Microflow systems temperature

Yoshida and coworkers also developed a microreaction system for cation pool-initiated polymerization [62]. Significant control of the molecular weight distribution (Mw/Mn) was achieved when N-acyliminium ion-initiated polymerization of butyl vinyl ether was carried out in a microflow system (an IMM micromixer and a microtube reactor). Initiator and monomer were mixed using a micromixer, which was connected to a microtube reactor for the propagation step. The polymerization reaction was quenched by an amine in a second micromixer. The tighter molecular weight distribution (Mw/M = 1.14) in the microflow system compared with that of the batch system (Mw/M > 2) was attributed to the very rapid mixing and precise control of the polymerization temperature in the microflow system. 

Figure 5.1 Aminocarbonylation of halobenzene by microflow system at elevated temperatures and pressures. Copyright Wiley-VCH Verlag GmbH Co. KGaA. Reproduced with permission...

The bromine-lithium exchange reaction of o-dibromobenzene is usually carried out at — 110°C or below in flask chemistry because the elimination of LiBr to form benzyne is very fast even at — 78 °C. However, by reducing the residence time using a microflow system, the reaction can be conducted at —78°C and o-bromophenyllithium can be effectively trapped with an electrophile before decomposition. Figure 6.23 shows a schematic diagram of the microflow system, in which reactions using methanol as an electrophile are conducted with varying temperatures and flow rates. 

When the reaction was performed on a 100 mg scale, the diene was obtained in 55% yield as a mixture of ( )- and (Z)-stereoisomers. However, when the scale was increased to lOOg, various by-products, such as cyclized products or alkyl group-migrated compounds, were produced presumably because of acid-catalyzed reactions of the diene. The formation of such by-products can be reduced using a microflow system composed of a micromixer and a microtube reactor. Thus, a solution of the allylic alcohol in tetrahydrofuran (THF) was mixed with a solution of p-toluenesulfonic acid (p-TsOH) in THF/toluene at 90 °C. After the reaction mixture was allowed to flow for 47 s, the reaction was quenched with a saturated NaHCOs solution at room temperature. In this case the desired diene was obtained in 80% yield. It is noteworthy that the acid-mediated by-products were not detected. This process was applied to the synthesis of pristane, a biologically important natural product that is widely used as an adjuvant for monoclonal antibody production. 

In this section, we discuss the cases where the use of microflow reactors allows us to conduct reactions under unconventional conditions, such as high temperatures, which significantly accelerate the rates of the reactions. In the macrobatch processes, however, the use of such reaction conditions may cause undesirable side reactions, such as the decomposition or subsequent reactions of products. Precise temperature control and short residence time, which minimize the consecutive side reactions, are responsible for successful reactions in microflow systems. 

As shown in Figure 8.13, the reaction of an acid fluoride and an amine, which are derived from the corresponding amino acids, in the presence of N-methylmorpholine has been carried out at several temperatures. The reaction was complete in 3 min at 90 °C, and the yield of the dipeptide was excellent. Reaction at higher temperatures and/or for a prolonged period leads to a decrease in the yield of the dipeptide and an increase in the yield of the tripeptide. Residence-time control in a microflow system is quite effective in reducing the amount of undesired tripeptide byproducts. Some other examples, which are combined with fluorous tag technology, " are shown in Scheme 8.12. In the first case, the reaction was complete in 3 min at 90 °C, whereas the corresponding conventional... 

Scheme 8.12 Synthesis of peptides using a microflow system at high temperatures...

The polymerization can be restarted when the same or a different monomer is added. The use of a different monomer leads to block copolymerization. Within the short residence time in a microflow system at low temperature, the polymer chain was really living. In fact, block copolymerization by adding the second monomer in the microflow system has already been achieved by using a strong proton acid, such as trifluoromethanesulfonic acid (TfOH), as an initiator in a microflow system (see Section 9.4.8). 

Polymerization of benzyl methacrylate (BMA) is much slower than that of BA. Although the yield of the polymer increased with an increase in the residence time, the polymerization did not complete within 12 min. The value of M /Mn was much smaller than that for BA, both in the microflow system and the macrobatch system. The effect of the microflow system on molecular-weight distribution control is, however, smaller than for the BA case. Probably, temperature control for BMA polymerization is better than that for BA polymerization, even in the macrobatch system, because heat generation per unit time for BMA polymerization seems to be much less than that for BA polymerization. 

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. 

Microflow systems serve as effective environments to perform various oxidation reactions using chemical reagents. The oxidation using dimethyl sulfoxide (DMSO), which is known as Moffatt-Swern type oxidation, is one of the most versatile and reliable methods for the oxidation of alcohols into carbonyl compounds in laboratory synthesis [1, 2]. However, it is well known that activation of DMSO leads to an inevitable side-reaction, Pummerer rearrangement, at temperatures above — 30°C (Scheme 7.1). Therefore, the reaction is usually carried out at low temperatures (—50 °C or below), where such a side-reaction is very slow [3, 4]. However, the requirement for such low temperatures causes severe limitations in the industrial use of this highly useful reaction. The use of microflow systems solves the problem. For example, the oxidation of cyclohexanol can be accomplished using a microflow... 

Oxidation of primary, secondary, cyclic and benxylic alcohols and cyclohexanol also takes place smoothly to give the corresponding carbonyl compounds in good yields and selectivities (Table 7.1). A dramatic effect of the microflow system seems to be attributable to precise temperature control and extremely fast mixing by virtue of a short diffusion path. A short residence time by fast transfer of the reactive intermediate to the next reactor also seems to be essential for the success of the... 

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). 

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