Halogen-Bond Preferences in Co-crystal Synthesis

Abstract

To examine the possibility of establishing a hierarchy of the relative importance of different halogen bonds in the solid state, twelve co-crystallization experiments were performed between three different ditopic halogen-bond acceptors, 1,1′-bis(pyridin-4-ylmethyl)-2,2′-biimidazole (A1), 1,1′-bis(pyridin-3-ylmethyl)-2,2′-biimidazole (A2) and 1,1′-bis(pyridin-2-ylmethyl)-2,2′-biimidazole (A3) and four perfluoroiodoalkanes. A ranking of potentially competing acceptor-sites was based on calculated molecular electrostatic surface potentials using DFT; the pyridine nitrogen atom found to be the best acceptor in all three acceptor molecules. An analysis of the outcome of all twelve attempted reactions using IR spectroscopy showed that eight of the twelve attempts resulted in a co-crystal, the equivalent of a 67 % total supramolecular yield. Six crystal structures were obtained and all show that halogen bonding involves the best acceptor site (pyridine) as ranked by the electrostatic potentials. The supramolecular yield increased with increasing charge on the acceptor site thereby underlying the importance of electrostatics in practical supramolecular synthesis of co-crystals driven by halogen bonding. A ranking of potentially competing halogen bond acceptor-sites was achieved using calculated molecular electrostatic surface potentials and successfully implemented in the practical synthesis of co-crystals with the desired connectivity.