The nucleophilic catalysed decomposition of N-methyl-N-nitroamides in aqueous buffers

Abstract

Rate constants for the decomposition of N-nitro-N-methylamides to N-nitro-N-methylamine and the corresponding carboxylic acid in aqueous buffer solutions are reported. For N-nitro-N-methylacetamide (1a) and N-nitro-N-methylbenzamide (1b), the pH-rate profiles indicate that below pH 5 the reaction is independent of [H⁺]. At pH values > 7 the reactions are strongly HO^– catalysed. Moreover, the basic component of the buffer also catalyses the decomposition reaction. Second-order rate constants, k_B, for this buffer catalysis are dependent on the structure of the base. Thus Brønsted plots of log k_Bversus base pK_a for (1a) and (1b) yield slopes of 0.64 and 0.60, respectively, for nitrogen bases. The oxygen bases AcO^–, HPO₄^2– and HO^– appear to fall on another line of slope ca. 0.5. Solvent deuterium kinetic isotope effects for both the AcO^– and HO^– catalysed reactions are ca. 1, whereas that for the non-catalysed reaction is ca. 2. Catalysis is found to be nucleophilic in nature; thus, for each of the reactions of (1b) with morpholine, piperidine and 4-chlorophenol the corresponding benzoylated base could be isolated. Further, the observed firstorder rate constants for the reaction of either (1a) or (1b) with imidazole reach a limiting value identical to that for N-acetylimidazole itself. For (1a), the ratios of k_B for piperidine to 2,2′,6,6′-tetramethylpiperidine and for pyridine to acetate are ca. 300 and 100, respectively. Again, this is consistent with nucleophilic catalysis. The aromatic substituent effect for the HO^– catalysed reaction yields a Hammett ρ value +2.8, whereas for the non-catalysed reaction a value of 0.8 is obtained. The data are discussed in terms of a mechanism in which nucleophilic attack of the catalyst at the carbonyl C-atom to form a tetrahedral intermediate is rate-limiting. Lack of ¹⁸O-exchange during hydrolysis is consistent with this proposal. This mechanism is unusual for amide hydrolysis and must reflect the enhanced nucleofugacity of the N-nitroamine fragment. The mechanism of the noncatalysed process is less clear. The substituent effects are much smaller than-those for HO^–, and therefore unlikely to involve attack of H₂O at the carbonyl carbon. N-Methyl cleavage via H₂O attack or thermal rearrangement are possible candidates.