Kinetic modeling of multi-step transformations using sequential dynamic flow experiments

Abstract

In this paper, we present the development of a kinetic model for multi-step transformations, comprising of a Paal–Knorr pyrrole reaction followed by a nucleophilic aromatic substitution within a continuous-flow process, utilizing data obtained from sequential dynamic flow experiments. The reaction networks were fitted to achieve successful parameter estimation (7 parameters in total) with a R² of 0.974 for the desired Paal–Knorr product and a R² of 0.998 for the nucleophilic aromatic substitution product. Model validation based on dynamic flow experiments was extended beyond the previously explored experimental space. In silico simulation involving a threefold higher concentration of the nucleophile than previously studied resulted in approximately 7% model predicted difference to the experimental results.