The results of heats of mixing experiments on a series of ortho-substituted phenols with an amide or an eater are described. Substituents were chosen to span a wide range of electronic and steric character. Enthalpy of mixing results do not correlate solely with the acid strength of the phenol, or with a Hammett linear free-energy analysis. Rather, interactions are favored by the presence of groups with the ability to weaken the base strength of the proton donor while simultaneously increasing its acid strength. Such groups share a combination of electron-withdrawing ability and/or steric bulk that causes an effective decrease in the electron density about the phenolic oxygen. Trifluoromethyl and tert-butyl, and to a lesser extent halogen and hydroxy substituents ortho to the phenolic OH, give the highest exothermic enthalpies of mixing and are thus the most effective at promoting intermolecular interactions with weak bases such as amides and esters. These results should be useful in designing miscible or compatible polymer blends in which specific interactions such as hydrogen bonding are important.