3,4,5-三甲氧基苯乙酸的合成

以3,4,5-三甲氧基苯甲醛为原料,经二氯卡宾反应、还原反应两步合成了米库氯铵的重要中间体——3,4,5-三甲氧基苯乙酸。较佳的合成工艺条件为:(1)二氯卡宾反应:以0.3 mol 3,4,5-三甲氧基苯甲醛为基准,在n(3,4,5-三甲氧基苯甲醛)∶n(CHCl3)=1∶3,复合相转移催化剂(PTC)2 g,w(NaOH)=40%的水溶液21 mL,反应温度60℃,反应时间7 h的条件下,反应收率为71.7%;(2)还原反应:以0.1 mol 3,4,5-三甲氧基扁桃酸为基准,在n(3,4,5-三甲氧基扁桃酸)∶n〔(CH3)3SiCl〕∶n(NaI)∶n(Zn)=1∶1.25∶1.25∶3,反应温度80℃,"一锅法"反应5 h的条件下,反应收率91.0%。两步反应总收率为65.2%。产物结构通过IR、1HNMR进行表征。

Synthesis of 3,4,5-trimethoxyphenyl acetic acid

3,4,5-Trimethoxyphenyl acetic acid,an important intermediate for preparation of mivacurium chloride,was synthesized from 3,4,5-trimethoxybenzaldehyde by dichlorocarbene reaction and reduction reaction.The optimum reaction conditions are as follows:(1)In dichlorocarbene reaction,the molar ratio of raw materials was n(3,4,5-trimethoxybenzaldehyde)∶n(chloroform)=1∶3(based on 0.3 mol 3,4,5-trimethoxybenzaldehyde),w(NaOH)=40% solution was 21 mL,the composite phase transfer catalyst(PTC) was 2 g,reaction time was 7 hours at 60 ℃.The yield of 3,4,5-trimethoxymandelic acid was 71.7%.(2)In reduction reaction,the molar ratio of raw materials was n(3,4,5-trimethoxymandelic acid)∶n(trimethylchlorosilane)∶n(sodium iodide)∶n(zinc)=1∶1.25∶1.25∶3(based on 0.1 mol 3,4,5-trimethoxymandelic acid),"one-pot" reaction time was 5 h at 80 ℃.The yield of the target product was 91.0%.The overall yield of the two steps of reaction reached 65.2% and the structures of the target compound were confirmed by means of IR and 1HNMR.