A Research Paper Published in Crystal Growth & Design

The work was focused on studying the propensity for halogen bonding of the sp3 hybridized cyclic sulfur atom in tetrahydro-4H-thiopyran-4-one and its imine derivatives. Two imines were prepared by a condensation reaction between tetrahydro-4H-thiopyran-4one and either N-aminomorpholine or N-(2-aminoethyl)morpholine, with the idea of obtaining a structurally more flexible bigger building block via the presence of an ethyl spacer. Both the ketone and the obtained imines were cocrystallized with a series of perfluorinated halogen bond donors: 1,4-, 1,3- and 1,2-diiodotetrafluorobenzene, 1,3,5-triiodo-2,4,6-trifluorobenzene, iodopentafluorobenzene and 1,4-dibromotetrafluorobenzene. Seven new cocrystals were prepared mechanochemically and by crystallization from reactant solutions, and were afterwards characterized by powder and single crystal X-ray diffraction and by differential scanning calorimetry. Structural analysis has confirmed the acceptor potential of the studied sulfur atom, albeit concluding that according to geometric parameters and statistics (participates in halogen bonding in 5 out of 7 cocrystals) it is a weaker halogen bond acceptor than the morpholine oxygen and imine nitrogen atoms present in the same compounds. Although a weaker acceptor than other types of sulfur atoms according to geometric parameters, it has been hypothesized that it is also more selective, because this sulfur atom doesn't participate in hydrogen bonding in either reactant crystals or cocrystals.

This research was performed as part of the project New building blocks for the supramolecular design of complex multi-component molecular crystals based on halogen bonds (HaloBond IP-2019-04-1868), financed by the Croatian Science Foundation