Flow Mode Synthesis

There are many reasons why chemical synthesis is advantageously performed in flow mode using a micro-contactor (or microreactor) rather than in a round-bottomed flask, well or vessel. In fact, if it was not for a long history of batch mode chemistry and the convenience of a handsized flask, the case would need to be made for employing batch methods. 

The most important paper to date on multistep synthesis in flow mode is the total synthesis of ( )-oxomaritidine, 81 [89]. This compound has been previously synthesized by our group in five steps and in 62% overall yield using only... 

Figure 1.20 Reconstructed ion chromatograms (RIC) of [M + H]+ species at m/z 240 (acetaldehyde-PFB-derivatives), m/z 266 ([M + H —18]+ ion of acetoin-PFB-derivatives), m/z 282 (diacetyl mono-PFB-derivatives), m/z 336 (IS-PFB-derivatives) and m/z 477 (diacetyl di-PFB-derivatives) of a Merlot wine at the first day of MLF (a), and after 5 days of MLF (b). Analytical conditions polyethylene glycol) (30m x 0.25 mm i.d. df 0.25 juim) fused silica capillary column programmed oven temperature 5 min at 60 °C, 3°C/min to 210 °C, 5 min at 210°C transfer line temperature 280 °C carrier gas He flow mode constant pressure 16psi. (Reprinted from Journal of Mass Spectrometry 40, Flamini et al., Monitoring of the principal carbonyl compounds involved in malolactic fermentation of wine by synthesis of 0-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine derivatives and solid-phase-microextraction positive-ion-chemical-ionization mass spectrometry analysis, p. 1563, Copyright 2005, with permission from John Wiley Sons Ltd)...

For examples of organocatalyzed reactions carried out under the continuous-flow mode see (a) Ishiara, K., Hasegawa, A. and Yamamoto, H. (2002) Synlett, 1296-8. (b) Briinjes, M., Sourkouni-Argirusi, G. and Kirschning, A. (2003) Advanced Synthesis Catalysis, 345, 635—42. 

Batchwise solid-phase synthesis, the original procedure of SPPS developed by Mer-rifield in 1966. Alternatively, SPPS can also be performed in a continuous-flow mode solid-phase peptide synthesis using resin-flUed columns. 

Macrostructure of "plan front" is optimal (dominant) under fast chemical processes ("knowhow") and corresponds to the quasi-plug-flow mode in turbulent flows. This structure of liquid flows mixing provides effective heat- and mass-exchange under not only fast chemical (polymerization, low-molecular products synthesis), but also mass-transfer physical processes (mixing, dispersion, extraction, etc.). 

Assabumrungrat S, Phongpatthanapanich J, Praserthdam P, Tagawa T and Goto S (2003), Theoretical study on the synthesis of methyl acetate from methanol and acetic add in pervaporation membrane reactors effect of continuous-flow modes , Chem EngJ, 95,57-65. 

A cell-free extract (S30) from E. coli K12 has been developed as an efficient coupled transcription/translation system which performs protein synthesis in vitro from the genes cloned in plasmids under the T7, T3, or SP6 promoter. Capping of the mRNA for eukaryotic proteins is apparently unnecessary with the S30 system. The coupled transcription/translation system, which was originally developed as the S3 0 translation system (122), can be used in a batchwise or continuous-flow mode (123,124). Use of the ribosome fraction collected from the S30 extracts is reported to improve the yield and efficacy further and more advantageously with nonlinearized plasmids than with linearized plasmids (125). 

Microfluidic devices allow for processing small volumes (10" to rnS) of fluid within channels and are compatible with continuous flow mode of operation (Fernandes, 2010). Hence, the use of microscale devices in preparation of ionic liquids is potentially as green as chemical synthesis can be as reagents are quantitatively converted into the final product, no solvents are needed for synthesis or purification and absolutely no waste is generated (Ehrfeld et al, 2000). Wikns et al. (2009) repwrted that less than 1 % of impurities, mostly unreacted starting material, are present in ionic fiquids synthesized within microfluidic devices. Hu et al. (2010) showed that microchannel reaction system is also suitable for the kinetic study of fast reactions with high heat release and/ or a viscous system, such as alkylation of imidazolium species. 

As C-C bond formation is an important step in organic synthesis, particularly for pharmaceutical applications, it is useful to look for operation modes of chemical micro processing that allow one to carry out combinatorial chemistry investigations. As such, the serial introduction of multiple reactant streams by flow switching was identified [66,67]. The wide availability of precursors for acyiiminium cations has led to the expression cation pool [66, 67]. 

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