Comment on "Topography of the free energy landscape of Claisen-Schmidt condensation: solvent and temperature effects on the rate-controlling step" by N. D. Coutinho, H. G. Machado, V. H. Carvalho-Silva and W. A. da Silva, , 2021, , 6738.

The referenced article in PCCP presents calculations of solvent kinetic isotope effects that indicate that the rate-limiting step in base-catalyzed chalcone formation in aqueous solution becomes the second enolization. This disputes our previous conclusion, based on experimental isotope effects in aqueous acetonitrile, that the rate-limiting step is the final loss of hydroxide and formation of the C-C double bond. That conclusion is here affirmed as general for any protic solvent, and it is further concluded that those calculations are flawed.