Method for producing deuterated aromatic compounds by using bubble tower reactor

Abstract

The invention discloses a method for producing a deuterated aromatic compound by using a bubble tower reactor. The method comprises the following steps: S1, preheating heavy water to obtain heavy water vapor; s2, introducing the heavy water vapor into a bubble tower reactor filled with an organic acid catalyst and an aromatic compound, and carrying out hydrogen-deuterium exchange reaction; and S3, separating the reaction mixture obtained by the hydrogen-deuterium exchange reaction to obtain the organic acid catalyst and the deuterated aromatic compound, returning the organic acid catalyst and the deuterated aromatic compound to the bubble tower reactor for continuous reaction, and after the reaction is completed, carrying out post-treatment to obtain the deuterated aromatic compound. The method is high in yield, high in deuteration degree, free of waste acid and suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of deuterated compound production, specifically relating to a method for producing deuterated aromatic compounds using a bubble column reactor. Background Technology

[0002] Deuterium (D) is a stable isotope of hydrogen, with two neutrons and one proton in its nucleus. Deuterated compounds are those in which some or all of the CH bonds are replaced by CD bonds. Because deuterium has one more neutron than hydrogen, the CD bond has a lower zero-point vibrational energy (1.2–1.5 kcal / mol), but its activation energy in the transition state remains essentially unchanged. Therefore, breaking the CD bond requires more energy, leading to improved stability when deuterium is introduced into the active site of the compound. In the field of materials science, the OLED (Organic Light-Emitting Diode) emissive layer mainly consists of a mixture of red, green, and blue light-emitting materials to produce white light. Blue light photons have the highest energy and therefore the shortest lifetime. Research has found that in OLED matrix materials, hydrogen / deuterium exchange in unstable heterocyclic carbon-hydrogen bonds can extend the device's lifetime without significantly altering other chemical properties. Furthermore, introducing deuterium atoms into blue light-emitting materials enhances the spin-orbit coupling of luminescent molecules, thereby improving phosphorescence generation and quantum efficiency. Replacing the CH bonds in the main structure of organic light-emitting materials with CD bonds allows OLED substrates to withstand significantly higher currents than non-deuterated materials, potentially extending the lifetime of OLED devices by 5-20 times. In the life sciences, the labeling effect of deuterated compounds, combined with tandem mass spectrometry, enables the study of the absorption, distribution, metabolism, and excretion (ADME) processes of drug molecules in vivo. Moreover, the deuteration kinetic isotope effect introduced by deuterium can alter the pharmacokinetics and metabolic pathways of drug molecules, thereby facilitating the improvement and development of new drugs.

[0003] Direct conversion of inactive carbon-hydrogen bonds is an efficient and clean method for preparing functional materials. Although the synthesis of deuterated aromatic derivatives has been extensively developed, the direct deuteration-hydrogen exchange reaction of aromatics is still limited by substrate versatility. Existing techniques often use D2O as the deuterium source and employ carbon-supported catalysts (Pd / C, Pt / C, Rh / C, Ru / C, etc.) to achieve deuteration with aromatics. For example, Chinese patents CN113979822A, CN118271146A, and CN105198685A use benzene compounds or benzene and heavy water to achieve hydrogen-deuterium exchange reactions under the action of carbon-supported noble metal catalysts. However, this technical route suffers from problems such as slow deuteration rate, low degree of deuteration, and low isotope utilization. Chinese patent CN114560748A discloses a process for producing deuterated benzene. Under carbon-supported noble metal catalysis, deuterated sulfuric acid reacts with benzene via a HD exchange reaction to produce deuterated benzene. This patented method generates a large amount of low-deuterated waste acid during the reaction, causing significant environmental pressure and direct loss of deuterium resources. Furthermore, sulfuric acid and benzene readily undergo aromatic sulfonation under the reaction conditions, generating benzenesulfonic acid byproducts. This side reaction is significantly aggravated by increasing reaction temperature and / or system acidity, leading to a substantial decrease in the main reaction yield of the target deuterated aromatic hydrocarbon, making product purification difficult, and severely impacting the process's economics. Existing technologies employ multi-reactor iterative techniques, requiring multiple material transfers, resulting in cumbersome processes, reduced material yields, and intermittent operation that hinders continuous improvement in production efficiency.

[0004] In summary, existing direct HD exchange technologies for aromatics based on carbon-supported noble metal catalysis and heavy water / acidic deuterium sources have significant shortcomings in terms of reaction efficiency, degree of deuteration, deuterium utilization, product selectivity, and environmental impact, which restricts their industrial application in the large-scale, highly selective synthesis of highly deuterated aromatic compounds. There is an urgent need to develop novel catalytic HD exchange methods that are more efficient, highly selective, environmentally friendly, and have better deuterium atom economy. Summary of the Invention

[0005] The purpose of this invention is to provide a method for the industrial production of deuterated aromatic compounds with high yield, high degree of deuteration, no waste acid generation, and suitability for industrial production.

[0006] To solve the above-mentioned technical problems, the technical solution of the present invention is as follows:

[0007] A method for producing deuterated aromatic compounds using a bubble column reactor includes the following steps:

[0008] Step S1: Preheat the heavy water to obtain superheated heavy water steam;

[0009] Step S2: Superheated heavy water steam is passed into a bubble column reactor containing organic acid catalysts and aromatic compounds to carry out a hydrogen-deuterium exchange reaction;

[0010] Step S3: The reaction mixture obtained from the hydrogen-deuterium exchange reaction is separated to obtain an organic acid catalyst and a deuterated aromatic compound, which are then returned to the bubble column reactor to continue the reaction. After the reaction is completed, post-processing is performed to obtain the deuterated aromatic compound.

[0011] In step S2, the aromatic compounds are represented by formulas 1 to 5:

[0012] , , , , ;

[0013] Where m1 is 1-10, n1 is 0-9, and m1 and n1 satisfy m1+n1=10; m2 is 1-8, n2 is 0-7, and m2 and n2 satisfy m2+n2=8; m3 is 1-10, n3 is 0-9, and m3 and n3 satisfy m3+n3=10; m4 is 1-6, n4 is 0-5, and m4 and n4 satisfy m4+n4=6; m5 is 1-8, n5 is 0-7, and m5 and n5 satisfy m5+n5=8; X1 is selected from single bond, CH2, C(CH3)2, O, S; X2 is selected from CH2, C(CH3)2, O, S, NH, NCH3, N(C6H5); X3 is selected from CH2, C(CH3)2, O, S, NH, NCH3, N(C6H5);

[0014] In Formulas 1 to 5, R1, R2, R3, R4, and R5 are substituents that do not contain deuterium atoms, and are each independently selected from halogens, substituted or unsubstituted (C1-C6) alkyl groups, substituted or unsubstituted (C1-C6) alkoxy groups, substituted or unsubstituted (C1-C6) alkoxycarbonyl groups, substituted or unsubstituted (C1-C6) alkanoyloxy groups, substituted or unsubstituted (C3-C6) cycloalkyl groups, preferably methyl, ethyl, methoxy, or ethoxy groups;

[0015] The substituents on the (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) alkoxycarbonyl, (C1-C6) alkanoyloxy, and (C3-C6) cycloalkyl groups are halogens;

[0016] In this process, the hydrogen-deuterium exchange reaction occurs on the hydrogen atom on the aromatic ring;

[0017] The organic acid catalyst is one or both of organic sulfonic acids or organic alkyl acids.

[0018] Step S1 is the preheating stage, and the process is as follows:

[0019] The heavy water from the heavy water storage tank is continuously pumped to the material inlet of the vaporization reactor via a heavy water feed pump. After initial mixing and vaporization in the vaporization reactor, the water enters the bottom gaseous material inlet of the shell-and-tube heat exchanger from the top gaseous material outlet of the vaporization reactor for further heating and vaporization, transforming into superheated heavy water steam.

[0020] Further, in step S1, the heavy water in the heavy water storage tank is continuously transported to the shell-side inlet at the bottom of the heat exchanger by a heavy water feed pump. After exchanging gas and liquid with the hot steam in the heat exchanger, it flows out from the shell-side outlet at the top of the heat exchanger and then enters the material inlet of the vaporization kettle.

[0021] Step S2 is the bubbling tower reaction section, and the process is as follows:

[0022] Superheated heavy water vapor overflows from the top gas phase outlet of the tube heat exchanger and enters the bottom inlet of the bubble column reactor. It then comes into contact with the organic acid catalyst and aromatic compounds packed inside the bubble column reactor to carry out the hydrogen-deuterium exchange reaction.

[0023] In step S2, the aromatic compound is further preferably one of biphenyl, diphenylmethane, naphthalene, anthracene, benzofuran, benzothiophene, indole, fluorene, dibenzofuran, dibenzothiophene, and carbazole;

[0024] In step S2, the organic acid catalyst is preferably one or more of methanesulfonic acid, butylsulfonic acid, trifluoromethanesulfonic acid, perfluorobenzenesulfonic acid, perfluorobutylsulfonic acid, perfluorooctylsulfonic acid, perfluorooctanoic acid, and perfluoroheptanoic acid, and more preferably one or more of methanesulfonic acid, butylsulfonic acid, and trifluoromethanesulfonic acid.

[0025] In step S2, the residence time t0 of the superheated heavy water vapor in the bubble column reactor is 3 to 300 seconds, preferably 3 to 120 seconds.

[0026] In step S2, the loading amount of aromatic compounds in the bubble column reactor is defined as X, the relative molecular mass of the aromatic compounds is M1, the number of hydrogen atoms in the aromatic ring of the molecule is a, the loading amount of organic sulfonic acid in the bubble column is defined as Y1, the loading amount of organic alkyl acid is defined as Y2, the relative molecular mass of the organic acid catalyst is M2, and the loading amounts of the aromatic compounds and the organic acid catalyst satisfy the following relationship: or ;

[0027] In step S2, the feed flow rate of the heavy water is defined as Z, its relative molecular mass is M3, and the total time of the hydrogen-deuterium exchange reaction is defined as t. Then, the total feed amount of heavy water and the loading amounts of aromatic compounds and organic acid catalysts satisfy the following relationship: or Preferably, or .

[0028] Furthermore, in step S2, an organic solvent may be added, wherein the organic solvent is selected from o-dichlorobenzene, p-dichlorobenzene, 2,6-dichlorotoluene, 1,2,4-trichlorobenzene, 2,4,6-trichlorotoluene, or decahydronaphthalene; the amount of the organic solvent added is defined as V0, and the amount V0 satisfies the following relationship: 0.1X ≤ V0 ≤ 10.0X.

[0029] Step S3 is the post-processing section, and the process is as follows:

[0030] Deuterium-containing water overflows from the top vapor outlet of the bubble column reactor and enters the distillation column. The heavy organic acid components separated by distillation flow back to the bubble column reactor from the lower side outlet of the distillation column. The light component deuterium-containing water enters the heat exchanger from the upper light component material outlet of the distillation column. After condensation, the light component material flows out from the bottom of the heat exchanger. Part of the material flows back to the top reflux port of the distillation column, and part of the material is sent to the upper liquid phase material inlet of the receiving tank. Then, it enters the separation tank for settling and separation. The deuterium-containing water phase is sent to the deuterium-containing water storage tank, and the phase containing deuterated aromatic compounds is sent to the deuterated aromatic compounds storage tank. The deuterated aromatic compounds in the deuterated aromatic compounds storage tank flow back to the bubble column reactor to continue the hydrogen-deuterium exchange reaction, continuously increasing the deuteration degree until the reaction is completed. After separation and purification, qualified deuterated aromatic compounds are obtained.

[0031] In step S3, the distillation column has 10-20 theoretical plates and a reflux ratio of 0.2-2.0:1.

[0032] In step S3, the specific post-processing operation includes cooling the bubble column reactor to a predetermined temperature, allowing it to stand and separate into layers to obtain the deuterated product phase and the high-deuterium organic acid phase, which are then discharged from the bottom outlet of the bubble column reactor.

[0033] Furthermore, if the deuterated product phase contains organic solvent, the deuterated product phase is transferred to a crystallization vessel for separation. After heating and cooling and filtration, a crude filter cake of deuterated aromatic compounds is obtained. If the deuterated product phase does not contain organic solvent, the crude product is directly purified.

[0034] Further, the crude deuterated aromatic compound is purified to obtain a refined deuterated aromatic compound; the purification process is selected from recrystallization or distillation; wherein, the recrystallization purification process includes contacting and mixing the crude deuterated aromatic compound with an organic solvent, and then sequentially filtering, washing, drying, and recrystallizing to obtain the refined deuterated aromatic compound; the distillation purification process includes transferring the crude deuterated aromatic compound to a distillation column and distilling it under atmospheric or reduced pressure to obtain the refined deuterated aromatic compound.

[0035] In step S3, the organic solvent includes any one, two, or three of n-hexane, cyclohexane, and ethyl acetate.

[0036] In step S3, the recrystallization solvent includes any one or both of chlorobenzene and dichlorobenzene.

[0037] The atmospheric boiling point of the sulfonic acid monohydrate or organic alkyl acid catalyst of the organic catalyst is A℃, and the atmospheric boiling point of the aromatic compound is B℃. The operating temperature C℃ of the vaporization vessel in step S1 satisfies the following relationship: 140≤C≤160<A. The operating temperature D℃ of the shell-and-tube heat exchanger in step S2 satisfies the following relationship: C+10≤D≤C+60≤A≤B. The operating temperature E℃ of the bubble column reactor in step S2 satisfies the following relationship: C+10≤E≤C+60≤A≤B, and 2≤DE≤10. The operating temperature F℃ of the top of the distillation column in step S3 satisfies the following relationship: 95≤F≤105.

[0038] As a preferred option, the deuterium-rich water collected in the deuterium-rich water storage tank can continue to serve as a deuterium source for the next batch of hydrogen-deuterium exchange reactions.

[0039] Compared with the prior art, the beneficial effects of the present invention are reflected in:

[0040] (1) This invention constructs a highly efficient gas-liquid isotope exchange system with heavy water as the core deuterium source. Through a high-temperature vaporization process, efficient gas-liquid hydrogen-deuterium exchange is achieved, which greatly enhances the mass transfer kinetics of deuterium isotopes from the gas phase (heavy water vapor) to the liquid phase (reaction substrate). This technical solution successfully overcomes the inherent limitations of slow reaction rate and kinetic lag in traditional liquid-phase exchange, achieves a significant leap in isotope exchange efficiency per unit time of deuteration reaction, and greatly shortens the process time required for the reaction to reach a high deuteration rate, providing key technical support for the industrial-scale, continuous preparation of deuterated products;

[0041] (2) This invention ingeniously utilizes the characteristic that the catalyst and product are easily separated after the reaction system is cooled, thus achieving efficient and low-loss separation of the catalyst and product. Specifically, after the deuteration reaction is completed, liquid-liquid phase separation between the deuterated product phase and the organic acid phase acting as the catalyst can be achieved through a simple cooling operation. This not only achieves efficient recovery of the catalyst but also simultaneously obtains high-value-added by-product deuterated organic acids. For the purification of the target deuterated product in the deuterated product phase, high-purity, high-deuteration target products can be obtained simply through phase regulation and recrystallization operations. This fundamentally avoids the cumbersome separation steps of traditional processes, simplifies the subsequent separation and purification process, reduces process steps, and lowers energy consumption and material loss. At the same time, it effectively avoids product degradation or isotope reverse exchange that may occur during the separation process, thereby simplifying the separation steps, reducing operating costs, and improving product stability in the overall process.

[0042] (3) This invention innovatively uses low-cost, readily available non-deuterated organic acids as catalysts, breaking through the economic bottleneck of using expensive deuterated catalysts (such as deuterated acids) and significantly reducing the raw material cost and usage threshold of catalysts. More importantly, during the catalytic cycle, the catalyst molecules themselves undergo reversible hydrogen-deuterium exchange with the heavy water deuterium source, converting it into high-value-added deuterated organic acid byproducts. This process realizes the multi-stage, stepwise utilization of deuterium atoms from heavy water to catalysts and then to the final products, greatly improving the atom economy of expensive deuterium sources (D2O). Ultimately, this technical solution transforms the traditional "catalyst consumption cost" into "high-value deuterated byproduct revenue," thereby maximizing the utilization of deuterium source value as a whole and forming a circular process mode that combines economy and atom efficiency. Attached Figure Description

[0043] Figure 1 This is a schematic diagram of the method for producing deuterated aromatic compounds using a bubble column reactor according to the present invention. In the diagram: 1 Heavy water storage tank; 2 Heavy water feed pump; 3 Vaporization vessel; 4 Shell and tube heat exchanger; 5 Bubble column reactor; 6 Distillation column; 7 Heat exchanger; 8 Receiving tank; 9 Layered tank; 10 Low-deuterium water storage tank; 11 Deuterated aromatic compound storage tank. Detailed Implementation

[0044] The technical solution of the present invention will be further described in detail below through specific embodiments.

[0045] Unless otherwise specified, the raw materials and equipment used in this invention can be purchased from the market or are commonly used in the field.

[0046] Unless otherwise specified, the methods described in the following embodiments are conventional methods in the art.

[0047] Example 1:

[0048] Step S1 Preheating Section: 1200g anthracene, 7200g decahydronaphthalene, and 336.82g trifluoromethanesulfonic acid are added to the bubble column reactor. The heating systems of the vaporization kettle, the shell and tube heat exchanger, and the bubble column reactor are turned on, and the operating temperatures are set to 160℃, 200℃, and 200℃, respectively. The heavy water in the heavy water storage tank 1 is continuously pumped to the material inlet of the vaporization kettle 3 through the heavy water feed pump 2 at a rate of 226.60g / h. After preliminary mixing and vaporization in the vaporization kettle 3, the vaporized water enters the bottom gaseous material inlet of the shell and tube heat exchanger 4 from the top gaseous material outlet of the vaporization kettle 3 for further heating and vaporization, and is converted into superheated heavy water steam.

[0049] Step S2 Bubble Tower Reaction Section: Superheated heavy water vapor overflows from the top gas phase outlet of the tube heat exchanger 4 and enters the bottom inlet of the bubble tower reactor 5. The superheated heavy water vapor rapidly passes through the bubble tower reactor 5 to carry out the hydrogen-deuterium exchange reaction, with a retention time of 20s.

[0050] Post-processing section (S3): Deuterium-rich water overflows from the top vapor outlet of the bubble column reactor 5 and enters the distillation column 6. The heavy organic acid components separated by distillation flow back to the bubble column reactor 5 from the lower side outlet of the distillation column 6. The light components flow from the upper light component outlet of the distillation column 6 into the heat exchanger 7. After condensation, the light component flows out from the bottom of the heat exchanger 7. Part of the material flows back to the top reflux port of the distillation column 6, and the other part is sent to the upper liquid inlet of the receiving tank 8. Then, it enters the stratification tank 9 for settling and stratification. The deuterium-rich water phase is then sent to the deuterium-rich water storage tank 10. The deuterated anthracene phase is transported to the deuterated aromatic compounds storage tank 11. The deuterated anthracene is then refluxed into the bubble column reactor 5 to continue the hydrogen-deuterium exchange reaction. After 27.50 hours of reaction, a sample is taken for testing. The deuteration degree of anthracene-d10 is >99.0%, indicating the end of the reaction. The bubble column reactor 5 is then cooled to 60°C and allowed to stand for stratification. The lower liquid phase, containing the byproduct deuterated trifluoromethanesulfonic acid, is discharged through the bottom outlet of the column. The upper liquid phase, containing the organic phase of anthracene-d10, is transferred from the bottom outlet of the bubble column to the crystallization vessel for separation. After heating, cooling, and filtration, the crude anthracene-d10 product is separated as a filter cake.

[0051] 2500 mL of cyclohexane organic solvent was added to the crude product, and the mixture was filtered, washed, dried, and recrystallized from chlorobenzene to obtain 1176.46 g of anthracene-d10 with a deuteration degree of 99.11%, a molar yield of 92.8%, and a purity of >99%.

[0052] Example 2

[0053] This embodiment is basically the same as Embodiment 1, except that: the aromatic compounds in the reaction system are replaced with benzofuran, and the amount added is 6000g; the flow rate of the heavy water feed pump is 307.96g / h; no organic solvent is added; the amount of acid catalyst added is 2540.71g; the operating temperatures of the vaporization kettle, the tubular heat exchanger, and the bubble column reactor are 150℃, 160℃, and 160℃, respectively; the retention time of hydrogen-deuterium exchange in the bubble column reaction section is 15s; after a reaction time of 91.92h, a sample is taken for testing, and the degree of deuteration of benzofuran-d6 is >99.0%. The reaction is then completed. The bubble column reactor 5 is cooled to 20℃ and allowed to stand for stratification. The lower organic acid phase and the upper benzofuran-d6 phase are discharged sequentially from the outlet of the bubble column reactor.

[0054] Example 3

[0055] This embodiment is basically the same as Embodiment 1, except that: the aromatic compounds in the reaction system are replaced with diphenylmethane, and the amount added is 7200g; the flow rate of the heavy water feed pump is 302.79g / h; no organic solvent is added; the acid catalyst is replaced with methanesulfonic acid, and the amount added is 881.52g; the operating temperatures of the vaporization kettle, the tubular heat exchanger, and the bubble column reactor are 150℃, 200℃, and 200℃, respectively; and the hydrogen-deuterium crosslinking in the bubble column reaction section is... The retention time was 13 s, and the reaction time was 109.58 h. After sampling and testing, the deuteration degree of diphenylmethane-d10 was >99.0%, and the reaction was completed. The bubble column reactor 5 was cooled to 40 °C and allowed to stand for stratification. The lower organic acid phase and the upper diphenylmethane-d10 phase were discharged sequentially from the bottom outlet of the bubble column reactor. The crude diphenylmethane-d10 was transferred to a distillation column and distilled under reduced pressure to obtain the refined diphenylmethane-d10.

[0056] Example 4

[0057] This embodiment is basically the same as Embodiment 1, except that: the aromatic compounds in the reaction system are replaced with naphthalene, and the amount added is 6000g; the flow rate of the heavy water feed pump is 285.03g / h; the acid catalyst is replaced with perfluorooctanoic acid, and the amount added is 3876.76g; no organic solvent is added; the operating temperatures of the vaporization kettle, the tubular heat exchanger, and the bubble column reactor are 160℃, 180℃, and 180℃, respectively; the retention time of hydrogen-deuterium exchange in the bubble column reaction section is 16s; after a reaction time of 110.53h, a sample is taken for testing; the deuteration degree of naphthalene-d8 is >99.0%; the reaction is completed; the bubble column reactor 5 is cooled to 80℃ and allowed to stand for stratification; the lower organic acid phase and the upper naphthalene-d8-containing phase are discharged sequentially from the outlet of the bubble column reactor; the upper naphthalene-d8-containing phase is transferred to the crystallization kettle; after heating and cooling and filtration, the crude naphthalene-d8 product is separated as a filter cake.

[0058] Example 5

[0059] This embodiment is basically the same as Embodiment 1, except that: the aromatic compound in the reaction system is replaced with dibenzothiophene, and the amount added is 4800g; the flow rate of the heavy water feed pump is 314.82g / h; the acid catalyst is replaced with butylsulfonic acid, and the amount added is 899.97g; the organic solvent is replaced with 2,6-dichlorotoluene, and the amount added is 2400g; and the operating temperatures of the vaporization kettle, the tubular heat exchanger, and the bubble column reactor are 160℃, 180℃, and 180℃, respectively. The retention time for hydrogen-deuterium exchange in the bubbling tower reaction section was 13 s. After a reaction time of 60.91 h, samples were taken for testing. The degree of deuteration of dibenzothiophene-d8 was >99.0%, and the reaction was completed. The bubbling tower reactor 5 was cooled to 60 °C and allowed to stand for stratification. The lower organic acid phase and the upper phase containing dibenzothiophene-d8 were discharged sequentially from the outlet of the bubbling tower reactor. The upper phase containing dibenzothiophene-d8 was transferred to the crystallization vessel. After heating, cooling, and filtration, the crude dibenzothiophene-d8 was separated as a filter cake.

[0060] Example 6

[0061] This embodiment is basically the same as Embodiment 1, except that: the aromatic compounds in the reaction system are replaced with carbazole, and the amount added is 2400g; the amount of acid catalyst added is 1347.29g; the flow rate of the heavy water feed pump is 214.91g / h; the retention time of hydrogen-deuterium exchange in the bubbling tower reaction section is 25s; and after a reaction time of 50.57h, a sample is taken for testing. The deuteration degree of carbazole-d8 is >99.0%, and the reaction is completed. The bubbling tower reactor 5 is cooled to 60℃ and allowed to stand for stratification. The lower organic acid phase and the upper carbazole-d8-containing phase are discharged sequentially from the outlet of the bubbling tower reactor. The upper carbazole-d8-containing phase is transferred to the crystallization kettle. After heating, cooling, and filtration, the crude carbazole-d8 product is separated as a filter cake.

[0062] Example 7

[0063] This embodiment is basically the same as Embodiment 1, except that: the flow rate of the heavy water feed pump in the reaction system of this embodiment is 151.06 g / h, the retention time of hydrogen-deuterium exchange in the bubbling tower reaction section is 30 s, and after the reaction time is 41.24 h, a sample is taken for testing. The deuteration degree of anthracene-d10 is >99.0%, and the reaction ends. The bubbling tower reactor 5 is cooled to 60°C and allowed to stand for stratification. The lower organic acid phase and the upper anthracene-d10-containing phase are discharged sequentially from the outlet of the bubbling tower reactor. The upper anthracene-d10-containing phase is transferred to the crystallization kettle. After heating, cooling, and filtration, the crude anthracene-d10 product is separated as a filter cake.

[0064] Example 8

[0065] This embodiment is basically the same as Embodiment 1, except that: the flow rate of the heavy water feed pump in the reaction system of this embodiment is 302.13 g / h, the retention time of hydrogen-deuterium exchange in the bubbling tower reaction section is 15 s, and after the reaction time is 20.62 h, a sample is taken for testing. The deuteration degree of anthracene-d10 is >99.0%, the reaction ends, the bubbling tower reactor 5 is cooled to 60°C, and allowed to stand for stratification. The lower organic acid phase and the upper anthracene-d10-containing phase are discharged from the outlet of the bubbling tower reactor in sequence. The upper anthracene-d10-containing phase is transferred to the crystallization kettle. After heating and cooling and filtration, the crude anthracene-d10 product is separated as a filter cake.

[0066] Comparative Example 1

[0067] This comparative example is basically the same as Example 1, except that: the flow rate of the heavy water feed pump is 226.60 g / h; the acid catalyst in the reaction system of this comparative example is replaced with 58% concentrated sulfuric acid, and the amount added is 380.00 g; the operating temperatures of the vaporization kettle, the shell and tube heat exchanger, and the bubble column reactor are 120℃, 160℃, and 160℃, respectively; the retention time of hydrogen-deuterium exchange in the reaction section of the bubble column is 18 s; and the reaction time is 7.86 h.

[0068] The process parameters and reaction data of the hydrogen-deuterium exchange reaction in Examples 2 to Comparative Example 1 are summarized in Table 1.

[0069] Table 1

[0070]

[0071] a These refer to the operating temperatures of the vaporization kettle, the shell-and-tube heat exchanger, and the bubble column reactor, respectively.

[0072] According to the data in Comparative Example 1 in Table 1, when 58% concentrated sulfuric acid is used as the acid catalyst, an aromatic ring sulfonation side reaction readily occurs between sulfuric acid and the substrate anthracene under these reaction conditions, generating byproducts such as anthracene sulfonic acid. The degree of this side reaction increases significantly with increasing reaction temperature. Obvious sulfonation byproducts can be observed after 7.86 hours of reaction, and the color of the reaction system gradually darkens to black, forcing the hydrogen-deuterium exchange reaction to stop. Ultimately, this results in a significant decrease in the degree of deuteration and yield of the target product.

[0073] The above embodiments are merely preferred embodiments of the present invention and are not intended to limit the invention in any way. Other variations and modifications are possible without departing from the scope of the claims. The bubble column reactor used in the embodiments, with its specifications (inner diameter 210 mm, column height 400 mm), is only a specific implementation reference. Those skilled in the art should understand that when applying the present invention to reactors of different sizes, parameters such as feed rate and residence time need to be adjusted proportionally according to the reactor size.

Claims

1. A method for producing deuterated aromatic compounds using a bubble column reactor, characterized in that, Includes the following steps: Step S1: Preheat the heavy water to obtain superheated heavy water steam; Step S2: Superheated heavy water steam is passed into a bubble column reactor containing organic acid catalysts and aromatic compounds to carry out a hydrogen-deuterium exchange reaction; Step S3: The reaction mixture obtained from the hydrogen-deuterium exchange reaction is separated to obtain an organic acid catalyst and a deuterated aromatic compound, which are then returned to the bubble column reactor to continue the reaction. After the reaction is completed, post-processing is performed to obtain the deuterated aromatic compound. In step S2, the aromatic compounds are represented by formulas 1 to 5: 、 、 、 、 ； Where m1 is 1-10, n1 is 0-9, and m1 and n1 satisfy m1+n1=10; m2 is 1-8, n2 is 0-7, and m2 and n2 satisfy m2+n2=8; m3 is 1-10, n3 is 0-9, and m3 and n3 satisfy m3+n3=10; m4 is 1-6, n4 is 0-5, and m4 and n4 satisfy m4+n4=6; m5 is 1-8, n5 is 0-7, and m5 and n5 satisfy m5+n5=8; X1 is selected from single bond, CH2, C(CH3)2, O, S; X2 is selected from CH2, C(CH3)2, O, S, NH, NCH3, N(C6H5); X3 is selected from CH2, C(CH3)2, O, S, NH, NCH3, N(C6H5); In Formulas 1 to 5, R1, R2, R3, R4, and R5 are substituents that do not contain deuterium atoms, and are each independently selected from halogens, substituted or unsubstituted (C1-C6) alkyl groups, substituted or unsubstituted (C1-C6) alkoxy groups, substituted or unsubstituted (C1-C6) alkoxycarbonyl groups, substituted or unsubstituted (C1-C6) alkanoyloxy groups, and substituted or unsubstituted (C3-C6) cycloalkyl groups. The substituents on the (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) alkoxycarbonyl, (C1-C6) alkanoyloxy, and (C3-C6) cycloalkyl groups are halogens; The organic acid catalyst is one or both of organic sulfonic acids or organic alkyl acids.

2. The method for producing deuterated aromatic compounds using a bubble column reactor according to claim 1, characterized in that, In step S1, the preheating process is as follows: The heavy water in the heavy water storage tank (1) is continuously transported to the material inlet of the vaporization vessel (3) through the heavy water feed pump (2). After initial mixing and vaporization in the vaporization vessel (3), the water enters the bottom gaseous material inlet of the shell-and-tube heat exchanger (4) from the top gaseous material outlet of the vaporization vessel (3) for further heating and vaporization, and is converted into superheated heavy water steam.

3. The method for producing deuterated aromatic compounds using a bubble column reactor according to claim 1 or 2, characterized in that, In step S2, the residence time t0 of the superheated heavy water vapor in the bubble column reactor is 3 to 300 seconds.

4. The method for producing deuterated aromatic compounds using a bubble column reactor according to claim 1, characterized in that, In step S2, the hydrogen-deuterium exchange reaction proceeds as follows: Superheated heavy water vapor overflowing from the top gas phase outlet of the tube heat exchanger (4) enters the bottom inlet of the bubble column reactor (5) and comes into contact with the organic acid catalyst and aromatic compounds packed inside the bubble column reactor (5) to carry out the hydrogen-deuterium exchange reaction. The reaction mixture overflows from the outlet of the bubble column reactor (5).

5. The method for producing deuterated aromatic compounds using a bubble column reactor according to claim 1 or 4, characterized in that, The aromatic compound is one of biphenyl, diphenylmethane, naphthalene, anthracene, benzofuran, benzothiophene, indole, fluorene, dibenzofuran, dibenzothiophene, and carbazole; The organic acid catalyst is one or more of methanesulfonic acid, butylsulfonic acid, trifluoromethanesulfonic acid, perfluorobenzenesulfonic acid, perfluorobutylsulfonic acid, perfluorooctylsulfonic acid, perfluorooctanoic acid, and perfluoroheptanoic acid, and is more preferably one or more of methanesulfonic acid, butylsulfonic acid, and trifluoromethanesulfonic acid.

6. The method for producing deuterated aromatic compounds using a bubble column reactor according to claim 1 or 4, characterized in that, In step S2, the loading amount of aromatic compounds in the bubble column reactor (5) is defined as X, the relative molecular mass of the aromatic compounds is M1, the number of hydrogen atoms in the aromatic ring of the molecule is a, the loading amount of organic sulfonic acid in the bubble column is defined as Y1, the loading amount of organic alkyl acid is defined as Y2, the relative molecular mass of the organic acid catalyst is M2, and the loading amounts of the aromatic compounds and the organic acid catalyst satisfy the following relationship: or .

7. The method for producing deuterated aromatic compounds using a bubble column reactor according to claim 6, characterized in that, In step S2, the feed flow rate of heavy water is defined as Z, its relative molecular mass is M3, and the total reaction time of hydrogen-deuterium exchange is defined as t. Then, the total feed amount of heavy water and the loading amounts of aromatic compounds and organic acid catalysts satisfy the following relationship: or .

8. The method for producing deuterated aromatic compounds using a bubble column reactor according to claim 7, characterized in that, In step S2, the bubble column reactor (5) is also filled with organic solvent; The organic solvent is selected from o-dichlorobenzene, p-dichlorobenzene, 2,6-dichlorotoluene, 1,2,4-trichlorobenzene, 2,4,6-trichlorotoluene, or decahydronaphthalene; the filling amount of the organic solvent is defined as V0, and the filling amount V0 satisfies the following relationship: 0.1X ≤ V0 ≤ 10.0X.

9. The method for producing deuterated aromatic compounds using a bubble column reactor according to claim 1, characterized in that, In step (3), the separation process is as follows: The reaction mixture overflowing from the top gas phase outlet of the bubble column reactor (5) enters the distillation column (6). The heavy organic acid components separated by distillation flow back to the bubble column reactor (5) from the lower side outlet of the distillation column (6). The light component low-deuterium water flows into the heat exchanger (7) from the upper light component material outlet of the distillation column (6). After the light component material condenses, it flows out from the bottom of the heat exchanger (7). Part of the material flows back to the top reflux port of the distillation column (6), and part of the material is transported to the upper liquid phase material inlet of the receiving tank (8). Then it enters the stratification tank (9) and is allowed to stand and stratify. The low-deuterium water phase is transported to the low-deuterium water storage tank (10), and the phase containing deuterated aromatic compounds is transported to the deuterated aromatic compound storage tank (11). The deuterated aromatic compounds in the deuterated aromatic compound storage tank (11) flow back to the bubble column reactor (5) to continue the hydrogen-deuterium exchange reaction. The distillation column has 10-20 theoretical plates and a reflux ratio of 0.2-2.0:

1.

10. The method for producing deuterated aromatic compounds using a bubble column reactor according to claim 1 or 9, characterized in that, The post-processing process includes: The bubble column reactor is cooled to a predetermined temperature and allowed to stand to separate into layers, yielding a deuterated product phase and a high-deuterium organic acid phase, which are discharged from the outlet of the bubble column reactor. The deuterated product phase was purified to obtain high-quality deuterated aromatic compounds.

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