Regiochemistry in EAS

Where an electrophile (E⁺) reacts on a mono-substituted benzene is referred to as regiochemistry or orientation of electrophilic attack.  Much like the rate, the regiochemistry depends intimately on the electron-donating/withdrawing abilities of the attached group (R).

We can classify groups on an aromatic ring as follows.

Ortho/Para Directing Activators: Stabilize the cyclohexadienyl cation (arenium ion) intermediate by induction (CH₃, R) and resonance (-OCH₃, -OR, -OH, NH₂) giving primarily the ortho and para-substituted products. These groups are EDG's and therefore activate the ring (increased reaction rate relative to unsubstituted benzene), because they donate electrons into the aromatic ring.  Notice most of them have lone pairs they can donate into the ring.

Ortho/Para Directing Deactivators: F, CI, Br, I deactivate (i.e. slow down the rate of EAS reaction) because of their high electronegativity (Induction), but are ortho, para directing because they stabilize the cyclohexadienyl cation by resonance (donate electron pairs).

Meta Directing Deactivators: Destabilize cyclohexadienyl cation for ortho and para cases thereby allowing more meta products to form. These groups are EWG's and therefore deactivate the ring, making the rate of substitution slow.  Typically have a π bond in conjugation with the aromatic ring and you can show resonance structures withdrawing electron density from the ring.

Examples

Nitration of Anisole

The -OCH₃ group is an ortho/para (o/p) directing activator since it is a strong resonance donator.  This reaction would proceed faster than that of benzene and the o/p directing group effect can be seen in the product distribution.  If you were asked to predict the major product you would draw the ortho and para products.

Nitration of Nitrobenzene

The -NO₂ group is a meta (m) directing deactivator since it is a strong resonance withdrawer.  This reaction would proceed slower than that of benzene.  If you were asked to predict the major product you would draw the meta product.