Benzamidinium compounds have found widespread use in both medicinal and supramolecular chemistry. In this work, we show that benzamidiniums hydrolyse at room temperature in aqueous base to give the corresponding primary amide. This reaction has a half-life of 300 days for unsubstituted benzamidinium at pH 9, but is relatively rapid at higher pHs (e.g. t1/2 = 6 days at pH 11 and 15 hours at pH 13). Quantum chemistry combined with first principles kinetic modelling can reproduce these trends and explain them in terms of the dominant pathway being initiated by attack of HO– on benzamidine. Incorporation of the amidinium motif into a hydrogen bonded framework offers a substantial protective effect against hydrolysis.
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