A method for preparing anthracene-d10

Abstract

The present invention discloses a preparation method of anthracene-d10. After mixing anthracene, deuterium source, acid, catalyst and solvent, a hydrogen-deuterium exchange reaction is carried out to obtain a crude product containing anthracene-d10, and the crude product is purified to obtain anthracene-d10; according to the mass ratio, the addition amount of raw materials satisfies anthracene∶the sum of acid and deuterium source∶catalyst∶solvent = 1∶2 - 3.5∶0.05 - 0.1∶5 - 10; wherein, the catalyst contains at least one benzene ring, and the electron cloud density of the catalyst is greater than that of anthracene. The present invention has high yield, high deuteration degree, low reaction temperature and is suitable for industrial production.

Description

Technical Field

[0001] The present invention relates to the technical field of the production of deuterated compounds, and particularly relates 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 atomic nucleus. A deuterated compound is one in which some or all of its C-H bonds are replaced by C-D bonds. Since deuterium has one more neutron than hydrogen, the C-D bond has a lower zero-point vibrational energy (1.2 - 1.5 kcal / mol) than the C-H bond. However, the activation energy of its reaction transition state remains basically unchanged. Therefore, the breaking of the C-D bond requires more energy. Thus, introducing deuterium at the active site of a compound will result in better stability. In the field of materials, the light-emitting layer of an OLED (Organic Light-Emitting Diode) is mainly composed of a mixture of red, green, and blue light-emitting materials to form white light. Since blue light photons have a higher energy, their lifespan is the shortest. Research has found that in the OLED matrix material, the hydrogen / deuterium exchange of unstable heterocyclic carbon-hydrogen bonds can extend the lifespan of the device, and there will be no obvious difference in other chemical properties. In addition, after introducing deuterium atoms into the blue light-emitting material, the spin-orbit coupling effect of the light-emitting molecules will be enhanced, which is conducive to the generation of phosphorescence and improves its quantum efficiency. By replacing the C-H bonds in the main structure of the organic light-emitting material with C-D bonds, the OLED matrix material can withstand a much larger current than the non-deuterated material, and the lifespan of the OLED device can be extended by 5 - 20 times. In the field of life sciences, using the labeling effect of deuterated compounds and combining with tandem mass spectrometry technology, it is possible to study the processes of drug molecule absorption, distribution, metabolism, and excretion (ADME) in the body. Moreover, the deuterium kinetic isotope effect brought about by introducing deuterium can change the pharmacokinetics and metabolic pathways of drug molecules, and new drugs can be improved and developed based on this.

[0003] Among them, anthracene-d10 (C 10 D 10 ) is the most basic constituent unit in new OLED materials and is also an important intermediate for synthesizing various fully deuterated OLED materials. The preparation of anthracene-d10 can be obtained by reacting anthracene with strong acid under high temperature and high pressure. Since the melting point of anthracene is 215 degrees Celsius, the general reaction temperature is higher than 215 degrees Celsius. On the other hand, due to the reaction conditions of strong acid under high temperature and high pressure, high requirements are put forward for 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] The prior art CN117126031A discloses a method for preparing anthracene-d10 using a supported catalyst, providing a catalyst of ruthenium supported on porous nitrogen-doped carbon. Anthracene and dichloromethane are added into a high-pressure reaction kettle. After completion, the supported catalyst is added, sealed, and filled with deuterium gas, and reacted at 50-70 °C for 10-15 h. It is cooled to room temperature, filtered, and dichloromethane is removed by rotary evaporation to obtain the deuterated anthracene; the preparation method of the supported catalyst includes: ruthenium trichloride and polyvinylpyrrolidone are dispersed in deionized water, an aqueous solution of sodium borohydride is added, and stirred for 2-3 h. Then, porous nitrogen-doped carbon is added, and stirred and mixed for 10-12 h, filtered and dried. The obtained solid is pyrolyzed to obtain the supported catalyst; the preparation method of the porous carbon includes: litchi pericarp is ground and dispersed in deionized water, and then hydrothermally treated for 20-24 h. The precipitate is filtered and dried. The obtained product and cellulose are dispersed in deionized water and stirred under magnetic stirring for 20-24 h, and then dried. The obtained mixture is calcined at a high temperature in a nitrogen atmosphere for 2-4 h. Finally, the calcined product is acid-treated in 1M hydrochloric acid to obtain porous nitrogen-doped carbon. However, the preparation process of the catalyst in this method is cumbersome and the cost is relatively high. Summary of the Invention

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

[0006] The technical solution adopted by the present invention to solve its technical problems is:

[0007] A method for preparing anthracene-d10, after mixing anthracene, deuterium source, acid, catalyst and solvent, a hydrogen-deuterium exchange reaction is carried out to obtain a crude product containing anthracene-d10, and the crude product is purified to obtain anthracene-d10; according to the mass ratio, the addition amount of the raw materials satisfies anthracene∶the sum of acid and deuterium source∶catalyst∶solvent = 1∶2-3.5∶0.05-0.1∶5-10; the hydrogen-deuterium exchange reaction is carried out for 3-10 rounds; the time of each round of the hydrogen-deuterium exchange reaction is 12-48 h, and the reaction temperature is 110-140 °C;

[0008] Among them, the catalyst contains at least one benzene ring, and the electron cloud density of the catalyst is greater than that of anthracene;

[0009] The structural general formula of the catalyst is , where R 1 -R 5 are each independently selected from one of hydrogen, methyl, ethyl, methoxy, and ethoxy;

[0010] Or the structural general formula of the catalyst is

[0011] , wherein R1 - R10 are each independently selected from one of hydrogen, methyl, ethyl, methoxy, and ethoxy, and at least one of R2, R3, and R4 is H.

[0012] 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.

[0013] The deuterium source is selected from at least one of heavy water, deuterated benzene, deuterated toluene, deuterated xylene, deuterated mesitylene, deuterated methanol, deuterated ethanol, deuterated isopropanol, deuterated n - propanol, and deuterated n - butanol.

[0014] The acid is selected from at least one of deuterated trifluoromethanesulfonic acid, deuterated methanesulfonic acid, deuterated trifluoroacetic acid, deuterated sulfuric acid, deuterated perfluorobutanesulfonic acid, and solid acid of sulfonic resin type.

[0015] The solvent is selected from at least one of chlorobenzene, dichlorobenzene, and dichlorotoluene.

[0016] The deuterium source and the acid are mixed to form a deuterium source solution of the acid before use, and the mass percentage of the acid in the deuterium source solution of the acid is 50 - 70%.

[0017] The catalyst provided by the present invention has a greater electron cloud density, so its reaction activity is much higher than that of anthracene. In the above reaction system, the catalyst is preferentially deuterated; further, due to the π - π interaction between the benzene ring of the catalyst and anthracene, the distance between anthracene and the benzene ring plane of the catalyst is relatively close. When the catalyst is activated at a higher temperature, the distance between the generated proton and anthracene will be relatively much closer. Thus, the total amount of activated molecules for the reaction of anthracene is greatly increased, thereby reducing the requirements for its reaction temperature and acidity; therefore, the reaction conditions are milder, and correspondingly, the by - products are also reduced. The present invention uses a suitable catalyst to reduce the activation energy of the anthracene deuteration reaction through the π - π interaction with anthracene, so that the reaction can be carried out at a lower temperature and lower acidity.

[0018] The purification treatment of the crude product includes: separating the aqueous phase by layering the crude product, and subjecting the organic phase to extraction, filtration, drying, and recrystallization in sequence to obtain anthracene - d10.

[0019] The beneficial effects of the present invention are:

[0020] ① The reaction temperature is low and the yield is high. Avoiding a large number of by - products brought by high temperature and high pressure, improving the reaction yield, and the yield of the crude anthracene - d10 ≥ 97%.

[0021] ② The 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 due to the reduction of acidity, the production cost is reduced.

[0022] ③ The production process is safer. It avoids high temperature, high pressure and high acidity, effectively reducing the safety risks. Description of the Drawings

[0023] Figure 1 It is the nuclear magnetic detection graph of the product of the present invention. Detailed Embodiments

[0024] The technical solution of the present invention will be further specifically described below through specific embodiments.

[0025] 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 are all conventional methods in the art unless otherwise specified.

[0026] Example 1

[0027] In this example, anthracene-d10 was prepared using diphenyl ether as a catalyst.

[0028] Anthracene (1 g, 0.006 mol), diphenyl ether (0.1 g, 0.0005 mol), chlorobenzene (7 g, 0.06 mol), and acid water (trifluoromethanesulfonic acid heavy aqueous solution, mass concentration 60%, 3.2 g) were added to the kettle. The reaction temperature was 110 °C and the reaction time was 48 h to obtain a reaction solution containing anthracene-d10. The deuteration degree of anthracene was about 68.2% (deuteration degree 97.0%);

[0029] The reaction solution was allowed to stand and separate to obtain an organic phase; acid water (deuterated trifluoromethanesulfonic acid heavy aqueous solution, mass concentration 60%, 3.2 g) was added again to the organic phase for the second round of hydrogen-deuterium exchange reaction. This step was repeated for a total of 4 rounds of exchange; an initial product containing anthracene-d10 was obtained, and the deuteration degree of anthracene was 98.1%.

[0030] 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 was obtained by filtration; at the same time, the mother liquor was allowed to stand and separate to obtain an organic phase, the solvent and a small amount of crude anthracene-d10 (0.98 g) were recovered by rectification, and then the crude anthracene-d10 was recrystallized to obtain 0.88 g of pure anthracene-d10.

[0031] 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).

[0032] 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.

[0033] 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.

[0034] 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.

[0035] 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.

[0036] 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.

[0037] 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.

[0038] 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.

[0039] Example 6 is different from Example 1 in that: m-methylanisole is used as the catalyst, and the addition amount is 0.07 g.

[0040] Example 7 is different from Example 1 in that: anisole is used as the catalyst, and the addition amount is 0.05 g.

[0041] Example 8 is different from Example 1 in that: xylene is used as the catalyst, and deuterated n-butanol solution of deuterated methanesulfonic acid with a mass concentration of 70% and 3.0 g is used as the acidic water.

[0042] Example 9 is different from Example 1 in that: deuterated benzene solution of deuterated trifluoroacetic acid with a mass concentration of 60% and 3.5 g is used as the acidic water.

[0043] Example 10 is different from Example 1 in that: deuterated methanol solution of deuterated perfluorobutanesulfonic acid with a mass concentration of 70% and 2 g is used as the acidic water.

[0044] Comparative Example 1 is different from Example 1 in that: no catalyst is added.

[0045] Comparative Example 2 is different from Example 1 in that: in the acidic water, the mass concentration of deuterated trifluoromethanesulfonic acid is 40%.

[0046] Comparative Example 3 is different from Example 1 in that: the reaction temperature is 150 °C.

[0047] The following tests are carried out on the obtained examples and comparative examples:

[0048] 1) Deuterium degree detection: Nuclear magnetic resonance hydrogen spectroscopy is used for deuterium degree detection, and the following formula is used for calculation:

[0049] ;

[0050] where A is the hydrogen peak area of the deuterated sample, D is the deuterium degree, 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.

[0051] 2) Purity detection: Gas chromatograph is used for detection.

[0052] 3) Yield detection: The calculation formula is the actual obtained weight of anthracene-d10 / the theoretically obtained weight of anthracene-d10 * %.

[0053] The specific test results are shown in Table 1.

[0054] Table 1

[0055] 。

[0056] According to Table 1, diphenyl ether was not added in Comparative Example 1, and the deuteration degree of the reaction decreased sharply, indicating that the deuteration reaction rate was significantly lower than that of the reaction solution with diphenyl ether added; in Comparative Example 2, the concentration of trifluoromethanesulfonic acid decreased to 40%, and the deuteration degree of the reaction also decreased sharply, indicating that this reaction was relatively sensitive to the concentration of trifluoromethanesulfonic acid, and a concentration of 40% would cause the reaction rate to decrease; according to the comparison between Example 1 and Comparative Example 3, increasing the reaction temperature would cause the reaction yield to decrease. The reason might be that increasing the reaction temperature led to an increase in side reactions. After detection, by-products of anthracene coupling with anthracene and anthracene coupling with diphenyl ether were found, which resulted in a decrease in the reaction yield.

[0057] In addition, the products prepared in Example 1 (anthracene-d10) were respectively subjected to NMR detection and HPLC (high performance liquid chromatography) detection. Among them, the NMR detection spectrum is shown in Figure 1 , and the deuteration degree of anthracene was 98.1%. The NMR data of anthracene-d10 were: 1 HNMR(400MHz,DMSO-d6)δ7.48(s,1.86H),8.05(s,1.36H),8.51(s,0.68H).

[0058] The GC (FIDI A, front signal) detection data of the product in Example 1 are shown in Table 2, and the purity was 99.9%.

[0059] Table 2:

[0060] 。

[0061] Among them, RT (Retention Time) is the time when the compound appears as a peak from the injection port into the detector, in minutes (min). The size of the retention time depends on the residence time of the compound in the chromatographic column. It can be seen from Table 1 that the retention time exceeds 5 min, and a longer retention time means a better separation degree of the compound 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, indicating the amount of the 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 contents of different compounds in the sample.

[0062] Although the present invention is disclosed as above, the scope of protection of the present invention is not limited thereto. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the present invention, and these changes and modifications will all fall within the scope of protection 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.; The catalyst contains at least one benzene ring, and the electron cloud density of the catalyst is greater than that of anthracene; the acid is selected from at least one of deuterated trifluoromethanesulfonic acid, deuterated methanesulfonic acid, deuterated trifluoroacetic acid, deuterated sulfuric acid, and deuterated perfluorobutylsulfonic acid; the deuterium source and the acid are mixed to form a deuterium source solution of the acid, and the mass percentage of the acid in the deuterium source solution of the acid is 50-70%; The catalyst is at least one of anisole, 2-methyl anisole, p-methyl anisole, and m-methyl anisole; 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 diphenyl ether, 4,4'-dimethyl diphenyl ether, 3,4'-dimethyl diphenyl ether and 3,3'-dimethyl diphenyl 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 methanol, deuterated ethanol, deuterated isopropanol, deuterated n-propanol, and deuterated n-butanol.

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

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