How Repulsive Are Lone Pairs? A Rotational Barrier-Based Experimental Study

Lone pair-lone pair (lp-lp) repulsion is commonly cited as a destabilizing interaction in organic and main group chemistry, yet its quantitative impact remains poorly defined. In this study, we experimentally evaluated the magnitude of lp-lp repulsion by comparing rotational barriers in two families of molecular rotors: one designed to position lone pairs in close through-space proximity to a carbonyl oxygen (rotor 1), and a matched steric control lacking such interactions (rotor 2). The study includes 23 rotational barriers per rotor, combining values from the literature with additional measurements spanning substituents with diverse steric and electronic profiles. Contrary to conventional assumptions, rotors capable of through-space lp-lp interactions exhibited no statistically significant increase in barrier height compared to steric-only controls. The average difference between lone pair and non-lone pair series was less than 0.5 kcal/mol and within the 95% confidence interval. These findings support computational studies suggesting that lp-lp interactions do not exert additional repulsive forces beyond traditional electrostatics and steric effects.