Sensitive single step fluorimetric method for monitoring solid-phase reactions on polystyrene resin-bound chloride groups

Georgina E Pina-Luis,Ignacio A Rivero Espejel,Marco A Zazueta Gómez,Marta E Díaz-García

doi:10.1590/s0103-50532011000600004

Abstract

Fluorescence spectroscopy has been used to monitor the chemical conversion of resin-bound chloride groups. The time-concentration profiles of different reactions involving the incorporation of hydroxyphenylethanone (HPE) derivatives to Merrifield resin and 2-aminobencylalcohol (ABA) to a chlorosulphonate resin are shown. The evaluation of the reaction progress was made using an immobilized fluorescent tracer (dansyl hydrazine) and by direct fluorescence measurements of the species formed on each step of the reactions on resin beads. Significant differences between these two methods were not observed. The results demonstrate that direct measurements on solid phase without using fluorescent markers represent a single step, rapid, non destructive and low cost analysis by monitoring reaction progress on chlorinated resins, which allows not only the study of reaction kinetics but also provides a valuable tool for the analytical quantification of chloride resin bound, without any sample preparation, except the transfer of resin bead of each reaction stage from the reaction vessel to the flow cell for the fluorescent measurement.

Highlights

Solid phase organic synthesis (SPOS) continues to play an important role in combinatorial chemistry, in the preparation of new drugs but in the development of materials with molecular recognition properties.[1,2,3,4,5,6,7] In spite of its extensive use, a critical step in this field is the lack of analytical techniques for monitoring the reaction progress.Monitoring the course of the reactions on solid phase requires, in many cases, the cleavage of intermediates and products from the support and to use classical techniques for characterization and quantification
In a previous work,[32] we have reported the use of a fluorescent tracer as a useful tool for the determination of resinbound hydroxyl groups, for the study reaction kinetics and for monitoring the progress of reactions
PS-chlorometyl resin, known as Merrifield resin, is a useful starting material extensively used in solid phase synthesis.[33,34]

Summary

Introduction

Solid phase organic synthesis (SPOS) continues to play an important role in combinatorial chemistry, in the preparation of new drugs but in the development of materials with molecular recognition properties.[1,2,3,4,5,6,7] In spite of its extensive use, a critical step in this field is the lack of analytical techniques for monitoring the reaction progress.Monitoring the course of the reactions on solid phase requires, in many cases, the cleavage of intermediates and products from the support and to use classical techniques for characterization and quantification. Despite of the efforts made in the development of new methods for monitoring the reaction progress on solid phase, many of the reported procedures involve several stages in their implementation, or/and may result expensive and destructive analysis, or/and may consume a long time of sample preparation.

Results

Conclusion