title: Improper hydrogen bonded cyclohexane C-Hax···Yax contacts: theoretical predictions and experimental evidence from 1H NMR spectroscopy of suitable axial cyclohexane models.
abstract: C-H(ax)···Y(ax) contacts are a textbook prototype of steric hindrance in organic chemistry. The nature of these contacts is investigated in this work. MP2/6-31+G(d,p) calculations predicted the presence of improper hydrogen bonded C-H(ax)···Y(ax) contacts of different strength in substituted cyclohexane rings. To support the theoretical predictions with experimental evidence, several synthetic 2-substituted adamantane analogues (1-24) with suitable improper H-bonded C-H(ax)···Y(ax) contacts of different strength were used as models of a substituted cyclohexane ring. The (1)H NMR signal separation, Δδ(γ-CH(2)), within the cyclohexane ring γ-CH(2)s is raised when the MP2/6-31+G(d,p) calculated parameters, reflecting the strength of the H-bonded C-H(ax)···Y(ax) contact, are increased. In molecules with enhanced improper H-bonded contacts C-H(ax)···Y(ax), like those having sterically crowded contacts (Y(ax) = t-Bu) or contacts including considerable electrostatic attractions (Y(ax) = O-C or O═C) the calculated DFT steric energies of the γ-axial hydrogens are considerably reduced reflecting their electron cloud compression. The results suggest that the proton H(ax) electron cloud compression, caused by the C-H(ax)···Y(ax) contacts, and the resulting increase in Δδ(γ-CH(2)) value can be effected not just from van der Waals spheres compression, but more generally from electrostatic attraction forces and van der Waals repulsion, both of which are improper H-bonding components.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Athens, Greece. ankol@pharm.uoa.gr
authors.forename: Antonios
authors.initials: A
authors.lastname: Kolocouris
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Zervos
authors.forename: Frank
authors.initials: F
authors.lastname: De Proft
authors.forename: Andreas
authors.initials: A
authors.lastname: Koch
mesh_terms: D003510:Cyclohexanes / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D011522:Protons; D011789:Quantum Theory
chemical_list: D003510:Cyclohexanes; D011522:Protons; C506365:Cyclohexane