AbstractIn molecular design, large alkyl groups are used to introduce bulk and steric crowding of the catalytic center to improve catalytic efficiency and selectivity. The bulky groups are highly polarizable, increasing their ability to participate in stabilizing noncovalent interactions. The rationalization of noncovalent interaction trends is of both fundamental and practical interest as it provides new design concepts for catalysis and synthesis. Highly congested molecules always present challenges to chemists. Crowded benzene systems are an important class of compounds with well-established thermodynamic properties. The latter were used in this work to develop tools to quantify the degree of stabilization or destabilization in benzene systems crowded with bulky isopropyl and tert-butyl substituents. The basic idea was to quantify the delicate balance between repulsive and attractive interactions inherent in crowded benzene systems. The ensemble of experimental thermodynamic data and DFT-D3 calculations enabled the development of quantitative scales of the dispersion contributions and their understanding at the molecular level.