Rate determining step in aromatic electrophilic substitution

Of the following two steps, step 1 (the formation of the arenium ion) is usually the rate-determining step in electrophilic aromatic substitution because of its higher free energy of activation ... 

To understand why some substituents make a benzene ring react faster than benzene itself (activators), whereas others make it react slower (deactivators), we must evaluate the rate-determining step (the first step) of the mechanism. Recall from Section 18.2 that the first step in electrophilic aromatic substitution is the addition of an electrophile (E ) to form a resonance-stabilized carbo-cation. The Hammond postulate (Section 7.15) makes it pos.sible to predict the relative rate of the reaction by looking at the stability of the carbocation intermediate. 

Product-Development Control. The rate-determining step in most aromatic electrophilic substitutions is well known to be the attack of the electrophile on the aromatic ring. The rate of such a reaction (like that of all reactions)... 

Recall from Fig. 15.3 and Section 15.2 that the slow step in electrophilic aromatic substitution, the step that determines the overall rate of reaction, is the first step. In this step an electron-seeking reagent reacts by accepting an electron pair from the benzene ring. 

Why, then, do electrophiles prefer to attack naphthalene at Cl rather than at C2 Closer inspection of the resonance contributors for the two cations reveals an important difference Attack at Cl allows two of the resonance forms of the intermediate to keep an intact benzene ring, with the full benefit of aromatic cyclic delocalization. Attack at C2 allows only one such structure, so the resulting carbocation is less stable and the transition state leading to it is less energetically favorable. Because the first step in electrophilic aromatic substitution is rate determining, attack is faster at Cl than at C2. 

First, it is important to note that most aromatic electrophilic substitution reactions are under kinetic, and not thermodynamic, control. This is because most of the reactions are irreversible, and the remainder are usually stopped before equilibrium is reached. In a kinetically controlled reaction, the distribution of products (or product spread), i.e. the ratio of the various products formed, is determined not by the thermodynamic stabilities of the products, but by the activation energy barrier that controls the rate determining step. In a two-step reaction, it is a reasonable assumption that the transition state of the rate determining step is close in energy to that of the intermediate, which in this case is the Wheland intermediate and so by invoking the Hammond postulate, one may assume that they have similar geometries. 

Vanadium complexes and in particular [VO(acac)2] are the most active catalysts for the oxidation of substituted anilines to nitro compounds. The effect of substituents upon reaction rate corresponds to a reaction involving an electron deficient transition state in that electron withdrawing groups decrease the rate and vice versa. The relative order of reactivity p-Me > m-Me > aniline > p-Cl > p-Br > m-Cl > m-Br is the same as observed in electrophilic aromatic substitution. Straight line correlations between the log of the relative rates and Hammett a or Brown constants were obtained with p values of— 1.42 and — 1.97, respectively, indicating an electron deficient transition state in the rate determining step. 

The evidence indicates that the mechanistic step in which the C—H bond is broken is not rate determining. (In the case cited, it makes no difference kinetically if a C—H or C—D bond is broken in electrophilic aromatic substitution.) This evidence is consistent with the two-step mechanism given in Section 15.2. The step in which the aromatic compound reacts with the electrophile (NO2+) is the slow rate-determining step. Proton (or deuteron) loss from the arenium ion to return to an aromatic system is a rapid step and has no effect on the overall rate. 

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... 

The active electrophile is formed by a subsequent reaction, often involving a Lewis acid. As discussed above with regard to nitration, the formation of the active electrophile may or may not be the rate-determining step. Scheme 10.1 indicates the structure of some of the electrophihc species that are involved in typical electrophilic aromatic substitution processes and the reactions involved in their formation. 

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 ... 

The rate-determining step is the electrophilic aromatic substitution as in the closely related Friedel-Crafts reaction. Both reactions have in common that a Lewis acid catalyst is used. For the Blanc reaction zinc chloride is generally employed, and the formation of the electrophilic species can be formulated as follows ... 

Novolacs are prepared with an excess of phenol over formaldehyde under acidic conditions (Fig. 7.6). A methylene glycol is protonated by an acid from the reaction medium, which then releases water to form a hydroxymethylene cation (step 1 in Fig. 7.6). This ion hydroxyalkylates a phenol via electrophilic aromatic substitution. The rate-determining step of the sequence occurs in step 2 where a pair of electrons from the phenol ring attacks the electrophile forming a car-bocation intermediate. The methylol group of the hydroxymethylated phenol is unstable in the presence of acid and loses water readily to form a benzylic carbo-nium ion (step 3). This ion then reacts with another phenol to form a methylene bridge in another electrophilic aromatic substitution. This major process repeats until the formaldehyde is exhausted. 

The first step is usually, but not always, rate determining. It can be seen that this mechanism greatly resembles the tetrahedral mechanism discussed in Chapter 10 and, in another way, the arenium ion mechanism of electrophilic aromatic substitution. In all three cases, the attacking species forms a bond with the... 

---