Co=1 / 1.32) binary catalyst prepared in Example 1 was added. At this point, the binary inexpensive metal catalyst accounted for 40% of the weight of the heterocyclic aromatic compound. The final yield of deuterated carbazole was 73.2%, and the deuteration rate was 94.5%.

[0109] The yield of deuterated carbazole in Comparative Example 1 decreased because when the amount of binary inexpensive metal catalyst is too high, the catalyst adsorbs a large amount of product, making it difficult to extract the product in the post-processing, resulting in low product yield and increased cost.

[0110] Comparative Example 2

[0111] The preparation method of the Fe-Co (Fe / Co=1 / 12) binary catalyst is the same as in Example 1, except that in step S1, ferric nitrate (0.01 mol) and cobalt chloride (0.12 mol) are dissolved in 50 mL of deionized water, heated to dissolve, and stirred until homogeneous to obtain Fe. 3+ and Co 2+ A mixed solution with a total concentration of 2.6 mol / L, wherein the molar ratio of Fe to Co is 1:12, was finally obtained as a Fe-Co (Fe / Co=1 / 12) binary catalyst with a loading of 5.4%.

[0112] Synthesis of deuterated carbazole: This comparative example 2 uses the same method as in Example 6, except that the ratio of the two ions in the Fe-Co binary catalyst is different. This comparative example uses the Fe / Co=1 / 12 binary catalyst prepared in this comparative example.

[0113] The final yield of deuterated carbazole was 85.7%, and the deuteration rate was 55.0%.

[0114] The yield and deuteration rate of deuterated carbazole in Comparative Example 1 decreased significantly. This is because when the molar ratio of the two ions in the binary catalyst is 1:12, which is outside the range provided by this invention, the proportion of one of the ions is too high. This causes the catalytic effect to favor the excessive amount of this metal ion during the catalytic process, thus rendering the role of the binary metal ion ineffective and affecting the hydrogen-deuterium replacement effect.

[0115] Comparative Example 3

[0116] Comparative Example 3 uses the same method as Example 6, except that a noble metal catalyst Ru / C is added (where the mass content of Ru is 5%).

[0117] Comparative Example 4

[0118] Comparative Example 4 uses the same method as Example 6, except that a noble metal catalyst Pd / C (of which the mass content of Pd is 5%) is added.

[0119] Comparative Example 5

[0120] Comparative Example 5 uses the same method as Example 6, except that a noble metal catalyst Pt / C (of which the mass content of Pt is 5%) is added.

[0121] Comparative Example 6

[0122] Comparative Example 6 uses the same method as Example 6, except that a noble metal catalyst Pt / C (with a molar content of 10% Pt) is added.

[0123] The experimental data results of the examples and comparative examples are shown in Table 1.

[0124] Table 1. Experimental data results of the examples and comparative examples.

[0125]

[0126] By comparing the reaction effects with those of noble metal catalysts Pd / C, Ru / C, and Pt / C in the embodiments of the present invention, it can be found that binary inexpensive metal catalysts can completely replace noble metal catalysts for hydrogen-deuterium replacement reactions.

[0127] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are exhaustively listed. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0128] For those skilled in the art, various modifications and improvements can be made without departing from the concept of the present invention, and these modifications and improvements are all within the scope of protection of the present invention. The scope of protection of the present invention is defined by the appended claims.

Claims

1. A method for hydrogen-deuterium substitution in heterocyclic aromatic hydrocarbons using a binary, inexpensive metal catalysis method, characterized in that, The method is as follows: using heterocyclic aromatic compounds as raw materials, with or without the addition of solvent, heavy water and a binary inexpensive metal catalyst are added, and under the protection of inert gas, a hydrogen-deuterium substitution reaction is carried out at 80~150℃. After the reaction is completed, the product is separated and purified to obtain a heterocyclic aromatic deuterated compound. The total loading of the binary low-cost metal catalyst is 5% to 30%. The heterocyclic aromatic compound is selected from one of the following: carbazole compounds, indole compounds, pyrrole compounds, furan compounds, and thiophene compounds; When the heterocyclic aromatic compound is in a liquid state, no solvent is added; When the heterocyclic aromatic compound is in a solid state, a solvent needs to be added. The solvent is any one of cyclohexane, decahydronaphthalene, and mesitylene. The mass ratio of the solvent to heavy water is (1~5):

1. The preparation method of binary low-cost metal catalysts includes the following steps: S1. Dissolve two inexpensive metal salts in deionized water to prepare a mixed solution. Then, spray the mixed solution evenly onto the SBA-15 molecular sieve support. After spraying, dry it with hot air for 2 hours. Then, transfer it to a muffle furnace and calcine it at 600℃~800℃ for 6~10 hours under inert conditions to obtain the precursor of the binary inexpensive metal catalyst. S2. The precursor of the binary low-cost metal catalyst is placed in a hydrogen atmosphere or reduced using other reducing agents to obtain a supported binary low-cost metal catalyst. In step S1, the two inexpensive metal salts are selected from any two of copper salts, iron salts, cobalt salts, molybdenum salts, silver salts, and nickel salts; In step S1, the total concentration of the two ions in the mixed solution is 0.5 mol / L to 2.0 mol / L, and the molar ratio of the two ions is 1:(1 to 5). The copper salt is CuCl; The iron salt is one of Fe(NO3)3 and FeCl3; The cobalt salt is one of CoSO4 and CoCl2; The molybdenum salt is one of (NH4)2MoSO4 and NaMoSO4; The silver salt is AgNO3; The nickel salt is one of NiCl2, NiSO4, Ni(NO3)3, and Ni(CH3COO)2.

2. The method for hydrogen-deuterium replacement of heterocyclic aromatic hydrocarbons using a binary low-cost metal catalysis according to claim 1, characterized in that, The molar ratio of the heterocyclic aromatic compound to heavy water is 1:(20~200). The binary low-cost metal catalyst comprises 1% to 30% of the weight of the heterocyclic aromatic compound.

3. The method for hydrogen-deuterium replacement of heterocyclic aromatic hydrocarbons using a binary low-cost metal catalysis according to claim 1, characterized in that, The heterocyclic aromatic compounds may be free of substituents or contain one or more substituents. The substituent is selected from at least one of fluorine, chlorine, bromine, iodine, alkyl, alkoxy, amino, and hydroxyl.

4. The method for hydrogen-deuterium replacement of heterocyclic aromatic hydrocarbons using a binary low-cost metal catalysis according to claim 1, characterized in that, The carbazole compound is one of carbazole, 4-phenylcarbazole, and 4-chlorocarbazole; The furan compound is 4-bromodibenzofuran; The thiophene compound is thiophene.

5. The method for hydrogen-deuterium replacement of heterocyclic aromatic hydrocarbons using a binary low-cost metal catalysis according to claim 1, characterized in that, In step S2, the hydrogen reduction temperature is 150~200℃ and the reduction time is 3~5 hours.

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