Structure, conformation, anomeric effects and rotational barriers in the HERON amides, N,N ′-diacyl-N,N ′-dialkoxyhydrazines

Abstract

N,NЈ-Diacyl-N,NЈ-dialkoxyhydrazines are HERON amides that exhibit theoretical and physical properties of bisheteroatom-substituted amides. Amide nitrogens are pyramidal and they adopt a preferential conformation which permits an anomeric interaction in which one nitrogen overlaps strongly with the adjacent N-O σ* orbital. A crystal structure of N,NЈ-di(p-chlorobenzoyl)-N,NЈ-diethoxyhydrazine 4d has been obtained which confirms these properties in the solid state. Infrared data for ten such hydrazines indicate unusually high carbonyl stretch frequencies in accord with pyramidality at nitrogen. Diastereotopic resonances and dynamic 1 H NMR studies indicate both a significant N-N rotational barrier of between 65 and 72 kJ mol Ϫ1 , which is consistent with a strong anomeric interaction, as well as a much smaller than usual amide rotation barrier of 54 kJ mol Ϫ1 , a direct consequence of pyramidality at nitrogen.

The HERON reaction — Origin, theoretical background, and prevalence

“…In anomeric amides both effects disappear on account of the sp 3 hybridization at nitrogen and barriers to isomerization have been found to be drastically reduced or are too low to be measured by dynamic NMR methods (4,10). Ab initio calculations confirm these properties (4,9,10,15).…”

“…In a recent study we have demonstrated that these hydrazines exhibit all the hallmarks of anomeric amides (15). Their carbonyl stretch frequencies in solution are in the range of 1700-1744 cm -1 , while those of their precursor hydroxamic esters are in the range 1680-1690 cm -1 (4,15).…”

“…In a recent study we have demonstrated that these hydrazines exhibit all the hallmarks of anomeric amides (15). Their carbonyl stretch frequencies in solution are in the range of 1700-1744 cm -1 , while those of their precursor hydroxamic esters are in the range 1680-1690 cm -1 (4,15). This accords with pyramidal nitrogen atoms, and in the case of N,N ′-diacetyl-N,N ′-di(p-chlorobenzyloxy)hydrazine, dynamic NMR methods afforded a low amide isomerization barrier of just 12.9 kcal mol -1 .…”

“…3b). Both structures exhibit a conformational preference that clearly optimizes either the n O -σ NO * or the n N -σ NO * overlap (15,16).…”

SN2 reactions at amide nitrogen – theoretical models for reactions of mutagenic N-acyloxy-N-alkoxyamides with bionucleophiles

“…5 Structurally, these mutagens are members of the class of so-called anomeric amides which have two electronegative atoms bonded to the amide nitrogen. [6][7][8][9] This results in strong pyramidalisation of the amide nitrogen to satisfy the electron demand of the heteroatoms and the nitrogen lone pair is consequently far less conjugated with the amide carbonyl than is the case in primary amides, secondary and tertiary N-alkylamides, or even hydroxamic esters which have only one oxy-substituent. Such amides have high carbonyl stretch frequencies (1720-1740cm -1 ) and low amide isomerisation barriers (Figure 1(a)) and, in addition, they can support an anomeric effect at the amide nitrogen.…”