Synthesis method of theophylline

Abstract

The invention discloses a synthesis method of theophylline, and relates to the technical field of preparation of heterocyclic compounds containing purine ring systems. The preparation method comprisesthe following steps: mixing cyanoacetic acid and acetic anhydride at 30-80 DEG C for reaction, adding a solvent and dimethylurea, cooling to room temperature after reflux reaction is finished, filtering, concentrating filtrate, combining solids to obtain dimethylacetamide, adding liquid caustic soda to adjust the pH to 8-11, and reacting at 80-100 DEG C to generate dimethyl 4AU; completely dissolving dimethyl 4AU in formic acid, adding sodium nitrite, reacting at room temperature, adding a catalyst and water, keeping the temperature at 30-70 DEG C, recovering the catalyst after the reaction is finished, and concentrating mother liquor to recover formic acid, thereby obtaining dimethyl FAU; adding dilute sulfuric acid into the dimethyl FAU to adjust the pH value to 36, heating to 90-100 DEG C, allowing the feed liquid to pass through an ozone reactor and a decolorizer, crystallizing by a crystallizer, and carrying out cold filtration to obtain theophylline. The method has the advantages of few reaction steps, mild reaction conditions, simple operation, high yield, stable product quality, small discharge capacity, reduction of the environmental protection treatment difficulty, and easy industrialization.

Description

technical field [0001] The invention relates to the technical field of preparation of heterocyclic compounds containing a purine ring system, in particular to a method for synthesizing theophylline. Background technique [0002] Theophylline (Theophylline) aliases: dioxodimethylpurine; 1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione; 1,3-dimethylxanthine . Theophylline is a methylpurine drug. It has the effects of strengthening the heart, diuresis, expanding coronary arteries, relaxing bronchial smooth muscle and stimulating the central nervous system. Mainly used for the treatment of bronchial asthma, emphysema, bronchitis, cardiac dyspnea. [0003] The currently known industrial synthesis method of theophylline is to use cyanoacetic acid and dimethyl urea as raw materials, and first generate the intermediate product theophylline sodium salt through steps such as condensation, cyclization, subization, water washing, hydrogenation, acylation ring closure, and filtration. , ...

AI Technical Summary

Problems solved by technology

For example, Liu Hui et al. have developed a new hydrogenation reduction system and invented a preparation method for N,N-1,3-dimethyl-4,5-diaminocarbazine (dimethyl DAU), which can Make the reaction more stable and controllable, improve the catalytic activity to stabilize the quality of dimethyl DAU, improve the yield and quality; The step of oxidizing impurities improves product yield and purity, saves the separation of 1,3-dimethyl-4-amino-5-carboxamidoureazine (dimethyl FAU), and shortens the production cycle; However, the above studies are all based on the existing technology, and the development and improvement of the reaction system or equipment, raw materials, etc. are carried out in a single step, so as to reduce the reaction steps, increase the reaction yield, improve the product quality or produce environmental protection. effect, but none of them substantially changed the original process or greatly reduced the reaction steps