What Is the Mechanism of Electrophilic Aromatic Substitution

In this section, we study several types of electrophilic aromatic substitution reactions—that is, reactions in which a hydrogen of an aromatic ring is replaced by an electrophile, E. The mechanisms of these reactions are actually very similar. In fact, they can be broken down into three common steps  

Step 1 Generation of the electrophile. This is a reaction pattern specific to each particular 

Step 2 Reaction of a nucleophile and an electrophile to form a new covalent bond. Attack of the electrophile on the aromatic ring to give a resonance-stabilized cation intermediate  

Step 3 Take a proton away. Proton transfer to a base to regenerate the aromatic ring  

The reactions we are about to study differ only in the way the electrophile is generated and in the base that removes the proton to re-form the aromatic ring. You should keep this principle in mind as we explore the details of each reaction. 

---

Electrophilic aromatic substitution is the most important reaction of aromatic compounds because it has broad applications for a wide variety of aromatic compounds. In contrast, nucleophilic aromatic substitution has restricted applications. In nucleophilic aromatic substitution, a strong nucleophile replaces a leaving group, such as a halide. What is the mechanism of nucleophilic aromatic substitution It cannot be the S]m2 mechanism because aryl halides cannot achieve the correct geometry fw back-side displacement The aromatic ring blocks approach of the nucleophile to the back of the carbon bearing the halogen. 

What is a likely structure for the yellow compound The isolation of this and related compounds is considered to be strong support for the mechanism of electrophilic aromatic substitution. Why should this be so ... 

When benzene is dissolved in D2SO4, its H NMR absorption at 8 = 7.27 ppm disappears and a new compound is formed having a molecular weight of 84. What is it Propose a mechanism for its formation. (Caution In all mechanisms of electrophilic aromatic substitution, always draw the H atom at the site of electrophilic attack.)... 

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 ... 

In this chapter we shall examine the methods that are used to measure these effects on reactivity and orientation, the results of these measurements, and a theory that accounts for these results. The theory is, of course, based on the most likely mechanism for electrophilic aromatic substitution we shall see what this mechanism is, and some of the evidence supporting it. First let us look at the facts. 

The accepted mechanism, which proceeds through the arenium cation intermediate, occurs as follows. First, protonation of the aryl species 2 occurs to afford the electrophilic o-complex 3. What follows is a two-step electrophilic aromatic substitution process whereby the electrophilic intermediate 3 is attacked by the adjacent aromatic ring to form a new carbon-carbon bond in intermediate 4. Deprotonation of 4 regenerates the aromatic species in intermediate 5. Finally, oxidation/aromatization of the product occurs with the formal expulsion of H2, resulting in the formation of 6. 

Now you have three basic mechanisms for aromatic rings — electrophilic aromatic substitution, Sj Ar, and elimination/addition. How do you choose among these The first consideration is what types of other reagents are present. If the reagents include an electrophile, then the reaction will be electrophilic aromatic substitution. The presence of a nucleophile may lead to either S Ar or elimination/addition. If the system meets the three requirements for SfjAr, then the reaction will follow that mechanism. If not, it will be an elimination/addition. 

The ability of azoles to electrophilic substitution reactions is determined by the activity of reagents, the basicity of substrates, and the acidity of media. This caused some uncertainty in the interpretation of results and complicated a comparison of the reactivity of various azoles. The situation has changed after Katritzky and Johnson [1] have reported the criteria allowing, with a sufficient degree of reliance, the establishment in what form (base or conjugative acid) the compound reacts. The information on the mechanism of nitration of azoles was basically borrowed from the extensive literature on the nitration of aromatic hydrocarbons [2-8] therefore, we have found expedient to discuss briefly some works in this field. 

No matter what electrophile is used, all electrophilic aromatic substitution reactions occur via a two-step mechanism addition of the electrophile to form a resonance-stabilized carboca-tion, followed by deprotonation with base, as shown in Mechanism 18.1. 

All the electrophilic aromatic substitutions shown in reaction 3 of Review Table 3 occur by the same two-step mechanism. The first step is similar to the first step in electrophilic addition to alkenes An electron-poor reagent reacts with the electron-rich aromatic ring. The second step is identical to what happens during E2 elimination A base abstract a hydrogen atom next to the positively charged carbon, and elimination of the proton occurs. 

On the other hand, a pure Eley-Rideal mechanism, in which the aromatic compound in the liquid phase reacts with the adsorbed acylating agent was first proposed by Venuto et alP1,22] and more recently by others.[23] However, for acylation reactions of polar substrates (anisole, veratrole), chemisorption of the latter must be taken into account in the kinetic law. A modification, the modified Eley-Rideal mechanism, has been proposed 114,24-26 an adsorbed molecule of acylating agent should react with a nonadsorbed aromatic substrate, within the porous volume of the catalyst. However, the substrate is also competitively adsorbed on the active sites of the zeolite, acting somehow as a poison of the acid sites. That is what we checked through different kinetic studies of various aromatic electrophilic substitution reactions.[24-26]... 

Electrophihc aromatic substitutions are unhke nucleophilic substitutions in that the large majority proceed by just one mechanism with respect to the substrate. In this mechanism, which we call the arenium ion mechanism, the electrophile (which can be viewed as a Lewis acid) is attacked by the 71-electrons of the aromatic ring (behaving as a Lewis base in most cases) in the first step. This reaction leads to formation of a new C—X bond and a new sp carbon in a positively charged intermediate called an arenium ion, where X is the electrophile. The positively charged intermediate (the arenium ion) is resonance stabilized, but not aromatic. Loss of a proton from the sp carbon that is adjacent to the positive carbon in the arenium ion, in what is effectively an El process (see p. 1487), is driven by rearomatization of the ring from the arenium ion to give the aromatic substitution product. A proton... 

PROBLEM 14.24 In addition to the mechanism following the path shown for pyrrole in Rgure 14.61, there is another reasonable mechanism for aromatic substitution of furan. Suggest one. Hint Think simple What are the possible reactions between electrophiles and double bonds (Chapters 9 and 10) Use the chlorination of furan as an example. 

---