3.5: The Direction of the Reaction

Substituents affect the orientation of the reaction.

The three possible disubstituted products—ortho, meta, and para—are usually not formed in equal amounts. Instead, the nature of the substituent initially present on the benzene ring determines the position of the second substitution. An –OH group directs substitution toward the ortho and para positions, for instance, while a carbonyl group such as –CHO directs substitution primarily toward the meta position. Table 1 lists experimental results for the nitration of some substituted benzenes.

Substituents can be classified into three groups, as shown in Figure \(\PageIndex{1}\): ortho- and para-directing activators, ortho- and para-directing deactivators, and meta-directing deactivators. There are no meta-directing activators. Notice how the directing effect of a group correlates with its reactivity. All meta-directing groups are strongly deactivating, and most ortho- and para-directing groups are activating. The halogens are unique in being ortho- and para-directing but weakly deactivating.

Worked Example \(\PageIndex{1}\): Predicting the Product of an Electrophilic Aromatic Substitution Reaction

Predict the major product of the sulfonation of toluene.

Strategy

Identify the substituent present on the ring, and decide whether it is ortho- and para-directing or meta-directing. According to Figure \(\PageIndex{1}\), an alkyl substituent is ortho- and para-directing, so sulfonation of toluene will primarily give a mixture of o -toluenesulfonic acid and p -toluenesulfonic acid.

Solution

The direction of the reaction

The activating group directs the reaction to the ortho or para position, meaning the electrophile substitutes for the hydrogen on carbon 2 or carbon 4. The deactivating group directs the reaction to the meta position, which means the electrophile substitutes for the hydrogen that is on carbon 3, with the exception of the halogens, which are deactivating groups but direct the ortho or para substitution.

Substituents determine the reaction direction by resonance or inductive effect

Resonance effect is the conjugation between the ring and the substituent, which means the delocalization of the \(\pi\) electrons between the ring and the substituent. Inductive effect is the withdrawal of the sigma ( the single bond ) electrons away from the ring toward the substituent, due to the higher electronegativity of the substituent compared to the carbon of the ring.

Substituents determine the reactivity of rings

The reaction of a substituted ring with an activating group is faster than the same reaction with benzene. On the other hand, a substituted ring with a deactivated group reacts more slowly than benzene.

Activating groups speed up reaction with electrophiles due to increased electron density on the ring. This stabilizes the carbocation intermediate, thereby decreasing the reaction's activation energy. On the other hand, deactivating groups withdraw electron density from the carbocation formed in the intermediate step, thereby increasing the activation energy and slowing the reaction.

The CH₃ Group is an ortho, para director

Alkyl groups are inductively donating, therefore are activators. This results in o/p attack to form a tertiary arenium carbocation, which speeds up the reaction.

The O-CH₃ Group is an ortho, para director

The methoxy group is an example of groups that are ortho, para directors by having an oxygen or nitrogen adjacent to the aromatic ring. This same activation is present with alcohols, amines, esters and amides (with the oxygen or nitrogen attached to the ring, not the carbonyl).

Groups with oxygen or nitrogen attached to the aromatic ring are ortho- and para-directing, since the O or N can withdraw electrons from the ring, making the ortho and para positions more reactive and stabilizing the arenium ion that forms. This causes ortho and para products to form faster than meta products. Generally, the para product is preferred because of steric effects.

Acyl groups are meta directors

Ketones are an example of groups that deactivate an aromatic ring through resonance. Similar deactivation also occurs with ammonium ions, nitro groups, aldehydes, nitriles, sulfonic acids, and groups with a carbonyl attached to the ring (amides, esters, carboxylic acids, and anhydrides).

Acyl groups are resonance deactivators. Ortho and para attack produce a resonance structure which places the arenium cation next to an additional cation. This destabilizes the arenium cation and slows down the reaction over the ortho and para positions. By default, the meta product forms faster because it lacks this destabilizing resonance structure.

Halogens

Halogens are an interesting hybrid case. They are ortho, para directors, but deactivators. Overall, they remove electron density from the ring, making it less reactive. However, due to their resonance donation to the ring, if it does react, it reacts primarily at ortho and para positions.

References

1. Schore, N.E. and P.C. Vollhardt. 2007. Organic Chemistry, structure and function, 5th ed. New York,NY: W.H. Freeman and Company.
2. Fryhle, C.B. and G. Solomons. 2008. Organic Chemistry, 9th ed.Danvers,MA: Wiley.

Study Notes

As you saw in Section 16.4, a substituent on a benzene ring can be an activator or a deactivator. At the same time, a substituent can also be a meta-directing or ortho/para-directing substituent. Of the four possible combinations, only three are known—there are no meta directing activators.

If you look at the data for the nitration of toluene, you will see that the yield of o‑nitrotoluene is 63% and that of p‑nitrotoluene is 34%. Statistically, we should expect to obtain twice as much ortho product as para product, because the former is produced by attack at either of two carbon atoms whereas the latter is produced by attack at only one carbon atom (see Figure below).

In this instance, the observed ortho/para ratio is almost 2:1, as we might expect. However, if we study the ortho/para ratio found in the nitration of a number of other arenes, we see that this is not always the case. Note that the data for the nitration of toluene given in the table below differ from those presented elsewhere. The variation may result from a difference in temperature, reaction conditions or reagent, and emphasizes the point that it is the trends which are important, not the numbers themselves.

Substrate	% ortho	% para	ortho/para ratio
toluene	58	37	1.57:1
ethylbenzene	45	49	0.92:1
isopropylbenzene	30	62	0.48:1
tert-butylbenzene	16	73	0.22:1

[Source: These data were taken from the audiocassette Some Organic Reaction Pathways, by Peter Sykes. London: Educational Techniques Subject Group, The Chemical Society, 1975.]

Table \(\PageIndex{1}\): Nitration of arenes

The table above shows us that as the size of the alkyl substituent already present in the ring increases, attack at the ortho position becomes more difficult, and the percentage of ortho isomers in the mixture of products decreases. This is an example of a steric effect—an effect caused by the size of the substituent—and we would say that as the size of the alkyl group increases, attack at the ortho position becomes less favorable as a result of steric hindrance. Note that the size of the electrophile can also be a factor in determining the ortho/para ratio: the larger the electrophile, the less able it is to attack at the ortho position, particularly if the substituent already present in the ring is itself quite bulky.

When drawing the resonance contributors to the carbocation formed during an electrophilic aromatic substitution, bear in mind that those of the type

are particularly important because, in such structures, each atom has a complete octet of electrons.

Note that, as do the hydroxyl and amino groups, the halogens have an inductive electron-withdrawing effect and a resonance electron-releasing effect on a benzene ring. The difference in behavior during electrophilic substitutions arises because, with the hydroxyl and amino groups, the resonance effect is much greater than the inductive effect, whereas with the halogens, there is a much finer balance. In the case of the latter, the inductive effect reduces the overall reactivity, but the resonance effect means that this reduction is felt less at the ortho and para positions than at the meta position.