Collect. Czech. Chem. Commun. 1982, 47, 3094-3113

Reactions of 11-chloro-11-phenyl-6,11-dihydrodibenzo[b,e]-thiepin with piperidine and some further nucleophiles

Miroslav Protiva, Karel Šindelář, Vladimír Valenta, Jiří Holubek, Emil Svátek, Miroslav Ryska, Jiří Schlanger, Jiří Urban and Marta Hrubantová

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


The title compound Vb affords with piperidine normal nucleophilic substitution product and the isomeric 3-piperidino derivative XXXII. The structure of XXXII was proven by (1) the 1H NMR and 13C NMR spectra, (2) an independent synthesis via the intermediates XXXV, XXXVI, XXX, IV and VIIIa, and (3) with the help of model reactions of the 2-methyl derivative VIb and the 3-methyl derivative VIIb with piperidine. The rearranged cation XXXVII is considered a precursor of the product XXXII. Similar mixtures are apparently formed in reactions of the chloro derivative Vb with a series of further amines where, however, mostly the normal substitution products (XV-XXI) were isolated and only in two cases the formation of the 3-substituted compounds (XXXIII, XXXIV) was noted. The 11-amino derivatives of the type XIII are unstable in ethanol in the presence of hydrogen chloride; the product of their acid catalyzed solvolysis is the ethoxy derivative XIV. Potassium phthalimide reacts with the compound Vb under the formation of the normal product XXII accompanied by 9-phenylanthracene (XXXVIII). Reaction of Vb with 3-dimethylaminopropylmagnesium chloride affords on the one hand the normal product XXIV, and the isomer on the other, to which the structure XXXIX is ascribed. The biological screening of the amines prepared showed with some compounds a rather significant antimicrobial activity in vitro (e.g. XXXIII) and some structurally less specific neurotropic effects, especially the spasmolytic (XXII, XXXIX) and the central depressant one (XX, XXXIII).