6-(3-甲基-4-对甲苯磺酰基-2-丁烯基)-2,3,4,5-四甲氧基甲苯的合成

Synthesis of 6-(3-Methyl-4-p-toluenesufonyl-2-butenyl)-2,3,4,5-tetramethoxytoluene

对甲酚(Ⅰ)在铁粉催化下与溴反应得到2,3,6 三溴 4 甲基苯酚(Ⅱ)(收率78%);Ⅱ在碘化亚铜催化下与甲醇钠反应后再与硫酸二甲酯反应得到2,3,4,5 四甲氧基甲苯(Ⅲ)(收率92 5%);Ⅲ与溴反应得到6 溴 2,3,4,5 四甲氧基甲苯(Ⅳ)(收率85%);Ⅳ与镁反应得到格氏试剂后,在碘化亚铜催化下与(E) 4 氯 2 甲基 1 对甲苯磺酰基 2 丁烯(Ⅴ)偶联反应合成了辅酶Q10中间体6 (3 甲基 4 对甲苯磺酰基 2 丁烯基) 2,3,4,5 四甲氧基甲苯(Ⅵ)(收率81%)。四步反应总收率49 6%,产物经1HNMR确证其双键为E 异构体。

6-(3-methyl-4-p-toluenesufonyl-2-butenyl)-2,3,4,5-tetramethoxytoluene(Ⅵ),an intermediate of coenzyme Q10,was synthesized from p-cresol(Ⅰ) via four step procedure in overall yield of 49.6%.Bromination of Ⅰ in the presence of Fe powder gave 2,3,6-tribromo-4-methyphenol (Ⅱ) in 78% yield.Ⅱ reacted with CH3ONa in the presence of CuI,and then with (CH3)2SO4 to give 2,3,4,5-tetramethoxytoluene (Ⅲ) in 92.5% yield.Compound Ⅲ was brominated to give 6-bromo-2,3,4,5-tetramethoxytoluene (Ⅳ) in 85% yield,Ⅳ reacted with Mg,followed by reaction with (E)-4-cholro-2-methyl-p-toluenesufonyl-2-butene (Ⅴ),to give compound Ⅵ in 81% yield.The double bond of compound Ⅵ was confirmed to be E-isomer by 1HNMR.