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Updated: Jul 17, 2026

Direct Detection of the Acetate-forming Activity of the Enzyme Acetate Kinase
Published on: December 19, 2011
Mechanism of thio acid/azide amidation
Robert V Kolakowski1, Ning Shangguan, Ronald R Sauers
1Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
Abstract:
A combined experimental and computational mechanistic study of amide formation from thio acids and azides is described. The data support two distinct mechanistic pathways dependent on the electronic character of the azide component. Relatively electron-rich azides undergo bimolecular coupling with thiocarboxylates via an anion-accelerated [3+2] cycloaddition to give a thiatriazoline. Highly electron-poor azides couple via bimolecular union of the terminal nitrogen of the azide with sulfur of the thiocarboxylate to give a linear adduct. Cyclization of this intermediate gives a thiatriazoline. Decomposition to amide is found to proceed via retro-[3+2] cycloaddition of the neutral thiatriazoline intermediates. Computational analysis (DFT, 6-31+G(d)) identified pathways by which both classes of azide undergo [3+2] cycloaddition with thio acid to give thiatriazoline intermediates, although these paths are higher in energy than the thiocarboxylate amidations. These studies also establish that the reaction profile of electron-poor azides is attributable to a prior capture mechanism followed by intramolecular acylation.
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