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Formation of 2-Trifluoromethylphenyl Grignard Reagent via Magnesium−Halogen Exchange: Process Safety Evaluation and Concentration Effect

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journal contribution
posted on 20.11.2009, 00:00 by Wenjun Tang, Max Sarvestani, Xudong Wei, Laurence J. Nummy, Nitinchandra Patel, Bikshandarkoil Narayanan, Denis Byrne, Heewon Lee, Nathan K. Yee, Chris H. Senanayake
The thermal stability profile for a solution of 2-trifluoromethylphenyl magnesium chloride at 1.5 M concentration in THF was determined using an Advanced Reactive System Screening Tool (ARSST). The solution generated by employing Knochel’s magnesium−halogen exchange protocol showed highly exothermic decomposition. The decomposition begins at a low-onset temperature accompanied by a rapid temperature and pressure rise. Analysis of the decomposition mixture revealed the destruction of trifluoromethyl group and formation of fluoride ion. This decomposition profile was substantially attenuated by reducing the concentration of the solution to 0.5−0.6 M. Thus, it is strongly recommended that selecting an appropriate concentration for the reagent based on calorimetric evaluation should be included with procedural and engineering controls when considering any strategy for safe scale-up of trifluoromethyl-substituted phenyl Grignard solutions.