Efficient synthesis method of indole-2-formic acid

Abstract

The invention relates to the technical field of organic synthesis, and particularly discloses an efficient synthesis method of indole-2-formic acid, which comprises the following steps: preparing a high-activity catalyst; the method comprises the following steps: preparing a solution containing nitrophenyl ethyl pyruvate by taking o-nitrotoluene and diethyl oxalate as initial raw materials; the method comprises the following steps: adding a solution containing ethyl nitrophenylpyruvate into a high-pressure kettle, adding a high-activity catalyst, introducing nitrogen into the high-pressure kettle to replace air, then carrying out catalytic hydrogenation reaction, cooling to room temperature after the reaction is finished, carrying out pressure relief, filtering the reaction liquid, removing a solvent from the filtrate, and recrystallizing the solid with ethanol to obtain indole-2-formic acid. According to the method, o-nitrotoluene and diethyl oxalate are taken as starting raw materials, a target product is synthesized through two-step reaction, the conditions are mild, the cost is low, and a catalyst adopted in the reaction process is high in catalytic activity, good in cycling stability and easy to recover.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a high-efficiency synthesis method of indole-2-carboxylic acid. Background Art

[0002] Indole-2-carboxylic acid is a colorless, odorless white crystal that is soluble in organic solvents such as ethanol and acetone. It is an important chemical raw material for the preparation of drugs, 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. The method is prepared by zinc powder reduction, which is not only costly, but also seriously pollutes the environment, and is difficult to separate and filter during production, and the production kettle is inefficient, takes many man-hours, and has high production costs, which makes it difficult to form large-scale production and cannot meet market demand; 2. Using PtO2 as a catalyst, in an acidic solvent medium, indole-2-ethyl carboxylate can be directly obtained by hydrogen reduction, but because PtO2 is more expensive as a catalyst, it is not suitable for large-scale use in industry; 3. Using o-nitrotoluene and diethyl oxalate as starting materials, after preparing an ethanol solution of ethyl o-nitrophenylpyruvate, directly using Raney nickel as a catalyst under alkaline conditions, synthesizing indole-2-carboxylic acid by a hydrogenation method, after the hydrogen absorption reaction is completed, the catalyst is filtered off, the filtrate is evaporated to dryness, and the residue is recrystallized from ethanol, the post-processing is simple, and the reaction yield is high, which not only avoids the problem of complicated post-processing operation and serious environmental pollution caused by zinc powder reduction, but also obtains a wide range of applications. However, the catalyst used in this method has poor cyclic stability and its catalytic activity needs to be further improved. Summary of the invention

[0004] The technical problem to be solved by the present invention is: in view of the shortcomings of the prior art, an efficient synthesis method of indole-2-carboxylic acid is provided. The method uses o-nitrotoluene and diethyl oxalate as starting materials and synthesizes the target product through a two-step reaction. The above conditions are mild and the cost is low. In addition, the catalyst used in the reaction process has high catalytic activity, good cyclic stability and is easy to recycle.

[0005] In order to solve the above technical problems, the technical solution of the present invention is:

[0006] An efficient synthesis method of indole-2-carboxylic acid comprises the following steps:

[0007] (1) immersing the bacterial cellulose membrane in a dopamine solution for treatment, then taking it out and adding it to a Tris buffer solution for further treatment, and after the treatment is completed, taking it out and washing it to obtain a modified bacterial cellulose membrane for standby use;

[0008] (2) adding Ti3AlC2 powder to a mixed solution of hydrochloric acid and lithium fluoride under stirring conditions, stirring at room temperature, and then centrifuging. After washing the precipitate to neutrality, the precipitate and the modified bacterial cellulose membrane obtained in step (1) are added to deionized water, ultrasonically dispersed under argon flow, and then centrifuged. The precipitate is dried to obtain a bacterial cellulose membrane / Mxene composite layered material;

[0009] (3) dispersing the bacterial cellulose membrane / MXene composite layered material in deionized water, adding polyvinyl pyrrolidone, and ultrasonically dispersing again to obtain a dispersion, adding nickel nitrate hexahydrate, cobalt nitrate hexahydrate and terephthalic acid to DMF, stirring until the solid is dissolved to obtain a solution A, adding solution A to the dispersion and ultrasonically treating it, transferring the obtained reaction solution to an autoclave for reaction, cooling the reaction solution to room temperature and filtering the obtained precipitate after washing and drying to obtain a highly active catalyst;

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

[0011] (5) Add the solution containing ethyl nitrophenylpyruvate to an autoclave, add a highly active catalyst, introduce nitrogen into the autoclave to replace the air, and then carry out a 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 using ethanol to obtain 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 treatment temperature in the dopamine solution is room temperature, and the treatment time is 7-8 h; the concentration of the Tris buffer solution is 10 mM, and the temperature for continued treatment in the Tris buffer solution is 30°C, and the treatment 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 dosage ratio 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 conditions at room temperature are: 1500-3000 rpm, 40-50 h.

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

[0016] As a preferred embodiment of the above technical solution, in step (3), in the dispersion, the concentrations of bacterial cellulose membrane / Mxene composite layered material and polyvinyl pyrrolidone 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 solution A to the dispersion is 1:1.

[0017] As a preferred embodiment of the above technical solution, in step (3), the reaction temperature is 120° C. and the reaction time is 10-20 hours.

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

[0019] As a preferred embodiment of the above technical solution, in step (4), the reaction temperature is 60-65°C and the reaction time is 1.5-2.5h.

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

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

[0022] Due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0023] 1. The present invention provides an efficient synthesis method of indole-2-carboxylic acid, wherein o-nitrotoluene and diethyl oxalate are used as starting materials to prepare ethyl nitrophenylpyruvate under certain conditions; ethyl nitrophenylpyruvate is subjected to a hydrogenation reduction reaction under the catalysis of a highly active catalyst to obtain a target product. The above conditions are mild, the process is simple, and the operation is easy. The catalyst is easy to separate and the product is easy to recover, and the method is suitable for industrial production.

[0024] 2. The highly active catalyst of the present invention is a supported catalyst, with bacterial cellulose / Mxene composite material as a carrier. The surface of the bacterial cellulose membrane modified with polydopamine has abundant hydroxyl groups, which is convenient for the anchoring and growth of metal particles. The Mxene material has a 2D morphology, good chemical stability, and abundant polar functional groups, which is also convenient for the adhesion and growth of metal particles. The above-mentioned carrier has a porous structure, which is conducive to the reactant molecules entering the inner surface of the catalyst and contacting more active sites, thereby improving the yield of the product.

[0025] 3. The catalytically active component of the catalyst of the present invention is Co / Ni-MOF, which is dispersed in the bacterial cellulose membrane / Mxene material to form a sandwich structure, providing dual active sites for the catalytic reaction. The catalyst of the present invention 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 dual active sites Co / Ni of the catalyst of the present invention have a certain synergistic effect. First, the co-existence of Co and Ni can enhance the activity of the catalyst by generating electron transfer and promote the reaction; secondly, the combination of Co and Ni can adjust the electronic structure of the catalyst, thereby optimizing the active sites, so that it can more effectively adsorb and activate the reactants and promote the smooth progress of the reaction; Co / Ni-MOF material has good thermal stability and chemical stability, so that it is not easy to deactivate during the reaction, and the service life of the catalyst is improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying creative work.

[0027] Figure 1 Indole-2-carboxylic acid prepared in Example 1 1 H-NMR spectrum (CDCl3, 400 MHz);

[0028] Figure 2 Indole-2-carboxylic acid standard 1 H-NMR spectrum (DMSO, 400 MHz). DETAILED DESCRIPTION

[0029] In order to more clearly understand the above-mentioned objectives, features and advantages of the present invention, the scheme of the present invention will be further described below. It should be noted that the embodiments of the present invention and the features in the embodiments can be combined with each other without conflict.

[0030] In order to further understand the present invention, preferred embodiments of the present invention are described below in conjunction with examples. However, it should be understood that these descriptions are only for further illustrating the features and advantages of the present invention, rather than limiting the claims of the present invention.

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

[0032] Indole-2-carboxylic acid yield (%) = actual product yield / theoretical yield × 100%.

[0033] Example 1

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

[0035] (1) The bacterial fiber membrane (20 mm × 20 mm × 2 mm) was immersed in 50 ml of a 2 g / L dopamine solution and treated at room temperature for 8 h. After that, it was taken out and added to 100 ml of a 10 mmol / L Tris buffer solution and treated at 30°C for 30 min. After the treatment, it was taken out and washed to obtain a modified bacterial cellulose membrane for standby use.

[0036] (2) At a stirring speed of 1500 rpm, 1.0 g of Ti3AlC2 powder was added to a 20 ml mixed solution of hydrochloric acid and lithium fluoride (in the mixed solution, the concentrations of hydrochloric acid and lithium fluoride were 9 mol / L and 0.05 g / ml, respectively), stirred at room temperature for 48 h, then centrifuged at 5000 rpm for 30 min, and after washing the precipitate to neutrality, 2 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, ultrasonically dispersed under argon flow and 500 W for 1 h, and then centrifuged at 3000 rpm for 30 min. The centrifugal precipitate was dried to obtain a bacterial cellulose membrane / Mxene composite layered material;

[0037] (3) 60 mg of the bacterial cellulose membrane / MXene composite layered material was dispersed in 40 ml of deionized water, 0.4 g of polyvinyl pyrrolidone 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 stirred until the solid was dissolved to obtain a solution A. Solution A was added to the dispersion liquid (the volume ratio of the dispersion liquid to 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 reacted 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 highly active catalyst;

[0038] (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, and the temperature was raised to 60° C. and reacted for 1.5 h. After the reaction was completed, the reaction solution was cooled to room temperature to obtain a solution containing ethyl nitrophenylpyruvate;

[0039] (5) The solution containing ethyl nitrophenylpyruvate prepared above was added to an autoclave, anhydrous methanol was added until the volume of the reaction system was 200 ml, 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 a catalytic hydrogenation reaction was carried out at 60° C., 1.5 MPa, and a stirring speed of 300 rpm for 4 hours. After the reaction was completed, it was cooled to room temperature, the reaction solution was filtered after the pressure was released, and the solvent was removed from the filtrate. The solid was recrystallized from 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 prepared by the present invention is indole-2-carboxylic acid.

[0041] Example 2

[0042] An efficient synthesis method of indole-2-carboxylic acid comprises the following steps:

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

[0044] (2) At a stirring speed of 2000 rpm, 1.0 g of Ti3AlC2 powder was added to a 20 ml mixed solution of hydrochloric acid and lithium fluoride (in the mixed solution, the concentrations of hydrochloric acid and lithium fluoride were 9 mol / L and 0.07 g / ml, respectively), stirred at room temperature for 48 h, then centrifuged at 5000 rpm for 30 min, the precipitate was washed to neutrality, 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, ultrasonically dispersed at 500 W for 1 h under an argon flow, then centrifuged at 3500 rpm for 30 min, and the centrifugal precipitate was dried to obtain a bacterial cellulose membrane / Mxene composite layered material;

[0045] (3) 60 mg of the bacterial cellulose membrane / MXene composite layered material was dispersed in 40 ml of deionized water, 0.4 g of polyvinyl pyrrolidone 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 stirred until the solid was dissolved to obtain a solution A. Solution A was added to the dispersion liquid (the volume ratio of the dispersion liquid to 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 reacted 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 highly active 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, and the temperature was raised to 60° C. and reacted for 2 h. After the reaction was completed, the reaction solution 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 until the volume of the reaction system was 200 ml, 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 a catalytic hydrogenation reaction was carried out at 60° C., 1.5 MPa, and a stirring speed of 300 rpm for 4 hours. After the reaction was completed, it was cooled to room temperature, the reaction solution was filtered after the pressure was released, and the solvent was removed from the filtrate. The solid was recrystallized from ethanol to obtain 15.47 g of indole-2-carboxylic acid with a yield of 96.0% and an HPLC content of ≥98%.

[0048] Example 3

[0049] An efficient synthesis method of indole-2-carboxylic acid comprises the following steps:

[0050] (1) Immerse the bacterial fiber membrane (20 mm × 20 mm × 2 mm) in 50 ml of a 3.5 g / L dopamine solution and treat it at room temperature for 8 h. Then, take it out and add it to 100 ml of a 10 mmol / L Tris buffer solution and continue to treat it at 30°C for 30 min. After the treatment, take it out and wash it to obtain a modified bacterial cellulose membrane for standby use.

[0051] (2) At a stirring speed of 2500 rpm, 1.0 g of Ti3AlC2 powder was added to a 20 ml mixed solution of hydrochloric acid and lithium fluoride (in the mixed solution, the concentrations of hydrochloric acid and lithium fluoride were 9 mol / L and 0.08 g / ml, respectively), stirred at room temperature for 48 h, then centrifuged at 5000 rpm for 30 min, and after washing the precipitate to neutrality, 3 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, ultrasonically dispersed under argon flow and 500 W for 2 h, and then centrifuged at 3500 rpm for 30 min. The centrifuged precipitate was dried to obtain a bacterial cellulose membrane / Mxene composite layered material;

[0052] (3) 60 mg of the bacterial cellulose membrane / MXene composite layered material was dispersed in 40 ml of deionized water, 0.4 g of polyvinyl pyrrolidone 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 stirred until the solid was dissolved to obtain a solution A. Solution A was added to the dispersion liquid (the volume ratio of the dispersion liquid to 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 reacted 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 highly active catalyst;

[0053] (4) Dissolve 5.94 g of sodium methoxide in 20 ml of anhydrous methanol, add a mixture of 13.7 g of o-nitrotoluene and 14.7 g of diethyl oxalate to the above system, heat to 60-65° C., react for 2 h, and after the reaction is completed, cool the reaction solution to room temperature to obtain a solution containing ethyl nitrophenylpyruvate;

[0054] (5) The solution containing ethyl nitrophenylpyruvate prepared above was added to an autoclave, anhydrous methanol was added until the volume of the reaction system was 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 a catalytic hydrogenation reaction was carried out at 60° C., 1.5 MPa, and a stirring speed of 300 rpm for 4 hours. After the reaction was completed, it was cooled to room temperature, the reaction solution was filtered after the pressure was released, and the solvent was removed from the filtrate. The solid was recrystallized from ethanol to obtain 15.60 g of indole-2-carboxylic acid with a yield of 96.8% and an HPLC content of ≥98%.

[0055] Example 4

[0056] An efficient synthesis method of indole-2-carboxylic acid comprises the following steps:

[0057] (1) Immerse the bacterial fiber membrane (20 mm × 20 mm × 2 mm) in 50 ml of a 3 g / L dopamine solution and treat it at room temperature for 8 h. Then, take it out and add it to 100 ml of a 10 mmol / L Tris buffer solution and continue to treat it at 30°C for 30 min. After the treatment, take it out and wash it to obtain a modified bacterial cellulose membrane for standby use.

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

[0059] (3) 60 mg of the bacterial cellulose membrane / MXene composite layered material was dispersed in 40 ml of deionized water, 0.4 g of polyvinyl pyrrolidone 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 stirred until the solid was dissolved to obtain a solution A. Solution A was added to the dispersion liquid (the volume ratio of the dispersion liquid to 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 reacted 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 highly active catalyst;

[0060] (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, and the temperature was raised to 60° C. and reacted for 2 h. After the reaction was completed, the reaction solution was cooled to room temperature to obtain a solution containing ethyl nitrophenylpyruvate;

[0061] (5) The above-prepared solution containing ethyl nitrophenylpyruvate was added to an autoclave, anhydrous methanol was added until the volume of the reaction system was 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, a 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 mixture was cooled to room temperature, the pressure was released, and the reaction solution was filtered. After the solvent was removed from the filtrate, the solid was recrystallized from 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 invention is described in detail below with reference to Example 4 and in combination with a plurality of comparative examples.

[0063] Comparative Example 1

[0064] Compared with Example 4, the difference is that in step (5), commercially available Raney nickel is used to replace the high-activity catalyst in Example 4, and other conditions are the same as Example 4, to obtain 10.93 g of indole-2-carboxylic acid, 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 that of Example 4, and the other conditions are the same as those of Example 4, and 13.23 g of indole-2-carboxylic acid is obtained, and the yield is 82.1%;

[0067] The preparation process of the catalyst of this comparative example is as follows: (1) at a stirring speed of 1500 rpm, 1.0 g of Ti3AlC2 powder was added to a mixed solution of 20 ml of hydrochloric acid and lithium fluoride (in the mixed solution, the concentrations of hydrochloric acid and lithium fluoride were 9 mol / L and 0.1 g / ml, respectively), stirred at room temperature for 48 h, then centrifuged at 5000 rpm for 30 min, the precipitate was washed to neutrality, 2 g of the precipitate was added to 300 ml of deionized water, ultrasonically dispersed for 2 h under argon flow and 500 W, then centrifuged at 3000 rpm for 30 min, and the centrifuged precipitate was dried to obtain Mxene material;

[0068] (3) 60 mg of the above-mentioned Mxene material was dispersed in 40 ml of deionized water, 0.4 g of polyvinyl pyrrolidone was added, and ultrasonic dispersion was performed at 500 W for 30 min to obtain a dispersion. 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 stirred until the solid was dissolved to obtain solution A. Solution A was added to the dispersion (the volume ratio of the dispersion to solution A was 1:1), and ultrasonic treatment was performed at 500 W for 20 min. The obtained reaction solution was transferred to an autoclave and reacted at 120 ° C for 16 h. After the reaction was completed, the reaction solution 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 the other conditions are the same as those of Example 4, and 12.01 g of indole-2-carboxylic acid is obtained, and the yield is 74.5%;

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

[0072] (1) Immerse the bacterial fiber membrane (20 mm × 20 mm × 2 mm) in 50 ml of a 3 g / L dopamine solution and treat it at room temperature for 8 h. Then, take it out and add it to 100 ml of a 10 mmol / L Tris buffer solution and continue to treat it at 30°C for 30 min. After the treatment, take it out and wash it to obtain a modified bacterial cellulose membrane for standby use.

[0073] (2) 60 mg of the bacterial cellulose film was dispersed in 40 ml of deionized water, 0.4 g of polyvinyl pyrrolidone was added, and ultrasonic dispersion was performed at 500 W for 30 min to obtain a dispersion. 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 stirred until the solid was dissolved to obtain a solution A. Solution A was added to the dispersion (the volume ratio of the dispersion to solution A was 1:1), and ultrasonic treatment was performed at 500 W for 20 min. The obtained reaction solution was transferred to an autoclave and reacted at 120° C. for 16 h. After the reaction was completed, the reaction solution 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 the other conditions are the same as those of Example 4, and 11.73 g of indole-2-carboxylic acid is obtained, and the yield is 72.8%;

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

[0077] (1) Immerse the bacterial fiber membrane (20 mm × 20 mm × 2 mm) in 50 ml of a 3 g / L dopamine solution and treat it at room temperature for 8 h. Then, take it out and add it to 100 ml of a 10 mmol / L Tris buffer solution and continue to treat it at 30°C for 30 min. After the treatment, take it out and wash it to obtain a modified bacterial cellulose membrane for standby use.

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

[0079] (3) 60 mg of the bacterial cellulose membrane / MXene composite layered material was dispersed in 40 ml of deionized water, 0.4 g of polyvinyl pyrrolidone was added, and ultrasonic dispersion was performed at 500 W for 30 min to obtain a dispersion. 0.446 g of nickel nitrate hexahydrate and 0.5 mmol of terephthalic acid were added to 40 ml of DMF and stirred until the solid was dissolved to obtain a solution A. Solution A was added to the dispersion (the volume ratio of the dispersion to solution A was 1:1), and ultrasonic treatment was performed at 500 W for 20 min. The obtained reaction solution was transferred to an autoclave and reacted at 120 ° C for 16 h. After the reaction was completed, the reaction solution 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 is that the preparation method of the catalyst is different from that of Example 4, and the other conditions are the same as those of Example 4, and 8.41 g of indole-2-carboxylic acid is obtained, and the yield is 52.2%;

[0082] In this comparative example, the preparation method of the catalyst is as follows:

[0083] (1) Immerse the bacterial fiber membrane (20 mm × 20 mm × 2 mm) in 50 ml of a 3 g / L dopamine solution and treat it at room temperature for 8 h. Then, take it out and add it to 100 ml of a 10 mmol / L Tris buffer solution and continue to treat it at 30°C for 30 min. After the treatment, take it out and wash it to obtain a modified bacterial cellulose membrane for standby use.

[0084] (2) At a stirring speed of 1500 rpm, 1.0 g of Ti3AlC2 powder was added to a 20 ml mixed solution of hydrochloric acid and lithium fluoride (in the mixed solution, the concentrations of hydrochloric acid and lithium fluoride were 9 mol / L and 0.1 g / ml, respectively), stirred at room temperature for 48 h, then centrifuged at 5000 rpm for 30 min, and after washing the precipitate to neutrality, 2 g of the precipitate and 1 g of the modified bacterial cellulose membrane obtained in step (1) were added to 300 ml of deionized water, ultrasonically dispersed under argon flow and 500 W for 2 h, and then centrifuged at 3000 rpm for 30 min. The centrifugal precipitate was dried to obtain a bacterial cellulose membrane / Mxene composite layered material;

[0085] (3) Disperse 60 mg of the above bacterial cellulose membrane / MXene composite layered material in 40 ml of deionized water, add 0.4 g of polyvinyl pyrrolidone, and ultrasonically disperse at 500 W for 30 min to obtain a dispersion. Add 0.446 g of cobalt nitrate hexahydrate and 0.5 mmol of terephthalic acid to 40 ml of DMF and stir until the solid is dissolved to obtain solution A. Add solution A to the dispersion (the volume ratio of the dispersion to solution A is 1:1), and ultrasonically treat at 500 W for 20 min. Transfer the obtained reaction solution to an autoclave and react at 120° C. for 16 h. After the reaction is completed, cool the reaction solution to room temperature and filter it. Wash the obtained precipitate and dry it to obtain a catalyst.

[0086] Comparative Example 6

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

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

[0089] In order to verify the cyclic stability of the high-activity catalyst of the present invention, a detailed verification description is given below in conjunction with application examples.

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

[0091] Table 1

[0092]

[0093] In summary, the catalyst of the present invention not only has high catalytic activity but also has good cycle stability, and after being recycled for 10 times, it still has high catalytic activity.

[0094] Specific examples are used herein to illustrate the principles and implementation methods of the present invention. The description of the above embodiments is only used to help understand the method of the present invention and its core ideas, including the best mode, and also enable any technician in the field to practice the present invention, including making and using any device or system, and implementing any combined method. It should be pointed out that for ordinary technicians in this technical field, without departing from the principle of the present invention, the present invention can also be improved and modified, and these improvements and modifications also fall within the scope of protection of the claims of the present invention. The scope of patent protection of the present invention is defined by the claims and may 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. An efficient synthesis method of indole-2-carboxylic acid, characterized in that: The following steps are involved: (1) immersing the bacterial cellulose membrane in a dopamine solution for treatment, then taking it out and adding it to a Tris buffer solution for further treatment, and after the treatment is completed, taking it out and washing it to obtain a modified bacterial cellulose membrane for standby use; (2) adding Ti3AlC2 powder to a mixed solution of hydrochloric acid and lithium fluoride under stirring conditions, stirring at room temperature, and then centrifuging. After washing the precipitate to neutrality, the precipitate and the modified bacterial cellulose membrane obtained in step (1) are added to deionized water, ultrasonically dispersed under argon flow, and then centrifuged. The precipitate is dried to obtain a bacterial cellulose membrane / Mxene composite layered material; (3) dispersing the bacterial cellulose membrane / MXene composite layered material in deionized water, adding polyvinyl pyrrolidone, and ultrasonically dispersing again to obtain a dispersion, adding nickel nitrate hexahydrate, cobalt nitrate hexahydrate and terephthalic acid to DMF, stirring until the solid is dissolved to obtain a solution A, adding solution A to the dispersion and ultrasonically treating it, transferring the obtained reaction solution to an autoclave for reaction, cooling the reaction solution to room temperature and filtering the obtained precipitate after washing and drying to obtain a highly active catalyst; (4) dissolving sodium methoxide in anhydrous methanol, adding a mixture of o-nitrotoluene and diethyl oxalate to the above system, heating the system for reaction, and cooling the reaction solution to room temperature after the reaction is completed to obtain a solution containing ethyl nitrophenylpyruvate; (5) Add the solution containing ethyl nitrophenylpyruvate to an autoclave, add a highly active catalyst, introduce nitrogen into the autoclave to replace the air, and then carry out a 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 using 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, the treatment temperature in the dopamine solution is room temperature, and the treatment time is 7-8 h; The concentration of the Tris buffer solution is 10 mM, and the treatment is continued in the Tris buffer solution at 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 dosage 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 amount ratio of precipitate, modified bacterial cellulose membrane and 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.

6. The efficient synthesis method of indole-2-carboxylic acid according to claim 1, characterized in that: In step (3), in the dispersion, the concentrations of bacterial cellulose membrane / Mxene composite layered material and polyvinyl pyrrolidone 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 reaction time is 10-20 h.

8. The efficient synthesis method of indole-2-carboxylic acid according to claim 1, characterized in that: In step (4), the usage 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 temperature-raising reaction is 60-65° C. and the time is 1.5-2.5 h.

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

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