Effects of Multiple Substituents on Electrophilic Aromatic Substitution

Effects of Multiple Substituents on Electrophilic Aromatic Substitution 

Two or more substituents estert a combined effect on the reactivity of an aromatic ring. If the groups reinforce each other, the result is easy to predict For example, we can predict that all the xylenes (dimethylbenzenes) are activated toward electrophilic substitution because the two methyl groups are both activating. In the case of a nitroben-zoic acid, both substituents are deactivating, so we predict that a nitrobenzoic acid is deactivated toward attack by an electrophile. 

The orientation of addition is easily predicted in many cases. For example, in m-xylene there are two positions ortho to one of the methyl groups and para to the other. Electrophilic substitution occurs primarily at these two equivalent positions. There may be some substitution at the position between the two methyl groups (ortho to both), but this position is sterically hindered, and it is less reactive than the other two activated positions. In p-nitrotoluene, the methyl group directs an electrophile toward its ortho positions. The nitro group directs toward die same locations because they are its meta positions. 

When the directing effects of two or more substituents conflict, it is more difficult to predict where an electrophile will react. In many cases, mixtures result. For example, o-xylene is activated at all the positions, so it gives mixtures of substitution products. 

When there is a conflict between an activating group and a deactivating group, the activating group usually directs the substitution. We can make an important generalization  

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