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 rea ctor design using a model system, the established synthesis of 4-cyanobiphe nyl based on a modified Suzuki coupling of an aryl halide and an organoboro n compound. The catalytic reaction was carried out in micro-channels (300 m u m wide and 115 mu m deep) etched into glass and sealed with a top plate. The mobility of the reagent solutions was achieved using electroosmotic flo w (EOF) assisted by the incorporation of a microporous silica structure wit hin the microreactor channels, which acted as both a micro-pump and an immo bilisation technique for the catalyst bed (1.8% palladium on silica). The y ield of 4-cyanobiphenyl was determined by GC-MS. The synthesis of 4-cyanobiphenyl at room temperature in a flow injection mi croreactor, 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-bro mobenzonitrile for 5 s, with a 25-s injection interval, into a continuous s tream of phenylboronic acid. A series of injections were performed over a 2 5-min period and the product collected for analysis. Palladium contaminatio n in the crude product was found to be in the range of 1.2-1.6 ppb, determi ned using ICP-MS, indicating a low leach rate from the immobilised catalyst . A conventional laboratory batch scale method was also performed for the sam e synthesis using the identical conditions as those used in the flow inject ion microreactor, with and without the addition of a base, at both room and elevated temperatures (75-80 degrees C) in an inert atmosphere under reflu x for 8 h. The product yield for the non-optimised bulk reaction was 10% (d etermined by GC-MS), significantly lower than with the flow injection micro reactor illustrating the potential of microreactors for clean efficient syn thesis. (C) 2000 Elsevier Science S.A. All rights reserved.