Evaluation of Azobenzene Ethers Carrying a Perhalogenated Moiety as Halogen Bond Donors by Cocrystallization with Nitrogen-Containing Acceptors

In this work, we synthesized three novel 4-iodotetrafluorophenoxy-azobenzene ethers, which contain different substituents (X = -H, -Cl, -CN) on the opposite side of the molecule in relation to the perhalogenated moiety carrying the iodine atom. To explore the halogen bond donor potential of the prepared compounds, we performed cocrystal screening with a series of nitrogen-containing acceptors: 1,4-diazabicyclo[2.2.2]-octane, 4-dimethylaminopyridine, 2,2'-bipyridine, 4,4'-bipyridine, 4,4'-azopyridine, N,N'-bis-(pyridin-4-yl)-methylenehydrazine, 1,2-bis-(pyridin-4-yl)-ethane, and 1,2-bis-(pyridin-4-yl)-ethylene. These three azobenzenes were selected in order to investigate how bent molecules carrying a perhalogenated moiety would act as halogen bond donors, as well as how different substituents on a distant part of the molecule could affect the formation of cocrystals. Out of 24 combinations, only 8 experiments yielded cocrystals suitable for single-crystal X-ray diffraction with two out of three azobenzene derivatives (X = -Cl and -CN). Structural analysis revealed that in all obtained cocrystals, the robust interaction is the I···N halogen bond between the azobenzene iodine atom and the acceptor nitrogen atom. A majority of cocrystals feature two donor molecules per one acceptor molecule and display crystal packing based on discrete trimeric halogen-bonded complexes. Only in the case of the 4,4'-bipyridine cocrystal with a 1:1 stoichiometry is the crystal structure based on discrete halogen-bonded dimers. In order to investigate changes in the halogen bond donor ability of the azobenzene derivatives, we have calculated values of the molecular electrostatic potential (MEP) for the DFT-optimized molecular geometries. Calculations showed that the electrostatic potential on the iodine atom only slightly depends on the functional group located on the opposite side of the molecule, with relatively large MEP values (+135 kJ mol-1 e-1 on average).