Preparation method of deuterated carbazole under hydrogen-free condition

Abstract

The invention discloses a preparation method of deuterated carbazole under a hydrogen-free condition, which comprises the following steps: mixing carbazole, a catalyst and deuterium water, heating and reacting in an inert gas environment at the reaction temperature of 70-140 DEG C for 12-48 hours, filtering the mixed solution after the reaction is completed to obtain a mixture of deuterium water and a product, adding an organic extraction agent for extraction and liquid separation, and filtering to obtain the deuterated carbazole. Collecting an organic phase to obtain a product deuterated carbazole; according to the catalyst, gamma-type aluminum oxide serves as a carrier, an active component is precious metal alloy Pt-Ru, the mass of precious metal Pt accounts for 1%-30% of the mass of aluminum oxide, and the mass ratio of Pt to Ru is 1: (0.01-0.5). The catalyst has good reaction activity and stability in the reaction process, the synthesis method of the deuterated carbazole is simple and efficient, the deuterated carbazole can be synthesized at the temperature of 70 DEG C or above, the conditions are mild, meanwhile, the yield is high and at least can reach 60% or above, the operation process is simple and convenient, the catalyst is easy to prepare, and the production cost is low.

Description

Technical Field

[0001] The invention belongs to the field of synthesis of deuterated compounds, and in particular relates to a method for preparing deuterated carbazole under hydrogen-free conditions. Background Art

[0002] Deuterium is a type of hydrogen isotope, consisting of a neutron and a proton. Due to the mass effect, the carbon-deuterium bond has a shorter bond length and higher bond energy than the carbon-hydrogen bond. Therefore, deuterated compounds are widely used in medicine, environmental analysis and testing, and the development of new materials. In the field of medicine, by replacing one or more carbon-hydrogen bonds (CH) in specific metabolic sites of drug molecules with carbon-deuterium bonds (CD), the drug metabolism cycle can be extended, the production of toxic metabolites can be reduced, thereby reducing the dosage, improving safety, and obtaining better efficacy. In 2017, the world's first deuterated drug AUSTEDO was approved for marketing by the US Food and Drug Administration (FDA), and several deuterated drugs are in Phase III clinical studies, which indicates that the FDA recognizes the role of deuterium in drug design that is different from ordinary hydrogen. In the field of new material development, searching for literature on Scifinder with the keyword "deuterium and OLED" can find 90 related patents, which shows that deuterated materials have important applications in the field of organic light-emitting. By introducing deuterium atoms into optoelectronic materials, the crystal morphology of optoelectronic materials can be adjusted, thereby changing the optoelectronic properties of optoelectronic materials. More importantly, by introducing deuterium atoms, the stability of the optoelectronic materials themselves can be improved, thereby obtaining more stable optoelectronic devices. In summary, the special properties of deuterated compounds that are different from non-deuterated compounds determine their special application value. At present, the demand for deuterated compounds with special structures is increasing, and it is imperative to develop new methods to synthesize deuterated compounds.

[0003] Direct conversion of inactive carbon-hydrogen bonds is an efficient and clean method for preparing functional materials. HD exchange reactions based on CH activation also provide valuable deuterium-labeled products, which are widely used in the scientific field. Nitrogen-containing heterocyclic drugs are among the most frequently approved small molecule drugs by the US FDA. For example, niacin and niacinamide are common vitamin structures. Among heterocyclic compounds, carbazole is often encountered in drug development, bioactive natural products and materials science. It is also mainly used in the manufacture of dyes, chemical reagents, explosives, pesticides, lubricants, rubber antioxidants, etc. Deuterated carbazole is increasingly widely used. Therefore, it is crucial to develop an effective hydrogen isotope labeling method for carbazole.

[0004] Hydrogen isotope labeling methods for nitrogen-containing heterocyclic structures represented by carbazole have been widely studied in the past few decades. Compared with the traditional multi-step synthesis method, metal-mediated hydrogen isotope exchange allows the later labeling of compounds, which is more advantageous in terms of time and cost.

[0005] Homogeneous catalysis allows molecules to be labeled with deuterium with high selectivity under mild conditions. For example, Chirik's team (J.Am.Chem.Soc.2019,141,5034–5044) used highly efficient α-diimine nickel complexes to achieve deuteration of n-heterocycles. However, homogeneous catalysis often requires the use of expensive ligands, and the reaction products are difficult to separate, reducing the economic feasibility of the reaction process.

[0006] On the other hand, heterogeneous catalysis has the advantages of high isotope incorporation and easy catalyst preparation and separation and recovery, and has also been widely used in H / D exchange. Sajiki and colleagues (HETEROCYCLES, Vol. 66, 2005) used the Pd / C-D2O-H2 system to deuterium label nucleosides, but the hydrogen atmosphere may lead to undesirable side reactions, such as hydrogenation reactions.

[0007] Despite these remarkable advances, developing efficient and convenient HIE processes for carbazoles remains a challenge.

[0008] At the same time, from the perspective of practical synthesis scale, the use of flammable hydrogen is problematic, and undesirable hydrogenation reactions may also occur in the SP2 heterocyclic structure during the deuteration process. This patent proposes a simple and mild HD exchange reaction of carbazole without adding H2. Summary of the invention

[0009] In view of the above problems, the present invention provides a method for preparing deuterated carbazole under hydrogen-free conditions with good efficiency, high yield and no by-products, so that the carbazole can undergo a simple and mild HD exchange reaction without adding H2, thereby solving the above technical problems existing in the prior art.

[0010] In order to achieve the above object, the technical solution adopted by the present invention is:

[0011] A method for preparing deuterated carbazole under hydrogen-free conditions, characterized in that it includes the following process: mixing carbazole, a catalyst and deuterated water, heating and reacting in an inert gas environment, the reaction temperature is 70°C to 140°C, the reaction time is 12-48 hours, after the reaction is completed, filtering the mixed solution to obtain a mixture of deuterated water and a product, adding an organic extractant for extraction and separation, and collecting the organic phase to obtain the product deuterated carbazole, and the reaction formula is as follows:

[0012]

[0013] The catalyst uses gamma-type alumina as a carrier, the active component is a noble metal alloy Pt-Ru, the mass of the noble metal Pt is 1-30% of the mass of the alumina, and the mass ratio of Pt to Ru is 1:0.01-0.5.

[0014] Furthermore, in the catalyst of the present invention, the mass of the precious metal Pt is 8-12% of the mass of the alumina, preferably 10%, and the mass ratio of Pt to Ru is 1:0.1-0.2.

[0015] Furthermore, the preparation method of the catalyst of the present invention comprises the following steps:

[0016] 1) Using pseudo-boehmite as a raw material, heating the pseudo-boehmite at 300° C.-800° C. for 4-8 hours to obtain gamma-type alumina powder;

[0017] 2) adding the alumina powder of step 1) into ethylene glycol and stirring the mixture to form a stable colloidal solution containing alumina;

[0018] 3) Add the Pt source solution and the Ru source solution dropwise to the colloidal solution obtained in step 2) in sequence, add alkali to adjust the pH to 10±0.5, and stir thoroughly at room temperature;

[0019] 4) The mixed solution obtained in step 3) is fully stirred at a heating temperature of 80-160° C. for 3-6 hours under inert gas conditions, and then filtered, washed and dried to obtain the catalyst.

[0020] Furthermore, in step 1), the heating temperature is 400-500° C., and the heating time is 5-6 hours.

[0021] Furthermore, in step 2), the feed ratio of ethylene glycol to alumina solid powder is 0.1-1 ml:1 mg, preferably 0.4-0.5 ml:1 mg.

[0022] Furthermore, in step 4), the heating temperature is 140-150° C. and the stirring time is 4-5 h.

[0023] Furthermore, the inert gas environment is argon, the reaction temperature is 70° C. to 100° C., and the reaction time is 12 to 24 hours.

[0024] Furthermore, the mass ratio of the catalyst to the carbazole is 0.5-1.3:1, and the mass volume ratio of the carbazole to the deuterated water is 1 mg: 0.1-0.4 mL, preferably 1 mg: 0.15-0.2 mL.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] 1) The preparation method of deuterated carbazole of the present invention uses deuterium water as a deuterium source, and uses carbazole and heavy water to react under the catalyst of Pt-Ru / Al2O3 catalyst in an inert gas environment at a temperature of 70°C or above to generate deuterated carbazole. The synthesis method of the deuterated carbazole designed by the present invention is simple and efficient, can be synthesized under conditions of 70°C or above, the conditions are relatively mild, and has a high yield of at least 60% or more. The operation process is simple, the catalyst is easy to prepare, and the production cost is low. It can be applied to large-scale industrial production, providing a new method for the research and development and application of deuterated carbazole.

[0027] 2) The present invention uses pseudo-boehmite as a raw material and gamma-type Al2O3 formed by heating at 400°C as a carrier, uses Pt-Ru alloy as an active component, and uses the catalyst prepared by the method of the present invention to prepare deuterated carbazole under hydrogen-free conditions, and has a good catalytic effect. The addition of platinum and the second metal in different mass ratios during the catalyst preparation process will also bring different effects to the catalytic effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 TEM images, electron diffraction patterns and corresponding HRTEM images of Pt10RuX (X=0.1, 0.2, 1, 2 or 5) / Al2O3-400 catalysts prepared in Examples 1 and 9-12 of the present application;

[0029] Figure 2 It is the XRD characterization diagram of the Pt10RuX (X=0.1, 0.2, 1, 2 or 5) / Al2O3-400 catalyst prepared in Examples 1 and 9-12 of the present application;

[0030] Figure 3 This is the experimental result of recycling the catalyst in Example 10 of the present application for 8 times;

[0031] Figure 4 is the GC-MS graph of pure carbazole before the reaction;

[0032] Figure 5 is the GC-MS graph of deuterated carbazole after the reaction;

[0033] Figure 6 is the NMR image of pure carbazole before the reaction;

[0034] Figure 7 This is the NMR image of deuterated carbazole after the reaction. DETAILED DESCRIPTION

[0035] To make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be described in detail below. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other implementation methods obtained by ordinary technicians in this field without creative work belong to the scope of protection of the present invention.

[0036] The following is a specific example, wherein carbazole is a monomer compound with a purity greater than 90% (HPLC), and the metal loading content of the catalyst is 10%. Deuterated carbazole is analyzed by GC-MS and nuclear magnetic hydrogen spectrum.

[0037] When calculating the deuteration rate of the product in the embodiment of the present invention, the product is first characterized by nuclear magnetic resonance hydrogen spectrum to obtain relevant data, and then the deuteration state of deuterated carbazole is calculated by internal standard method test with 1,4-dioxane as internal standard.

[0038] The calculation process of the deuteration rate of the target product in the embodiment of the present invention is unified as follows:

[0039]

[0040] 1. The preparation example of deuterated carbazole is as follows:

[0041] Example 1

[0042] Add 20 mg of carbazole, 2 ml of deuterated water, 25.1 mg of Pt10-Ru1 / Al2O3-500 catalyst into a reaction container, fill with argon gas 1 MPa, react at 70 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, gas quality detection is deuterated carbazole, and the deuteration rate is 68%.

[0043] The preparation process of Pt10-Ru1 / Al2O3-500 catalyst is as follows:

[0044] 1) Using pseudo-boehmite as raw material, the pseudo-boehmite was heated at 500°C for 6 hours to synthesize Al2O3-500.

[0045] 2) Take 100 mg of the treated Al2O3 white solid powder and put it into a 100 mL round-bottom flask, add 50 mL of ethylene glycol to obtain a mixed solution of Al2O3-500 and ethylene glycol, and stir well;

[0046] 3) Prepare 50 ml of Pt 4+ Add 1 mL of chloroplatinic acid solution with an ion concentration of 10 mg / mL to the stirred ethylene glycol mixture prepared in step 2). 3+0.1 mL of ruthenium chloride solution with an ion concentration of 10 mg / mL was added dropwise to the stirred ethylene glycol mixture and stirred for 1 h to form a stable Pt10-Ru1 ethylene glycol sol;

[0047] 4) adding a 0.1 mol / L NaOH solution dropwise to the stirred ethylene glycol sol in step 3), adjusting the pH to 10 and stirring for 1 hour;

[0048] 5) The reactor was evacuated, inert gas N2 was introduced, heated to 150°C, and stirred for 5 hours. After the reaction, the mixture was filtered, washed, and dried to obtain the finished Pt10-Ru1 / Al2O3-500 catalyst.

[0049] Example 2

[0050] The preparation steps of deuterated carbazole were repeated in Example 1, except that the amount of deuterated water was replaced by 3 mL, and other conditions remained unchanged. The final experimental results were: deuterated carbazole liquid was obtained, and the gas quality detection was deuterated carbazole, and the deuteration rate was 76%.

[0051] Example 3

[0052] The preparation steps of deuterated carbazole were repeated in Example 1, except that the amount of deuterated water was replaced by 4 mL, and other conditions remained unchanged. The final experimental results were: deuterated carbazole liquid was obtained, and the gas quality detection was deuterated carbazole, and the deuteration rate was 75%.

[0053] Example 4

[0054] The preparation steps of deuterated carbazole were repeated in Example 1, except that the amount of deuterated water was replaced by 5 mL, and other conditions remained unchanged. The final experimental results were: deuterated carbazole liquid was obtained, and the gas quality detection was deuterated carbazole, and the deuteration rate was 76%.

[0055] Example 5

[0056] Add 20 mg of carbazole, 3 ml of deuterated water, 25.1 mg of Pt10-Ru1 / Al2O3-400 catalyst into a reaction container, fill with argon gas 1 MPa, react at 70 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, gas quality detection is deuterated carbazole, and the deuteration rate is 80%.

[0057] The preparation process of the Pt10-Ru1 / Al2O3-400 catalyst is to repeat the preparation process of the Pt10-Ru1 / Al2O3-500 catalyst in Example 1, with the only difference being that "in step 1), the heating temperature of the pseudo-boehmite is replaced from 500°C to 400°C", and other conditions remain unchanged, i.e., the finished product Pt10-Ru1 / Al2O3-400 catalyst is obtained.

[0058] Example 6

[0059] Add 20 mg of carbazole, 3 ml of deuterated water, 25.1 mg of Pt10-Ru1 / Al2O3-600 catalyst into a reaction container, fill with argon gas 1 MPa, react at 70 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, gas quality detection is deuterated carbazole, and the deuteration rate is 73%.

[0060] The preparation process of the Pt10-Ru1 / Al2O3-600 catalyst is to repeat the preparation process of the Pt10-Ru1 / Al2O3-500 catalyst in Example 1, with the only difference being that "in step 1), the heating temperature of the pseudo-boehmite is replaced from 500°C to 600°C", and other conditions remain unchanged, i.e., the finished product Pt10-Ru1 / Al2O3-600 catalyst is obtained.

[0061] Example 7

[0062] Add 20 mg of carbazole, 3 ml of deuterated water, 25.1 mg of Pt10-Ru1 / Al2O3-700 catalyst into a reaction container, fill with argon gas 1 MPa, react at 70 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, gas quality detection is deuterated carbazole, and the deuteration rate is 68%.

[0063] The preparation process of the Pt10-Ru1 / Al2O3-700 catalyst is to repeat the preparation process of the Pt10-Ru1 / Al2O3-500 catalyst in Example 1, with the only difference being that "in step 1), the heating temperature of the pseudo-boehmite is replaced from 500°C to 700°C", and other conditions remain unchanged, i.e., the finished product Pt10-Ru1 / Al2O3-700 catalyst is obtained.

[0064] Example 8

[0065] Add 20 mg of carbazole, 3 ml of deuterated water, 25.1 mg of Pt10-Ru1 / Al2O3-800 catalyst into a reaction container, fill with argon gas 1 MPa, react at 70 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, gas quality detection is deuterated carbazole, and the deuteration rate is 54%.

[0066] The preparation process of the Pt10-Ru1 / Al2O3-800 catalyst is to repeat the preparation process of the Pt10-Ru1 / Al2O3-500 catalyst in Example 1, with the only difference being that "in step 1), the heating temperature of the pseudo-boehmite is replaced from 500°C to 800°C", and other conditions remain unchanged, i.e., the finished product Pt10-Ru1 / Al2O3-800 catalyst is obtained.

[0067] Example 9

[0068] Add 20 mg of carbazole, 3 ml of deuterated water, 25.1 mg of Pt10-Ru0.1 / Al2O3-400 catalyst into a reaction container, fill with argon gas 1 MPa, react at 70 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, gas quality detection is deuterated carbazole, and the deuteration rate is 54%.

[0069] The preparation process of Pt10-Ru0.1 / Al2O3-400 catalyst is as follows:

[0070] 1) Using pseudo-boehmite as raw material, the pseudo-boehmite was heated at 400°C for 6 hours to synthesize Al2O3-400.

[0071] 2) 100 mg of the treated Al2O-400 white solid powder was placed in a 100 mL round-bottom flask, and 50 mL of ethylene glycol was added to obtain a mixed solution of Al2O-400 and ethylene glycol, which was fully stirred;

[0072] 3) Prepare 50 ml of Pt 4+ Add 1 mL of chloroplatinic acid solution with an ion concentration of 10 mg / mL to the stirred ethylene glycol mixture prepared in step 2). 3+ 0.01 mL of ruthenium chloride solution with an ion concentration of 10 mg / mL was added dropwise to the stirred ethylene glycol mixture and stirred for 1 h to form a stable Pt10-Ru0.1 ethylene glycol sol;

[0073] 4) adding a 0.1 mol / L NaOH solution dropwise to the stirred ethylene glycol sol in step 3), adjusting the pH to 10 and stirring for 1 hour;

[0074] 5) The reactor was evacuated, inert gas N2 was introduced, heated to 150°C, and stirred for 5 hours. After the reaction, the mixture was filtered, washed, and dried to obtain the finished Pt10-Ru0.1 / Al2O3-400 catalyst.

[0075] Example 10

[0076] Add 20 mg of carbazole, 3 ml of deuterated water, 25.1 mg of Pt10-Ru2 / Al2O3-400 catalyst into a reaction container, fill with argon gas 1 MPa, react at 70 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, gas quality detection is deuterated carbazole, and the deuteration rate is 84%.

[0077] The preparation of the Pt10-Ru2 / Al2O3-400 catalyst was carried out by repeating the preparation process of the Pt10-Ru0.1 / Al2O3-400 catalyst in Example 9, except that in step 3), Ru 3+ The drop volume of the ruthenium chloride solution with an ion concentration of 10 mg / mL was replaced from 0.01 mL to 0.2 mL", and other conditions remained unchanged, and the final product Pt10-Ru2 / Al2O3-400 catalyst was obtained.

[0078] The results of the deuterated detection of the reactant carbazole and the reaction product of Example 10 are as follows: Figure 4-7 As shown. Figure 4 The highest peak of the mass spectrum of standard carbazole before the reaction is 167, indicating that the relative molecular mass of undeuterated carbazole is 167. Figure 5 In the mass spectrum of deuterated carbazole after the reaction, the highest value is 173, indicating that several hydrogen positions are deuterated (it may be exactly 6 or all 8 CH bonds are deuterated), but the specific deuteration effect needs to be combined with NMR hydrogen spectrum analysis. The product is deuterated carbazole. In order to further verify this structure, NMR tests are performed on the reactant carbazole and the reaction product deuterated carbazole, such as Figure 6 As shown in the figure, pure carbazole before the reaction has large peaks between 6-9 and 11-12 on the horizontal axis, which belong to the hydrogen on the benzene ring and the hydrogen on the N position of carbazole, respectively. Figure 7 In the figure, the peaks between 6-9 and 11-12 on the horizontal axis become very small. For comparison, the samples used in the two tests are of the same mass. After the internal standard method test, 1,4-dioxane was used as the internal standard to calculate the deuterated state of deuterated carbazole, and the average deuterated rate was 84%:

[0079]

[0080] In addition, the catalyst recycling experiment was carried out according to the experimental conditions of Example 10, and the operation flow after each reaction was as follows:

[0081] 1. Filter the mixed solution after the reaction to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, and detect and calculate the deuteration rate;

[0082] 2. The upper layer of deuterium water and catalyst suspension was filtered several times to remove organic matter, and the solid catalyst powder was dried in a vacuum drying oven at 70°C. The catalyst powder was then heated at 200°C for 10 minutes in a N2 environment. The catalyst powder finally entered the next cycle catalytic experiment. The catalytic reaction conditions were "20 mg of carbazole, 3 ml of deuterium water, 25.1 mg of Pt10-Ru2 / Al2O3-400 catalyst, filled with argon 1 MPa, and reacted at 70 degrees Celsius for 12 hours".

[0083] According to the above experimental process, the experimental results of the catalyst cycle 8 times are as follows Figure 3 As shown in the figure, it can be seen that after 8 cycles, the deuteration performance of the catalyst dropped from 84% to below 80%, and it still maintained a very high catalytic activity.

[0084] Embodiment 11

[0085] Add 20 mg of carbazole, 3 ml of deuterated water, 25.1 mg of Pt10-Ru0.5 / Al2O3-400 catalyst into a reaction container, fill with argon gas 1 MPa, react at 70 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, gas quality detection is deuterated carbazole, and the deuteration rate is 55%.

[0086] The preparation of Pt10-Ru0.5 / Al2O3-400 catalyst was carried out by repeating the preparation process of Pt10-Ru0.1 / Al2O3-400 catalyst in Example 9, except that in step 3), Ru 3+ The drop volume of the ruthenium chloride solution with an ion concentration of 10 mg / mL was replaced from 0.01 mL to 0.05 mL", and other conditions remained unchanged, and the final product Pt10-Ru0.5 / Al2O3-400 catalyst was obtained.

[0087] Example 12

[0088] Add 20 mg of carbazole, 3 ml of deuterated water, 25.1 mg of Pt10-Ru5 / Al2O3-400 catalyst into a reaction container, fill with argon gas 1 MPa, react at 70 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, gas quality detection is deuterated carbazole, and the deuteration rate is 70%.

[0089] The preparation of Pt10-Ru5 / Al2O3-400 catalyst was carried out by repeating the preparation process of Pt10-Ru0.1 / Al2O3-400 catalyst in Example 9, except that in step 3), Ru 3+The drop volume of the ruthenium chloride solution with an ion concentration of 10 mg / mL was changed from 0.01 mL to 0.5 mL", and other conditions remained unchanged, and the final product Pt10-Ru5 / Al2O3-400 catalyst was obtained.

[0090] In the catalyst of the present invention, the most stable carrier is Al2O3-400, so the catalyst of the present invention is preferably a Pt10RuX (X = 0.1, 0.5, 1, 2, 5) active component loaded on Al2O3-400. The relevant characterization TEM images, electron diffraction patterns and corresponding HRTEM images of the preferred representative catalyst Pt10RuX / Al2O3-400 are as follows: Figure 1 shown. Figure 1 The first row of TEM sub-graphs corresponds to the TEM image results of Pt10Ru0.1 / Al2O3-400, the second row of TEM sub-graphs corresponds to the TEM image results of Pt10Ru0.5 / Al2O3-400, the third row of TEM sub-graphs corresponds to the TEM image results of Pt10Ru1 / Al2O3-400, the fourth row of TEM sub-graphs corresponds to the TEM image results of Pt10Ru2 / Al2O3-400, and the fifth row of TEM sub-graphs corresponds to the TEM image results of Pt10Ru5 / Al2O3-400. The particle size distribution results of Pt10Ru0.1 / Al2O3-400, Pt10Ru0.5 / Al2O3-400, Pt10Ru1 / Al2O3-400, Pt10Ru2 / Al2O3-400, and Pt10Ru5 / Al2O3-400 correspond to: Figure 1 Particle size distribution histograms for the first, second, third, fourth and fifth rows in FIG.

[0091] Figure 1 The characterization results show that the morphology of the PtRuX / Al2O3-400 catalyst carrier prepared by adding different amounts of Ru precursor is basically the same, without obvious aggregation or structural damage. As the amount of Ru added increases, the particle size of the metal particles changes, from about 6 nanometers to about 2 nm. This indicates that as the smaller Ru atoms form a bimetallic alloy with Pt, the alloy particle size is in between the two. The addition of Ru can improve the dispersion of Pt nanoparticles on the alumina carrier in the PtRux / Al2O3-400 catalyst, while the metal nanoparticles of the catalyst with a relatively large Pt / Ru ratio (such as the Pt10Ru0.1 / Al2O3-400 catalyst) show severe aggregation.

[0092] The XRD characterization diagram of the above Pt10RuX (X = 0.1, 0.2, 1, 2 or 5) / Al2O3-400 catalyst is as follows Figure 2As shown, it can be seen that all catalysts show typical γ-Al2O3 (JCPDS29-0063) and a small amount of AlO(OH) (JCPDS 49-0133) characteristic peaks corresponding to the catalyst support. All catalysts only show obvious characteristic diffraction peaks of platinum (JCPDS 04-0802), and no diffraction peaks corresponding to Ru are found in all catalysts, which may be due to their overlap with the Pt diffraction peaks and the low loading of Ru active components. As the content of Ru in PtRu increases, the width of the diffraction peak becomes larger, which indicates that when Ru and Pt form a bimetallic alloy, the lattice constant decreases.

[0093] Embodiment 13

[0094] Add 20 mg of carbazole, 3 ml of deuterated water, 25.1 mg of Pt10-Ru2 / Al2O3-400 catalyst into the reaction container, fill with argon gas 3 MPa, react at 70 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, gas quality detection is deuterated carbazole, and the deuteration rate is 83%.

[0095] The preparation of Pt10-Ru2 / Al2O3-400 catalyst refers to Example 10.

[0096] Embodiment 14

[0097] Add 20 mg of carbazole, 3 ml of deuterated water, 25.1 mg of Pt10-Ru2 / Al2O3-400 catalyst into a reaction container, fill with argon gas 1 MPa, react at 100 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, gas quality detection is deuterated carbazole, and the deuteration rate is 85%.

[0098] The preparation of Pt10-Ru2 / Al2O3-400 catalyst refers to Example 10.

[0099] Embodiment 15

[0100] Add 20 mg of carbazole, 3 ml of deuterated water, 25.1 mg of Pt10-Ru2 / Al2O3-400 catalyst into a reaction container, fill with argon gas 1 MPa, react at 120 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, gas quality detection is deuterated carbazole, and the deuteration rate is 86%.

[0101] The preparation of Pt10-Ru2 / Al2O3-400 catalyst refers to Example 10.

[0102] Example 16

[0103] Add 20 mg of carbazole, 3 ml of deuterated water, 25.1 mg of Pt10-Ru2 / Al2O3-400 catalyst into a reaction container, fill with argon gas 1 MPa, react at 70 degrees Celsius for 24 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, gas quality detection is deuterated carbazole, and the deuteration rate is 88%.

[0104] The preparation of Pt10-Ru2 / Al2O3-400 catalyst refers to Example 10.

[0105] Embodiment 17

[0106] 40 mg of carbazole, 3 ml of deuterated water, 25.1 mg of Pt10-Ru2 / Al2O3-400 catalyst were added to the reaction container, and 1 MPa of argon was filled in. The reaction was carried out at 70 degrees Celsius for 12 hours. The mixed solution was filtered to obtain a mixture of deuterated water and the product, and dichloromethane was added. The lower layer of liquid was collected to obtain the product deuterated carbazole liquid. The gas quality detection showed that it was deuterated carbazole, and the deuteration rate was 82%.

[0107] The preparation of Pt10-Ru2 / Al2O3-400 catalyst refers to Example 10.

[0108] Comparative Example 1

[0109] Add 20 mg of carbazole, 3 ml of deuterated water, 25.1 mg of Ru1 / Al2O3-500 catalyst into the reaction container, fill with argon gas 1 MPa, react at 70 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, and only the carbazole peak is found in the gas chromatography-mass spectrometry, but it is not deuterated carbazole.

[0110] The preparation process of Ru1 / Al2O3-500 catalyst is as follows:

[0111] 1) Using pseudo-boehmite as raw material, the pseudo-boehmite was heated at 500°C for 6 hours to synthesize Al2O3-500.

[0112] 2) Take 100 mg of the treated Al2O3-500 white solid powder and put it into a 100 mL round-bottom flask, add 50 mL of ethylene glycol to obtain a mixed solution of Al2O3-500 and ethylene glycol, and stir well;

[0113] 3) Prepare 50ml of Ru 3+ 0.1 mL of ruthenium chloride solution with an ion concentration of 10 mg / mL was added dropwise to the stirred ethylene glycol mixture prepared above and stirred for 1 h to form a stable Ru1 ethylene glycol sol;

[0114] 4) adding a 0.1 mol / L NaOH solution dropwise to the stirred ethylene glycol sol in step 3), adjusting the pH to 10 and stirring for 1 hour;

[0115] 5) The reactor was evacuated, inert gas N2 was introduced, heated to 150°C, and stirred for 5 hours. After the reaction, the mixture was filtered, washed, and dried to obtain the Ru1 / Al2O3-500 catalyst.

[0116] Comparative Example 2

[0117] Add 20 mg of carbazole, 3 ml of deuterated water, 25.1 mg of Pt10 / Al2O3-400 catalyst into a reaction container, fill with argon gas 1 MPa, react at 70 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, gas quality detection is deuterated carbazole, and the deuteration rate is 55%.

[0118] The preparation process of Pt10 / Al2O3-400 catalyst is as follows:

[0119] 1) Using pseudo-boehmite as raw material, the pseudo-boehmite was heated at 400°C for 6 hours to synthesize Al2O3-400.

[0120] 2) Take 100 mg of the treated Al2O3-400 white solid powder and put it into a 100 mL round-bottom flask, add 50 mL of ethylene glycol to obtain a mixed solution of Al2O3-400 and ethylene glycol, and stir well;

[0121] 3) Prepare 50 ml of Pt 4+ 1 mL of chloroplatinic acid solution with an ion concentration of 10 mg / mL was added dropwise to the stirred ethylene glycol mixture prepared above and stirred for 1 h to form a stable Pt10 ethylene glycol sol;

[0122] 4) Prepare 50 mL of a 0.1 mol / L NaOH solution, add it dropwise to the stirred platinum ion-ethylene glycol sol, adjust the pH to 10, and stir for 1 hour;

[0123] 5) The reactor was evacuated, inert gas N2 was introduced, heated to 150°C, and stirred for 5 hours. After the reaction, the mixture was filtered, washed, and dried to obtain the finished Pt10 / Al2O3-400 catalyst.

[0124] Comparative Example 3

[0125] 20 mg of carbazole, 3 ml of deuterated water, and 25.1 mg of Pt10-Ru2 / Al2O3-400 catalyst were added to a reaction container, 1 MPa of hydrogen was introduced, and the reaction was carried out at 70 degrees Celsius for 4 hours. The mixed liquid was filtered to obtain a mixture of deuterated water and the product, dichloromethane was added, and the lower layer of liquid was collected to obtain the product deuterated carbazole liquid. Gas chromatography-mass spectrometry showed deuterated carbazole and a large amount of hydrogenation by-products. The deuterated carbazole yield was only 12%, and the deuteration rate was 99%.

[0126] The deuteration rate is the average deuteration rate of each hydrogen position of the target deuterated product being replaced by deuterium, and the yield is 12% of the target deuterated product deuterated carbazole according to gas phase analysis, and the rest is the by-product after hydrogenation. Because a large amount of carbazole's benzene ring is hydrogenated, its main ring structure changes, so the yield of deuterated carbazole in comparative example 3 is extremely low.

[0127] The preparation process of the catalyst is as follows:

[0128] 1) Using pseudo-boehmite as raw material, the pseudo-boehmite was heated at 400°C for 6 hours to synthesize Al2O3-400.

[0129] 2) Take 100 mg of the treated Al2O3-400 white solid powder and put it into a 100 mL round-bottom flask, add 50 mL of ethylene glycol to obtain a mixed solution of Al2O3-400 and ethylene glycol, and stir well;

[0130] 3) Prepare 50 ml of Pt 4+ Add 1 mL of chloroplatinic acid solution with an ion concentration of 10 mg / mL to the stirred ethylene glycol mixture prepared above. Prepare 50 mL of Ru 3+ 0.2 mL of ruthenium chloride solution with an ion concentration of 10 mg / mL was added dropwise to the stirred ethylene glycol mixture prepared above and stirred for 1 h to form a stable Pt10-Ru2 ethylene glycol sol;

[0131] 4) adding a 0.1 mol / L NaOH solution dropwise to the stirred ethylene glycol sol in step 3), adjusting the pH to 10 and stirring for 1 hour;

[0132] 5) The reactor was evacuated, inert gas N2 was introduced, heated to 150°C, and stirred for 5 hours. After the reaction, the mixture was filtered, washed, and dried to obtain the finished Pt10-Ru2 / Al2O3-400 catalyst.

[0133] Comparative Example 4

[0134] Add 20 mg of carbazole, 3 ml of deuterated water, and 25.1 mg of Pt10-Ru2 / γ-Al2O3 catalyst into the reaction container, fill with 1 MPa of argon, react at 70 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, and the gas quality detection is deuterated carbazole, and the deuteration rate is 68%.

[0135] The preparation process of Pt10-Ru2 / γ-Al2O3 catalyst is as follows:

[0136] 1) The carrier is commercially available γ-Al2O3 (McLean).

[0137] 2) Take 100 mg of γ-Al2O3 white solid powder and put it into a 100 mL round-bottom flask, add 50 mL of ethylene glycol to obtain a mixed solution of γ-Al2O3 and ethylene glycol, and stir well;

[0138] 3) Prepare 50 ml of Pt 4+ Add 1 mL of chloroplatinic acid solution with an ion concentration of 10 mg / mL to the stirred ethylene glycol mixture prepared above. Prepare 50 mL of Ru 3+ 0.2 mL of ruthenium chloride solution with an ion concentration of 10 mg / mL was added dropwise to the stirred ethylene glycol mixture prepared above and stirred for 1 h to form a stable Pt10-Ru2 ethylene glycol sol;

[0139] 4) adding a 0.1 mol / L NaOH solution dropwise to the stirred ethylene glycol sol in step 3), adjusting the pH to 10 and stirring for 1 hour;

[0140] 5) The reactor was evacuated, inert gas N2 was introduced, heated to 150°C, and stirred for 5 hours. After the reaction, the product was filtered, washed, and dried to obtain the finished Pt10-Ru2 / γ-Al2O3 catalyst.

[0141] Comparative Example 5

[0142] Add 20 mg of carbazole, 3 ml of deuterated water, and 25.1 mg of Pt10-Ru2 / Al2O3-400 (sodium borohydride reduction) catalyst into the reaction container, fill with 1 MPa of argon, react at 70 degrees Celsius for 12 hours, filter the mixed solution to obtain a mixture of deuterated water and the product, add dichloromethane, collect the lower layer of liquid to obtain the product deuterated carbazole liquid, and the gas quality detection is deuterated carbazole, and the deuteration rate is 53%.

[0143] The preparation process of Pt10-Ru2 / Al2O3-400 (sodium borohydride reduction) catalyst is as follows:

[0144] 1) Using pseudo-boehmite as raw material, the pseudo-boehmite was heated at 400°C for 6 hours to synthesize Al2O3-400;

[0145] 2) Take 100 mg of the treated Al2O3-400 white solid powder and put it into a 100 mL beaker, add 50 mL of deionized water to obtain a mixture of Al2O3-400 and deionized water, and stir well;

[0146] 3) Prepare 50 ml of Pt 4+ Add 1 mL of chloroplatinic acid solution with an ion concentration of 10 mg / mL to the stirred ethylene glycol mixture prepared in step 2). 3+ Add 0.2 mL of ruthenium chloride solution with an ion concentration of 10 mg / mL to the stirred ethylene glycol mixture and stir for 1 h;

[0147] 4) 0.25 mL of 180 mM sodium borohydride (NaBH4) was slowly added, and the solution was stirred for 2 hours. The nanoparticle solution was centrifuged at 10,000 rpm for 15 minutes to remove unreacted reactants.

[0148] 5) After completion, the product is filtered, washed and dried to obtain the finished Pt10-Ru2 / Al2O3-400 (sodium borohydride reduction) catalyst.

[0149] In the above embodiments and comparative examples, except for the different gas conditions, other conditions are the same, and a consistent conclusion can be obtained: under hydrogen conditions, the deuteration reaction is faster, and a very high deuteration rate can be achieved within the reaction time, but there is also a huge disadvantage, that is, the yield of the reactant is very low, because under hydrogen conditions, hydrogen will participate in the reaction, and side reactions such as N-heterocyclic hydrogenation will occur, which is difficult to avoid, and is extremely harmful to both product purity and process economic effects. On the contrary, in the method proposed in this patent, the occurrence of side reactions can be avoided to a great extent. To achieve a high yield, it is only necessary to optimize the separation process, and the deuteration rate can be improved by extending the reaction time, which is also an advantage of this method.

[0150] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described examples are described. 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.

[0151] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A method for preparing deuterated carbazole under hydrogen-free conditions, characterized in that: The method comprises the following process: mixing carbazole, a catalyst and deuterated water, heating and reacting in an inert gas environment, the reaction temperature being 70°C to 140°C, the reaction time being 12-48 hours, filtering the mixed solution after the reaction is completed to obtain a mixture of deuterated water and a product, adding an organic extractant to extract and separate the liquids, and collecting the organic phase to obtain the product deuterated carbazole; wherein the catalyst uses gamma-type alumina as a carrier, the active component is a noble metal alloy Pt-Ru, the mass of the noble metal Pt is 1-30% of the mass of the alumina, and the mass ratio of Pt to Ru is 1:0.01-0.

5.

2. The method for preparing deuterated carbazole under hydrogen-free conditions according to claim 1, characterized in that: The mass of the precious metal Pt is 8-12% of the mass of the aluminum oxide, preferably 10%, and the mass ratio of Pt to Ru is 1:0.1-0.

2.

3. The method for preparing deuterated carbazole under hydrogen-free conditions according to claim 1, characterized in that: The preparation method of the catalyst comprises the following steps: 1) Using pseudo-boehmite as a raw material, heating the pseudo-boehmite at 300° C.-800° C. for 4-8 hours to obtain gamma-type alumina powder; 2) adding the alumina powder of step 1) into ethylene glycol and stirring the mixture to form a stable colloidal solution containing alumina; 3) Add the Pt source solution and the Ru source solution dropwise to the colloidal solution obtained in step 2) in sequence, add alkali to adjust the pH to 10±0.5, and stir thoroughly at room temperature; 4) The mixed solution obtained in step 3) is fully stirred at a heating temperature of 80-160° C. for 3-6 hours under inert gas conditions, and then filtered, washed and dried to obtain the catalyst.

4. The method for preparing deuterated carbazole under hydrogen-free conditions according to claim 3, characterized in that: In step 1), the heating temperature is 400-500° C. and the heating time is 5-6 hours.

5. The method for preparing deuterated carbazole under hydrogen-free conditions according to claim 3, characterized in that: In step 2), the feed ratio of ethylene glycol to alumina solid powder is 0.1-1 ml:1 mg, preferably 0.4-0.5 ml:1 mg.

6. The method for preparing deuterated carbazole under hydrogen-free conditions according to claim 3, characterized in that: In step 4), the heating temperature is 140-150° C. and the stirring time is 4-5 h.

7. The method for preparing deuterated carbazole under hydrogen-free conditions according to claim 1, characterized in that: The inert gas environment is argon, the reaction temperature is 70° C. to 100° C., and the reaction time is 12 to 24 hours.

8. The method for preparing deuterated carbazole under hydrogen-free conditions according to claim 1, characterized in that: The mass ratio of the catalyst to the carbazole is 0.5-1.3:1, and the mass volume ratio of the carbazole to the deuterated water is 1 mg: 0.1-0.4 mL, preferably 1 mg: 0.15-0.2 mL.

9. The method for preparing deuterated carbazole under hydrogen-free conditions according to claim 1, characterized in that: The chemical formula of the product deuterated carbazole is:

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