DFT, ab initio, NMR, and NBO analyses of Nα-substituted hydrazino acetamides: Experimental vs theoretical values

• Published in: Tetrahedron 2010-03, Vol.66 (13), p.2322-2330
• Main Authors: Dabbagh, Hossein A., Rasti, Elham, Le Grel, Philippe, Hocquet, Alexandre
• Format: Article
• Language: English
• Subjects: Aliphatic compounds; Aza-β3-peptide; Chemical Sciences; Chemistry; Exact sciences and technology; Hydrazinoturn; Hydrogen bond; Kinetics and mechanisms; NBO analysis; NMR; Organic chemistry; Peptides; Preparations and properties; Reactivity and mechanisms
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2010.02.007

We studied the DFT (B3LYP) and HF at 6-31+G/6-31+G∗∗ levels of theory in order to throw light on the conformation, structure, intramolecular hydrogen bond network, as well as proton and nitrogen NMR (GIAO method) of a series of model primary amides in the gas phase and/or in solution (chloroform, methanol, water, dimethyl sulfoxide, and heptane). In this manner, it was possible to show that the amidic group of these model compounds acts as the H-bond donor and interacts with two different H-bond acceptors, thus stabilizing the C8 pseudocycle. The study was conducted to gain a better understanding of the conformation (both experimentally and theoretically) adopted by hydrazino acetamides (model compounds for aza-β3-peptides). In the light of this, we were able to explain why aza-β3-peptides develop a different H-bond network in comparison to their isosteric β3-peptide analogues (an extension of the β-peptide concept). [Display omitted]