Collect. Czech. Chem. Commun. 1990, 55, 782-796

Open-ring models of hetero-cannabinoids: Synthesis of 2-(alkylthio)-5-(2-aminoethyl)hydroquinone derivatives

Karel Šindelář, Jiří Holubek, Emil Svátek, Jiří Schlanger, Antonín Dlabač, Martin Valchář, Marta Hrubantová and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


2,5-Dimethoxythiophenol was S-alkylated with pentyl bromide and heptyl bromide, the sulfides IVa,b were chloromethylated and the products were transformed to the nitriles VIIa,b. Reduction with aluminium hydride gave the amines XIIIa,b which were transformed to N-methyl- and N,N-dimethyl derivatives XVa,b and XVIa,b. Alkylation of the nitriles VIIa,b with 2-propyl bromide and the following reduction with aluminium hydride led under simultaneous partial demethylation to monophenolic amines XVIIIa,b. Methylation of these amines gave the N-(monomethyl) compound XIXa and the N,N-dimethyl compound XXb. The complete O-demethylation of XXb with boron tribromide or iodotrimethylsilane gave the hydroquinone XXI in the form of the corresponding salt (hydrobromide, hydroiodide). Compound XIIIb (hydrogen maleate VUFB-16 519) exhibited interesting antireserpine activity in two tests and may be considered a potential antidepressant.