【作者】 尹国辉；

【导师】 高欣钦；

【作者基本信息】 大连理工大学 ， 应用化学， 2010， 硕士

【摘要】 盐酸美金刚是出德国Merz公司开发的一种低中等程度亲和力的非竞争性N-甲基-D-天冬氨酸受体拮抗剂,2003年被美国食品和药品管理局(FDA)批准用于治疗中、重度阿尔茨海默病。本文建立了一条以苊为起始原料,经过催化加氢、重排、乙酰胺基化、水解、成盐等反应合成盐酸美金刚的合成路线。该合成路线最大的优点是省去目前常用盐酸美金刚合成路线中1,3-二甲基金刚烷澳化这一步反应,简化了反应步骤。另外,该路线的起始原料苊廉价易得。近年来,N-杂环卡宾被广泛应用于配位化学和均相催化领域。大位阻的N-杂环卡宾因有利于催化活性物质的生成并能促进催化循环中的还原消除步骤而受到格外关注。目前,将大位阻的N-杂环卡宾应用于Pd催化的偶联反应越来越来流行。本文以盐酸美金刚为原料,合成了含大位阻3,5-二甲基金刚烷取代基的N-杂环卡宾前体：1,3-二(3,5-二甲基金刚烷基)咪唑啉盐酸盐、1,3-二(3,5-二甲基金刚烷基)咪唑盐酸盐和1-苄基-3-(N-3,5-二甲基金刚烷基乙酰胺基)咪唑盐酸盐。另外,将1-苄基-3-(N-3,5-二甲基金刚烷基乙酰胺基)咪唑盐酸盐用于Pd配合物的制备以期待获得高活性的Pd催化剂,其催化活性用卤代芳烃与苯硼酸之间的Suzuki-Miyaura反应进行了初步检测。更多还原

【Abstract】 Memantine hydrochloride. developed by Merz Pharmaceuticals, is a moderate affinity, uncompetitive N-methyl-D-aspartate receptor antagonist. It was approved by FDA in 2003 for the treatment of moderate to severe Alzheimer’s disease.A short and economical process route has been developed for the synthesis of memantine hydrochloride in this thesis. Starting from acenaphthene, the procedure involves sequential reactions such as catalytic hydrogenation, rearrangement, amidation, hydrolysis and acidation. Without bromination of 1,3-dimethyl-adamantane is regarded as a significant advantage of this synthetic route. Besides, acenaphthene is an inexpensive, commercially available raw material.In recent years N-heterocyclic carbene (NHC) ligands have been widely used in the fields of coordination chemistry and homogeneous catalysis. Sterically very demanding NHCs are particularly attractive because they may facilitate the formation of catalytically active species, as well as enhance the reductive elimination step. Therefore, the use of sterically demanding NHCs in palladium-catalyzed cross-coupling reactions is rapidly gaining in popularity.Starting from memantine hydrochloride, imidazol(in)ium chlorides bearing bulky 3,5-dimethyladamantyl substituent, 1,3-bis-(3,5-dimethyladamantyl)imidazolinium chloride, 1,3-bis-(3,5-dimethyladamantyl)imidazolium chloride and 1-benzyl-3-(N-3,5-dimethyladama-ntan-1-ylacetamido) imidazolium chloride were synthesized in this thesis. In order to find more efficient palladium catalysts, 1-benzyl-3-(N-3,5-dimethyladamantan-1-ylacetamido) imidazol-2-ylidene Pd complexe was prepared and its catalytic activity was simply examined in Suzuki-Miyaura reaction.更多还原