Halogen Bonding in Sulphonamide Co-Crystals: X···π Preferred over X···O/N?

Sulphonamides have been one of the major pharmaceutical compound classes since their introduction in the 1930s. Co-crystallisation of sulphonamides with halogen bonding (XB) might lead to a new class of pharmaceutical-relevant co-crystals. We present the synthesis and structural analysis of seven new co-crystals of simple sulphonamides N-methylbenzenesulphonamide (NMBSA), N-phenylmethanesulphonamide (NPMSA), and N-phenylbenzenesulphonamide (BSA), as well as of an anti-diabetic agent Chlorpropamide (CPA), with the model XB-donors 1,4-diiodotetrafluorobenzene (14DITFB), 1,4-dibromotetrafluorobenzene (14DBTFB), and 1,2-diiodotetrafluorobenzene (12DITFB). In the reported co-crystals, X···O/N bonds do not represent the most common intermolecular interaction. Against our rational design expectations and the results of our statistical CSD analysis, the normally less often present X···π interaction dominates the crystal packing. Furthermore, the general interaction pattern in model sulphonamides and the CPA multicomponent crystals differ, mainly due to strong hydrogen bonds blocking possible interaction sites.