Electrophilic Aromatic Substitution | Organic Chemistry 2

Electrophilic aromatic substitutions of benzene are studied in this chapter: electrophilic aromatic substitution, halogenation, nitration, and sulfonation of benzene, Friedel-Crafts alkylation and acylation, activating and deactivating substituents, inductive and resonance effects, meta- ortho- para- directing substituents, aromatic substitution of mono and disubstituted benzene

Electrophilic Aromatic Substitution

Benzene reactivity:

  • Benzene has 6 π electrons delocalized in 6 p orbitals that overlap above and below the ring plane ⇒ the benzene ring is electron rich and thus reacts with electrophiles.
  • Benzene is aromatic and thus particularly stable ⇒ reactions that keep the aromatic ring intact are favored.

Electrophilic aromatic substitution:

Typical reactions of benzene in which a hydrogen atom is replaced by an electrophile.
The halogenation, nitration and sulfonation of benzene as well as the Friedel-Crafts alkylation and acylation work in the same way:


  1. Activation of the electrophile ⇒ formation of a 'super-electrophile' E+.
  2. Addition of the electrophile to form a resonance-stabilized carbocation.

  3. Loss of a proton to regenerate the aromatic ring.

Halogenation of Benzene


Replacement of H by Cl or Br, resulting in the formation of an aryl halide.

  1. Activation of bromine by the Lewis acid FeBr3.

  2. Addition of the activated electrophile to form a carbocation.

  3. Loss of a proton to regenerate the aromatic ring.

Nitration of Benzene


Replacement of H by NO2 resulting in the formation of a nitro compound.

  1. Activation of nitric acid by sulfuric acid to form a nitronium ion (+NO2)

  2. Addition of the activated nitronium ion to form a carbocation - aromatic nitration.

  3. Loss of a proton to regenerate the aromatic ring.

Sulfonation of Benzene


Replacement of H by SO3H resulting in the formation of benzenesulfonic acid.

  1. Activation of sulfur trioxide by protonation.

  2. Addition of the activated +SO3H to form a carbocation - aromatic sulfonation.

  3. Loss of a proton to regenerate the aromatic ring.


The sulfonyl group is a good leaving group: upon heating with dilute sulfuric acid, the sulfonyl group can be removed ⇒ the reaction is reversible.

Friedel-Crafts Alkylation

Friedel-Crafts alkylation:


Replacement of H by R resulting in the formation of an alkyl benzene.

  1. Activation of the alkyl halide with a Lewis acid catalyst to generate a reactive electrophile.

  2. Addition of the electrophile to form a carbocation.

  3. Loss of a proton to regenerate the aromatic ring.

Vinyl halides and aryl halides do not react in Friedel-Crafts alkylation.


Limitations of the Friedel-Crafts reaction:

  • Carbocation rearrangement: possibility of carbocation rearrangement, leading to the formation of undesired alkylated products.
  • Polyalkylation: electron donor alkyl group activates benzene ring, which is now more reactive to further electrophilic substitution ⇒ the reaction is difficult to control.

Friedel-Crafts Acylation

Friedel-Crafts acylation:


Replacement of H by RCO resulting in the formation of an acyl benzene.

  1. Activation of the acid chloride with a Lewis acid catalyst to generate an acylium ion.

  2. Addition of the acylium ion to form a carbocation - electrophilic acylation.

  3. Loss of a proton to regenerate the aromatic ring.


Advantages over Friedel-Crafts alkylation:

  • Avoidance of carbocation rearrangement: no carbocation intermediates involving the acyl group, eliminating the risk of rearrangement ⇒ greater predictability in product formation.
  • Selective monoacylation: electron-withdrawing acyl group deactivates the ring towards another electrophilic addition ⇒ better control and selectivity.

Inductive and Resonance Effects

To predict whether a substituted benzene is more or less electron rich than benzene itself, we must consider the net balance of the inductive and resonance effects.


Inductive effects:

These effects result from the electronegativity of the atoms in the substituent and the polarizability of the substituent group.

  • Atoms more electronegative than carbon (e.g., N, O, and X) pull electron density away from carbon ⇒ electron-withdrawing inductive effect.
  • Polarizable alkyl groups donate electron density ⇒ electron-donating inductive effect.

When a halogen is bonded to a benzene ring, the inductive effect dominates over the resonance effect and the net effect is electron withdrawal.

Electron-withdrawing inductive effect:

Electron-donating inductive effect:


Resonance effects:

These effects result from the delocalization of electrons within the molecular structure.

  • In systems represented by C6H5-Y=Z, where Z is more electronegative than Y, the delocalization of electrons towards Z occurs ⇒ electron-withdrawing resonance effect, with resonance structures placing a positive charge on carbons of the benzene ring.
  • Atoms having a lone pair of electrons and directly bonded to a benzene ring contribute electrons to the benzene ring ⇒ electron-donating resonance effect, with resonance structures placing a negative charge on carbons of the ring effect.

In cases where a neutral O or N atom is directly attached to a benzene ring, the resonance effect dominates over the inductive effect and the net effect is electron donation.


Electron-withdrawing resonance effect:

Electron-donating resonance effect:


Common electron-donating and withdrawing groups:

  • Electron-donating groups: alkyl group or groups with a lone pair bonded to the benzene ring such as N or O atom.
  • Electron-withdrawing groups: halogens or groups with an atom Y bearing a full (+) or partial (δ+) positive charge bonded to the benzene ring.


EAS of Substituted Benzene

Activating and deactivating groups:

Inductive effect and resonance are the 2 main effects that explain the donor or acceptor character of a substituent. The substituents of benzene can be grouped into:

  • Activating group (electron donor): electrophilic attack occurs at the ortho and para positions of the substituent.
  • Deactivating group (electron acceptor): electrophilic attack occurs to the meta positions of the substituent.

Exception: halogens deactivate a benzene ring but are ortho/para directing.


Activated Benzene:


D ⇒ Donor:
- NH2, OH (strongly activating)
- NHCOR, OR (moderately activating)
- alkyl, aryl (weakly activating)


The position of attack is controlled by the strongest activating substituent and then by steric effects. Because of the sterics, the para product will be preferred over the ortho product.


Deactivated Benzene:


A ⇒ Acceptor:
- N+R3, NO2, CF3, CN, SO3H (strongly deactivating)
- COH, COR, COOH, COOR, CONH2 (moderately deactivating)

EAS of Disubstituted Benzene

Strength of activating and deactivating groups:

  • Activating groups (ortho, para directors):


Strong: substituents with a lone pair immediately adjacent to the ring

-NH2, -NHR, -OH
(-OR is a moderate activator)


Moderate: substituents with a lone pair already participating in resonance outside of the ring



Weak: alkyl groups



  • Deactivating groups (meta directors):


Strong: substituents with an extremely electron poor atom

-NO2, NR3+, SO3H, CX3


Moderate: substituents with a π bond conjugated to the ring and attached to a heteroatom



Weak: halogens (but halogens are ortho/para directing)

-F, -Cl, -Br, -I


To determine the aromatic substitution product of a disubstituted benzene:

  1. Identify the nature of each substituent (e.g., strong activator, weak activator, strong deactivator).
  2. Select the position directed by 2 groups with reinforcing directing effects.
    If the directing effects oppose each other, select the ortho and para positions of the strongest activator.
  3. Identify the unoccupied positions. Avoid positions that are sterically hindered (e.g., next to an isopropyl substituent or between 2 meta substituents).


NH2 and CH3 are 2 activating groups (ortho, para directors). 
NH2 is a stronger activator than CH3 ⇒ the electrophilic aromatic substitution will occur at the ortho position of NH2.

Synthesis Strategies

Change the position of the electrophilic attack:


Lock / Unlock a position on benzene:



Moderate the donor character of a substituent:


Check your knowledge about this Chapter

Electrophilic Aromatic Substitution (EAS) is a reaction where an aromatic compound, such as benzene, reacts with an electrophile, resulting in the substitution of a hydrogen atom on the aromatic ring by the electrophile. This differs from an addition reaction, where the double bonds of the aromatic ring would be completely broken, adding two substituents and destroying the aromaticity. In EAS, the aromaticity is preserved because the ring keeps its delocalized π electron system intact after the reaction proceeds through a resonance-stabilized carbocation intermediate, and a subsequent loss of a proton restores the aromatic system.

The stability of the benzene ring is pivotal in electrophilic aromatic substitution (EAS) reactions because it drives the regeneration of the aromatic system after the initial formation of a non-aromatic carbocation intermediate. During an EAS reaction, the aromaticity of benzene is momentarily lost when the electrophile forms a sigma bond with the ring, creating a high-energy carbocation intermediate. This destabilization provides a powerful driving force for the subsequent step where a base removes a proton from the carbon adjacent to the carbocation, restoring the aromaticity and lowering the overall energy of the system. The restoration of the aromatic system is energetically favorable and is the reason why EAS reactions are thermodynamically feasible, despite the high activation energy required to disrupt aromaticity in the first step.

Halogenation of benzene occurs through an electrophilic aromatic substitution mechanism where a benzene ring reacts with a halogen in the presence of a Lewis acid catalyst, such as FeCl3 or AlCl3. The catalyst facilitates the formation of a highly reactive electrophilic halogen species, which the benzene ring can attack, resulting in the substitution of a hydrogen atom on the benzene with a halogen atom. After the initial formation of the sigma complex (cyclohexadienyl cation), deprotonation restores the aromaticity, yielding halogenated benzene.

The mechanism for the nitration of benzene involves the generation of the electrophile, nitronium ion (NO2+), which is formed by the reaction of nitric acid (HNO3) with a strong acid catalyst, usually sulfuric acid (H2SO4). Benzene reacts with the nitronium ion in an electrophilic aromatic substitution (EAS) reaction. The process includes the formation of a sigma complex (arenium ion), followed by deprotonation to restore aromaticity and yield nitrobenzene as the final product.

The sulfonation of benzene involves the addition of a sulfonyl group (SO3H) to the benzene ring through the use of fuming sulfuric acid (H2S2O7) or sulfur trioxide (SO3). This reaction occurs via an electrophilic aromatic substitution where the electrophile, often generated in situ, is sulfur trioxide, which reacts with the benzene to form benzene sulfonic acid. The reaction is reversible because the sulfonyl group is a good leaving group; upon heating with dilute sulfuric acid, the sulfonyl group can be removed, reverting to the original benzene molecule.

The Friedel-Crafts alkylation of benzene involves the formation of a carbocation intermediate that acts as the electrophile. Initially, a Lewis acid catalyst, like aluminum chloride (AlCl3), reacts with an alkyl halide to form a complex. This complex loses a halide ion, creating a highly reactive carbocation. Benzene, with its high electron density due to the delocalized π electrons, then reacts with the carbocation, forming a sigma complex. Finally, the complex loses a proton to the AlCl4-, regenerating the catalyst and yielding the alkylated benzene product.

Friedel-Crafts acylation and alkylation are both electrophilic aromatic substitution reactions that introduce different groups onto the benzene ring:

  • Acylation involves the introduction of an acyl group (RC(O)-) to an aromatic ring, typically using an acid chloride (RCOCl) and a Lewis acid catalyst like AlCl3. This reaction adds a carbonyl group (C=O) adjacent to the ring, forming a ketone.
  • Alkylation, on the other hand, introduces an alkyl group (R-) using an alkyl halide (RX) and a similar Lewis acid catalyst.

However, Friedel-Crafts alkylation can suffer from polyalkylation (adding more than one alkyl group) and carbocation rearrangement, which can lead to a mixture of products. Acylation avoids these issues as the introduced acyl group withdraws electron density from the ring and deactivates it to further substitution, and acyl cations do not rearrange.

The problem with polyalkylation in Friedel-Crafts alkylation is that the alkyl group added to the benzene ring is an activating group. It makes the benzene more reactive towards further alkylation, leading to multiple alkyl groups attaching to the benzene, which often results in a mixture of products that can be difficult to separate.

To avoid polyalkylation, one can use an excess of benzene, which ensures that the concentration of unreacted benzene is much higher than that of the monoalkylated product, thus reducing the likelihood of further alkylation. Alternatively, one may use a bulky alkyl halide to hinder the approach of the electrophile to positions already substituted, or employ a Friedel-Crafts acylation followed by a Clemmensen or Wolff-Kishner reduction to introduce only one alkyl group.

Friedel-Crafts reactions, both alkylation and acylation, require the presence of a strong Lewis acid catalyst like aluminum chloride (AlCl3) to generate a highly reactive electrophile. However, benzene rings that possess strong deactivating groups, such as nitro (-NO2) or sulfonyl (-SO3H) groups, are less electron-rich due to their electron-withdrawing characteristics through inductive and/or resonance effects. This makes the benzene ring less nucleophilic and thus less reactive towards the electrophilic species formed in Friedel-Crafts reactions. Moreover, strong deactivating groups can also bind to the catalyst, reducing its effectiveness and further inhibiting the reaction.

  • In substituted benzene compounds, the inductive effect refers to the transmission of electronic effects through sigma bonds due to the electronegativity of substituents. Electronegative groups pull electron density away from the benzene ring, making it less reactive towards electrophilic aromatic substitution, while electron-donating groups push electron density towards the ring, increasing its reactivity.
  • Resonance effects involve the delocalization of electrons within π bonds of the aromatic ring and any attached functional groups. Substituents capable of donating electron density via resonance stabilize the positive charge of the intermediate carbocation during electrophilic aromatic substitution, enhancing the reaction rate, while groups withdrawing electron density via resonance destabilize this intermediate, thus slowing down the reaction.

Electron-donating groups (EDGs) activate benzene rings towards electrophilic aromatic substitution (EAS) by increasing electron density, which makes the ring more reactive to electrophiles. Electron-withdrawing groups (EWGs) deactivate the ring by decreasing electron density, making the benzene less reactive to electrophiles. Additionally, EDGs and EWGs can direct incoming substituents to specific positions on the benzene ring: EDGs typically direct substitution to the ortho and para positions, whereas EWGs direct substitution primarily to the meta position, due to the stabilization or destabilization of the resulting carbocation intermediate.

The directing effect in monosubstituted benzene describes how the existing substituent influences the position where a new substituent will be added during an electrophilic aromatic substitution (EAS) reaction. A substituent can be either ortho/para-directing, typically donating electron density through resonance or hyperconjugation, or meta-directing, which often withdraws electron density due to inductive or resonance effects. This effect directs the incoming electrophile to certain positions on the ring (ortho, meta, or para relative to the substituent) based on the electronic nature of the substituent, thus impacting reactivity and regioselectivity of the EAS process.


To determine the aromatic substitution product of a disubstituted benzene, assess the nature of each substituent (strong activator, weak activator, or strong deactivator). Choose positions directed by reinforcing effects when substituents share similar directing influences. In cases of opposing effects, employ the ortho and para strategy based on the strength of the activator. Additionally, identify unoccupied positions for substitution while avoiding sterically hindered locations, such as those adjacent to isopropyl substituents or between two meta-substituents.

In multi-step electrophilic aromatic substitution synthesis, the reactivity order of substituents determines the outcome of subsequent reactions. Substituents can be activating or deactivating and can direct new substituents to ortho/meta/para positions relative to themselves. This hierarchy affects the rate and the position of further aromatic substitutions, enabling the chemist to predict and plan the synthesis to obtain the desired compound selectively. Therefore, understanding the influence of existing substituents on the aromatic ring is essential for designing a successful synthetic route.

  1. When synthesizing a complex aromatic compound via electrophilic aromatic substitution, strategy is based on the directing effects of the substituents present on the benzene ring. Substituents can be activating, deactivating, ortho/para-directing, or meta-directing, influencing both the rate of reaction and the position of electrophilic attack.
  2. Consider using protecting groups if an existing group interferes with the desired substitution pattern.
  3. Additionally, think about the order of introduction of substituents, as one may impact the reactivity towards subsequent EAS steps; typically, introducing electron-donating groups first facilitates further substitutions.
  4. Finally, select the appropriate EAS reaction—halogenation, nitration, sulfonation, Friedel-Crafts alkylation, or acylation—based on the desired substituent you wish to introduce to the aromatic ring.

In cases where the directing effects of substituents in a disubstituted benzene oppose each other, aromatic substitution occurs at the ortho and para positions of the strongest activator due to the increased electron density at these positions.