Chemical Synthesis in Flow Reactors

This problem could, evidently, be circumvented by incorporating a supported catalyst within the microreactor. To create a catalyst bed within a microreactor, the device was fabricated from a top block and two etched plates (placed back to back), which enabled a deeper catalyst bed to be achieved (Fig. 14.9). The main channels were 130 pm wide and 50 pm deep and the catalyst bed was 800 pm wide, 100 pm deep and 10 mm long. 

Having elucidated the optimum conditions for the Knoevenagel reaction in a flow reactor, a range of other reactions using different activated methylene derivatives and aldehydes (Table 14.3) was conducted. In all cases excellent product purities and yields were obtained. The reaction of benzaldehyde and ethyl cyanoacetate was also performed using 3-(dimethylamino)propyl-functionalized silica gel, 3-aminopropyl-functionalised silica gel, 3-(l,3,4,6,7,8-hexahydro-2H-pyrimidojl, 2-l]pyrimidino)propyl-functionalized silica gel and polymer-supported diazabicyclo[2.2.2]octane, whereby excellent conversions were obtained ( 99.0%) in all cases [37]. 

The methodology was then applied to acid-catalyzed reactions, namely the synthesis of acetals [38] from a premixed solution of aldehyde or ketone and trimethylorthoformate. The reaction products were subsequently collected and concentrated in vacuo before analysis of the crude product by NMR spectroscopy. As Table 14.4 illustrates, using this approach, excellent product purities and yields were again obtained. 

Having demonstrated the preparation of an array of small organic compounds in high purity and yield, multistep reactions were then conducted by spatially incorporating two supported reagents into a continuous flow reactor. As Fig. 14.11 illustrates, the first step of the reaction consists of an acid-catalyzed acetal deprotection to afford the respective aldehyde and the second step involves the base-catalyzed condensation of the aldehyde with an activated methylene. Using this approach, 100% deprotection of the acetal to aldehyde was observed and 99% conversion of the aldehyde to the desired unsaturated product was observed to an give analytically pure product in 99.6% yield. 

Compared with the use of pressure-driven flow, electroosmotic flow (EOF) is advantageous as it is simple to use, employs no mechanical parts and generates minimal back-pressure the latter is particularly important with respect to the use 

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Photochemistry can potentially provide an environmental-friendly and green approach to chemical synthesis however, the ability to scale-up such photochemical processes is marred with problems, which are mainly associated with the power of light sources. The fact that a large number of microreactors are manufactured in glass, quartz, or transparent polymers is ideal for conducting photochemical processes, as the path length of such reactors is small meaning that it is very easy to irradiate the reaction mixture within the channel. Compared to other examples of chemical synthesis in flow reactors, the number of photochemical transformations performed under flow conditions has until recently been very limited. Early examples included benzopinacol formation [1], synthesis of cycloaddition products [2], and photosensitized diastereodifferentiation [3]. 

Wiles C., Watts P. Enhanced chemical synthesis in flow reactors. Chim. Oggl2009 27(3) 34—36. 

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