Collect. Czech. Chem. Commun. 1985, 50, 503-509

Synthesis of spiro(piperidine-4,6'-dibenz[b,e]-1,4-oxathiepin) and its 1-methyl derivative as potential antidepressant agents

Karel Šindelář, Jiří Holubek, Jiří Schlanger, Antonín Dlabač, Martin Valchář and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


Starting from 2-chloronitrobenzene and 2-fluorothiophenol, the synthesis of 2-bromo-2'-fluorodiphenyl sulfide (X) was carried out in three steps. The product was converted to the Grignard reagent which reacted with 1-ethoxycarbonyl-4-piperidone and gave the alcohol XIII. Cyclization of this compound with sodium hydride in dimethylformamide afforded 1-ethoxycarbonylspiro(piperidine-4,6'-dibenz[b,e]-1,4-oxathiepin) (V) which was hydrolyzed to the title compound IV. Reduction of compound V with sodium dihydridobis(2-methoxyethoxy)aluminate afforded the 1-methyl derivative III which exhibited antireserpine activity and showed the pharmacological profile of a potential antidepressant.