Monitoring solid phase synthesis by infrared spectroscopic techniques

The paper describes the use of attenuated total reflection fourier transform-infrared (ATR FT-IR) microspectroscopic techniques for the verification of the structure of chemical compounds synthesised on polystyrene beads in combinatorial chemistry. A six step reaction sequence is characterised completely by infrared (IR) spectroscopic investigations of single beads. Incomplete reactions or the occurrence of side products are clearly indicated. Quantitative information can be extracted with high precision using absorption bands of the polymer matrix as internal standard. Compared to other IR techniques, the ATR micro IR technique shows clear advantages with respect to sensitivity and resolution. The technique has the potential to be used for the characterisation of single beads in split and combined synthesis techniques. (C) 1999 Elsevier Science B.V. All rights reserved.