Internal rotation around single bonds and conformational preferences in heterocyclic analogues of benzyl methyl sulphoxide studied with NMR techniques

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Abstract

The conformational equilibrium related to the internal rotation processes occurring in sulphoxides of the type ArCH2SOCH3 (where Ar=2-thienyl, 2-furyl, 2-pyridinyl and (3-methyl)2-pyridinyl rings) were studied with 1H and 13C NMR spectroscopy. Proton chemical shifts and long-range coupling constants nJ(H,H) were obtained from the iterative analysis of the multiplets and were employed, together with 13C chemical shifts, long-range nJ(C,H) and relaxation parameters (NOE and non-selective T1 values) to obtain stereochemical relationships between the protons present in these molecules. Conformational predictions at a qualitative level were also derived from total molecular energies calculated with the semi-empirical AM1/MNDO method as a function of internal coordinates. The different approaches converged to indicate that the heterocyclic rings adopt an average orientation similar to the perpendicular orientation of the phenyl ring in benzyl methyl sulphoxide and, 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 ArCH2SOR moiety (Ar and R are substituted 2-pyridinyl and 2-benzimidazolyl groups, respectively). With respect to the other compounds examined, the orientation of the Ar ring does not significantly differ and the benzimidazole ring seems to prefer an orientation stereochemically equivalent to that of the methyl group.

References (48)

  • O.H. Manscher, J.P. Jacobsen and K. Schaumburg, mimer, QCPE Program no. 394, Chemistry Department, Indiana...
  • M. Nishio

    Chem. Commun.

    (1969)
  • M. Nishio

    Chem. Pharm. Bull.

    (1969)
  • F. Taddei

    J. Chem. Soc., Perkin Trans. 2

    (1970)
  • L. Antolini et al.

    J. Chem. Soc., Perkin Trans. 2

    (1991)
  • D. Neuhaus et al.

    The Nuclear Overhauser Effect in Structural and Conformational Analysis

    (1989)
  • J.H. Noggle et al.

    The Nuclear Overhauser Effect

    (1971)
  • K. Griesbaum et al.

    J. Am. Chem. Soc.

    (1963)
    F. Taddei

    Boll. Sci. Fac. Chim. Ind. Bologna

    (1965)
    K. Mislow et al.

    J. Am. Chem. Soc.

    (1965)
    M. Nishio et al.

    Chem. Pharm. Bull.

    (1965)
    M. Nishio

    Chem. Pharm. Bull.

    (1967)
    E. Bullock et al.

    Chem. Commun.

    (1967)
    E. Strom et al.

    Chem. Commun.

    (1969)
  • S. Wolfe et al.

    Chem. Commun.

    (1966)
  • R.R. Fraser et al.

    Can J. Chem.

    (1969)
  • A. Rauk et al.

    J. Am. Chem. Soc.

    (1965)
  • J.E. Baldwin et al.

    Chem. Commun.

    (1969)
  • M. Cinquini et al.

    Chem. Commun.

    (1969)
  • K. Nishihata et al.

    J. Chem. Soc., Perkin Trans. 2

    (1972)
  • G.H. Penner et al.

    Can. J. Chem.

    (1987)
  • C. Arvanitakis et al.
  • Ya.L. Gol'dfarb et al.

    Khim. Geterotsikl. Soedin.

    (1971)
  • N. Furukawa et al.

    J. Chem. Soc., Perkin Trans. 1

    (1984)
  • R. Benassi et al.

    J. Mol. Struct.

    (1991)
  • G.E. Jeoromin et al.

    Chem. Ber.

    (1987)
  • O.W. Sorensen et al.

    J. Magn. Reson.

    (1983)
  • A. Bax

    J. Magn. Reson.

    (1984)
  • A. Bax et al.

    J. Magn. Reson.

    (1983)
  • A. Bax et al.

    J. Am. Chem. Soc.

    (1986)
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