综合创新型实验:乙胺嘧啶合成的设计与教学实践

Design and Teaching Practice of Pyrimidine Synthesis in a Comprehensive Innovative Experiment

乙胺嘧啶(商品名:达拉匹林)是一种抗寄生虫药物,改进了合成方法,并设计转化为创新型综合教学实验。从对氯苯乙腈出发,使用丙酸乙酯为酰化试剂,在叔丁醇钾作用下得到烯醇前体。在三甲基氧鎓四氟硼酸盐(Me3O·BF4,Meerwein盐)和碱作用下进行选择性甲基化反应得到烯醇甲醚后,与胍在碱性条件下环化得到最终产物达拉匹林,并通过红外光谱、核磁共振对其结构进行表征。改进后的实验方法具有重现性好、毒性低、操作方便、实验微型化等优点。实验过程中不仅提升了学生的实验技能和科研思维,更提高了学生的创新能力和绿色环保意识。

Pyrimethamine(Trade name:Daraprim)is an antiparasitic drug.We improved its synthetic method and developed it into an innovative experiment for teaching.With KOtBu as the base and ethyl propionate as an acylation reagent,(4-chlorophenyl)acetonitrile was easily converted to the enol precursor,which can be selectively methylated with Me3O·BF4 to provide the methyl enol ether.After the cyclization step with guanidine carbonate under basic conditions,the obtained pyrimethamine was recrystallized from ethanol,and characterized by IR and NMR analysis.This modified synthetic procedure features good reproducibility,convenient operations,low toxicity and microscale compatibility.Through the training of this experiment,the students not only improved their experimental skills and scientific thinking,but also enhanced their ability of innovation and awareness of environmental issues.