The use of a novel microreactor for high throughput continuous flow organic synthesis

The aim of this study was to investigate the performance characteristics of a flow injection microreactor with reference to both the chemistry and reactor design using a model system, the established synthesis of 4-cyanobiphenyl based on a modified Suzuki coupling of an aryl halide and an organoboron compound. The catalytic reaction was carried out in micro-channels (300 μm wide and 115 μm deep) etched into glass and sealed with a top plate. The mobility of the reagent solutions was achieved using electroosmotic flow (EOF) assisted by the incorporation of a microporous silica structure within the microreactor channels, which acted as both a micro-pump and an immobilisation technique for the catalyst bed (1.8% palladium on silica). The yield of 4-cyanobiphenyl was determined by GC–MS. nthesis of 4-cyanobiphenyl at room temperature in a flow injection microreactor, using a supported catalyst, without the addition of a base gave a product yield of 67±7% (n=6). This was achieved by injecting 4-bromobenzonitrile for 5 s, with a 25-s injection interval, into a continuous stream of phenylboronic acid. A series of injections were performed over a 25-min period and the product collected for analysis. Palladium contamination in the crude product was found to be in the range of 1.2–1.6 ppb, determined using ICP–MS, indicating a low leach rate from the immobilised catalyst. entional laboratory batch scale method was also performed for the same synthesis using the identical conditions as those used in the flow injection microreactor, with and without the addition of a base, at both room and elevated temperatures (75–80°C) in an inert atmosphere under reflux for 8 h. The product yield for the non-optimised bulk reaction was 10% (determined by GC–MS), significantly lower than with the flow injection microreactor illustrating the potential of microreactors for clean efficient synthesis.