摘要
在以三甲氧基苯甲醛为原料合成三甲氧苄二氨嘧啶的环化工艺中 ,提出了改 1次回流为 2次回流、环化阶段加入溶剂使反应从原来的固相状态改为液相状态下进行的新工艺 ,收率提高到 90 % ,由单因素实验和正交实验确定出工艺条件为 :“单甲醚”用量为 1 0 g时 ,第 1次回流温度为 80℃ ,回流时间 2 h,第 2次回流温度为 84～ 86℃ ,时间 3 h,环化阶段加入乙二醇单甲醚为溶剂 ,用量为 3 0 m L,硝酸胍用量为 1 1 g,反应温度1 0 0℃ ,反应时间 4h。产物经 IR、吸光度、熔点等分析鉴定 ,各项性能指标均符合中华人民共和国药典要求。
The cyclization process was carried out by double reflux instead of conventional single reflux and at the cyclization stage a solvent was added to the reaction mixture during the synthesis of trimethoprim(TMP) from 3,4,5-trimethoxy benzaldehyde. Cyclization yield was raised to 90% based on condensation product consisting of 80% α-(3,4,5-trimethoxy-benzal)-β-alkoxy-propionitrile and 20% α-(3,4,5-trimethoxy-benzyl)-β-alkoxy-acrylonitrile. The cyclization conditions were obtained by orthogonal factors and single factors experiments. When the mass of condensation product was 10 g, the temperature/time of the first and 2nd reflux were 80 ℃/2h, and 84～86 ℃/3h respectively, the amount of ethylene glycol monomethylether was 30 mL, the mass of guanidine nitrate was 11 g, at 100 ℃ for 4 h, TMP yield could be reached 90%.
出处
《应用化学》
CAS
CSCD
北大核心
2002年第11期1072-1075,共4页
Chinese Journal of Applied Chemistry
基金
河南省教育厅科技攻关项目 (2 0 0 0 5 3 0 0 0 8)
