Monitoring solid phase synthesis reactions with electrochemical impedance spectroscopy (EIS)

Abstract

This work describes the use of electrochemical impedance spectroscopy (EIS) as a means to monitor solid phase synthesis on resin beads. EIS was used to track changes during the swelling of beads in various solvents, during three typical reactions and throughout cleavage of the final product from the bead. The impedance response was investigated in a chemical reactor and was found to be faintly sensitive to the resin swelling and solvent flow. The position of the electrode within the reactor was found to be critical as polystyrene based beads float or sink dependent upon the solvent used. However, by choosing electrode position it was possible to monitor reaction progress on beads or within the bulk reactant/product mixture. Of the three typical chemical reactions studied impedance spectroscopy successfully followed two. Fitting of the impedance data to an equivalent electrical circuit provided an estimate as to the relative contribution of capacitive and resistive components to the overall response. Kinetic data from two reactions were also modelled, in both cases complex kinetics was observed, in close agreement with other studies.

A New Colorimetric Test for Solid-Phase Amines and Thiols

“…5 In SPOS, it is more difficult to monitor the reaction because the chemical transformations proceed on insoluble resin beads, and, therefore, fast solution-phase analysis methods, such as TLC and LCMS, are not directly applicable for SPOS. Also NMR, 6 IR 7 and electrochemical impedance spectroscopy 8 (EIS) experiments are not straightforward on resin. This makes the monitoring of solid-phase reactions a challenging subject.…”

Colorimetric Monitoring of Solid-Phase Aldehydes Using 2,4-Dinitrophenylhydrazine

“…Solid-phase reactions should be monitored because incomplete incorporations reduce overall yields and affect purities of products isolated after final cleavage. Classical techniques for following the course of reactions, such as TLC, are clearly not applicable in the solid-phase mode, while on-resin NMR, − IR, − MS, ,, and more recently, electrochemical impedance spectroscopy (ESI) experiments are not straightforward. A viable way to probe progress of a solid-phase reaction is to cleave the intermediate from the linker/support , and to use classical techniques for characterization and quantitation.…”

4-(9-Fluorenylmethyloxycarbonyl)phenylhydrazine (FmPH): A New Chromophoric Reagent for Quantitative Monitoring of Solid-Phase Aldehydes1-3

“…The solid-phase mode presents several chal-lenges, because classical techniques for following the course of reactions, such as TLC, do not apply to polymersupported intermediates. Additionally, on-bead NMR, [23][24][25][26][27][28][29][30][31] IR, 32-36 MS, 22,37,38 and more recently electrochemical impedance spectroscopy 39 (ESI) experiments are not straightforward. A viable way to probe the progress of a solid-phase reaction is to cleave the intermediate from the linker/support 40,41 and then use classical techniques for characterization and/or quantitation.…”