Diastereoisomeric forms of 11-ethyl-6,11-dihydro-5H-dibenzo[b,e]azepine-6-carboxamide: syntheses and the molecular and supramolecular structure of the minor form (6RS,11RS)-11-ethyl-6,11-dihydro-5H-dibenzo[b,e]azepine-6-carboxamide

Abstract

Compounds containing the tricyclic dibenzo[b,e]azepine system have potential activity in the treatment of a number of diseases. Continuing with our studies on the synthesis of new small and potentially bioactive molecules, a synthetic route, involving acid-catalysed intramolecular Friedel-Crafts cyclization, to the readily separable diastereoisomers of 11-ethyl-6,11-dihydro-5H-dibenzo[b,e]azepine-6-carboxamide, a potentially useful precursor in the synthesis of analogues of some anti-allergenic, antidepressant and antihistaminic drugs currently in use, has been developed starting from 2-allylphenylamine and methyl 2-bromo-2-phenylacetate and proceeding via racemic methyl 2-[(2-allylphenyl)amino]-2-phenylacetate (A) and racemic 2-[(2-allylphenyl)amino]-2-phenylacetamide (B), to give the two diastereoisomers (I) and (II), C17H18N2O. Isomers (I) and (II), and their precursors (A) and (B), have all been fully characterized spectroscopically. Structure analysis of the minor isomer (I) shows that it has the (6RS,11RS) configuration, and that the azepine ring adopts a conformation intermediate between the boat and twist-boat forms, with the carboxamide and ethyl substituents both occupying quasi-equatorial sites. The molecules of (I) are linked by a combination of N-H...O, N-H...π(arene) and C-H...π(arene) hydrogen bonds to form complex sheets. Comparisons are made with the structures of some related compounds.