American Chemical Society
jo0503106_si_002.cif (11.55 kB)

Controlling the Outcome of an N-Alkylation Reaction by Using N-Oxide Functional Groups

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posted on 2005-06-24, 00:00 authored by Russell J. Pearson, Kathryn M. Evans, Alexandra M. Z. Slawin, Douglas Philp, Nicholas J. Westwood
Covalent modifiers of proteins are of importance in chemical proteomics, an emerging chemical technology used to assign protein function. In this study, high-field 1H NMR techniques were used to analyze the reaction of the bioactive compound, 2,3-bis(bromomethyl)quinoxaline 1,4-dioxide, with amines (a model system for proteins containing nitrogen-based nucleophiles). Unexpectedly, the results show that a double nucleophilic substitution reaction involving 2 equiv of the amine is preferred to an intramolecular cyclization pathway. A direct comparison with the reaction carried out on a substrate lacking the N-oxide functional groups is also provided. X-ray crystal structures and computational studies are used to rationalize the observed differences in reactivity between the two systems.