In these chemistry notes, we learn about Reaction of Aromatic Compounds. We also learn about electrophilic aromatic substitution, electrophilic substitution reaction, electrophilic aromatic substitution mechanism. Structure of aromatic compounds and nucleophilic aromatic substitution reactions.
Electrophilic Aromatic Substitution – Reaction of Aromatic Compounds
Introduction to Reaction of Aromatic Compounds
- Aromatic rings are unusually stable, making benzene uncreative in most of the reactions.
- Benzene acts as a nucleophile with certain electrophiles, yielding substitution products.
- The aromatic ring remains intact after Electrophilic Aromatic Substitution.
Electrophilic Aromatic Substitution
- Benzene has six π electrons delocalized in six p orbitals that overlap above and below the plane of the ring. These loosely held π electrons make the benzene ring electron rich, and so it reacts with electrophiles.
- Because benzene’s six π electrons satisfy Hückel’s rule, benzene is especially stable. Reactions that keep the aromatic ring intact are therefore favoured.
- Therefore, the characteristic reaction of benzene is electrophilic aromatic substitution-a hydrogen atom is replaced by an electrophile.
- Benzene does not undergo addition reactions, because addition reaction would yield a product that is not aromatic.
The product is not aromatic.
The product is aromatic.
- Benzene is less reactive towards electrophiles than an alkene, even though it has more π electrons than an alkene.
- The π electrons of benzene are delocalized over the six carbon atoms of the ring, increasing benzene’s stability and making them less available for electron donation.
- The two π electrons in alkene are localized between the two C’s making them more nucleophilic and thus more reactive with an electrophile than the delocalized electrons in benzene.
Electrophilic substitution reactions – The General Mechanism
- Electrophilic substitution reactions of benzene occur via a two-step mechanism:
- The first step is addition of the electrophile E+ to form a resonance-stabilized carbocation.
- The second step is deprotonation with base.
Table 1: Five examples of electrophilic aromatic substitution
Halogenation—Replacement of H by X (Cl or Br)
Nitration—Replacement of H by NO2
Sulfonation—Replacement of H by SO3H
Friedel–Crafts alkylation—Replacement of H by R
Friedel–Crafts acylation—Replacement of H by RCO
General Mechanism: Electrophilic Aromatic Substitution
Step 1: Addition of the electrophile (E+) to form a carbocation
· Addition of the electrophile (E+) forms a new C–E bond using two π electrons from the benzene ring, and generating a carbocation.
· This carbocation intermediate is not aromatic, but it is resonance stabilized-three resonance structures can be drawn.
· Step 1 is rate-determining because the aromaticity of the benzene ring is lost.
Step 2: Loss of a proton to re-form the aromatic ring
· In Step 2, a base (B:) removes the proton from the carbon bearing the electrophile, thus reforming the aromatic ring.
· Step 2 is fast because the aromaticity of the benzene ring is restored.
- Always draw the hydrogen atom on the carbon bonded to the electrophile E.
- The carbon in the carbocation intermediate is sp3 hybridized.
- In the hybrid structure, the charge is delocalized over three atoms of the ring.
- The addition of an electrophile (E+) followed by elimination of a proton (H+) is substitution of E for H.
- The energy changes in electrophilic aromatic substitution are shown in figure below.
- The mechanism consists of two steps, so the energy diagram has two energy barriers.
- Because the first step is rate-determining, its transition state is higher in energy.
- The mechanism has two steps, so there are two energy barriers.
- Step 1 is rate-determining; its transition state is at higher energy.
- In halogenation reactions, benzene molecule reacts with Cl2 or Br2 in the presence of a Lewis acid catalyst, such as FeCl3 or FeBr3, to give the aryl halides chlorobenzene or bromobenzene, respectively.
- Halogenation reactions with I2 and F2 are not synthetically useful because I2 is too unreactive and F2 reacts too violently.
- In bromination, the Lewis acid FeBr3 reacts with Br2 to form a Lewis acid– base complex that weakens and polarizes the Br – Br bond, making it more electrophilic (Step 1).
- Step 2 and 3 follow directly from the general mechanism for electrophilic aromatic substitution:
- Addition of the electrophile (Br+ in this case) forms a resonance-stabilized carbocation (Step 2).
- Loss of a proton regenerates the aromatic ring (Step 3).
Mechanism: Bromination of Benzene
Step 1: Generation of the electrophile
· Lewis acid–base reaction of Br2 with FeBr3 forms a species with a weakened and polarized Br – Br bond. This adducts serves as a source of Br+ in the next step.
Step 2: Addition of the electrophile to form a carbocation
· Addition of the electrophile forms a new C– Br bond and generates a carbocation.
· This carbocation intermediate is resonance stabilized (three resonance structures).
· The FeBr4– also formed in this reaction is the base used in Step 3.
Step 3: Loss of a proton to re-form the aromatic ring
· FeBr4– removes the proton from the carbon bearing the Br, thus reforming the aromatic ring.
· FeBr3, a catalyst, is also regenerated for another reaction cycle.
Nitration and Sulfonation
- Nitration of benzene introduces a nitro group on an aromatic ring.
- The Nitration is an important reaction because a nitro group can then be reduced to an NH2 group, a common benzene substituent.
- The formation of electrophile in both nitration and sulfonation requires strong acid.
- In nitration, the electrophile is +NO2 (the nitronium ion), formed by protonation of HNO3 followed by loss of water.
Mechanism: Formation of the Nitronium Ion (+NO2) for Nitration
- In sulfonation, protonation of sulfur trioxide, SO3, forms a positively charged sulfur species (+SO3H) that acts as an electrophile.
Mechanism: Formation of the Electrophile +SO3H for Sulfonation
Mechanism for the nitration of a benzene ring
Generation of the electrophile +NO2
Two-step mechanism for substitution
Friedel–Crafts Alkylation and Friedel–Crafts Acylation
- In Friedel–Crafts alkylation and Friedel–Crafts acylation there is formation a new carbon–carbon bond.
- In Friedel–Crafts alkylation, reaction of benzene with an alkyl halide and a Lewis acid (AlCl3) forms alkyl benzene.
- Alkylation reactions results in transfer of an alkyl group from one atom to another (from Cl to benzene).
- In Friedel–Crafts acylation, a benzene ring reacts with an acid chloride (RCOCl) and AlCl3 to form a ketone.
- The new group which bond to the benzene ring is called an acyl group.
- The transfer of an acyl group from one atom to another is called acylation.
Mechanism: Mechanisms Of Alkylation And Acylation
- The mechanisms of alkylation and acylation proceed in the same manner s to those for halogenation, nitration, and sulfonation.
- In Friedel–Crafts alkylation reaction, the Lewis acid AlCl3 reacts with the alkyl chloride to form a Lewis acid–base complex.
- Examples of alkyl chlorides: CH3CH2Cl and (CH3)3CCl
Mechanism: Formation of the Electrophile in Friedel–Crafts Alkylation—Two Possibilities
- For primary RCl (Example: CH3Cl), the Lewis acid–base complex itself serves as the electrophile for electrophilic aromatic substitution.
- With secondary and tertiary RCl, the Lewis acid–base complex reacts further to give a secondary or tertiary carbocation, which serves as the electrophile.
- Carbocation formation occurs only with secondary and tertiary alkyl chlorides, because they produce a more stable carbocations.
- In both cases, the electrophile goes on to react with benzene in the two-step mechanism characteristic of electrophilic aromatic substitution.
Mechanism: Friedel–Crafts Alkylation Using a 3° Carbocation
- Addition of the electrophile (a 3° carbocation) forms a new carbon–carbon bond in Step 1.
- Then AlCl4 removes a proton on the carbon bearing the new substituent, thus reforming the aromatic ring in Step 2.
- In Friedel–Crafts acylation reaction, the Lewis acid AlCl3 ionizes the carbon–halogen bond of the acid chloride.
- Therefore it forms a positively charged carbon electrophile called an acylium ion, which is resonance stabilized.
- The positively charged present on the carbon atom of the acylium ion then goes on to react with benzene in the two-step mechanism of electrophilic aromatic substitution.
Mechanism: Formation of the Electrophile in Friedel–Crafts Acylation
Mechanism for the following Friedel–Crafts acylation.
Generation of the electrophile (CH3CO)+
Two-step mechanism for substitution
Important facts about Friedel–Crafts Alkylation
- In Friedel–Crafts alkylation compound such as vinyl halides and aryl halides do not react.
- Most Friedel–Crafts reactions involve carbocation electrophiles.
- The carbocations derived from vinyl halides and aryl halides are highly unstable and do not readily form, these organic halides do not undergo Friedel–Crafts alkylation.
Unreactive halides in the Friedel–Crafts alkylation
- Rearrangements can occur.
- Friedel–Crafts reaction can yield products having rearranged carbon skeletons when 1° and 2° alkyl halides are used as starting materials, as shown in the equation below.
- In the reactions below, the carbon atom bonded to the halogen atom in the starting material is not bonded to the benzene ring in the product, this shows that a rearrangement has occurred.
- The reaction shows a carbocation rearrangement involving a 1,2-hydride shift where the less stable 2° carbocation (formed from the 2° halide) rearranges to a more stable 3° carbocation.
Mechanism: Friedel–Crafts Alkylation Involving Carbocation Rearrangement
Steps 1 and 2: Formation of a 2° carbocation
- Reaction of the alkyl chloride with AlCl3 forms a complex that decomposes in Step 2 to form a 2° carbocation.
Step 3: Carbocation rearrangement
- 1,2-Hydride shift converts the less stable 2° carbocation to a more stable 3° carbocation.
Steps 4 and 5: Addition of the carbocation and loss of a proton
- Friedel–Crafts alkylation occurs by the usual two-step process:
- Addition of the carbocation
- Loss of a proton to form the alkylated product.
- Rearrangement reactions can take place even when no free carbocation is formed initially.
- For example, the 1° alkyl chloride in equation 2 forms a complex with AlCl3, which does not decompose to an unstable 1° carbocation, as shown in the mechanism below.
- Instead, a 1,2-hydride shift forms a 2° carbocation, which then serves as the electrophile in the two-step mechanism for electrophilic aromatic substitution.
Mechanism: A Rearrangement Reaction Beginning with a 1° Alkyl Chloride
- Other functional groups that readily form carbocations can be used as starting materials.
- Any compound that readily forms a carbocation can be used instead.
- The two most common functional groups are alkenes and alcohols, both can form carbocations in the presence of strong acid.
- Protonation of an alkene forms a carbocation, which can then serve as an electrophile in a Friedel–Crafts alkylation.
- Protonation of an alcohol, followed by loss of water, likewise forms a carbocation.
- Each carbocation can react with benzene to form a product of electrophilic aromatic substitution.
- For example:
- Substituted benzene rings undergo electrophilic aromatic substitution.
- Example of substituents includes halogens, OH, NH2, alkyl, and many functional groups that contain a carbonyl.
- Each substituent present on the benzene ring either increases or decreases the electron density in the benzene ring, and this affects the position of electrophilic aromatic substitution.
- Inductive effects come from the electronegativity of the atoms in the substituent and the polarizability of the substituent group.
- Atoms more electronegative than carbon including N, O, and X pull electron density away from carbon and thus exhibit an electron-withdrawing inductive effect.
- Polarizable alkyl groups provide electron density, and thus exhibit an electron-donating inductive effect.
- For examples, NH2 group withdraws electron density and CH3 donates electron density.
Electron-withdrawing inductive effect
- N is more electronegative than C.
- N inductively withdraws electron density.
Electron-donating inductive effect
- Alkyl groups are polarizable; therefore they are electron-donating groups.
- Resonance effects can either donate or withdraw electron density, depending on whether they place a positive or negative charge on the benzene ring.
- A resonance effect is electron donating when resonance structures place a negative charge on carbons of the benzene ring.
- A resonance effect is electron withdrawing when resonance structures place a positive charge on carbons of the benzene ring.
- An electron-donating resonance effect is observed whenever an atom Z having a lone pair of electrons is directly bonded to a benzene ring (general structure–C6H5 – Z:).
- Some examples of Z include N, O, and halogen.
- For example, five resonance structures can be drawn for aniline(C6H5NH2). Because three of them place a negative charge on a carbon atom of the benzene ring, an NH2 group donates electron density to a benzene ring by a resonance effect.
- In a substituted benzenes having the general structure C6H5 –Y=Z, where Z is more electronegative than Y, an electron-withdrawing resonance effect is observed in the ring
- For example, seven resonance structures can be drawn for benzaldehyde (C6H5CHO). Because three of them place a positive charge on a carbon atom of the benzene ring, a CHO group withdraws electron density from a benzene ring by a resonance effect.
Considering Both Inductive and Resonance Effects
- We need to take in consideration the net balance of both the inductive and the resonance effects to predict whether substituted benzene is more or less electron rich than benzene itself.
- An alkyl group is an electron-donating group and alkyl benzene is more electron rich than benzene.
- Alkyl groups, for instance, donate electrons by an inductive effect, but they have no resonance effect because they lack non-bonded electron pairs or π bonds.
- When electronegative atoms, such as N, O, or halogen, are bonded to the benzene ring, they inductively withdraw electron density from the ring. All of these groups also have a non-bonded pair of electrons, so they donate electron density to the ring by resonance.
- The identity of the element determines the net balance of these opposing effects.
Inductively withdraw electron density
- These elements are electronegative, so they inductively withdraw electron density.
Donate electron density by resonance
These elements have a lone pair, so they can donate electron density by resonance.
- When a neutral O or N atom is bonded directly to a benzene ring, the resonance effect dominates and the net effect is electron donation.
- When a halogen X is bonded to a benzene ring, the inductive effect dominates and the net effect is electron withdrawal.
- Thus, NH2 and OH are electron-donating groups because the resonance effect predominates, whereas Cl and Br are electron-withdrawing groups because the inductive effect predominates.
- In a substituted benzenes having the general structure C6H5 –Y=Z, where Z is more electronegative than Y, The inductive effects and resonance effects in compounds are both electron withdrawing; in other words, the two effects reinforce each other.
- The NH2 group donates electron density, making the benzene ring more electron rich, whereas the CHO group withdraws electron density, making the benzene ring less electron rich.
- NH2 group is electron donating, so the benzene ring of aniline (C6H5NH2) has more electron density than benzene.
- An aldehyde group (CHO), on the other hand, is electron withdrawing, so the benzene ring of benzaldehyde (C6H5CHO) has less electron density than benzene.
- Examples of electron-donating and electron-withdrawing substituents:
Electron Donating Groups
- An O atom with a lone pair bonded directly to the benzene ring
- An electron-donating group
Electron Withdrawing Groups
- An atom with a partial (+) charge bonded directly to the benzene ring
- An electron-withdrawing group
- Common electron-donating groups are alkyl groups or groups with an N or O atom (with a lone pair) bonded to the benzene ring.
- Common electron-withdrawing groups are halogens or groups with an atom Y bearing a full or partial positive charge bonded to the benzene ring.
Electrophilic aromatic substitution of substituted benzenes
- A substituent affects two aspects of electrophilic aromatic substitution:
- The rate of reaction: Substituted benzene reacts faster or slower than benzene itself.
- The orientation: The new functional group is located either ortho, meta, or para to the existing substituent.
- The nature of the first substituent determines the position of the second substituent.
Examples of electrophilic aromatic substitution of substituted benzenes:
- Toluene reacts more rapidly than benzene in all substitution reactions.
- CH3 is an electron-donating group which activates the benzene ringto electrophilic attack.
- Although three products are possible,the ortho and para position to the CH3 are more favourable for the substitution of the new substituent.
- The CH3 group is therefore called an ortho, para director.
- Nitrobenzene compound reacts more slowly than benzene in all electrophilic aromatic substitution reactions.
- NO2 is an electron withdrawing group, therefore, it deactivates the benzene ring to electrophilic attack.
- Although three products are possible,the meta position to the NO2 group is more favourable for the substitution of the new substituent.
- Therefore NO2 group is called a meta director.
Activating, Ortho, Para-Directors
- Substituents that activate a benzene ring and direct substitution ortho and para.
- Substituents that direct substitution meta.
- All meta directors deactivate the ring.
Ortho, para deactivators
- Substituents such as halogens deactivate a benzene ring and direct substitution ortho and para.
Example of ortho, para activator
- The lone pair on N makes this group an ortho, para activator. This compound reacts faster than benzene.
Example meta deactivator
- The δ+ on this C makes the group a meta deactivator. This compound reacts more slowly than benzene.
Orientation Effects in Substituted Benzenes
- All ortho, para directors are R groups or have a non-bonded electron pair on the atom bonded to the benzene ring.
- All meta directors contain a full or partial positive charge on the atom bonded to the benzene ring.
How to determine the directing effects of a particular substituent
- Draw all resonance structures for the carbocation formed from attack of an electrophile E+ at the ortho, meta, and para positions of a substituted benzene (C6H5 – A).
- There are at least three resonance structures for each site of reaction.
- Each resonance structure places a positive charge ortho or para to the new C–E bond.
- Evaluate the stability of the intermediate resonance structures.
- The electrophile attacks at those positions that give the most stable carbocation.
Directing Effects of Substituents
The CH3 Group- An ortho, para Director
CH3 group directs electrophilic aromatic substitution to the ortho and para positions
Resonance structures at the ortho positions to the CH3 group
Resonance structures at the meta positions to the CH3 group
Resonance structures at the para positions to the CH3 group
- Attack at ortho or para to CH3 generates a resonance structure that places a positive charge on a carbon atom with the CH3 group.
- The electron-donating CH3 group stabilizes the adjacent positive charge.
- On the other hand, attack at meta to the CH3 group does not generate any resonance structure stabilized by electron donation.
- We can conclude that CH3 group are ortho and para directors because an electron-donating inductive effect stabilizes the carbocation intermediate.
The NH2 Group- An ortho, para Director
- Amino group (NH2) directs electrophilic aromatic substitution to the ortho and para positions.
Resonance structures at the ortho positions to the NH2 group
Resonance structures at the meta positions to the NH2 group
- Resonance structures at the para positions to the NH2 group
- Attack at the meta position generates the usual three resonance structures.
- Because of the lone pair on the N atom, attack at the ortho and para positions generates a fourth resonance structure, which is stabilized because every atom has an octet of electrons.
- This additional resonance structure can be drawn for all substituents that have an N, O, or halogen atom bonded directly to the benzene ring.
- The NH2 group directs electrophilic attack ortho and para to itself because the carbocation intermediate has additional resonance stabilization.
The NO2 Group- A meta Director
- Nitro group (NO2) directs electrophilic aromatic substitution to the meta position.
Resonance structures at the ortho positions to the NO2 group
Resonance structures at the meta positions to the NO2 group
Resonance structures at the para positions to the NO2 group
- Electrophilic substitution at each position generates three resonance structures.
- One resonance structure resulting from attack at the ortho and para positions is especially destabilized, because it contains a positive charge on two adjacent atoms.
- Attack at the meta position does not generate any particularly unstable resonance structures.
- The NO2 group (meta directors) directs electrophilic attack meta to itself because attack at the ortho or para position gives a destabilized carbocation intermediate.
Summary of the reactivity and directing effects of substituted benzenes
Limitations on electrophilic substitution reactions with substituted benzenes
Halogenation of Activated Benzenes
- Substituted benzene rings undergo polyhalogenation when treated with X2 and FeX3 when the ring is activated by strong electron-donating groups such as OH, NH2, and their alkyl derivatives (OR, NHR, and NR2).
- For example, aniline (C6H5NH2) and phenol (C6H5OH) both give a tribromo derivative when treated with Br2 and FeBr3.
- Substitution occurs at all hydrogen atoms ortho and para to the NH2 and OH groups.
- Monosubstitution of H by Br occurs with Br2 alone without added catalyst to form a mixture of ortho and para products.
Limitations in Friedel–Crafts reactions
- Friedel–Crafts reactions are the most difficult electrophilic aromatic substitution reactions to carry out in the laboratory.
- For example, they do not occur when the benzene ring is substituted with NO2 (a strong deactivator) or with NH2, NHR, or NR2 (strong activators).
- An aromatic benzene ring deactivated by a strong electron-withdrawing group (meta directors) is not electron rich enough to undergo Friedel–Crafts reactions.
- Friedel–Crafts reactions also do not occur with NH2 groups, which are strong activating groups.
- NH2 groups are strong Lewis bases (due to the nonbonded electron pair on N), so they react with AlCl3, the Lewis acid needed for alkylation or acylation.
- The resulting product contains a positive charge adjacent to the benzene ring, so the ring is now strongly deactivated and therefore unreactive in Friedel–Crafts reactions.
- Another limitation of the Friedel–Crafts alkylation arises because of polyalkylation.
- Reaction of benzene with an alkyl halide and AlCl3 places an electron-donor R group on the ring.
- Because R groups activate a ring, the alkylated product (C6H5R) is now more reactive than benzene itself towards further substitution, and it reacts again with RCl to give products of polyalkylation.
- Polysubstitution does not occur with Friedel–Crafts acylation, because the product now has an electron-withdrawing group that deactivates the ring towards another electrophilic substitution.
- When the directing effects of two groups reinforce, the new substituent is located on the position directed by both groups.
- For example, the CH3 group in p-nitrotoluene is an ortho, para director and the NO2 group is a meta director.
- These two effects reinforce each other so that one product is formed on treatment with Br2 and FeBr3.
- Notice that the position para to the CH3 group is “blocked” by a nitro group so no substitution can occur on that carbon.
- When the directing effects of two different functional groups oppose each other, the more dominant activator directs the new substituent.
- In the compound below, the NHCOCH3 group on the benzene ring activates its two ortho positions, and the CH3 group activatesits two ortho positions to reaction with electrophiles.
- Because the NHCOCH3 is a strongeractivator, substitution occurs ortho to it.
- No substitution occurs between two meta substituents because of crowding.
- For example, no substitution occurs at the carbon atom between the two CH3 groups in the compound below, even though two CH3 groups activate that position.
- OH and CH3 groups are ortho, para directors.
- Because the OH group is a stronger activator, substitution occurs ortho to it.
- Both the OH and CH3 groups are ortho, para directors whose directing effects reinforce each other in this case.
- No substitution occurs between the two meta substituents, however, so two products result.
Learn more about reactions of aromatic compounds in part 2 –