Shaking up conjugates between chitosan and aldehydes via mechanochemistry†

A solid-state mechanochemical protocol to synthesize Schiff base and N-alkyl chitosan derivatives is described. The transition from a liquid reaction medium to a solid-state reaction allowed for a more efficient conjugation between the added hydrophobic aldehydes and hydrophilic chitosan by circumventing the generally observed solubility mismatch. Furthermore, for the reductive amination, the utilization of NaBH₄ was facilitated instead of NaCNBH₃. The overall sustainable character of the reaction was compared to other solution-based methods via the calculation of the RME and PMI green metrics.