Single‐crystal X‐ray analysis of the diketo form of asymmetric curcuminoids and coupled with <scp>NMR</scp> insights into its <i>β</i>‐Keto‐enol tautomerization at ambient temperature

Abstract In this study, we present a detailed analysis of the structural forms of asymmetric curcuminoids through single‐crystal X‐ray diffraction and nuclear magnetic resonance (NMR) spectroscopy. Curcuminoids substituted with electron‐withdrawing groups (Cl and Br) predominantly adopt the β ‐keto‐enol form, whereas those with an OMe group exhibit both diketo and β ‐keto‐enol forms. Variable‐temperature X‐ray diffraction studies confirm that the structural state of curcuminoids is influenced by temperature. Our findings also reveal that the β ‐keto‐enol form is favored in acidic and neutral conditions, while the diketo form is more prevalent in basic environments. The theoretical Density Functional Theory (DFT) calculations further elucidate the energy differences between the diketo and β ‐keto‐enol forms, emphasizing the significance of electronic effects and temperature on tautomeric distributions. These insights enhance our understanding of the structural dynamics of curcuminoids, with implications for their biological activity and pharmacological applications.