Involvement of O Atoms of Carboxyl Group in Hydrogen and Halogen Bonds

Both the carbonyl and hydroxyl O atoms of the carboxyl group are capable of acting as electron donor in the context of noncovalent bonds. These two O atoms of acetic acid are each allowed to form an H‐bond with HCl and a halogen bond with IF, and the interactions are monitored by quantum chemical calculations. The electrostatic potential on the carbonyl O is more negative than that on OH, and the HOMO is weighted toward the carbonyl. The interaction energies are consequently considerably stronger for the CO. A series of ligands are added to the carboxyl group that extract electron density from the carbonyl O and add density to OH. These arrangements enhance the interaction energies involving OH, some by nearly 50%. These same ligands have a lesser effect on bonds involving CO, many of which are actually strengthened, despite the reduced magnitude of its negative potential. Consequently, the CO remains the favored site for an electrophile, regardless of the ligands that might be present.