Interestingly, H. Charville et al. proposed a mechanism for direct uncatalysed amide bond formation, which involves a nucleophilic attack of an amine to one carboxylic acid molecule from a carboxylic acid hydrogen-bonded dimer. They proposed a concerted proton transfer mechanism in which second carboxylic acid molecule acts as a proton acceptor from which water molecule is eventually lost. In the case of our crystalline reaction intermediate 4, carboxylic acids do not form hydrogen-bonded dimers but interact with single O-H•••O hydrogen bonds (ESI Fig. ). Also, the mechanism proposed by H. Charville et al. includes neutral species and avoids ammonium carboxylate zwitterion formation. Still, the similarity to our case is having the presence of an additional carboxylic acid molecule close to the reaction centre where amide bond eventually forms.