A General Mechanism for Electrophilic Aromatic Substitution

The TT electrons of benzene react with strong electrophiles. In this respect, benzene has something in common with alkenes. When an aUcene reacts with an electrophile, as in the addition of HBr (Section 8.2), electrons from the aUcene tt bond react with the electrophile, leading to a carbocation intermediate. 

The carbocation formed from the alkene then reacts with the nucleophilic bromide ion to form the addition product. 

The similarity of benzene reactivity with that of an alkene ends, however, at the carbocation stage, prior to nucleophihc attack. As we saw in Chapter 14, benzene s closed shell of six TT electrons give it special stabihty. 

Substitution reactions allow the aromatic sextet of tt electrons in benzene to be regenerated after attack by the electrophile. We can see how this happens if we examine a general mechanism for electrophihc aromatic substitution. 

Experimental evidence indicates that electrophiles attack the tt system of benzene to form a nonaromatic cyclohexadienyl carbocation known as an arenium ion. In showing this step, it is convenient to use Kekule structures, because these make it much easier to keep track of the tt electrons  

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Now that we ve outlined the general mechanism for electrophilic aromatic substitution we need only identify the specific electrophile m the nitration of benzene to have a fairly clear idea of how the reaction occurs... 

In bromination (Mechanism 18.2), the Lewis acid FeBr3 reacts with Br2 to form a Lewis acid-base complex that weakens and polarizes the Br- Br bond, making it more electrophilic. This reaction is Step [1] of the mechanism for the bromination of benzene. The remaining two steps follow directly from the general mechanism for electrophilic aromatic substitution addition of the electrophile (Br in this case) forms a resonance-stabilized carbocation, and loss of a proton regenerates the aromatic ring. 

This mechanism would attribute position selectivity to a different structural feature than does the general mechanism for electrophilic aromatic substitution. If the radical pair intermediate were involved, position selectivity would be determined by the collapse to the a complex. The product distribution should then be governed by the distribution of unpaired spin in the aromatic radical cation. This would be expected to exhibit the normal orthOy para preference but might differ quantitatively from the usual mechanism. Detailed consideration of the electron transfer step has,... 

We account for these patterns by means of the general mechanism for electrophilic aromatic substitution first presented in Section 9.5. Let us extend that mechanism to consider how a group already present on the ring might affect the relative stabilities of cation intermediates formed during a second substitution reaction. 

The scope of electrophilic aromatic substitution is quite large both the aromatic com pound and the electrophilic reagent are capable of wide variation Indeed it is this breadth of scope that makes electrophilic aromatic substitution so important Elec trophilic aromatic substitution is the method by which substituted derivatives of benzene are prepared We can gam a feeling for these reactions by examining a few typical exam pies m which benzene is the substrate These examples are listed m Table 12 1 and each will be discussed m more detail m Sections 12 3 through 12 7 First however let us look at the general mechanism of electrophilic aromatic substitution... 

If the Lewis base ( Y ) had acted as a nucleophile and bonded to carbon the prod uct would have been a nonaromatic cyclohexadiene derivative Addition and substitution products arise by alternative reaction paths of a cyclohexadienyl cation Substitution occurs preferentially because there is a substantial driving force favoring rearomatization Figure 12 1 is a potential energy diagram describing the general mechanism of electrophilic aromatic substitution For electrophilic aromatic substitution reactions to... 

Figure 12.1 is a potential energy diagram describing the general mechanism of electrophilic aromatic substitution. For electrophilic aromatic substitution reactions to... 

Now we can remove the "blocking group" - SO3H and next form the final product 2,4-D. To do this we treat 2-hydroxy 3,5-dichloropbenzenesulfonic acid with steam at 120°C with a trace of acid catalyst. This is essentially the reverse of sulfonation, or "desulfonation." We note that sulfonation is the only one of the common electrophilic aromatic substitutions that is reversible and the question arises why this is so. This calls for an analysis of the general mechanism of electrophilic aromatic substitution. The idealized energy profile for such a reaction (chlorination) is ... 

A substantial body of data, including reaction kinetics, isotope effects, and structure-reactivity relationships, has permitted a thorough understanding of the steps in aromatic nitration. As anticipated from the general mechanism for electrophilic substitution, there are three distinct steps ... 

Resole syntheses entail substitution of formaldehyde (or formaldehyde derivatives) on phenolic ortho and para positions followed by methylol condensation reactions which form dimers and oligomers. Under basic conditions, pheno-late rings are the reactive species for electrophilic aromatic substitution reactions. A simplified mechanism is generally used to depict the formaldehyde substitution on the phenol rings (Fig. 7.21). It should be noted that this mechanism does not account for pH effects, the type of catalyst, or the formation of hemiformals. Mixtures of mono-, di-, and trihydroxymethyl-substituted phenols are produced. 

A general mechanism for the electrophilic aromatic substitution reaction is outlined in Figure 17.1. The process... 

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