Preparation method of 1,3-dimethylxanthine

Abstract

The present invention provides a method for preparing 1,3-dimethylxanthine, the method comprising the following steps: obtaining 1,3-dimethyl-4-iminoureazines; dissolving 1,3-dimethyl-4-iminoureazines in formic acid, adding sodium nitrite and nitrogen-doped platinum-carbon catalyst, collecting mother liquor after completion of the reaction, concentrating the mother liquor to remove formic acid, and obtaining 1,3-dimethyl-4-amino-5-formamidoureazines; adding dilute sulfuric acid to 1,3-dimethyl-4-amino-5-formamidoureazines to adjust pH=3-6, heating to 90-100°C, decolorizing the feed liquid by ozone and cold filtering after crystallization, and obtaining 1,3-dimethylxanthines. The preparation method of 1,3-dimethylxanthines of the present invention has mild reaction conditions, simple operation and low energy consumption. By adopting nitrogen-doped platinum-carbon catalyst, the reaction activation energy can be effectively reduced, the reaction rate can be improved, the reaction product purity is high, and the yield is high.

Description

Technical Field

[0001] The present invention relates to the field of medicines, and in particular to a method for preparing 1,3-dimethylxanthine. Background Art

[0002] 1,3-Dimethylxanthine, also known as theophylline, is a compound widely used in the pharmaceutical field. It has attracted much attention due to its unique pharmacological effects, mainly as a non-selective phosphodiesterase (PDE) inhibitor, adenosine receptor blocker and histone deacetylase (HDAC) activator. These properties make theophylline show significant effects in the treatment of various diseases.

[0003] As a phosphodiesterase (PDE) inhibitor, theophylline can inhibit the activity of PDE, thereby preventing the degradation of intracellular cAMP (cyclic adenosine monophosphate) and cGMP (cyclic guanosine monophosphate). These two compounds play an important role in signal transduction in cells, and their accumulation can promote a variety of physiological processes, such as smooth muscle relaxation and vasodilation. Therefore, when theophylline is used to treat cardiovascular diseases such as angina pectoris, it can effectively relieve patients' symptoms by increasing coronary blood flow and reducing myocardial oxygen consumption.

[0004] Theophylline also acts as an adenosine receptor blocker. Adenosine is a nucleoside widely present in organisms and has a variety of physiological effects, such as reducing heart rate and myocardial oxygen consumption. Theophylline plays an important role in the treatment of cardiovascular and respiratory diseases by blocking adenosine receptors and reducing the physiological effects of adenosine. For example, in the treatment of asthma and chronic obstructive pulmonary disease, theophylline can block adenosine receptors, reduce the tension of airway smooth muscles, relieve airway spasms, and thus improve the patient's breathing condition.

[0005] Theophylline is also a histone deacetylase (HDAC) activator. HDAC is an enzyme that can remove histone acetyl groups and is involved in the regulation of gene expression. Theophylline activates HDAC, affecting gene expression, and then exerts multiple effects such as anti-inflammatory and antioxidant effects. These effects are particularly important in the treatment of diseases such as cellulitis, which can effectively reduce inflammatory responses and promote tissue repair.

[0006] The currently known industrial synthesis method of theophylline is to use cyanoacetic acid and dimethylurea as raw materials, and first generate the intermediate product theophylline sodium salt through the steps of condensation, cyclization, subization, water washing, hydrogenation, acylation ring closure, filtration, etc., and then produce the finished product theophylline through the steps of acid adjustment, refining, crystallization, filtration, drying, granulation and crushing.

[0007] This process has many disadvantages, such as complicated process steps, long route, many side reactions and long production cycle. In actual production, in order to ensure the quality of subsequent finished products, it is necessary to add filtration and separation operations in multiple intermediate steps to allow some impurities to leave the reaction system with the mother liquor, thereby generating a large amount of wastewater discharge, with high COD and salinity, posing a considerable challenge to environmental protection treatment. The refining and impurity removal process uses traditional potassium permanganate oxidation and activated carbon decolorization methods, resulting in manganese ion residues in the finished product and the use of hazardous waste. At the same time, multi-step reactions and filtration and purification operations also inhibit the improvement of yield, with the total yield being less than 80%. In addition, since this process uses a large amount of equipment and is an intermittent reaction, it requires a lot of manpower and energy, which increases a lot of costs. Summary of the invention

[0008] The invention provides a method for preparing 1,3-dimethylxanthine to improve the preparation efficiency of 1,3-dimethylxanthine.

[0009] A method for preparing 1,3-dimethylxanthine, characterized in that the method comprises the following steps:

[0010] Obtaining 1,3-dimethyl-4-imidoureazoline;

[0011] Dissolve 1,3-dimethyl-4-aminoureazimine in formic acid, add sodium nitrite and nitrogen-doped platinum-carbon catalyst, collect mother liquor after the reaction is completed, concentrate the mother liquor and filter out formic acid to obtain 1,3-dimethyl-4-amino-5-formamidoureazimine;

[0012] Add dilute sulfuric acid to 1,3-dimethyl-4-amino-5-formamidoureaazine to adjust the pH to 3-6, heat to 90-100° C., decolorize the feed solution with ozone, crystallize it, and then cold filter it to obtain 1,3-dimethylxanthine.

[0013] Furthermore, the mass ratio of 1,3-dimethyl-4-iminoureaazine to formic acid is 1:(4-10).

[0014] Furthermore, the molar ratio of sodium nitrite to 1,3-dimethyl-4-imidourea is (1-1.5):1.

[0015] Furthermore, the mass ratio of the nitrogen-doped platinum carbon catalyst to 1,3-dimethyl-4-imidoureaazine is (0.005-0.05):1.

[0016] Furthermore, the preparation method of the 1,3-dimethyl-4-iminoureaazine comprises the following steps:

[0017] Mix cyanoacetic acid and acetic anhydride, heat to 30-80°C, add solvent and dimethylurea, cool to room temperature after reflux reaction, collect solid matter by filtration, concentrate the filtrate to obtain crystallized solid, combine the solid collected by filtration to obtain dimethylcyanoacetyl urea, add liquid alkali to adjust pH to 8-11, and then react at 80-100°C to generate 1,3-dimethyl-4-imidourea.

[0018] Furthermore, the preparation method of the nitrogen-doped platinum-carbon catalyst comprises the following steps:

[0019] Taking a porous carbon precursor, heating it in a carbon dioxide atmosphere to obtain a carbon support;

[0020] The carbon carrier, the nitrogen source and the organic alcohol are uniformly mixed, and calcined at 800-850° C. to obtain a nitrogen-doped carbon carrier;

[0021] The nitrogen-doped carbon carrier, sodium fluoride and pure water are mixed and stirred, and an ethylene glycol solution of a platinum precursor is added dropwise during the stirring process. The mixture is heated in an oil bath and refluxed and stirred. After the reaction is completed, the solid product is washed and dried to obtain the nitrogen-doped platinum-carbon catalyst.

[0022] Furthermore, the porous carbon precursor includes at least one of mesoporous carbon and Ketjen black.

[0023] Furthermore, the heating temperature is 900-950° C. and the heating time is 30-60 min in a carbon dioxide atmosphere.

[0024] Furthermore, the mass ratio of the carbon carrier, the nitrogen source, and the organic alcohol is (3-5): (6-10): (25-35).

[0025] Furthermore, the platinum precursor includes at least one of chloroplatinic acid and trimethylplatinum.

[0026] The beneficial effects of the present invention are:

[0027] The invention has mild reaction conditions, simple operation and low energy consumption. By adopting nitrogen-doped platinum-carbon catalyst, the reaction activation energy can be effectively reduced, the reaction rate can be increased, and the reaction product has high purity and high yield.

[0028] In addition, the nitrogen-doped platinum-carbon catalyst prepared by the method for preparing the nitrogen-doped platinum-carbon catalyst further proposed in the present invention has a specific surface area of ​​500-650 m 2 / g, where the particle size of platinum is 2.5-5.3nm, with high catalytic activity and catalytic efficiency. DETAILED DESCRIPTION

[0029] It should be noted that, in the absence of conflict, the embodiments of the present invention and the features in the embodiments may be combined with each other.

[0030] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are purchased from conventional biochemical reagent stores unless otherwise specified. In addition, except for special instructions in this example, the terms and processes involved in this example are understood according to the general knowledge and conventional methods in the prior art.

[0031] A method for preparing 1,3-dimethylxanthine, the method comprising the following steps:

[0032] 1,3-dimethyl-4-aminourea zine (also known as dimethyl 4AU) is obtained. Dimethyl 4AU is added to formic acid, stirred until completely dissolved, cooled to -5-10°C, sodium nitrite and nitrogen-doped platinum carbon catalyst are added, heated to room temperature for reaction, and the mother liquor is collected after the reaction is completed, and the mother liquor is concentrated and filtered to remove formic acid to obtain 1,3-dimethyl-4-amino-5-formamidourea zine (also known as dimethyl FAU). Dimethyl FAU is placed in a four-necked bottle, dilute sulfuric acid is added to the four-necked bottle, pH is adjusted to 3-6, heated to 90-100°C, the feed liquid is passed through an ozone reactor and a high-efficiency decolorizer, and crystallized in a crystallizer and then cold filtered to obtain 1,3-dimethylxanthine. In the above steps, the mass ratio of dimethyl 4AU to formic acid is 1:(4-10), the molar ratio of sodium nitrite to dimethyl 4AU is (1-1.5):1, and the mass ratio of nitrogen-doped platinum carbon catalyst to dimethyl 4AU is (0.005-0.05):1.

[0033] The invention has mild reaction conditions, simple operation and low energy consumption. By adopting nitrogen-doped platinum-carbon catalyst, the reaction activation energy can be effectively reduced, the reaction rate can be increased, and the reaction product has high purity and high yield.

[0034] The preparation method of the above dimethyl 4AU comprises the following steps:

[0035] Mix cyanoacetic acid and acetic anhydride, heat to 30-80°C for reaction for 1 hour, add solvent and dimethylurea, cool to room temperature after reflux reaction, collect solid matter by filtration, concentrate the filtrate to crystallize solid, combine the solid collected by filtration to obtain dimethylcyanoacetylurea, add liquid alkali to adjust pH to 8-11, and react at 80-100°C to generate dimethyl 4AU. The above solvent includes at least one of toluene and benzene. The above liquid alkali includes at least one of sodium hydroxide solution and potassium hydroxide solution. The molar ratio of the above cyanoacetic acid, acetic anhydride and dimethylurea is 1: (1-1.2): (1-1.2).

[0036] In order to further reduce the reaction activation energy, the preparation method of the nitrogen-doped platinum-carbon catalyst comprises the following steps:

[0037] A porous carbon precursor is taken and heated in a carbon dioxide atmosphere at a temperature of 900-950°C for a heating time of 30-60 minutes to obtain a carbon carrier with a dominant pore structure. The carbon carrier, nitrogen source and organic alcohol are mixed evenly and calcined at 800-850°C to obtain a nitrogen-doped carbon carrier. The mass ratio of the carbon carrier, nitrogen source and organic alcohol is (3-5): (6-10): (25-35). The nitrogen-doped carbon carrier, sodium fluoride and pure water are mixed and stirred, and an ethylene glycol solution of a platinum precursor is added dropwise during the stirring process. The mixture is heated in an oil bath and refluxed and stirred. After the reaction is completed, the solid and liquid are centrifuged and separated. The solid product is washed with acetone and deionized water and dried to obtain the nitrogen-doped platinum carbon catalyst. The porous carbon precursor includes at least one of mesoporous carbon and Ketjen black. The primary particle size of the carbon carrier formed by carbon dioxide activation of the porous carbon precursor can reach 300-500nm, and the specific surface area can reach 1000-3000m 2 / g. The platinum precursor includes at least one of chloroplatinic acid and trimethylplatinum. The mass ratio of the nitrogen-doped carbon carrier to sodium fluoride is (3-7): (5-9). The concentration of the ethylene glycol solution of chloroplatinic acid is 0.05-0.08 mol / L. The mass ratio of the nitrogen-doped carbon carrier to the ethylene glycol solution of the platinum precursor is (10-15): (1-3). The nitrogen source includes at least one of triethylamine and ethylenediamine. The organic alcohol includes at least one of methanol and ethanol.

[0038] The porous carbon precursor is activated with carbon dioxide by this method, and the obtained carbon carrier has an advantageous pore structure, which can increase the dispersibility of platinum and the contact area between platinum and the substrate, thereby improving the reaction activity. In addition, the carbon carrier is doped with nitrogen, so that the surface of the carbon carrier can easily become a trap center to capture various atoms, so that the defects on the surface of the carbon carrier are more likely to load platinum, which is more conducive to the stable loading of platinum, and the nitrogen doping is conducive to improving the catalytic activity of platinum. The platinum loading process uses ethylene glycol for in-situ reduction, which has the advantages of simple and efficient operation. In addition, the addition of sodium fluoride is conducive to improving the microscopic morphology of the loaded platinum, making the particle size of platinum smaller and the catalytic activity higher.

[0039] The nitrogen-doped platinum-carbon catalyst prepared by the above method has a specific surface area of ​​500-650m 2 / g, where the particle size of platinum is 2.5-5.3nm, with high catalytic activity and catalytic efficiency.

[0040] The specific implementation scheme of the present invention is described in detail below.

[0041] Example 1

[0042] Preparation of dimethyl 4AU: Mix cyanoacetic acid and acetic anhydride, heat to 30°C for 1 hour, add toluene and dimethylurea, cool to room temperature after reflux reaction, collect solid matter by filtration, concentrate the filtrate to obtain crystallized solid, combine the solid collected by filtration to obtain dimethylcyanoacetylurea, add sodium hydroxide solution to adjust pH to 8, and react at 80°C to generate dimethyl 4AU. The molar ratio of cyanoacetic acid, acetic anhydride and dimethylurea is 1:1:1.

[0043] Preparation of nitrogen-doped platinum-carbon catalyst: Take mesoporous carbon, heat it in a carbon dioxide atmosphere at a heating temperature of 900°C and a heating time of 60min to obtain a carbon carrier with a dominant pore structure. The carbon carrier, triethylamine and methanol are mixed evenly and calcined at 800°C to obtain a nitrogen-doped carbon carrier. The mass ratio of carbon carrier, triethylamine and methanol is 3:6:25. The nitrogen-doped carbon carrier, sodium fluoride and pure water are mixed and stirred, and an ethylene glycol solution of chloroplatinic acid is added dropwise during the stirring process, heated in an oil bath, refluxed and stirred, and the reaction is completed by solid-liquid centrifugation. The solid product is washed with acetone and deionized water, and dried to obtain the nitrogen-doped platinum-carbon catalyst. The mass ratio of the above-mentioned nitrogen-doped carbon carrier to sodium fluoride is 3:5. The concentration of the ethylene glycol solution of chloroplatinic acid is 0.05 mol / L. The mass ratio of the nitrogen-doped carbon carrier to the ethylene glycol solution of chloroplatinic acid is 10:1.

[0044] Preparation of 1,3-dimethylxanthine: Add dimethyl 4AU to formic acid, stir until completely dissolved, cool to 0°C, add sodium nitrite and nitrogen-doped platinum carbon catalyst, heat to room temperature for reaction, collect mother liquor after the reaction is complete, concentrate the mother liquor to filter out formic acid, and obtain dimethyl FAU. Place dimethyl FAU in a four-necked bottle, add dilute sulfuric acid to the four-necked bottle, adjust pH to 3, heat to 90°C, pass the feed liquid through an ozone reactor and a high-efficiency decolorizer, and cold filter after crystallization in a crystallizer to obtain 1,3-dimethylxanthine. In the above steps, the mass ratio of dimethyl 4AU to formic acid is 1:4, the molar ratio of sodium nitrite to dimethyl 4AU is 1:1, and the mass ratio of nitrogen-doped platinum carbon catalyst to dimethyl 4AU is 0.005:1.

[0045] The total yield of this embodiment is 91.5%, and the purity of 1,3-dimethylxanthine is 99.3%.

[0046] Example 2

[0047] Preparation of dimethyl 4AU: Mix cyanoacetic acid and acetic anhydride, heat to 80°C for 1 hour, add benzene and dimethylurea, cool to room temperature after reflux reaction, collect solid matter by filtration, concentrate the filtrate to obtain crystallized solid, combine the solid collected by filtration to obtain dimethylcyanoacetylurea, add sodium hydroxide solution to adjust pH to 11, and react at 100°C to generate dimethyl 4AU. The molar ratio of the above cyanoacetic acid, acetic anhydride and dimethylurea is 1:1.3:1.3.

[0048] Preparation of nitrogen-doped platinum-carbon catalyst: Take Ketjen black, heat it in a carbon dioxide atmosphere, the heating temperature is 950°C, the heating time is 30min, and a carbon carrier with a dominant pore structure is obtained. The carbon carrier, ethylenediamine, and ethanol are mixed evenly and calcined at 850°C to obtain a nitrogen-doped carbon carrier. The mass ratio of carbon carrier, ethylenediamine, and ethanol is 5:10:35. The nitrogen-doped carbon carrier, sodium fluoride, and pure water are mixed and stirred, and an ethylene glycol solution of trimethyl platinum is added dropwise during the stirring process, heated in an oil bath, refluxed and stirred, and the reaction is completed. The solid-liquid centrifugal separation, the solid product is washed with acetone and deionized water, and dried to obtain the nitrogen-doped platinum-carbon catalyst. The mass ratio of the above-mentioned nitrogen-doped carbon carrier to sodium fluoride is 7:9. The concentration of the ethylene glycol solution of trimethyl platinum is 0.08 mol / L. The mass ratio of the nitrogen-doped carbon carrier to the ethylene glycol solution of chloroplatinic acid is 15:3.

[0049] Preparation of 1,3-dimethylxanthine: Add dimethyl 4AU to formic acid, stir until completely dissolved, cool to 10°C, add sodium nitrite and nitrogen-doped platinum carbon catalyst, heat to room temperature for reaction, collect mother liquor after the reaction is complete, concentrate the mother liquor and filter out formic acid to obtain dimethyl FAU. Place dimethyl FAU in a four-necked bottle, add dilute sulfuric acid to the four-necked bottle, adjust pH to 6, heat to 100°C, pass the feed liquid through an ozone reactor and a high-efficiency decolorizer, and cold filter after crystallization in a crystallizer to obtain 1,3-dimethylxanthine. In the above steps, the mass ratio of dimethyl 4AU to formic acid is 1:10, the molar ratio of sodium nitrite to dimethyl 4AU is 1.5:1, and the mass ratio of nitrogen-doped platinum carbon catalyst to dimethyl 4AU is 0.05:1.

[0050] The total yield of this example is 92.1%, and the purity of 1,3-dimethylxanthine is 99.2%.

[0051] Example 3

[0052] Preparation of dimethyl 4AU: Mix cyanoacetic acid and acetic anhydride, heat to 50°C for 1 hour, add toluene and dimethylurea, cool to room temperature after reflux reaction, collect solid matter by filtration, concentrate the filtrate to obtain crystallized solid, combine the solid collected by filtration to obtain dimethylcyanoacetylurea, add sodium hydroxide solution to adjust pH to 9, and react at 90°C to generate dimethyl 4AU. The molar ratio of cyanoacetic acid, acetic anhydride and dimethylurea is 1:1.1:1.2.

[0053] Preparation of nitrogen-doped platinum carbon catalyst: Take mesoporous carbon, heat it in a carbon dioxide atmosphere, the heating temperature is 920°C, the heating time is 40min, and a carbon carrier with a dominant pore structure is obtained. The carbon carrier, triethylamine and methanol are mixed evenly and calcined at 850°C to obtain a nitrogen-doped carbon carrier. The mass ratio of carbon carrier, triethylamine and methanol is 4:6:30. The nitrogen-doped carbon carrier, sodium fluoride and pure water are mixed and stirred, and an ethylene glycol solution of chloroplatinic acid is added dropwise during the stirring process, heated in an oil bath, refluxed and stirred, and the reaction is completed by solid-liquid centrifugation. The solid product is washed with acetone and deionized water, and dried to obtain the nitrogen-doped platinum carbon catalyst. The mass ratio of the above-mentioned nitrogen-doped carbon carrier to sodium fluoride is 5:9. The concentration of the ethylene glycol solution of chloroplatinic acid is 0.07 mol / L. The mass ratio of the nitrogen-doped carbon carrier to the ethylene glycol solution of chloroplatinic acid is 15:1.

[0054] Preparation of 1,3-dimethylxanthine: Add dimethyl 4AU to formic acid, stir until completely dissolved, cool to 5°C, add sodium nitrite and nitrogen-doped platinum carbon catalyst, heat to room temperature for reaction, collect mother liquor after the reaction is complete, concentrate the mother liquor to filter out formic acid, and obtain dimethyl FAU. Place dimethyl FAU in a four-necked bottle, add dilute sulfuric acid to the four-necked bottle, adjust pH to 5, heat to 95°C, pass the feed liquid through an ozone reactor and a high-efficiency decolorizer, and cold filter after crystallization in a crystallizer to obtain 1,3-dimethylxanthine. In the above steps, the mass ratio of dimethyl 4AU to formic acid is 1:8, the molar ratio of sodium nitrite to dimethyl 4AU is 1:1, and the mass ratio of nitrogen-doped platinum carbon catalyst to dimethyl 4AU is 0.01:1.

[0055] The total yield of this embodiment is 93%, and the purity of 1,3-dimethylxanthine is 99.3%.

[0056] Example 4

[0057] Preparation of dimethyl 4AU: Mix cyanoacetic acid and acetic anhydride, heat to 60°C for 1 hour, add benzene and dimethylurea, cool to room temperature after reflux reaction, collect solid matter by filtration, concentrate the filtrate to obtain crystallized solid, combine the solid collected by filtration to obtain dimethylcyanoacetylurea, add liquid alkali to adjust pH to 10, and react at 90°C to generate dimethyl 4AU. The molar ratio of cyanoacetic acid, acetic anhydride and dimethylurea is 1:1.2:1.1.

[0058] Preparation of nitrogen-doped platinum-carbon catalyst: Take Ketjen black, heat it in a carbon dioxide atmosphere, the heating temperature is 930°C, the heating time is 30min, and a carbon carrier with a dominant pore structure is obtained. The carbon carrier, ethylenediamine, and ethanol are mixed evenly and calcined at 830°C to obtain a nitrogen-doped carbon carrier. The mass ratio of carbon carrier, ethylenediamine, and ethanol is 5:8:30. The nitrogen-doped carbon carrier, sodium fluoride, and pure water are mixed and stirred, and a trimethyl platinum ethylene glycol solution is added dropwise during the stirring process, heated in an oil bath, refluxed and stirred, and the reaction is completed. The solid-liquid centrifugal separation, the solid product is washed with acetone and deionized water, and dried to obtain the nitrogen-doped platinum-carbon catalyst. The mass ratio of the above-mentioned nitrogen-doped carbon carrier to sodium fluoride is 4:6. The concentration of the ethylene glycol solution of trimethyl platinum is 0.06 mol / L. The mass ratio of the nitrogen-doped carbon carrier to the ethylene glycol solution of trimethyl platinum is 14:3.

[0059] Preparation of 1,3-dimethylxanthine: Add dimethyl 4AU to formic acid, stir until completely dissolved, cool to 10°C, add sodium nitrite and nitrogen-doped platinum carbon catalyst, heat to room temperature for reaction, collect mother liquor after the reaction is complete, concentrate the mother liquor and filter out formic acid to obtain dimethyl FAU. Place dimethyl FAU in a four-necked bottle, add dilute sulfuric acid to the four-necked bottle, adjust pH to 6, heat to 100°C, pass the feed liquid through an ozone reactor and a high-efficiency decolorizer, and cold filter after crystallization in a crystallizer to obtain 1,3-dimethylxanthine. In the above steps, the mass ratio of dimethyl 4AU to formic acid is 1:5, the molar ratio of sodium nitrite to dimethyl 4AU is 1.3:1, and the mass ratio of nitrogen-doped platinum carbon catalyst to dimethyl 4AU is 0.03:1.

[0060] The total yield of this embodiment is 92.5%, and the purity of 1,3-dimethylxanthine is 99%.

[0061] Comparative Example 1

[0062] Preparation of dimethyl 4AU: Mix cyanoacetic acid and acetic anhydride, heat to 30°C for 1 hour, add toluene and dimethylurea, cool to room temperature after reflux reaction, collect solid matter by filtration, concentrate the filtrate to obtain crystallized solid, combine the solid collected by filtration to obtain dimethylcyanoacetylurea, add sodium hydroxide solution to adjust pH to 8, and react at 80°C to generate dimethyl 4AU. The molar ratio of cyanoacetic acid, acetic anhydride and dimethylurea is 1:1:1.

[0063] Preparation of platinum-carbon catalyst: Take mesoporous carbon, heat it in a carbon dioxide atmosphere at 900°C for 60 minutes to obtain a carbon carrier with a dominant pore structure. Mix the carbon carrier, sodium fluoride and pure water, add a solution of chloroplatinic acid in ethylene glycol dropwise during the stirring process, heat in an oil bath, reflux and stir, separate the solid and liquid by centrifugation after the reaction is completed, wash the solid product with acetone and deionized water, and dry it to obtain the platinum-carbon catalyst.

[0064] Preparation of 1,3-dimethylxanthine: Add dimethyl 4AU to formic acid, stir until completely dissolved, cool to 0°C, add sodium nitrite and platinum carbon catalyst, heat to room temperature for reaction, collect mother liquor after the reaction is complete, concentrate the mother liquor to filter out formic acid, and obtain dimethyl FAU. Place dimethyl FAU in a four-necked bottle, add dilute sulfuric acid to the four-necked bottle, adjust pH to 3, heat to 90°C, pass the feed liquid through an ozone reactor and a high-efficiency decolorizer, and cold filter after crystallization in a crystallizer to obtain 1,3-dimethylxanthine. In the above steps, the mass ratio of dimethyl 4AU to formic acid is 1:4, the molar ratio of sodium nitrite to dimethyl 4AU is 1:1, and the mass ratio of nitrogen-doped platinum carbon catalyst to dimethyl 4AU is 0.005:1.

[0065] The difference between this comparative example and Example 1 is that the platinum-carbon catalyst of this comparative example does not have a nitrogen doping process. The total yield of this comparative example is 86.5%, and the purity of 1,3-dimethylxanthine is 96.1%.

[0066] Comparative Example 2

[0067] Preparation of dimethyl 4AU: Mix cyanoacetic acid and acetic anhydride, heat to 30°C for 1 hour, add toluene and dimethylurea, cool to room temperature after reflux reaction, collect solid matter by filtration, concentrate the filtrate to obtain crystallized solid, combine the solid collected by filtration to obtain dimethylcyanoacetylurea, add sodium hydroxide solution to adjust pH to 8, and react at 80°C to generate dimethyl 4AU. The molar ratio of cyanoacetic acid, acetic anhydride and dimethylurea is 1:1:1.

[0068] Preparation of nitrogen-doped platinum carbon catalyst: Take a mesoporous carbon carrier, triethylamine, and methanol and mix them evenly, calcine at 800°C to obtain a nitrogen-doped carbon carrier. The mass ratio of carbon carrier, triethylamine, and methanol is 3:6:25. The nitrogen-doped carbon carrier, sodium fluoride, and pure water are mixed and stirred, and an ethylene glycol solution of chloroplatinic acid is added dropwise during the stirring process, heated in an oil bath, refluxed and stirred, and the reaction is completed by solid-liquid centrifugation. The solid product is washed with acetone and deionized water, and dried to obtain the nitrogen-doped platinum carbon catalyst. The mass ratio of the above-mentioned nitrogen-doped carbon carrier to sodium fluoride is 3:5. The concentration of the ethylene glycol solution of chloroplatinic acid is 0.05 mol / L. The mass ratio of the nitrogen-doped carbon carrier to the ethylene glycol solution of chloroplatinic acid is 10:1.

[0069] Preparation of 1,3-dimethylxanthine: Add dimethyl 4AU to formic acid, stir until completely dissolved, cool to 0°C, add sodium nitrite and nitrogen-doped platinum carbon catalyst, heat to room temperature for reaction, collect mother liquor after the reaction is complete, concentrate the mother liquor to filter out formic acid, and obtain dimethyl FAU. Place dimethyl FAU in a four-necked bottle, add dilute sulfuric acid to the four-necked bottle, adjust pH to 3, heat to 90°C, pass the feed liquid through an ozone reactor and a high-efficiency decolorizer, and cold filter after crystallization in a crystallizer to obtain 1,3-dimethylxanthine. In the above steps, the mass ratio of dimethyl 4AU to formic acid is 1:4, the molar ratio of sodium nitrite to dimethyl 4AU is 1:1, and the mass ratio of nitrogen-doped platinum carbon catalyst to dimethyl 4AU is 0.005:1.

[0070] The difference between this comparative example and Example 1 is that when preparing the nitrogen-doped platinum-carbon catalyst in this comparative example, no carbon dioxide activation process is performed. The total yield of this comparative example is 85.9%, and the purity of 1,3-dimethylxanthine is 96.5%.

[0071] Comparative Example 3

[0072] Preparation of dimethyl 4AU: Mix cyanoacetic acid and acetic anhydride, heat to 30°C for 1 hour, add toluene and dimethylurea, cool to room temperature after reflux reaction, collect solid matter by filtration, concentrate the filtrate to obtain crystallized solid, combine the solid collected by filtration to obtain dimethylcyanoacetylurea, add sodium hydroxide solution to adjust pH to 8, and react at 80°C to generate dimethyl 4AU. The molar ratio of cyanoacetic acid, acetic anhydride and dimethylurea is 1:1:1.

[0073] Preparation of nitrogen-doped platinum-carbon catalyst: Take mesoporous carbon, heat it in a carbon dioxide atmosphere at a temperature of 900°C and a heating time of 60 minutes to obtain a carbon carrier with a dominant pore structure. The carbon carrier, triethylamine and methanol are mixed evenly and calcined at 800°C to obtain a nitrogen-doped carbon carrier. The mass ratio of carbon carrier, triethylamine and methanol is 3:6:25. The nitrogen-doped carbon carrier is mixed and stirred with pure water, and an ethylene glycol solution of chloroplatinic acid is added dropwise during the stirring process, heated in an oil bath, refluxed and stirred, and the reaction is completed by solid-liquid centrifugation. The solid product is washed with acetone and deionized water, and dried to obtain the nitrogen-doped platinum-carbon catalyst. The concentration of the ethylene glycol solution of chloroplatinic acid is 0.05 mol / L. The mass ratio of the nitrogen-doped carbon carrier to the ethylene glycol solution of chloroplatinic acid is 10:1.

[0074] Preparation of 1,3-dimethylxanthine: Add dimethyl 4AU to formic acid, stir until completely dissolved, cool to 0°C, add sodium nitrite and nitrogen-doped platinum carbon catalyst, heat to room temperature for reaction, collect mother liquor after the reaction is complete, concentrate the mother liquor to filter out formic acid, and obtain dimethyl FAU. Place dimethyl FAU in a four-necked bottle, add dilute sulfuric acid to the four-necked bottle, adjust pH to 3, heat to 90°C, pass the feed liquid through an ozone reactor and a high-efficiency decolorizer, and cold filter after crystallization in a crystallizer to obtain 1,3-dimethylxanthine. In the above steps, the mass ratio of dimethyl 4AU to formic acid is 1:4, the molar ratio of sodium nitrite to dimethyl 4AU is 1:1, and the mass ratio of nitrogen-doped platinum carbon catalyst to dimethyl 4AU is 0.005:1.

[0075] The difference between this comparative example and Example 1 is that sodium fluoride is not added when preparing the nitrogen-doped platinum-carbon catalyst in this comparative example. The total yield of this comparative example is 87.5%, and the purity of 1,3-dimethylxanthine is 95.1%.

[0076] Comparative Example 4

[0077] Preparation of dimethyl 4AU: Mix cyanoacetic acid and acetic anhydride, heat to 30°C for 1 hour, add toluene and dimethylurea, cool to room temperature after reflux reaction, collect solid matter by filtration, concentrate the filtrate to obtain crystallized solid, combine the solid collected by filtration to obtain dimethylcyanoacetylurea, add sodium hydroxide solution to adjust pH to 8, and react at 80°C to generate dimethyl 4AU. The molar ratio of cyanoacetic acid, acetic anhydride and dimethylurea is 1:1:1.

[0078] Purchase commercially available platinum-carbon catalysts.

[0079] Preparation of 1,3-dimethylxanthine: Add dimethyl 4AU to formic acid, stir until completely dissolved, cool to 0°C, add sodium nitrite and nitrogen-doped platinum carbon catalyst, heat to room temperature for reaction, collect mother liquor after the reaction is complete, concentrate the mother liquor to filter out formic acid, and obtain dimethyl FAU. Place dimethyl FAU in a four-necked bottle, add dilute sulfuric acid to the four-necked bottle, adjust pH to 3, heat to 90°C, pass the feed liquid through an ozone reactor and a high-efficiency decolorizer, and cold filter after crystallization in a crystallizer to obtain 1,3-dimethylxanthine. In the above steps, the mass ratio of dimethyl 4AU to formic acid is 1:4, the molar ratio of sodium nitrite to dimethyl 4AU is 1:1, and the mass ratio of nitrogen-doped platinum carbon catalyst to dimethyl 4AU is 0.005:1.

[0080] The difference between this comparative example and Example 1 is that the platinum-carbon catalyst in this comparative example is purchased from outside. The total yield of this comparative example is 81.1%, and the purity of 1,3-dimethylxanthine is 93.9%.

[0081] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0082] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

Claims

1. A method for preparing 1,3-dimethylxanthine, characterized in that: The method comprises the following steps: Obtaining 1,3-dimethyl-4-imidoureazoline; Dissolve 1,3-dimethyl-4-aminoureazimine in formic acid, add sodium nitrite and nitrogen-doped platinum-carbon catalyst, collect mother liquor after the reaction is completed, concentrate the mother liquor and filter out formic acid to obtain 1,3-dimethyl-4-amino-5-formamidoureazimine; Add dilute sulfuric acid to 1,3-dimethyl-4-amino-5-formamidoureaazine to adjust the pH to 3-6, heat to 90-100° C., decolorize the feed solution with ozone, crystallize it, and then cold filter it to obtain 1,3-dimethylxanthine; Wherein, the nitrogen-doped platinum-carbon catalyst is prepared by the following preparation method: Taking a porous carbon precursor, heating it in a carbon dioxide atmosphere to obtain a carbon carrier, wherein the porous carbon precursor is selected from at least one of mesoporous carbon and Ketjen black, and the heating temperature in the carbon dioxide atmosphere is 900-950° C., and the heating time is 30-60 min; The carbon carrier, the nitrogen source and the organic alcohol are uniformly mixed, and calcined at 800-850° C. to obtain a nitrogen-doped carbon carrier, wherein the mass ratio of the carbon carrier, the nitrogen source and the organic alcohol is (3-5): (6-10): (25-35), the nitrogen source is selected from at least one of triethylamine and ethylenediamine, and the organic alcohol is selected from at least one of methanol and ethanol; The nitrogen-doped carbon carrier, sodium fluoride and pure water are mixed and stirred, and an ethylene glycol solution of a platinum precursor is added dropwise during the stirring process. The mixture is heated in an oil bath and refluxed with stirring. After the reaction is completed, the solid product is washed and dried to obtain the nitrogen-doped platinum-carbon catalyst, wherein the mass ratio of the nitrogen-doped carbon carrier to the sodium fluoride is (3-7): (5-9), and the mass ratio of the nitrogen-doped carbon carrier to the ethylene glycol solution of the platinum precursor is (10-15): (1-3).

2. The method for preparing 1,3-dimethylxanthine according to claim 1, characterized in that: The mass ratio of 1,3-dimethyl-4-iminoureaazine to formic acid is 1:(4-10).

3. The method for preparing 1,3-dimethylxanthine according to claim 1, characterized in that: The molar ratio of sodium nitrite to 1,3-dimethyl-4-imidourea is (1-1.5):

1.

4. The method for preparing 1,3-dimethylxanthine according to claim 1, characterized in that: The mass ratio of nitrogen-doped platinum carbon catalyst to 1,3-dimethyl-4-imidoureaazine is (0.005-0.05):

1.

5. The method for preparing 1,3-dimethylxanthine according to claim 1, characterized in that: The preparation method of the 1,3-dimethyl-4-imidourea zine comprises the following steps: Mix cyanoacetic acid and acetic anhydride, heat to 30-80°C, add solvent and dimethylurea, cool to room temperature after reflux reaction, collect solid matter by filtration, concentrate the filtrate to obtain crystallized solid, combine the solid collected by filtration to obtain dimethylcyanoacetyl urea, add liquid alkali to adjust pH to 8-11, and then react at 80-100°C to generate 1,3-dimethyl-4-imidourea.

6. The method for preparing 1,3-dimethylxanthine according to claim 1, characterized in that: The platinum precursor is selected from at least one of chloroplatinic acid and trimethylplatinum.