S'N'2 Substitution Reactions at the Amide Nitrogen in the Anomeric Mutagens, 'N-Acyloxy-N-alkoxyamides'

Author(s)
Cavanagh, Katie Lee
Glover, Stephen
Price, Helen
Schumacher, Rhiannon Rose
Publication Date
2009
Abstract
N-Acyloxy-N-alkoxyamides '1a' are unusual anomeric amides that are pyramidal at the nitrogen because of bis oxyl substitution. Through this configuration, they lose most of their amide character and resemble α-haloketones in reactivity. They are susceptible to SN2 reactions at nitrogen, a process that is responsible for their mutagenic behaviour. Kinetic studies have been carried out with the nucleophile N-methylaniline that show that, like SN2 reactions at carbon centres, the rate constant for SN2 displacement of carboxylate is lowered by branching β to the nitrogen centre, or bulky groups on the alkoxyl side chain. Branching or bulky groups on the carboxylate leaving group, however, do not impact on the rate of substitution, which is mostly controlled by the pKA of the departing carboxylate group. These results are in line with computed properties for the model reaction of ammonia with N-acetoxy-N-methoxyacetamide but are in contrast to the role of steric effects on their mutagenicity.
Citation
Australian Journal of Chemistry, 62(7), p. 700-710
ISSN
1445-0038
0004-9425
Link
Publisher
CSIRO Publishing
Title
S'N'2 Substitution Reactions at the Amide Nitrogen in the Anomeric Mutagens, 'N-Acyloxy-N-alkoxyamides'
Type of document
Journal Article
Entity Type
Publication

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