# Probing Proximal Intramolecular Hydrogen Bonding Interactions on a Norbornane Scaffold

## TL;DR

This study explores how different chemical groups interact with an OH group in a rigid molecule through hydrogen bonding.

## Contribution

The study demonstrates that P and S acceptor groups can form significant hydrogen bonds with an OH donor in a rigid scaffold.

## Key findings

- Conformations with OH···A hydrogen bonds had lower electronic energies than those without.
- OH stretching frequencies decreased significantly in the presence of hydrogen bonds.
- QTAIM analysis confirmed hydrogen bond formation with typical electron densities.

## Abstract

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.