Quantification and Prediction of Imine Formation Kinetics in Aqueous Solution by Microfluidic NMR.

Quantitatively predicting the reactivity of dynamic covalent reaction is essential to understand and rationally design complex structures and reaction networks. In this work, we quantified the reactivity of aldehydes and amines in various rapid imine formation in aqueous solution by microfluidic NMR. Investigation of reaction kinetics allows us to quantify the forward rate constants k + by an empirical equation, of which three independent parameters were introduced as reactivity parameters of aldehydes ( S E , E ) and amines ( N ). Furthermore, these reactivity parameters were successfully used to predict the unknown forward rate constants of imine formation. Finally, two competitive reaction networks were rationally designed based on the proposed reactivity parameters. Our work has demonstrated the capability of microfluidic NMR in quantifying the kinetics of label-free chemical reactions, especially rapid reactions that complete in minutes.