基于Perkin反应的α-细辛脑合成工艺优化

Optimization ofα-asarone synthesis process based on Perkin reaction

以2,4,5-三甲氧基苯甲醛为原料,利用Perkin反应,通过控制反应温度和丙酸酐的比例,使反应直接向生成α-细辛脑的方向进行,以提高反应收率和产品质量。对Perkin反应中影响产品收率和质量的投料比、反应温度和反应时间三个因素,设计了三水平三因素的正交试验,所得产品经熔点、有关物质检查、紫外分光光度法、红外光谱法、HPLC法确证。2,4,5-三甲氧基苯甲醛∶丙酸酐∶丙酸钠投料比为1∶1.2∶2.0,反应温度为210℃,反应时间7 h为最佳工艺,反应收率为65.8%,HPLC法测得α-细辛脑含量99.2%。经工艺条件优化后,以2,4,5-三甲氧基苯甲醛为原料,通过Perkin反应合成α-细辛脑的反应收率和产品质量显著提高,产品质量符合2015年版国家药品质量标准,可用于大规模工业化生产。

In order to improve yield and quality of the reaction,we use 2,4,5-trimethoxybenzaldehyde as the raw material,and control the temperature and the proportion of propionic anhydride to make the reaction direct to the direction ofα-asarone formation by Perkin reaction.Orthogonal experiments were carried out at three levels,including the feed ratio,reaction temperature and reaction time,which affected the yield and quality of the product in Perkin reaction,and the product quality was confirmed by melting point,related substances inspection,ultraviolet spectrophotometry,infrared spectroscopy and HPLC.The ratio of 2,4,5-trimethoxybenzaldehyde to propionic anhydride and sodium propionate is 1∶1.2∶2.0,the reaction temperature is 210℃,and the reaction time is 7 h.The yield is 65.8%.The content ofα-asarone is 99.2%by HPLC.After optimization of process conditions,the yield and product quality of Perkin reaction for synthesis ofα-asarone from 2,4,5-trimethoxybenzaldehyde are significantly improved.The product quality meets the national drug quality standard of 2015 edition and can be used in large-scale industrial production.