The favorable effect of 2-hydroxyphenyl groups for ketimine formation with benzophenone was demonstrated by combining computational and experimental studies. Although direct imine formation between benzophenone and primary amines is challenging, 2-hydroxybenzophenone or 2,2'-dihydroxybenzophenone was readily used for ketimine formation with various primary alkyl amines and anilines. Measured activation parameters and calculated energy profiles indicated that the 2-hydroxyphenyl group can lower both activation barriers and equilibrium energies by establishing intramolecular and intermolecular hydrogen-bonding interactions.