Quantitative Determination of Intermolecular Interactions with Fluorinated Aromatic Rings

The chemical double mutant cycle approach has been used to investigate substituent effects on intermolecular interactions between aromatic rings and pentafluorophenyl π‐systems. The complexes have been characterised using 1H and 19F NMR titrations, X‐ray crystal structures of model compounds and molecular mechanics calculations. In the molecular zipper system used for these experiments, H‐bonds and the geometries of the interacting surfaces favour the approach of the edge of the aromatic ring with the face of the pentafluorophenyl π‐system. The interactions are generally repulsive and this repulsion increases with more electron‐withdrawing substituents up to a limit of +2.2 kJ mol−1, when the complex distorts to minimise the unfavourable interaction. Strongly electron‐donating groups cause a change in the geometry of the aromatic interaction and attractive stacking interactions are found (−1.6 kJ mol−1 for NMe2). These results are generally consistent with an electrostatic model: the polarisation of the pentafluorophenyl ring leads to a partial positive charge located at the centre and this leads to repulsive interactions with the positive charges on the protons on the edge of the aromatic ring; when the aromatic ring has a high π‐electron density there is a large electrostatic driving force in favour of the stacked geometry which places this π‐electron density over the centre of the positive charge on the pentafluorophenyl group. Perfluorination of an aromatic ring causes a dramatic change in the way it interacts with other functional groups. The electron‐withdrawing fluorines lead to a net positive charge on the face of the π‐system and so edge‐to‐face aromatic interactions (see figure) that involve pentafluorophenyl are found to be repulsive.