反式-4-(N-乙酰氨基)环己醇的合成  

Synthesis of Trans-4-(N-Acetylamido)Cyclohexanol

作　　者：赵萌萌[1] 徐崇福[1] 宋蕴丽[1] 富利祥[1] 李嘉骏[1] 

机构地区：[1]常州大学石油化工学院,江苏常州213164

出　　处：《常州大学学报（自然科学版）》2012年第4期28-32,共5页Journal of Changzhou University：Natural Science Edition

摘　　要：反式-4-(N-乙酰氨基)环己醇是合成药物中间体反式-4-氨基环己醇盐酸盐的重要先行体。报道两步法合成反式-4-(N-乙酰氨基)环己醇研究结果,首先将起始原料对氨基苯酚用乙酸酐酰化,转化为对-(N-乙酰氨基)苯酚,接下来以5%Ru/C为催化剂,在有碱性助剂存在,5.0MPa,120℃条件下,将其氢化为顺式和反式混合的4-(N-乙酰氨基)环己醇,转化率为100%,4-乙酰氨基环己醇的选择性达到96.9%,根据高效液相色谱法检测得知,其反式与顺式比值为78∶22。最后通过重结晶分离出反式目标产物,总产率为67.0%。系统考察了多种因素对4-(N-乙酰氨基)苯酚的合成及后续催化氢化的影响。每步合成过程均由高效液相色谱监控。所有产物通过IR、1 H NMR、13C NMR光谱进行了结构表征。Trans-4-（N-acetylamido）cyclohexanol is an important precursor for the synthesis of pharmaceutical intermediate,hydrochloride salt of trans-4-aminocyclohexanol.Study of synthesizing trans-4-（N-acetylamido）cyclohexanol by two step processes was reported in this article.Starting material p-aminophenol was initially acetylated with acetic anhydride to yield 4-（N-acetylamido）-p-phenol,subsequent hydrogenation of this aromatic compound catalyzed by 5% Ru/C in presence of alkaline auxiliary at 5.0 MPa and 120 ℃ afforded the mixed trans-and cis-4-（N-acetylamido）cyclohexanol with 96.9% selectivity and 100% reactant conversion.The trans to cis ratio was 78 to 22 monitored by HPLC analysis.The targeted trans-isomer was isolated via recrystallization with 67.0% overall yield.Effects of myriad factors on the catalytic hydrogenation of 4-（N-acetylamido）phenol as well as acetylation of p-aminophenol were investigated.Processes of each synthetic step were monitored by HPLC.The molecular structures of all the products were characterized using infrared and 1H and 13C NMR spectroscopy respectively.

关 键 词：反式-4-(N-乙酰氨基)环己醇 催化加氢 顺反异构 重结晶 

分 类 号：O624.6[理学—有机化学]