Finding the simplest mechanistic kinetic model describing the homogeneous catalytic hydrogenation of avermectin to ivermectin

Abstract

Six mechanistic kinetic models of increasing complexity are analyzed to describe the RhCl(Ph3P)3 catalyzed hydrogenation process to produce ivermectin from avermectins B1a and B1b. Global sensitivity analysis (GSA) usefulness for selecting the simplest and the most suitable model is shown. First-order and total effect sensitivity indices for model parameters computed from GSA have been used for establishing those elementary reaction steps which were the most important in an extensive reaction framework. The prediction capability of the chosen model is corroborated by comparing its predictions with experimental data from both a lab-scale reactor and an industrial-scale reactor operating under isothermal and nonisothermal conditions, respectively. The best model is simple to use while resulting in a significant computational effort saving because there is no need to perform iterative algorithms for solving model equations. Another interesting feature is that ODEs for such a model have an analytical solution for isothermal hydrogenation processes. These features make modeling more amenable for cost-effective simulation and to include the selected model into computational frameworks for design of the hydrogenation process and control systems of the most usual catalytic method for producing ivermectin.