X-Ray data for two N-acyloxy-N-alkoxyamides, a class of direct-acting mutagens, indicate extreme pyramidalisation at the amide nitrogen in keeping with spectroscopic and theoretically determined properties of amides with bisoxosubstitution at nitrogen. The combined electronegativity of two oxygens leads to average angles at nitrogen of 107.8 and 108.1 degrees and [chiN] of 66 degrees and 65 degrees. The sp3 nature of nitrogen results in negligible amide resonance as evidenced by long N-C(O) bonds, high IR carbonyl stretch frequencies, carbonyl 13C NMR data and very low amide isomerisation barriers. In addition, conformations in the solid state support a strong n(O)-sigma*(NOAc), anomeric interaction as predicted by molecular orbital theory. HF/6-31G* calculations on formamide, N-methoxyformamide and N-formyloxy-N-methoxyformamide support these findings.

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Addition of furanoidic sugars having vicinal cis-diol functionality to aqueous alkaline silicate solutions results in the spontaneous formation of a family of organosilicate complexes in which silicon is either penta-or hexacoordinated. Silicon complexation occurs with 1,4-anhydroerythritol, apiose and ribose, as well as with ribonucleosides (adenosine, cytidine, guanosine) and ribonucleotides (including ATP and NAD ϩ ). Silicon-29 and carbon-13 NMR analysis indicates the occurrence of three main complexes containing pentacoordinated silicon. Two hexacoordinated silicon species are also observed in most instances, these being favoured over the pentacoordinated complexes as solution pH is increased, temperature decreased, or the sugar-to-silicon concentration ratio increased. Ribose, which has two vicinal cis-dihydroxy sites for binding silicon, yields a much wider array of complexes.

Abstract:The origin of the HERON reaction is reviewed from a historical perspective and shown to have its foundation in the unusual properties of bisheteroatom-substituted amides, so-called anomeric amides. The reaction involves migration of anomerically destabilized oxo-substituents on an amide nitrogen to the amide carbon and dissociation of the amide bond. Computational work providing a theoretical basis for the reaction is presented, together with physical organic measurements that support results therefrom. The rearrangement has been observed in a number of chemical transformations of N-alkoxy-N-aminoamides, reactions of 1-acyloxy-1-alkoxydiazenes, N-alkoxy-N-aminocarbamates, Nalkoxyhydroxamic acids, as well as in the gas-phase reactions of N-acyloxy-N-alkoxyamides.Key words: HERON reaction, anomeric amides, rearrangements, hindered esters, concerted reactions. Résumé :On a fait une revue historique de l'origine de la réaction HERON et on montre que sa base réside dans les propriétés inhabituelles des amides portant des substituants bishétéroatomiques, les amides dits anomères. La réaction implique la migration de substituants oxo anomériquement déstabilisée de l'azote d'un amide vers le carbone de l'amide accompagnée d'une dissociation de la liaison amide. On présente un ensemble de calculs théoriques qui sert de base pour expliquer la réaction ainsi que des mesures de chimie organique physique qui supportent les résultats de ces calculs. Le réarrangement a été observé dans un certain nombre de transformations chimiques de N-alkoxy-N-aminoamides, dans les réactions de 1-acyloxy-1-alkyoxydiazènes, de N-alkoxy-N-aminocarbamates et d'acides N-alkoxyhydroxamiques ainsi que dans les réactions en phase gazeuse de N-acyloxy-N-alkoxyamides.

N-acyloxy-N-alkoxyamides are direct-acting mutagens in Salmonella typhimurium TA100 and react with DNA at N7 of guanine and N3 of adenine. From extensive mutagenicity data a quantitative structure–activity relationship (QSAR) has been derived that predicts activity to be dependent upon hydrophobicity (represented by log P) and stability to chemical reactions (through the pKA value of the leaving carboxylic acid group). Sterically bulky substituents (represented by Taft ES parameters) reduce activity. Deviations from this QSAR highlight structural features that can enhance or impede association of small molecules with DNA. Naphthyl, pyrenyl, and fluorenyl substituents raise activity significantly, possibly through an intercalative effect. The influence of a single sterically bulky tert-butyl group remote from the reactive nitrogen is adequately modelled by the QSAR. However, substrates with two or more such groups show radically reduced activity, most likely through a groove exclusion process. Branching close to the reactive centre strongly reduces activity in line with a steric inhibition of reaction with DNA.