Sedighi, MasoumehBarbero-Moreno, AnaLarquier, MarieRuiz Serrano, MiriamMenéndez Ramos, José CarlosLópez-Alvarado Gutiérrez, María Pilar2025-12-182025-12-182025Miriam Ruiz-Serrano, Masoumeh Sedighi, Ana Barbero-Moreno, Marie Larquier, Pilar López-Alvarado, and J. Carlos Menéndez ACS Sustainable Chemistry & Engineering 2025 13 (45), 19536-19550 DOI: 10.1021/acssuschemeng.5c0730710.1021/acssuschemeng.5c07307https://hdl.handle.net/20.500.14352/129322A general two-step, one-pot mechanochemical procedure for carrying out reductive amination under solvent-free conditions is described. The method involves milling the starting materials in stainless steel jar and balls in the presence of zinc chloride and sodium cyanoborohydride, and was applied to a broad range of carbonyl compounds, including aromatic and aliphatic aldehydes and ketones, and also two drug molecules (benzocaine and sulphathiazole) and four natural products (vainillin, menthone, cinnamaldehyde andtryptamine). Its use in target-oriented synthesis was demonstrated by the fully mechanochemical preparation of two active pharmaceutical ingredients, the anti-Parkinson monoamino oxidase B inhibitors rasagiline and safinamide, with improved green metrics in comparison with solution chemistry.engjournal article2168-0485https://doi.org/10.1021/acssuschemeng.5c07307open access547Ball millingMechanochemistrySolid-state synthesisTwo-stepOne-pot reactionsLate-stage functionalizationAPI synthesisQuímica orgánica (Química)2306 Química Orgánica