6-(4-苯磺酰基-3-甲基-2-丁烯)-基-2,3-二甲氧基-5-甲基氢醌双苄醚的合成

Synthesis of 6-(4-phenylsulfonyl-3-methyl-2-butenyl)-2,3-dimethoxy-5-methyl hydroquinone-O,O′-dibenzyl ether

以异戊二烯为原料,经与苯磺酰氯加成、水解乙酰化、皂化3步反应,制得末端羟基取代的异戊二烯短侧链——(E)-1-苯磺酰基-2-甲基-4-羟基-2-丁烯(简称产物A),并用乙酸乙酯-乙醚混合溶剂对产物A进行提纯精制。以还原型辅酶Q0(氢醌)为母环,杂多酸为催化剂,与产物A进行偶联反应,然后采用溴化苄对母环羟基进行保护,用乙醚-异丙醚的混合溶剂进行提纯精制,选择性结晶得到了侧链延长法合成辅酶Q10的关键中间体辅酶Q1前体,即6-(4-苯磺酰基-3-甲基-2-丁烯)-基-2,3-二甲氧基-5-甲基氢醌双苄醚(简称产物B)。探讨了各主要影响因素对合成反应过程及结果的影响,目标产物B收率达75%(以产物A为基准)。产物A与目标产物B经测熔点、1H NMR分析和FTIR分析鉴定,确证其为(E)-异构体。

（E）- 1-phenylsulfonyl-2-methyl-4-hydroxy-2-butene （product A ） was synthesized through the three-step process （ addition, acetolysis and saponification） by using isoprene as the starting material and purified by crystallization from ether-ethyl acetate mixtures. 6-（4-phenylsulfonyl-3-methyl-2- butenyl）-2,3-dimethoxy-5-methylhydroquinone-O,O′-dibenzyl ether （product B） was synthesized by coupling reaction between hydroquinone and product A by using heteropoly acid as catalyst and with the hydroxyl group on hydroquinone protected by bromobenzyl. The end product B was purified by crystallization from ether-diisopropyl ether mixtures. The influence factors of the synthesis process were also studied. The yield of end product B was 75% （based on product A） . This process has distinct advantages, such as simple process, much milder reaction conditions, green chemical catalytic technology and so on. The structures of product A and end product B were identified by FTIR and ^1H NMR.