Multitechnique Investigation of Conformational Features of Small Molecules: the Case of Methyl Phenyl Sulfoxide

The conformational distribution of methyl phenyl sulfoxide (a molecule representative of a very importantclass of reagents widely used in asymmetric synthesis) has been studied in two different phases of matter(gas phase and solution) by a comprehensive approach including theoretical calculations, microwavespectroscopy, liquid crystal NMR experiments, and atomistic molecular dynamics computer simulations. Theaim was to investigate the combined action of intra- and intermolecular interactions in determining themolecule’s conformational equilibrium, upon which important physicochemical properties (inter alia, thechemoselectivity) significantly depend. Basically, the results converge in describing the tendency of the moleculeto favor stable conformations governed by intramolecular interactions (in particular, the expected optimizationbetween steric repulsion and conjugation of ð systems). However, significant solvent effects (whose “absolute”magnitude is actually difficult to assess, due to a certain “method-dependence” of the results) have been alsodetected.