Quantum Chemical Prediction of Equilibrium Acidities of Ureas, Deltamides, Squaramides, and Croconamides

Robust quantum chemical methods are employed to predict the pK_a’s of several families of dual hydrogen-bonding organocatalysts/anion receptors, including deltamides and croconamides as well as their thio derivatives. The average accuracy of these predictions is ∼1 pK_a unit and allows for a comparison of the acidity between classes of receptors and for quantitative studies of substituent effects. These computational insights further explain the relationship between pK_a and chloride anion affinity of these receptors that will be important for designing future anion receptors and organocatalysts.