Representative Electrophilic Aromatic Substitution Reactions of Benzene

What about nucleophilic substitution in aryl halides  

In Chapter 8, we noted that aryl halides are normally much less reactive toward nucleophilic substitution than alkyl halides. In the present chapter we ll see examples of novel, useful, and mechanistically interesting nucleophilic aromatic substitutions and explore the structural features responsible for these reactions. 

1 Representative Electrophilic Aromatic Substitution Reactions of Benzene 

The scope of electrophilic aromatic substitution is quite large both the aromatic compound and the electrophilic reagent are capable of wide variation. Indeed, it is this breadth of scope that makes electrophilic aromatic substitution so important. Electrophilic aromatic substitution is the method by which substituted derivatives of benzene are prepared. We can gain a feeling for these reactions by examining a few typical examples in which benzene is the substrate. These examples are listed in Table 12.1, and each will be discussed in more detail in Sections 12.3 through 12.7. First, however, let us look at the general mechanism of electrophilic aromatic substitution. 

The scope of electrophilic aromatic substitution is quite large both the aromatic compound and the electrophilic reagent are capable of wide variation. Indeed, it is this breadth of scope that makes electrophilic aromatic substitution so important. Electrophilic aromatic 

Chapter 12 Reactions of Arenes Electrophilic and Nucleophilic Aromatic Substitution 

Nitration Warming benzene with a mixture of nitric acid and sulfuric acid gives nitrobenzene. A nitro group (—NO2) replaces one of the ring hydrogens. 

1 REPRESENTATIVE ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS OF BENZENE 

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TABLE 12.1 Representative Electrophilic Aromatic Substitution Reactions of Benzene... 

Representative Electrophilic Aromatic Substitution Reactions of Benzene 457 Mechanistic Principles of Electrophilic Aromatic Substitution 458 Nitration of Benzene 459 Sulfonation of Benzene 461 Halogenation of Benzene 462 Biosynthetic Halogenation 464 Friedel-Crafts Alkylation of Benzene Friedel-Crafts Acylation of Benzene Synthesis of Alkylbenzenes by Acylation-Reduction 469 Rate and Regioselectivity in Electrophilic Aromatic Substitution 470 Rate and Regioselectivity in the Nitration ofToluene 472... 

The chemistry of benzenes is summed up by the imperative Preserve the circle In plain English, that statement means that there is a strong thermodynamic driving force to preserve the delocalization energy—more than 30 kcal/mol—that the circle represents. In this chapter, the classic aromatic substitution reaction in which an electrophile replaces (substitutes for) one of the hydrogens on the ring is introduced. In Chapter 14, this prototypal reaction will be expanded in many ways. 

Aromatic compounds have a special place in ground-state chemistry because of their enhanced thermodynamic stability, which is associated with the presence of a closed she of (4n + 2) pi-electrons. The thermal chemistry of benzene and related compounds is dominated by substitution reactions, especially electrophilic substitutions, in which the aromatic system is preserved in the overall process. In the photochemistry of aromatic compounds such thermodynamic factors are of secondary importance the electronically excited state is sufficiently energetic, and sufficiently different in electron distribution and electron donor-acceptor properties, ior pathways to be accessible that lead to products which are not characteristic of ground-state processes. Often these products are thermodynamically unstable (though kinetically stable) with respect to the substrates from which they are formed, or they represent an orientational preference different from the one that predominates thermally. 

Electrophilic Substitution Reactivity Much of the electrophilic reactivity of aromatics is described in great detail in a comprehensive recent book of Taylor [10]. We shall focus attention on the electrophilic substitution reactivity of annelated benzenes and try to interpret the orientational ability of fused small rings. For this purpose we consider here Wheland transition states of the electrophilic substitution reactions. It is also convenient to take the proton as a model of the electrophilic reagent. In order to delineate rehybridization and 7r-electron localization effects, let us consider a series of angularly deformed benzenes (Fig. 21), where two vicinal CH bonds bent toward each other mimick a fused small ring. Angles c of 110° and 94° simulate five and four membered... 

Instead, these heterocycles and their derivatives most commonly undergo electrophilic substitution nitration, sulfonation, halogenation. Friedel-Crafts acylation, even the Reimer-Tiemann reaction and coupling with diazonium salts. Heats of combustion indicate resonance stabilization to the extent of 22-28 kcal/ mole somewhat less than the resonance energy of benzene (36 kcal/mde), but much greater than that of most conjugateci dienes (about Tlccal/mole). On the basis of these properties, pyrrole, furan, and thiophene must be considered aromatic. Clearly, formulas I, II, and III do not adequately represent the structures of these compounds. 

Equimolar mixtures of toluene and benzene were passed over beds of DHY at low temperatures (25-60°) in experiments where the two aromatics of different reactivity competed for the electrophilic deuterium (75). The distribution of deuterium between toluene and benzene (apparent ACeHsCHs/fcCeHe) and among the ring positions of the toluene-di samples was determined. A plot of log pt vs selectivity factor (St) for these data from the competitive experiments at 25-60° (Fig. 20, black circles) falls on the line obtained from a study of 47 electrophilic substitution reactions by H. C. Brown and associates (83). The partial rate factors pt and mt give the rate of substitution of the para position and one of the meta positions in toluene, relative to the rate of substitution of one of the six equivalent ring positions of benzene. Points a, b, c, d, and e fall quite close to the line, which represents a linear free energy relationship in both positional and substrate selectivity. 

CsHi4 CsHs + 4H2 Benzene is the simplest aromatic hydrocarbon. It shows characteristic electrophilic substitution reactions, which are difficult to explain assuming a simple unsaturated structure (such as Kekule s (1865) or Dewar s (1867) formulae). This anomolous behavior can now be explained by assuming that the six pi electrons are delocalized and that benzene is, therefore, a resonance hybrid. It consists of two Kekule structures and three Dewar structures, the former contributing 80% and the latter 20% to the hybrid. Benzene is usually represented by either a Kekule structure or a hexagon containing a circle (which denotes the delocalized electrons). 

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