Hydroxylamine reacts with aspirin in aqueous solution at 25 °C predominantly through oxygen, to give O-acetylhydroxylamine as the initial product (Scheme 3). The reaction is much faster than the intramolecular general base catalysed hydrolysis of the carboxylate anion, as it is also for the CO 2 H form of aspirin. Both reactions are faster than expected, consistent with moderate activation and/or proton transfer catalysis of hydroxylaminolysis by both CO 2 – and CO 2 H groups. Calculations support oxygen attack as the preferred reaction, but do not permit a clear choice between mechanisms involving NH 2 OH and + NH 3 –O – as the effective nucleophile.