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Overview

We have already seen that the characteristic reactions of benzene involve substitution, in which the resonance stabilized ring system is preserved. What kind of reagents and mechanisms are involved in the implementation of these substitution reactions ?

Above and below the plane of the benzene ring, there is a cloud of pi electrons. Through resonance, these pi electrons are more involved in holding together carbon nuclei than are the pi electrons of a C=C double bond. And yet, in comparison with sigma electrons, these pi electrons are loosely held and are available to a reagent that is seeking electrons.

Thus, it is not surprising that in its typical reaction, the benzene ring acts as a source of electrons - or as a base. The compounds with which it reacts are deficient in electrons. Thus they are electrophilic reagents - or acids. Just as the typical reactions of the alkenes are electrophilic addition reactions, so the typical reactions of the aromatics are electrophilic substitution reactions.

I. Nitration

The commonly accepted mechanism for nitration with a mixture of nitric and sulfuric acids involves the following sequence of reactions:

Step 1) generates the nitronium ion NO2+ which is the electrophilic particle that attacks the benzene ring. (This reaction is simply an acid-base equilibrium in which sulfuric acid serves as the acid and the much weaker nitric acid serves as a base). Needing electrons, the nitronium ion finds them particularly available in the pi cloud of the benzene ring. Thus in step 2), it attaches itself to one of the C atoms by a covalent bond. This forms the carbocation, often called a benzonium ion.

What is the structure of this carbocation ? We find that we can represent it by three structures ( I, II, III) that differ from each other only in the position of double bonds and positive charge. The actual ion must then be a resonance hybrid of these three structures.

This means, of course, that the positive charge is not localized on one C atom, but is distributed over the molecule, being particularly strong in the C atom ortho and para to the carbon bearing the -NO2 group. The dispersal of the positive charge over the molecule by resonance makes this ion more stable than anion with a localized positive charge. it is probably because of this stabilization that the carbocation forms at all, in view of the stability of the original benzene itself. The hybrid carbocation can be represented by IV, where the broken line stands for fractional or partial bonds resulting from delocalized pi electrons.

Thus far the reaction is like addition to alkenes. An electrophilic particle, attracted by the pi electrons, attaches itself to the molecule to form a carbocation. But the fate of this carbocation is different form the fate of the ion formed form an alkene. Attachment of a basic group to the benzonium ion to yield the addition product would destroy the aromatic character of the ring. Instead, the basic ion, HSO4-, abstracts a proton ("fast" step 3) to yield the substitution product, which retains the resonance-stabilized ring. Loss of a proton, as we have seen, is one of the reactions typical of a carbocation. It is the preferred reaction in this case.

Thus, in EAS (as in previous cases) it is the formation of the carbocation that is the more difficult (rate determining) step. Once formed, the carbocation rapidly loses a proton to form the products.

II. Sulfonation

Sulfonation of many aromatic compounds involves the following steps:

Step 1) which generates the electrophilic sulfur trioxide, is simply an acid-base equilibrium - this time between molecules of sulfuric acid. For sulfonation we commonly use sulfuric acid containing an excess of SO3. Even if this is not done, it appears that SO3 formed in the first step can be the electrophile.

Step 2): the electrophilic reagent SO3 attaches itself to the benzene ring to form the intermediate carbocation. Although SO3 is not positively charged, there is an electron deficiency on the S atom, making it an acid.

Step 3) is the loss of a proton to form the resonance-stabilized substitution product, which is this time the anion of benzosulfonic acid which, being a strong acid, is highly dissociated (Step 4).  

With some aromatic substrates and at certain levels of acidity, the electrophile may be HSO3+ or molecules that can readily transfer SO3 or HSO3+ to the aromatic ring.

III. Friedel-Crafts Alkylation

In this case, the electrophile is typically a carbocation. It, too, is formed in acid-base equilibrium, this time in the Lewis sense.

In certain cases, there is no free carbocation involved. Instead, the alkyl group is transferred - without an electron pair - directly to the aromatic ring from the polar complex, I, between AlCl3 and the alkyl halide.

The electrophile is thus either R+ or a molecule like I that can readily transfer R+ to the aromatic ring. This duality of mechanism is common in EAS. In either case, the Lewis acid R+ is displaced from RCl by the other Lewis acid, AlCl3.

IV. Halogenation

Aromatic halogenation, illustrated here for chlorination, involves the following steps:

The key step 2) is the attachment of positive chlorine to the aromatic ring. It seems unlikely, though, that a free Cl+ ion is involved. Instead, ferric chloride combines with Cl2 to form complex II, from which chlorine is transferred, without its electrons, directly to the ring.

Addition of halogens to alkenes, we have seen, also involves attack by positive halogen to form an intermediate cation. The loosely held pi electrons of an alkene make it more reactive, however, and positive halogen is transferred form the halogen molecule itself, X2, with loss of Cl-. The less reactive benzene molecule needs the assistance of a Lewis acid. The reaction occurs with the loss of the better leaving group, FeCl4-. Indeed, more highly reactive aromatic compounds, that is, those whose pi electrons are more available, do react with halogens in the absence of any added Lewis acid.

V. Desulfonation / Protonation

When an aromatic sulfonic acid is heated to 100 - 175 degrees C with aqueous acid, it is converted into sulfuric acid and an aromatic hydrocarbon. This desulfonation is the exact reverse of the sulfonation process by which sulfonic acid was originally made.

By applying the usual principles of chemical equilibrium, we can select conditions which will drive the reaction in the direction we want it to go. To sulfonate we use a large excess of concentrated or fuming sulfuric acid. High concentration of sulfonating agent and low concentration of water (or its removal by reaction with SO3) shift the equilibrium toward sulfonic acid. To desulfonate, we use dilute acid and often pass superheated stem through the reaction mixture. High concentration of water and removal of the relatively volatile hydrocarbon by steam distillation shift the equilibrium toward hydrocarbon.

According to the principle of microscopic reversibilty, the mechanism of desulfonation must be the exact reverse of the mechanism of sulfonation. The reaction is simply another example of EAS. The electrophile is the proton, and the reaction is protonation (or proto-desulfonation). Sulfonation is unique among EAS reactions in its reversibilty.

~~ Electrophilic Aromatic Substitution ~~

EAS reactions seem, then, to proceed by a single common mechanism - whatever reagent is involved. This can be summarized for the reagent YZ as follows:

Two essential steps are involved:

1) Attack by an electrophilic reagent up on the ring to form a carbocation.

2) Abstraction of a proton from the carbocation by some base.

In each case, these is a preliminary acid-base reaction which generates the electrophile. The proposed substitution, however, is contained in these two steps.

Using the effects of isotopes, there is sufficient evidence to indicate that the mechanism of our proposed reaction sequence is indeed valid, as opposed to the single step reaction mechanism illustrated below.

Regarding whether or not the first step is rate controlling, we consider the following reaction sequence. In this case, it is the reverse reaction that must be much slower than step 2) if step 1) is to be truly rate-determining. Summarized in terms of the rate constants:

We can see why reactions like these are not reversible. In the reverse reaction, nitrobenzene is protonated to form the carbocation. But this would simply result in the rapid formation of nitrobenzene.

Unlike most other EAS reactions, sulfonation is reversible. This means that the carbocation

can lose SO3 to form the hydrocarbon. Evidently here reaction 2) is not much faster than the reverse reaction 1). In sulfonation, the energy barriers on either side of the carbocation must be roughly the same height. Some ions go one way, some go the other way. 

Theory of Reactivity

We have seen that certain groups activate the benzene ring and direct substitution to ortho and para positions, while other groups deactivate the ring and (except halogens) direct substitution to meta positions. Let us try to rationalize this on the basis of what we know.

Recall that reactivity and orientation both depend on relative rates of reaction. Methyl activates the ring because it causes the ring to react faster than benzene. It causes ortho, para orientation because it makes the ortho & para positions react faster than meta positions.

Now we know that, whatever the specific reagent involved, the rate of EAS is determined by the same slow step - attack of the electrophile on the ring to form a carbocation:

Any differences in the rate of substitution must therefore be due to differences in the rate of carbocation formation.

For closely related reactions, a difference in rate of formation of carbocations is largely determined by a difference in activation energy, E(act) -- that is, by a difference in the stability of transition states. As with other carbocation reactions we have studied, factors that stabilize the ion by dispersing the positive charge should (for the same reasons) stabilize the incipient carbocation of the transition state. Again we expect the more stable carbocation to be formed more rapidly. We shall therefore focus on the relative stabilities of carbocations.

In EAS, the intermediate carbocation is  a hybrid of structures I, II and II, in which the positive charge is distributed about the ring, being strongest at the positions ortho and para to the carbon atom under attack.

A group already attached to the benzene ring should affect the stability of the carbocation by dispersing or intensifying the positive charge, depending upon its electron-releasing or electron-withdrawing nature. It is evident from the structure of the ion (I - III) that this stabilizing effect should be especially important when the group is attached ortho or para to the carbon atom being attacked.

In order to compare rates of substitution in benzene, toluene, and nitrobenzene, we compare the structures of carbocations formed form the three compounds.

By releasing electrons, the methyl group (II) tends to neutralize the positive charge of the ring and so become more positive itself. The dispersal of charge thus stabilizes the carbocation. Similarly, the inductive effect stabilizes the developing positive charge in the transition state and thus leads to a faster reaction.

The -NO2 group, on the other hand, has an electron-withdrawing inductive effect (III). This tends to intensify the positive charge, destabilizes the carbocation, and reduces the rate of reaction. In conclusion:

Reactivity in EAS depends upon the tendency of a substituent group to release or withdraw electrons.

1) A group that releases electrons (nucleophilic) activates the ring.

2) A group that withdraws electrons (electrophilic) deactivates the ring.

Thus, like CH3, other alkyl groups release electrons and activate the ring. Not all ring activation is due to the inductive effects of charge dispersal. As we shall see later, electron release by NH2 and OH (and by their derivatives NHCOCH and OCH3) is due to resonance.

We have already seen the electron-withdrawing effects of of the halogens on alcohols. The full-fledged positive charge of the N(CH3)3+ group has a powerful attraction for electrons. In other deactivating groups, (e.g. NO2, CN, COOH) the atom next to the ring is attached by a multiple bond to oxygen or nitrogen. These electronegative atoms attract the mobile pi electrons, making the atom next to the ring electron-deficient and electron-withdrawing.

We might expect replacement of hydrogen in CH3 by halogen to decrease the electron-releasing tendency of the group, and perhaps to convert it into an electron-withdrawing group. This is found to be the case. Toward nitration, toluene is 25 times as reactive as benzene. Benzyl chloride, however, is only one-third as reactive as benzene. The CH2Cl group is thus weakly deactivating. Further replacement of hydrogen by halogen to yield CHCl2 and CCl3 groups result in stronger deactivation.

Theory of Orientation

Before attempting to account of orientation effects in EAS, let's examine the facts.

1) An activating group activates all positions of the benzene ring to some degree. It simply directs ortho and para positions more than meta positions.

2)  A deactivating group deactivates all positions in the ring, even the positions meta to it. It directs meta simply because it deactivates ortho and para positions even more than meta positions.

3) Thus, both ortho, para orientation and meta orientation arise in the same way.

4) The effect of any group is strongest at the ortho & para positions.

I. CH3 Group: Activator.

Let's compare carbocations formed by attack at the para and meta positions of toluene (an activator). Each of these is a hybrid of three structures ( I - III and IV - VI respectively). In one of these six structures (II) the positive charge is located on the carbon atom to which the activating group (CH3) is attached. Although CH3 releases electrons to all positions of the ring, it does so most strongly to the carbon atom nearest to it. Thus, structure II is a particularly stable one. Because of contribution form structure II, the hybrid carbocation resulting from attack at the para position is more stable than the carbocation resulting from attack at the meta position. Para substitution thus occurs faster than meta substitution. 

Similarly, it can be seen that attack at the ortho position (VII - IX) also yield s amore stable carbocation (through contributions form (IX) than attack at a meta position. Thus:

In toluene, ortho, para substitution is faster than meta substitution because electron release by CH3 is more effective during attack at the positions ortho and para to it.

II. NO2 Group - Deactivator 

Next, let us compare the carbocations formed by attack at the para and meta positions of nitrobenzene - a deactivator. Each of these is a hybrid of three structures: (X - XII) for para attack, (XIII - XV) for meta attack. In one of these structures (XI) the positive charge is located on the carbon atom to which the NO2 group is attached. Although NO2 withdraws electrons from all positions, it does so most strongly from the carbon atom nearest to it. hence this C atom, already positive, has little tendency to accommodate the positive charge of the carbocation.

Structure XI is this particularly unstable and does little to help stabilize the ion resulting from attack at the para position. Thus, the ion for para attack is virtually a hybrid of only two structures (X and XII). The positive charge is mainly restricted to only two carbon atoms. It is less stable than the ion resulting from attack at a meta position, which is a hybrid of three structures, and in which the positive charge is accommodated by three C atoms. Thus, in nitrobenzene, para substitution occurs more slowly than meta substitution. 

Similarly, it can be seen that attack at an ortho position (XVI - XVIII) yields a less stable carbocation (instability of XVIII), than attack at a meta position.

Thus, in nitrobenzene, ortho, para substitution occurs more slowly than meta substitution because electron withdrawal by NO2 is more effective during attack at the positions ortho & para to it.

Thus we see that both ortho, para orientation by activating groups and meta orientation by deactivating groups follow logically from the structure of the intermediate carbocation. The charge of the ion is strongest at the positions ortho and para to the point of attack. Thus, a group attached to one of those positions can exert the strongest effect, whether activating or deactivating.

Electron Release via Resonance

We have seen that a substituent group affects both reactivity and orientation in EAS by its tendency to release or withdraw electrons. So far we have considered electron release and withdrawal only as inductive effects - that it, as effects due of the electronegativity of the particular substituent group concerned.

But certain groups (e.g. NH2, OH and derivatives) act as powerful activators toward EAS even though they contain electronegative atoms and can be shown in other ways to have electron-withdrawing inductive effects. if our approach to the problem is valid, these groups must release electrons in some other way than through their inductive effects. they are believed to do this by a resonance effect. Let us consider this.

I. NH2 Group - Activator

Although electronegative, the nitrogen of the NH2 group is basic and tends to share its last pair of electrons and acquire a positive charge. Just as ammonia accepts a proton to form the ammonium ion (NH4+), so organic compounds related to ammonia accept protons to form substituted ammonium ions.

The OH group shows similar but weaker basicity. We are already familiar with oxonium ions, ROH2+.

The effects of NH2 and OH on EAS can be accounted for by making the following assumptions regarding N and O atoms.

1) N and O share more than one pair of electrons with the ring

2) N and O can accommodate a positive charge.

The carbocation formed by attack para to the NH2 group of aniline is considered to be a hybrid not only of structures (I - III) with positive charges located on the C atoms of the ring, but also of structure IV in which the positive charge is carried by the N atom.

Structure IV is especially stable, since in it every atom (except H) has a complete octet of electrons. This carbocation is much more stable than the one obtained by attack on benzene itself, or the one obtained (V - VII) from attack meta to the NH2 group of aniline. In neither of these cases is a structure like VI possible.

Examination of the corresponding structures (VIII - XI) shows that ortho attack is much like para attack. Thus:

Substitution in aniline occurs faster than substitution in benzene, and occurs predominantly at the positions ortho & para to the activating substituent group NH2.

II. OH Group - Activator

Similarly, activation and ortho, para orientation by the OH group is accounted for by contribution of structures like XII and XIII, in which every atom has a complete octet of electrons.

III. Derivative Groups - Activators

The similar effects of the derivatives of NH2 and OH are accounted for by similar structures (shown only for para attack.)

Effect of Halogens on EAS

Halogens are unique in their role as ortho, para directing deactivators. Why ?

Halogen withdraws electrons through its inductive effect, and releases electrons through its resonance effect. So presumably, can the NH2 and OH groups - but there the much stronger resonance effect greatly outweighs the other. For halogens, the two effects are more evenly balanced, and we observe both.

Let us first consider reactivity. Electrophilic attack on benzene yields carbocation I, attack on chlorobenzene yields carbocation II. The elctron-withdrawing inductive effect of 

chlorine intensifies the positive charge in carbocation II, making the ion less stable and reducing the rate of reaction.

Next, to understand orientation, let us compare the structures of the carbocations formed by attack at the para and meta positions of chlorobenzene. Each of these is a hybrid of three structures, III - V for para, VI - VIII for meta. In one of these six structures (IV) the positive charge is located on the C atom to which chlorine is attached. 

Through its inductive effect, chlorine withdraws electrons most form the carbon to which it is joined, and thus makes structure IV especially unstable. As before, we expect IV to make little contribution to the hybrid, which should therefore be less stable than the hybrid ion resulting from attack at the meta positions. If only the inductive effect were involved, then, we would expect not only deactivation but also meta orientation.

But the existence of halonium ions has shown us that halogen can share more than one pair of electrons and can also accommodate a positive charge. If we apply the idea to the present case, what do we find ? The ion resulting from para attack is a hybrid not only of structures II - V, but also of structure IX, in which chlorine bears a positive charge and is joined to the ring by a double bond.

This structure should be comparatively stable, since in it every atom has a complete octet of electrons. No such structure is possible for the ion resulting from meta attack. To the extent that structure IX contributes to the hybrid, it makes the ion resulting from para attack more stable than the ion resulting from meta attack. Although we could not have predicted the relative importance of the two factors (the instability of IV and the stabilization by IX) the result indicates that the contribution from IX is the more significant.

In the same way, it can be seen that attack at an ortho position also yields an ion (X - XIII) that can be stabilized by accommodation of the positive charge by chlorine.

Through its inductive effect, halogen tends to withdraw electrons and thus to destabilize the intermediate carbocation. This effect is felt for attack at all positions, but particularly for attack at the positions ortho & para to the halogen.

Through its resonance effect, halogen tends to release electrons and thus to stabilize the intermediate carbocation. This electron release is effective only for attack at the positions ortho & para to the halogen.

The inductive effect is stronger than the resonance effect and causes a net electron withdrawal - and hence deactivation - for attack at all positions. The resonance effect tends to oppose the inductive effect for attack at the ortho & para positions, and hence makes the deactivation less for ortho, para attack than for meta.

Reactivity is thus controlled by the stronger inductive effect, and orientation is controlled by the resonance effect, which, although weaker, is more selective.