Collect. Czech. Chem. Commun. 1986, 51, 2848-2868

5-Substituted and 5,7-disubstituted 5,7-dihydrodibenzo[c,e]thiepins and the corresponding S-oxygenated compounds: Alkylamines, carboxylic acids, and carboxamides; synthesis and pharmacological screening

Karel Šindelář, Jiří Holubek, Miroslav Ryska, Ivan Koruna and Miroslav Protiva

Research Institute of Pharmacy and Biochemistry, 130 60 Prague 3


Reaction of 5,7-dihydrodibenzo[c,e]thiepin (I) with n-butyllithium resulted in the partial sulfur extrusion and in the formation of the 9,10-dihydrophenanthrene-9-thiolate anion (B). Its further transformations (by hydrolysis, aminoalkylation and spontaneous dehydrogenation) led to phenanthrene-9-thiol (IX), the corresponding disulfide X, and the S-(2-dimethylaminoethyl) derivatives XI and XIV. Reactions of 5-chloro-5,7-dihydrodibenzo[c,e]thiepin (II) with the corresponding Grignard reagents were only a poor source of the amines III and IV. Reaction of the sulfoxide XVIII with n-butyllithium or with sodium hydride and the following treatment with 2-dimethylaminoethyl chloride gave the amine XIX in a low yield. Only the sulfone X was found more useful for preparing the 5- and 5,7-substituted derivatives. Treatment with n-butyllithium and following carbonation afforded mixtures of the monocarboxylic acid XXI and dicarboxylic acid XXVIII. Via acid chlorides they were transformed to the methylamides XXII and XXIX, and to the dimethylamides XXIII and XXX. The amide XXIII was reduced to the 5-(dimethylaminomethyl) compound XXV. Lithiation of the sulfone XX or treatment with sodium hydride, and the following action of 2-dimethylaminoethyl chloride and 3-dimethylaminopropyl chloride gave the amines XXVI, XXVII, and XXXI. Only the phenanthrene derivatives XI and XIV, and the amino sulfone XXVII showed clear indications of thymoleptic activity as potential antidepressants.