A systematic computational study was conducted on 12 unique 2,6-disubstituted norbornane derivatives to assess the ability of various acceptor groups (A = F, Cl, Br, OH, OCH3, SH, SCH3, NHCH3, N(CH3)2, PH2, PHCH3, and P(CH3)2) to engage in intramolecular hydrogen bonding with a proximal OH donor. 32 unique minima have been characterized with M06-2X and df-MP2 geometry optimizations as well as PNO-LCCSD(T)-F12 single point energy computations. Conformations with the OH donor oriented toward the acceptor to form an OH···A contact (+HB) consistently had lower electronic energies (by approximately 2 to 8 kcal mol-1) than their counterparts with the OH directed away from the acceptor (-HB). Additional M06-2X computations revealed that these intramolecular contacts also induce significant shifts to lower energy in the OH stretching frequencies (usually by -50 to -100 cm-1, but more than -200 cm-1 for OH···N interactions) and notable deshielding of the hydrogen atom (with shifts in the isotropic nuclear magnetic resonance (NMR) chemical shielding constants ranging from -1 to -5 ppm). Quantum theory of atoms in molecules (QTAIM) analysis confirms the presence of bond critical points with electron densities (ca. 0.02 to 0.03 e bohr-3) that are within the typical range of values for hydrogen bonds. These findings demonstrate the capacity of not only N and O, but also P and S, acceptor groups, to establish appreciable attractive intramolecular interactions with a proximal OH group on a rather rigid molecular scaffold.
Rock et al. (Wed,) studied this question.