Collect. Czech. Chem. Commun. 1987, 52, 793-803

2-(tert.amino)-11-(4-methylpiperazino)dibenzo[b,f]thiepins and their 10,11-dihydro derivatives; Synthesis and neuroleptic activity

Vojtěch Kmoníček, Jiří Holubek, Emil Svátek, Jiřina Metyšová and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


Reactions of (2-iodophenyl)acetic acid with 4-(dimethylamino)thiophenol, 4-piperidinothiophenol, and 4-morpholinothiophenol in boiling aqueous potassium hydroxide solutions in the presence of copper gave the arylacetic acids IVabc which were cyclized with polyphosphoric acid at 130 °C to 8-(tert.amino)dibenzo[b,f]thiepin-10(11H)-ones Vabc. The following reactions with 1-methylpiperazine in boiling benzene in the presence of titanium tetrachloride afforded the enamines IIabc. Compounds IIa and IIc were reduced with diborane to the 10,11-dihydro compounds Ia and Ic. Compound Ia (the 8-dimethylamino derivative of perathiepin) is a typical incisive neuroleptic agent with very strong cataleptic, antiapomorphine, central depressant, and antiadrenergic activities. The morpholino derivative Ic and the enamines IIb and IIc are less active.