Electrophilic aromatic substitution of benzene

Notice that the mechanism of the reaction is the same as the mechanism for electrophilic aromatic substitution of benzene (Section 19.3). 

The electron-withdrawing nitrogen atom makes the intermediate obtained from electrophilic aromatic substitution of pyridine less stable than the carbocation intermediate obtained from electrophilic aromatic substitution of benzene. Pyridine, therefore, is less reactive than benzene. Indeed, it is even less reactive than nitrobenzene. (Recall from Section 19.14 that an electron-withdrawing nitro group strongly deactivates a benzene ring toward electrophilic aromatic substitution.)... 

In Summary Naphthalene is activated with respect to electrophilic aromatic substitution favored attack takes place at Cl. Electrophilic attack on a substituted naphthalene takes place on an activated ring and away from a deactivated ring, with regioselectivity in accordance with the general rules developed for electrophilic aromatic substitution of benzene derivatives. Similar considerations apply to the higher polycyclic aromatic hydrocarbons. 

General mechanism for electrophilic aromatic substitution of benzene... 

Since benzenesulfonyl peroxide was used as an initiator in polymerization reactions, it was thought that a free radical aromatic substitution of benzene by the benzenesulfonoxy radical takes place. A detailed study by Dannley and Knipple reveals that attachment of the sulfonoxy group derived from a bis(arylsulfonyl) peroxide to the aromatic ring occurs by electrophilic aromatic substitution (equation 5) °. 

Electrophilic aromatic substitution Electrophilic aromatic substitution of indole occurs on the five-membered pyrrole ring, because it is more reactive towards such reaction than a benzene ring. As an electron-rich heterocycle, indole undergoes electrophilic aromatic substitution primarily at C-3, for example bromination of indole. 

A priori, the two most likely mechanisms for electrophilic aromatic substitution on benzene, in the absence of strong base,156 are (1) direct displacement, the transition state for which is shown in 65, and (2) a two-step reaction in which... 

In another example of an electrophilic aromatic substitution reaction, benzene reacts with a mixture of concentrated nitric and sulfuric acids to create nitrobenzene. 

By far the most common methods for the preparation of dibenzoselenophenes and 2-benzoselenophenes, like the synthesis of 1-benzoselenophenes, rely upon the annulation of the heterocyclic ring system onto a preformed benzene ring and mostly involve the formation of one or two Se-C bonds as their key steps, with only a few exceptions [1, 119, 120], Intramolecular electrophilic aromatic substitution of biphenyl-2-yl trifluoromethylselenide to 5-(trifluoromethyl)dibenzoselenopheni um triflate (62) [99, 143] and synthesis of tetramethoxydibenzoselenophene (95) (Scheme 26) [144, 145] are examples. 

A more interesting problem than the influence of substituents in the electrophilic reagent of azo coupling is the extremely high selectivity of the C-coupling reactions, relative to other electrophilic aromatic substitutions. Unsubstituted benzene does not react with any arenediazonium ion, 1,3,5-trimethoxybenzene reacts very slowly with strongly electrophilic diazonium ions only aromatic amines (e.g. N,N-dimethyl-aniline) or phenolate ions react very fast, in some cases close to diffusion control. 

The electrophilic aromatic substitution of aryl halides takes place less readily than with benzene (electron-withdrawing effect), but occurs at the ortho and para positions (the lone pairs on the halogen assist in delocalizing the positive charge in the intermediate). Further chlorination of chlorobenzene, in the presence of aluminium or iron trichlorides, gives 1,4-dichlorobenzene and some 1,2-dichlorobenzene. Nitration normally occurs to give the 2- and 4-nitro- and 2,4-dinitrochlorobenzenes (Scheme 4.13). 

We begin with the basic features and mechanism of electrophilic aromatic substitution (Sections 18.1-18.5), the basic reaction of benzene. Next, we discuss the electrophilic aromatic substitution of substituted benzenes (Sections 18.6-18.12), and conclude with other useful reactions of benzene derivatives (Sections 18.13-18.14). The ability to interconvert resonance structures and evaluate their relative stabilities is crucial to understanding this material. 

Why Substituents Activate or Deactivate a Benzene Ring Figure 18.6 Energy diagrams comparing the rate of electrophilic aromatic substitution of substituted benzenes... 

The previous sections leave no doubts that aromatic compounds, react with positively charged electrophiles to form a-complexes-arenium ions. But are they the primary intermediates It is not by accident that the problem of preliminary formation of radical cations has arisen. Its statement is an attempts to explain the orientational peculiarities of electrophilic aromatic substitution of hydrogen. The widespread view that the orientation in the reactions of aromatic compounds with electrophiles is dictated by the relative stabilities of the cr-complexes explains but a part of the accumulated material. In the first place this refers to the meta- and para-orienting effects of electron-releasing substituents in benzene in terms of the QCT -approach and to that of the relative reactivity of various aromatic substrates... 

In the electrophilic aromatic substitution of a monosubstituted benzene, three isomeric products are possible The new group may be oriented ortho, meta, or para to the existing group. On the basis of a wealth of experimental observations, chemists have made the... 

The inductive effect of halogens. The halogens are more electronegative than carbon and have an electron-withdravdng inductive effect. Aryl halides, therefore, react more slowly in electrophilic aromatic substitution than benzene does. 

To explain electrophilic aromatic substitution of substituted benzene derivatives, a generic benzene derivative, 61, is used in Figure 21.1, with a substituent X. This is used rather than a specific example in order to show the similarities and differences in reactivity for electron-releasing versus electron-withdrawing groups. The carbon of the benzene ring attached to the substituent is defined as the ipso carbon ( ) in Figure 21.1. There are only three possible arenium ion intermediates for the reaction of any monosubstituted benzene derivative 61 with an electrophile such as Br+ 62, 63, and 64. 

In anthracene (123), there are three different positions (Cl, C2, and C9) and there are five different positions (Cl, C2, C4, C5, and C9) in phenanthrene (124). Electrophilic aromatic substitution of anthracene leads to substitution primarily at C9 because that gives an intermediate with the most resonance forms and the most intact benzene rings. A comparison of attack at Cl and at C2 in anthracene will show that there are more resonance forms for attack at Cl and more fully aromatic rings. Attack at C9 leads to an intermediate with even more resonance, and electrophilic substitution of anthracene leads to C9 and Cl products, with little reaction at C2. 

Recently, it has been shown that 3-pyridinecarboxal-dehyde undergoes the same reaction in weaker acid solutions of sulfuric acid with H, values around -9. NMR analysis definitively established that the dication shown below is generated under the reaction conditions, and the two positive charges enhance the electrophilic aromatic substitution with benzene. 

Electrophilic aromatic substitution in benzene proceeds by addition of the electrophile followed by proton loss... 

Working with the Concepts Predicting Regiochemistry in Electrophilic Aromatic Substitutions of Di- and More Highly Substituted Benzenes... 

In Summary Electrophilic aromatic substitution of multiply substituted benzenes is controlled by the strongest activator and, to a certain extent, by steric effects. The greatest product selectivity appears when there is only one dominant activator or when the substitution pattern minimizes the number of isomers that can be formed. 

As expected for aromatic systems, the l-hetero-2,4-cyclopentadienes undergo electrophilic substitution. There are two sites of possible attack, at C2 and at C3. Which one should be more reactive An answer can be found by the same procedure used to predict the regiose-lectivity of electrophilic aromatic substitution of substituted benzenes (Chapter 16) enumeration of all the possible resonance forms for the two modes of reaction. 

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