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

Abstract

We report fast, selective, and scalable continuous-flow ammonolysis of glycerol-derived oxiranes 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 pilot-scale translation. For glycidol, we achieve >99% conversion and >98% selectivity to 3-amino-2,3-propanediol (2a) in 30 s (120 °C), surpassing prior art. Mechanistic studies reveal a decisive 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 oxazolidin-2-one 3a 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, the ammonolysis with neat ammonia can be finaly tuned to access either 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, multi-kg productivity) 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.