Interplay of Phenol and Isopropyl Isomerism in Propofol from Broadband Chirped-Pulse Microwave Spectroscopy

The conformational equilibrium of the general anaesthetic propofol (2,6-di-isopropylphenol) has been studied in a supersonic expansion using broadband chirped-pulse microwave spectroscopy. Three conformers originated by the combined internal rotation of the hydroxyl and the two isopropyl groups have been detected in the jet-cooled rotational spectrum. The most stable conformer exhibits tunnelling splittings associated to the internal rotation of the hydroxyl group, from which we determined the torsional potential and barrier heights (905 and 940 cm-1). A carbon backbone structure derived from spectral assignments of all twelve 13C monosubtituted isotopologues of this conformer in natural abundance confirmed a plane-symmetric gauche orientation of the two isopropyl groups (Gg). In the other two detected conformers (EG and GE), one of the isopropyl groups is eclipsed respect to the ring plane while the other is gauche, differing in the orientation of the hydroxyl group. Supporting ab initio calculations provided information on the potential energy surface and molecular properties of the title compound.