盐酸罂粟碱的合成路线图解

Graphical Synthetic Routes of Papaverine Hydrochloride

盐酸罂粟碱是一类抗痉挛药物,在临床上应用广泛。对盐酸罂粟碱及其中间体的合成路线进行了综述,对国内两条罂粟碱合成路线进行了对比分析,并提出了具有工业化生产前景的合成路线:以邻苯二乙醚和丙烯腈为起始原料,经过加成反应、水解反应、霍夫曼酰胺降解反应,得到中间体3,4-二甲氧基苯乙胺;以邻苯二乙醚和草酰氯单乙酯为起始原料,经过傅克反应、沃尔夫-凯惜纳-黄鸣龙还原反应,得到中间体3,4-二甲氧基苯乙酸。再将上述得到的2个中间体经缩合、环合、脱氢、成盐等步骤制备盐酸罂粟碱,与其他工艺相比,该工艺原料易得,操作简单,收率高,成本低。

Papaverine hydrochloride is one class of anticonvulsant drugs and widely used in the clinical treatment.This article reviews the synthetic routes of papaverine hydrochloride and its intermediates,and makes a comparative analysis of two domestic synthetic routes of papaverine in China.A potential industrial production route was proposed as follows:starting from 1,2-diethoxybenzene and acrylonitrile,through addition reaction,hydrolysis reaction,and Huffman rearrangement,intermediate 3,4-dimethoxyphenethylamine was obtained.1,2-diethoxybenzene and ethyl oxalyl monochloride were used as the starting materials,the intermediate 3,4-dimethoxyphenylacetic acid was obtained through the Friedel-Crafts reaction and Wolff-Kishner-Huang min lon-Reduction reaction.The two intermediates obtained above were then subjected to the steps of condensation,cyclization,dehydrogenation,and salt formation to prepare papaverine hydrochloride.Compared with other processes,this process has the advantages of available raw materials,simple operation,high yield and low cost.