JACs Image Challenge
Oct 2011
Ho J., Easton C. J., Coote M.L. The Distal Effect of Electron-Withdrawing Groups and Hydrogen Bonding on the Stability of Peptide Enolates. J. Am. Chem. Soc. (2010), 132, 5515-5521 http://dx.doi.org/10.1021/ja100996z
Amides are normally weaker carbon acids than ketones mainly because the amide nitrogen attenuates the resonance stabilization of the corresponding enolates (via resonance contributor III) through cross conjugation (via resonance contributor I). Accordingly, the placement of electron-withdrawing groups on the amide nitrogen should increase the acidity of the alpha-carbonyl CH proton. Please rank Acetone(1), Dimethylacetamide(2), N-benzylacetamide(3), and N-trifluoromethanesulfonylacetamide(4) in order of increasing alpha-carbonyl CH acidity.
(A) 1 < 2 < 3 < 4
(B) 2 < 3 < 4 < 1
(C) 2 < 3 < 1 < 4
(D) 4 < 3 < 2 < 1
