Inline Analysis in Microreaction Technology: A Suitable Tool for Process Screening and Optimization

A procedure is described for successfully benchmarking different inline spectroscopic techniques in a microreaction plant. The objective was to identify the highest calibration precision for the real‐time quantification of the main product. Investigated methods were Raman‐, near infrared‐, and visible spectroscopy. Besides microreaction technology, the procedure comprises chemometric approaches using statistical experimental design tools and multivariate calibration methods. A calibration model was set up and validated within a defined parameter space (temperature, stoichiometry, and flow rate). The experimental basis was the investigation of toluene nitration using two different nitrating agents. The first reaction was a homogeneous nitration with pure nitric acid as the nitrating agent. It was found that Raman‐spectroscopy generates the highest precision. In the second reaction, a heterogeneous liquid‐liquid system was obtained using mixed acids. In this case, the precision is very similar for all methods with no preferences for a specific method. As well as investigating the calibration model, additional testing of the observed flow patterns was undertaken for the latter reaction, using the sensitive and very fast AOTF‐NIR‐spectroscopy. A procedure is de‐scribed for successfully benchmarking different inline spectroscopic techniques (Raman, near infrared, and visible) in a microreaction plant. The experimental basis is the investigation of toluene nitration using two different nitrating agents. A calibration model is set up and validated within a defined parameter space.