Experimental Quantification of Halogen⋅⋅⋅Arene van der Waals Contacts

Abstract

Crystallographic and computational studies suggest the occurrence of favourable interactions between polarizable arenes and halogen atoms. However, the systematic experimental quantification of halogen⋅⋅⋅arene interactions in solution has been hindered by the large variance in the steric demands of the halogens. Here we have synthesized molecular balances to quantify halogen⋅⋅⋅arene contacts in 17 solvents and solvent mixtures using 1H NMR spectroscopy. Calculations indicate that favourable halogen⋅⋅⋅arene interactions arise from London dispersion in the gas phase. In contrast, comparison of our experimental measurements with partitioned SAPT0 energies indicate that dispersion is sufficiently attenuated by the solvent that the halogen⋅⋅⋅arene interaction trend was instead aligned with increasing exchange repulsion as the halogen increased in size (ΔGX⋅⋅⋅Ph=0 to +1.5 kJ mol−1). Halogen⋅⋅⋅arene contacts were slightly less disfavoured in solvents with higher solvophobicities and lower polarizabilities, but strikingly, were always less favoured than CH3⋅⋅⋅arene contacts (ΔGMe⋅⋅⋅Ph=0 to −1.4 kJ mol−1).

Context-Dependent Significance of London Dispersion

“…Halogen–arene and CH 3 –arene interactions in side-on geometries have also been investigated in seminal works by Oki and Schneider . Similar to the findings determined using the Wilcox balance shown in Figure A, Oki’s early studies using triptycene molecular balances (Figure B found Cl–arene and Br–arene interactions to be repulsive but, in contrast, less repulsive than CH 3 –arene interactions. Meanwhile, Schneider used porphyrin complexes with a series of smaller aromatic guests and found that the complexes became more stable as the polarizability of the substituents increased (i.e., increased in the order F < Me < Cl < Br < I).…”

“…Chem., Int. Ed.202362e202309682 . This work underlines the importance of sterics and electrostatic forces as competitors to LD forces.…”

“…However, the use of intramolecular systems brings other context-dependent caveats, such as steric strain. , Meanwhile, the geometries of specific functional group interactions in intramolecular contexts may differ from those of intermolecular complexes, which may be closer to the isolated equilibrium separation and geometry. In addition, electron delocalization via induction/polarization makes larger contributions to molecular interactions at short separations, which may further cloud the view of LD. ,,− More generally, electrostatic interactions frequently dominate over LD since their energies scale with a 1/ r 2 distance dependence, while dispersion has ∼1/ r 6 dependence. The contrasting findings of the experimental studies of alkyl–alkyl, alkyl–arene, halogen–arene, and aromatic stacking interactions presented in this Account provide very good examples where the role of LD has proven to be challenging to isolate, due in part to contextual dependency.…”

“…Wilcox’s balance was originally designed to examine edge-to-face aromatic interactions, but the scaffold has also permitted the study of other interactions. For example, Cockroft and co-workers used the modified balance design shown in Figure A to study halogen–arene interactions . This molecular balance was chosen to place halogen atoms in contact with aromatic rings and to compare such halogen–arene interactions with CH 3 –arene interactions.…”

“…For example, Cockroft and coworkers used the modified balance design shown in Figure 4A to study halogen−arene interactions. 2 This molecular balance was chosen to place halogen atoms in contact with aromatic rings and to compare such halogen−arene interactions with CH 3 −arene interactions. The choice of the Wilcox balance design stemmed from its intrinsic flexibility, which enabled the varied steric demands of the halogens to be accommodated.…”