Syntheses and conformational analyses of new naphth[1,2-e][1,3]oxazino[3,2-c]quinazolin-13-ones

The syntheses of naphth[1,2-e][1,3]oxazino[3,2-c]quinazolin-13-one derivatives (3a–f) were achieved by the solvent-free heating of benzyloxycarbonyl-protected intermediates (2a–f) with MeONa. For intermediates 2a–f, prepared by the reactions of substituted aminonaphthols with benzyl N-(2-formylphenyl)carbamate, not only the expected trans ring form B and chain form A1, but also the rearranged chain form A2 as a new tautomer were detected in DMSO at room temperature. The quantity of A2 in the tautomeric mixture was changed with time. Conformational analyses of the target heterocycles 3a–f by NMR spectroscopy and accompanying theoretical calculations at the DFT level of theory revealed that the oxazine ring preferred a twisted chair conformation and the quinazolone ring was planar. Besides the conformations, both the configurations at C-7a and C-15 and the preferred rotamers of the 1-naphthyl substituent at C-15 were assigned, which allowed evaluation of the aryl substituent-dependent steric hindrance in this part of the molecules. Configurational assignments were corroborated by quantifying the ring current effect of 15-aryl in terms of spatial NICS.