Functionalized graphene material, preparation method and application thereof in preparation of phenylpyruvic acid

Abstract

The application discloses a kind of functionalized graphene materials, preparation method and its application in phenylpyruvic acid preparation, belong to graphene catalytic organic drug synthesis technical field, 4-dimethylaminopyridine is added to the prepared graphene solution, ultrasonic treatment is then carried out under the condition of 120~180 DEG C for 12~36h, the product is filtered, washed and dried after reaction is finished and naturally cooled to room temperature, and black solid is obtained as functionalized graphene material DMAP-rGO, which is used as catalyst to prepare phenylpyruvic acid, has better stability and reusability, and can be widely used in industrial production.

Description

Technical Field

[0001] This invention provides a functionalized graphene material, its preparation method, and its application in the preparation of phenylpyruvic acid, belonging to the field of graphene-catalyzed organic drug synthesis technology. Background Technology

[0002] Phenylacetic acid, a natural amino acid metabolite, plays an irreplaceable role in pharmaceutical and pesticide synthesis. It is an important raw material and intermediate in organic synthesis and can be used as a key intermediate for α-ketophenylalanine calcium, a major component of compound α-keto acid tablets. It is widely used in the synthesis of drugs for treating tumors, hypertension, depression, and glaucoma, as well as sedatives, antibacterial agents, and plant germination promoters. In recent years, chronic kidney disease (CKD) has shown a high incidence rate and a trend towards affecting younger people, attracting increasing attention. Currently, compound α-keto acid tablets are used in the market as a treatment for uremia, demonstrating significant medical efficacy in treating this disease. The main methods for preparing phenylpylacetic acid include obtaining a precursor first, followed by preparation through methods such as the addition of alkali, such as the hydrolysis of benzylidene hydantoin and the synthesis of acetophenone. Currently, the publicly available methods include: Ding Wei, in his master's thesis "Synthesis of Several α-Keto Acids and α-Keto Salts by the Hyne Method," mentioned that phenylpyruvic acid was obtained by hydrolyzing phenylpyruvic acid with 5 times the molar amount of benzylidene hydantoin in 20% NaOH solution, with a yield of 85.4%; Zhou Jingliang et al. (Fine Chemical Intermediates, 2010, 40(01):31-32+45) obtained phenylpyruvic acid by hydrolyzing phenylpyruvic acid with 5 times the molar amount of benzylidene hydantoin in 70% NaOH solution, with a yield of 92.7%; David Crich et al. mentioned a method for synthesizing phenylpyruvic acid using perfluorooctyl tyrosine selenic acid or dis(perfluorooctyl)diselenic acid as a catalyst in J.Org.Chem. 2005, 70, 3309-3311, with a yield of 80%. Both the benzylidene hydantoin hydrolysis method and the acetophenone synthesis method have certain drawbacks, such as too many steps, excessive amount of alkali, large amount of waste from the reaction, excessive acid used during neutralization, low yield, and high cost. Therefore, there is an urgent need to find a catalytic system to reduce the amount of alkali used, simplify the reaction steps, and improve the yield of phenylpyruvic acid.

[0003] Graphene is a two-dimensional planar carbon nanomolecule with advantages such as large specific area, high chemical stability, and good electrical conductivity. It can be used as a catalyst support or the catalyst itself, exhibiting excellent catalytic performance. The catalytic functionalization of graphene can be achieved by controlling the type and density of its surface functional groups. Therefore, graphene catalysts have wide applications in the field of catalysis. Summary of the Invention

[0004] To address the problems in the prior art, this invention synthesizes a functionalized graphene (DMAP-rGO) and applies it to the catalytic synthesis of phenylpyruvic acid. The purpose is to reduce the amount of ethanolamine and sodium hydroxide used, thereby reducing the amount of sulfuric acid used in the post-processing and increasing the yield of phenylpyruvic acid.

[0005] The first objective of this invention is to provide a functionalized graphene material (DMAP-rGO), the structural formula of which is as follows:

[0006]

[0007] The second objective of this invention is to provide a method for preparing functionalized graphene material (DMAP-rGO), comprising the following steps: adding 4-dimethylaminopyridine (DMAP) to a prepared graphene (GO) solution, ultrasonically treating the solution, and then reacting at 120–180°C for 12–36 h. After the reaction is completed, the solution is naturally cooled to room temperature, and the product is filtered, washed, and dried to obtain a black solid, which is the functionalized graphene material (DMAP-rGO).

[0008] Preferably:

[0009] The mass ratio of DMAP to GO added is DMAP:GO = 0.5 to 2:1.

[0010] The third objective of this invention is to provide an application of functionalized graphene material (DMAP-rGO) in the preparation of phenylpyruvic acid, comprising the following steps: using hydantoin and benzaldehyde as starting materials, ethanolamine and sodium hydroxide as bases, functionalized graphene material (DMAP-rGO) as catalyst, and deionized water as solvent, phenylpyruvic acid is synthesized by a two-step one-pot method, without the need for separation of intermediates.

[0011] The reaction process involved in this invention is as follows:

[0012]

[0013] Further preferred settings are:

[0014] In the reaction, the molar ratio of ethanolamine to hydantoin is 0.2 to 0.5:1, and the molar ratio of sodium hydroxide to isobutylene hydantoin is 1 to 2:1.

[0015] In the reaction, the catalyst is a functionalized graphene material (DMAP-rGO), and its amount is 1.0% to 3.0% of the mass of hydantoin.

[0016] The first step of the reaction is carried out at 65°C with magnetic stirring for 8–12 hours, and the second step is carried out under reflux with magnetic stirring for 4–6 hours.

[0017] After the first step of the reaction is completed, sodium hydroxide (NaOH) is directly added to carry out the next step of the reaction. After the second step of the reaction is completed, dilute sulfuric acid is used for acidification.

[0018] After the reaction is complete, the mixture is cooled to room temperature, filtered, acidified, extracted, concentrated and dried to obtain a white solid product, phenylpyruvic acid.

[0019] The beneficial effects of this invention are as follows:

[0020] 1. This invention prepares a novel functionalized graphene (DMAP-rGO), which exhibits excellent catalytic performance as a catalyst for the preparation of phenylpyruvic acid. Furthermore, compared to other catalysts, this catalyst demonstrates better stability and reusability, making it widely applicable in industrial production.

[0021] 2. Experiments revealed that using the aforementioned functionalized graphene (DMAP-rGO) as a catalyst in a two-step, one-pot process for preparing phenylpyruvic acid allows for efficient recycling, reduces post-reaction processing steps, lowers the amount of alkali and sulfuric acid used in post-processing, and increases the yield of phenylpyruvic acid. This invention solves the technical difficulties of existing processes, such as numerous post-reaction steps, large amounts of alkali and acid, and low yield.

[0022] 3. This invention conducts the reaction at a lower temperature, avoiding the safety hazards caused by high-temperature reactions, making the reaction easier to control. At the same time, the reaction operation process and post-processing are simple.

[0023] 4. The process provided by the invention is simple and the conditions are mild. The catalyst can be recycled, which reduces the preparation cost while obtaining high yield and high purity products. It shows better reaction advantages and economic advantages and is more suitable for industrial production.

[0024] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. Attached Figure Description

[0025] Figure 1 The infrared spectrum of the functionalized graphene (DMAP-rGO) prepared in Example 1.

[0026] Figure 2 XPS image of the functionalized graphene (DMAP-rGO) prepared in Example 1.

[0027] Figure 3 The 1H NMR spectrum of phenylpyruvic acid prepared in Application Example 1. Detailed Implementation

[0028] Example 1: Preparation of Functionalized Graphene (DMAP-rGO) Catalyst

[0029] 0.15 g of 4-dimethylaminopyridine (DMAP) powder was added to 60 ml of freshly prepared graphene (GO) solution (2.5 mg / ml). After sonication for 0.5 h, the solution was transferred to a 100 ml pressure-resistant bottle and reacted at 140 °C for 24 h. After the reaction was completed and the solution was allowed to cool naturally to room temperature, the resulting black flocculent product was filtered through a 0.22 μm PTFE membrane and washed three or more times with a large amount of N,N-dimethylformamide (DMF), deionized water, and ethanol to thoroughly remove reaction impurities. The washed filter cake was dried in a vacuum oven to obtain 0.18 g of black solid, which is the functionalized graphene (DMAP-rGO).

[0030] Product confirmation:

[0031] like Figure 1 The image shows the infrared spectrum of functionalized graphene (DMAP-rGO), with the 1580 cm⁻¹ value as an example. -1 The vibrating area is near the graphene C-cell framework, 1200 cm⁻¹. -1 The vicinity is experiencing CN stretching vibration; Figure 2 The XPS plot of functionalized graphene (DMAP-rGO) shows a strong C peak near 284 eV, a weak O peak near 533 eV, and an N peak near 400 eV.

[0032] Examples 2-4: Preparation of Functionalized Graphene Using Different Ratios of DMAP / GO

[0033] The preparation method is the same as in Example 1, except that the mass of DMAP added is adjusted, and the functionalized graphene prepared by using 0.075g, 0.15g, 0.225g, and 0.3g of DMAP are respectively labeled as DMAP-rGO-1, DMAP-rGO-2, DMAP-rGO-3, and DMAP-rGO-4.

[0034] Table 1: Elemental analysis data of functionalized graphene products prepared in different embodiments

[0035]

[0036] Application Example 1: Functionalized Graphene (DMAP-rGO) in the Preparation of Phenylacetic Acid

[0037] In a 100 ml three-necked flask, 0.1 g of the functionalized graphene (DMAP-rGO-2) prepared in Example 1 was added, followed by 50 ml of deionized water, and then 5 g (0.05 mol) of hydantoin and 1.52 g (0.025 mol) of ethanolamine were added sequentially. The mixture was heated to 65 °C with magnetic stirring, and 5.3 g (0.05 mol) of benzaldehyde was added dropwise. The reaction was allowed to proceed for 10 h. After the first step of the reaction was completed, the mixture was cooled to room temperature, and 4 g (0.10 mol) of sodium hydroxide was added. The mixture was heated to reflux and reacted for 6 h. After the second step of the reaction was completed, the functionalized graphene catalyst was obtained by suction filtration using a Buchner funnel and reused. The crude filtrate was acidified to pH 3 with dilute sulfuric acid and filtered a second time using a Buchner funnel to remove impurities. The filtrate after the second filtration was extracted with ethyl acetate / water, the organic phases were combined, concentrated and dried to obtain a white solid product, namely phenylpyruvic acid, with a yield of 90.4%.

[0038] Its product characterization is as follows Figure 3 As shown: 1 H NMR (400MHz, Deuterium Oxide) δ7.38 (dd, J=8.1, 6.5Hz, 2H), 7.33 (d, J=7.1Hz, 1H), 7.25–7.21 (m, 2H), 4.07 (s, 2H).

[0039] Replacement Example 1-12

[0040] The preparation methods of substitution examples 1-12 are the same as those of application example 1, except that the amount of ethanolamine, the amount of NaOH, and the type of catalyst are adjusted, and their effects on the reaction are tested respectively, as shown in Table 2.

[0041] Table 2

[0042]

[0043] As can be seen from Table 2:

[0044] Considering both cost and yield, the functionalized graphene (DMAP-rGO-2) catalyst exhibited the best catalytic performance. Furthermore, the highest reaction yield (90.4%) was achieved when the amount of functionalized graphene catalyst (DMAP-rGO-2) was 2% (0.1 g) of hydantoin, the molar ratio of ethanolamine to hydantoin was 0.5:1, and the molar ratio of sodium hydroxide to isobutylene hydantoin was 2:1.

[0045] Application Example 2: Catalyst Recovery and Utilization

[0046] The functionalized graphene catalyst recovered by filtration in Application Example 1 was washed three times with 10 mL of ethanol, air-dried, and then directly added to a 100 mL three-necked flask. The reaction operation steps and conditions were the same as in Application Example 1. After the reaction was completed, the solid catalyst was recovered and used for the next reaction. The product purification was the same as in Application Example, and the yield was calculated. This cycle was repeated until the third time, and the effect of different cycle numbers on the product yield was recorded, as shown in Table 3.

[0047] Table 3. Effect of cycle number on product yield

[0048] Functionalized graphene (DMAP-rGO-2) catalyst reuse count / time Yield / % 1 90.4 2 90.2 3 90.1 .

[0049] As shown in Table 3:

[0050] The functionalized graphene (DMAP-rGO-2) of this invention retains excellent catalytic performance even after multiple uses. Even after the third cycle, the yield remains above 90%, demonstrating that the catalyst of this invention can be recycled at least three times, exhibiting promising prospects for industrial applications.

[0051] Summarize:

[0052] 1. This invention prepares a novel functionalized graphene (DMAP-rGO), which can be used as a catalyst to prepare phenylpyruvic acid and has a very good catalytic effect.

[0053] 2. Experiments showed that using the aforementioned functionalized graphene (DMAP-rGO) as a catalyst to prepare phenylpyruvic acid can be well recycled, which improves the yield and reduces the amount of ethanolamine, sodium hydroxide and sulfuric acid used in the reaction process and post-treatment.

[0054] It is understood that the above detailed description of the present invention is for illustrative purposes only and is not intended to limit the technical solutions described in the embodiments of the present invention. Those skilled in the art should understand that modifications or equivalent substitutions can still be made to the present invention to achieve the same technical effects; as long as the usage requirements are met, they are all within the protection scope of the present invention.

Claims

1. The application of a functionalized graphene material in the preparation of phenylpyruvic acid, comprising the following steps: Using hydantoin and benzaldehyde as starting materials, ethanolamine and sodium hydroxide as bases, functionalized graphene materials as catalysts, and deionized water as solvent, phenylpyruvic acid is synthesized in a two-step one-pot method without the need for intermediate separation. The two-step one-pot method involves the first step of the reaction being a reaction of hydantoin and benzaldehyde in the presence of ethanolamine at 65°C with magnetic stirring for 8-12 hours. The second step is to add sodium hydroxide after the first step is completed and then reflux the reaction under magnetic stirring for 4-6 hours. The functionalized graphene material has the following structural formula: 。 2. The application of the functionalized graphene material according to claim 1 in the preparation of phenylpyruvic acid, characterized in that: The molar ratio of ethanolamine to hydantoin is 0.2 to 0.5:

1.

3. The application of the functionalized graphene material according to claim 1 in the preparation of phenylpyruvic acid, characterized in that: The molar ratio of sodium hydroxide to hydantoin is 1 to 2:

1.

4. The application of the functionalized graphene material according to claim 1 in the preparation of phenylpyruvic acid, characterized in that: In the reaction, the amount of catalyst-functionalized graphene material used is 1.0% to 3.0% of the mass of hydantoin.

5. The application of the functionalized graphene material according to claim 1 in the preparation of phenylpyruvic acid, characterized in that: After the first step of the reaction is completed, sodium hydroxide is directly added to carry out the second step of the reaction. After the second step of the reaction is completed, dilute sulfuric acid is used for acidification.

6. The application of the functionalized graphene material according to claim 1 in the preparation of phenylpyruvic acid, characterized in that: After the second step of the reaction is completed, the mixture is cooled to room temperature, filtered, acidified, extracted, concentrated and dried to obtain a white solid product, phenylpyruvic acid.

7. The application of the functionalized graphene material according to claim 1 in the preparation of phenylpyruvic acid, characterized in that: The functionalized graphene material is prepared by the following method: 4-dimethylaminopyridine is added to the prepared graphene solution, ultrasonically treated, and then reacted at 120-180℃ for 12-36 h. After the reaction is completed, the mixture is naturally cooled to room temperature, and the product is filtered, washed, and dried to obtain a black solid, which is the functionalized graphene material DMAP-rGO.

8. The application of a functionalized graphene material according to claim 7 in the preparation of phenylpyruvic acid, characterized in that: The mass ratio of 4-dimethylaminopyridine to graphene added is 0.5~2:1.

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