Identification of Lactam–Lactim Tautomers of Aromatic Heterocycles in Aqueous Solution Using 2D IR Spectroscopy

The tautomerism of aromatic heterocycles is of great interest because it directly affects their chemical properties and biological function. The tautomerism of 2-pyridone, 6-chloro-2-pyridone, and 4-pyrimidinone has been examined in D2O using FTIR, two-dimensional IR (2D IR) spectroscopy, and density functional theory (DFT) calculations. Using the 2D IR cross-peak patterns, the lactim tautomer of 6-chloro-2-pyridone was separated from the lactam tautomer, and its population was observed to increase with temperature. The equilibrium constant of [lactam]/[lactim] was determined to be 2.1 at room temperature for 6-chloro-2-pyridone. Similarly, the N1H and N3H lactam tautomers of 4-pyrimidinone were identified with 2D IR. To assign the vibrational modes of different tautomers, DFT calculations of these chemical species were performed with explicit water molecules, and the hydration effects on the vibrational frequencies and intensities were established.