Introduction

There are two main effects of substituents.  The substituent will affect the rate of reaction (aka reactivity) of the ring, and it will also affect the position of attack (called “directing effects”) on the ring by the incoming electrophile.  Thus we need to answer the following questions:

• Does the substituent activate or deactivate the aromatic ring?
• Where will the incoming group go?

Reactivity: Activation and deactivation

Because benzene acts as a nucleophile in electrophilic aromatic substitution, substituents that make the benzene more electron-rich can accelerate the reaction. Substituents that make the benzene moor electron-poor can retard the reaction. In the mid-twentieth century, physical organic chemists including Christopher Ingold conducted a number of kinetic studies on electrophilic aromatic substitution reactions. In table 1, you can see that some substituents confer a rate of reaction that is much higher than that of benzene (R = H). Phenol, C₆H₅OH, undergoes nitration a thousand times faster than benzene does.  Nitrobenzene, C₆H₅NO₂, undergoes the reaction millions of times more slowly.

These observations are consistent with the role of the aromatic as a nucleophile in this reaction. Substituents that draw electron density away from the aromatic ring slow the reaction down. These groups are called deactivating groups in this reaction. Substituents that readily donate electron density to the ring, or that effectively stabilize the cationic intermediate, promote the reaction. These groups are called activating groups in this reaction.

The roles of these groups are related to their electronic interactions with the electrons in the ring.  Some groups (e.g., H₂N-, HO-, RO-) have lone pairs and act as π-donors, providing additional electron density to the benzene ring via resonance.  This is often called a +R (for resonance) effect, and this activates the ring towards EAS.

Other groups contain an electronegative atom attached via a π-bond (e.g., C=O) that makes the group electron-withdrawing.  These groups act as π-acceptors, drawing electron density away from the ring via resonance.  This may be called a –R effect, and this deactivates the ring towards EAS.

Some groups act only through the sigma bonds via the inductive effect (I), which is based purely on electronegativity without any resonance.  These effects are usually less than resonance effects, but they are still significant.  Since an sp³ carbon is less electronegative than an sp² carbon, a methyl or similar sp³ alkyl (R) group can act as a σ-donor, putting some extra electron density into the ring, giving a +I effect (activating).  Groups based on more electronegative atoms (O, F, Cl) may be σ-acceptors, drawing electron density away from the ring via a simple inductive effect which arises from the electronegativity of the substituent.  This deactivates the ring, and is often referred to as a –I effect.

In some cases (e.g., OH, Cl), there may be multiple effects, and the overall influence of the substituents is determined by the balance of the R and I effects.  One effect may be stronger in one case than the other, so it wins out in one case and loses in another.  The substituent effects on reactivity have been studied experimentally, and the following chart summarizes the reactivity order, with strongest activators (in green) on the left and strongest deactivators (in red) on the right.  Thus amino groups are the strongest activators listed, and nitro groups are the strongest deactivators.

Directing Effects

In addition to exerting an effect on the speed of reaction, substituents on the benzene ring also influence the regiochemistry of the reaction. That is, they control where the new substituent appears in the product.

Remember, there are three different positions on the benzene ring where a new substituent can attach, relative to the original substituent.  Substitution could actually occur on five positions around the ring, but two pairs are related by symmetry. Isomerism in disubstituted benzenes can be described by numbering the substituents (1,2- etc) or by the relationships ortho-, meta– and para-.  There are two positions ortho– to the initial substituent and two positions meta– to it.

Ingold and colleagues investigated the question of regiochemistry in nitration.  They reported the following observations:

In looking at the table, you might see that there are two groups of substituents. One group reacts to make mixtures of ortho– and para– products. There may be different ratios of ortho– to para– and there may be small amounts of meta-, but don’t get bogged down in the details. Focus on the bigger picture. Some groups are “ortho/para directors”.

The other group reacts to make mostly meta-substituted products. Here may be small amounts of ortho– and para– products, but these groups are best described as “meta-directors”. These regiochemical effects are very closely related to the activating and directing effects we have already seen. If we want to understand these data, we need to think about things like π-donation, π-acceptance, inductive effects and cation stability.