112403-68-6Relevant academic research and scientific papers
Hindered ester formation by SN2 azidation of N-acetoxy-N-alkoxyamides and N-alkoxy-N-chloroamides-novel application of HERON rearrangements
Glover, Stephen A.,Mo, Guoning
, p. 1728 - 1739 (2007/10/03)
Treatment of N-acetoxy-N-alkoxyamides or N-alkoxy-N-chloroamides with sodium azide in aqueous acetonitrile results in SN2 displacement of chloride and the formation of reactive N-alkoxy-N-azidoamides. The reaction with N-acetoxy-N-benzyloxybenzamide has been studied kinetically (k294 = 2 L mol-1 s-1) and azidation of N-formyloxy-N-methoxyformamide has been modeled computationally at the pBP/DN*//HF/6-31G* level of theory. The anomeric amides N-alkoxy-N-azidoamides decompose intermolecularly and spontaneously to esters and two equivalents of nitrogen. This extremely exothermic process facilitates the formation, in excellent yields, of highly hindered esters.
A comparison of the reactivity and mutagenicity of n-(benzoyloxy)-n-(benzyloxy)benzamides
Glover, Stephen A.,Hammond, Gerard P.,Bonin, Antonio M.
, p. 9684 - 9689 (2007/10/03)
A new series of N-(acyloxy)-N-alkoxybenzamides, AT-(benzoyloxy)-JV-(benzyloxy)benzamides 7 have been synthesized and have been found to be direct acting mutagens in Salmonella TA100. They undergo AAl1 solvolysis to give N-benzoyl-N-(benzyloxy)nitrenium ions 3 under conditions of acid catalysis as well as unusual BAl2 reactions at nitrogen with hydroxide. The latter process affords as intermediates the anomeric hydroxamic esters 4 which rearrange intramolecularly to esters in a HERON reaction. Rates of acid-catalyzed solvolysis and reaction with hydroxide ions correlate with Hammett σ values with low sensitivity (ρ = +0.32 and +0.55, respectively) in accordance with the AAl1 and BAl2 mechanisms. Mutagenicity for the series also appears to correlate with Hammett σ values but with low, negative sensitivity (p = -0.57), and their biological activity may be attributable to their stability under conditions of the Ames assay and hydrophobic binding to DNA, rather than their chemical reactivity.
Evidence for the Formation of Nitrenium Ions in the Acid-catalysed Solvolysis of Mutagenic N-Acetoxy-N-Alkoxybenzamides
Campbell, John J.,Glover, Stephen A.,Hammond, Gerard P.,Rowbottom, Colleen A.
, p. 2067 - 2080 (2007/10/02)
In aqueous acetonitrile, N-acetoxy-N-alkoxybenzamides undergo acid-catalysed solvolysis by the AAl1 mechanism to give acetic acid and nitrenium ions.This is indicated by an inverse dependence of the acid-independent rate constant, kH, upon the activity of water, a solvent kinetic isotope effect of 0.44 and positive Σ(excit.) values.In addition, relief of steric compression at the nitrogen enhances the rate of solvolysis.Hammett correlations with ?+ substituent constants were found for the rates of solvolysis of para-substituted-N-acetoxy-N-butoxybenzamides and N-acetoxy-N-(para-substituted benzyloxy) benzamides.This fact and the low ρ-values of -1.35 and -1.56, respectively, are indicative of a strong build-up of positive charge in the transition state which has both nitrenium ion and oxonium ion character and is in accordance with computed molecular-orbital properties of N-alkoxynitrenium ions.Greater levels of mutagenicity have been measured for those compounds which are more readily solvolysed to nitrenium ions.
N-ALKOXY-N-ACYLNITRENIUM IONS IN INTRAMOLECULAR AROMATIC ADDITION REACTIONS
Glover, Stephen A.,Goosen, Andre,McCleland, Cedric W.,Schoonraad, Johan L.
, p. 2577 - 2592 (2007/10/02)
N-alkoxy-N-acylnitrenium ions are generated by treatment of N-alkoxy-N-chloroamides with silver ions in ethereal solvents.These intermediates readily cyclise onto aromatic nuclei on alkoxy side-chains to give benzoxazines and benzoxazepines and on the acyl side-chains to give γ, δ and ε benzolactams.Spirane products are formed by ipso addition when a 4-methoxy substituent is present on the side-chain aromatic rings.The yields and regioselectivities of these reactions have been ascribed to different transition structures for cyclisation onto the acyl and alkoxy side-chains which involve respectively an exocyclic and endocyclic N-O ?-bond.Evidence for this exeptionally high ?-bond character has been obtained from MNDO calculations which predict a ?-bond order of 0.9 and a rotational barrier of 29.7 kcalmol-1
