42015-13-4Relevant articles and documents
Synthesis and Hydrolytic Lability of α-Phenoxyacetamides Containing Hydroxy Groups in the N-alkyl Residue
Anelli, Pier Lucio,Brocchetta, Marino,Canipari, Sonia,Losi, Pietro,Manfredi, Giuseppe,et al.
, p. 135 - 142 (2007/10/03)
Secondary and tertiary amides of 3,5-biscarbonyl>phenoxyacetic acid bearing hydroxy groups in positions β (β-OH) and γ (γ-OH) relative to the acetamide nitrogen atom have been synthesized.Such amides easily undergo cleavage of the acetamide bond in water at neutral pH.Hydrolysis rate constant for a series of such amides and protonation constants for the corresponding leaving amines were determined.No simple correlation between the two parameters could be found.A study of the dependence of these parameters on the structural features of the substrates, such as the presence of an N-methyl group and number of β-OH and γ-OH groups, was carried out.All these features lead to enhancement of the amide hydrolysis rate and a synergistic effect is operative when both N-methyl and β-OH groups are contained in the substrate.Presence of a methyl group increases the basicity of amines whereas β-OH and γ-OH groups have the opposite effect.Mechanistic speculations seem to indicate that the abnormal lability of the acetamide bond is due to protic-like catalysis by an intramolecular OH...N hydrogen bond.
