Synthesis Of Memantine Hydrocloride, N-heterocyclic Carbene Precursors And NHC-Pd Complexes

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.