A cinnamic acid derivative having high antioxidative activity and a method for preparing the same

Abstract

This invention belongs to the field of medicinal chemistry, specifically relating to a highly antioxidant cinnamic acid derivative and its preparation method. The preparation method involves preparing a copper triazole-modified mesoporous silica nanocatalytic support, including the preparation and amination of mesoporous silica, grafting of triazole functional groups, copper ion coordination chelation, and high-temperature heat treatment stabilization steps. Then, using this catalytic support, a one-pot condensation reaction is carried out with trihydroxybenzaldehyde and malonic acid as raw materials under heating and ultrasonic assistance. After simple operations such as centrifugation, acid-base adjustment for precipitation, and vacuum filtration and drying, the cinnamic acid derivative is obtained. The catalytic support prepared by this invention has a novel and stable structure, effectively catalyzing the reaction and inhibiting the loss of metal ions. The preparation process of the derivative is extremely simple and mild, the catalyst can be recycled, and the obtained product has extremely high antioxidant activity, making it suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of medicinal chemistry technology, specifically relating to a highly antioxidant cinnamic acid derivative and its preparation method. Background Technology

[0002] Cinnamic acid and its derivatives are a class of naturally occurring phenylpropanoid compounds widely found in plants. The unique unsaturated acrylic acid side chains and phenolic hydroxyl functional groups in their chemical structures endow these compounds with a variety of important biological activities. Studies have shown that cinnamic acid derivatives exhibit significant antioxidant effects in scavenging free radicals and inhibiting lipid peroxidation, while also showing broad application prospects in anti-inflammatory, antibacterial, neuroprotective, and ultraviolet absorption fields. With the increasing demand for natural antioxidants, the development of cinnamic acid derivatives with higher antioxidant activity has become a research hotspot in medicinal chemistry and food science. Currently, combining cinnamic acid with other active pharmacophores through molecular hybridization strategies has been proven to be an effective way to enhance its free radical scavenging ability, and related research provides important theoretical basis for the design and development of novel antioxidants.

[0003] In existing technologies, the synthesis of cinnamic acid derivatives typically employs the classic Knoevenagel condensation reaction, where aromatic aldehydes and malonic acid condense and dehydrate under organic base catalysis to generate the target product. However, traditional synthetic methods have several limitations: First, commonly used catalysts such as pyridine and piperidine are not only consumed in large quantities but are also difficult to recycle, resulting in large amounts of nitrogen-containing wastewater after the reaction, which is inconsistent with the development concept of green chemistry. Second, traditional homogeneous catalytic systems often require long reaction times and high reaction temperatures, leading to high energy consumption and low production efficiency. Third, the product separation and purification process is cumbersome, usually involving multiple extraction, washing, and recrystallization operations, which not only consume large amounts of organic solvents but also makes it difficult to guarantee product yield. Fourth, the antioxidant activity of cinnamic acid derivatives prepared by existing methods still has room for improvement, making it difficult to meet the demand for highly efficient antioxidants in the high-value-added pharmaceutical and cosmetic fields. To address these issues, researchers have attempted to develop heterogeneous catalysts to achieve green improvements in the Knoevenagel condensation reaction, such as using amino-functionalized mesoporous materials to catalyze this reaction, achieving preliminary success.

[0004] In recent years, inorganic functional materials have made groundbreaking progress in the application of catalysis. Mesoporous silica nanoparticles, due to their high specific surface area, ordered pore structure, and good biocompatibility, have been widely used as catalyst supports. However, there are currently no reports on the use of copper-triazole functionalized mesoporous silica nanomaterials for the synthesis of cinnamic acid derivatives and the synergistic enhancement of the antioxidant activity of the products. Therefore, developing a simple preparation process, a recyclable catalyst, and a method for synthesizing cinnamic acid derivatives with significantly enhanced antioxidant activity has important theoretical significance and practical application value. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide a highly antioxidant cinnamic acid derivative and its preparation method.

[0006] In a first aspect, the present invention provides a method for preparing a cinnamic acid derivative with high antioxidant activity, comprising the following steps: S1. By weight, mix 0.8-1.2 parts of 3,4-dihydroxybenzaldehyde, 0.8-2 parts of malonic acid, 0.2-1 parts of copper-triazole modified mesoporous silica nanocatalyst support, and 20-100 parts of deionized water to obtain a mixture; under water bath conditions of 58-62℃, perform an ultrasonic-assisted reaction to obtain a reaction solution; S2. Cool the reaction solution to room temperature, separate the copper-triazole modified mesoporous silica nanocatalyst support by centrifugation and collect the supernatant; adjust the pH of the supernatant to obtain a mixture of precipitated solids; wash the copper-triazole modified mesoporous silica nanocatalyst support with ethanol and water, vacuum dry it and then reuse it. S3. Filter the mixture of precipitated solids to obtain a filter cake. Wash the filter cake with deionized water to obtain a washed filter cake. Dry the washed filter cake under vacuum at 48-52℃.

[0007] In this invention, the preparation mechanism of the highly antioxidant cinnamic acid derivative relies on the multiple synergistic effects of the catalyst. In the presence of a copper-triazole modified mesoporous silica support, 3,4-dihydroxybenzaldehyde and malonic acid undergo a Knoevenagel condensation reaction in a mild aqueous environment. Copper ions act as Lewis acids to activate the aldehyde carbonyl group, lowering the activation energy; simultaneously, the nitrogen heterocycle of the triazole group stabilizes the enol intermediate through a hydrogen bonding network, accelerating the condensation process. After the reaction, adjusting the pH of the system to acidic conditions causes carboxyl groups in the product molecule to become protonated, significantly reducing its water solubility and promoting the precipitation of 3,4-dihydroxycinnamic acid as a light yellow solid. This process requires no complex post-treatment; the catalyst can be recovered through simple centrifugation, and the supernatant is acidified to precipitate the product. After filtration, washing, and direct drying, a high-purity target compound is obtained. This product, due to the strong electron-donating ability provided by the catechol structure in its molecule, can efficiently scavenge free radicals. Its antioxidant activity originates from the synergistic effect of the phenolic hydroxyl group and the conjugated system, resulting in a free radical scavenging efficiency far exceeding that of ordinary cinnamic acid derivatives.

[0008] According to a preferred embodiment of the present invention, in step S1, the time for ultrasonic-assisted reaction of the mixture is 30-60 min.

[0009] According to a preferred embodiment of the present invention, in step S2, the pH of the supernatant is adjusted to 2-3.

[0010] According to a preferred embodiment of the present invention, in step S3, the vacuum drying time at 48-52°C is 6-8 hours.

[0011] According to a preferred embodiment of the present invention, the method for preparing the copper-triazole modified mesoporous silica nanocatalytic support includes: A1. Dissolve 0.8-1.2 parts by weight of hexadecyltrimethylammonium bromide in a mixture of 200-300 parts of deionized water and 3-6 parts of sodium hydroxide solution, add 4-6 parts of tetraethyl orthosilicate, and stir the reaction at 78-82℃ to obtain a reaction mixture; centrifuge, wash, and dry the reaction mixture, and calcine it at 545-555℃ to obtain mesoporous silica nanoparticles; disperse the mesoporous silica nanoparticles in 30-60 parts of anhydrous toluene, add 2-4 parts of 3-aminopropyltriethoxysilane, and reflux the reaction at 108-112℃ under nitrogen protection; after the reaction is completed, centrifuge to obtain a solid, wash the solid with toluene and ethanol, and dry it under vacuum at 58-62℃ to obtain amino-functionalized mesoporous silica; A2. Amino-functionalized mesoporous silica was ultrasonically dispersed in 30-60 parts of anhydrous N,N-dimethylformamide, and 1.5-2.5 parts of 1H-1,2,4-triazole-3-carboxylic acid, 1-2 parts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 0.5-1.5 parts of 4-dimethylaminopyridine were added. The mixture was stirred at room temperature to obtain a reaction solution. The reaction solution was centrifuged to obtain a solid. The solid was washed with N,N-dimethylformamide, deionized water and ethanol to obtain triazole-functionalized mesoporous silica. A3. Disperse triazole-functionalized mesoporous silica in 80-120 parts of deionized water, add 80-120 parts of copper acetate aqueous solution, stir and react in a water bath at 48-52℃ to obtain a mixture; centrifuge the mixture to obtain a solid, wash the solid with deionized water, and dry it under vacuum at 38-42℃ to obtain the product; A4. Place the product in a tube furnace and calcine it at 345-355℃ under a nitrogen atmosphere.

[0012] In this invention, the preparation mechanism of copper-triazole modified mesoporous silica nanocatalytic support is based on multi-level chemical modification and coordination. First, mesoporous silica nanoparticles are synthesized using a hexadecyltrimethylammonium bromide template method, and their surfaces are treated with 3-aminopropyltriethoxysilane to introduce amino functional groups. Subsequently, using a catalytic system of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 4-dimethylaminopyridine, 1H-1,2,4-triazole-3-carboxylic acid is covalently grafted onto the aminosilane surface via amide bonds, forming a stable triazole-functionalized mesoporous silica structure. In this step, the carboxyl and amino groups undergo a dehydration condensation reaction, and the triazole ring acts as a rigid ligand firmly anchored to the silica framework. Next, the triazole-functionalized mesoporous silica reacts with a copper salt solution, and the heterocyclic nitrogen atom on the triazole ring forms a coordination bond with copper ions via its lone pair electrons, allowing copper species to be uniformly dispersed within the mesoporous channels, forming a copper-triazole synergistic coordination structure. Finally, the heat treatment process under nitrogen atmosphere effectively removes weakly adsorbed solvents and unbound organic components from the surface, strengthens the bonding strength of the copper-support interface, constructs a thermodynamically stable composite interface, and significantly inhibits the leaching of copper ions in the catalytic reaction, thereby obtaining a highly stable catalytic support.

[0013] According to a preferred embodiment of the present invention, in step A1, the stirring reaction time at 78-82°C is 2-4 hours.

[0014] According to a preferred embodiment of the present invention, in step A2, the stirring reaction time at room temperature is 48-50 h.

[0015] According to a preferred embodiment of the present invention, in step A3, the stirring reaction time in a water bath at 48-52°C is 12-14 hours.

[0016] According to a preferred embodiment of the present invention, in step A4, the calcination time at 345-355°C is 4-6 hours.

[0017] In a second aspect, the present invention provides a highly antioxidant cinnamic acid derivative, wherein the highly antioxidant cinnamic acid derivative is prepared according to the preparation method of the highly antioxidant cinnamic acid derivative described above.

[0018] Compared with the prior art, the present invention has the following beneficial effects: (1) The highly antioxidant cinnamic acid derivative prepared by this invention has excellent free radical scavenging ability, and its antioxidant performance is significantly better than that of similar compounds prepared by traditional methods. The derivative is 3,4-dihydroxycinnamic acid, and its molecular structure contains an ortho-dihydroxyl group and an unsaturated carboxylic acid conjugated system. The ortho-dihydroxyl group is an excellent hydrogen atom donor, which can effectively capture and neutralize free radicals to terminate the oxidation chain reaction, while the unsaturated carboxylic acid conjugated structure helps to stabilize the phenoloxy free radical intermediate generated during the reaction. In the catalytic synthesis process, the copper triazole modified mesoporous silica nanocatalytic carrier not only plays a highly efficient catalytic role, but the triazole group and copper center on its surface may also affect the electron cloud distribution of the product molecule through non-covalent interactions, further enhancing its antioxidant activity. Experiments show that the product prepared by this invention has a low half-maximum inhibitory concentration (ICP) for free radicals, and has extremely high application value in the fields of food antioxidants, pharmaceutical intermediates and cosmetic additives, which can meet the urgent demand of high-value-added products for highly efficient antioxidant components; (2) The preparation method of the present invention achieves a perfect balance between process complexity and ease of operation. On the one hand, although the preparation of copper triazole-modified mesoporous silica nanocatalytic support involves multiple delicate steps such as mesoporous silica synthesis, amination modification, triazole grafting, copper ion coordination and high-temperature heat treatment, all raw materials are conventional commercially available chemicals, which are easy to obtain and cost-controllable. The high-temperature heat treatment process effectively enhances the interaction between copper species and the support, forming a structurally stable catalytic material, significantly inhibiting the leaching and aggregation of metal ions during the catalytic process, and ensuring the long-term stability of the catalyst. On the other hand, the synthesis steps of the target cinnamic acid derivative are extremely simple. It only requires mixing 3,4-dihydroxybenzaldehyde, malonic acid and the catalytic support in deionized water, and reacting under mild heating and ultrasonic assistance conditions. There is no need to use toxic organic solvents and corrosive acid and base catalysts. After the reaction, the catalytic support can be recovered by simple centrifugation. After adjusting the acidity of the supernatant, the target product is directly precipitated. After filtration and drying, a high-purity product is obtained. The whole process is simple to operate, mild in conditions and short in time, and is suitable for industrial scale-up production. (3) The catalytic system used in this invention exhibits excellent catalytic activity and recyclability. The copper triazole-modified mesoporous silica nanocatalytic support has a synergistic catalytic mechanism with multiple active sites. The copper center, as a Lewis acid, can effectively activate the carbonyl carbon of 3,4-dihydroxybenzaldehyde, promoting the nucleophilic addition of malonic acid. At the same time, the triazole groups on the support surface stabilize the reaction intermediate through hydrogen bonding, accelerating the condensation and dehydration process. Ultrasonic assistance further enhances the mass transfer efficiency and reaction rate. The catalytic support recovered by centrifugation can be directly recycled after simple washing with ethanol and water and vacuum drying. It can still maintain high catalytic activity and product yield after multiple cycles, significantly reducing catalyst cost and waste generation. In addition, the entire synthesis process uses deionized water as the reaction medium, avoiding the environmental and safety risks caused by the use of toxic organic bases such as pyridine and piperidine and large amounts of organic solvents in traditional methods. It is in line with the development concept of green chemistry and has good economic and environmental benefits. Detailed Implementation

[0019] To facilitate understanding of the present invention, the following embodiments are provided. Those skilled in the art should understand that these embodiments are merely illustrative and should not be construed as limiting the scope of the invention.

[0020] Example 1: This example provides a method for preparing a cinnamic acid derivative with high antioxidant activity. First, copper-triazole modified mesoporous silica nanocatalytic supports were prepared, and the specific steps are as follows: A1. Dissolve 1.0 g of hexadecyltrimethylammonium bromide in a mixture of 250 mL of deionized water and 5.0 mL of 2 mol / L sodium hydroxide solution. Place the mixture in a 500 mL round-bottom flask and, under vigorous stirring in an 80 °C oil bath, add 5.0 g of tetraethyl orthosilicate dropwise at a rate of 1 drop per second using a constant-pressure dropping funnel. After the addition is complete, continue stirring for 3 h. Centrifuge the reaction mixture at 8000 rpm for 5 min to separate the solid. Wash the solid twice with 50 mL of deionized water and twice with 50 mL of ethanol. Dry the washed solid in a vacuum drying oven at 60 °C for 12 h. Then, place the dried solid in a muffle furnace and heat it to 550 °C at a heating rate of 2 °C / min. Calcinate at this temperature for 6 h to remove the template agent. Allow it to cool naturally to room temperature to obtain white... Mesoporous silica nanoparticles in powder form were prepared. 1.0 g of the mesoporous silica nanoparticles were ultrasonically dispersed in 45 mL of anhydrous toluene at a power of 200 W, a frequency of 40 kHz, and a time of 10 min. The mixture was then transferred to a 100 mL round-bottom flask, and 3.0 g of 3-aminopropyltriethoxysilane was added. The mixture was refluxed at 110 °C for 24 h under nitrogen protection. The reflux apparatus was equipped with a condenser and a drying tube. After the reaction was completed, the mixture was cooled to room temperature and centrifuged at 8000 rpm for 5 min to separate the solid. The solid was washed three times with 30 mL of toluene and three times with 30 mL of ethanol. The solid was then placed in a vacuum drying oven and dried at 60 °C for 12 h to obtain amino-functionalized mesoporous silica.

[0021] A2. Take 0.8 g of the amino-functionalized mesoporous silica, add 45 mL of anhydrous N,N-dimethylformamide, and ultrasonically disperse for 15 min under ultrasonic power of 200 W and frequency of 40 kHz. Transfer to a 100 mL round-bottom flask, and add 2.0 g of 1H-1,2,4-triazole-3-carboxylic acid, 1.5 g of 1-ethyl-3-dimethylaminopropylcarbodiimide hydrochloride and 1.0 g of 4-dimethylaminopyridine in sequence. Stir magnetically at room temperature for 48 h at a stirring speed of 300 rpm. After the reaction is completed, centrifuge the reaction solution at 8000 rpm for 5 min to separate the solid. Wash the solid three times with 30 mL of N,N-dimethylformamide, three times with 30 mL of deionized water, and three times with 30 mL of ethanol in sequence. Place the solid in a vacuum drying oven and dry at 40 °C for 12 h to obtain triazole-functionalized mesoporous silica.

[0022] A3. Take 0.5g of the triazole-functionalized mesoporous silica, add 100mL of deionized water, and ultrasonically disperse for 15min under ultrasonic power of 200W and frequency of 40kHz. Transfer to a 250mL round-bottom flask, add 100mL of 0.5mol / L copper acetate aqueous solution, and react magnetically in a 50℃ water bath for 13h at a stirring speed of 300rpm. After the reaction, centrifuge the mixture at 8000rpm for 5min to separate the solid. Wash the solid with 100mL of deionized water. Repeat the washing operation, centrifuging at 8000rpm for 5min after each washing to collect the solid until 5mL of the last washing liquid is added to 1mL of 0.1% dithizone carbon tetrachloride solution and shaken. If the carbon tetrachloride layer does not change color, it indicates that no copper ions are detected in the washing liquid. Place the washed solid in a vacuum drying oven and dry at 40℃ for 12h to obtain the solid product.

[0023] A4. Spread the product evenly in a quartz boat, place it in the center of a quartz tube in a tubular furnace, seal both ends of the tubular furnace with furnace plugs, introduce nitrogen gas, control the nitrogen flow rate at 100 mL / min, and ventilate for 30 min to remove air from the tube. Then, under continuous nitrogen venting, raise the temperature from room temperature to 350°C at a rate of 2°C / min, calcine at 350°C for 5 h, and after calcineation, allow it to cool naturally to room temperature. Turn off the nitrogen gas, remove the solid, and obtain a copper-triazole modified mesoporous silica nanocatalytic support.

[0024] Then, a cinnamic acid derivative with high antioxidant activity was prepared, and the specific steps are as follows: S1. Take 1.0g of 3,4-dihydroxybenzaldehyde, 1.2g of malonic acid, 0.5g of the copper-triazole modified mesoporous silica nanocatalyst carrier prepared above, and 50mL of deionized water, and add them sequentially to a 100mL round-bottom flask. Place the flask in a 60℃ water bath, adjust the power of the ultrasonic cleaner to 200W and the frequency to 40kHz, fix the flask in the water bath so that the liquid level is lower than the water bath liquid level, turn on the ultrasonic-assisted reaction for 45min, and keep the water bath temperature constant during the process to obtain a light yellow reaction solution.

[0025] S2. Cool the reaction solution to room temperature, transfer the reaction solution to a centrifuge tube, centrifuge at 8000 rpm for 5 min, collect the supernatant in a beaker, the solid obtained by centrifugation is copper-triazole modified mesoporous silica nanocatalytic support, wash the solid once with 20 mL of ethanol and twice with 20 mL of deionized water, centrifuge at 8000 rpm for 5 min after each wash to collect the solid, place the washed solid in a vacuum drying oven and dry at 50 °C for 6 h to obtain the recovered catalyst for later use; add 1 mol / L dilute hydrochloric acid dropwise to the supernatant while stirring with a glass rod, monitor the pH change with a pH meter, when the pH value is adjusted to 2.5, a large amount of light yellow solid begins to precipitate in the solution, continue stirring for 5 min to complete the precipitation, and obtain a mixture containing the precipitated solid.

[0026] S3. Filter the mixture containing the precipitated solid using a Buchner funnel and a vacuum filtration flask with 9 cm diameter filter paper until no obvious droplets fall, obtaining a filter cake. Transfer the filter cake to a beaker, add 30 mL of deionized water cooled in an ice-water bath, stir and wash for 2 min, filter again, and repeat the washing operation twice. Transfer the washed filter cake to a watch glass and dry it in a vacuum drying oven at 50 °C for 7 h to obtain the target product 3,4-dihydroxycinnamic acid.

[0027] Example 2: The difference between this example and Example 1 is that, firstly, a copper-triazole modified mesoporous silica nanocatalytic support is prepared. The specific steps are as follows: A1. Dissolve 0.8 g of hexadecyltrimethylammonium bromide in a mixture of 200 mL of deionized water and 3.0 mL of 2 mol / L sodium hydroxide solution. Place the mixture in a 500 mL round-bottom flask. Add 4.0 g of tetraethyl orthosilicate dropwise using a constant-pressure dropping funnel while vigorously stirring in an oil bath at 78 °C. After the addition is complete, continue stirring for 2 h. Centrifuge the reaction mixture at 8000 rpm for 5 min to separate the solid. Wash the solid successively with deionized water and ethanol. Dry the washed solid in a vacuum drying oven at 58 °C for 12 h. The dried solid was then placed in a muffle furnace and heated to 545°C at a heating rate of 2°C / min, and calcined at this temperature for 6 hours. After natural cooling to room temperature, mesoporous silica nanoparticles were obtained. 1.0 g of the mesoporous silica nanoparticles were ultrasonically dispersed in 30 mL of anhydrous toluene, and 2.0 g of 3-aminopropyltriethoxysilane was added. The mixture was refluxed at 108°C for 24 hours under nitrogen protection. After the reaction was completed, the solid was centrifuged to separate the solid, washed with toluene and ethanol, and dried under vacuum at 58°C for 12 hours to obtain amino-functionalized mesoporous silica.

[0028] A2. Take 0.8 g of the amino-functionalized mesoporous silica and ultrasonically disperse it in 30 mL of anhydrous N,N-dimethylformamide. Add 1.5 g of 1H-1,2,4-triazole-3-carboxylic acid, 1.0 g of 1-ethyl-3-dimethylaminopropylcarbodiimide hydrochloride and 0.5 g of 4-dimethylaminopyridine. Stir the mixture at room temperature for 48 h. After the reaction is complete, centrifuge to separate the solid. Wash the solid with N,N-dimethylformamide, deionized water and ethanol. Dry it under vacuum at 38 °C for 12 h to obtain triazole-functionalized mesoporous silica.

[0029] A3. Take 0.5g of the triazole-functionalized mesoporous silica and disperse it in 80mL of deionized water. Add 80mL of 0.5mol / L copper acetate aqueous solution and stir the reaction in a water bath at 48℃ for 12h. After the reaction is completed, centrifuge to separate the solid. Wash the solid repeatedly with deionized water until no copper ions can be detected in the washing liquid. Dry it under vacuum at 38℃ for 12h to obtain the product.

[0030] A4. The product is placed in a tube furnace and heated to 345°C at a heating rate of 2°C / min under a nitrogen atmosphere. It is then calcined at this temperature for 4 hours and allowed to cool naturally to room temperature to obtain a copper-triazole modified mesoporous silica nanocatalytic support.

[0031] Then, a cinnamic acid derivative with high antioxidant activity was prepared, and the specific steps are as follows: S1. Take 0.8g of 3,4-dihydroxybenzaldehyde, 0.8g of malonic acid, 0.2g of the copper-triazole modified mesoporous silica nanocatalyst carrier prepared above, and 20mL of deionized water, mix them, and react with ultrasound at 58℃ for 30min to obtain the reaction solution.

[0032] S2. Cool the reaction solution to room temperature, centrifuge to recover the catalyst and collect the supernatant; adjust the pH of the supernatant to 2.0 with dilute hydrochloric acid to obtain a mixture of precipitated solids; wash the recovered catalyst with ethanol and water, and vacuum dry it for later use.

[0033] S3. Filter the mixture of precipitated solids, wash the filter cake with deionized water, and dry it under vacuum at 48°C for 6 hours to obtain the target product 3,4-dihydroxycinnamic acid.

[0034] Example 3: The difference between this example and Example 1 is that, firstly, a copper-triazole modified mesoporous silica nanocatalytic support is prepared. The specific steps are as follows: A1. Dissolve 1.2 g of hexadecyltrimethylammonium bromide in a mixture of 300 mL of deionized water and 6.0 mL of 2 mol / L sodium hydroxide solution. Place the mixture in a 500 mL round-bottom flask and add 6.0 g of tetraethyl orthosilicate dropwise under vigorous stirring in an oil bath at 82 °C. Stir the reaction mixture for 4 h. Centrifuge, wash, and dry the reaction mixture, then calcine it at 555 °C for 6 h to obtain mesoporous silica nanoparticles. Disperse 1.0 g of the mesoporous silica nanoparticles in 60 mL of anhydrous toluene and add 4.0 g of 3-aminopropyltriethoxysilane. Reflux the mixture at 112 °C for 24 h under nitrogen protection. After the reaction is complete, centrifuge to separate the solid. Wash the solid with toluene and ethanol and dry it under vacuum at 62 °C for 12 h to obtain amino-functionalized mesoporous silica.

[0035] A2. Take 0.8 g of the amino-functionalized mesoporous silica and ultrasonically disperse it in 60 mL of anhydrous N,N-dimethylformamide. Add 2.5 g of 1H-1,2,4-triazole-3-carboxylic acid, 2.0 g of 1-ethyl-3-dimethylaminopropylcarbodiimide hydrochloride and 1.5 g of 4-dimethylaminopyridine. Stir the mixture at room temperature for 50 h. After the reaction is complete, centrifuge to separate the solid. Wash the solid with N,N-dimethylformamide, deionized water and ethanol. Dry it under vacuum at 42 °C for 12 h to obtain triazole-functionalized mesoporous silica.

[0036] A3. Take 0.5g of the triazole-functionalized mesoporous silica and disperse it in 120mL of deionized water. Add 120mL of 0.5mol / L copper acetate aqueous solution and stir the reaction in a water bath at 52℃ for 14h. After the reaction is completed, centrifuge to separate the solid. Wash the solid repeatedly with deionized water until no copper ions can be detected in the washing liquid. Dry it under vacuum at 42℃ for 12h to obtain the product.

[0037] A4. The product is placed in a tube furnace and heated to 355°C at a heating rate of 2°C / min under a nitrogen atmosphere. It is then calcined at this temperature for 6 hours and allowed to cool naturally to room temperature to obtain a copper-triazole modified mesoporous silica nanocatalytic support.

[0038] Then, a cinnamic acid derivative with high antioxidant activity was prepared, and the specific steps are as follows: S1. Take 1.2g of 3,4-dihydroxybenzaldehyde, 2.0g of malonic acid, 1.0g of the copper-triazole modified mesoporous silica nanocatalyst carrier prepared above, and 100mL of deionized water, mix them, and react with ultrasound at 62℃ for 60min to obtain the reaction solution.

[0039] S2. Cool the reaction solution to room temperature, centrifuge to recover the catalyst and collect the supernatant; adjust the pH of the supernatant to 3.0 with dilute hydrochloric acid to obtain a mixture of precipitated solids; wash the recovered catalyst with ethanol and water, and vacuum dry it for later use.

[0040] S3. Filter the mixture of precipitated solids, wash the filter cake with deionized water, and dry it under vacuum at 52°C for 8 hours to obtain the target product 3,4-dihydroxycinnamic acid.

[0041] Comparative Example 1 The difference between this comparative example and Example 1 is that, firstly, the comparative catalytic material was prepared, and the specific steps are as follows: A1. Dissolve 1.0 g of hexadecyltrimethylammonium bromide in a mixture of 250 mL of deionized water and 5.0 mL of 2 mol / L sodium hydroxide solution. Add 5.0 g of tetraethyl orthosilicate dropwise under vigorous stirring in an oil bath at 80 °C and stir for 3 h. Centrifuge, wash, and dry the reaction mixture, then calcine at 550 °C for 6 h to obtain mesoporous silica nanoparticles. Disperse 1.0 g of the mesoporous silica nanoparticles in 45 mL of anhydrous toluene, add 3.0 g of 3-aminopropyltriethoxysilane, and reflux at 110 °C for 24 h under nitrogen protection. After the reaction is complete, centrifuge to separate the solid, wash the solid with toluene and ethanol, and dry it under vacuum at 60 °C to obtain amino-functionalized mesoporous silica.

[0042] A2. 0.8 g of the amino-functionalized mesoporous silica was ultrasonically dispersed in 45 mL of anhydrous N,N-dimethylformamide, and 2.0 g of 1H-1,2,4-triazole-3-carboxylic acid, 1.5 g of 1-ethyl-3-dimethylaminopropylcarbodiimide hydrochloride and 1.0 g of 4-dimethylaminopyridine were added. The mixture was stirred at room temperature for 48 h. The reaction solution was centrifuged to separate the solid, and the solid was washed with N,N-dimethylformamide, deionized water and ethanol to obtain triazole-functionalized mesoporous silica.

[0043] A3. Disperse 0.5g of the triazole-functionalized mesoporous silica in 100mL of deionized water, add 100mL of deionized water, and stir the mixture in a 50℃ water bath for 13h. Centrifuge the mixture to separate the solid, wash the solid with deionized water, and dry it under vacuum at 40℃ to obtain the product.

[0044] A4. The product is placed in a tube furnace and heated to 350°C at a heating rate of 2°C / min under a nitrogen atmosphere, and calcined at a constant temperature for 5 hours to obtain the comparative catalyst material.

[0045] Then, cinnamic acid derivatives are prepared, and the specific steps are as follows: S1. Take 1.0g of 3,4-dihydroxybenzaldehyde, 1.2g of malonic acid, 0.5g of the comparative catalyst material prepared above, and 50mL of deionized water, mix them, and react with ultrasound at 60℃ for 45min to obtain the reaction solution.

[0046] S2. Cool the reaction solution to room temperature, centrifuge to recover the comparative catalyst material and collect the supernatant; adjust the pH of the supernatant to 2.5 with dilute hydrochloric acid to obtain a mixture of precipitated solids.

[0047] S3. Filter the mixture of precipitated solids, wash the filter cake with deionized water, and dry it under vacuum at 50°C for 7 hours to obtain the product.

[0048] Comparative Example 2 The difference between this comparative example and Example 1 is that, firstly, the comparative catalytic material was prepared, and the specific steps are as follows: A1. Dissolve 1.0 g of hexadecyltrimethylammonium bromide in a mixture of 250 mL of deionized water and 5.0 mL of 2 mol / L sodium hydroxide solution. Add 5.0 g of tetraethyl orthosilicate dropwise under vigorous stirring in an oil bath at 80 °C and stir for 3 h. Centrifuge, wash, and dry the reaction mixture, then calcine at 550 °C for 6 h to obtain mesoporous silica nanoparticles. Disperse 1.0 g of the mesoporous silica nanoparticles in 45 mL of anhydrous toluene, add 3.0 g of 3-aminopropyltriethoxysilane, and reflux at 110 °C for 24 h under nitrogen protection. After the reaction is complete, centrifuge to separate the solid, wash the solid with toluene and ethanol, and dry it under vacuum at 60 °C to obtain amino-functionalized mesoporous silica.

[0049] A2. Omitting the triazole grafting step, ultrasonically disperse 0.8g of the amino-functionalized mesoporous silica in 45mL of anhydrous N,N-dimethylformamide. After stirring at room temperature for 48h, directly centrifuge to separate the solid. Wash the solid with N,N-dimethylformamide, deionized water and ethanol to obtain unfunctionalized mesoporous silica.

[0050] A3. Disperse 0.5g of the unfunctionalized mesoporous silica in 100mL of deionized water, add 100mL of 0.5mol / L copper acetate aqueous solution, and stir the mixture in a 50℃ water bath for 13h. Centrifuge the mixture to separate the solid, wash the solid with deionized water until no copper ions are detected in the washing liquid, and dry it under vacuum at 40℃ to obtain the product.

[0051] A4. The product is placed in a tube furnace and heated to 350°C at a heating rate of 2°C / min under a nitrogen atmosphere, and calcined at a constant temperature for 5 hours to obtain the comparative catalyst material.

[0052] Then, cinnamic acid derivatives are prepared, and the specific steps are as follows: S1. Take 1.0g of 3,4-dihydroxybenzaldehyde, 1.2g of malonic acid, 0.5g of the comparative catalyst material prepared above, and 50mL of deionized water, mix them, and react with ultrasound at 60℃ for 45min to obtain the reaction solution.

[0053] S2. Cool the reaction solution to room temperature, centrifuge to recover the comparative catalyst material and collect the supernatant; adjust the pH of the supernatant to 2.5 with dilute hydrochloric acid to obtain a mixture of precipitated solids.

[0054] S3. Filter the mixture of precipitated solids, wash the filter cake with deionized water, and dry it under vacuum at 50°C for 7 hours to obtain the product.

[0055] Comparative Example 3 The difference between this comparative example and Example 1 is that, firstly, the comparative catalytic material was prepared, and the specific steps are as follows: A1. Dissolve 1.0 g of hexadecyltrimethylammonium bromide in a mixture of 250 mL of deionized water and 5.0 mL of 2 mol / L sodium hydroxide solution. Add 5.0 g of tetraethyl orthosilicate dropwise in an oil bath at 80 °C with vigorous stirring and stir for 3 h. Centrifuge the reaction mixture, wash with deionized water and ethanol, dry it, and calcine it at 550 °C for 6 h to obtain mesoporous silica nanoparticles, i.e., the comparative catalytic material.

[0056] Then, the cinnamic acid derivative is prepared, and the specific steps are as follows: S1. Take 1.0g of 3,4-dihydroxybenzaldehyde, 1.2g of malonic acid, 0.5g of the comparative catalyst material prepared above, and 50mL of deionized water, mix them, and react with ultrasound at 60℃ for 45min to obtain the reaction solution.

[0057] S2. Cool the reaction solution to room temperature, recover the comparative catalyst material by centrifugation and collect the supernatant; adjust the pH of the supernatant to 2.5 with dilute hydrochloric acid to obtain a mixture of precipitated solids.

[0058] S3. Filter the mixture of precipitated solids, wash the filter cake with deionized water, and dry it under vacuum at 50°C for 7 hours to obtain the product.

[0059] The performance of the highly antioxidant cinnamic acid derivatives provided in the above embodiments and comparative examples was tested using the following methods: The product yield was determined as follows: The final products prepared in Examples 1-3 and Comparative Examples 1-3 were collected respectively. The products were placed in a vacuum drying oven and dried at 50°C to constant weight. The mass of the dried product was accurately weighed using an analytical balance to an accuracy of 0.1 mg. The product yield was calculated according to the following formula: Yield (%) = (actual product mass / theoretical product mass) × 100%, where the theoretical product mass was calculated based on 3,4-dihydroxybenzaldehyde according to the reaction equation.

[0060] The antioxidant activity of the products was determined using the DPPH free radical scavenging method. The specific steps are as follows: Accurately weigh 2,2-diphenyl-1-picrylhydrazine (DPPH) standard, prepare a 0.1 mmol / L DPPH ethanol solution with anhydrous ethanol, and store it in the dark for later use; accurately weigh 10.0 mg each of the products prepared in Examples 1 to 3 and Comparative Examples 1 to 3, place them in a 10 mL amber volumetric flask, dissolve them in anhydrous ethanol, and dilute to the mark to prepare a 1.0 mL solution. The sample stock solution was prepared at a concentration of g / mL; the stock solution was serially diluted with anhydrous ethanol to obtain a series of sample solutions with concentrations of 2.0 μg / mL, 4.0 μg / mL, 6.0 μg / mL, 8.0 μg / mL, 10.0 μg / mL, 12.0 μg / mL, 14.0 μg / mL, 16.0 μg / mL, 18.0 μg / mL and 20.0 μg / mL; 2.0 mL of each sample solution and 2.0 mL of the solution were added sequentially to 10 mL stoppered test tubes. 0 mL of 0.1 mmol / L DPPH ethanol solution was shaken well and reacted at room temperature in the dark for 30 min. A control group was set up: 2.0 mL of anhydrous ethanol was added to 2.0 mL of 0.1 mmol / L DPPH ethanol solution. A background control group was set up: 2.0 mL of the test sample solution was added to 2.0 mL of anhydrous ethanol. After the reaction, the absorbance of each solution was measured at 517 nm using a UV-Vis spectrophotometer. Each sample was measured in triplicate, and the average value was taken. The DPPH free radical scavenging rate was calculated using the following formula: Scavenging rate (%) = [1 - (A sample - A background) / A control] × 100%, where A sample is the absorbance of the sample reaction solution, A background is the absorbance of the sample background control, and A control is the absorbance of the control group. A curve was plotted with sample concentration on the x-axis and scavenging rate on the y-axis. The sample concentration at which the scavenging rate was 50% was calculated by fitting the curve equation using linear regression. This is the half-maximal inhibitory concentration (IC50) value, expressed in μg / mL.

[0061] The catalyst recycling performance test method is as follows: The copper-triazole modified mesoporous silica nanocatalytic support, which was centrifuged and recovered in step S2 of Example 1, washed with ethanol and water, and vacuum dried, was used to repeat the synthesis reaction of cinnamic acid derivatives in the same way as steps S1-S3 of Example 1. After each reaction, the catalyst was recovered in the same way and used for the next reaction. It was recycled for a total of 5 times. The product yield of each cycle reaction was measured and the yield of the first use and the second to fifth uses were recorded as a percentage. The catalyst materials or comparative catalyst materials used in Examples 1, 2, 3 and Comparative Examples 1 to 3 were also recovered according to their respective recovery methods, and the product yield of their 5 cycles was tested according to the same procedure. The yield data of each cycle were recorded.

[0062] The performance test data above are shown in Table 1.

[0063] Table 1 Performance Test Results

[0064] As can be seen from the above, Embodiments 1-3 of the present invention have significant advantages over Comparative Examples 1-3 in several key performance indicators. These advantages directly correspond to and solve several technical problems existing in the prior art.

[0065] First, regarding product yield, the yields of Examples 1-3 reached 96.8%, 94.2%, and 95.7%, respectively, while the yields of Comparative Examples 1-3 were only 52.3%, 61.8%, and 18.5%. This indicates that the copper-triazole modified mesoporous silica nanocatalytic support used in this invention effectively solves the technical problem of low catalytic efficiency of traditional catalysts or unmodified materials. Copper ions, as Lewis acid centers, can efficiently activate carbonyl compounds, and triazole groups stabilize reaction intermediates through hydrogen bonds. The synergistic effect of the two significantly improves the yield of the Knoevenagel condensation reaction.

[0066] Secondly, regarding antioxidant activity, the IC50 values ​​of the products in Examples 1-3 were 7.2 μg / mL, 8.1 μg / mL, and 7.6 μg / mL, respectively, which were much lower than the 18.6 μg / mL, 15.4 μg / mL, and 35.7 μg / mL of Comparative Examples 1-3. The lower the IC50 value, the stronger the antioxidant activity. Therefore, the product of this invention has extremely high free radical scavenging ability, which solves the technical problem of insufficient antioxidant activity of cinnamic acid derivatives prepared by existing technologies. The reason for this is that the copper-triazole modified mesoporous silica nanocatalytic support not only catalyzes the reaction efficiently, but the triazole groups and copper centers on its surface may also affect the electron cloud distribution of the product molecules through non-covalent interactions, thereby further enhancing its antioxidant performance.

[0067] Regarding the catalyst recycling performance, the catalyst of Example 1 maintained a yield of 90.1% after 5 cycles, Example 2 maintained 87.3%, and Example 3 maintained 88.8%. However, the yield of Comparative Example 1 dropped sharply to 19.4% after 5 cycles, Comparative Example 2 dropped to 31.5%, and Comparative Example 3 dropped to 12.6%. This indicates that the present invention effectively solves the technical problems of easy loss of metal ions, poor stability, and inability to recycle traditional catalysts by coordinating and anchoring copper ions to the surface of triazole-functionalized mesoporous silica and enhancing the metal-support interaction through high-temperature heat treatment. This enables multiple reuses of the catalyst and significantly reduces production costs and waste emissions.

[0068] In summary, this invention, by designing a copper-triazole modified mesoporous silica nanocatalytic support, simultaneously introduces Lewis acid catalytic centers and hydrogen bond stabilizing groups, and leverages the high specific surface area of ​​mesoporous silica and the structural stabilization effect of high-temperature treatment, synergistically solves three major technical problems in the synthesis of cinnamic acid derivatives in the prior art: low catalytic efficiency, insufficient antioxidant activity of the product, and inability to recycle the catalyst, achieving unexpected technical results.

Claims

1. A method for preparing a cinnamic acid derivative with high antioxidant activity, characterized in that, Includes the following steps: S1. By weight, mix 0.8-1.2 parts of 3,4-dihydroxybenzaldehyde, 0.8-2 parts of malonic acid, 0.2-1 parts of copper-triazole modified mesoporous silica nanocatalyst support, and 20-100 parts of deionized water to obtain a mixture; under water bath conditions of 58-62℃, perform an ultrasonic-assisted reaction to obtain a reaction solution; S2. Cool the reaction solution to room temperature, separate the copper-triazole modified mesoporous silica nanocatalyst support by centrifugation and collect the supernatant; adjust the pH of the supernatant to obtain a mixture of precipitated solids; wash the copper-triazole modified mesoporous silica nanocatalyst support with ethanol and water, vacuum dry it and then reuse it. S3. Filter the mixture of precipitated solids to obtain a filter cake. Wash the filter cake with deionized water to obtain a washed filter cake. Dry the washed filter cake under vacuum at 48-52℃.

2. The method for preparing the highly antioxidant cinnamic acid derivative according to claim 1, characterized in that, In step S1, the mixture is subjected to an ultrasonic-assisted reaction for 30-60 minutes.

3. The method for preparing the highly antioxidant cinnamic acid derivative according to claim 1, characterized in that, In step S2, the pH of the supernatant is adjusted to 2-3.

4. The method for preparing the highly antioxidant cinnamic acid derivative according to claim 1, characterized in that, In step S3, the vacuum drying time at 48-52℃ is 6-8 hours.

5. The method for preparing the highly antioxidant cinnamic acid derivative according to any one of claims 1-4, characterized in that, The preparation method of the copper-triazole modified mesoporous silica nanocatalytic support includes: A1. Dissolve 0.8-1.2 parts by weight of hexadecyltrimethylammonium bromide in a mixture of 200-300 parts of deionized water and 3-6 parts of sodium hydroxide solution, add 4-6 parts of tetraethyl orthosilicate, and stir the reaction at 78-82℃ to obtain a reaction mixture; centrifuge, wash, and dry the reaction mixture, and calcine it at 545-555℃ to obtain mesoporous silica nanoparticles; disperse the mesoporous silica nanoparticles in 30-60 parts of anhydrous toluene, add 2-4 parts of 3-aminopropyltriethoxysilane, and reflux the reaction at 108-112℃ under nitrogen protection; after the reaction is completed, centrifuge to obtain a solid, wash the solid with toluene and ethanol, and dry it under vacuum at 58-62℃ to obtain amino-functionalized mesoporous silica; A2. Amino-functionalized mesoporous silica was ultrasonically dispersed in 30-60 parts of anhydrous N,N-dimethylformamide, and 1.5-2.5 parts of 1H-1,2,4-triazole-3-carboxylic acid, 1-2 parts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and 0.5-1.5 parts of 4-dimethylaminopyridine were added. The mixture was stirred at room temperature to obtain a reaction solution. The reaction solution was centrifuged to obtain a solid. The solid was washed with N,N-dimethylformamide, deionized water and ethanol to obtain triazole-functionalized mesoporous silica. A3. Disperse triazole-functionalized mesoporous silica in 80-120 parts of deionized water, add 80-120 parts of copper acetate aqueous solution, stir and react in a water bath at 48-52℃ to obtain a mixture; centrifuge the mixture to obtain a solid, wash the solid with deionized water, and dry it under vacuum at 38-42℃ to obtain the product; A4. Place the product in a tube furnace and calcine it at 345-355℃ under a nitrogen atmosphere.

6. The method for preparing the highly antioxidant cinnamic acid derivative according to claim 5, characterized in that, In step A1, the reaction is stirred at 78-82℃ for 2-4 hours.

7. The method for preparing the highly antioxidant cinnamic acid derivative according to claim 5, characterized in that, In step A2, the reaction is stirred at room temperature for 48-50 hours.

8. The method for preparing the highly antioxidant cinnamic acid derivative according to claim 5, characterized in that, In step A3, the reaction is stirred in a water bath at 48-52℃ for 12-14 hours.

9. The method for preparing the highly antioxidant cinnamic acid derivative according to claim 5, characterized in that, In step A4, the calcination time at 345-355℃ is 4-6 hours.

10. A cinnamic acid derivative with high antioxidant activity, characterized in that, The highly antioxidant cinnamic acid derivative is prepared by the method according to any one of claims 1-9.

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