Preparation method of anthracene-d10

Abstract

The invention discloses a preparation method of anthracene-d10, which comprises the following steps: mixing anthracene, a deuterium source, an acid, a catalyst and a solvent, carrying out hydrogen-deuterium exchange reaction to obtain a head product containing anthracene-d10, and purifying the head product to obtain anthracene-d10; the addition amount of the raw materials meets the condition that the ratio of anthracene to the sum of the acid and the deuterium source to the catalyst to the solvent is 1: (2-3.5): (0.05-0.1): (5-10) according to the mass ratio; wherein the catalyst contains at least one benzene ring, and the electron cloud density of the catalyst is greater than that of anthracene. The method is high in yield, high in deuteration degree, low in reaction temperature and suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the technical field of deuterated compound production, and in particular to a method for preparing anthracene-d10. Background Art

[0002] Deuterium (D) is a stable isotope of hydrogen with two neutrons and one proton in its nucleus. Deuterated compounds are compounds in which some or all of the CH bonds are replaced by CD bonds. Since deuterium has one more neutron than hydrogen, the CD bond has a lower zero-point vibration energy (1.2–1.5 kcal / mol) than the CH bond, but the activation energy of its reaction transition state remains basically unchanged, so the breaking of the CD bond requires more energy. Therefore, the introduction of deuterium into the active site of the compound will lead to better stability. In the field of materials, the OLED (Organic Light-Emitting Diode) light-emitting layer is mainly composed of a mixture of red, green and blue materials to form white light. Since blue light photons have higher energy, their lifespan is also the shortest. Studies have found that in OLED matrix materials, hydrogen / deuterium exchange of unstable heterocyclic carbon-hydrogen bonds can extend the life of the device, and there will be no significant difference in other chemical properties. In addition, after the introduction of deuterium atoms into the blue light material, the spin-orbit coupling of the luminescent molecules will be enhanced, which is conducive to the generation of phosphorescence and improves its quantum efficiency. By replacing the CH bond in the main structure of the organic light-emitting material with a CD bond, the OLED matrix material can withstand a much larger current than the non-deuterated material, and the life of the OLED device can be extended by 5-20 times. In the field of life sciences, the labeling effect of deuterated compounds combined with tandem mass spectrometry can be used to study the absorption, distribution, metabolism and excretion process (ADME) of drug molecules in the body, and the deuterium kinetic isotope effect brought about by the introduction of deuterium can change the pharmacokinetics and metabolic pathways of drug molecules, based on which new drugs can be improved and developed.

[0003] Among them, anthracene-d10 (C 10 D 10 ) is the most basic building block in new OLED materials and an important intermediate for synthesizing various fully deuterated OLED materials. Anthracene-d10 can be prepared by reacting anthracene with strong acid at high temperature and high pressure. Since the melting point of anthracene is 215 degrees Celsius, the reaction temperature is generally higher than 215 degrees Celsius. On the other hand, due to the reaction conditions of strong acid, high temperature and high pressure, high requirements are placed on the reaction equipment; at the same time, as the temperature and acidity increase, there will be more side reactions, resulting in a lower reaction yield.

[0004] Prior art CN117126031A discloses a method for preparing anthracene-d10 using a supported catalyst, and provides a porous nitrogen-doped carbon supported ruthenium catalyst, anthracene and dichloromethane are added to a high-pressure reactor, and after completion, the supported catalyst is added, sealed and filled with deuterium gas, reacted at 50-70°C for 10-15h, cooled to room temperature, filtered, and dichloromethane is spun out to obtain the deuterated anthracene; the supported catalyst preparation method comprises: dispersing ruthenium trichloride and polyvinyl pyrrolidone in deionized water, adding sodium borohydride aqueous solution, stirring for 2-3h, then adding porous nitrogen-doped carbon, stirring and mixing for 10-12h, filtering, drying, and the obtained solid is subjected to pyrolysis treatment to obtain the supported catalyst; the porous carbon preparation method comprises: grinding litchi peel and dispersing it in deionized water, and then hydrothermally heating it for 20-24h. The precipitate is filtered and dried. The obtained product and cellulose are dispersed in deionized water, stirred under magnetic stirring for 20-24h, and then dried. The obtained mixture is calcined at high temperature for 2-4 hours under nitrogen atmosphere. Finally, the calcined product is treated with acid in 1M hydrochloric acid to obtain porous nitrogen-doped carbon. However, the preparation process of the catalyst in this method is complicated and the cost is high. Summary of the invention

[0005] The object of the present invention is to provide a method for preparing anthracene-d10, which has high yield, high degree of deuteration, low reaction temperature and is suitable for industrial production.

[0006] The technical solution adopted by the present invention to solve its technical problem is: A method for preparing anthracene-d10 comprises mixing anthracene, a deuterium source, an acid, a catalyst and a solvent, performing a hydrogen-deuterium exchange reaction to obtain a primary product containing anthracene-d10, and purifying the primary product to obtain anthracene-d10; according to the mass ratio, the addition amount of the raw materials satisfies the following ratio: anthracene: the sum of the acid and the deuterium source: the catalyst: the solvent = 1: 2-3.5: 0.05-0.1: 5-10; the hydrogen-deuterium exchange reaction is performed for 3-10 rounds; the time of each round of the hydrogen-deuterium exchange reaction is 12-48 hours, and the reaction temperature is 110-140° C.; Wherein, the catalyst contains at least one benzene ring, and the electron cloud density of the catalyst is greater than the electron cloud density of anthracene; The general structural formula of the catalyst is , wherein R1-R5 are independently selected from one of hydrogen, methyl, ethyl, methoxy and ethoxy; Or the general structural formula of the catalyst is , wherein R1-R10 are independently selected from one of hydrogen, methyl, ethyl, methoxy, and ethoxy, and at least one of R2, R3, and R4 is H.

[0007] The catalyst is specifically at least one of xylene, mesitylene, anisole, 2-methylanisole, p-methylanisole, m-methylanisole, diphenyl ether, 4,4'-dimethyldiphenyl ether, 3,4'-dimethyldiphenyl ether, and 3,3'-dimethyldiphenyl ether.

[0008] The deuterium source is selected from at least one of heavy water, deuterated benzene, deuterated toluene, deuterated xylene, deuterated trimethylolbenzene, deuterated ethanol, deuterated isopropanol, deuterated n-propanol, and deuterated n-butanol.

[0009] The acid is at least one selected from deuterated trifluoromethanesulfonic acid, deuterated methanesulfonic acid, deuterated trifluoroacetic acid, deuterated sulfuric acid, deuterated perfluorobutylsulfonic acid, and sulfonic acid resin solid acid.

[0010] The solvent is selected from at least one of chlorobenzene, dichlorobenzene and dichlorotoluene.

[0011] The deuterium source and the acid are mixed to form an acid deuterium source solution for use, wherein the mass percentage of the acid in the acid deuterium source solution is 50-70%.

[0012] The electron cloud density of the catalyst provided by the present invention is greater, so its reaction activity is much higher than that of anthracene. In the above reaction system, the catalyst preferentially undergoes deuteration; further, due to the π-π effect between the benzene ring of the catalyst and anthracene, the distance between anthracene and the benzene ring plane of the catalyst is relatively close, and when the catalyst is activated at a higher temperature, the distance between the protons produced and anthracene will be relatively close, thereby greatly increasing the total amount of activated molecules of the anthracene reaction, thereby reducing the requirements for its reaction temperature and acidity; thus, the reaction conditions are milder, and accordingly, the by-products are also reduced. The present invention uses a suitable catalyst to reduce the activation energy of the anthracene deuteration reaction by the π-π effect with anthracene, so that the reaction can be carried out at a lower temperature and lower acidity.

[0013] The purification treatment of the primary product includes: separating the primary product into layers and recovering the aqueous phase, and sequentially extracting, filtering, drying and recrystallizing the organic phase to obtain anthracene-d10.

[0014] The beneficial effects of the present invention are: ① Low reaction temperature and high yield. Avoiding the large amount of by-products caused by high temperature and high pressure, improving the reaction yield, the yield of anthracene-d10 crude product is ≥97%.

[0015] ②The production process is more environmentally friendly. Since it can be carried out under normal pressure and low acidity, the requirements for equipment are greatly reduced, and the production cost is reduced due to the lower acidity.

[0016] ③The production process is safer. It avoids high temperature, high pressure and high acidity, effectively reducing safety risks. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 It is the nuclear magnetic resonance detection image of the product of the present invention. DETAILED DESCRIPTION

[0018] The technical solution of the present invention is further described in detail below through specific embodiments.

[0019] In the present invention, unless otherwise specified, the raw materials and equipment used can be purchased from the market or are commonly used in the art. The methods in the following embodiments, unless otherwise specified, are all conventional methods in the art.

[0020] Example 1 In this example, diphenyl ether was used as a catalyst to prepare anthracene-d10.

[0021] Anthracene (1 g, 0.006 mol), diphenyl ether (0.1 g, 0.0005 mol), chlorobenzene (7 g, 0.06 mol), and acid water (heavy aqueous solution of trifluoromethanesulfonic acid, mass concentration 60%, 3.2 g) were added into a kettle, the reaction temperature was 110°C, the reaction time was 48 h, and a reaction solution containing anthracene-d10 was obtained, and the deuteration degree of anthracene was about 68.2% (deuteration degree 97.0%); The reaction solution was allowed to stand for stratification to obtain an organic phase; acid water (deuterated trifluoromethanesulfonic acid heavy aqueous solution, mass concentration 60%, 3.2 g) was added to the organic phase to perform a second round of hydrogen-deuterium exchange reaction. This step was repeated for a total of 4 rounds of exchange; a primary product containing anthracene-d10 was obtained, and the deuteration degree of anthracene was 98.1%.

[0022] The initial product was allowed to stand, the upper organic phase was taken, 2 g of ethyl acetate was added, then the temperature was lowered, 5 g of saturated sodium bicarbonate solution was added, and after stirring for 3 hours, the crude anthracene-d10 product was obtained by filtration; at the same time, the mother liquor was allowed to stand and layered to obtain an organic phase, and the solvent and a small amount of crude anthracene-d10 product 0.98 g were recovered by distillation, and then the crude anthracene-d10 product was recrystallized to obtain 0.88 g of fine anthracene-d10 product.

[0023] The reaction technology route of this embodiment is: using chlorobenzene as a reaction solvent, avoiding the reaction temperature to react above the melting point of anthracene, 215 degrees Celsius. At the same time, the diphenyl ether therein has two main functions, one is to serve as a temporary storage reagent for deuterium, and the second is to close the distance between diphenyl ether and anthracene through the π-π action of diphenyl ether and anthracene, so that the proton generated when the strong acid activates diphenyl ether is close to the distance between anthracene, thereby reducing its reaction activation energy, thereby reducing the reaction temperature and acidity. Since the electron cloud density of diphenyl ether is much higher than that of anthracene, diphenyl ether is preferentially deuterated, and then diphenyl ether is used as a deuterium source to react with anthracene under the catalysis of acid to deuterate, thereby realizing the transfer of deuterium from the heavy water solution of acid to anthracene, and realizing the deuteration of anthracene (the principles of other catalysts and solvents refer to this embodiment).

[0024] In this embodiment, by adding diphenyl ether and chlorobenzene, not only a higher yield is obtained, the crude yield of anthracene-d10 is greater than 97%, and it has higher safety. The preparation method of anthracene-d10 in this embodiment has the advantages of high product yield, suitability for industrial large-scale production and safety.

[0025] In some embodiments, the deuteration efficiency of the reaction is reduced when the amount of diphenyl ether (catalyst) is too high. This is because diphenyl ether itself also participates in the distribution of deuterium. Therefore, as the amount of diphenyl ether increases, the absolute amount of deuterium occupied by diphenyl ether increases, thereby reducing the absolute amount of deuterium distributed to anthracene, that is, its deuteration degree decreases, so the deuteration efficiency of the reaction decreases.

[0026] In order to remove the impurities and residues that may be present in the primary product and ensure the purity and quality of the final product, the primary product is subjected to recrystallization purification in this embodiment. Impurities and residues in the anthracene-d10 crude product can be effectively removed, which helps to obtain a high-purity anthracene-d10 product.

[0027] The difference between Example 2 and Example 1 is that in the acid water, the mass concentration of deuterated trifluoromethanesulfonic acid is 50%, and the number of deuteration rounds is 10.

[0028] The difference between Example 3 and Example 1 is that the reaction conditions are 140° C., 12 h, and the number of deuteration rounds is 3.

[0029] The difference between Example 4 and Example 1 is that 2-methylanisole is used as the catalyst, dichlorobenzene is used as the solvent, and the added amount is 10 g; the reaction conditions are 120° C. and 24 h.

[0030] The difference between Example 5 and Example 1 is that 3,4'-dimethyldiphenyl ether is used as a catalyst, dichlorotoluene is used as a solvent, and the added amount is 5 g.

[0031] The difference between Example 6 and Example 1 is that meta-methylanisole is used as a catalyst, and the added amount is 0.07 g.

[0032] The difference between Example 7 and Example 1 is that anisole is used as a catalyst, and the added amount is 0.05 g.

[0033] The difference between Example 8 and Example 1 is that xylene is used as the catalyst, and the acid water is a deuterated n-butanol solution of deuterated methanesulfonic acid with a mass concentration of 70%, 3.0 g.

[0034] The difference between Example 9 and Example 1 is that the acid water uses a deuterated benzene solution of deuterated trifluoroacetic acid with a mass concentration of 60%, 3.5 g.

[0035] The difference between Example 10 and Example 1 is that the acid water uses a deuterated methanol solution of deuterated perfluorobutanesulfonic acid with a mass concentration of 70%, 2 g.

[0036] The difference between Comparative Example 1 and Example 1 is that no catalyst is added.

[0037] The difference between Comparative Example 2 and Example 1 is that in the acid water, the mass concentration of deuterated trifluoromethanesulfonic acid is 40%.

[0038] The difference between Comparative Example 3 and Example 1 is that the reaction temperature is 150°C.

[0039] The following tests were performed on the obtained embodiments and comparative examples: 1) Deuterium substitution detection: The deuterium substitution is detected by nuclear magnetic resonance hydrogen spectroscopy and calculated using the following formula: ; Wherein, A is the hydrogen peak area of ​​the deuterated sample, D is the degree of deuteration, m1 is the added mass of the deuterated sample in g, n1 is the number of H atoms to be deuterated in the deuterated sample, M1 is the relative molecular mass of the sample before deuteration in g, m2 is the added mass of the internal standard in g, n2 is the number of H atoms in the deuterated sample, and M2 is the relative molecular mass of the internal standard.

[0040] 2) Purity detection: gas chromatography is used for detection.

[0041] 3) Yield detection: The calculation formula is actual weight of anthracene-d10 / theoretical weight of anthracene-d10*%.

[0042] The specific test results are shown in Table 1.

[0043] Table 1 .

[0044] According to Table 1, in Comparative Example 1, no diphenyl ether was added, and the deuteration degree of the reaction dropped sharply, indicating that the deuteration reaction rate was obviously not as good as that of the reaction solution with diphenyl ether added; in Comparative Example 2, the concentration of trifluoromethanesulfonic acid dropped to 40%, and the deuteration degree of the reaction also dropped sharply, indicating that this reaction was relatively sensitive to the concentration of trifluoromethanesulfonic acid, and a concentration of 40% would cause a decrease in the reaction rate; According to the comparison between Example 1 and Comparative Example 3, an increase in the reaction temperature would lead to a decrease in the reaction yield, and the reason may be that the increase in the reaction temperature leads to an increase in side reactions. After detection, it was found that there were by-products of coupling of anthracene and anthracene and coupling of anthracene and diphenyl ether, which led to a decrease in the reaction yield.

[0045] In addition, the product (anthracene-d10) prepared in Example 1 was subjected to nuclear magnetic resonance (NMR) and HPLC (liquid chromatography) detection. Figure 1, the deuteration degree of anthracene is 98.1%. The NMR data of anthracene-d10 is: 1 HNMR (400MHz, DMSO-d6) δ7.48 (s, 1.86H), 8.05 (s, 1.36H), 8.51 (s, 0.68H).

[0046] The GC (FIDI A, front signal) detection data of the product of Example 1 is shown in Table 2, and the purity is 99.9%.

[0047] Table 2: .

[0048] Among them, RT (Retention Time) is the time when the compound peak appears when it is injected from the injection port to the detector, in minutes (min). The retention time depends on the residence time of the compound in the chromatographic column. According to Table 1, the retention time exceeds 5 minutes, and a longer retention time means that the compound is better separated in the column. Height refers to the maximum height of the chromatographic peak, that is, the maximum measured value of the peak. The peak height reflects the signal intensity of the compound in the detector, and a high peak indicates a higher concentration of the compound. Area refers to the area under the chromatographic peak, which indicates the amount of compound contained in the chromatographic peak. A larger area means a higher concentration of the compound. Area percent refers to the percentage of the area of ​​the chromatographic peak to the total area, indicating the relative content of each compound in the sample, and is used to compare the relative content of different compounds in the sample.

[0049] Although the present invention is disclosed as above, the protection scope of the present invention is not limited thereto. Those skilled in the art may make various changes and modifications without departing from the spirit and scope of the present invention, and these changes and modifications will fall within the protection scope of the present invention.

Claims

1. A method for preparing anthracene-d10, characterized in that: Anthracene, a deuterium source, an acid, a catalyst and a solvent are mixed, and a hydrogen-deuterium exchange reaction is performed to obtain a primary product containing anthracene-d10, and the primary product is purified to obtain anthracene-d10; according to the mass ratio, the amount of raw materials added satisfies anthracene: the sum of the acid and the deuterium source: the catalyst: the solvent = 1: 2-3.5: 0.05-0.1: 5-10; the hydrogen-deuterium exchange reaction is performed for 3-10 rounds; the time of each round of the hydrogen-deuterium exchange reaction is 12-48 hours, and the reaction temperature is 110-140° C.; Wherein, the catalyst contains at least one benzene ring, and the electron cloud density of the catalyst is greater than the electron cloud density of anthracene; The general structural formula of the catalyst is , wherein R1-R5 are independently selected from one of hydrogen, methyl, ethyl, methoxy and ethoxy; Or the general structural formula of the catalyst is , wherein R1-R10 are independently selected from one of hydrogen, methyl, ethyl, methoxy, and ethoxy, and at least one of R2, R3, and R4 is H.

2. The preparation method according to claim 1, characterized in that: The catalyst is specifically at least one of xylene, mesitylene, anisole, 2-methylanisole, p-methylanisole, m-methylanisole, diphenyl ether, 4,4'-dimethyldiphenyl ether, 3,4'-dimethyldiphenyl ether, and 3,3'-dimethyldiphenyl ether.

3. The preparation method according to claim 1, characterized in that: The deuterium source is selected from at least one of heavy water, deuterated benzene, deuterated toluene, deuterated xylene, deuterated trimethylolbenzene, deuterated ethanol, deuterated isopropanol, deuterated n-propanol, and deuterated n-butanol.

4. The preparation method according to claim 1, characterized in that: The acid is at least one selected from deuterated trifluoromethanesulfonic acid, deuterated methanesulfonic acid, deuterated trifluoroacetic acid, deuterated sulfuric acid, deuterated perfluorobutylsulfonic acid, and sulfonic acid resin solid acid.

5. The preparation method according to claim 1, characterized in that: The solvent is selected from at least one of chlorobenzene, dichlorobenzene and dichlorotoluene.

6. The preparation method according to claim 1, characterized in that: The deuterium source and the acid are mixed to form an acid deuterium source solution for use, wherein the mass percentage of the acid in the acid deuterium source solution is 50-70%.

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