Fig. 2.

A time course of predicted Raman concentrations of phenol and ether for a second pilot plant batch, with off-line HPLC and theoretical limit of ether. In situ Raman spectroscopy was used to control a heterogeneous etherification reaction, with Raman measurements of ether %w/w used to predict end of reaction. Reagent was added from 0 to ~180 min followed by a line wash, which accounts for the profile disturbance at ~ 240 min. In the process description and batch sheet, the reaction would have been completed at ~ 1250 min and at that time a sample would be collected for offline HPLC analysis (square in figure). In situ Raman data showed reaction completion nearly 600 min before stipulated time. The data suggest that batch cycle time could be reduced by several hours when moving up to the commercial manufacturing scale, improving process efficiency. Reprinted with permission from Hart, Richard J., Nicholas I. Pedge, Alan R. Steven, and Kevin Sutcliffe. “In Situ Monitoring of a Heterogeneous Etherification Reaction Using Quantitative Raman Spectroscopy.” Organic Process Research & Development 19, no. 1 (January 16, 2015): 196–202. doi:10.1021/op500027w. Copyright 2016 American Chemical Society