超声波促进3-(4-苯磺酰基-3-甲基-2-丁烯基)-4,5,6-三甲氧基-2-甲基苯基苄基醚的合成

以3,4,5-三甲氧基甲苯(Ⅰ)为原料,经过Vilsmeier-Haack反应合成了6-甲基-2,3,4-三甲氧基苯甲醛(Ⅱ),收率94.1,Ⅱ经过Dakin反应得到2,3,4-三甲氧基-6-甲基苯酚(Ⅲ),收率96.2,用溴化苄对Ⅲ进行酚羟基保护得到2,3,4-三甲氧基-6-甲基苯基苄基醚(Ⅳ),收率95.0,Ⅳ在有机碱作用下发生溴代反应,得到6-甲基-5-溴-2,3,4-三甲氧基苯基苄基醚(Ⅴ),收率92.2,Ⅴ在超声波作用下制成格氏试剂(Ⅵ),再与4-溴-2-甲基-1-苯磺酰基-2-丁烯发生格氏偶联反应得到辅酶Q10的关键中间体3-(4-苯磺酰基-3-甲基-2-丁烯基)-4,5,6-三甲氧基-2-甲基苯基苄基醚(Ⅶ),收率72.0,五步反应总收率为57.1,产物经FTIR和1H NMR确定结构。

Synthesis of 3-(3-Methyl-4-benzenesulfonyl-2-butenyl)-4,5,6-trimethoxy-2-methylphenyl Benzyl Ether by Ultrasonic

3-(3-Methyl-4-benzenesulfonyl-2-butenyl)-4,5,6-trimethoxy-2-methylphenyl benzyl ether,a key intermediate of coenzyme Q10,was synthesized from 3,4,5-trimethoxytoluene(Ⅰ) in overall yield of 57.1%.6-Methyl-2,3,4-tri-methoxybenzaldehyde(Ⅱ) was obtained from Ⅰ via Vilsmeier-Haack reaction in 94.1% yield and converted to 6-methyl-2,3,4-trimethoxyphenol(Ⅲ) via Dakin reaction in 96.2% yield.Phenolic hydroxyl protection of Ⅲ with benzyl bromide produced 6-methyl-2,3,4-trimethoxyphenyl benzyl ether(Ⅳ) in 95.0% yield.Bromination of Ⅳ in the presence of organic base produced 5-bromo-2,3,4-trimethoxy-6-methylphenyl benzyl ether(Ⅴ) in 92.2% yield.Under the condition of ultrasonic,Grignard reagent was prepared from Ⅴ,and then coupled with 4-bromo-2-methyl-1-benzenesulfonyl-2-butene to give the target product in 72.0% yield.Structure of the products were confirmed by FTIR and 1HNMR