Disentangling the Conformational Space and Structural Preferences of Tetrahydrofurfuryl Alcohol Using Rotational Spectroscopy and Computational Chemistry.

The influence of the hydroxymethyl (CH 2 OH) group on the tetrahydrofuran (THF) ring structure was investigated by disentangling the gas phase conformational landscape of the sugar analogue tetrahydrofurfuryl alcohol (THFA). By combining rotational spectroscopy (6-20 GHz) and quantum chemical calculations, transitions corresponding to two stable conformers of THFA and their 13 C isotopologues were observed and assigned in the rotational spectrum. The positions of the C atoms were precisely determined to unambiguously distinguish between nearly isoenergetic pairs of conformers that differ in their ring configurations: envelope (E) versus twist (T). The rotational spectrum confirms that the E ring geometry is favoured when the CH 2 OH fragment lies gauche (-) to the THF backbone (OCCO ~-60°) whereas the T form is more stable for the gauche (+) alignment of the substituent (OCCO ~+60°). The observed spectral intensities suggest that conformational relaxation of the THF geometry (E↔T) to the more stable form readily occurs within the pairs of g- and g+ conformers which is consistent with the low barriers (1.5-1.7 kJ mol -1 ) for conversion determined via transition state calculations. Insights into the intramolecular hydrogen bonding and other weak interactions stabilizing the lowest energy structures of THFA were derived and rationalized using non-covalent interaction analyses.