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

Abstract

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.