Haloakanes and Haloarenes - Nucleophilic reaction of Haloarenes

  • In the previous lectures, we discussed the nucleophilic substitution reactions of haloalkanes.
  • Today, we will focus on the nucleophilic reactions of haloarenes.
  • Let’s start by understanding the properties of haloarenes.

Properties of Haloarenes

  • Haloarenes are aromatic compounds in which one or more hydrogen atoms in the aromatic ring are replaced by halogen atoms.
  • They are less reactive than haloalkanes due to the stabilizing effect of resonance in the aromatic ring.
  • The most common halogen atoms present in haloarenes are chlorine, bromine, and iodine.
  • The reactivity of haloarenes towards nucleophilic substitution reactions depends on several factors.

Factors Affecting Reactivity of Haloarenes

The reactivity of haloarenes towards nucleophilic substitution reactions is influenced by the following factors:

  1. Nature of the halogen atom present
  1. Position of the halogen atom in the aromatic ring
  1. Nature of the nucleophile
  1. Presence of any other functional groups in the molecule Let’s discuss each factor in detail.

Nature of Halogen Atom

  • The reactivity of haloarenes increases with the decrease in bond dissociation energy (BDE) of C-X bond.
  • BDE decreases in the order: C-F > C-Cl > C-Br > C-I.
  • Therefore, haloarenes with iodine as the halogen atom are most reactive towards nucleophilic substitution reactions. Example: C6H5I (Iodo-benzene)

Position of Halogen Atom

  • The reactivity of haloarenes also depends on the position of the halogen atom in the aromatic ring.
  • The ortho and para positions (positions 2 and 4) are more reactive than the meta position (position 3) due to the greater availability of the aromatic ring for substitution. Example: Ortho and para isomers of bromobenzene (C6H5Br)

Nature of Nucleophile

  • The nature of the nucleophile determines the mechanism of the nucleophilic substitution reaction.
  • Strong nucleophiles, such as OH-, OR-, NH2-, etc., prefer the SN2 mechanism.
  • Weak nucleophiles, such as H2O, prefer the SN1 mechanism. Example: SN2 reaction of chlorobenzene (C6H5Cl) with sodium hydroxide (NaOH)

Presence of Other Functional Groups

  • The presence of certain functional groups in the molecule can either enhance or hinder the nucleophilic substitution reactions.
  • Electron-withdrawing groups (EWG) such as NO2, CN, COOH, etc., enhance the reactivity of haloarenes.
  • Electron-donating groups (EDG) such as -OH, -NH2, -OR, etc., hinder the reactivity of haloarenes. Example: Comparison of reactivity of chlorobenzene (C6H5Cl) and nitrobenzene (C6H5NO2)

Mechanism of Nucleophilic Substitution in Haloarenes

  • The mechanism of nucleophilic substitution reactions in haloarenes can proceed via two pathways: SN1 and SN2.
  • The choice of mechanism depends on the nature of nucleophile, solvent, and reactant.
  • Let’s briefly discuss both mechanisms.

SN2 Mechanism

  • SN2 (Substitution Nucleophilic Bimolecular) mechanism occurs in one step.
  • In this mechanism, the nucleophile attacks the carbon atom bearing the halogen as the leaving group.
  • The inversion of configuration occurs at the carbon atom.
  • This mechanism is favored in haloarenes with strong nucleophiles and hindered substrates. Example: Reaction of bromobenzene (C6H5Br) with sodium hydroxide (NaOH) C6H5Br + NaOH -> C6H5OH + NaBr

SN1 Mechanism

  • SN1 (Substitution Nucleophilic Unimolecular) mechanism occurs in two steps.
  • In the first step, the halogen atom leaves, generating a carbocation intermediate.
  • In the second step, the nucleophile attacks the carbocation.
  • The configuration at the carbon atom can be either inversion or retention.
  • This mechanism is favored in haloarenes with weak nucleophiles and stabilized carbocations. Example: Reaction of chlorobenzene (C6H5Cl) with sodium hydroxide (NaOH) C6H5Cl + NaOH -> C6H5OH + NaCl

Nucleophilic Aromatic Substitution (SNAr)

  • Another type of nucleophilic substitution reaction that can occur in haloarenes is the Nucleophilic Aromatic Substitution (SNAr) reaction.
  • SNAr reactions involve the replacement of a leaving group on an aromatic ring with a nucleophile.
  • These reactions follow a different mechanism compared to the SN1 and SN2 mechanisms.
  • SNAr reactions are also known as the Benzyne Mechanism or Addition-Elimination Mechanism.

Mechanism of Nucleophilic Aromatic Substitution (SNAr)

The mechanism of Nucleophilic Aromatic Substitution (SNAr) involves the following steps:

  1. Generation of a resonance-stabilized anionic intermediate by attacking the electrophilic carbon.
  1. Rearrangement of the intermediate to form a more stable structure.
  1. Attack of the nucleophile on the intermediate, leading to the substitution of the leaving group. Let’s discuss these steps with an example.

Example of Nucleophilic Aromatic Substitution (SNAr)

An example of Nucleophilic Aromatic Substitution (SNAr) is the reaction between chlorobenzene and sodium azide.

  1. The nucleophile, sodium azide (NaN3), attacks the chlorobenzene, forming a resonance-stabilized intermediate.
  1. The intermediate undergoes a rearrangement, forming a more stable structure.
  1. Finally, the nucleophile, sodium azide (NaN3), attacks the intermediate, substituting the leaving group (chlorine). The overall reaction is: C6H5Cl + NaN3 -> C6H5N3 + NaCl

Summary of Nucleophilic Reactions of Haloarenes

  • Haloarenes can undergo nucleophilic substitution reactions.
  • The reactivity of haloarenes depends on the nature of the halogen atom, position of the halogen atom in the aromatic ring, nature of the nucleophile, and presence of other functional groups.
  • Two main mechanisms of nucleophilic substitution in haloarenes are SN1 and SN2.
  • SNAr reactions, also known as the Benzyne Mechanism, can also occur in haloarenes. Let’s move on to some practice problems to reinforce our understanding.

Practice Problem 1

Predict the major product for the following reaction: C6H5Br + KOH -> ?

  • C6H5OH + KBr
  • C6H5K + KBr
  • C6H5Br + BrK
  • C6H5OH + BrK Explain your answer.

Practice Problem 2

What is the major product formed when chlorobenzene reacts with sodium iodide in acetone? Explain your answer.

Practice Problem 3

Predict the outcome of the following reaction: C6H5Cl + NH2OH -> ? Explain your answer and identify the type of nucleophilic substitution mechanism involved.

Practice Problem 4

Which of the following compounds would undergo nucleophilic substitution faster in an SN2 reaction? a) C6H5Cl b) C6H5CH3 c) C6H5OH d) C6H5NH2 Explain your answer.

Summary

To recap:

  • Haloarenes undergo nucleophilic substitution reactions.
  • The reactivity of haloarenes depends on factors like the nature of the halogen atom, position of the halogen atom, nature of the nucleophile, and presence of other functional groups.
  • SN1, SN2, and SNAr mechanisms can occur in haloarenes.
  • Practice problems help deepen our understanding of these concepts. Let’s move on to the next topic - Aromaticity and Electrophilic Aromatic Substitution.

Thank You!

  • Any questions or clarifications on nucleophilic reactions of haloarenes?
  • We will continue our discussion on Aromaticity and Electrophilic Aromatic Substitution in the next lecture.
  • Stay tuned and keep up the good work! Any final questions before we conclude?

Aromaticity

  • Aromaticity is a property exhibited by certain ring compounds that have a high degree of stability.
  • Aromatic compounds follow Hückel’s rule, which states that a compound is aromatic if it has a planar, cyclic, and fully conjugated π system with (4n + 2)π electrons, where n is an integer.
  • Aromatic compounds are characterized by their unique stability, low reactivity, and resonance energy. Examples of aromatic compounds: benzene, naphthalene, pyridine.

Electrophilic Aromatic Substitution

  • Electrophilic aromatic substitution is a reaction in which an electrophile replaces a hydrogen atom in an aromatic ring.
  • The reaction proceeds through the formation of a resonance-stabilized intermediate called a sigma complex.
  • Different electrophiles can undergo substitution reactions with aromatic compounds. Example: Nitration of benzene using nitric acid and sulfuric acid.

Nitration of Benzene

  • Nitration of benzene involves the substitution of a hydrogen atom in the benzene ring with a nitro group (NO2).
  • The reaction is carried out in the presence of a mixture of concentrated nitric acid and concentrated sulfuric acid as a catalyst.
  • Nitronium ion (NO2+) acts as the electrophile in the reaction. Reaction equation: C6H6 + HNO3 -> C6H5NO2 + H2O

Friedel-Crafts Alkylation

  • Friedel-Crafts alkylation is a reaction in which an alkyl group is introduced onto an aromatic ring.
  • The reaction is catalyzed by a Lewis acid, typically aluminum chloride (AlCl3).
  • The alkyl group acts as the electrophile in the reaction. Example: Alkylation of benzene with chloroethane. Reaction equation: C6H6 + CH3CH2Cl -> C6H5CH2CH3 + HCl

Friedel-Crafts Acylation

  • Friedel-Crafts acylation is a reaction in which an acyl group (-C=O) is introduced onto an aromatic ring.
  • The reaction is catalyzed by a Lewis acid, typically aluminum chloride (AlCl3).
  • The acyl group acts as the electrophile in the reaction. Example: Acylation of benzene with acetyl chloride. Reaction equation: C6H6 + CH3C(O)Cl -> C6H5C(O)CH3 + HCl

Halogenation of Aromatic Compounds

  • Halogenation of aromatic compounds involves the substitution of a hydrogen atom in the aromatic ring with a halogen atom.
  • The reaction is catalyzed by a Lewis acid, typically iron chloride (FeCl3).
  • The halogen acts as the electrophile in the reaction. Example: Chlorination of benzene using chlorine gas. Reaction equation: C6H6 + Cl2 -> C6H5Cl + HCl

Sulphonation of Aromatic Compounds

  • Sulphonation of aromatic compounds involves the substitution of a hydrogen atom in the aromatic ring with a sulphonic acid group (-SO3H).
  • The reaction is carried out by treating the aromatic compound with concentrated sulphuric acid (H2SO4) and fuming sulphuric acid (H2SO4/SO3).
  • The sulphonic acid group acts as the electrophile in the reaction. Example: Sulphonation of benzene using concentrated sulphuric acid. Reaction equation: C6H6 + H2SO4 -> C6H5SO3H + H2O

Summary

  • Aromaticity is a property exhibited by certain ring compounds that have a high degree of stability.
  • Electrophilic aromatic substitution is a reaction in which an electrophile replaces a hydrogen atom in an aromatic ring.
  • Examples of electrophilic aromatic substitution reactions include nitration, Friedel-Crafts alkylation, Friedel-Crafts acylation, halogenation, and sulphonation.
  • Each reaction involves the formation of a sigma complex and the subsequent substitution of a hydrogen atom. Let’s move on to some practice problems.

Practice Problem 1

Predict the major product for the following reaction: C6H6 + HNO3 -> ? Explain your answer.

Practice Problem 2

What product would you expect from the Friedel-Crafts acylation reaction between benzene and acetyl chloride in the presence of aluminum chloride catalyst? Explain your answer.

Summary

To recap:

  • Aromatic compounds exhibit aromaticity and follow Hückel’s rule.
  • Electrophilic aromatic substitution involves the substitution of a hydrogen atom in an aromatic ring.
  • Examples of electrophilic aromatic substitution reactions include nitration, Friedel-Crafts alkylation, Friedel-Crafts acylation, halogenation, and sulphonation.
  • Practice problems help reinforce the understanding of these reactions. Thank you for attending today’s lecture! Feel free to ask any final questions before we conclude.