Synthesis and conformational analysis of naphth[1,2-e][1,3]oxazino[4,3-a][1,3]isoquinoline and naphth[2,1-e][1,3]oxazino[4,3-a]isoquinoline derivatives

Through the cyclization of 1-(β-hydroxynaphthyl)-1,2,3,4-tetrahydroisoquinoline and 1-(α-hydroxynaphthyl)-1,2,3,4-tetrahydroisoquinoline with formaldehyde, phosgene, p-nitrobenzaldehyde or p-chlorophenyl isothiocyanate, 8-substituted 10,11-dihydro-8H,15bH-naphth[1,2-e][1,3]oxazino[4,3-a]isoquinolines (3 and 4) and 10,11-dihydro-8H,15bH-naphth[2,1-e][1,3]oxazino[4,3-a]isoquinolines (15 and 16) were prepared. Conformational analysis of both the piperidine and the 1,3-oxazine moieties of these heterocycles by NMR spectroscopy and an accompanying theoretical study revealed that these two conformationally flexible six-membered ring moieties prefer twisted chair conformers.