Deciphering the Role of Solution-Phase Species in the Ring-Opening of Unsymmetric Epoxides by Ammonia – A Combination of Experimental Analysis and DFT-Informed Microkinetic Modeling

Abstract Alkanolamines, a group of versatile chemicals in gas treatment, personal care, metalworking, and coatings, are commonly synthesized through the ring opening of epoxides by amines. For unsymmetric epoxides, such as propylene oxide, aminolysis can generate multiple regioisomers and sequential secondary or tertiary amine products. In aqueous systems, this reaction network may be further complicated by the participation of solution-phase species, including water, ammonium ions, and alkanolamine products, which could influence reaction rates and selectivity through hydrogen bonding interactions. Here, we combined flow reactor kinetic measurements, explicit-solvation DFT calculations, and microkinetic modeling to investigate the ring opening of propylene oxide by ammonia in water. Experimental measurements across a broad range of initial conditions revealed unusual kinetic behavior with respect to water, including a low apparent activation energy and an apparent water order greater than two, suggesting the participation of multiple water molecules. These observations were used to guide the development of a detailed microkinetic model in which elementary step rate coefficients were informed by DFT calculations including explicit solution-phase species. These results indicate that, during the reaction, multiple water molecules lower the apparent activation energy by stabilizing the PO ring and bridging NH3 during ring opening, while other solution-phase species, including alkanolamine products, can also stabilize PO and contribute to product-assisted catalysis. More broadly, this work establishes a framework for connecting flow reactor kinetics with molecular-scale modeling to understand complex liquid-phase reaction networks involving explicit solvent and product participation.