Direct Infrared Spectroscopic Analysis of Reagent Partitioning in Polystyrene Bead Supported Solid Phase Reaction Chemistry

Abstract

Throughout the evolution of polymer support based combinatorial synthesis, many issues have been raised concerning chemistry at the interior of the support bead. Long standing questions regarding size exclusion, reagent diffusion, and reaction kinetics remain unresolved, largely due to limited analytical capabilities which address chemical activity at the core of the solid phase support bead. A variety of novel infrared spectroscopic techniques for the direct evaluation of intrabead reagent dynamics are presented in this work. Specifically, these spectroscopic tools facilitate analysis and understanding of reagent penetration and intra-bead reagent mobility parameters. Data from these studies downplay size exclusion as a consequential factor in the delivery of small molecule reagents throughout synthesis on polystyrene-based resins. Experiments presented here, however, illustrate the first direct spectroscopic evidence of thermodynamic reagent partitioning between the support bead and surrounding solvent as an essential factor in efficient delivery of reagent to the solid phase support interior.