Fast, selective and scalable flow ammonolysis of oxiranes accessible from glycerol toward bio-based amines

We report a fast, selective, and scalable continuous-flow ammonolysis of oxiranes accessible from glycerol as a sustainable route to amine-functionalized products. Our objective was to upgrade glycidol (1a) and epichlorohydrin (1b) using aqueous and neat liquid ammonia with rigorous process control and successful pilot-scale translation. For glycidol, we achieve >99% conversion and >98% selectivity to 1-amino-2,3-propanediol (2a) in 30 s (120 °C). Mechanistic studies reveal a strong solvent effect, with water promoting epoxide activation and guiding the choice between aqueous and liquid NH3 regimes based on the inherent reactivity of substrates 1a,b. Downstream, 2a is converted to oxazolidinone 3 through an organocatalytic carbonylation using neat dimethyl carbonate, with the assistance of a dedicated in-line methanol-removal module to address equilibrium limitations. For epichlorohydrin (1b), the ammonolysis with neat ammonia can be finely tuned to access either 1-amino-3-chloro-2-propanol (2b) or 1,3-diamino-2-propanol (2c) with high yield and selectivity. The platform delivers strong process metrics (E-factor ≤ 6.6, STY up to 166 kg day−1 L−1) and is validated at pilot scale for both ammonia sources on glycidol and epichlorohydrin. Overall, this integrated strategy offers an industrially relevant, safe, and low-waste alternative to classical batch aminolysis for producing bio-based amine derivatives from glycerol.