A General Liquid-Liquid Partitioning Equation and Its Consequences: Learning from the pH Dependent Extraction of a Pharmaceutical Intermediate

We observed that the product of a Buchwald-Hartwig coupling reaction extracted from the organic phase easily, relative to the starting aryl bromide as the pH was lowered. This was surprising given the similarity of their pK(a)'s. The product's extraction curve was also significantly steeper than expected. A consideration of the relevant equilibria, including all three of the product's pK(a)'s, led to a general model for the liquid-liquid extraction behavior of ionizable molecules. This model predicts the observed, useful extraction behavior.