A comparison of various FTIR and FT Raman methods: Applications in the reaction optimization stage of combinatorial chemistry

Four different FTIR methods-single-bead FTIR, beam condenser, macro attenua ted total reflection (macro-ATR), and KBr pellet methods-and macro and sing le-bead FT Raman methods have been investigated, and the relative utility w as compared for the analysis of resin-bound organic compounds and the monit oring of solid-phase organic reactions. Furthermore, the comparison include s two additional methods from the literature: diffuse reflectance infrared Fourier transform spectroscopy and photoacoustic spectroscopy. While all of these methods have some utility for solid-phase sample analysis, the relat ive merits of these methods vary particularly in such areas as the informat ion content, spectral quality, sensitivity, speed, sample requirement, and the instrument cost. Both single-bead FTIR and beam condenser FTIR methods have been found to be superb methods in each of these aspects. In the follo wing way, these methods meet many of the essential requirements for a thin layer chromatography (TLC) equivalent for solid-phase synthesis: (1) Only a single bead or 50-100 beads are needed for analysis so that reaction is no t interrupted and is monitored in real-time. (2) A high-quality spectrum ca n be recorded within a few minutes. (3) No sample preparation is required, making the anarysis time even Shorter than that for TLC analysis. (4) These two FTIR methods provide qualitative, quantitative (the percentage of conv ersion), and kinetics information on organic reactions carried out on resin supports. Finally, from the synthetic chemist's point of view, the additio nal advantages of the beam condenser method, such as the low cost and the e ase of operation, make it a more suitable choice as a equivalent for solid- phaseorganic synthesis applications.