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Hydrolysis of Naptalam and Structurally Related Amides: Inhibition by Dissolved Metal Ions and Metal (Hydr)Oxide Surfaces
journal contribution
posted on 1999-09-18, 00:00 authored by Ching-Hua Huang, Alan T. StoneIn metal ion-free solutions, the secondary amide naptalam hydrolyzes more rapidly as the pH is
decreased; intramolecular nucleophilic attack by a carboxylate side group is very likely involved.
Millimolar levels of dissolved CuII and ZnII inhibit hydrolysis between pH 3.6 and pH 6.5. Metal
ion−naptalam complex formation is important since addition of the competitive ligand citrate lessens
the inhibitory effect. The metal (hydr)oxide surfaces Al2O3 and FeOOH inhibit naptalam hydrolysis
to a lesser degree; inhibition is proportional to the extent of naptalam adsorbed. Secondary amides
(propanil, salicylanilide, and N-1-naphthylacetamide) and tertiary amides (N-methyl-N-1-naphthylacetamide, furalaxyl, and N,N-diethylsalicylamide) that lack carboxylate side groups do not hydrolyze
within 45 days of reaction, even when millimolar CuII concentrations are present. Tertiary amides
possessing carboxylate side groups (N,N-diethyl-3,6-difluorophthalamic acid and N,N-dimethylsuccinamic acid) do hydrolyze but are insensitive to the presence or absence of CuII. The inhibitory
effect is believed to occur via metal coordination of (1) the carbonyl group of naptalam, which induces
deprotonation of the amide group and makes the substrate less reactive toward nucleophilic attack;
(2) the free carboxylate group of naptalam, which blocks intramolecular nucleophilic attack; or (3)
a combination of the two.
Keywords: Naptalam; amide hydrolysis; metal catalysis; metal inhibition; phthalamic acid
derivatives.