INTERNAL-ROTATION AROUND SINGLE BONDS AND CONFORMATIONAL PREFERENCES IN HETEROCYCLIC-ANALOGS OF BENZYL METHYL SULFOXIDE STUDIED WITH NMR TECHNIQUES

The conformational equilibrium related to the internal rotation proces ses occurring in sulphoxides of the type ArCH2SOCH3 (where Ar=2-thieny l, 2-furyl, 2-pyridinyl and (3-methyl)2-pyridinyl rings) were studied with H-1 and C-13 NMR spectroscopy. Proton chemical shifts and long-ra nge coupling constants (n)J(H, H) were obtained from the iterative ana lysis of the multiplets and were employed, together with C-13 chemical shifts, long-range (n)J(C, H) and relaxation parameters (NOE and non- selective T-1 values) to obtain stereochemical relationships between t he protons present in these molecules. Conformational predictions at a qualitative level were also derived from total molecular energies cal culated with the semi-empirical AM1/MNDO method as a function of inter nal coordinates. The different approaches converged to indicate that t he heterocyclic rings adopt an average orientation similar to the perp endicular orientation of the phenyl ring in benzyl methyl sulphoxide a nd, as regards rotation around the CH2-S bond, the prevalent conformer shows that the methyl group is symmetrically oriented with respect to the methylenic protons, The barriers for internal rotation are rather low and the equilibrium between conformers is dependent on the medium properties. Attempts to obtain conformational results were performed for the molecule of omeprazole, an antiulcer drug which contains the A rCH2SO-R moiety (Ar and R are substituted 2-pyridinyl and 2-benzimidaz olyl groups, respectively). With respect to the other compounds examin ed, the orientation of the Ar ring does not significantly differ and t he benzimidazole ring seems to prefer an orientation stereochemically equivalent to that of the methyl group.