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

The Use of Gases in Flow Synthesis

“…1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 (Figure 3). 58 The use of ethylmagnesium bromide as a Grignard exchange reagent was used due to the stability of the reagent, allowing the authors to conduct the reaction at 30 °C. As part of the study, the size of the T-mixer was investigated to avoid blockage of the system due to precipitation.…”

Synthesis of Organometallic Compounds in Flow

“…Carboxylic acids can be prepared by reaction of a Grignard reagent and CO 2 . The group of Shen and Zhang reported the synthesis of 2,4,5‐trifluorobenzoic acid through sequential Br−Mg exchange and carboxylation …”

“…The group of Shen and Zhang reported the synthesis of 2,4,5-trifluorobenzoic acid through sequential BrÀ Mg exchange and carboxylation. [68] The reaction of 1-bromo-2,4,5-trifluorobenzene with EtMgBr was conducted in a reactor made of a Tmixer and a delay loop at 30°C, while the carboxylation reaction occurred at atmospheric pressure in a falling film microreactor (FFMR) (Figure 17). The stream of generated Grignard entered in the top of the FFMR while CO 2 was introduced from the bottom.…”

Flow Technology for Organometallic-Mediated Synthesis

“…Deng and coworkers reported a continuous-flow protocol for synthesizing the industrial relevant precursor 2,4,5-trifluorobenzoic acid 36, used in the manufacture of fluoroquinolone antibiotics, via an unstable aryl-Grignard reagent that reacted with gaseous CO 2 [35].…”