Biphasic flow system

Figure 4.27 Heck reactions accelerated by biphasic flow system.

As summarized in this chapter, various synthetic protocols have made advantageous use of biphasic liquid-liquid systems in microreactors. Apart from reaction optimization and acceleration of processes, the application of biphasic flow systems has already led to the development and design of novel protocols, and it is expected that this area of research will grow in future. 

The synthesis of 3,3-disubstituted 2-oxindoles by palladium-catalyzed a-arylation/alkylation sequences in a biphasic flow system has been achieved by Buchwald et al. [44]. The reaction sequence consisted of two steps, the arylation followed by the alkylation. The first reaction system contains the substrate and aryl halide in toluene in one solution, the second the pre-catalyst in toluene, and a third solution containing potassium hydroxide and tetrabutyl ammonium bromide (TBAB) (Scheme 8.11). This is then mixed in a packed-bed mixer and heated to 100 °C for arylation. This system is then fed into a second T-piece where the alkyl halide is introduced, further mixing is applied in the second packed-bed reactor for the alkylation. This product mixture is then quenched with monosodium phosphate and extracted with ethyl acetate. The overall reaction proceeded in a 93% yield and could also be stopped at the arylation step by the addition of a switch valve before the alkylation step. Palladium-catalyzed hydrogenations have also been investigated under organic/aqueous biphasic conditions and an enhancement has been observed when using polymeric encapsulation [45]. 

The more important physical aspects of the flow of gas -containing systems are analyzed for a uni-phase and a biphase flow. Equations are developed for a qualitative description of these systems. 

Hydroformylations were also carried out in IL/SCCO2 biphasic reaction systems [7]. In particular, it was demonstrated that continuous-flow systems could be operated successfully for the Rh-catalysed hydroformylation of hex-I-ene [24] and I-dodecene [25]. 

The biphasic solvent system composed of PEG and scC02 is ideally suited for the lipase-catalyzed acylation of alcohols, both batch and continuous-flow acylations are possible (Scheme 3.1) [14]. 

In rhodium catalysed hydroformylation reactions, conversions achieved using a biphasic system were lower than those achieved in pure ionic liquid 40% in [Bmim][PF6]-scC02 99% in [Bmim][PF6] alone.However, the selectivity of linear to branched isomer was reversed and therefore these results were highly significant. This approach led to the development of a continuous-flow system for hydroformylation of alkenes, and under careful control the system could be used for several weeks without any visible sign of catalyst degradation. It should be noted that biocatalysts have also been used and recycled using biphasic ionic-liquid-carbon dioxide approaches. 

In analytical procedures with two immiscible aqueous phases, the traditional organic solvents used in LLE can be replaced by nontoxic, nonflammable and nonvolatile solvents [154,155,197], The feasibility of implementing aqueous biphasic extraction in flow analysis was recently demonstrated by the fluorimetric determination of lead by reaction with 8-hydroxyquinoline-5-sulfonic acid [198]. The flow system was rugged and the interface formed between the different aqueous plugs acted as an extraction (enrichment) and reaction interface. This innovation is environmentally friendly as it relies on the utilisation of two immiscible phases that are intrinsically aqueous. 

C.I.C. Silvestre, S. Rodrigues, J.L.M. Santos, J.L.F.C. Lima, E.A.G. Zagatto, Exploitation of a single interface flow system for on-line aqueous biphasic extraction, Talanta 81 (2010) 1847. 

The biphasic SCCO2/IL separation concept was further extended to the hydro-formylahon of an aUcene in a continuous-flow system [35]. The active rhodium complex was immobilized in the IL [BMIM][PFg] with the help of the modified phosphine [l-propyl-3-methylimidazoliumj2[PhP(C5H4S03-3)2 and investigated for the hydroformylation of 1-octene. In this continuous-flow process the substrate, gases, and products were transported in and out of the reactor dissolved in SCCO2. The catalyst system exhibited a constant rate of more than 20 h with a rhodium metal content of less than 1 ppm in the collected product. 

Similar results were recently published for the continuous-flow gas-phase hydroformylation of propene [51]. This time, the supported system was prepared by direct impregnation of an unmodified silica gel with methanol solution containing [Rh(CO)2(acac)j, the ligand, and the IL. The sulfonated xantphos used in this investigation must be added in large excess (10-20 equiv. per Rh) to afford the expected selectivity for the linear aldehyde n/i = 16.9). The performance of the optimized catalytic support remains stable up to 5 h before a decrease in activity and selectivity was observed. This work was also completed using other ligands derived from the series developed in classical biphasic IL systems, and applied to the continuous hydroformylation of propene and 1-octene [52]. 

Biphasic microflow systems allow the product flow to be separated from the electrolyte flow in order to eliminate work-up steps and to allow recycling of electrolyte [49]. Finally, a salt cell design was suggested with supporting electrolyte present as a separate phase to allow redox processes even in humidified hexane [50]. 

Applications of microreactors to biphasic catalytic reactions constitute a topac of interest. The benefits of having an exceedingly high surface-to-volume ratio and efficient mass-transfer in microchannels have led many researchers to study continuous flow systems using microreactors for catalytic reactions. The excellent mass transfer characteristics within and between the catalyst carrier phase and reaction medium, together with the minimal catalytic pore diffusion resistances at the micrometer scale, make such biphasic catalysis an attractive alternative to conventional catalysis operation (Wieflmeier, 1996 Rahman et al., 2006). 

Differential shock Differential shock, like thermal shock, occurs in biphase systems. It can occur whenever steam and condensate flow in the same line, but at different velocities, such as in condensate return lines. 

In biphase systems velocity of the steam is often 10 times the velocity of the liquid. If condensate waves rise and fill a pipe, a seal is formed with the pressure of the steam behind it (Fig. 2). Since the steam cannot flow through the condensate seal, pressure drops on the downstream side. The condensate seal now becomes a piston accelerated downstream by this pressure differential. As it is driven downstream it picks up more liquid, which adds to the existing mass of the slug, and the velocity increases. 

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