Continuous Preparation of Arylmagnesium Reagents in Flow with Inline IR Monitoring

Abstract

A newly developed microscale ReactIR flow cell was used as a convenient and versatile inline analytical tool for Grignard formation in continuous flow chemical processing. The LiCl-mediated halogen/Mg exchange reaction was used for the preparation of functionalized arylmagnesium compounds from aryl iodides or bromides. Furthermore, inline IR monitoring was used for the analysis of conversion and possible byproduct formation, as well as a potential tool for elucidation of mechanistic details. The results described herein indicate that the continuous flow systems are effective for highly exothermic reactions such as the Grignard exchange reaction due to fast mixing and efficient heat transfer.

The route from problem to solution in multistep continuous flow synthesis of pharmaceutical compounds

“…7,72,73 Several different analytical systems were used successfully, such as in-line FT-IR (predominantly with Attenuated Total Reflectance (ATR) cells), [74][75][76][77][78][79][80] NIR, 81,82 Raman 83 and NMR spectroscopy, 84,85 as well as on-line MS 86,87 and HPLC. 88,89 However, everyday application of these approaches is hindered by the fact that off-line solutions are usually more convenient, since a wider toolbox (consisting of existing equipment) is available for the analysis of less demanding analytes (i.e.…”

Flow Technology for Organometallic-Mediated Synthesis

“…However, in striking contrast, the scaled batch process is costly and inefficient, requiring low-temperature operations and slow controlled addition of one reagent into the other. Brodmann and coworkers reported a continuous-flow process for the preparation of aryl-and heteroaryl Grignard reagents by a halogenMg exchange reaction using i-PrMgCl-LiCl (Scheme 22) [36].…”

The continuous flow synthesis of 2,4,5-trifluorobenzoic acid via sequential Grignard exchange and carboxylation reactions using microreactors

“…The arylmagnesium reagent can be formed by the reaction of magnesium with bromide but sometimes difficult especially for large-scale production [42][43][44]. The success of the reaction often depends critically on its initiation process and prior activation of magnesium surface is usually required to start the reaction [17].…”