Electrophilic aromatic mechanism

This led to the introduction of the concepts of inductive and resonance effects and to the establishment of the mechanism of electrophilic aromatic substitution. 

A more detailed classification of chemical reactions will give specifications on the mechanism of a reaction electrophilic aromatic substitution, nucleophilic aliphatic substitution, etc. Details on this mechanism can be included to various degrees thus, nucleophilic aliphatic substitutions can further be classified into Sf l and reactions. However, as reaction conditions such as a change in solvent can shift a mechanism from one type to another, such details are of interest in the discussion of reaction mechanism but less so in reaction classification. 

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... 

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... 

Figure 12 3 adapts the general mechanism of electrophilic aromatic substitution to the nitration of benzene The first step is rate determining m it benzene reacts with nitro mum ion to give the cyclohexadienyl cation intermediate In the second step the aro maticity of the ring is restored by loss of a proton from the cyclohexadienyl cation... 

Complexation of bromine with iron(III) bromide makes bromine more elec trophilic and it attacks benzene to give a cyclohexadienyl intermediate as shown m step 1 of the mechanism (Figure 12 6) In step 2 as m nitration and sulfonation loss of a proton from the cyclohexadienyl cation is rapid and gives the product of electrophilic aromatic substitution... 

Section 12 2 The mechanism of electrophilic aromatic substitution involves two stages attack of the electrophile on the tt electrons of the ring (slow rate determining) followed by loss of a proton to restore the aromaticity of the ring... 

Diazo coupling follows the rules of orientation of substituents in aromatic systems in accordance with the mechanism of electrophilic aromatic substitution and the concept of resonance. 

The azo coupling reaction proceeds by the electrophilic aromatic substitution mechanism. In the case of 4-chlorobenzenediazonium compound with l-naphthol-4-sulfonic acid [84-87-7] the reaction is not base-catalyzed, but that with l-naphthol-3-sulfonic acid and 2-naphthol-8-sulfonic acid [92-40-0] is moderately and strongly base-catalyzed, respectively. The different rates of reaction agree with kinetic studies of hydrogen isotope effects in coupling components. The magnitude of the isotope effect increases with increased steric hindrance at the coupler reaction site. The addition of bases, even if pH is not changed, can affect the reaction rate. In polar aprotic media, reaction rate is different with alkyl-ammonium ions. Cationic, anionic, and nonionic surfactants can also influence the reaction rate (27). 

Electrophilic aromatic substitution reactions are important for synthetic purposes and also are one of the most thoroughly studied classes of organic reactions from a mechanistic point of view. The synthetic aspects of these reactions are discussed in Chapter 11 of Part B. The discussion here will emphasize the mechanisms of several of the most completely studied reactions. These mechanistic ideas are the foundation for the structure-reactivity relationships in aromatic electrophilic substitution which will be discussed in Section 10.2... 

Scheme 10.2. Generalized Mechanism for Electrophilic Aromatic Substitution...

Isotope effects are also useful in providing insight into other aspects of the mechanisms of individual electrophilic aromatic substitution reactions. In particular, because primary isotope effects are expected only when the breakdown of the c-complex to product is rate-determining, the observation of a substantial points to a rate-... 

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 general, the reaction between a phenol and an aldehyde is classified as an electrophilic aromatic substitution, though some researchers have classed it as a nucleophilic substitution (Sn2) on aldehyde [84]. These mechanisms are probably indistinguishable on the basis of kinetics, though the charge-dispersed sp carbon structure of phenate does not fit our normal concept of a good nucleophile. In phenol-formaldehyde resins, the observed hydroxymethylation kinetics are second-order, first-order in phenol and first-order in formaldehyde. 

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

Despite the synthetic utility of this transformation, nearly eighty years elapsed between the discovery of the Bischler-Napieralski reaction and the first detailed studies of its mechanism. " Early mechanistic proposals regarding the Bischler-Napieralski reaction involved protonation of the amide oxygen by traces of acid present in P2O5 or POCI3 followed by electrophilic aromatic substitution to provide intermediate 5, which upon dehydration would afford the observed product 2. However, this proposed mechanism fails to account for the formation of several side products that are observed under these conditions vide infra), and is no longer favored. 

The reason for this difference in selectivity of different electrophilic reagents between the 2- and 3-positions must be sought in the finer details of the mechanism of electrophilic aromatic substitution Melander and co-workers are studying this problem by means of isotope effects. 

The optimal pH-value for the coupling reaction depends on the reactant. Phenols are predominantly coupled in slightly alkaline solution, in order to first convert an otherwise unreactive phenol into the reactive phenoxide anion. The reaction mechanism can be formulated as electrophilic aromatic substitution taking place at the electron-rich aromatic substrate, with the arenediazonium ion being the electrophile ... 

The mechanism for that step is closely related to that of the Friedel-Crafts acylation. Upon subsequent hydrolysis the o-substituted Lewis acid-coordinated phenolate 7 is converted to the free o-acylphenol 2. By an analogous route, involving an electrophilic aromatic substitution para to the phenolate oxygen, the corresponding para-acylphenol is formed. 

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. 

The C-nitrosation of aromatic compounds is characterized by similar reaction conditions and mechanisms to those discussed earlier in this section. The reaction is normally carried out in a strongly acidic solution, and in most cases it is the nitrosyl ion which attacks the aromatic ring in the manner of an electrophilic aromatic substitution, i. e., via a a-complex as steady-state intermediate (see review by Williams, 1988, p. 58). We mention C-nitrosation here because it may interfere with diazotization of strongly basic aromatic amines if the reaction is carried out in concentrated sulfuric acid. Little information on such unwanted C-nitrosations of aromatic amines has been published (Blangey, 1938 see Sec. 2.2). 

Figure 7.6 Mechanism of novolac synthesis via electrophilic aromatic substitution.

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. 

Arenediazonium ions can, of course, bring about electrophilic aromatic substitution giving aromatic azo-compounds. Using PhN=N and PhO , polarized signals have been observed in the N-spectrum (6 MHz) of the coupled product (A, A) and reactant, suggesting that the reaction proceeds, at least in part, by a mechanism involving preliminary reversible electron transfer between the reactants (Bubnov et al., 1972). 

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