Disguised chemical selectivity

How does a reaction take place when it proceeds faster than mixing What kinds of problems are encountered when extremely fast reactions are conducted by mixing two reaction components It is known that when the reaction is faster than mixing, product selectivity of the reaction is often not determined by the kinetics, but by the manner of mixing. Of course, if only one product can be produced under any conditions, there is no problem of product selectivity. However, if there is a possibility that two or more products are produced by competing reactions, we have to consider the product selectivity. There are, in principle, two cases for competing reactions, i.e. competitive parallel 

In competitive parallel reactions, the reaction of compound A to give product PI competes with the reaction of A to give product P2. Both reactions take place simultaneously. If the rate constant ki for the first reaction is much larger than 2 for the second reaction, we expect the predominant formation of PI over P2. 

This type of reaction scheme is fairly common in organic synthesis. If the second reaction is faster than the first reaction ( i 2)j h is difficult to stop the reaction at the first stage. P2 is formed as a major product. If the first reaction is faster than the second reaction ki 2) there is a chance to obtain PI selectively. When one equivalent of A relative to B is used, PI should be obtained selectively. In other words, when the stoichiometric ratio of two reaction components is approximately unity (A/B = 1), the selectivity for the primary product PI should be high. Experiments, 

Why is such disguised selectivity observed for extremely fast reactions Rys explained it as follows  

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There is another way to solve the problem of disguised chemical selectivity of extremely fast competitive reactions, which does not need to slow the reactions, i.e. micromixing, based on microstructures that makes the diffusion path very short. 

In a previous section (Section 6.1.3), we discussed the problem of disguised chemical selectivity for extremely fast competitive consecutive reactions. This problem could be solved using micromixers, in which the mixing takes place in a very short period by virtue of a small diffusion path caused by the microstructure. Friedel-Crafts alkylation using N-acyliminium ion pools provides a nice example of the effectiveness of micromixing. 

Disguised Chemical Selectivity in Competitive Parallel Reactions... 

Disguised chemical selectivity of competitive parallel reactions caused by slower mixing has been discussed by Rys based on the eddy model as follows ... 

Micromixers are the key elements of microflow systems for flash chemistry because extremely fast mixing is essential for conducting an extremely fast reaction between two reaction components As described in Chapter 6, the conventional approach to mixing often leads to disguised chemical selectivity. Fast mixing by virtue of a short diffusion path in... 

Therefore, the observed selectivity is the disguised chemical selectivity caused by an extremely fast reaction. The reaction using a microflow system, however, gives rise to a dramatic increase in the product selectivity. The monoalkylation product was obtained in excellent selectivity and the amount of dialkylation product was very small. In this case, a solution of the N-acyliminium ion and that of trimethoxy-benzene are introduced to a multilamination-type micromixer at —78°C and the product solution leaving the device was immediately quenched with triethylamine in order to avoid the consecutive reactions. Extremely fast 1 1 mixing using the micromixer and efficient heat transfer in the microflow system seem to be responsible for the dramatic increase in the product selectivity. 

The outcome of the reaction with heteroaromatic compounds is also affected by the manner of mixing. For example, the reaction with thiophene using a microflow system took place smoothly to give the monoalkylation product exclusively, while the reaction in a macrobatch reactor gave a significant amount of the dialkylation product. A similar tendency was also observed for the reaction of furan and N-methylpyrrole. These results indicate that the reactions with such heteroaromatic compounds also suffer from the problem of disguised chemical selectivity... 

Both the reaction of an initiator (In) with a monomer (M) and the reactions of propagating polymer (Pn) with a monomer (M) are very fast (Scheme 9.8). Therefore, we have to consider the possibility of disguised chemical selectivity, which is observed for Friedel-Crafts reactions of reactive aromatic compounds and a cation pool. If mixing is slow, the consecutive propagation reactions take place before all of the initiators react with monomers, even if the consecutive propagation reactions are slower than the initiation reaction. This is also an example of disguised... 

Increasing the reaction rate further increases the effect of the laminar flow width, or the diffusion time. Table 7.3 shows the results of CFD simulations carried out with the rate constant ki of 10 LmoF s and the rate constant 2 of 10" LmoF s. The selectivity under ideal mixing is the same as described above, whereas the selectivity is reversed to 25 75 with the laminar flow width of 100 am, apparentiy due to disguised chemical selectivity. With the laminar flow width of 25 pm, the selectivity becomes substantially 1 1. With the laminar flow width of 2.5 pm, however, the selectivity is 95 5, which is close to the selectivity based on the kinetics. 

Like Friedel-Crafts reactions, halogenation such as bromination and iodination of aromatic compounds are classified as electrophilic aromatic substitution reactions. Bromine and iodine substituents are weakly electron-withdrawing groups, and introduction of such substituents causes a decrease in reactivity, and therefore, the first halogenation is faster than the second halogenation. However, the reactions in batch macroreactors suffer from the problem of disguised chemical selectivity, i.e, the formation of dihalogenated products. 

The reactions of electron-rich aromatic compounds with F generated by electrochemical oxidation of F in CH3CN also suffer from the problem of disguised chemical selectivity. The flow microreactor system incorporating a micromixer... 

To control the molecular weight, all polymer chains need to start propagating at the same time. To enable this, the initiation reaction needs to be faster than the propagating reaction. However, when the reaction is very fast and is faster than mixing, the problem of disguised chemical selectivity occurs as we learned in Chap. 7. This can be particularly problematic in batch macroreactors. The flow microreactor system incorporating a micromixer would be effective in solving this problem. 

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