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

J Org Chem. 2018 Apr 6;83(7):4270-4274. doi: 10.1021/acs.joc.8b00309. Epub 2018 Mar 23.

Abstract

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 p Ka'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 p Ka's, led to a general model for the liquid-liquid extraction behavior of ionizable molecules. This model predicts the observed, useful extraction behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hydrogen-Ion Concentration
  • Liquid-Liquid Extraction*
  • Molecular Structure
  • Pharmaceutical Preparations / chemistry
  • Pharmaceutical Preparations / isolation & purification*

Substances

  • Pharmaceutical Preparations