摘要
为优化以2,4,5-三氨基-6-羟基嘧啶硫酸盐为原料的叶酸合成工艺,降低反应过程中的用水量,提高叶酸的选择性,将2,4,5-三氨基-6-羟基嘧啶硫酸盐与等物质的量的碳酸钾反应进行预处理后,再用于叶酸的合成,并经精制制备叶酸产品。通过HPLC、FTIR和1HNMR对叶酸产品表征确证其结构,考察了碱的类型、反应温度、反应时间、反应物用量、相转移催化剂以及所得滤液的循环使用对叶酸合成的影响,探究酸类型和碱精制溶液pH对叶酸精制的影响。结果表明,预处理可有效改善2,4,5-三氨基-6-羟基嘧啶硫酸盐的水溶性,当n(2,4,5-三氨基-6-羟基嘧啶硫酸盐)∶n(碳酸钾)∶n(N-对氨基苯甲酰-L-谷氨酸)∶n(三氯丙酮)=1.2∶1.2∶1.0∶2.6时,以四丁基溴化铵为相转移催化剂,反应温度40℃,在pH为2.5~2.8和3.2~3.5条件下依次反应3 h,得到叶酸粗品,质量分数为72.81%,收率为82.22%。用盐酸对叶酸粗品进行酸精制,再在pH=8.5的条件下进行碱精制,最终得到叶酸产品,质量分数为97.69%,收率为66.35%。相较于传统工艺,该工艺制备的叶酸产品收率增加6.18%,用水量减少了33%。
In order to optimize the synthesis of folate from 2,4,5-triamino-6-hydroxypyrimidine sulfate,reduce the water consumption in the reaction process and improve the selectivity of folic acid,2,4,5-triamino-6-hydroxypyrimidine sulfate was pretreated with an equal amount of potassium carbonate before being used for the synthesis of folic acid,and then refined to prepare folic acid product.The structure of folic acid product was characterized by HPLC,FTIR and 1HNMR.The effects of alkali type,reaction temperature,reaction time,reactant dosage,phase transfer catalyst and recycling of the resulting filtrate on folic acid synthesis was evaluated,while the influence of acid type and pH of alkali refining solution on folic acid refining were explored.The results showed that pretreatment could effectively improve the water solubility of 2,4,5-triamino-6-hydroxypyrimidine sulfate.Under the conditions of n(2,4,5-triamino-6-hydroxypyrimidine sulfate)∶n(potassium carbonate)∶n(N-p-aminobenzoylt-L-glutamic acid)∶n(trichloroacetone)=1.2∶1.2∶1.0∶2.6,tetrabutylammonium bromide as phase transfer catalyst,reaction temperature 40℃,and pH=2.5~2.8 and 3.2~3.5 for 3 h,respectively,crude folic acid with a mass fraction of 72.81%and a yield of 82.22%was obtained,which was further was refined with hydrochloric acid,and then alkali solution with pH=8.5 to obtain folic acid product with a mass fraction of 97.69%and a yield of 66.35%.Compared with traditional process,this synthesis process increased the yield of folic acid product by 6.18%and reduced the water consumption by 33%.
作者
张瀛舟
陆露
牛鹏飞
张宝
宋健
ZHANG Yingzhou;LU Lu;NIU Pengfei;ZHANG Bao;SONG Jian(School of Chemical and Engineering and Technology,Tianjin University,Tianjin 300354,China)
出处
《精细化工》
北大核心
2025年第9期2082-2088,共7页
Fine Chemicals
关键词
叶酸合成
碱溶法
合成优化
母液套用
精制优化
精细化工中间体
folic acid synthesis
alkali solution method
synthesis optimization
mother liquid application
refining optimization
fine chemical intermediates
