SATURATED HETEROCYCLES .200. SYNTHESIS AND CONFORMATIONAL-ANALYSIS OF CONDENSED-SKELETON SATURATED 1,3-HETEROCYCLES

Transformations of versatile trifunctional synthons, 6,7-dialkoxy-1-[bis-(hydroxymethyl)methyl]-1,2,3,4-tetrahydroisoquinolines, furnished tetrahydroisoquinoline-fused azetidines and tetrahydroisoquinoline-fused 1,3-heterocycles (e.g. 1,3-oxazines, 1,3-oxazin-2-ones, 1,3-oxazin-4-ones, 1,3-thiazines, pyrimidinones and related 2-phenylimino-1,3-heterocycles). Conformational analysis of the above heterocycles by NMR and X-ray methods were performed. The ring-chain tautomerism of saturated fused-skeleton 1,3-oxazines, described by the equation log K(X) = (0.76 +/- 0.04) sigma+ + log K(X=H), is discussed. Ring closure reactions of 1-hydrazido- and 1-hydrazidomethyltetrahydroisoquinolines with aromatic aldehydes and ketones were performed and the relative configurations of the products were determined by means of DNOE measurements. The synthesis of a new family of the pyracridone group, 2-azapyracridones, is reported and an intermolecular hydrogen-transfer reaction is discussed. The synthesis of 1,3-heterocycles, e.g. 3-substituted and 2,3-disubstituted pyrimidin-4(3H)-ones, was achieved in retro Diels-Alder reactions. The unambigous synthetic pathway permitted the correction of erroneous structures in the earlier literature. A similar retro Diels-Alder process was developed for the synthesis of uracils and thiouracils. Bicyclic hetero derivatives, e.g. pyrimido[2,1-b]thiazine, were also prepared via retro Diels-Alder splitting.