Mapping out the synthetic landscape for re-crystallization, co-crystallization and salt formation

Abstract

In order to examine the balance between co-crystallization and proton transfer in a set of acid–base reactions, molecular electrostatic potential (MEP) surface calculations for substituted pyridines were correlated with their ability to communicate with a series of carboxylic acids via intermolecular interactions in the solid state. The calculated (AM1) charges on the hydrogen-bond acceptor in these N-heterocyclic compounds provide overall excellent guidelines for predicting when a salt or a co-crystal will form. The charges can also be related to the supramolecular yield of the reactions between seven derivatives of 2-aminopyridine and fifteen aromatic/aliphatic carboxylic acids. The outcome of all reactions was screened using IR spectroscopy, and twelve crystal structures were used to verify the spectroscopic assignments and to examine the exact nature of the primary intermolecular interactions.