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

• Published in: Sensors and actuators. B, Chemical Chemical, 2000-05, Vol.63 (3), p.153-158
• Main Authors: Greenway, Gillian M, Haswell, Stephen J, Morgan, David O, Skelton, Victoria, Styring, Peter
• Format: Article
• Language: English
• Subjects: Catalysts; Electroosmosis; Heterogeneous catalysis; Microreactor; Palladium; Porosity; Porous silicon; Silica; Synthesis (chemical); Synthesis design
• ISSN: 0925-4005; 1873-3077
• DOI: 10.1016/S0925-4005(00)00352-X

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. The synthesis 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. A conventional 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.