Ring Size Dependent Lactam-Lactim Tautomeric Equilibrium in Imidazolin-2-Chalcogenones and Pyrimidin-2-Chalcogenones: A Role of Aromaticity

The dynamic nature of tautomerism has profound implications for structure, function, and reactivity of biologically important molecules. This study investigates the effect of ring size and aromaticity on tautomeric stability of Imidazolin-2-chalcogenones and Pyrimidin-2-chalcogenones using quantum mechanical methods. Analysis of the tautomerisation energies reveals that five-membered unsaturated analogues favor lactams, whereas six-membered ones prefer lactims, a reversal in tautomeric preference not observed in saturated lactams or acyclic amides. Charge and population analyses reveal that the nature of CN(CN)/CX(CX) bonds contribute to tautomeric stability. EDA-NOCV analysis indicates that the primary difference in CN(CN) bonds between the five- and six-membered analogues lies in the low $∆$E_π in six-membered lactams, supported by low NICSzz (1) values. The tautomerisation of six-membered lactams to lactims results in gain in aromatic stabilization, which plays a crucial role in reversal of tautomeric stability in Pyrimidin-2-chalcogenones, overcoming the intrinsic stability of CN(CN) bonds in Imidazolin-2-chalcogenones.