Morpholine Nitrogen and Oxygen Atoms as Halogen Bond Acceptors in Different Environments: Cocrystals of Amino-, Imino- or Amide-Linked Bis(morpholine) Derivatives with Perfluorinated Iodohydrocarbons

The propensity of the morpholine oxygen as a halogen bond acceptor in the presence of potentially competing halogen bond acceptor groups was studied by preparing a series of three bis(morpholine) derivatives in which the morpholine rings are interconnected via diamine, diimine, and diamide linkers and cocrystallizing them with an excess of 1,2-diiodotetrafluorobenzene, 1,3-diiodotetrafluorobenzene, 1,4-diiodotetrafluorobenzene, 1,3,5-triiodotrfluorobenzene, and 1,4-diiodooctafluorobutane as halogen bond donors. This yielded a total of 11 cocrystals. Both the diamide and the diimine yielded four cocrystals (with all the aromatic donors), with morpholine oxygen atoms participating in halogen bonding in only two diamide cocrystals and in all four diimines, reflecting the more negative electrostatic potential of the amide nitrogen in comparison to the imide. The diamide acceptor, however, formed only three cocrystals, all three featuring halogen bonds with morpholine oxygen as well as amide oxygen atoms, despite amide oxygen being the most negative site. This can generally be attributed to competing interactions, such as hydrogen bonding of a water molecule to the amide oxygen as well as general packing effects.