Strength from Weakness: Conformational Divergence between Solid and Solution States of Substituted Cyclitols Facilitated by CH···O Hydrogen Bonding

We
have investigated the conformational preferences of a series
of cyclitol derivatives, namely mono- and diesters of 1,2:5,6-di-O-isopropylidene-myo-inositol and 1,2:5,6-di-O-cyclohexylidene-myo-inositol, in both
solid and solution states. The solid-state conformations were determined
by single-crystal X-ray analysis. The solution-state conformations
were determined by using NMR. The experimental 3JHH values were applied in the Haasnoot–Altona
equation to calculate the dihedral angle (ϕ) between the respective
vicinal protons. By fixing the dihedral angle between different sets
of vicinal protons, the molecules were energy-minimized by MM2 method
to visualize their conformation in solution. As the solvent polarities
can influence the conformational preference, we have determined the
conformations of these molecules in various solvents of different
polarities such as benzene-d6, chloroform-d, acetonitrile-d3, acetone-d6, methanol-d4,
and DMSO-d6. All of the compounds adopted
boat conformations in solution irrespective of the solvents, acyl
groups, or alkylidene protecting groups. This conformation places
H6 and O3 of the cyclitol ring in proximity, such that an intramolecular
CH···O hydrogen bond between them stabilizes this otherwise
unstable conformation. However, in the solid state, several intermolecular
CH···O hydrogen bonds force these molecules to adopt
the chair conformation. This study uncovers the role of weak noncovalent
interactions in influencing the molecular conformations differentially
in different states.