Method for preparing formyl deuterated aromatic aldehyde compound by using supported catalyst

Abstract

The invention discloses a method for preparing formyl deuterated aromatic aldehyde by using a supported catalyst, and relates to the technical field of fine chemical synthesis. According to the method, an aromatic aldehyde compound is used as a raw material, heavy water is used as a deuterium source, a noble metal supported catalyst is adopted, and a fixed-point hydrogen-deuterium exchange reaction is performed under the inert atmosphere condition to obtain the formyl deuterated aromatic aldehyde compound. A carrier in the catalyst comprises an oxide, a nitride or a carbide, and the mass percentage of the noble metal in the catalyst is 1-8wt%. The formyl deuterated aldehyde compound is obtained by selectively catalyzing the formyl of the aromatic aldehyde compound to generate the hydrogen-deuterium exchange reaction under the hydrogen-free atmosphere condition, and has the following advantages that an additional organic deuterated reagent does not need to be used, the operation steps are few, the product is easy to separate, the yield and the deuterated rate are high, the deuterium source is cheap and easy to obtain, and the method is suitable for industrial production. The catalyst is easy to prepare and recyclable, has the characteristics of greenness, high efficiency and practicability, and provides a new technical method for synthesizing the formyl deuterated aldehyde.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of fine chemical synthesis, and particularly relates to a method for preparing formyl deuterated aromatic aldehyde compounds by using a supported catalyst. BACKGROUND

[0002] Deuterium-labeled chemicals have wide application value in the fields of chemistry, biology, medicine, and optoelectronic semiconductor materials (Nature. 2024, 634, 592-599). Among many applications, the research on deuterium labeling in the field of medicinal chemistry has shown an explosive growth trend in the past decade (Nat. Rev. Drug. Discov. 2023, 22, 562-584). Site-specific deuterium labeling at the "metabolic soft spot" in the structure of a drug molecule can effectively regulate the absorption, distribution, metabolism, excretion, and toxicity (ADME) properties of the drug. In 2017, the U.S. Food and Drug Administration (FDA) approved the first deuterated drug, deutetrabenazine, for marketing, which is used for the treatment of Huntington's disease and tardive dyskinesia. The successful marketing of the deuterated drug has greatly promoted the rapid development of the synthesis technology of deuterated drugs and their key deuterated intermediates. Therefore, with the continuous growth of the demand for deuterated molecules and deuterated intermediates in various fields, it is necessary to develop more efficient, practical, and scalable synthesis technologies for deuterated molecules.

[0003] Aldehyde compounds have always been important basic raw materials in organic synthesis, and they have diverse structures and high reactivity, and can derive a variety of functionalized products. Using formyl deuterated aldehyde as a deuterated synthesis unit can not only expand the synthesis route of deuterated compounds, but also significantly improve the application development potential of deuterated compounds in the fields of drugs and materials, thereby accelerating the research and development process of deuterated new drugs or deuterated new materials. Therefore, developing a new synthesis technology for formyl deuterated aldehyde compounds with high efficiency and high selectivity is crucial for promoting the research of deuterated compounds. So far, several methods for synthesizing formyl deuterated aldehyde have been developed, which can be generally classified into two categories: functional group transformation and hydrogen isotope exchange (HIE). The former mainly relies on the reduction of carboxylic acid derivatives and the carbonylation of aryl halides, often requiring expensive deuterated reducing agents (LiAlD4 / NaBD4) and a multi-step synthesis process. The latter achieves direct deuterium substitution through the HIE method, which is simple in route, but still relies on homogeneous catalyst systems. However, the preparation process of homogeneous catalysts is complex, usually involving expensive organic ligands, and there are still limitations in separation, purification, and recycling. In contrast, heterogeneous deuterium catalysts exhibit significant advantages in catalyzing deuterium substitution reactions due to their easy separation after reaction and recyclability. However, the existing technology still has deficiencies in terms of site-specific deuterium substitution selectivity, deuterium enrichment, and chemical purity of the product, which to some extent cannot meet the application requirements of deuterated compounds in the fields of drugs and new materials. SUMMARY

[0004] To solve the above technical problems, the applicant has developed a supported catalyst system and proposes a method for preparing formyl deuterated aromatic aldehyde compounds by using a supported catalyst, which is economical, practical, and has high site-specific deuteration selectivity and high deuteration abundance. The method uses aromatic aldehyde compounds as raw materials, inexpensive and readily available heavy water as a deuterium source, and a noble metal supported catalyst to achieve site-specific deuteration of the formyl group of aromatic aldehyde compounds under a hydrogen-free atmosphere, thereby obtaining the target deuterated product. The present application provides a green and efficient heterogeneous catalytic site-specific deuteration technology, which provides a new technical approach for the preparation of formyl deuterated aromatic aldehyde compounds.

[0005] To achieve the above-mentioned purpose, the technical scheme adopted by the present application is: A method for preparing formyl deuterated aromatic aldehyde compounds by using a supported catalyst, which includes using aromatic aldehyde compounds as raw materials, heavy water as a deuterium source, and a noble metal supported catalyst to achieve site-specific hydrogen-deuterium exchange reaction under an inert atmosphere to obtain formyl deuterated aromatic aldehyde compounds; the carrier in the catalyst includes oxides, nitrides, or carbides; the mass percentage of noble metal in the catalyst is 1-8 wt.%; The aromatic aldehyde compounds include one or more of the compounds represented by formula (1), and the formyl deuterated aromatic aldehyde compounds are one or more of the compounds represented by formula (2); Formula (1); Formula (2) Wherein, R is selected from aryl, substituted aryl, polycyclic aryl, substituted polycyclic aryl, heterocyclic aryl, substituted heterocyclic aryl; The substituents in the substituted aryl, substituted polycyclic aryl, or substituted heterocyclic aryl are one or more alkyl, alkoxy, hydroxyl, amino, nitro, cyano, or halogen functional groups.

[0006] The number of carbon atoms in the aryl group in the aryl, substituted aryl, polycyclic aryl, substituted polycyclic aryl, substituted heterocyclic aryl, or heterocyclic aryl ranges from C 6-20 ; the number of carbon atoms in the heterocyclic ring in the heterocyclic aryl, substituted heterocyclic aryl ranges from C 2-10 ; the type of heteroatom in the heterocyclic aryl or substituted heterocyclic aryl is N, O, or S; the number of carbon atoms in the alkyl or alkoxy group in the substituent ranges from C 1-10 .

[0007] The aromatic aldehyde compounds include one or more of the following structural formulas: The oxide includes one or more of cerium oxide, lanthanum oxide, aluminum oxide, and titanium dioxide; the nitride includes boron nitride; and the carbide includes boron carbide.

[0008] The precious metals include one or more of palladium, ruthenium, platinum and rhodium.

[0009] It also includes a pre-treatment of the oxides by calcination. The calcination temperature is 400~600℃, and the calcination time is 6 h.

[0010] The catalyst was obtained by impregnation.

[0011] Specifically, the steps include the following: S1 involves adding aromatic aldehydes, heavy water, and a catalyst to an organic solvent and then ultrasonically mixing them until homogeneous. S2 was subjected to multiple displacements under an inert atmosphere, followed by the introduction of an inert atmosphere, and the reaction was carried out by heating and stirring. After the reaction was completed, the mixture was cooled to room temperature, and the catalyst was separated by filtration. The resulting filtrate was a mixed solution of organic solvent containing formyl deuterated aryl aldehydes and heavy water. S3 Add the extractant to the mixed solution, and after the addition is complete, let it stand to separate into layers, remove the heavy water, and collect the organic phase; S4 removes the extractant by vacuum rotary evaporation to obtain the target deuterated product.

[0012] The molar amount of noble metal in the catalyst is 2% to 5% of the molar amount of aromatic aldehyde compounds.

[0013] The molar ratio of the aromatic aldehyde compound to the volume of heavy water used is 1:10~20 mmol / mL.

[0014] The organic solvent mentioned in S1 includes one of tetrahydrofuran, dimethyl sulfoxide, and dioxane; the volume ratio of the organic solvent to heavy water is 1:2~5.

[0015] The number of inert gas replacements in S2 is greater than or equal to two.

[0016] The reaction is carried out at 0.1~0.5 MPa.

[0017] The inert atmosphere is argon or nitrogen.

[0018] The reaction temperature is 90~150℃. The reaction time is 1~12 h.

[0019] The stirring speed in S2 is 600~1000 rpm.

[0020] The amount of extractant used in S3 is 5 to 10 times the volume of heavy water. The extractant is dichloromethane.

[0021] The beneficial effects of this invention are as follows: This invention utilizes heavy water as the deuterium source and aromatic aldehydes as the reaction substrate. Under an inert atmosphere, a noble metal-supported catalyst is used to efficiently synthesize formyl deuterated aromatic aldehydes via a site-directed hydrogen-deuterium exchange reaction of the formyl group. During this reaction, oxygen-, nitrogen-, or carbon-deficient sites in the catalyst support serve as selective adsorption sites for the formyl group, effectively improving the site-directed deuteration selectivity. Simultaneously, under the catalytic action of the noble metal active sites, heavy water first dissociates to generate active deuterium species, which then undergo a selective deuteration reaction with the adsorbed formyl group to generate the target deuterated compound. The synthetic method for formyl deuterated aromatic aldehydes designed in this invention features simple operation, high deuteration performance, and mild reaction conditions. The target product synthesized via the hydrogen-deuterium exchange reaction has a high yield, with a deuteration rate of over 95% in the formyl functional group. The supported catalyst used is easy to prepare in large quantities, facilitates separation from the deuterated product, and maintains stable deuteration performance even after six cycles, demonstrating good reusability and economy. Furthermore, this invention utilizes inexpensive and readily available heavy water as a deuterium source to achieve highly selective synthesis of formyl deuterated aromatic aldehydes via a heterogeneous catalytic pathway, providing a new technical approach for the research and application of downstream deuterated compounds.

[0022] Compared to traditional techniques that use deuterated organic reagents as deuterium sources and require multi-step chemical synthesis, this invention offers the following advantages: simplified reaction steps, milder conditions, no need for toxic, highly volatile, and expensive deuterated organic reagents, and readily available and inexpensive raw materials; high product purity, ensuring both high yield and high deuteration rate. The oxygen vacancies in the support effectively mitigate problems such as poor deuteration selectivity, low deuterium abundance, and low yield in heterogeneous catalytic systems. Furthermore, the catalyst can be recycled after simple reduction treatment, significantly reducing catalyst costs and demonstrating potential for large-scale application. Attached Figure Description

[0023] Figure 1 TEM and XPS electronic structure characterization images of the cerium oxide-supported Pt-based catalyst.

[0024] Figure 2 The mass spectrum (MS) of deuterated 4-methylbenzaldehyde obtained in Example 1 is shown.

[0025] Figure 3 The 1H NMR spectrum of deuterated 4-methylbenzaldehyde obtained in Example 1 ( 1 (H NMR) image.

[0026] Figure 4 The nuclear magnetic resonance deuterium spectrum of deuterated 4-methylbenzaldehyde obtained in Example 1 ( 2 (H NMR) image.

[0027] Figure 5 The figures show the catalytic cycle performance of the catalyst in Example 1 and the 1H NMR and mass spectra of the gram-level products. Detailed Implementation

[0028] The present invention will be further described in detail below with reference to the embodiments, but the embodiments described are not intended to limit the scope of protection of the present invention.

[0029] The cerium oxide treatment steps in the example are as follows: 500 mg of commercial cerium oxide support is weighed, placed in a muffle furnace, heated to 400~600℃ at a heating rate of 5℃ / min in air atmosphere, and calcined in this temperature range for 6 h to obtain a catalyst support with oxygen vacancy defects.

[0030] The preparation steps of the noble metal supported catalyst are as follows: First, a noble metal aqueous solution of a certain concentration is prepared. Using the pretreated cerium oxide, commercial alumina, commercial titanium dioxide, commercial lanthanum oxide, commercial boron nitride, or commercial boron carbide as supports, the noble metal salts are loaded onto these supports via impregnation. The mass percentage of the noble metal (Ru / Pt / Pd) is 1~8 wt.%. Subsequently, under a synthesis air atmosphere, the temperature is increased to 400℃ at a heating rate of 5℃ / min and maintained for 2 hours, then decreased to 300℃. The atmosphere is switched to a mixture of 10% H2 / 90% Ar, and this temperature is maintained for another 2 hours, followed by natural cooling to room temperature to obtain the supported noble metal catalyst. The microstructure characterization of the cerium oxide supported Pt-based catalyst (5 wt% Pt) is as follows: Figure 1 As shown in (a, b), high-resolution transmission electron microscopy images reveal that Pt nanoparticles are uniformly dispersed on a cerium oxide support, with a statistically average particle size of approximately 2.8 nm. The electronic structure characterization of the catalyst is as follows: Figure 2 As shown in (c, d), peak fitting statistics were performed on the high-resolution XPS spectra of the Ce 3d orbitals. 3+ The content ratio is approximately 38.9%; according to the peak fitting statistics of the high-resolution XPS spectrum of the O 1s orbital, the oxygen vacancy content ratio is approximately 34.6%.

[0031] Synthesis of deuterated 4-methylbenzaldehyde Equation (3) Example 1 0.4 mmol (48.1 mg) of 4-methylbenzaldehyde, 0.5 mL of heavy water (99.9%), 3 mL of tetrahydrofuran solution (99.9%), and 10 mg of 5 wt.% cerium oxide-supported Pt-based catalyst were added to a 25 mL Schlenk tube. After the reaction tube was evacuated to reduced pressure, the residual air in the reaction system was replaced twice with argon gas (99.999%). Finally, 0.1 MPa of argon gas (99.999%) was introduced, and the reaction tube was placed in a preheated 140°C oil bath. The reaction was carried out at a stirring rate of 800 rpm for 24 h, and then cooled to room temperature. The catalyst was removed through a filter to obtain a mixed solution of heavy water, tetrahydrofuran, and crude product. The mixed solution was extracted with dichloromethane in three portions, 10 mL each time, to separate the organic layer and the heavy water layer. The upper organic liquid was collected. Subsequently, 10 mg of anhydrous magnesium sulfate was added as a drying agent to remove residual heavy water. Finally, the organic solution was removed by rotary evaporation under reduced pressure at 40 °C to obtain 44.2 mg of the target deuterated product, with a yield of 92% and a formyl deuteration rate of 99%. The MS spectrum of deuterated 4-methylbenzaldehyde is shown below. Figure 2 As shown, 1 H NMR spectrum as follows Figure 3 As shown, 2 H NMR spectrum as follows Figure 4 As shown. Figure 5 a, Figure 5 b shows a photograph of the gram-level deuterated product. The catalyst was washed twice with ethanol and dried in a vacuum oven at 60°C for 8 h. Then, it was reduced at 300°C for 2 h in a mixed atmosphere (10% H2 / 90% Ar) and reused. Its cycle stability is as follows: Figure 5 As shown in c.

[0032] Example 2-11 Same as Example 1, but the noble metal composition, loading amount, and support type of the noble metal supported catalyst were adjusted. The formyl deuteration rate and the yield of deuterated aldehyde of its deuterated products are shown in Table 1.

[0033] Table 1: Formyl deuteration rate and deuterated aldehyde yield for each catalyst Example Catalyst Loading / wt% Deuterium rate / % Yield / % 2 [Ru / CeO2] 5 93 94 3 [Pd / CeO2] 5 80 97 4 Pt / CeO2 1 79 95 5 Pt / CeO2 3 96 93 6 Pt / CeO2 8 99 91 7 Pt / La203 5 78 83 8 Pt / Al203 5 82 83 9 Pt / TiO2 5 90 93 10 Pt / BN 5 91 91 11 Pt / B4C 5 97 77 Synthesis of deuterated benzaldehyde Equation (4) Example 12 0.4 mmol (42.4 mg) of benzaldehyde, 0.5 mL of heavy water (99.9%), 3 mL of tetrahydrofuran solution (99.9%), and 10 mg of 5 wt.% cerium oxide-supported Pt-based catalyst were added to a 25 mL Schlenk tube. After the reaction tube was evacuated to reduced pressure, the residual air in the reaction system was replaced twice with argon gas (99.999%). Finally, 0.1 MPa of argon gas (99.999%) was introduced, and the reaction tube was placed in a preheated 140°C oil bath. The reaction was carried out at a stirring rate of 800 rpm for 24 h, and then cooled to room temperature. The catalyst was removed through a filter to obtain a mixed solution of heavy water, tetrahydrofuran, and crude product. The mixed solution was extracted with dichloromethane in three portions, 10 mL each time, to separate the organic layer and the heavy water layer. The upper organic liquid was collected. Subsequently, 10 mg of anhydrous magnesium sulfate was added as a drying agent to remove residual heavy water. Finally, the organic solution was removed by rotary evaporation under reduced pressure at 40°C to obtain 38.5 mg of the target deuterated product, with a yield of 91% and a formyl deuteration rate of 95%.

[0034] Synthesis of deuterated 4-methoxybenzaldehyde Equation (5) Example 13 0.4 mmol (54.5 mg) of 4-methoxybenzaldehyde, 0.5 mL of heavy water (99.9%), 3 mL of tetrahydrofuran solution (99.9%), and 10 mg of 5 wt.% cerium oxide-supported Pt-based catalyst were added to a 25 mL Schlenk tube. After the reaction tube was evacuated to reduced pressure, the residual air in the reaction system was replaced twice with argon gas (99.999%). Finally, 0.1 MPa of argon gas (99.999%) was introduced, and the reaction tube was placed in a preheated 140°C oil bath. The reaction was carried out at a stirring rate of 800 rpm for 24 h, and then cooled to room temperature. The catalyst was removed through a filter to obtain a mixed solution of heavy water, tetrahydrofuran, and crude product. The mixed solution was extracted with dichloromethane in three portions, 10 mL each time, to separate the organic layer and the heavy water layer. The upper organic liquid was collected. Subsequently, 10 mg of anhydrous magnesium sulfate was added as a drying agent to remove residual heavy water. Finally, the organic solution was removed by rotary evaporation under reduced pressure at 40°C to obtain 50.6 mg of the target deuterated product, with a yield of 93% and a formyl deuteration rate of 97%.

[0035] Synthesis of deuterated 3-methoxybenzaldehyde Equation (6) Example 14 0.4 mmol (54.5 mg) of 3-methoxybenzaldehyde, 0.5 mL of heavy water (99.9%), 3 mL of tetrahydrofuran solution (99.9%), and 10 mg of 5 wt.% cerium oxide-supported Pt-based catalyst were added to a 25 mL Schlenk tube. After the reaction tube was evacuated to reduced pressure, the residual air in the reaction system was replaced twice with argon gas (99.999%). Finally, 0.1 MPa of argon gas (99.999%) was introduced, and the reaction tube was placed in a preheated 140°C oil bath. The reaction was carried out at a stirring rate of 800 rpm for 24 h, and then cooled to room temperature. The catalyst was removed through a filter to obtain a mixed solution of heavy water, tetrahydrofuran, and crude product. The mixed solution was extracted with dichloromethane in three portions, 10 mL each time, to separate the organic layer and the heavy water layer. The upper organic liquid was collected. Subsequently, 10 mg of anhydrous magnesium sulfate was added as a drying agent to remove residual heavy water. Finally, the organic solution was removed by rotary evaporation under reduced pressure at 40°C to obtain 49.5 mg of the target deuterated product, with a yield of 91% and a formyl deuteration rate of 86%.

[0036] Synthesis of deuterated 2-methoxybenzaldehyde Equation (7) Example 15 0.4 mmol (54.5 mg) of 2-methoxybenzaldehyde, 0.5 mL of heavy water (99.9%), 3 mL of tetrahydrofuran solution (99.9%), and 10 mg of 5 wt.% cerium oxide-supported Pt-based catalyst were added to a 25 mL Schlenk tube. After the reaction tube was evacuated to reduced pressure, the residual air in the reaction system was replaced twice with argon gas (99.999%). Finally, 0.1 MPa of argon gas (99.999%) was introduced, and the reaction tube was placed in a preheated 140°C oil bath. The reaction was carried out at a stirring rate of 800 rpm for 24 h, and then cooled to room temperature. The catalyst was removed through a filter to obtain a mixed solution of heavy water, tetrahydrofuran, and crude product. The mixed solution was extracted with dichloromethane in three portions, 10 mL each time, to separate the organic layer and the heavy water layer. The upper organic liquid was collected. Subsequently, 10 mg of anhydrous magnesium sulfate was added as a drying agent to remove residual heavy water. Finally, the organic solution was removed by rotary evaporation under reduced pressure at 40°C to obtain 38.1 mg of the target deuterated product, with a yield of 70% and a formyl deuteration rate of 68%.

[0037] Synthesis of deuterated 4-chlorobenzaldehyde Equation (8) Example 16 0.4 mmol (56.2 mg) of 4-chlorobenzaldehyde, 0.5 mL of heavy water (99.9%), 3 mL of tetrahydrofuran solution (99.9%), and 10 mg of 5 wt.% cerium oxide-supported Pt-based catalyst were added to a 25 mL Schlenk tube. After the reaction tube was evacuated to reduced pressure, the residual air in the reaction system was replaced twice with argon gas (99.999%). Finally, 0.1 MPa of argon gas (99.999%) was introduced, and the reaction tube was placed in a preheated 140 °C oil bath. The reaction was carried out at a stirring rate of 800 rpm for 24 h, and then cooled to room temperature. The catalyst was removed through a filter to obtain a mixed solution of heavy water, tetrahydrofuran, and crude product. The mixed solution was extracted with dichloromethane in three portions, 10 mL each time, to separate the organic layer and the heavy water layer. The upper organic liquid was collected. Subsequently, 10 mg of anhydrous magnesium sulfate was added as a drying agent to remove residual heavy water. Finally, the organic solution was removed by rotary evaporation under reduced pressure at 40°C to obtain 52.9 mg of the target deuterated product, with a yield of 93% and a formyl deuteration rate of 95%.

[0038] Synthesis of deuterated 4-bromobenzaldehyde Equation (9) Example 17 0.4 mmol (74.0 mg) of 4-bromobenzaldehyde, 0.5 mL of heavy water (99.9%), 3 mL of tetrahydrofuran solution (99.9%), and 10 mg of 5 wt.% cerium oxide-supported Pt-based catalyst were added to a 25 mL Schlenk tube. After the reaction tube was evacuated to reduced pressure, the residual air in the reaction system was replaced twice with argon gas (99.999%). Finally, 0.1 MPa of argon gas (99.999%) was introduced, and the reaction tube was placed in a preheated 140 °C oil bath. The reaction was carried out at a stirring rate of 800 rpm for 24 h, and then cooled to room temperature. The catalyst was removed through a filter to obtain a mixed solution of heavy water, tetrahydrofuran, and crude product. The mixed solution was extracted with dichloromethane in three portions, 10 mL each time, to separate the organic layer and the heavy water layer. The upper organic liquid was collected. Subsequently, 10 mg of anhydrous magnesium sulfate was added as a drying agent to remove residual heavy water. Finally, the organic solution was removed by rotary evaporation under reduced pressure at 40°C to obtain 62.3 mg of the target deuterated product, with a yield of 85% and a formyl deuteration rate of 77%.

[0039] Synthesis of deuterated indole-3-benzaldehyde Equation (10) Example 18 0.4 mmol (58.1 mg) of indole-3-carboxaldehyde, 0.5 mL of heavy water (99.9%), 3 mL of tetrahydrofuran solution (99.9%), and 10 mg of 5 wt.% cerium oxide-supported Pt-based catalyst were added to a 25 mL Schlenk tube. After the reaction tube was evacuated to reduced pressure, the residual air in the reaction system was replaced twice with argon gas (99.999%). Finally, 0.1 MPa of argon gas (99.999%) was introduced, and the reaction tube was placed in a preheated 140 °C oil bath. The reaction was carried out at a stirring rate of 800 rpm for 24 h, and then cooled to room temperature. The catalyst was removed through a filter to obtain a mixed solution of heavy water, tetrahydrofuran, and crude product. The mixed solution was extracted with dichloromethane in three portions, 10 mL each time, to separate the organic layer and the heavy water layer. The upper organic liquid was collected. Subsequently, 10 mg of anhydrous magnesium sulfate was added as a drying agent to remove residual heavy water. Finally, the organic solution was removed by rotary evaporation under reduced pressure at 40°C to obtain 46.4 mg of the target deuterated product, with a yield of 80% and a formyl deuteration rate of 81%.

[0040] Synthesis of deuterated 2,6-dimethylbenzaldehyde Equation (11) Example 19 0.4 mmol (53.7 mg) of 2,6-dimethylbenzaldehyde, 0.5 mL of heavy water (99.9%), 3 mL of tetrahydrofuran solution (99.9%), and 10 mg of 5 wt.% cerium oxide-supported Pt-based catalyst were added to a 25 mL Schlenk tube. After the reaction tube was evacuated to reduced pressure, the residual air in the reaction system was replaced twice with argon gas (99.999%). Finally, 0.1 MPa of argon gas (99.999%) was introduced, and the reaction tube was placed in a preheated 140°C oil bath. The reaction was carried out at a stirring rate of 800 rpm for 24 h, and then cooled to room temperature. The catalyst was removed through a filter to obtain a mixed solution of heavy water, tetrahydrofuran, and crude product. The mixed solution was extracted with dichloromethane in three portions, 10 mL each time, to separate the organic layer and the heavy water layer. The upper organic liquid was collected. Subsequently, 10 mg of anhydrous magnesium sulfate was added as a drying agent to remove residual heavy water. Finally, the organic solution was removed by rotary evaporation under reduced pressure at 40°C to obtain 33.3 mg of the target deuterated product, with a yield of 62% and a formyl deuteration rate of 66%.

[0041] Synthesis of deuterated 3,5-di-tert-butylbenzaldehyde Equation (12) Example 20 0.4 mmol (87.3 mg) of 3,5-di-tert-butylbenzaldehyde, 0.5 mL of heavy water (99.9%), 3 mL of tetrahydrofuran solution (99.9%), and 10 mg of 5 wt.% cerium oxide-supported Pt-based catalyst were added to a 25 mL Schlenk tube. After the reaction tube was evacuated to reduced pressure, the residual air in the reaction system was replaced twice with argon gas (99.999%). Finally, 0.1 MPa of argon gas (99.999%) was introduced, and the reaction tube was placed in a preheated 140°C oil bath. The reaction was carried out at a stirring rate of 800 rpm for 24 h, and then cooled to room temperature. The catalyst was removed through a filter to obtain a mixed solution of heavy water, tetrahydrofuran, and crude product. The product was extracted with dichloromethane in three portions, 10 mL each time, to separate the organic layer and the heavy water layer. The upper organic liquid was collected. Subsequently, 10 mg of anhydrous magnesium sulfate was added as a drying agent to remove residual heavy water. Finally, the organic solution was removed by rotary evaporation under reduced pressure at 40°C to obtain 61.1 mg of the target deuterated product, with a yield of 75% and a formyl deuteration rate of 79%.

[0042] Synthesis of deuterated 2-naphthaldehyde Equation (13) Example 21 0.4 mmol (62.5 mg) of 2-naphthaldehyde, 0.5 mL of heavy water (99.9%), 3 mL of tetrahydrofuran solution (99.9%), and 10 mg of 5 wt.% cerium oxide-supported Pt-based catalyst were added to a 25 mL Schlenk tube. After the reaction tube was evacuated to reduced pressure, the residual air in the reaction system was replaced twice with argon gas (99.999%). Finally, 0.1 MPa of argon gas (99.999%) was introduced, and the reaction tube was placed in a preheated 140 °C oil bath. The reaction was carried out at a stirring rate of 800 rpm for 24 h, and then cooled to room temperature. The catalyst was removed through a filter to obtain a mixed solution of heavy water, tetrahydrofuran, and crude product. The mixed solution was extracted with dichloromethane in three portions, 10 mL each time, to separate the organic layer and the heavy water layer. The upper organic liquid was collected. Subsequently, 10 mg of anhydrous magnesium sulfate was added as a drying agent to remove residual heavy water. Finally, the organic solution was removed by rotary evaporation under reduced pressure at 40°C to obtain 60.0 mg of the target deuterated product, with a yield of 96% and a formyl deuteration rate of 99%.

[0043] Synthesis of deuterated 4-biphenylformaldehyde Equation (14) Example 22 0.4 mmol (72.9 mg) of 4-biphenylaldehyde, 0.5 mL of heavy water (99.9%), 3 mL of tetrahydrofuran solution (99.9%), and 10 mg of 5 wt.% cerium oxide-supported Pt-based catalyst were added to a 25 mL Schlenk tube. After the reaction tube was evacuated to reduced pressure, the residual air in the reaction system was replaced twice with argon gas (99.999%). Finally, 0.1 MPa of argon gas (99.999%) was introduced, and the reaction tube was placed in a preheated 140°C oil bath. The reaction was carried out at a stirring rate of 800 rpm for 24 h, and then cooled to room temperature. The catalyst was removed through a filter to obtain a mixed solution of heavy water, tetrahydrofuran, and crude product. The mixed solution was extracted with dichloromethane in three portions, 10 mL each time, to separate the organic layer and the heavy water layer. The upper organic liquid was collected. Subsequently, 10 mg of anhydrous magnesium sulfate was added as a drying agent to remove residual heavy water. Finally, the organic solution was removed by rotary evaporation under reduced pressure at 40°C to obtain 55.4 mg of the target deuterated product, with a yield of 76% and a formyl deuteration rate of 80%.

[0044] Synthesis of deuterated 9-anthracene carboxaldehyde (15) Example 23 0.4 mmol (82.5 mg) of 9-anthracene carboxaldehyde, 0.5 mL of heavy water (99.9%), 3 mL of tetrahydrofuran solution (99.9%), and 10 mg of 5 wt.% cerium oxide-supported Pt-based catalyst were added to a 25 mL Schlenk tube. After the reaction tube was evacuated to reduced pressure, the residual air in the reaction system was replaced twice with argon gas (99.999%). Finally, 0.1 MPa of argon gas (99.999%) was introduced, and the reaction tube was placed in a preheated 140 °C oil bath. The reaction was carried out at a stirring rate of 800 rpm for 24 h, and then cooled to room temperature. The catalyst was removed through a filter to obtain a mixed solution of heavy water, tetrahydrofuran, and crude product. The mixed solution was extracted with dichloromethane in three portions, 10 mL each time, to separate the organic layer and the heavy water layer. The upper organic liquid was collected. Subsequently, 10 mg of anhydrous magnesium sulfate was added as a drying agent to remove residual heavy water. Finally, the organic solution was removed by rotary evaporation under reduced pressure at 40°C to obtain 66.8 mg of the target deuterated product, with a yield of 81% and a formyl deuteration rate of 80%.

Claims

1. A method for preparing formyl deuterated aromatic aldehydes using a supported catalyst, characterized in that: This includes the use of aromatic aldehydes as raw materials, heavy water as the deuterium source, and a noble metal supported catalyst to carry out a site-directed hydrogen-deuterium exchange reaction under an inert atmosphere to obtain formyl deuterated aromatic aldehydes; the catalyst support includes oxides, nitrides, or carbides; and the noble metal accounts for 1-8 wt.% of the catalyst. The aromatic aldehyde compounds include one or more of the compounds shown in formula (1), and the formyl deuterated aromatic aldehyde compounds are one or more of the compounds shown in formula (2); Equation (1); Equation (2) Wherein, R is selected from aryl, substituted aryl, polycyclic aryl, substituted polycyclic aryl, heterocyclic aryl, and substituted heterocyclic aryl; The substituents in the substituted aryl, substituted polycyclic aryl, or substituted heterocyclic aryl groups refer to those that are substituted by one or more identical or different alkyl, alkoxy, hydroxyl, amino, nitro, cyano, or halogen functional groups.

2. The method for preparing formyl deuterated aromatic aldehydes using a supported catalyst as described in claim 1, characterized in that: The aryl group, substituted aryl group, polycyclic aryl group, substituted polycyclic aryl group, substituted heterocyclic aryl group, or heterocyclic aryl group mentioned above has a carbon number range of C. 6-20 ; The number of carbon atoms in the heterocyclic aryl group and the substituted heterocyclic aryl group ranges from C1 to C2. 2-10 The heterocycle in the heterocyclic aryl or substituted heterocyclic aryl group is N, O, or S; the carbon number range of the alkyl or alkoxy group in the substituent is C. 1-10 .

3. The method for preparing formyl deuterated aromatic aldehydes using a supported catalyst as described in claim 1 or 2, characterized in that: The aromatic aldehyde compounds include one or more of the following structural formulas: 。 4. The method for preparing formyl deuterated aromatic aldehydes using a supported catalyst as described in claim 1, characterized in that: The oxide includes one or more of cerium oxide, lanthanum oxide, aluminum oxide, and titanium dioxide; the nitride includes boron nitride; the carbide includes boron carbide; and / or, The precious metals include one or more of palladium, ruthenium, platinum and rhodium.

5. A method for preparing formyl deuterated aromatic aldehydes using a supported catalyst as described in claim 1 or 4, characterized in that: It also includes pretreatment of oxides by roasting.

6. The method for preparing formyl deuterated aromatic aldehydes using a supported catalyst as described in claim 1, specifically comprising the following steps: S1 Aromatic aldehydes, heavy water, and catalyst are added to an organic solvent and then ultrasonically mixed until homogeneous. S2 was subjected to multiple displacements under an inert atmosphere, followed by the introduction of an inert atmosphere, and the reaction was carried out by heating and stirring. After the reaction was completed, the mixture was cooled to room temperature, and the catalyst was separated by filtration. The resulting filtrate was a mixed solution of organic solvent containing formyl deuterated aryl aldehydes and heavy water. S3 Add the extractant to the mixed solution, and after the addition is complete, let it stand to separate into layers, remove the heavy water, and collect the organic phase; S4 removes the extractant by vacuum rotary evaporation to obtain the target deuterated product.

7. A method for preparing formyl deuterated aromatic aldehydes using a supported catalyst as described in claim 1 or 6, characterized in that: The molar amount of noble metal in the catalyst is 2% to 5% of the molar amount of aromatic aldehyde compounds; and / or, The molar ratio of the aromatic aldehyde compound to the volume of heavy water used is 1:10~20 mmol / mL.

8. The method for preparing formyl deuterated aromatic aldehydes using a supported catalyst as described in claim 6, characterized in that: The organic solvent described in S1 includes one of tetrahydrofuran, dimethyl sulfoxide, and dioxane; and / or, The volume ratio of organic solvent to heavy water is 1:2~5.

9. The method for preparing formyl deuterated aromatic aldehydes using a supported catalyst as described in claim 6, characterized in that: The stirring speed in S2 is 600~1000 rpm.

10. A method for preparing formyl deuterated aromatic aldehydes using a supported catalyst as described in claim 1 or 6, characterized in that: The reaction is carried out at 0.1–0.5 MPa; and / or, The reaction temperature is 90~150℃.

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