Synthesis Of 1-benzyl-3-methyl-6,7-dimethoxy-3,4- dihydroisoquinoline to be used as a potential hybrid drug

The existence of multiple functional groups in isoquinoline derivatives determines their potential as drug compounds. This research aims at the synthesis of such new isoquinoline based products. The compound 1-benzyl- 3-methyl-6,7-dimethoxy-3,4-dihydroisoquinoline containing methyl, methoxy, and benzyl groups has a potential of simultaneous acting antitumour, antimalarial and antivirus properties. Its synthesis from eugenol methyl ether is achieved through the latter conversion to a secondary alcohol, followed by Ritter reaction with benzyl cyanide and a cyclization reaction of the amide obtained to isoquinoline using sulfuric acid. The addition reaction between eugenol methyl ether and formic acid yields 1-(3,4-dimethoxyphenyl)-2-propyl formate (86,46 ). Its hydrolysis with KOH results in the formation of 1-(3,4-dimethoxyphenyl)-2-propanol (86,4 ). The latter reaction with benzyl cyanide in the course of Ritter reaction yields N-1-benzyl-2-(3,4-dimethoxyphenyl)ethyl-2-phenyl-acetamide (34,70 %). The subsequent cyclization with sulfuric acid and purification results in 1-benzyl-3-methyl-6,7-dimethoxy-3,4- dihydroisoquinoline as the main target with an yield of 45.19 %. An experimental verification of the corresponding products obtained is provided by FTIR, 1H-NMR, and GC-MS. © 2018, University of Chemical Technology and Metallurgy.