Structural Insights into N,N-Diethyl-2-hydroxyacetamide Using Matrix Isolation Infrared Spectroscopy and DFT...

The conformational space of N,N-diethyl-2-hydroxyacetamide (DEHyA) was elucidated through an integrated experimental-computational approach combining matrix isolation infrared spectroscopy and density functional theory (DFT) calculations. Quantum chemical analysis revealed 15 distinct conformers, with the CC(g^±g^±) form constituting the global minimum and the closely related CC(g^±g^∓) geometry lying slightly higher in energy. Infrared spectral evidence for these conformers was obtained from the O-H, C=O, and C-O stretching regions in N₂ and Ar matrices at cryogenic temperatures. Both low-energy structures are primarily stabilized by intramolecular hydrogen bonding, further modulated by hyperconjugative and weak tetrel interactions. The relative energetic and electronic contributions of these effects were quantified through Non-Covalent Interaction (NCI), Electrostatic Potential (ESP) mapping, Intrinsic Bond Strength Index (IBSI), and Natural Bond Orbital (NBO) analyses. These results establish hydrogen bonding as the principal stabilizing force, complemented by secondary hyperconjugative and tetrel effects. Targeted orbital deletion studies further demonstrated that charge-transfer electron delocalization governs the conformational preference, underscoring the cooperative nature of noncovalent interactions in defining the structural stability of DEHyA. A comprehensive comparison with the higher homologue, N,N-dioctyl-2-hydroxyacetamide (DOHyA), was undertaken to elucidate whether conformational modulation arises solely from intrinsic electronic factors or is additionally influenced by steric encumbrance imposed by bulky alkyl substituents.