Nucleophilic Ion Pairs. 5. Facile Cleavage of Amide Substrates by a Hydroxamate Anion in Aprotic Solvents. Efficient Inhibition by Minute Amounts of Water

A quaternary ammonium salt of the hydroxamate anion was found to cleave several N-methylanilide substrates very readily at room temperature in dry, aprotic media. In contrast, the reaction was very slow in protic media and, for example, a rate difference of >105 was observed between dimethylformamide and formamide media for the reaction of N-methyl-p-nitroacetanilide and tetraethylammonium N-methylmyristohydroxamate. The reaction was efficiently suppressed by minute amounts of water and a kinetic isitope effect (KH2O/KD2O) of 1.3-1.5 was observed for some substrates. These results indicate that both the nucleophilic attack and the proton transfer to the tetrahedral intermediate were facilitated in dry, aprotic media. The reaction of the hydroxamate and p-nitrophenyl acetate was facilitated in dry, aprotic media and in aqueous cationic micelles. Thus, the complete suppression of the amide cleavage in the cationic micelle was attributed to the inefficient proton transfer to the tetrahedral intermedate.