Synthesis continuous flow

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. 

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... 

Scheme 7. Continuous flow synthesis of the natural product Oxomaritidine...

Baumann M, Baxendale IR, Ley SV, Smith CD, Tranmer GK (2006) Fully Automated Continuous Flow Synthesis of 4,5-Disubstituted Oxazoles. Org Lett 9 1521-1524... 

Figure 25. Schematic illustrating the continuous flow synthesis of 2-phenyl-l,3-dithiane [41],...

Nikbin, N. and Watts, P. (2004). Solid-Supported Continuous Flow Synthesis in Microreactors Using Electroosmotic Flow. OPRand D, 8, 942-944. 

The fact that macroporous, highly cross-linked polystyrene does not swell makes this support particularly interesting for continuous-flow synthesis in columns. This support has also been successfully used as an alternative to CPG for the solid-phase synthesis of oligonucleotides [90,91]. Furthermore, because reagents do not need to penetrate into the polystyrene network, enzyme-mediated reactions should also proceed smoothly on macroporous polystyrene [85]. 

Different forms of silicon dioxide have been used as supports for solid-phase organic synthesis. Silica gel is a rigid, insoluble material, which does not swell in organic solvents. Commercially available silica gel differs in particle size, pore size (typically 2-10 nm), and surface area (typically 200-800 m2/g). Like macroporous, highly cross-linked polystyrene, silica gel enables efficient and rapid transfer of solvents and reagents to its entire surface. Because the synthetic intermediates are only located on the surface of the support, enzyme-mediated reactions can be realized on silica [189,190], Silica gel is particularly well suited for continuous-flow synthesis because its volume stays constant and diffusion rates are high. 

Employing a staked plate microreactor (channel dimensions = 100 pm, total volume = 2 ml), Acke and Stevens (2007) reported the continuous flow synthesis of a series of chromenones via a multicomponent route consisting of a sequential Strecker reaction-intramolecular nucleophilic addition and tautomerization, as depicted in Scheme 2. 

Scheme 32 Schematic illustrating the general reaction conditions employed for the continuous flow synthesis of thiazoles and imidazoles.

Table 30 Summary of the results obtained for the continuous flow synthesis of a spiro lactone 201...

Scheme 73 The continuous flow synthesis of a HIV-1 RTI analog 255 from a-bromoamide 259.

Figure 5 A schematic illustration of a multistep continuous-flow synthesis system for making ZnS-coated CdSe composite particles. Luminescence spectra of uncoated CdSe from CdSe portion and coated particles from the outlet at different flow rates. Labels denote the flow volume of the two syringes for the CdSe and ZnS raw feedstock. Uncoated CdSe nanoparticles were obtained using a flow rate of 100 pi min 1 images reproduced, with permission, from Wang et al, 2004).

Microreactors provide a safe means by which reactions, including multistage schemes, can be undertaken where, otherwise, products involving unstable intermediates may be formed. This is exemplified by Fortt who showed that for a serial diazonium salt formation and chlorination reaction performed in a microreactor under hydrodynamic pumping, significant yield enhancements (15-20%) could be observed and attributed them to enhanced heat and mass transfer [77]. This demonstrates the advantage of microreactor-based synthesis where diazonium salts are sensitive to electromagnetic radiation and static electricity, which in turn can lead to rapid decomposition. Microreactors facilitate the ability to achieve continuous-flow synthesis, which is often not possible with conventional macroscale reactors and batch production. 

FIGURE 8.1 Continuous flow synthesis using microreactor and affinity separation system. Ac, acetyl Bn, benzyl TfO, triflate Troc, trichloroethoxycarbonyl. 

Vagner, J., Kocna, P., and Krchnak, V. (1991) Continuous-flow synthesis of a-ghadin peptides in an ultrasonic field and assay of their inhibition of intestinal sucrase activity. Peptide Res. 4, 284—288. 

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