Isotope Effects On Acidity Resolved

The answer to a 50-year-old question about the origin of secondary isotope effects on acidity could lead to new insights on molecular structure and reactivity. Secondary deuterium effects on acidity stem from substituting deuterium for hydrogen at intact (nonacidic) bonds in acid molecules. The reduced acidity that results is known to be caused by deuteration-induced reductions in bond vibration frequencies and ground-state energies. Researchers have wondered whether inductive effects from reduced dipole moments in carbon-deuterium bonds, exhibited as entropy changes, also contribute to the effects, but the entropy changes couldn’t be measured. Charles L. Perrin and Agnes Flach of the University of California, San Diego, have now used an NMR titration method to show that no entropy change occurs upon acid deuteration, rejecting the possibility that inductive effects contribute to reduced acidity (Angew. Chem. Int. Ed., DOI: 10.1002/anie.201102125). The experiments “are beautifully conceived and executed and appear to be definitive,” comments Andrew Streitwieser of UC Berkeley. The study “is sure to make its way into advanced organic chemistry textbooks,” adds Daniel O’Leary of Pomona College, in Claremont, Calif.