A Microreactor for Microwave-Assisted Capillary (Continuous Flow) Organic Synthesis

Abstract

A capillary-based flow system has been developed for conducting microscale organic synthesis with the aid of microwave irradiation. The capillary internal diameter investigated ranged from 200 to 1200 mum, while the flow rate was varied between 2 and 40 muL/min, which corresponds to the sample being irradiated approximately 4 min. Other parameters investigated include reaction concentration and power setting of the microwave. Excellent conversion was observed in a variety of cross coupling and ring-closing metathesis (RCM) reactions employing metal catalysts and in nucleophilic aromatic substitution and Wittig reactions that do not employ metals. Reactions that have solids in them do not seem to pose a significant concern for the method, such as blocked channels. It was shown that capillaries coated internally with thin films of Pd metal show tremendous rate accelerations and that the thin films themselves are capable of catalyzing Suzuki-Miyaura reactions with no exogenous catalyst added. Importantly, it has been demonstrated that reagents in separate syringes can be coinjected into the capillary, mix, and react with none of the laminar flow problems that plague microreactor (lab on a chip) technology. This paves the way to use microwave-assisted, flow capillary synthesis as a powerful and efficient means to replace "one-at-a-time" microwave synthesis to provide libraries of compounds in a scale suitable for biological screening purposes.

Microwave-assisted Cu-catalyzed Ullmann ether synthesis in a continuous-flow milli-plant

“…Copper catalyst leaching for both reactors appeared to be only significant after 24 h on-stream and this could partially be avoided by thermal treatment of the reactor after each cycle. Up to 60 % yield could be obtained using the Cu/ZnO wall-coated reactor for two 25 consecutive runs without there being a significant activity drop if a thermal pre-treatment of the reactor (350 o C for 24 h) was undertaken prior to testing. The Cu/TiO 2 fixed-bed reactor showed lower yields due to catalyst leaching, however reactor productivities of up to 55 kg prod /(m R 3 •h) suggested a better performance than the Cu/ZnO wall-coated reactor.…”

“…The authors employed the concepts of "Novel Process Windows", as introduced by Hessel et al, and discussed the multiple opportunities for operating and controlling organic reactions at elevated temperatures and pressures [22,23]. Organ and co-workers also contributed to state-of-art microwave-assisted capillary-type flow-reactors for metal-catalyzed organic reactions [24,25]. Many examples have been reported of dedicated flow systems being used in combination with microwave heating for large-scale synthesis and industrial applications [26].…”

Microwave Apparatus for Kinetic Studies and in-situ Observations in Hydrothermal or High-Pressure Ionic Liquid System

“…Figures 2 and 3 show cover shot of the setup and photograph of high pressure vessel (2 ~ 6 in Figure 1), respectively. The setup consists of a multimode microwave generator (1) -Reactor, SMW-087, 2.45 GHz, maximum power 700 W, Shikoku Keisoku, Takamtsu, Japan) with a K-type thermocouple (2), a stirring system (5 and 15), a control box (16:, a high pressure reactor (consists of 3, 4, 6 and 7), a pressure gauge (8), an inert gas (Ar or N2) cylinder (13), a cooling water tank (18) and a vacuum pump (14). The reactor was composed of an inner thick-wall Pyrex glass tube (4: HPG-10, volume 10 ml, maximum supporting pressure 10 MPa, TaiatsuTechno.…”

“…There have been many papers on microwave-assisted organic synthesis [1,[5][6][7][8][9] and only a limited number of studies have been reported about biomass conversion into a chemical block [10][11][12][13] . Here, we introduce four experimental results of biomass conversion in hydrothermal condition and ionic liquid systems.…”

Reproducibility and Scalability of Microwave-Assisted Reactions

“…The combination of composite-based flow-through reactors with microwave irradiation may lead to new and effective methods to scale up organic reactions. Recently, Organ has prepared highly porous Pd films composed of nanometer-sized particles (Comer & Organ, 2005). These Pd films served as an excellent catalyst for Heck reactions under continuous flow microwave conditions.…”