Real time quantitation of a chemical reaction by fiber optic near-infrared spectroscopy

In this paper, a quantitative method for following the progression of an industrially significant reaction using chemometrics, fiber-optic near-infrared (NIR) spectroscopy, and a single fiber transmission probe is reported. This method is based on a calibration for the reaction developed by sampling aliquots of a typical reaction for off-line HPLC analysis immediately after acquiring a spectrum. A comparison of HPLC peak areas to the spectra was used to develop a calibration for monitoring realtime product formation. A partial least squares (PLS) calibration model was developed from the characteristic reaction data and was applied to a 30-g-scale reaction. The model successfully predicted the formation of the product. An advantageous feature of this method is that although the product contained a specific absorbance in the NIR, by-product generation during the reaction could also be monitored by NIR. Based on the PLS model generated from both the product and by-product, the product concentration can be predicted directly from the spectral data with a correlation greater than 0.9, and required only a single PLS factor. (C) 1999 Elsevier Science B.V. All rights reserved.