End-point determination on-line and reaction co-ordinate modelling of homogeneous and heterogeneous reactions in principal component space using periodic near-infrared monitoring

Abstract

Advancement of organic homogeneous and heterogeneous reactions to their steady state end-points has been determined directly using near-infrared spectroscopy and fibre optic probes. The reaction times can be obtained without specifically measuring decay of individual starting materials or formation of products. The technique is passive and can be generally applied to most organic reactions in the laboratory or chemical plant. This report uses the formation of zopolrestat ethyl ester and its saponification to zopolrestat sodium salt, as typical examples of a heterogeneous and a homogeneous reaction matrix, respectively. Data has been collected directly from full size chemical reactors. The steady state is detected when the change in the spectra does not change significantly with time. The end-point can be confirmed computationally shortly after the data has been collected using open ended models. These can be constructed directly from the spectral data using commercially available software. The end-point can be confirmed with multivariate calibration methods using dendrograms derived from hierarchical cluster analysis or scores plots obtained from principal component analysis. The reaction co-ordinate can be modelled in principal component space using the locus of the spectral scores plot.