Study On The Crystallization Process Of NAU

Purple uric acid(6-amino-1,3-dimethyl-5-nitrosouracil,NAU)is an important in-termediate for the synthesis of caffeine and theophylline in industrial production.It is usually prepared in the form of monohydrate by reactive crystallization.However,the theoretical research on NAU crystallization process is very scarce,and industrial pro-duction is also faced with the problems of poor crystal habit and high moisture content of products.In order to solve these problems,the crystallization process of NAU was studied in detail.Solvent is an important factor that affects the crystallization process.The effect of solvent on NAU crystallization process was first studied.It is found that the three sol-vents of water,DMSO,DMF have a great influence on the crystal habit and crystal form of crystal products.Molecule surface electrostatic potential analysis(ESP),radial distribution function analysis(RDF),calculation of related molecular structure energy,experimental and theoretical nuclear magnetic resonance(~1H NMR)were used to study the solvent-solute interaction in sulfoxide solution.It is found that the hydrogen bond between solvent and solute greatly affects the tautomeric of NAU.The molecular be-havior of NAU in water and N,N-dimethylformamide was studied through the similar-ity of molecular structure and the calculations of related structure energy.The crystal growth units in the crystallization process of three solvates were judged.The additives used in the crystallization process may also affect the crystal habit and crystal form of the crystal product.Aiming at the bad crystal habit of NAU mono-hydrate in industrial applications,7 weak acids and 7 common surfactants were sued to control the crystal habit of NAU monohydrate.It is found that weak acids will promote the aggregation of NAU monohydrate when its concentration is high enough.Sodium carboxymethylcellulose(CMC-Na)has a significant effect on the regulation of crystal habit of NAU monohydrate.And all additives used don’t affect the crystal form of crys-tal product.The crystal habit of NAU monohydrate was also calculated using the adhe-sion energy model(AE).Simulation results show that the adsorpotion of water mole-cules on specific crystal planes is the reason why NAU monohydrate is flaky.The syn-ergistic effect of the side chain carboxyl structure and the chain structure of CMC ion is the reason why the NAU monohydrate is blocky.In order to deepen the research on the reaction crystallization process of NAU monohydrate,crystal form,habit moisture content and yield of crystal products were used to evaluate the influence of feeding method,operation conditions,process conti-nuity.Moisture content and yield of NAU monohydrate are greatly influenced by feed-ing methods.The effect of temperature on the reaction crystallization process is differ-ent under different p H conditions.The moisture content of NAU monohydrate will be lower if p H is lower under different temperature conditions.In addition,the moisture content will be lower if the process is continuous.