Continuous flow chemistry

J. K., Lane, W., Mathewson, A., Berney, H., Application of magnetohydrodynamic actuation to continuous flow chemistry, Lab Chip 2002, 2, 224-230. 

There is considerable interest in continuous-flow chemistry at the present time, for rapid analog synthesis in medicinal chemistry in addition to scale-up. A true continuous-flow microwave reactor is available in the Milestone FlowSYNTH... 

This chapter is an overview of recent advances that continuous flow chemistry can offer for heterocyclic chemistry. Our discussion is however not an exhaustive sampling of aU known examples but rather a compilation of various examples to illustrate the principles, features, and advantages of flow chemistry. 

For recent reviews on continuous flow chemistry, see (a) Wegner, J., Ceylan,... 

The Heck-Matsuda reaction has also been subjected to continuous flow chemistry conditions, as reported by Wirth et al. [100]. The reaction that was studied involved the reaction between an in situ generated diazonium ion and/r-fluorostyrene to give ( )-/ -fluorostilbene (Scheme 1.35) and the device used by this group relied on a segmented flow (liquid-liquid slug flow) to increase reaction rates in microfluidic flow. They used perfluorodecalin as an inert and immiscible liquid spacer. 

An important analytical application of enzymatic microreactors is their use in biocatalysis, in order to transform a difficult-to-measure analyte into an easily measurable form. This could be represented by microreactors designed for digestion of proteins to convert them to more readily measured peptides. Applications of microreactors in continuous-flow chemistry have expanded rapidly over the past two decades, with numerous reports of higher conversions and yields compared to conventional batch equipment. In this chapter, a comprehensive discussion on the most recent trends in the development of enzymatic microreactors and their current applications are covered. 

Intensification of processes, for instance using continuous (flow) chemistry to improve space-time yields from manufacturing plants Development and industrialisation of biocatalysts to improve process metrics e.g. by obviating the need for protecting groups) or enable novel routes to APIs or intermediates... 

Kockmann, N., Gottsponer, M., Zirrunermann, B., and Roberge, D.M. (2008) Enabling continuous-flow chemistry in microstructured devices for pharmaceutical and flne-chemical production. Chem. Eur. J., 14,... 

Hebrault, D. (2014) New Continuous Flow Chemistry Webinar - Recent Advances in Organic Chemistry Part 8. Available from http //us.mt.com/us/en/home/events/ webinar/ondemand/continuous-flow-chemistry-II-organic-chemistry.html [accessed 10 November 2014]. 

A limited overview of the process chemistry used at these sites is presented. This paper will also attempt to bridge, at least partly, the gap between ongoing fundamental plutonium research and development and applied technology needs. We believe it is important to bridge this gap, since a continuous flow of knowledge about plutonium chemistry from academic and government laboratories to the plant is necessary and beneficial... 

Micro reactors are continuous-flow devices consuming small reaction volumes and allowing defined setting of reaction parameters and fast changes. Hence they are ideal tools for process screening and optimization studies to develop solution-based chemistries. 

Boleininger, J., Kurz, A., Reuss, V. and Sonnichsen, C. (2006) Microfluidic continuous flow synthesis of rod-shaped gold and silver nanocrystals. Physical Chemistry Chemical Physics, 8, 3824-3827. 

Gunasingham, H. and Fleet, B., Hydrodynamic voltammetry in continuous-flow analysis, in Electroanalytical Chemistry A Series of Advances, Vol. 16, Bard, A. J., Ed., Marcel Dekker, New York, 1989, 89. 

Figure 7.9 Continuous-flow H NMR spectrum (400 MHz) of diallylphthalate in supercritical carbon dioxide (flow-rate 2mLmin 1, pressure approximately 136 bar, and temperature 321 K). After Richter et al. [153]. Reprinted with permission from B.E. Richter et al., Analytical Chemistry, 68, 1033-1039. Copyright (1996), American Chemical Society...

Leckrone, K. J. and Hayes, J. M. (1998) Water induced errors in continuous flow carhon isotope ratio mass spectrometry. Analytical Chemistry 70, 2737 2744. 

Reaction scale-up using the Voyager system in genuine continuous-flow format is achieved by the use of special coiled flow-through cells. The reaction coils are made of glass or Teflon (Fig. 3.24) with a maximum flow rate of 20 mL min-1 and operational limits of 250 °C or 17 bar. The continuous-flow format should only be used for homogeneous solution-phase chemistry, as slurried mixtures may cause prob-... 

Recently published examples of continuous-flow organic microwave synthesis include, for example, 1,3-dipolar cydoaddition chemistry in the CEM CF Voyager system (see Figs. 3.23 and 3.24). The cycloaddition of dimethyl acetylenedicarboxy-late with benzyl azide in toluene was first carefully optimized with respect to solvent, temperature, and time under batch conditions. The best protocol was then translated to a continuous-flow procedure in which a solution 0.33 m in both build-... 

Figure 6.30. Schematic diagram of a reactor used continuously for up to 500 h for fluorous biphasic reactions without gaseous reagents. [81] (A. Yoshidaetal, Development of the continuous-flow reaction system based on the Lewis acid-catalysed reactions in a fluorous biphasic system, Green Chemisty, 5, (2003), 555) Reproduced by permission of The Royal Society of Chemistry.

Various approaches to the analysis of dissolved silicon have been tried. Most of them are based on the formation of /J-molybdosilic acid [ 199-203 ]. Dissolved silicon exists in seawater almost entirely as undissociated orthosilicic acid. This form and its dimer, termed reactive silicate , combine with molybdosilicic acid to form a- and /I-molybdosilicic acid [180]. The molybdosilicic acid can be reduced to molybdenum blue, which is determined photometrically [206]. The photometric determination of silicate as molybdenum blue is sufficiently sensitive for most seawater samples. It is amenable to automated analysis by segmented continuous flow analysers [206-208]. Most recent analyses of silicate in seawater have, therefore, used this chemistry. Furthermore, reactive silicate is probably the only silicon species in seawater that can be used by siliceous organisms [204]. 

Nikbin N, Watts P (2004) Solid-supported continuous flow synthesis in micro-reactors using electroosmotic flow. Org Process Res Dev 8 942 Overbeek JTG (1952) Electro chemistry of double layer. In Kruyt HR (ed) Colloid science, Vol. 1. Elsevier, Amsterdam... 

One of the obvious areas where flow chemistry comes into its own is in the arena of catalysed reactions and continuous processing. An excellent example of this is the Suzuki reaction (for recent reviews on the Suzuki Cross-Coupling reaction, see Miura 2004 Beilina et al. 2004 ... 

---