HIV病毒抑制剂中间体3,5-二羟基戊苯(olivetol)的新合成方法  

New Preparation Method of 3,5-Dihydroxy-1-pentylbenzene,Intermediate for HIV Restrainer

作　　者：徐宇伦[1] 张龙[1] 金鑫 宋义新 

机构地区：[1]长春工业大学化工学院,吉林长春130012 [2]大连兆科生物化工有限公司,辽宁大连116620

出　　处：《精细化工》2006年第4期382-385,共4页Fine Chemicals

摘　　要：以工业级的3,5-二甲氧基苯甲酸为起始原料,与L iH于室温下在四氢呋喃中反应5 h生成3,5-二甲氧基苯甲酸锂(Ⅰ),不需精制,直接与正丁基锂在冰浴中进行酰化反应制得3,5-二甲氧基苯戊酮(Ⅱ),收率85.06%;进而在210℃以下通过乌尔夫-黄鸣龙反应将Ⅱ还原为3,5-二甲氧基戊苯(Ⅲ),Ⅲ与熔融的吡啶盐酸盐在200℃回流2 h,脱甲基制得目标产物3,5-二羟基戊苯(Ⅳ),总收率为60.90%,质量分数为98.22%。利用IR1、HNMR、GC、HLPC-MS等分析手段对各步产物进行了表征。结果表明:该文所提出合成路线是可行的,具有工艺简单、收率高等特点,优于目前所报道的其他合成路线。目前正在进行放大实验。A new process for the preparation of 3,5-dihydroxy-l-pentylbenzene which is used as medicinal intermediate and raw material for the synthesis of HIV restrainer was proposed in this paper. Technical 3,5-dimethoxybenzoic acid reacted with lithium hydride to form salt（ Ⅰ ）which acylated n- butyllithium directly to give 1-（3,5-dimethoxyphenyl）-1-pentanone（ Ⅱ ）in 85.06% yield. Then Ⅱ was reduced through Wolff-K-Huangminglong reaction at 210 ℃ to give 3,5-dimethoxy-1- pentylbenzene （ Ⅲ ）. Finally, Ⅲ refluxed with melt pyridine hydrochloride at 200 ℃ for 2 h to afford the target product 3,5-dihydroxy-1-pentylbenzene（ Ⅳ ）. The total yield of Ⅳ amounted to 60.90% and its mass percentage was 98.22%. The products were characterized by means of IR,^1HNMR, GC and HLPC - MS. The results indicated that this synthesis route was feasible, characterized by simple process and high yield,superior to the published ones. Enlarged preparation experiment is being carried out now.

关 键 词：HIV病毒抑制剂 3 5-二羟基戊苯 3 5-二甲氧基苯甲酸 酰化 乌尔夫-黄鸣龙还原 脱甲基化 

分 类 号：O625.31[理学—有机化学]