Electrophilic aromatic substitution reaction kinds

Section 12 17 Polycyclic aromatic hydrocarbons undergo the same kind of electrophilic aromatic substitution reactions as benzene... 

The first product is derived from a normal electrophilic aromatic substitution reaction of the kind described in the text. The second product is derived from ipso electrophilic aromatic substitution. The mechanism is exactly the same, but in the last step z-Pr+ is lost instead of H+. 

At this point, attention can be given to specific electrophilic aromatic substitution reactions. The kinds of data that have been especially pertinent to elucidating mechanistic detail include linear free-energy relationships, kinetic studies, isotope effects, and selectivity patterns. In general, the basic questions that need to be asked about each mechanism are (1) What is the active electrophile (2) Which step in the general mechanism for electrophilic aromatic substitution is rate-determining (3) What are the orientation and selectivity patterns ... 

There are many other kinds of electrophilic aromatic substitutions besides bromination, and all are thought to occur by the same general mechanism. Let s look at some of these other reactions briefly. 

In considering quantitatively the response of these groups to high electron-demand there are certain caveats. In the first place it must be remembered that amino and related groups are liable to be protonated in the kind of media often used for studying electrophilic aromatic substitution. The observed substituent effect will then be that of the positive pole. Secondly, the straightforward application of the tr+ scale to electron-demanding reactions is not necessarily appropriate. It may well be that some form of multiparameter treatment is needed, perhaps the Yukawa-Tsuno equation (Section II.B). 

However, the formation of molecular complexes between nucleophile and electrophile (with a possible participation of solvents) in both electrophilic aromatic substitutions and nucleophilic aromatic substitutions is clearly expected, as shown by the conventional use of the terms electrophile and nucleophile these reactions belong to apparently different fields of organic chemistry, but the unification of the two kinds of reaction is mainly a matter of terminology and of details. 

By use of especially selected aromatic substrates—highly hindered ones—isotope effects can be detected in other kinds of electrophilic aromatic substitution, even in nitration. In certain reactions the size of the isotope can be deliberately varied by changes in experimental conditions- and in a way that shows dependence on the relative rates of (2) and the reverse of (I). There can be little doubt that all these reactions follow the same two-step mechanism, but with differences in the shape of potential energy curves. In isotope effects the chemist has an exceedingly delicate probe for the examination of organic reaction mechanisms. 

This duality of mechanism does not reflect exceptional behavior, but is usual for electrophilic aromatic substitution. It also fits into the usual pattern for nucleophilic aliphatic substitution (Sec. 14.16), which—from the standpoint of the alkyl halide—is the kind of reaction taking place. Furthermore, the particular halides (T and methyl) which appear to react by this second mechanism are just the ones that would have been expected to do so. 

Aromatic rings act as nucleophiles toward all kinds of electrophiles in the aromatic substitution reaction (Chapter 13), so perhaps we can use the n system of the phenyl ring in 3-phenyl-2-hutyl tosylate as a nucleophile. If the n system displaces the tosylate, it must do so from the rear. The result is the phoioniumion shown in Figure 21.26. 

Chlorine and iodine can be introduced into aromatic rings by electrophilic substitution reactions, but fluorine is too reactive and only poor yields of monofluoro-aromatic products are obtained by direct fluorinafion. Aromatic rings react with CI2 in the presence of FeCl3 catalyst to yield chlorobenzenes, just as they react with Bi 2 and FeBr3. This kind of reaction is used in the synthesis of numerous pharmaceutical agents, including the antianxiety agent diazepam, marketed as Valium. 

Functionalization of C—H bonds via aromatic substitution is an important means of adding functional groups to all kinds of arenes and as such is of significant relevance to many areas of chemistry. Notably, the key step in several industrially important reactions is an electrophilic attack on aromatic Jt-systems by carbocations or other strong electrophiles. 

An additional criterion, in our opinion a very important one, but which is not a property of the ground state, is reactivity. Generally, aromatic compounds undergo electrophilic substitution reactions (aromatic substitution) more easily than addition, which is often expressed as a typical tendency of these kinds of systems to retain their initial tr-electron structure [16, 17]. 

In earlier chapters we revealed how some reactive intermediates can be prepared, usually under special conditions rather different from those of the reaction under study, as a reassurance that some of these unlikely looking species can have real existence. Intermediates of this kind include the carboca-tion in the S l reaction (Chapter 17), the cations and anions in electrophilic (Chapter 22) and nucleophilic (Chapter 23) aromatic substitutions, and the enols and enolates in various reactions of carbonyl compounds (Chapters 21 and 26-29). We have also used labelling in this chapter to show that symmetrical intermediates are probably involved in, for example, nucleophilic aromatic substitution with a benzyne intermediate (Chapter 23). 

Ambident anions are mesomeric, nucleophilic anions which have at least two reactive centers with a substantial fraction of the negative charge distributed over these cen-ters ) ). Such ambident anions are capable of forming two types of products in nucleophilic substitution reactions with electrophilic reactants . Examples of this kind of anion are the enolates of 1,3-dicarbonyl compounds, phenolate, cyanide, thiocyanide, and nitrite ions, the anions of nitro compounds, oximes, amides, the anions of heterocyclic aromatic compounds e.g. pyrrole, hydroxypyridines, hydroxypyrimidines) and others cf. Fig. 5-17. 

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