Abstract
This review describes how resonance in amides is greatly affected upon substitution at nitrogen by two electronegative atoms. Nitrogen becomes strongly pyramidal and resonance stabilisation, evaluated computationally, can be reduced to as little as 50% that of N,N-dimethylacetamide. However, this occurs without significant twisting about the amide bond, which is borne out both experimentally and theoretically. In certain configurations, reduced resonance and pronounced anomeric effects between heteroatom substituents are instrumental in driving the HERON (Heteroatom Rearrangement On Nitrogen) reaction, in which the more electronegative atom migrates from nitrogen to the carbonyl carbon in concert with heterolysis of the amide bond, to generate acyl derivatives and heteroatom-substituted nitrenes. In other cases the anomeric effect facilitates SN1 and SN2 reactivity at the amide nitrogen.
Highlights
Amides are prevalent in a range of molecules such as peptides, proteins, lactams, and many synthetic polymers [1]
The contemporary understanding of the resonance interaction between the nitrogen and the carbonyl in amides is that of an interaction between the lowest unoccupied molecular orbital (LUMO) of the carbonyl, π*C=O, and the highest occupied molecular orbital (HOMO) of the amide nitrogen (N2pz ) (Figure 1)
This molecular orbital model highlights the small contribution of the carbonyl oxygen to the LUMO, which indicates that limited charge transfer to oxygen occurs, in line with the resonance model presented in Figure 2, which signifies that charge at oxygen is similar to that in polarized ketones or aldehydes and nitrogen lone pair density is transferred to electron deficient carbon rather than to oxygen
Summary
Amides are prevalent in a range of molecules such as peptides, proteins, lactams, and many synthetic polymers [1]. The contemporary understanding of the resonance interaction between the nitrogen and the carbonyl in amides is that of an interaction between the lowest unoccupied molecular orbital (LUMO) of the carbonyl, π*C=O , and the highest occupied molecular orbital (HOMO) of the amide nitrogen (N2pz ) (Figure 1). This molecular orbital model highlights the small contribution of the carbonyl oxygen to the LUMO, which indicates that limited charge transfer to oxygen occurs, in line with the resonance model presented, which signifies that charge at oxygen is similar to that in polarized ketones or aldehydes and nitrogen lone pair density is transferred to electron deficient carbon rather than to oxygen.
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