布洛芬-扑热息痛孪药的合成

doi:10.3724/SP.J.1095.2014.30430

摘要/Abstract

摘要： 以布洛芬（IPF）和扑热息痛（PCM）为原料，无水丙酮和乙酸乙酯为溶剂，二环己基碳二亚胺（DCC）为脱水剂，4-二甲氨基吡啶（DMAP）为催化剂，合成了布洛芬-扑热息痛孪药（PHI），以重结晶法对目标产物进行纯化，产物结构经IR和1H NMR确定。探讨了原料比例、脱水剂用量、催化剂用量、反应时间和溶媒用量对目标物产率的影响，并采用正交试验筛选最优合成工艺，最终确定的最优反应条件为:n(PCM)∶n(IPF)=1∶1.5，催化剂的最佳用量为布洛芬质量的10%，反应时间为8 h，溶媒体积为70 mL（V(乙酸乙酯)∶V(丙酮)=1∶1），在该条件下，目标物PHI的产率为66.53%。

关键词: 布洛芬, 扑热息痛, 孪药, 二环己基碳二亚胺/二甲氨基吡啶

Abstract: The twin drug(PHI) was synthesized by coupling ibuprofen(IPF) and paracetamol(PCM) using dicyclohexylcarbodiimide（DCC） as dehydrating agent, 4-dimethylaminopyridine(DMAP) as catalyst, and anhydrous acetone and ethyl acetate as reaction solvents. PHI was purified by recrystallization and its structure was confirmed by IR and 1H NMR spectroscopy. The effect of catalyst, dehydrating agent, reaction time, feed ratio and reaction solvents on the yield of the product was investigated. The reaction conditions were optimized by the orthogonal test. The optimized reaction conditions are:the molar ratio of raw materials is n(PCM)∶(IPF)=1∶1.5, the optimal amount of DMAP is 10% mass fraction of ibuprofen; the volume of solvent is 70 mL(the volume ratio of ethyl acetate and acetone is 1∶1) and the reaction time is 8 h. Under the optimized conditions, the yield of target is 66.5%.

Key words: Ibuprofen, paracetamol, twin drug, dicyclohexylcarbodiimide/dimethylaminopyridine

中图分类号:

O625.3

金超, 符华林, 张伟, 张艳丽, 曹航, 周涛, 卢朝成, 刘梦娇, 周建瑜. 布洛芬-扑热息痛孪药的合成[J]. 应用化学, DOI: 10.3724/SP.J.1095.2014.30430.

JIN Chao1, FU Hualin1,2*, ZHANG Wei1, ZHANG Yanli1, CAO Hang1, ZHOU Tao1, LU Chaocheng1, LIU Mengjiao1, ZHOU Jianyu1. Synthesis of the Twin Drug of Ibuprofen and Paracetamol[J]. Chinese Journal of Applied Chemistry, DOI: 10.3724/SP.J.1095.2014.30430.

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