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, kB, for this buffer catalysis are dependent on the structure of the base. Thus Bronsted plots of log kBversus base pKa for (1a) and (1b) yield slopes of 0.64 and 0.60, respectively, for nitrogen bases. The oxygen bases AcO–, HPO42– 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 kB 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.