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Overview

Let us now turn our attention to a new class of compounds, where the aromatic ring will be viewed not as a functional group, but as a substituent. Like the double bond, we will find that the ring exerts powerful effects, with its conjugated electrons creating a strong nucleophile for an electrophilic carbocation containing the desired alkyl group. We will therefore expect to see a fair amount of electrophilic aromatic substitution (EAS) in these compounds.

Thus, to the aromatic ring there can be attached any one (or tow or three) of dozens of different substituents. These substituents modify the effects of the ring, and make substituted phenyl groups the most widely used of probes into the electronic demands of organic reactions.  

Many important hydrocarbon compounds are not simply aliphatic or aromatic, but rather contain both aliphatic and aromatic components. Compounds of this type are commonly called arenes. Ethylbenzene, for example, contains a benzene ring and an aliphatic side chain.

Since the arenes are composed of two different chemical groups, we might expect them to show two different sets of chemical properties. The ring of ethylbenzene should undergo the electrophilic substitution characteristic of benzene, and the side chain should

undergo the free-radical substitution characteristic of ethane. Also, the properties of each portion of the molecule should be modified by the presence of the other portion. The ethyl group should modify the aromatic properties of the ring, and the ring should modify the aliphatic properties of the side chain. These predictions are correct:

1) Treatment of ethylbenzene with nitric acid and sulfuric acid introduces a nitro group into the ring. Because of the ethyl group, nitration takes place more rapidly than with benzene itself, and occurs chiefly at the positions ortho and para to the ethyl group.

2) Treatment with bromine in the presence of light introduces a bromine atom into the side chain. Because of the ring, bromination takes place more readily than with ethane, and occurs exclusively on the carbon atom nearer to the ring.

Thus, each portion of the molecule affects the reactivity of the other portion and determines the orientation of attack.

We shall first examine those arenes which, like ethylbenzene, are made up of aromatic and alkane units: the alkylbenzenes (and their derivatives). This will lead us to aromatic - alkene compounds (alkenylbenzenes) as well as to aromatic-alkyne compounds (alkynylbenzenes). 

Alkylbenzenes: Industrial Source

It would be difficult to overemphasize the importance to the chemical industry and to our entire economy of the large-scale production of benzene and the alkylbenzenes. Just as the alkanes obtained form petroleum are ultimately the source of nearly all out aliphatic compounds, so benzene and the alkylbenzenes are ultimately the source of nearly all our aromatic compounds.

There are two large reservoirs of organic material: coal and petroleum. Aromatic compounds are obtained from both. Aromatic compounds are separated as such from coal tar, and are synthesized form the alkanes of petroleum.    

By far, the larger portion of coal that is mined today is converted into coke, which is needed for the smelting of iron ore into steel. When coal is heated in the absence of air, it is partly broken down into simpler, volatile compounds which are driven out. The residue is coke. The volatiles consist of coal gas and a liquid known as coal tar.

From coal tar, by distillation, there are obtained a number of aromatic compounds. Upon coking, one ton of soft coal may yield about 120 pounds of coal tar. From this 120 pounds, the following aromatic compounds can be separated:

Benzene: 2.0 pounds

Toluene:  0.5 pound

Xylene:    0.1 pound

Phenol:    0.5 pound

Cresols:   2.0 pounds

Napthalene: 5 pounds

Additional quantities of aromatic compounds are synthesized form alkanes by the process of catalytic reforming. This can bring about not only dehydrogenation, (as in the formation of toluene from methylcyclohexane) but also cyclization and isomerization, as in the formation of toluene from n-heptane or 1,2-dimethylcyclopentane. In an analogous way, benzene is obtained form cyclohexane and methylcyclopentane as well as from the hydro-alkylation of toluene.

Today, petroleum is the chief source of the enormous quantities of benzene, toluene, and the xylenes required for chemicals and fuels.

Preparation of Alkylbenzenes

Although a number of simpler alkylbenzenes are available from industrial sources, the more complex compounds must be synthesized in one of the following ways.

Friedel-Crafts alkylation is extremely useful since it permits the direct attachment of an alkyl group to the aromatic ring. There are, however, a number if limitations of its use, including the fact that the alkyl group that attaches to the ring is not always the same as the alkyl group of the parent halide.

There are also aromatic compounds containing aliphatic side chains that are not simple alkyl groups. An alkylbenzene can be prepared form one of these compounds by converting the side chain into an alkyl group. Although there is an aromatic ring in the molecule, this conversion is essentially the preparation of a alkane from some other aliphatic compound. The methods used are those that we have already learned for the preparation of alkanes: E.G. hydrogenation of a C=C double bond in a side chain. The most important side-chain conversion involves reduction of ketones either by amalgamated zinc and HCl (Clemmensen reduction) or by hydrazine and strong base (Wolff-Kishner reduction).

As we shall soon see, alkylbenzenes are extremely useful precursors of the compounds that are formally their derivatives: halides, alcohols and related compounds.

I. Friedel-Crafts Alkylation

If a small amount of anhydrous aluminum chloride is added to a mixture of benzene and methyl chloride, a vigorous reaction occurs, hydrogen chloride gas is evolved, and toluene can be isolated from the reaction products.

In the various modifications to this famous reaction (first discovered in 1877 at the University of Paris by American chemists Charles Friedel and James Crafts), each of the components can be varied. The alkyl halide may contain an alkyl group more complicated than methyl, and a halogen atom other than chlorine. In some cases alcohols are used, or even alkenes (mostly in industry). Substituted alkyl halides (e.g. benzyl chloride) can also be used. Because of the low reactivity of halogen attached to an aromatic ring, aryl halides cannot be used in place of alkyl halides.

The aromatic ring to which the side chain becomes attached may be that of benzene itself, certain substituted benzenes (mainly alkylbenzenes and halobenzenes) or more complicated aromatic ring systems like napthalene and anthracene.

Since the attachment of n alkyl side chain makes the ring more susceptible to further attack, steps must be taken to limit substitution to monoalkylation. As in the halogenation of alkanes, this is accomplished by using an excess of the hydrocarbon. In this way an alkyl carbocation seeking an aromatic ring is more likely to encounter an unsubstituted ring than a substituted one. Frequently the aromatic compound serves a dual purpose, acting as solvent as well as reactant.

Also, from polyhalogenated alkanes, it is possible to prepare compounds containing multiple aromatic rings.

Mechanism of Reaction

There are two distinct possible mechanisms of Friedel-Crafts alkylation. Both involve electrophilic aromatic substitution. But they differ as to the nature of the electrophile. One mechanism consists of the following steps:

in which the electrophile is an alkyl cation. The function of the aluminum chloride is to generate this carbocation by abstracting the halogen from the alkyl halide. it is not surprising that the other Lewis acids can function in the same way and thus take the place of aluminum chloride:

We might expect the benzene ring to be attacked by carbocations generated in other ways. E.G. Carbocations could be generated by the action of acid on alcohols.

E.G. Carbocations could also be generated by the action of acid on alkenes.

These expectations are correct. In the presence of acids, alcohols and alkenes tend to alkylate aromatic rings in what we may view as a modification of the Friedel-Crafts reaction.

We might also expect the reaction to be accomplished by the type of rearrangement characteristic of carbocation reactions. This is also correct. Alkylbenzenes containing rearranged alkyl groups not only are formed but are sometimes the sole products.

In each case, we see that the particular kind of arrangement corresponds to what we would expect if a less stable (primary) carbocation were to rearrange by a 1,2-shift to a more stable (secondary or tertiary) carbocation.

Thus, we can make an addendum to our list of carbocation reactions.

A carbocation may:

a) Combine with a negative ion or other basic molecule

b) Rearrange to a more stable carbocation

c) Eliminate a hydrogen ion to form an alkene

d) Add to an alkene to form a larger carbocation

e) Alkylate an aromatic ring

In alkylation, as in other reactions, the carbocation gains a pair of electrons to complete the octet of the electron-deficient carbon - in this case from the pi cloud of an aromatic ring.

There is also evidence that makes it very likely that there is second mechanism for Friedel -Crafts alkylation. In this mechanism, the electrophile is not an alkyl cation but an acid-base complex of an alkyl halide and a Lewis acid, from which the alkyl group is transferred in one step from halogen to the aromatic ring as follows:

This duality of mechanism does not reflect exceptional behavior, but is usual for electrophilic aromatic substitution (EAS). It also fits into a familiar pattern for nucleophilic substitution, which -- from the standpoint of the alkyl halide -- is the kind of reaction taking place. Moreover, the particular halides (primary and methyl) which appear to react by this second, bimolecular mechanism are exactly the ones that would have been expected to do so.

II. Reactions of Alkylbenzenes

The most important reactions of alkylbenzenes are outlined below, with toluene and ethylbenzene as specific examples. Essentially the same behavior is shown by compounds bearing other side chains. Except for hydrogenation and oxidation, these reactions involve wither electrophilic substitution in the aromatic ring or free-radical substitution in the aliphatic side-chain. 

Although benzene and alkanes are quite unreactive toward the usual oxidizing agents (KMnO4, K2Cr2O7, etc.) the benzene ring renders an aliphatic side chain quite susceptible to oxidation. The side chain is oxidized down to the ring, with only a carboxyl group (COOH) remaining to indicate the position of the original side chain.

This reaction is used for two purposes:

a)  Synthesis of carboxylic acids. This simply requires the choice of the proper alkylbenzene. Substituent groups (e.g. methyl, CH3 or nitro, NO2) in the positions para to the substitution site are typically preserved.

b)  Identification of alkylbenzenes. The number and relative positions of side chains can frequently be determined by oxidation to the corresponding acids. These acids (e.g. ortho, meta or para) or their derivatives can readily be distinguished from each other by their melting points.

EAS in Alkylbenzenes

Many reactions involving alkylbenzenes, or arenes, include ring substitution via electrophilic aromatic substitution. Because of its electron-releasing effect, an alkyl group activates a benzene ring to which it is attached, and directs to the ortho and para positions.

Halogenation: Ring vs. Side Chain

Of the two potential sites of attack, the side chain is alkane-like and should undergo halogenation as alkanes do: via free-radical substitution. This reaction requires conditions under which halogen atoms are formed: high temperatures or light. 

The ring is benzene-like, and should undergo substitution as benzene does: via electrophilic substitution. This reaction involves transfer of positive halogen, which is promoted by acid catalysts like ferric chloride.  

We must expect, then, that the position of attack in, say, toluene would be governed by which attacking particle is involved, and therefore by the conditions employed. This is, indeed, the case. If chlorine is bubbled into boiling toluene that is exposed to UV light, substitution occurs almost exclusively in the side chain. In the absence of light and in the presence of ferric chloride, substitution occurs mostly in the ring.

Like nitration and sulfonation, ring halogenation yields chiefly the ortho and para isomers.

Similar results are obtained with other alkylbenzenes, and with bromine as well as chlorine.

Side-chain halogenation, like halogenation of alkanes, may yield polyhalogenated products. Even when the reaction is limited to monohalogenation, it may yield a mixture of isomers.

Side-chain chlorination of toluene can yield successively the mono-, di-, and trichloro compounds. These are known as benzyl chloride, benzal chloride, and benzotrichloride. Such compounds are important intermediates in the synthesis of alcohols, aldehydes and acids.

Side-chain Halogenation

Chlorination and bromination of side chains differ from one another in orientation and reactivity in one very significant way. An alkylbenzene with a side chain more complex than methyl may offer more than one position for attack. We must then consider a mixture of isomers. Bromination of ethylbenzene, for example, could yield two products:

Yet the only product is the former. Abstraction of the hydrogens attached to the carbon next to he ring is greatly preferred.

Hydrogen atoms attached to carbon joined directly to an aromatic ring are called benzylic hydrogens.

The relative ease with which benzylic hydrogens are abstracted is shown not only by orientation of bromination -- but also by comparison of compound reactivities. E.G. A benzylic hydrogen of toluene is 3.3 times as reactive toward bromine atoms as the tertiary hydrogen of an alkane -- and nearly 100 million times as reactive as a hydrogen of methane. Thus:

Side-chain halogenation of alkylbenzenes proceeds by the same mechanism as halogenation of alkanes. Bromination of toluene, for example, includes the following steps:

The fact that benzylic hydrogens are unusually easy to abstract means that benzyl radicals are unusually easy to form.

We can now expand the sequence of radical stabilities. Relative to the hydrocarbon form which each is formed, the relative stability of free radicals is:

Orientation of chlorination shows that chlorine atoms, like bromine atoms, preferentially attack benzylic hydrogen. But, as we see, the preference is less marked:

Benzyl Radical: Resonance Stabilization

Bond dissociation energies indicate that 19 kcal/mole less energy (104 vs. 85) is needed to form the benzyl radical from toluene than to form the methyl radical from methane.

Toluene contains the benzene ring and is therefore a hybrid of the two Kekule structures I and II.

 Similarly, the benzyl radical is a hybrid of the two Kekule structures, III and IV.

This resonance causes stabilization (lowers the energy content). However, resonance involving Kekule structures presumably stabilizes both molecule and radical to the same extent, and hence does not affect the difference in their energy contents. If there were no other factors involved, we might then expect the bond dissociation energy for a benzylic hydrogen to be about the same as that of a methane hydrogen. 

Considering further, however, we find that we can draw three additional structures for the radical: V. VI, and VII. In these structures, there is a double bond between the side chain and the ring, and the odd electron is located on the carbon atoms in positions ortho and para to the side chain. Thus, the odd electron is delocalized, being distributed evenly about the ring. We cannot draw similar structures for the toluene molecule.   

We say then that the benzyl radical is stabilized by resonance, implying that the the benzyl radical is stabilized to a greater extent than the compound from which it was formed.

In terms of orbitals, delocalization results from overlap of the p orbital occupied by the odd electron with the pi cloud of the ring.

Like the allyl radical, we see that the benzyl radical is a conjugated molecule. Here the p orbital on the carbon bearing the odd electron is conjugated -- not just with one double bond, but with the entire pi-bond system of the benzene ring.

Stability of the Benzyl Cation

Recall (Unit 13: Conjugation) that the conjugation that stabilizes the allyl free radical also stabilizes the allyl cation.

Relative to he substrate from which each cation is generated, the benzyl cation is about as stable as the allyl or isopropyl cation. Thus our sequence can be expanded as follows:

The presence of a phenyl group in place of a hydrogen or methyl chloride thus stabilizes the cation by 61 kcal/mol. As we did for the free benzyl radical, we attribute the stabilization to conjugation with the benzene ring, and account for it on the basis of resonance. Both the benzyl cation and the substrate from which it is made are hybrids of Kekule structures. In addition, the carbocation can be represented by three other structures I, II, and III, in which the positive charge is located on the ortho and para

positioned carbon atoms. Whether considered as resonance stabilization or simply as dispersal of charge, contribution form these structures stabilizes the carbocation.

The orbital picture of the benzyl cation is similar to that of the benzyl free radical except that the p orbital that overlaps the pi cloud is an empty one. The p orbital contributes no electrons, but permits further delocalization of pi electrons to include the carbon nucleus of the side chain. 

Nucleophilic Substitution

Let us turn our attention now to the behavior of benzylic substrates in nucleophilic substitution. We begin with the SN1 type of reaction, in which the reaction depends upon the rate of formation of a carbocation. Although formally primary, a benzyl cation is about as stable as secondary carbocation. Thus, as we might expect, benzyl substrates undergo SN1 reactions about as fast as secondary substrates.

By introducing various substituents into the aromatic ring, we can prepare scores of different benzylic substrates. Substituents at the meta or ortho position have no effect on steric hindrance at the benzylic carbon, but can change the polar effect of the aryl group in either direction and to varying degrees. From the para position, for example, OCH3 exerts powerful electron release, and NO2 powerful electron withdrawal.

As we might expect, electron release increases the stability of a benzylic cation, and electron withdrawal decreases its stability. With these changes in cation stability, there occur corresponding changes in the rate at which substrates undergo SN1.

The effects of these substituents here parallel their effects on electrophilic aromatic substitution, and for good reason. In both kinds of reaction, a positive charge is developing in the aromatic ring. A substituent can either disperse or intensify the charge., and thus either stabilize or destabilize the incipient carbocation. 

The rate of an SN2 reaction, as we have seen, depends largely upon steric factors. Here benzyl substrates enjoy the same advantage as an allyl substrate. They are primary and offer relatively little steric hindrance to nucleophilic attack -- and so they undergo SN2 about as fast as primary substrates. 

Substituents on the alpha carbon of benzylic substrates have the kind of effects that we would expect. Additional phenyl groups raise the stability of the cation still further, and speed up its formation by SN1. At the same time, they increase steric hindrance to nucleophilic attack and slow down SN2. The result is a familiar one: the tendency to undergo a shift in mechanism from bimolecular to unimolecular as branching increases.

Preparation of Alkenyl Benzenes

An aromatic hydrocarbon with a side chain containing a double bond can be prepared by essentially the same methods as simple alkenes: by 1,2-eilimnaiotn. The presence of the aromatic ring in the molecule may affect the orientation of elimination and the ease with which it takes place.

On an industrial scale, the elimination generally involves dehydrogenation. For example, styrene - one of the most important synthetic aromatic compounds - can be prepared by simply heating ethylbenzene to about 600 degrees C in the presence of a catalyst. The ethylbenzene, in turn, is prepared by a Friedel-Crafts reaction between two simple hydrocarbons: benzene and ethylene.

In the laboratory, however, we are most likely to use dehydrohalogenation or dehydration.

In the following examples, note the possible formation of two products, while in actuality  in both cases, only one of these is formed. We saw earlier that where isomeric alkenes can

be formed by such elimination, the preferred product is generally the more stable alkene. This is the case here, too. That 1-phenylpropene is much more stable than its isomer is evidenced by the fact that 3-phenylpropene is rapidly converted into 1-phenylpropene by treatment with hot alkali. 

A double bond that is separated from a benzene ring by one single bond is said to be conjugated with the ring. Such conjugation confers unusual stability on a molecule. This stability is reflected in a faster rate of formation, which affects not only orientation of elimination, but also the ease with which elimination occurs.

Reactions of Alkenyl Benzenes

As we might expect, alkenylbenzenes undergo two sets of reactions: substitution in the ring, and addition to the double bond in the side chain. Since both ring an double bond are good sources of electrons, there may be competition between the two sites for certain electrophilic reagents. It is not surprising that, in general, the double bond shows higher reactivity than the resonance-stabilized benzene ring. Our main interest in these reactions will be the way in which the aromatic ring affects the reactions of the double bond.

Although both the benzene ring and the C=C double bond can be hydrogenated catalytically, the conditions required for the double bond are much less extreme.

Thus, by proper selection of conditions, it is quite easy to hydrogenate the side chain without touching the aromatic ring.

Mild oxidation of the double bond yields a 1,2-diol; more vigorous oxidation cleaves the C=C double bond and generally gives a carboxylic acid in which the COOH group is attached directly to the ring.

Both double bond and ring react with halogens by heterolytic mechanisms that have essentially the same first step: attack on the pi cloud by positively charged halogen. Halogen is consumed by the double bond first, and only after the side chain is completely saturated does substitution in the ring occur. Ring halogenated alkenylbenzenes must be prepared, therefore, by generation of the double bond after halogen is already present in the ring.  

Similarly, alkenylbenzenes undergo the other addition reactions characteristic of the C=C double bond. In conjugated systems, the ring affects both orientation and reactivity.

Addition to Conjugated Alkenylbenzenes

Addition of an unsymmetrical reagent to a C=C double bond may yield two different products via two different orientations. Here, the aromatic ring is attached to one of the doubly bonded carbon atoms, and determines what this orientation will be. This effect can well be illustrated by a single example: addition of HBr to 1-phenylpropene.

1) In the absence of peroxides, bromine becomes attached to the C atom adjacent to the ring.

2) In the presence of peroxides, bromine becomes attached to the C atom once removed from the ring.

The first step of each of these reactions occurs in the way that yields the benzyl cation or the benzyl free radical rather than the alternative secondary action or secondary free radical. Once more, we see, the first step of addition takes place in the way that yields the more stable particle, carbocation or free radical. The same fundamental factor, conjugation with the aromatic ring, which determines the orientation in the formation of alkenylbenzenes, also determines orientation in their reactions.

Now, on the basis of the greater stability of the benzylic particle being formed, we might expect addition to a conjugated alkenylbenzene to occur faster than addition to  a simple alkene. Alternatively, we have seen that conjugated alkenylbenzenes are more stable than simple alkenes. Thus we might expect addition to conjugated alkenylbenzenes to occur more slowly than to simple alkenes.

The relative rates of these two reactions depend chiefly upon the energy barriers, E(act), for the reaction. Resonance stabilization of the incipient benzylic particle lowers the energy level of the transition state. Stabilization of the alkene lowers the energy of the reactant. Whether reaction is faster or slower than for simple alkenes depends upon which is stabilized more: reactant or transition state.

The fact is that conjugated alkenylbenzenes are much more reactive than simple alkenes toward both ionic and free radical addition. Here (as in most cases of this nature) resonance stabilization of the transition state leading to a carbocation or free radical is more important than resonance stabilization of the reactant.