Crystal Engineering with Iodoethynylnitrobenzenes: A Group of Highly Effective Halogen-Bond Donors

The benefits of employing a “double activation” strategy for promoting effective practical co-crystal synthesis through halogen bonding was explored in a systematic supramolecular synthetic study of iodoethynylnitrobenzenes. The positive electrostatic potential on the iodine atom was enhanced through a combination of an sp-hybridized carbon atom and one or more electron-withdrawing nitro groups. Three model compounds, 1-(iodoethynyl)-4-nitrobenzene (4N-I), 1-(iodoethynyl)-3-nitrobenzene (3N-I), and 1-(iodoethynyl)-3,5-dinitrobenzene (3,5DN-I) were synthesized and characterized, and calculated molecular electrostatic surface potential values on the halogen-bond donor site were about 20–40 kJ/mol higher than those observed for previously well-established halogen-bond donors. The ability of these molecules to drive co-crystal formation was evaluated through a total of 45 co-crystallization experiments with 15 different acceptor molecules. IR spectroscopic data for the resulting products showed that each reaction resulted in the formation of a co-crystal driven by either C–I···N or C–I···O halogen bonds. The bromo-compound analogues displayed a 60% success rate whereas the chloro-analogues did not yield any co-crystals, emphasizing the importance of the magnitude of the electrostatic aspects of halogen bonding for practical supramolecular synthesis. Ten new crystal structures are presented and the outcome (in terms of stoichiometry and connectivity) is largely predictable. A comparison of I···acceptor distances found in these structures with relevant data from the CSD shows that iodoethynylnitrobenzenes consistently give rise to a larger reduction of combined van der Waals radii (for C–I···acceptor) than do other well-known halogen bond donor moieties.