格氏试剂制备时引发小技巧.pdfVIP

Organic Process Research Development 2005, 9, 365−371 Technical Notes Safety Improvement of a Grignard Reaction Using On-Line NIR Monitoring Jacques Wiss,*,† Markus La¨nzlinger,‡ and Markus Wermuth‡ No artis Pharma AG, Chemical Analytical Deelopment, Basel, Switzerland, and Solias AG, BU Online Technologies, Basel, Switzerland Abstract: Scheme 1. Synthesis of the Product AB A quantitative on-line NIR (near-infrared) method for the monitoring of the formation of a Grignard reagent was developed on laboratory scale using chemometrics and tested in a 630 L pilot plant reactor. Good accuracy of the model was obtained, and feasibility of the on-line measurement was demonstrated. The concentrations of the added reagent (and thus its degree of accumulation) and of the formed Grignard reagent (indication of the reaction initiation) can be determined in real time. Therefore, the safety of the highly exothermic process and its robustness are significantly improved. Further- more, the method is applicable to monitoring concentrations hydrocarbons, alcohols, carboxylic acids, and other com- during the following cross-coupling reaction so that it can be pounds.1,2 used to determine in real time the reaction yield. By using on- The formation reaction occurs on the surface of the line spectroscopy, the product quality and performance can be magnesium which is insoluble. The Grignard reagent formed guaranteed on an industrial scale. Moreover, the cycle times