Probing Proximal Intramolecular Hydrogen Bonding Interactions on a Norbornane Scaffold

High Resolution Image Download MS PowerPoint Slide 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, OCH 3, SH, SCH 3, NHCH 3, N(CH 3 ) 2, PH 2, PHCH 3, and P(CH 3 ) 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.