Synthesis and detailed conformational analysis of new naphthoxazino [2,3-a]benz [c]azepine and naphthoxazino [2,3-a]thieno [3,2-c]pyridine derivatives

New naphth[1,3]oxazino-benzazepines and -thienopyridines were synthesized using a modified Mannich-type synthetic pathway by the reaction of 4,5-dihydro-3H-benz[c]azepine or 6,7-dihydrothieno [3,2-clpyridine and different substituted aminonaphthols. Reaction conditions were optimized using microwave irradiation, with relatively short reaction times and a temperature of 80 degrees C. The formation of undesired naphthoxazine by-products made the separation/purification of the products challenging, therefore the reactions were repeated and systematically studied, starting from secondary and tertiary aminonaphthol derivatives, when the isolation of an ortho-quinonemethide structure occurred unexpectedly. Scope and limitations of its formation were also investigated. Conformational studies including ring inversion of a selection of the novel polyheterocycles were performed using NMR methods and supplementary DFT modelling. (C) 2017 Elsevier Ltd. All rights reserved.