比沙可啶的合成工艺研究

Synthesis of Bisacodyl

以2-吡啶甲醛为起始原料,在浓硫酸催化下,与苯酚缩合得到4,4'-二羟基二苯基-(2-吡啶)-甲烷和2,4'-二羟基二苯基-(2-吡啶)-甲烷,利用二者在乙酸乙酯中溶解度的差别,分离得到4,4'-二羟基二苯基-(2-吡啶)-甲烷,用氢氧化钠转变得到酚钠盐后,经乙酰化得到比沙可啶。其结构经核磁共振氢谱确证,纯度经液相色谱分析为99%。改进后的合成工艺操作简便,收率可达58%。

Pyridine-2-aldehyde(2)was reacted with phenol(3)in the presence of concentrated sulfuric acid to give a mixture of 4,4'-dihydroxy-diphenyl-(2-pyridyl)-methane(4)and 2,4'-dihydroxy-diphenyl-(2-pyridyl)-methane(5).4 was isolated from the mixture with purity of 99%(LC)due to its low solubility in ethyl acetate and was transformed to sodium salt with sodium hydroxide.Further acetylation of the sodium salt gave the title compound bisacodyl(1)in overall yield of 58%,that the structure was confirmed by 1H NMR.