Continuous microflow system

Fukuyama T, Rahman T, Kamata N et al (2009) Radical carbonylations using a continuous microflow system. Beilstein J Org Chem 5 No. 34... 

Radical addition to carbon-carbon unsaturated bonds has also been carried out in microflow reactors. Tributyltin hydride-mediated radical reactions of organic halides have been successfully carried out in a continuous microflow system [20]. Rapidly decomposing radical initiators such as V-65 and V-70 are fairly effective and the reactions proceed within a very short period of time. The continuous flow reaction system can be applied to gram-scale synthesis (7.6 g, 185 min) of a key intermediate for furofuran lignans (Figure 5.2). 

The microflow reaction has been successfully applied to a multildlogram synthesis of pristane, a biologically important natural product, which is now widely used as an adjuvant for monoclonal antibody production. The application of a continuous microflow system to the dehydration reaction as the key step can lead to the 5 kg-scale synthesis in 80% overall yield from farnesol (Figure 5.4). Finally, hydrogenation in the presence of 10% Pd/C under a hydrogen atmosphere provides pristine of 99% purity in 50-55% overall yield from farnesol. 

Living cationic polymerization of vinyl ethers initiated by an SnCU/RCl catalytic system can be carried out in a continuous microflow system, which consists of a mutilamination micromixer M (channel width = 40 pm, IMM) and a microtube reactor R (Figure 14.1). A solution of a monomer and RCI is mixed with a solution of SnCU using the micromixer at —78 °C and the resulting mixture was allowed to react in the microtube reactor at the same temperature. For example, isobutyl vinyl ether (IBVE) was polymerized using functionalized initiators to obtain end-functionalized polymers of narrow molecular weight distribution (Mw/M < 1.2) (Scheme 14.4). 

The continuous microflow system was composed of a T-shaped micromixer (i.d. = 500 [xm) and the reactor, two gas/liquid feed stainless tube and an outlet. 

Following similar trials with the formation of diarylbenzenes [63-65], the same research group has reported a multistep synthesis of photochromic diarylethenes using a microflow system that contained two linked micromixers and microreactors (MRi 2) [66]. Similarly to the previously reported linked microreactors, the reactors used in this setup were made of stainless steel tubes and T-shaped micromixers. Initial experiments were conducted in two steps in a continuous sequence to afford symmetrical octasubstitued diaryUiexafluoro cyclopentene (Scheme 29). 

In a detailed process optimization study, the impact of the type of micromixers and process parameters was determined [56]. As a result, a pilot with a Toray Hi-mixer connected to a shell and tube microheat exchanger was constructed. Continuous operation for 24 h was carried out to obtain pentafluorobenzene (PFB) after protonation (92% yield). In this time, 14.7 kg of the product was produced, that is, about 5 t/a. Thus, the industrial-scale production carried out using a batch reactor (10 m3) can be replaced by adding only four microflow systems of the scale investigated. The pilot plant produces 0.5 kg in 6h continuous operation, thus about 730kg/a (see Figure 5.19). The name of the industrial company was not disclosed. 

QCqmlfPFg] [C4C1im][Tf2N] Pd-phosphine carbene complex Pr3N 130-150 °C. Arylation of butyl acrylate with iodobenzene in a microflow-system with continuous recycling of the ionic liquid-catalyst phase product extracted with hexane. [77]... 

Munaf E, Takeuchi T, Ishii D, et al. 1991. Continuous monitoring system for total mercury in waste water by cold vapour atomic-absorption spectrometry and continuous-microflow analysis. Anal Sci 7(4) 605-609. 

The example described above indicates that a numbering-up microflow system consisting of several microtube reactors is quite effective for conducting radical polymerization. Precise temperature control by effective heat transfer, which is one of the inherent advantages of microflow systems, seems to be responsible for the effective control of the molecular-weight distribution. The data obtained with the continuous operation of the pilot plant demonstrate that the microflow system can be applied to relatively large-scale production, and speaks well for the potential of microchemical plants in the polymer industry. 

J. (2006) Radical polymerization using microflow system numbering-up of microreactois and continuous operation. Org. Process Res. Dev., 10 (6), 1126-1131. 

P-Dicarbonyl compounds can be converted to the corresponding fluorinated compounds in formic acid using 10% F2 in N2 in a microflow system by continuous... 

Carbonylation using microreactors is not necessarily restricted to metalradical reactions proceeded more rapidly in a microreactor than in a batch reactor [15]. They also investigated radical carbonylation using a continuous microflow reactor system consisting of a MiChS micromixer... 

As reported by Santos and Metzger [50], Ziegler-Natta polymerization can be carried out in a microflow system coupled directly to the ESI source of a Q-TOF mass spectrometer (Figure 14.12). In the first micromixer, catalyst (Cp2ZrCl2-MAO) and monomer solutions are mixed continuously to initiate the polymerization. The polymerization occurs in the microtube reactor. The solution thus obtained is introduced into the second micromixer M2, where the polymerization is quenched by acetonitrile. The quenched solution is fed directly into the ESI source. The transient cationic species can be characterized by mass spectrometry. This is the first case where an alkyl zirconium cation intermediate in the homogeneous Ziegler-Natta polymerization of ethylene is detected directly. 

More recently, Lowe and coworkers reported a detailed study on the addition of secondary amines to ethyl acrylate and acrylonitrile using a continuous microreaction process based on an IMM micromixer and tabular reactor [16]. In the best case, space-time yields (g/ml h) for the microflow system were much higher than those for the batch system, by a factor of 650. 

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