Feedback Control of Oximation Reaction by Inline Raman Spectroscopy

Although the process analytical technology for ensuring constant product quality and tight control over the manufacturing process, which is especially important in the case of hazardous chemical reactions, has initiated extensive use of real-time spectroscopic methods (ATR-UV/vis, ATR-FTIR, or Raman) for monitoring of chemical reactions, control of chemical syntheses on the basis of inline Raman spectroscopic detection has not been implemented yet. The present paper reports the development of an effective feedback control on the basis of Raman spectroscopy governing a potentially hazardous, exothermic model reaction. The control approach allowed the quantification of reaction components and an unstable intermediate and, furthermore, determined the end point of the reaction. The spectrum of the unstable intermediate was identified using the multivariate curve resolution-alternating least-squares (MCR-ALS) method. The implementation of the feedback control required the development of a program operating the Raman spectrometer and coordinating the real-time CLS chemometric evaluation, while another program was designed to communicate with the previous one and was responsible for the closed-loop control of the process.