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.
出处
《常州大学学报(自然科学版)》
CAS
2012年第4期28-32,共5页
Journal of Changzhou University:Natural Science Edition
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
trans-4-(N-acetylamido)cyclohexanol
catalytic hydrogenation
cis and trans isomerism
recrystalization