In this section we propose a selection of articles from some of the major scientific publications, aimed at updating the topic of:
Flow Chemistry and Microreactors

Using Anilines as Masked Cross-Coupling Partners: Design of a Telescoped Three-Step Flow Diazotization, Iododediazotization, Cross-Coupling Process

The conversion of commercially available anilines into biaryl and biarylacetylene products was realized by using a telescoped, three-reactor flow diazotization/iododediazotization/cross-coupling process. The segmented flow stream created by off-gassing during the Sandmeyer sequence was restored to a continuous column of reaction solution by using a specially designed continuous-flow unit controlled by custom software created in-house. The resultant aryl iodide was then combined with a stream of cross-coupling solution that fed into the final reactor. The system proved versatile as modifications to the diazotization/iododediazotization sequence could be made rapidly to account for any substrate specificity (e.g., solubility problems), leading to a wide substrate scope of Suzuki-Miyaura and Sonogashira cross-coupled products.

Source: Teci M. et al. Chemistry. 2016 Nov 21;22(48):17407-17415.
DOI: 10.1002/chem.201603626

Thermomyces lanuginosus lipase-catalyzed synthesis of natural flavor esters in a continuous flow microreactor

Enzymatic catalysis is considered to be among the most environmental friendly processes for the synthesis of fine chemicals. In this study, lipase from Thermomyces lanuginosus (Lecitase Ultra™) was used to catalyze the synthesis of flavor esters, i.e., methyl butanoate and methyl benzoate by esterification of the acids with methanol in a microfluidic system. Maximum reaction rates of 195 and 115 mM min^-1 corresponding to catalytic efficiencies (k _cat/K _M) of 0.30 and 0.24 min^-1 mM^-1 as well as yield conversion of 54 and 41 % were observed in methyl butanoate and methyl benzoate synthesis, respectively. Catalytic turnover (k _cat) was higher for methyl butanoate synthesis.
Rate of synthesis and yield decreased with increasing flow rates. For both esters, increase in microfluidic flow rate resulted in increased advective transport over molecular diffusion and reaction rate, thus lower conversion. In microfluidic synthesis using T. lanuginosus lipase, the following reaction conditions were 40 °C, flow rate 0.1 mL min^-1, and 123 U g^-1 enzyme loading found to be the optimum operating limits. The work demonstrated the application of enzyme(s) in a microreactor system for the synthesis of industrially important esters.

Source: Gumel A.M. et al.  3 Biotech. 2016 Jun;6(1):24.
DOI: 10.1007/s13205-015-0355-9

Oscillatory multiphase flow strategy for chemistry and biology

Continuous multiphase flow strategies are commonly employed for high-throughput parameter screening of physical, chemical, and biological processes as well as continuous preparation of a wide range of fine chemicals and micro/nano particles with processing times up to 10 min. The inter-dependency of mixing and residence times, and their direct correlation with reactor length have limited the adaptation of multiphase flow strategies for studies of processes with relatively long processing times (0.5-24 h). In this frontier article, we describe an oscillatory multiphase flow strategy to decouple mixing and residence times and enable investigation of longer timescale experiments than typically feasible with conventional continuous multiphase flow approaches. We review current oscillatory multiphase flow technologies, provide an overview of the advancements of this relatively new strategy in chemistry and biology, and close with a perspective on future opportunities.

Source: Abolhasani M. et al. Lab Chip. 2016 Jul 19;16(15):2775-84.
DOI: 10.1039/c6lc00728g

1,6-Conjugate addition of zinc alkyls to para-quinone methides in a continuous-flow microreactor

An efficient method for the synthesis of alkyl diarylmethanes through the 1,6-conjugate addition of dialkylzinc reagents to para-quinone methides (p-QMs) has been developed under continuous flow conditions using a microreactor. This protocol allows to access unsymmetrical alkyl diarylmethanes in moderate to excellent yields using a wide range of p-QMs and dialkylzinc reagents. Interestingly, this transformation worked well without the requirement of a catalyst.

Source: Jadhav AS et al. Org Biomol Chem. 2016 Dec 20;15(1):56-60.
DOI: 10.1039/c6ob02277d