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Chemistry 2131:
Organic Chemistry for the Life Sciences (3)
Effects of Substituents on Aromatic Substitution
1. Directing Effects of Substituents on Benzene:
- we have looked at a number of examples of electrophilic aromatic substitution reactions. We have only considered the substitution of unsubstituted benzene to date. We will now explore the effects of substituents on the reactivity of the ring.
- substituents have two major effects on reactivity, they can direct substitution to specific carbon atoms in the aromatic ring and they can activate or deactivate the ring.
- we'll start with a discussion of the directing effects of substituents. In benzene all of the carbon atoms are identical. If we introduce a group onto one carbon atom, the other carbon atoms become different relative to the position of the original group.
- let's look at an example. If we started with bromobenzene and treated it with concentrated nitric acid in the presence of sulfuric acid we would obtain a disubstituted product. In theory we could get ortho (1,2), meta (1,3) or para (1,4) products. If the addition were completely random we would expect a product ration of 2:2:1 ortho:meta:para. In actual fact the observed products are more like 36% ortho, 2% meta and 62% para.
- this result can be extended with the observation that other substitutions of bromobenzene give mostly ortho and para products. Thus, the bromo group is called an ortho, para-directing group.
- if on the other hand we started with nitrobenzene and reacted it with bromine in the presence of the ferric bromide we get almost exclusively meta-bromonitrobenzene. Thus, the nitro group is called a meta-directing group.
- please note that it is the group already on the ring that directs the substitution of the new group. The table below summarizes the groups:
Substituent group Name Directing effect Activating/deactivating -NH2, -NR2 amino o,p + -OH hydroxy o,p + -OR alkoxy o,p + -NHCOR acylamino o,p + -OCOR acyloxy o,p + -R alkyl o,p + -F, -Cl, -Br, -I halogens o,p - -COOH, -COOR, -CONH2 carboxy- m - -COR acyl m - -SO3H sulfonyl m - -CN cyano m - -NO2 nitro m - - why does this happen? The directing effect arises because the initial addition event becomes favoured at specific carbon atoms. In the unsubstituted case the carbons are all in competition with each other equally. Once a substitution has occurred that is no longer true.
- we'll start by looking at the orhto, para-directors. All of the ortho, para directors except the alkyl group have at least one lone pair on the atom attached to the ring.
- to explore what effect this has on the substitution reaction let's look at the example of methoxybenzene (also called anisole). Let's use the general example for the electrophile E+. Draw the initial intermediates following ortho, meta and para attack. Next draw the contributing resonance structures for the intermediate.
- for the meta attack there are three possible resonance structures. For the ortho and para attacks there is an additional resonance form possible from the contribution of one of the lone pairs on oxygen.
- in other words, for the meta attack the carbocation is never on the substituted carbon, therefore the lone pair on the oxygen can't contribute to resonance stabilization.
- since the rate limiting step in many of these electrophilic aromatic substitution reactions is the formation of the carbocation intermediate, then it is logical that the formation of a more stable carbocation is favoured. This is reminiscent of Markovnikov's Rule.
- in support of this is Hammond's postulate. The postulate basically says that the more stable carbocation should be formed more rapidly.
- to extend this, the products most likely to be formed are those that correspond to the more rapidly formed, the more stable carbocations
- so, groups in which the atom directly attached to the aromatic ring has at least one unshared electron pair are ortho, para directors.
- this explanation doesn't explain the ortho, para directing effect of alkyl groups. This is however a simple matter, since one of the carbocation resonance structures following ortho or para attack is a tertiary carbocation, therefore more stable than the other secondary carbocations
- let's move on to the meta directors. These groups are all electronegative groups. The atom attached to the ring is either electronegative (but without a lone pair) or electron deficient.
- the nitro group is a potent example. Let's look at the addition of an electrophile to nitrobenzene in the ortho, meta and para positions. All three additions give rise to only three resonance structures. The difference here is that one of these is much less stable than the others. When the positive charge sits on the substituted carbon there are two positive charges on neighbouring atoms. The repulsion makes this resonance structure less favourable than the others.
- not all meta-directors have a full positive charge, but they are all electron deficient
- so, the meta-directing effect is more of a negative contribution than further substitution as seen for the ortho, para directors.
2. Activating and Deactivating Effects of Substituents:
- we have seen how substituents can effect the position or regioselectivity of substitution reactions, but what about the rates at which these reactions occur. Some groups cause the benzene ring to react more rapidly, these groups are called activating groups. For example the Friedel-Crafts acylation of methoxybenzene is 300 000 times faster that the reaction with benzene
- other groups tend to make the ring react more slowly, these are called deactivating groups. For example the bromination of nitrobenzene takes place less than 10-5 times as fast as the bromination of benzene
- why should this be? There are three generalizations concerning this effect:
- all meta-directing groups are deactivating
- all ortho, para-directing groups are activating except the halogens
- the halogens are deactivating
- two properties of the substituents come into play here, the resonance effect and the polar effect
- the resonance effect is what we talked about for the directing effects. If extra resonance structures exist to stabilize the carbocation intermediate, then the reaction proceeds more rapidly
- the second effect is the polar effect, this is the tendency of the substituent to pull electrons away from the ring, so this is based on the electronegativity of the molecule.
- an electronegative atom adjacent to the ring pulls electrons towards itself, leaving the ring partially electron deficient, bearing a partial positive charge. Since like charges repel, this destabilizes the carbocation intermediate
- so, these two effects pull the reaction in opposite ways. For the ortho, para-directors it's a balance between the two that dictates whether the group activates or deactivates. For meta-directors there is no positive contribution to resonance, only a negative polar effect.
- the case of the halogens is that in which the polar effect outweighs the resonance effect. The halogens are so electronegative that the resonance effect is outweighed.
