Electrophilic aromatic substitution kinds

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

At this point, attention can be given to specific electrophilic substitution reactions. The kinds of data that have been especially useful for determining mechanistic details include linear ffee-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). 

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+. 

The structural theory of organic chemistry was developed in the last half of the nineteenth century. It led to the concept that chemical, physical and biological properties of all kinds must be a function of structural change. The earliest structure-property relationships (SPR) were qualitative. Examples are the directional effect of substituents on the benzene ring with respect to electrophilic aromatic substitution and orientation in... 

Exercise 22-24 Draw the structures of the intermediate cations for nitration of nitrobenzene in the 2, 3, and 4 positions. Use the structures to explain why the nitro group is meta-orienting with deactivation. Use the same kind of arguments to explain the orientation observed with —CF3, —CHO, —CH2Ci, and —NH2 groups in electrophilic aromatic substitution (Table 22-6),... 

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. 

For the dimerization of 4,4 -dimethoxystilbene, it has been possible to demonstrate spectroelectrochemically [115] and at the rotating ring-disk electrode [116] that the product is formed mainly by radical dimerization of the intermediate radical cations [path B, Eq. (13)]. Fast derivative CV, however, supports for the same olefin a complex ECE pathway [path A, Eq. (13) [117]. Depending on the oxidation potential and the kind of the nucleophiles (acetate, water, or methanol), a tetrahydronaphthalene derivative (Table 6, number 3) [118], a monomer diacetate [118], a tetrahydrofuran [115], or a dimer dimethoxy compound is found. When methanol is replaced by aqueous dichloromethane or by aqueous acetonitrile emulsions as solvent, styrene (Table 6, number 4) [119a] and a-methylstyrene [119b] yield 2,5-diphenyltetrahydrofurans. In some cases cyclization occurs by electrophilic aromatic substitution (analogous to Table 6, number 3). 

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. 

In nucleophilic as in electrophilic aromatic substitution, then, a substituent group affects reactivity by its ability to attract or release electrons in nucleophilic as in electrophilic aromatic substitution, a substituent group exerts its effect chiefly at the position ortho and para to it. The kind of effect that each group exerts, however, is exactly opposite to the kind of effect it exerts in electrophilic aromatic substitution. In nucleophilic aromatic substitution electron withdrawal causes activation, and electron release causes deactivation. 

Modulating the reactivity of an amino-substituted benzene by forming an amide is a useful trick that allows many kinds of electrophilic aromatic substitutions to be carried out that would otherwise be impossible. A good example is the preparation of the so-called sulfa drugs. 

We have actually already seen one way to achieve this kind of transformation. It was called the Clemmensen reduction, which we explored in Chapter 3 (electrophilic aromatic substitution). We will also see one more way to achieve this transformation in the upcoming section. 

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