Preparation method of 3,7-dimethylxanthine

Abstract

The present invention provides a kind of preparation method of 3,7-dimethylxanthine, the method comprises the following steps: obtain 3-methyl-4-iminoureazines; dissolve 3-methyl-4-iminoureazines in formic acid, add sodium nitrite and boron nitrogen doped platinum carbon catalyst, collect mother liquor after completion of the reaction, concentrate the mother liquor to filter out formic acid, and obtain 3-methyl-4-amino-5-formamidoureazines; mix 3-methyl-4-amino-5-formamidoureazines, liquid caustic soda and water, add acid to neutral after completion of the reaction, and obtain 3-methylxanthine; carry out methylation reaction and refinement of the 3-methylxanthine to obtain 3,7-dimethylxanthine. The preparation method of 3,7-dimethylxanthine of the present invention has mild reaction conditions, simple operation and low energy consumption. By adopting boron 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 invention relates to the field of medicines, and in particular to a method for preparing 3,7-dimethylxanthine. Background Art

[0002] 3,7-Dimethylxanthine, also known as theobromine, is a purine compound that not only has unique chemical properties but also has multiple biological effects on the human body.

[0003] First, it has a significant diuretic effect, which can help the body excrete excess water and salt, thereby helping to regulate fluid balance and blood pressure. Secondly, theobromine can excite the myocardium, enhance the contractility and frequency of the heart, and improve the heart's pumping function. In addition, it can also dilate blood vessels, reduce vascular resistance, and lower blood pressure, which helps improve blood circulation and reduce the burden on the heart. Finally, theobromine also has the effect of smooth muscle relaxation, which can relieve muscle spasms and pain.

[0004] In the pharmaceutical field, theobromine's multiple effects make it an important drug raw material. It can be used as a diuretic to treat edema, hypertension and other diseases. At the same time, it can also be used as a bittering agent to adjust the taste of medicines. In addition, because theobromine has the effect of promoting fat metabolism, it is also used in the preparation of weight loss drugs.

[0005] In addition to the pharmaceutical field, theobromine is also widely used in the chemical industry. It is the raw material of pentoxifylline, which is an important organic synthesis intermediate that can be used to prepare a variety of organic compounds. In addition, theobromine can also be used in the preparation of chemical products such as dyes and fragrances.

[0006] There are four main methods for preparing theobromine: the first is the methylurea method, which uses methylurea and cyanoacetic acid as starting materials, and obtains a crude product through condensation, nitrosation, reduction, acylation, ring closure, and methylation reactions, and then refines the crude product twice. This method has a long process, complicated process steps, a long production cycle, and many side reactions, which produces a large amount of sewage discharge, and the COD and salinity are both high; the second is the caffeine method, which uses caffeine as a raw material to synthesize theobromine through reactions such as ring opening, cyanidation, and ring closure under alkaline conditions. This method has simple steps, but the yield is low, less than 40%, the conversion rate is not high, the caffeine residue is high, and the amount of alkali used in the process is large, which discharges a large amount of COD-containing wastewater. Summary of the invention

[0007] The invention provides a method for preparing 3,7-dimethylxanthine to improve the preparation efficiency of 3,7-dimethylxanthine.

[0008] A method for preparing 3,7-dimethylxanthine, characterized in that the method comprises the following steps:

[0009] Obtaining 3-methyl-4-imidoureazoline;

[0010] Dissolve 3-methyl-4-aminoureazimine in formic acid, add sodium nitrite and boron nitrogen-doped platinum-carbon catalyst, collect mother liquor after the reaction is completed, concentrate the mother liquor and filter out formic acid to obtain 3-methyl-4-amino-5-formamidoureazimine;

[0011] 3-methyl-4-amino-5-formamidoureaazine, liquid alkali and water are mixed, and after the reaction is completed, acid is added to adjust to neutrality to obtain 3-methylxanthine; the 3-methylxanthine is subjected to methylation reaction and purification to obtain 3,7-dimethylxanthine.

[0012] Furthermore, the mass ratio of 3-methyl-4-imidoureaazine to formic acid is 1:(4-10).

[0013] Furthermore, the molar ratio of sodium nitrite to 3-methyl-4-imidoureazoline is (1-1.5):1.

[0014] Furthermore, the mass ratio of the boron nitrogen doped platinum carbon catalyst to 3-methyl-4-imidoureaazine is (0.01-0.03):1.

[0015] Furthermore, the preparation method of the 3-methyl-4-imidourea zine comprises the following steps:

[0016] -10-20°C, adding cyanoacetic acid and oxalyl chloride to a solvent, concentrating the reaction solution after the reaction is completed, removing the solvent and excess oxalyl chloride, controlling the temperature to 0-30°C, adding monomethylurea and a solvent, and adding a base as an acid-binding agent, adding water after the reaction, stirring, and filtering to obtain monomethylcyanoacetyl urea;

[0017] Dissolve monomethylcyanoacetyl urea in water, add liquid alkali to adjust the pH to 8-11, and react at 80-100°C to generate 3-methyl-4-imidourea.

[0018] Furthermore, the preparation method of the boron-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 borane amine compound and the organic alcohol are uniformly mixed, and calcined at 800-850° C. to obtain a boron-nitrogen doped carbon carrier;

[0021] The boron 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 boron 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 borane amine compound 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 boron 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 boron-nitrogen-doped platinum-carbon catalyst prepared by the boron-nitrogen-doped platinum-carbon catalyst preparation method further proposed in the present invention 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. 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 3,7-dimethylxanthine, the method comprising the following steps:

[0032] Obtain 3-methyl-4-aminourea (also known as monomethyl 4AU). Dissolve monomethyl 4AU in formic acid, add sodium nitrite and boron nitrogen doped platinum carbon catalyst at -10-10°C, collect the mother liquor after the reaction is completed, concentrate the mother liquor and filter out formic acid to obtain 3-methyl-4-amino-5-formamidourea (also known as monomethyl FAU). Mix monomethyl FAU, liquid alkali and water, add acid to neutralize after the reaction is completed to obtain 3-methylxanthine; perform methylation reaction and refine the 3-methylxanthine to obtain 3,7-dimethylxanthine. In the above steps, the mass ratio of monomethyl 4AU to formic acid is 1: (4-10), the molar ratio of sodium nitrite to monomethyl 4AU is (1-1.5): 1, and the mass ratio of boron nitrogen doped platinum carbon catalyst to monomethyl 4AU is (0.01-0.03): 1.

[0033] The preparation method of the monomethyl 4AU specifically comprises the following steps:

[0034] -10-20℃, mix cyanoacetic acid and solvent, add oxalyl chloride to the solution, the reaction is completed after 1-5 hours, concentrate the reaction solution, remove the solvent and excess oxalyl chloride, control the temperature to 0-30℃, slowly add monomethylurea and solvent, and add alkali as acid binding agent, add water and stir after 3-7 hours of reaction, filter to obtain monomethylcyanoacetylurea. Dissolve monomethylcyanoacetylurea in water, add liquid alkali to adjust pH to 8-11, react at 80-100℃ to generate monomethyl 4AU. The solvent is one of dichloromethane and trichloromethane. The molar ratio of cyanoacetic acid, monomethylurea and oxalyl chloride is 1: (1-1.3): (1-1.5). The alkali is one of sodium hydroxide and potassium hydroxide.

[0035] In order to further reduce the reaction activation energy, the preparation method of the boron nitrogen doped platinum carbon catalyst comprises the following steps:

[0036] 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, borane amine compound and organic alcohol are mixed evenly and calcined at 800-850°C to obtain a boron-nitrogen doped carbon carrier. The mass ratio of the carbon carrier, borane amine compound and organic alcohol is (3-5): (6-10): (25-35). The boron-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, heated in an oil bath, refluxed and stirred, and solid-liquid centrifugation is performed after the reaction is completed. The solid product is washed with acetone and deionized water and dried to obtain the boron-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 1000-3000m2 / g. The platinum precursor includes at least one of chloroplatinic acid and trimethyl platinum. The mass ratio of the boron 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 boron nitrogen doped carbon carrier to the ethylene glycol solution of the platinum precursor is (10-15): (1-3). The borane amine compound includes at least one of borane dimethylamine and borane triethylamine. The organic alcohol includes at least one of methanol and ethanol.

[0037] 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.

[0038] The boron-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.

[0039] The specific implementation scheme of the present invention is described in detail below.

[0040] Example 1

[0041] Preparation of monomethyl 4AU: Mix cyanoacetic acid and solvent at -10°C, add oxalyl chloride to the solution, the reaction is complete after 1 to 5 hours, concentrate the reaction solution, remove the solvent and excess oxalyl chloride, control the temperature to 0°C, slowly add monomethylurea and solvent, and add alkali as an acid binding agent, add water and stir after 7 hours of reaction, filter to obtain monomethylcyanoacetylurea. Dissolve monomethylcyanoacetylurea in water, add liquid alkali to adjust pH to 8, react at 80°C to generate monomethyl 4AU. The solvent is dichloromethane. The molar ratio of cyanoacetic acid, monomethylurea and oxalyl chloride is 1:1:1. The alkali is sodium hydroxide.

[0042] Preparation of boron nitrogen doped platinum carbon catalyst: Take mesoporous carbon, heat it in a carbon dioxide atmosphere, the heating temperature is 900 ° C, the heating time is 60min, and a carbon carrier with a dominant pore structure is obtained. The carbon carrier, borane dimethylamine, and methanol are mixed evenly and calcined at 800 ° C to obtain a boron nitrogen doped carbon carrier. The mass ratio of carbon carrier, borane dimethylamine, and methanol is 3:6:25. The boron nitrogen doped carbon carrier, sodium fluoride and pure water are mixed and stirred, and the 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. The solid-liquid centrifugation is separated, the solid product is washed with acetone and deionized water, and dried to obtain the boron nitrogen doped platinum carbon catalyst. The mass ratio of the above-mentioned boron 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 boron nitrogen doped carbon carrier to the ethylene glycol solution of chloroplatinic acid is 10:1.

[0043] Preparation of 3,7-dimethylxanthine: dissolve monomethyl 4AU in formic acid, stir until completely dissolved, cool to 0°C, add sodium nitrite and boron nitrogen doped platinum carbon catalyst, collect mother liquor after reaction, concentrate mother liquor to remove formic acid, and obtain monomethyl FAU; mix monomethyl FAU, liquid alkali and water, add acid to neutral after reaction, and obtain 3-methylxanthine; perform methylation reaction and refine the 3-methylxanthine to obtain 3,7-dimethylxanthine. In the above steps, the mass ratio of monomethyl 4AU to formic acid is 1:4, the molar ratio of sodium nitrite to monomethyl 4AU is 1:1, and the mass ratio of boron nitrogen doped platinum carbon catalyst to monomethyl 4AU is 0.01:1.

[0044] The total yield of this embodiment is 92%, and the purity of 3,7-dimethylxanthine is 99.1%.

[0045] Example 2

[0046] Preparation of monomethyl 4AU: Mix cyanoacetic acid and solvent at 20°C, add oxalyl chloride to the solution, the reaction is completed after 1 to 5 hours, concentrate the reaction solution, remove the solvent and excess oxalyl chloride, control the temperature to 30°C, slowly add monomethylurea and solvent, and add alkali as an acid binding agent, add water and stir after reacting for 3 to 7 hours, filter to obtain monomethylcyanoacetylurea. Dissolve monomethylcyanoacetylurea in water, add liquid alkali to adjust pH to 11, react at 100°C to generate monomethyl 4AU. The solvent is chloroform. The molar ratio of cyanoacetic acid, monomethylurea and oxalyl chloride is 1:1.3:1.5. The alkali is potassium hydroxide.

[0047] Preparation of boron 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, borane triethylamine, and ethanol are mixed evenly and calcined at 850 ° C to obtain a boron nitrogen doped carbon carrier. The mass ratio of carbon carrier, borane triethylamine, and ethanol is 5:10:35. The boron 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, oil bath heating, reflux stirring, and the reaction is completed. Solid-liquid centrifugation separation, the solid product is washed with acetone and deionized water, and dried to obtain the boron nitrogen doped platinum carbon catalyst. The mass ratio of the above-mentioned boron 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 boron nitrogen doped carbon carrier to the ethylene glycol solution of chloroplatinic acid is 15:3.

[0048] Preparation of 3,7-dimethylxanthine: dissolve monomethyl 4AU in formic acid, add sodium nitrite and boron nitrogen doped platinum carbon catalyst at 10°C, collect the mother liquor after the reaction is completed, concentrate the mother liquor to filter out formic acid, and obtain monomethyl FAU. Mix monomethyl FAU, liquid alkali and water, add acid to neutralize after the reaction is completed, and obtain 3-methylxanthine; perform methylation reaction and refine the 3-methylxanthine to obtain 3,7-dimethylxanthine. In the above steps, the mass ratio of monomethyl 4AU to formic acid is 1:5, the molar ratio of sodium nitrite to monomethyl 4AU is 1.3:1, and the mass ratio of boron nitrogen doped platinum carbon catalyst to monomethyl 4AU is 0.02:1.

[0049] The total yield of this embodiment is 93.2%, and the purity of 3,7-dimethylxanthine is 98.1%.

[0050] Example 3

[0051] Preparation of monomethyl 4AU: Mix cyanoacetic acid and solvent at 15°C, add oxalyl chloride to the solution, the reaction is completed after 1 to 5 hours, concentrate the reaction solution, remove the solvent and excess oxalyl chloride, control the temperature to 25°C, slowly add monomethylurea and solvent, and add alkali as an acid binding agent, react for 3 to 7 hours, add water and stir, filter to obtain monomethylcyanoacetylurea. Dissolve monomethylcyanoacetylurea in water, add liquid alkali to adjust pH to 9, react at 90°C to generate monomethyl 4AU. The solvent is dichloromethane. The molar ratio of cyanoacetic acid, monomethylurea and oxalyl chloride is 1:1.1:1.3. The alkali is sodium hydroxide.

[0052] Preparation of boron 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, borane dimethylamine, and methanol are mixed evenly and calcined at 850 ° C to obtain a boron nitrogen doped carbon carrier. The mass ratio of carbon carrier, borane dimethylamine, and methanol is 4:6:30. The boron nitrogen doped carbon carrier, sodium fluoride and pure water are mixed and stirred, and the 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 boron nitrogen doped platinum carbon catalyst. The mass ratio of the above-mentioned boron 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 boron nitrogen doped carbon carrier to the ethylene glycol solution of chloroplatinic acid is 15:1.

[0053] Preparation of 3,7-dimethylxanthine: dissolve monomethyl 4AU in formic acid, add sodium nitrite and boron nitrogen doped platinum carbon catalyst at 5°C, collect mother liquor after reaction, concentrate mother liquor to remove formic acid, and obtain monomethyl FAU; mix monomethyl FAU, liquid alkali and water, add acid to neutral after reaction, and obtain 3-methylxanthine; perform methylation reaction and refinement on 3-methylxanthine to obtain 3,7-dimethylxanthine. In the above steps, the mass ratio of monomethyl 4AU to formic acid is 1:8, the molar ratio of sodium nitrite to monomethyl 4AU is 1.1:1, and the mass ratio of boron nitrogen doped platinum carbon catalyst to monomethyl 4AU is 0.015:1.

[0054] The total yield of this embodiment is 93.5%, and the purity of 3,7-dimethylxanthine is 97.5%.

[0055] Example 4

[0056] Preparation of monomethyl 4AU: Mix cyanoacetic acid and solvent at -4°C, add oxalyl chloride to the solution, the reaction is completed after 1 to 5 hours, concentrate the reaction solution, remove the solvent and excess oxalyl chloride, control the temperature to 10°C, slowly add monomethylurea and solvent, and add alkali as an acid binding agent, react for 3 to 7 hours, add water and stir, filter to obtain monomethylcyanoacetylurea. Dissolve monomethylcyanoacetylurea in water, add liquid alkali to adjust pH to 10, react at 95°C to generate monomethyl 4AU. The solvent is chloroform. The molar ratio of cyanoacetic acid, monomethylurea and oxalyl chloride is 1:1.3:1.5. The alkali is potassium hydroxide.

[0057] Preparation of boron 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, borane triethylamine, and ethanol are mixed evenly and calcined at 830 ° C to obtain a boron nitrogen doped carbon carrier. The mass ratio of carbon carrier, borane triethylamine, and ethanol is 5:8:30. The boron 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. Solid-liquid centrifugal separation, the solid product is washed with acetone and deionized water, and dried to obtain the boron nitrogen doped platinum carbon catalyst. The mass ratio of the above-mentioned boron 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 boron nitrogen doped carbon carrier to the ethylene glycol solution of trimethyl platinum is 14:3.

[0058] Preparation of 3,7-dimethylxanthine: dissolve monomethyl 4AU in formic acid, add sodium nitrite and boron nitrogen doped platinum carbon catalyst at -4°C, collect mother liquor after reaction, concentrate mother liquor to remove formic acid, and obtain monomethyl FAU; mix monomethyl FAU, liquid alkali and water, add acid to neutral after reaction, and obtain 3-methylxanthine; perform methylation reaction and refinement on 3-methylxanthine to obtain 3,7-dimethylxanthine. In the above steps, the mass ratio of monomethyl 4AU to formic acid is 1:9, the molar ratio of sodium nitrite to monomethyl 4AU is 1:1, and the mass ratio of boron nitrogen doped platinum carbon catalyst to monomethyl 4AU is 0.025:1.

[0059] The total yield of this embodiment is 91.5%, and the purity of 3,7-dimethylxanthine is 99%.

[0060] Comparative Example 1

[0061] Preparation of monomethyl 4AU: Mix cyanoacetic acid and solvent at -10°C, add oxalyl chloride to the solution, the reaction is complete after 1 to 5 hours, concentrate the reaction solution, remove the solvent and excess oxalyl chloride, control the temperature to 0°C, slowly add monomethylurea and solvent, and add alkali as an acid binding agent, add water and stir after 7 hours of reaction, filter to obtain monomethylcyanoacetylurea. Dissolve monomethylcyanoacetylurea in water, add liquid alkali to adjust pH to 8, react at 80°C to generate monomethyl 4AU. The solvent is dichloromethane. The molar ratio of cyanoacetic acid, monomethylurea and oxalyl chloride is 1:1:1. The alkali is sodium hydroxide.

[0062] Preparation of platinum-carbon catalyst: Take mesoporous carbon, heat it in a carbon dioxide atmosphere at a temperature of 900°C for 60 minutes to obtain a carbon carrier with a dominant pore structure. Mix and stir the carbon carrier, sodium fluoride and pure water, add a glycol solution of chloroplatinic acid dropwise during stirring, heat in an oil bath, reflux and stir, complete the reaction, centrifuge the solid and liquid, wash the solid product with acetone and deionized water, and dry it to obtain the platinum-carbon catalyst. The mass ratio of the above-mentioned 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 carbon carrier to the ethylene glycol solution of chloroplatinic acid is 10:1.

[0063] Preparation of 3,7-dimethylxanthine: dissolve monomethyl 4AU in formic acid, stir until completely dissolved, cool to 0°C, add sodium nitrite and platinum carbon catalyst, collect mother liquor after the reaction is completed, concentrate the mother liquor to filter out formic acid, and obtain monomethyl FAU. Mix monomethyl FAU, liquid alkali and water, add acid to neutralize after the reaction is completed, and obtain 3-methylxanthine; perform methylation reaction and refine the 3-methylxanthine to obtain 3,7-dimethylxanthine. In the above steps, the mass ratio of monomethyl 4AU to formic acid is 1:4, the molar ratio of sodium nitrite to monomethyl 4AU is 1:1, and the mass ratio of platinum carbon catalyst to monomethyl 4AU is 0.01:1.

[0064] The difference between this comparative example and Example 1 is that the platinum-carbon catalyst of this comparative example does not have a boron-nitrogen doping process. The total yield of this comparative example is 85%, and the purity of 3,7-dimethylxanthine is 96%.

[0065] Comparative Example 2

[0066] Preparation of monomethyl 4AU: Mix cyanoacetic acid and solvent at -10°C, add oxalyl chloride to the solution, the reaction is complete after 1 to 5 hours, concentrate the reaction solution, remove the solvent and excess oxalyl chloride, control the temperature to 0°C, slowly add monomethylurea and solvent, and add alkali as an acid binding agent, add water and stir after 7 hours of reaction, filter to obtain monomethylcyanoacetylurea. Dissolve monomethylcyanoacetylurea in water, add liquid alkali to adjust pH to 8, react at 80°C to generate monomethyl 4AU. The solvent is dichloromethane. The molar ratio of cyanoacetic acid, monomethylurea and oxalyl chloride is 1:1:1. The alkali is sodium hydroxide.

[0067] Preparation of boron nitrogen doped platinum carbon catalyst: take mesoporous carbon, borane dimethylamine, and methanol and mix them evenly, calcine at 800 ° C to obtain a boron nitrogen doped carbon carrier. The mass ratio of mesoporous carbon, borane dimethylamine, and methanol is 3:6:25. The boron nitrogen doped carbon carrier, sodium fluoride and pure water are mixed and stirred, and the 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 boron nitrogen doped platinum carbon catalyst. The mass ratio of the above-mentioned boron 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 boron nitrogen doped carbon carrier to the ethylene glycol solution of chloroplatinic acid is 10:1.

[0068] Preparation of 3,7-dimethylxanthine: dissolve monomethyl 4AU in formic acid, stir until completely dissolved, cool to 0°C, add sodium nitrite and boron nitrogen doped platinum carbon catalyst, collect mother liquor after reaction, concentrate mother liquor to remove formic acid, and obtain monomethyl FAU; mix monomethyl FAU, liquid alkali and water, add acid to neutral after reaction, and obtain 3-methylxanthine; perform methylation reaction and refine the 3-methylxanthine to obtain 3,7-dimethylxanthine. In the above steps, the mass ratio of monomethyl 4AU to formic acid is 1:4, the molar ratio of sodium nitrite to monomethyl 4AU is 1:1, and the mass ratio of boron nitrogen doped platinum carbon catalyst to monomethyl 4AU is 0.01:1.

[0069] The difference between this comparative example and Example 1 is that when preparing the boron nitrogen doped platinum carbon catalyst in this comparative example, the mesoporous carbon is not activated by carbon dioxide. The total yield of this comparative example is 85.9%, and the purity of 3,7-dimethylxanthine is 95.5%.

[0070] Comparative Example 3

[0071] Preparation of monomethyl 4AU: Mix cyanoacetic acid and solvent at -10°C, add oxalyl chloride to the solution, the reaction is complete after 1 to 5 hours, concentrate the reaction solution, remove the solvent and excess oxalyl chloride, control the temperature to 0°C, slowly add monomethylurea and solvent, and add alkali as an acid binding agent, add water and stir after 7 hours of reaction, filter to obtain monomethylcyanoacetylurea. Dissolve monomethylcyanoacetylurea in water, add liquid alkali to adjust pH to 8, react at 80°C to generate monomethyl 4AU. The solvent is dichloromethane. The molar ratio of cyanoacetic acid, monomethylurea and oxalyl chloride is 1:1:1. The alkali is sodium hydroxide.

[0072] Preparation of boron nitrogen doped platinum carbon catalyst: Take mesoporous carbon, heat it in a carbon dioxide atmosphere, the heating temperature is 900 ° C, the heating time is 60min, and a carbon carrier with a dominant pore structure is obtained. The carbon carrier, borane dimethylamine, and methanol are mixed evenly and calcined at 800 ° C to obtain a boron nitrogen doped carbon carrier. The mass ratio of carbon carrier, borane dimethylamine, and methanol is 3:6:25. The boron 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 boron nitrogen doped platinum carbon catalyst. The mass ratio of the above-mentioned boron 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 boron nitrogen doped carbon carrier to the ethylene glycol solution of chloroplatinic acid is 10:1.

[0073] Preparation of 3,7-dimethylxanthine: dissolve monomethyl 4AU in formic acid, stir until completely dissolved, cool to 0°C, add sodium nitrite and boron nitrogen doped platinum carbon catalyst, collect mother liquor after reaction, concentrate mother liquor to remove formic acid, and obtain monomethyl FAU; mix monomethyl FAU, liquid alkali and water, add acid to neutral after reaction, and obtain 3-methylxanthine; perform methylation reaction and refine the 3-methylxanthine to obtain 3,7-dimethylxanthine. In the above steps, the mass ratio of monomethyl 4AU to formic acid is 1:4, the molar ratio of sodium nitrite to monomethyl 4AU is 1:1, and the mass ratio of boron nitrogen doped platinum carbon catalyst to monomethyl 4AU is 0.01:1.

[0074] The difference between this comparative example and Example 1 is that sodium fluoride is not added when preparing the boron nitrogen doped platinum carbon catalyst in this comparative example. The total yield of this comparative example is 85.3%, and the purity of 3,7-dimethylxanthine is 92.1%.

[0075] Comparative Example 4

[0076] Preparation of monomethyl 4AU: Mix cyanoacetic acid and solvent at -10°C, add oxalyl chloride to the solution, the reaction is complete after 1 to 5 hours, concentrate the reaction solution, remove the solvent and excess oxalyl chloride, control the temperature to 0°C, slowly add monomethylurea and solvent, and add alkali as an acid binding agent, add water and stir after 7 hours of reaction, filter to obtain monomethylcyanoacetylurea. Dissolve monomethylcyanoacetylurea in water, add liquid alkali to adjust pH to 8, react at 80°C to generate monomethyl 4AU. The solvent is dichloromethane. The molar ratio of cyanoacetic acid, monomethylurea and oxalyl chloride is 1:1:1. The alkali is sodium hydroxide.

[0077] Purchase commercially available platinum-carbon catalysts.

[0078] Preparation of 3,7-dimethylxanthine: dissolve monomethyl 4AU in formic acid, stir until completely dissolved, cool to 0°C, add sodium nitrite and boron nitrogen doped platinum carbon catalyst, collect mother liquor after reaction, concentrate mother liquor to remove formic acid, and obtain monomethyl FAU; mix monomethyl FAU, liquid alkali and water, add acid to neutral after reaction, and obtain 3-methylxanthine; perform methylation reaction and refine the 3-methylxanthine to obtain 3,7-dimethylxanthine. In the above steps, the mass ratio of monomethyl 4AU to formic acid is 1:4, the molar ratio of sodium nitrite to monomethyl 4AU is 1:1, and the mass ratio of boron nitrogen doped platinum carbon catalyst to monomethyl 4AU is 0.01:1.

[0079] 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 80.1%, and the purity of 3,7-dimethylxanthine is 91.5%.

[0080] 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.

[0081] 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 3,7-dimethylxanthine, characterized in that: The method comprises the following steps: Obtaining 3-methyl-4-imidoureazoline; Dissolve 3-methyl-4-aminoureazimine in formic acid, add sodium nitrite and boron nitrogen-doped platinum-carbon catalyst, collect mother liquor after the reaction is completed, concentrate the mother liquor and filter out formic acid to obtain 3-methyl-4-amino-5-formamidoureazimine; Mixing 3-methyl-4-amino-5-formamidoureaazine, liquid alkali and water, adding acid to adjust to neutral after the reaction is completed to obtain 3-methylxanthine; performing methylation reaction and refining on the 3-methylxanthine to obtain 3,7-dimethylxanthine; Wherein, the boron 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 borane amine compound and the organic alcohol are uniformly mixed, and calcined at 800-850° C. to obtain a boron-nitrogen doped carbon carrier, wherein the mass ratio of the carbon carrier, the borane amine compound and the organic alcohol is (3-5): (6-10): (25-35), the borane amine compound is selected from at least one of borane dimethylamine and borane triethylamine, and the organic alcohol is selected from at least one of methanol and ethanol; The boron 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 boron nitrogen doped platinum carbon catalyst, wherein the mass ratio of the boron nitrogen doped carbon carrier to sodium fluoride is (3-7): (5-9), and the mass ratio of the boron nitrogen doped carbon carrier to the ethylene glycol solution of the platinum precursor is (10-15): (1-3).

2. A method for preparing 3,7-dimethylxanthine according to claim 1, characterized in that: The mass ratio of 3-methyl-4-imidoureaazine to formic acid is 1:(4-10).

3. A method for preparing 3,7-dimethylxanthine according to claim 1, characterized in that: The molar ratio of sodium nitrite to 3-methyl-4-imidourea is (1-1.5):

1.

4. A method for preparing 3,7-dimethylxanthine according to claim 1, characterized in that, The mass ratio of boron nitrogen doped platinum carbon catalyst to 3-methyl-4-imidoureaazine is (0.01-0.03):

1.

5. A method for preparing 3,7-dimethylxanthine according to claim 1, characterized in that: The preparation method of the 3-methyl-4-imidourea zine comprises the following steps: -10-20°C, adding cyanoacetic acid and oxalyl chloride to a solvent, concentrating the reaction solution after the reaction is completed, removing the solvent and excess oxalyl chloride, controlling the temperature to 0-30°C, adding monomethylurea and a solvent, and adding a base as an acid-binding agent, adding water after the reaction, stirring, and filtering to obtain monomethylcyanoacetyl urea; Dissolve monomethylcyanoacetyl urea in water, add liquid alkali to adjust the pH to 8-11, and react at 80-100°C to generate 3-methyl-4-imidourea.

6. The method for preparing 3,7-dimethylxanthine according to claim 1, characterized in that: The platinum precursor is selected from at least one of chloroplatinic acid and trimethylplatinum.