Structures of N,N-Dialkoxyamides: Pyramidal Anomeric Amides with Low Amidicity

• Published in: Journal of organic chemistry 2011-12, Vol.76 (23), p.9757-9763
• Main Authors: Glover, Stephen A, White, Jonathan M, Rosser, Adam A, Digianantonio, Katherine M
• Format: Article
• Language: English
• Subjects: Aliphatic compounds; Amides - chemistry; Chemistry; Crystallography, X-Ray; Exact sciences and technology; Models, Molecular; Molecular Structure; Organic chemistry; Preparations and properties
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo201856u

The first X-ray structures of two anomeric N,N-dialkoxyamides (2 and 3) have been obtained, which confirm that they are highly pyramidalized at nitrogen and have long N–CO bonds, a characteristic of other anomeric amides and a consequence of drastically reduced amidicity. The crystals also demonstrate chirality at the amide nitrogen in the solid state. The structures are well-predicted by density functional calculations using N,N-dimethoxyacetamide as a model. The amidicity of N,N-dimethoxyacetamide has been estimated by two independent methods, COSNAR and a new transamidation method, which give almost identical resonance stabilization energies of −8.6 kcal mol–1 and only 47% that of N,N-dimethylacetamide computed at the same level. The total destabilization is composed of a resonance and an inductive contribution, which we have evaluated separately. The electronegative oxygens at nitrogen are responsible for localization of the nitrogen lone pair on the amide nitrogen, a factor that contributes to a loss of resonance over and above the impact of pyramidalization at nitrogen, as well as the fact that N,N-dimethoxyacetamide is predicted to protonate on the carbonyl oxygen in preference to nitrogen.