A highly efficient synthesis of indole-2-carboxylic acid

Abstract

The application relates to the technical field of organic synthesis, and particularly discloses a high-efficiency synthesis method of indole-2-carboxylic acid, which comprises the following steps: preparing a high-activity catalyst; preparing a solution containing ethyl nitrophenyl pyruvate by taking o-nitrotoluene and diethyl oxalate as starting materials; adding the solution containing ethyl nitrophenyl pyruvate into a high-pressure kettle, adding the high-activity catalyst, replacing air in the high-pressure kettle with nitrogen, then performing a catalytic hydrogenation reaction, cooling to room temperature after the reaction is completed, filtering the reaction liquid after pressure relief, removing the solvent from the filtrate, and recrystallizing the solid with ethanol to obtain indole-2-carboxylic acid. The application takes o-nitrotoluene and diethyl oxalate as starting materials, synthesizes the target product through two-step reactions, the above conditions are mild and low in cost, the catalyst used in the reaction process is high in catalytic activity, good in cycle stability and easy to recycle.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, in particular to a high-efficiency synthesis method of indole-2-carboxylic acid. BACKGROUND

[0002] Indole-2-carboxylic acid is a colorless, odorless white crystal, which can be dissolved in ethanol, acetone and other organic solvents, is an important chemical raw material for preparing medicines, dyes and other products, and is widely used in the pharmaceutical industry.

[0003] At present, the methods for preparing indole-2-carboxylic acid mainly include the following: 1. Zinc powder reduction method is used for preparation, which not only has high cost and serious environmental pollution, but also has low production pot efficiency, consumes more working hours, has high production cost, is difficult to form large-scale production, and cannot meet the market demand; 2. PtO2 is used as a catalyst, and indole-2-carboxylic acid ethyl ester can be directly obtained by hydrogen reduction in an acidic solvent medium, but PtO2 as a catalyst has high cost and is not suitable for large-scale use in industry; 3. Ethyl o-nitrophenylpyruvate ethanol solution is prepared from o-nitrotoluene and diethyl oxalate, and then indole-2-carboxylic acid is synthesized by hydrogenation method under alkaline conditions with Raney nickel as a catalyst. After the hydrogen absorption reaction is completed, the catalyst is filtered out, the filtrate is evaporated to dryness, and the residue is recrystallized with ethanol. The post-treatment is simple, the reaction yield is high, the problem of complicated post-treatment operation and serious environmental pollution after zinc powder reduction is avoided, and therefore, the method has been widely used. However, the catalyst used in the method has poor cycle stability, and the catalytic activity needs to be further improved. SUMMARY

[0004] The technical problem to be solved by the present application is to provide a high-efficiency synthesis method of indole-2-carboxylic acid in view of the deficiencies in the prior art, which uses o-nitrotoluene and diethyl oxalate as starting materials, and synthesizes the target product through two-step reaction. The above-mentioned conditions are mild and low in cost, and the catalyst used in the reaction process has high catalytic activity and good cycle stability, and is easy to recover.

[0005] To solve the above technical problems, the technical scheme of the present application is as follows:

[0006] A high-efficiency synthesis method of indole-2-carboxylic acid, comprising the following steps:

[0007] (1) The bacterial cellulose membrane is immersed in a dopamine solution for treatment, then taken out and added to a Tris buffer solution for continuous treatment, and after the treatment is completed, the modified bacterial cellulose membrane is obtained after washing, and is ready for use.

[0008] (2) stirring under the condition of adding Ti3AlC2 powder into the mixed solution of hydrochloric acid and lithium fluoride, stirring treatment at room temperature, then centrifugation, washing the precipitate to neutral, then adding the precipitate and the modified bacterial cellulose film obtained in step (1) into deionized water, ultrasonic dispersion under argon flow, then centrifugation, drying the precipitate, obtaining a bacterial cellulose film / Mxene composite layered material;

[0009] (3) dispersing the above bacterial cellulose film / Mxene composite layered material in deionized water, adding polyvinylpyrrolidone, ultrasonic dispersion again, obtaining a dispersion liquid, adding nickel nitrate hexahydrate, cobalt nitrate hexahydrate and terephthalic acid into DMF, stirring until the solid is dissolved, obtaining solution A, ultrasonic treatment of solution A into the dispersion liquid, transferring the obtained reaction liquid into an autoclave for reaction, after the reaction is completed, cooling the reaction liquid to room temperature for filtration, drying the precipitate after washing, obtaining a high-activity catalyst;

[0010] (4) dissolving sodium methoxide in anhydrous methanol, adding a mixture of o-nitrotoluene and diethyl oxalate into the above system, warming reaction, after the reaction is completed, cooling the reaction liquid to room temperature, obtaining a solution containing ethyl nitrophenylpyruvate;

[0011] (5) adding the solution containing ethyl nitrophenylpyruvate into an autoclave, adding the high-activity catalyst, introducing nitrogen into the autoclave to replace air, then performing catalytic hydrogenation reaction, after the reaction is completed, cooling to room temperature, after pressure relief, filtering the reaction liquid, after removing the solvent of the filtrate, recrystallizing the solid with ethanol, obtaining indole-2-carboxylic acid.

[0012] As a preferred embodiment of the above technical solution, in step (1), the concentration of the dopamine solution is 2-4 g / L, the temperature for treatment in the dopamine solution is room temperature, and the time is 7-8 h; the concentration of the Tris buffer solution is 10 mM, the temperature for further treatment in the Tris buffer solution is 30℃, and the time is 20-30 min.

[0013] As a preferred embodiment of the above technical solution, in step (2), the concentrations of hydrochloric acid and lithium fluoride in the mixed solution are 9 mol / L and (0.05-0.1) g / ml, respectively; the ratio of the amount of Ti3AlC2 powder to the mixed solution is (1-2) g:20 ml.

[0014] As a preferred embodiment of the above technical solution, in step (2), the stirring treatment at room temperature is under the condition of 1500-3000 rpm for 40-50 h.

[0015] As the preferred technical scheme of the above, in step (2), the ratio of the amount of the precipitate, the modified bacterial cellulose membrane and the deionized water during ultrasonic treatment is (2-3) g: 1 g: (300-400) ml, the power of ultrasonic treatment is 300-500 W, and the time is 1-2 h. The speed of centrifugation is 3000-4000 rpm, and the centrifugation time is 20-30 min.

[0016] As the preferred technical scheme of the above, in step (3), the concentration of the bacterial cellulose membrane / Mxene composite layered material and polyvinylpyrrolidone in the dispersion liquid is 0.001-0.002 g / ml and 0.01 g / ml respectively, the concentration of nickel nitrate hexahydrate, cobalt nitrate hexahydrate and terephthalic acid in solution A is 0.2-0.5 mmol / ml, 0.01-0.02 mmol / ml and 0.01-0.03 mmol / ml respectively, and the volume ratio of solution A and the dispersion liquid is 1:1.

[0017] As the preferred technical scheme of the above, in step (3), the temperature of the reaction is 120℃, and the time is 10-20 h.

[0018] As the preferred technical scheme of the above, in step (4), the ratio of the amount of sodium methoxide, methanol, o-nitrotoluene and diethyl oxalate is (5-6) g: (20-30) ml: (13-14) g: (14-15) g.

[0019] As the preferred technical scheme of the above, in step (4), the temperature of the reaction is 60-65℃, and the time is 1.5-2.5 h.

[0020] As the preferred technical scheme of the above, in step (5), the addition amount of the high-activity catalyst is 5-8% of the mass of diethyl oxalate.

[0021] As the preferred technical scheme of the above, in step (5), the reaction conditions are: 60℃, 1-1.5 MPa, the stirring speed is 300 rpm, and the time is 3-4 h.

[0022] Due to the adoption of the above technical scheme, the present application has the following beneficial effects:

[0023] 1. The present application provides a high-efficiency synthesis method of indole-2-carboxylic acid, which uses o-nitrotoluene and diethyl oxalate as starting materials to prepare ethyl nitrophenylpyruvate under certain conditions; the ethyl nitrophenylpyruvate is subjected to hydrogenation reduction reaction under the catalysis of a high-activity catalyst to obtain the target product, the above conditions are mild, the process is simple, easy to operate, the catalyst is easy to separate, the product is easy to recover, and the method is suitable for industrial production.

[0024] 2、The high-activity catalyst of the present application is a supported catalyst, with bacterial cellulose / Mxene composite material as the carrier, the polydopamine modified bacterial cellulose film surface has rich hydroxyl groups, which is beneficial to the anchoring and growth of metal particles, the Mxene material has a 2D morphology, good chemical stability, and rich polar functional groups, which is also beneficial to the adhesion and growth of metal particles; the above carrier has a porous structure, which is beneficial to the entry of reactant molecules into the inner surface of the catalyst and the contact with more active sites, thereby improving the yield of the product.

[0025] 3、The catalytic activity component of the catalyst of the present application is Co / Ni-MOF, which is dispersed in the bacterial cellulose film / Mxene material to form a sandwich structure, providing double active sites for the catalytic reaction. The catalyst of the present application has a rough surface, a large specific surface area, and a two-dimensional structure that exposes more active sites, giving the catalyst high activity. In addition, the double active sites Co / Ni of the catalyst of the present application have a certain synergistic effect. First, the coexistence of Co and Ni can enhance the activity of the catalyst by producing electron transfer and promote the reaction. Second, the combination of Co and Ni can adjust the electronic structure of the catalyst, thereby optimizing the active sites so that they can more effectively adsorb and activate the reactants and promote the smooth progress of the reaction. The Co / Ni-MOF material has good thermal stability and chemical stability, so it is not easy to deactivate during the reaction, thereby improving the service life of the catalyst. BRIEF DESCRIPTION OF DRAWINGS

[0026] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or prior art description. Obviously, the drawings in the following description are only embodiments of the present application, and for those skilled in the art, other drawings can also be obtained without creative labor on the basis of the provided drawings.

[0027] Figure 1 Preparation of indole-2-carboxylic acid by Example 1 1 H-NMR spectrum (CDCI3, 400MHz);

[0028] Figure 2 Preparation of indole-2-carboxylic acid by Example 1 1 H-NMR spectrum (DMSO, 400MHz). DETAILED DESCRIPTION

[0029] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or prior art description. Obviously, the drawings in the following description are only embodiments of the present application, and for those skilled in the art, other drawings can also be obtained without creative labor on the basis of the provided drawings.

[0030] For a further understanding of the present application, preferred embodiments thereof will be described in conjunction with examples below, it should be understood, however, that these descriptions are merely by way of further illustration of the features and advantages of the present application, but not to limit the claims of the present application.

[0031] The raw materials used in the following examples and comparative examples are all commercially available unless otherwise specified, and the conditions are all conventional conditions in the art unless otherwise specified.

[0032] The yield of indole-2-carboxylic acid (%) = actual yield of product / theoretical yield of product x 100%.

[0033] Example 1

[0034] A highly efficient synthesis method of indole-2-carboxylic acid comprises the following steps:

[0035] (1) The bacterial cellulose film (20 mm x 20 mm x 2 mm) was immersed in 50 ml of dopamine solution with a concentration of 2 g / L, treated at room temperature for 8 h, then taken out and added to 100 ml of Tris buffer solution with a concentration of 10 mmol / L, and continued to be treated at 30°C for 30 min. After the treatment, the modified bacterial cellulose film was obtained after washing and was ready for use;

[0036] (2) 1.0 g of Ti3AlC2 powder was added to 20 ml of a mixed solution of hydrochloric acid and lithium fluoride (the concentrations of hydrochloric acid and lithium fluoride in the mixed solution were 9 mol / L and 0.05 g / ml, respectively) under a stirring speed of 1500 rpm, and stirred at room temperature for 48 h. Then, the precipitate was washed to neutral and centrifuged at 5000 rpm for 30 min. 2 g of the precipitate and 1 g of the modified bacterial cellulose film obtained in step (1) were added to 400 ml of deionized water, and ultrasonic dispersion was performed under argon flow and 500 W for 1 h. Then, the mixture was centrifuged at 3000 rpm for 30 min, and the centrifugal precipitate was dried to obtain a bacterial cellulose film / Mxene composite layered material;

[0037] (3) 60 mg of the bacterial cellulose film / Mxene composite layered material was dispersed in 40 ml of deionized water, and 0.4 g of polyvinylpyrrolidone was added. Ultrasonic dispersion was performed at 500 W for 30 min to obtain a dispersion liquid. 0.3 g of nickel nitrate hexahydrate, 0.146 g of cobalt nitrate hexahydrate, and 0.75 mmol of terephthalic acid were added to 40 ml of DMF, and the mixture was stirred until the solids were dissolved to obtain a solution A. The solution A was added to the dispersion liquid (the volume ratio of the dispersion liquid to the solution A was 1:1), and ultrasonic treatment was performed at 500 W for 20 min. The obtained reaction liquid was transferred to an autoclave, and reaction was performed at 120°C for 16 h. After the reaction, the reaction liquid was cooled to room temperature and filtered. The obtained precipitate was washed and dried to obtain a high-activity catalyst.

[0038] (4) Dissolve 5.94 g sodium methoxide in 20 ml anhydrous methanol, add a mixture of 13.7 g o-nitrotoluene and 14.7 g diethyl oxalate to the above system, heat to 60 °C, react for 1.5 h, and after the reaction is completed, cool the reaction solution to room temperature to obtain a solution containing ethyl nitrophenyl pyruvate.

[0039] (5) The solution containing ethyl nitrophenylpyruvate obtained above was added to a high-pressure reactor, and anhydrous methanol was added to make the volume of the reaction system 200 ml. A highly active catalyst (6% of the mass of diethyl oxalate) was added, and nitrogen was introduced into the high-pressure reactor to replace the air. Then, the catalytic hydrogenation reaction was carried out at 60 °C, 1.5 MPa and a stirring speed of 300 rpm for 4 h. After the reaction was completed, the mixture was cooled to room temperature, and after depressurization, the reaction solution was filtered. After removing the solvent from the filtrate, the solid was recrystallized with ethanol to obtain 15.44 g of indole-2-carboxylic acid, with a yield of 95.8% and an HPLC content of ≥98%.

[0040] from Figure 1 and Figure 2 It can be seen that the product obtained by this invention is indole-2-carboxylic acid.

[0041] Example 2

[0042] An efficient method for synthesizing indole-2-carboxylic acid includes the following steps:

[0043] (1) Immerse the bacterial cellulose membrane (20mm×20mm×2mm) in 50ml of dopamine solution with a concentration of 2.5g / L and treat it at room temperature for 8h. Then, take it out and add it to 100ml of Tris buffer solution with a concentration of 10mmol / L. Continue to treat it at 30℃ for 30min. After treatment, take it out and wash it to obtain the modified bacterial cellulose membrane for later use.

[0044] (2) At a stirring speed of 2000 rpm, 1.0 g Ti3AlC2 powder was added to 20 ml of a mixed solution of hydrochloric acid and lithium fluoride (the concentrations of hydrochloric acid and lithium fluoride in the mixed solution were 9 mol / L and 0.07 g / ml, respectively). The mixture was stirred at room temperature for 48 h. After that, it was centrifuged at 5000 rpm for 30 min. After washing the precipitate to neutral, 2.5 g of the precipitate and 1 g of the modified bacterial cellulose membrane obtained in step (1) were added to 400 ml of deionized water. The mixture was ultrasonically dispersed at 500 W for 1 h under an argon flow. After that, it was centrifuged at 3500 rpm for 30 min. The precipitate was dried by centrifugation to obtain the bacterial cellulose membrane / Mxene composite layered material.

[0045] (3) 60 mg of the above bacterial cellulose film / Mxene composite layered material was dispersed in 40 ml of deionized water, 0.4 g of polyvinylpyrrolidone was added, and ultrasonic dispersion was performed at 500 W for 30 min to obtain a dispersion liquid. 0.3 g of nickel nitrate hexahydrate, 0.146 g of cobalt nitrate hexahydrate, and 0.75 mmol of terephthalic acid were added to 40 ml of DMF, and the mixture was stirred until the solids were dissolved to obtain a solution A. The solution A was added to the dispersion liquid (volume ratio of the dispersion liquid to the solution A was 1:1), and ultrasonic treatment was performed at 500 W for 20 min. The obtained reaction liquid was transferred into an autoclave, and reaction was performed at 120°C for 16 h. After the reaction was completed, the reaction liquid was cooled to room temperature and filtered to obtain a precipitate. The precipitate was washed and dried to obtain a high-activity catalyst;

[0046] (4) 5.94 g of sodium methoxide was dissolved in 20 ml of anhydrous methanol, and a mixture of 13.7 g of o-nitrotoluene and 14.7 g of diethyl oxalate was added to the above system. The mixture was heated to 60°C and reacted for 2 h. After the reaction was completed, the reaction liquid was cooled to room temperature to obtain a solution containing ethyl nitrophenylpyruvate;

[0047] (5) The above prepared solution containing ethyl nitrophenylpyruvate was added to an autoclave, anhydrous methanol was added to the reaction system to a volume of 200 ml, and a high-activity catalyst (6% of the mass of diethyl oxalate) was added. Nitrogen was introduced into the autoclave to replace the air, and then catalytic hydrogenation was performed at 60°C, 1.5 MPa, and a stirring speed of 300 rpm for 4 h. After the reaction was completed, the reaction liquid was cooled to room temperature, and then depressurized and filtered. The filtrate was subjected to solvent removal, and the solid was recrystallized with ethanol to obtain 15.47 g of indole-2-carboxylic acid at a yield of 96.0% and an HPLC content of ≥98%.

[0048] Example 3

[0049] A high-efficiency synthesis method of indole-2-carboxylic acid includes the following steps:

[0050] (1) A bacterial cellulose film (20 mm x 20 mm x 2 mm) was immersed in 50 ml of a dopamine solution with a concentration of 3.5 g / L, and treated at room temperature for 8 h. Then, the film was taken out and added to 100 ml of a Tris buffer solution with a concentration of 10 mmol / L, and treated at 30°C for 30 min. After the treatment was completed, the film was taken out and washed to obtain a modified bacterial cellulose film, which was used as needed.

[0051] (2) 1.0 g of Ti3AlC2 powder was added into a mixed solution of hydrochloric acid and lithium fluoride (the concentrations of hydrochloric acid and lithium fluoride in the mixed solution were 9 mol / L and 0.08 g / ml, respectively) at a stirring speed of 2500 rpm, and stirred at room temperature for 48 h. Then, the precipitate was washed to neutral, and 3 g of the precipitate and 1 g of the modified bacterial cellulose film obtained in step (1) were added into 400 ml of deionized water. The mixture was ultrasonically dispersed under an argon stream at 500 W for 2 h, and then centrifuged at 3500 rpm for 30 min. The centrifugal precipitate was dried to obtain a bacterial cellulose film / Mxene composite layered material;

[0052] (3) 60 mg of the bacterial cellulose film / Mxene composite layered material was dispersed in 40 ml of deionized water, and 0.4 g of polyvinylpyrrolidone was added. The mixture was ultrasonically dispersed at 500 W for 30 min to obtain a dispersion liquid. 0.3 g of nickel nitrate hexahydrate, 0.146 g of cobalt nitrate hexahydrate, and 0.75 mmol of terephthalic acid were added into 40 ml of DMF, and stirred until the solids were dissolved to obtain a solution A. The solution A was added into the dispersion liquid (the volume ratio of the dispersion liquid to the solution A was 1:1), and ultrasonically treated at 500 W for 20 min. The obtained reaction liquid was transferred into an autoclave, and reacted at 120°C for 16 h. After the reaction was completed, the reaction liquid was cooled to room temperature and filtered to obtain a precipitate. The precipitate was washed and dried to obtain a high-activity catalyst;

[0053] (4) 5.94 g of sodium methoxide was dissolved in 20 ml of anhydrous methanol, and a mixture of 13.7 g of o-nitrotoluene and 14.7 g of diethyl oxalate was added into the above system. The system was heated to 60-65°C, and reacted for 2 h. After the reaction was completed, the reaction liquid was cooled to room temperature to obtain a solution containing ethyl nitrophenylpyruvate;

[0054] (5) The above prepared solution containing ethyl nitrophenylpyruvate was added into an autoclave, and anhydrous methanol was added to make the volume of the reaction system 200 ml. A high-activity catalyst (8% of the mass of diethyl oxalate) was added, and nitrogen was introduced into the autoclave to replace the air. Then, the system was subjected to catalytic hydrogenation at 60°C, 1.5 MPa, and a stirring speed of 300 rpm for 4 h. After the reaction was completed, the system was cooled to room temperature, and then depressurized. The reaction liquid was filtered, and the filtrate was subjected to solvent removal. The solid was recrystallized with ethanol to obtain 15.60 g of indole-2-carboxylic acid at a yield of 96.8% and an HPLC content of ≥98%.

[0055] Example 4

[0056] A high-efficiency synthesis method of indole-2-carboxylic acid, comprising the following steps:

[0057] (1) The bacterial cellulose film (20mm x 20mm x 2mm) was immersed in 50ml dopamine solution with a concentration of 3g / L, and treated at room temperature for 8h. Then, the film was taken out and added to 100ml Tris buffer solution with a concentration of 10mmol / L, and treated at 30℃ for 30min. After the treatment, the modified bacterial cellulose film was obtained after washing and was ready for use;

[0058] (2) 1.0g Ti3AlC2 powder was added to 20ml mixed solution of hydrochloric acid and lithium fluoride (the concentrations of hydrochloric acid and lithium fluoride in the mixed solution were 9mol / L and 0.1g / ml, respectively) under stirring at a speed of 1500rpm, and stirred at room temperature for 48h. Then, the precipitate was washed to neutral and centrifuged at 5000rpm for 30min. 2g of the precipitate and 1g of the modified bacterial cellulose film obtained in step (1) were added to 300ml deionized water, and ultrasonically dispersed under argon flow at 500W for 2h. Then, the mixture was centrifuged at 3000rpm for 30min, and the precipitate was dried to obtain the bacterial cellulose film / Mxene composite layered material;

[0059] (3) 60mg of the bacterial cellulose film / Mxene composite layered material was dispersed in 40ml deionized water, and 0.4g of polyvinylpyrrolidone was added. The mixture was ultrasonically dispersed at 500W for 30min to obtain a dispersion liquid. 0.3g of nickel nitrate hexahydrate, 0.146g of cobalt nitrate hexahydrate and 0.75mmol of terephthalic acid were added to 40ml DMF, and the mixture was stirred until the solids were dissolved to obtain solution A. Solution A was added to the dispersion liquid (the volume ratio of the dispersion liquid to solution A was 1:1), and the mixture was ultrasonically treated at 500W for 20min. The obtained reaction liquid was transferred to an autoclave, and reacted at 120℃ for 16h. After the reaction, the reaction liquid was cooled to room temperature and filtered. The obtained precipitate was washed and dried to obtain a high-activity catalyst;

[0060] (4) 5.94g of sodium methoxide was dissolved in 20ml anhydrous methanol, and a mixture of 13.7g of o-nitrotoluene and 14.7g of diethyl oxalate was added to the above system. The mixture was heated to 60℃ and reacted for 2h. After the reaction, the reaction liquid was cooled to room temperature to obtain a solution containing nitrophenylpyruvic acid ethyl ester;

[0061] (5) The solution containing ethyl nitrophenylpyruvate prepared above was added to an autoclave, anhydrous methanol was added to the reaction system to a volume of 200 ml, a high-activity catalyst (8% of the mass of diethyl oxalate) was added, nitrogen was introduced into the autoclave to replace the air, and then the catalytic hydrogenation reaction was carried out at 60°C, 1.5 MPa, and a stirring speed of 300 rpm for 4 h. After the reaction was completed, the reaction solution was cooled to room temperature, and after pressure relief, the reaction solution was filtered, the filtrate was removed from the solvent, and the solid was recrystallized with ethanol to obtain 15.66 g of indole-2-carboxylic acid, with a yield of 97.2% and an HPLC content of ≥98%.

[0062] The present application will be described in detail below with reference to Example 4 and in combination with several comparative examples.

[0063] Comparative Example 1

[0064] Compared with Example 4, the difference is that in step (5), commercially available Raney nickel is used instead of the high-activity catalyst in Example 4, and the other conditions are the same as in Example 4, and 10.93 g of indole-2-carboxylic acid is obtained, with a yield of 67.8%.

[0065] Comparative Example 2

[0066] Compared with Example 4, the difference is that the preparation method of the high-activity catalyst is the same as in Example 4, and the other conditions are the same as in Example 4, and 13.23 g of indole-2-carboxylic acid is obtained, with a yield of 82.1%.

[0067] The preparation process of the catalyst of the present comparative example is as follows: (1) 1.0 g of Ti3AlC2 powder was added to a mixed solution of hydrochloric acid and lithium fluoride (the concentrations of hydrochloric acid and lithium fluoride in the mixed solution were 9 mol / L and 0.1 g / ml, respectively) under a stirring speed of 1500 rpm, and the mixture was stirred at room temperature for 48 h, and then centrifuged at 5000 rpm for 30 min. The precipitate was washed to neutral, 2 g of the precipitate was added to 300 ml of deionized water, and ultrasonic dispersion was carried out under an argon flow and 500 W for 2 h. Then, the mixture was centrifuged at 3000 rpm for 30 min, and the centrifugal precipitate was dried to obtain a Mxene material.

[0068] (3) 60 mg of the above-mentioned Mxene material was dispersed in 40 ml of deionized water, 0.4 g of polyvinylpyrrolidone was added, and ultrasonic dispersion was performed at 500 W for 30 min to obtain a dispersion liquid. 0.3 g of nickel nitrate hexahydrate, 0.146 g of cobalt nitrate hexahydrate, and 0.75 mmol of terephthalic acid were added to 40 ml of DMF, and stirring was performed until the solids were dissolved to obtain a solution A. The solution A was added to the dispersion liquid (the volume ratio of the dispersion liquid and the solution A was 1:1), and ultrasonic treatment was performed at 500 W for 20 min. The obtained reaction liquid was transferred to an autoclave, and reaction was performed at 120°C for 16 h. After the reaction was completed, the reaction liquid was cooled to room temperature and filtered. The obtained precipitate was washed and dried to obtain a catalyst.

[0069] Comparative Example 3

[0070] Compared with Example 4, the difference is that the preparation method of the high-activity catalyst is different from that of Example 4, and other conditions are the same as those of Example 4. 12.01 g of indole-2-carboxylic acid is obtained, and the yield is 74.5%.

[0071] The preparation method of the catalyst of the present comparative example is as follows:

[0072] (1) The bacterial cellulose membrane (20 mm x 20 mm x 2 mm) was immersed in 50 ml of a dopamine solution with a concentration of 3 g / L, and treated at room temperature for 8 h. Then, it was taken out and added to 100 ml of a Tris buffer solution with a concentration of 10 mmol / L, and treated at 30°C for 30 min. After the treatment was completed, it was taken out, washed, and used as a modified bacterial cellulose membrane.

[0073] (2) 60 mg of the above-mentioned bacterial cellulose membrane was dispersed in 40 ml of deionized water, 0.4 g of polyvinylpyrrolidone was added, and ultrasonic dispersion was performed at 500 W for 30 min to obtain a dispersion liquid. 0.3 g of nickel nitrate hexahydrate, 0.146 g of cobalt nitrate hexahydrate, and 0.75 mmol of terephthalic acid were added to 40 ml of DMF, and stirring was performed until the solids were dissolved to obtain a solution A. The solution A was added to the dispersion liquid (the volume ratio of the dispersion liquid and the solution A was 1:1), and ultrasonic treatment was performed at 500 W for 20 min. The obtained reaction liquid was transferred to an autoclave, and reaction was performed at 120°C for 16 h. After the reaction was completed, the reaction liquid was cooled to room temperature and filtered. The obtained precipitate was washed and dried to obtain a catalyst.

[0074] Comparative Example 4

[0075] Compared with Example 4, the difference is that the preparation method of the catalyst is different from that of Example 4, and other conditions are the same as those of Example 4. 11.73 g of indole-2-carboxylic acid is obtained, and the yield is 72.8%.

[0076] In the present comparative example, the preparation method of the catalyst is as follows:

[0077] (1) The bacterial cellulose film (20 mm x 20 mm x 2 mm) was immersed in 50 ml of a dopamine solution with a concentration of 3 g / L, treated at room temperature for 8 h, then taken out and added to 100 ml of a Tris buffer solution with a concentration of 10 mmol / L, and continued to be treated at 30 °C for 30 min. After the treatment was completed, the modified bacterial cellulose film was taken out, washed, and used as needed.

[0078] (2) 1.0 g of Ti3AlC2 powder was added to 20 ml of a mixed solution of hydrochloric acid and lithium fluoride (the concentrations of hydrochloric acid and lithium fluoride in the mixed solution were 9 mol / L and 0.1 g / ml, respectively), stirred at a stirring speed of 1500 rpm for 48 h at room temperature, then centrifuged at 5000 rpm for 30 min. After the precipitate was washed to neutral, 2 g of the precipitate and 1 g of the modified bacterial cellulose film obtained in step (1) were added to 300 ml of deionized water, ultrasonically dispersed in an argon stream at 500 W for 2 h, then centrifuged at 3000 rpm for 30 min. The centrifugal precipitate was dried to obtain a bacterial cellulose film / Mxene composite layered material.

[0079] (3) 60 mg of the above bacterial cellulose film / Mxene composite layered material was dispersed in 40 ml of deionized water, 0.4 g of polyvinylpyrrolidone was added, and ultrasonic dispersion was performed at 500 W for 30 min to obtain a dispersion liquid. 0.446 g of nickel nitrate hexahydrate and 0.5 mmol of terephthalic acid were added to 40 ml of DMF, stirred until the solids were dissolved to obtain a solution A. The solution A was added to the dispersion liquid (the volume ratio of the dispersion liquid to the solution A was 1:1), and ultrasonic treatment was performed at 500 W for 20 min. The obtained reaction liquid was transferred into an autoclave, and reaction was performed at 120 °C for 16 h. After the reaction was completed, the reaction liquid was cooled to room temperature and filtered. The obtained precipitate was washed and dried to obtain a catalyst.

[0080] Comparative Example 5

[0081] Compared with Example 4, the difference lies in that the preparation method of the catalyst is different from that of Example 4, and other conditions are the same as those of Example 4. 8.41 g of indole-2-carboxylic acid was obtained with a yield of 52.2%.

[0082] In the present comparative example, the catalyst was prepared as follows:

[0083] (1) The bacterial cellulose film (20 mm x 20 mm x 2 mm) was immersed in 50 ml of a dopamine solution with a concentration of 3 g / L, treated at room temperature for 8 h, then taken out and added to 100 ml of a Tris buffer solution with a concentration of 10 mmol / L, and continued to be treated at 30 °C for 30 min. After the treatment was completed, the modified bacterial cellulose film was taken out, washed, and used as needed.

[0084] (2) 1.0 g of Ti3AlC2 powder was added into a mixed solution of hydrochloric acid and lithium fluoride (the concentrations of hydrochloric acid and lithium fluoride in the mixed solution were 9 mol / L and 0.1 g / ml, respectively) at a stirring speed of 1500 rpm, and stirring treatment was performed at room temperature for 48 h, followed by centrifugation at 5000 rpm for 30 min. After the precipitate was washed to neutral, 2 g of the precipitate and 1 g of the modified bacterial cellulose film obtained in step (1) were added into 300 ml of deionized water, and ultrasonic dispersion was performed under argon flow and at 500 W for 2 h. After centrifugation at 3000 rpm for 30 min, the centrifugal precipitate was dried to obtain a bacterial cellulose film / Mxene composite layered material;

[0085] (3) 60 mg of the bacterial cellulose film / Mxene composite layered material was dispersed in 40 ml of deionized water, and 0.4 g of polyvinylpyrrolidone was added. Ultrasonic dispersion was performed at 500 W for 30 min to obtain a dispersion liquid. 0.446 g of cobalt nitrate hexahydrate and 0.5 mmol of terephthalic acid were added into 40 ml of DMF, and stirring was performed until the solid was dissolved to obtain a solution A. The solution A was added into the dispersion liquid (the volume ratio of the dispersion liquid to the solution A was 1:1), and ultrasonic treatment was performed at 500 W for 20 min. The obtained reaction liquid was transferred into an autoclave, and reaction was performed at 120℃ for 16 h. After the reaction was completed, the reaction liquid was cooled to room temperature and filtered to obtain a precipitate. After the precipitate was washed and dried, a catalyst was obtained.

[0086] Comparative Example 6

[0087] Compared with Example 4, the difference was that in step (5), the addition amount of the high-activity catalyst was 10% of the mass of diethyl oxalate, and other conditions were the same as those in Example 4. 15.68 g of indole-2-carboxylic acid was obtained, and the yield was 97.3%.

[0088] In summary, compared with the comparative examples, the catalyst prepared by optimizing the composition of the catalyst and the synthesis conditions has high catalytic activity and good stability, and greatly improves the yield of the product.

[0089] In order to verify the cycle stability of the high-activity catalyst of the present application, the following application examples are used for detailed verification and description.

[0090] The high-activity catalyst of Example 4 was used for indole-2-carboxylic acid synthesis after being recycled for 3 times, 5 times and 10 times, respectively. The yield of the product was used as an index of the catalytic activity of the catalyst, and the results are shown in Table 1.

[0091] Table 1

[0092]

[0093] In summary, the catalyst of the present application has high catalytic activity and good cycle stability, and still has high catalytic activity after 10 cycles.

[0094] The principles and implementations of the present application are described herein by using specific examples, and the above examples are only used to help understand the method and core idea of the present application, including the best mode, and also enable any person skilled in the art to practice the present application, including manufacturing and using any device or system, and implementing any combined method. It should be noted that, for those skilled in the art, some improvements and modifications can be made to the present application without departing from the principles of the present application, and these improvements and modifications also fall within the protection scope of the claims of the present application. The scope of patent protection of the present application is defined by the claims, and can include other embodiments that can be thought of by those skilled in the art. If these other embodiments have structural elements similar to the literal expression of the claims, or if they include equivalent structural elements that are not substantially different from the literal expression of the claims, then these other embodiments should also be included in the scope of the claims.

Claims

1. A highly efficient method for synthesizing indole-2-carboxylic acid, characterized in that, Includes the following steps: (1) The bacterial cellulose membrane was immersed in dopamine solution for treatment. Then, it was taken out and added to Tris buffer solution for further treatment. After treatment, it was taken out and washed to obtain the modified bacterial cellulose membrane for later use. (2) Under stirring conditions, Ti3AlC2 powder was added to a mixed solution of hydrochloric acid and lithium fluoride, stirred at room temperature, then centrifuged, and the precipitate was washed until neutral. The precipitate and the modified bacterial cellulose membrane obtained in step (1) were added to deionized water, ultrasonically dispersed under argon flow, then centrifuged, and the precipitate was dried to obtain bacterial cellulose membrane / Mxene composite layered material. (3) The above bacterial cellulose membrane / Mxene composite layered material was dispersed in deionized water, polyvinylpyrrolidone was added, and the mixture was ultrasonically dispersed again to obtain a dispersion. Nickel nitrate hexahydrate, cobalt nitrate hexahydrate and terephthalic acid were added to DMF and stirred until the solid dissolved to obtain solution A. Solution A was added to the dispersion and ultrasonically treated. The resulting reaction solution was transferred to an autoclave for reaction. After the reaction was completed, the reaction solution was cooled to room temperature and filtered. The precipitate was washed and dried to obtain a highly active catalyst. (4) Dissolve sodium methoxide in anhydrous methanol, add a mixture of o-nitrotoluene and diethyl oxalate to the above system, heat the reaction, and after the reaction is completed, cool the reaction solution to room temperature to obtain a solution containing ethyl nitrophenyl pyruvate. (5) Add the solution containing ethyl nitrophenylpyruvate to the autoclave, add a highly active catalyst, and introduce nitrogen into the autoclave to replace the air. Then carry out the catalytic hydrogenation reaction. After the reaction is completed, cool to room temperature, release the pressure, filter the reaction solution, remove the solvent from the filtrate, and recrystallize the solid with ethanol to obtain indole-2-carboxylic acid.

2. The efficient synthesis method of indole-2-carboxylic acid according to claim 1, characterized in that, In step (1), the concentration of the dopamine solution is 2-4 g / L, and the treatment temperature in the dopamine solution is room temperature for 7-8 hours. The concentration of the Tris buffer solution is 10 mM, and the treatment is continued in the Tris buffer solution at a temperature of 30°C for 20-30 min.

3. The efficient synthesis method of indole-2-carboxylic acid according to claim 1, characterized in that, In step (2), the concentrations of hydrochloric acid and lithium fluoride in the mixed solution are 9 mol / L and (0.05-0.1) g / ml, respectively; the ratio of Ti3AlC2 powder to the mixed solution is (1-2) g: 20 ml.

4. The efficient synthesis method of indole-2-carboxylic acid according to claim 1, characterized in that, In step (2), the stirring conditions at room temperature are: 1500-3000 rpm, 40-50 h.

5. The efficient synthesis method of indole-2-carboxylic acid according to claim 1, characterized in that, In step (2), the ratio of the amount of precipitate, modified bacterial cellulose membrane and deionized water used in ultrasonic treatment is (2-3)g:1g:(300-400)ml, the power of ultrasonic treatment is 300-500W, and the time is 1-2h.

6. The efficient synthesis method of indole-2-carboxylic acid according to claim 1, characterized in that, In step (3), the concentrations of bacterial cellulose membrane / Mxene composite layered material and polyvinylpyrrolidone in the dispersion are 0.001-0.002 g / ml and 0.01 g / ml, respectively; in solution A, the concentrations of nickel nitrate hexahydrate, cobalt nitrate hexahydrate, and terephthalic acid are 0.2-0.5 mmol / ml, 0.01-0.02 mmol / ml, and 0.01-0.03 mmol / ml, respectively, and the volume ratio of the dispersion to solution A is 1:

1.

7. The efficient synthesis method of indole-2-carboxylic acid according to claim 1, characterized in that, In step (3), the reaction temperature is 120°C and the time is 10-20h.

8. The efficient synthesis method of indole-2-carboxylic acid according to claim 1, characterized in that, In step (4), the ratio of sodium methoxide, methanol, o-nitrotoluene, and diethyl oxalate is (5-6)g:(20-30)ml:(13-14)g:(14-15)g.

9. The efficient synthesis method of indole-2-carboxylic acid according to claim 1, characterized in that, In step (4), the temperature of the heating reaction is 60-65℃ and the time is 1.5-2.5h.

10. The efficient synthesis method of indole-2-carboxylic acid according to claim 1, characterized in that, In step (5), the amount of highly active catalyst added is 5-8% of the mass of diethyl oxalate; The reaction conditions are: 60℃, 1-1.5MPa, stirring speed of 300rpm, and time of 3-4h.

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