Substituent influences on the stability of the ring and chain tautomers in1,3-O,N-heterocyclic systems: Characterization by C-13 NMR chemical shifts, PM3 charge densities, and isodesmic reactions

Substituent effects on the stabilities of the ring and chain forms in a tau tomeric equilibrium of five series of 2-phenyloxazolidines or -perhydro-1,3 -oxazines possessing nine different substitutions at the phenyl moiety have been studied with the aid of C-13 NMR spectroscopy and PM3 charge density and energy calculations. Reaction energies of the isodesmic reactions, obta ined from the calculated energies of formation, show that electron-donating substituents stabilize both the chain and ring tautomers but the effect is stronger on the stability of the chain form than on that of the ring form. The C-13 chemical shift changes induced by the phenyl substituents (SCS) w ere analyzed by several different single and dual substituent parameter app roaches. The best correlations were obtained by equation SCS = rho (F)sigma (F) + rho (R)sigma (R). In all cases the rho (F) values and in most cases also the rho (R) values were negative at both the C=N and C-2 carbons, indi cating a reverse behavior of the electron density. This concept could be ve rified by the charge density calculations. The C-13 chemical shifts of the C=N and C-2 carbons show a normal dependence on the charge density (q(tot)) , but the charge density shows a reverse dependence on substitution. Correl ation analysis of the C-13 chemical shifts, solvent effect (CDCl3 vs DMSO-d (6)) on the NMR behavior as well as the effect of substituents on the elect ron densities and on the stabilities of the ring and chain tautomers show t hat the substituent dependence of the relative stability of the ring and ch ain tautomers in equilibrium is governed by several different electronic ef fects. At least intramolecular hydrogen bonding between the imine nitrogen and the hydroxyl group as well as polarization of the C=N bond seem to cont ribute in the chain form. Stereoelectronic and electrostatic effects are po ssible to explain the increase in stability of the ring form by electron-do nating substituents.