Abstract 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.
LI Qiu-Lian, WAN Hong, GONG Yue-Fa, LU Deng-Fu. Design and Teaching Practice of Pyrimidine Synthesis in a Comprehensive Innovative Experiment[J]. Chinese Journal of Chemical Education, 2020, 41(8): 63-66.
