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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.

~~~~  Effect of Substituent Groups ~~~~

Like benzene, toluene undergoes EAS. (e.g. sulfonation). Although there are three possible products, this reaction yields appreciable amounts of only two of them: the ortho and para isomers.

Benzene and toluene are insoluble in sulfuric acid. Whereas the sulfonic acids are readily soluble. Completion of the reaction is indicated simply by disappearance of the hydrocarbon layer. When shaken with fuming sulfuric acid at room temperature, benzene reacts completely within 20 to 30 minutes, whereas toluene is found to react within only a minute or two.

Studies of other reactions give similar results. For some reason, the methyl group makes the ring more reactive than unsubstituted benzene, and directs the attacking reagent to the ortho and para positions of the ring. We cal the methyl group an activating group and also an ortho, para director.

Alternatively, nitrobenzene has been found to undergo substitution more slowly than benzene, and to yield chiefly the meta isomer. We call the nitro group a deactivating group and also a meta director.. 

Like methyl or nitro, any substituent group attached to a benzene ring affects the reactivity of the ring and determines the orientation of substitution. I.E. When an electrophilic reagent attacks an aromatic ring in EAS, it is the group already attached to the ring that determines how readily the attack occurs and also specifies the location of where it occurs.

The following table summarizes the orientation of nitration in a number of substituted benzenes. Of the five positions open to attack, three (60%) are ortho and para to the substituent group, and two (40%) are meta to the group. Thus, if there were no selectivity in the substitution reactions, we would expect the ortho and para isomers to make up 60% of the product, and the meta to make up 40%. Instead we see that seven of the groups direct 96 -100% of nitration to the ortho and para positions. The other six direct 72-94% of the nitration to the meta position.

A given group causes the same general kind of orientation (ortho/para or meta) whatever t the electrophilic reagent involved. The actual distribution of isomers nay vary, however, form reaction to reaction. Compare the distribution of isomers obtained form toluene by sulfonation or bromination with that obtained by nitration.

The following reaction scheme is one example of the way in which relative reactivities can be measured quantitatively. Competitive reactions are carried out, in which the compounds to be compared are allowed to compete for a limited amount of reagent.

In this particular case, results indicate that toluene is about 25 times as reactive as benzene. Alternatively, chlorobenzene is only one-thirtieth as reactive as benzene. The chloro group is thus classified as de-activating (1:30); the methyl group as activating (25:1). Aniline (C6H5NH2) is roughly one million times as reactive as benzene. Nitrobenzene (C6H5NO2) is roughly one millionth as reactive as benzene.

The methods described here have been used to determine the effects of a large number of groups on EAS. (Note that the halogens constitute a group by themselves. They are the only deactivating substituents which act as ortho, para directors vs. meta directors).

The presence of two substituents on a ring makes the problem of orientation more complicated. But even here we can often make very definite predictions.

First of all, the two substituents may be located so that the directive influence of one reinforces that of the other. For example, in I, II and II the orientation clearly must be that indicated by the arrows.

On the other hand, when the directive effect of one group opposes that of the other, it may be difficult to predict the major product. In such cases, mixtures are often obtained. It is however, sometimes still possible in certain cases to make predictions.

1) Strongly activating groups generally win out over deactivating or weakly acitvating groups. The differences in directive power in the sequence

are great enough to be used in planning feasible synthesis. For example:

There must be, however, a fairly large difference in the effects of the two groups for clear-cut results. otherwise one gets results like these:

There is often little substitution between two groups that are meta to each other. In many cases it seems as though there is just not enough room between two groups located meta to each other for appreciable substitution to occur there, as illustrated by IV and V:

In the synthesis of pure aromatic compounds, we must consider the order in which we introduce the various substituents into the ring. E.G. In the preparation of nitrobenzene, it is obvious that if we nitrate first and then brominate, we will obtain the meta isomer. Whereas if we brominate first and then nitrate, we will obtain a mixture of ortho and para isomers. The order in which we proceed depends on which isomer we desire.

If our synthesis involves conversion of one group to another, we must consider the proper time for conversion. E.G. Oxidation of a methyl group yields a carbonyl group. In the preparation of nitrobenzoic acid form toluene, the particular product obtained depends upon whether oxidation or nitration is carried out first. 

Substitution controlled by an activating group yields a mixture of ortho and para isomers. Nevertheless, we must often make use of such reactions. it is usually possible to obtain the pure para isomer from the mixture by fractional crystallization. As the more symmetrical isomer, it is the less soluble and crystallizes while the solvent still retains the soluble ortho isomer. Some para isomer remains in solution to contaminate the ortho isomer which is difficult to purify. Special approaches are thus needed in order to prepare ortho isomers.

In the special case of nitro compounds, the difference in boiling points is often large enough that both ortho and para isomers can be obtained in pure form by fractional distillation. Thus, many aromatic compounds are best prepared not by direct substitution, but by conversion of one group to another -- with the final step starting form an original nitro compound.