2，3—二甲氧基—5—甲基—6—（3—甲基—2—羟基—3—烯—1—丁基）—1，4—对苯二酚—O，O—二苄醚的合成与工艺优化

【作者】 黄雁明；

【导师】 尹红； 陈志荣；

【作者基本信息】 浙江大学 ， 应用化学， 2004， 硕士

【摘要】 2，3—二甲氧基—5—甲基—6—（3—甲基—2—羟基—3—烯—1—丁基）—1，4—对苯二酚—O，O—二苄醚是合成原料药辅酶Q₁₀的重要中间体，本文以辅酶Q₀为起始原料，经过催化加氢、烷基化、苄基化、环氧化及异构化5步反应合成了2，3—二甲氧基—5—甲基—6—（3—甲基—2—羟基—3—烯—1—丁基）—1，4—对苯二酚—O，O—二苄醚。 本文对这5步反应进行了优化研究，最终得到了较高的反应收率。第一步即Pd／C催化的辅酶Q₀氢化反应可以几乎定量完成，产物不需分离即可进行下一步反应。通过单因素实验法对影响第二步的各个因素进行了优化，得到较佳的反应条件为：原料Q₀：甲基丁烯醇=1：1.5（摩尔比），催化剂用量（与辅酶Q₀摩尔比）为0.19，反应温度是45℃，滴加时间是30min，反应时间2—2.5小时，得到产物的含量为95.42％，收率为90.24％。对影响第三步苄基化反应的因素进行优化，得到较佳的反应条件为：烷基化原料：氢化钠=1：2.4（摩尔比），反应温度为25℃，反应时间3小时，且加入少量的还原剂H可以提高反应收率和产物的纯度，反应收率可达91.91％。苄基化产物在0℃以下几乎可以定量地与过氧乙酸进行反应，收率可达98.6％，在后处理过程中用溶剂E结晶代替柱分离提纯环氧化产品，结晶总收率可达94.8％，大大降低了生产成本。第五步异构化反应收率为92％，与文献报道相同，产物纯度也很高，完全达到了后续反应的要求。更多还原

【Abstract】 6-(2’-Hydroxy-3’-methylbut-3’-enyl)-2,3-dimethoxy-5-methylhydroquinone O,O’-dibenzyl ether is an important medical intermediate of Coenzyme Q10. A commercial and practical synthesis route with Coenzyme Q0 as material by catalytic hydrogenation, alkylation, benzylation, following epoxidation and isomerization is chosen in this paper.The condition of the first reaction is moderate. The hydrogenation of Q0 catalyzed by Pd/C could almost be carried out quantificationally and the product can be used as material of the next reaction without purification. The optimized conditions of the second to reaction are : the ratio of m(Qo) to m(catalyst) to m(2-Hydroxy-2-methlbut-3-ene) equals tol:0.19:1.5, reaction temperature is 45℃, reaction time is 2 ~2.5hours and droping time is 30min. The yield 90.24% and the content is 95.24%. The optimized conditions of the third reaction are : the ratio of m (alkylation material) to m(NaH) is 1:2.4, reaction temperature is 25℃, reaction time is 3 hours and the reducing agent H was added to improve reaction yield and product purity. The yield of this step is 91.91%. Benzylation product could react with peracetic acid quantificationally under 0℃ and the yield is 98.6%. The solvent E was used to replace silica gel chromatography for separation of epoxide during purification. The yield of the crystallization is 91.91% and the cost is greatly reduced. The yield of the isomerization is 92% and the product with high purity can be used in the following reactions.更多还原