Slide 1: Haloakanes and Haloarenes - Preparation of Haloarenes

  • Haloarenes are aromatic compounds in which one or more hydrogen atoms have been replaced by halogen atoms.
  • They can be prepared through electrophilic substitution reactions.
    • Examples include:
      • Chlorobenzene (C6H5Cl)
      • Bromobenzene (C6H5Br)
      • Iodobenzene (C6H5I)

Slide 2: Electrophilic Substitution Reactions

  • Electrophilic substitution reactions involve the replacement of a hydrogen atom on an aromatic ring by an electrophile.
  • The reaction occurs due to the high electron density of the aromatic ring.
  • The electrophile attacks the electron-rich aromatic ring, resulting in the substitution of a hydrogen atom.
  • Electrophilic substitution reactions are a key method for synthesizing haloarenes.

Slide 3: Preparation of Haloarenes

  • There are various methods for the preparation of haloarenes.
  • One common method is through the electrophilic substitution of an aromatic compound with a halogen.
  • The reaction is generally carried out in the presence of a Lewis acid catalyst.
  • The halogenation of benzene is a well-known example of the preparation of haloarenes.

Slide 4: Halogenation of Benzene

  • The halogenation of benzene involves the substitution of a hydrogen atom in benzene with a halogen atom.
  • The reaction is carried out in the presence of a Lewis acid catalyst, such as FeCl3 or FeBr3.
  • The halogenation can occur in different positions of the benzene ring, resulting in the formation of different haloarenes.
  • For example, bromination of benzene can lead to the formation of bromobenzene.

Slide 5: Conditions for Halogenation of Benzene

  • The halogenation of benzene requires certain conditions to proceed smoothly.
  • The reaction is typically carried out in the presence of anhydrous halogen gas (Cl2 or Br2) and a Lewis acid catalyst.
  • The reaction mixture is often heated to a moderate temperature to facilitate the reaction.
  • The Lewis acid catalyst helps in the formation of the electrophilic species needed for the substitution reaction.

Slide 6: Mechanism of Halogenation of Benzene

  • The halogenation of benzene occurs via an electrophilic aromatic substitution mechanism.
  • The Lewis acid catalyst, such as FeCl3 or FeBr3, interacts with the halogen to generate an electrophilic species.
  • The electrophilic species attacks the electron-rich benzene ring, leading to the substitution of a hydrogen atom with a halogen atom.
  • The reaction proceeds through the formation of a sigma complex intermediate.

Slide 7: Example: Bromination of Benzene

  • Let’s consider the bromination of benzene as an example.
  • The reaction is carried out in the presence of FeBr3 as the Lewis acid catalyst.
  • Bromine gas (Br2) is used as the halogenating agent.
  • The reaction proceeds as follows:
    • Step 1: Formation of the electrophile (bromonium ion) from Br2 and FeBr3
    • Step 2: Attack of the benzene ring on the electrophile
    • Step 3: Regeneration of the catalyst and formation of bromobenzene

Slide 8: Preparation of Chlorobenzene

  • Chlorobenzene can also be prepared through electrophilic substitution reactions.
  • The reaction is similar to the bromination of benzene, but with chlorine (Cl2) as the halogenating agent.
  • FeCl3 is used as the Lewis acid catalyst.
  • The reaction proceeds via the formation of a chloronium ion as the electrophile.

Slide 9: Preparation of Iodobenzene

  • Iodobenzene can be prepared through electrophilic substitution reactions as well.
  • The reaction is carried out using iodine (I2) as the halogenating agent.
  • FeCl3 or FeBr3 can be used as the Lewis acid catalyst.
  • The generation of the electrophile (iodonium ion) and the substitution of the hydrogen atom on benzene follow a similar mechanism as bromination and chlorination.

Slide 10: Summary

  • Haloarenes are aromatic compounds in which one or more hydrogen atoms have been replaced by halogen atoms.
  • They can be prepared through electrophilic substitution reactions.
  • Examples include chlorobenzene, bromobenzene, and iodobenzene.
  • The halogenation of benzene is a common method used to prepare haloarenes.
  • The reaction requires a Lewis acid catalyst and anhydrous halogen gas.
  • The mechanism involves the formation of an electrophilic species that attacks the electron-rich benzene ring.

Slide 11: Distinction between Haloalkanes and Haloarenes

  • Haloalkanes are alkyl halides in which one or more hydrogen atoms have been replaced by halogen atoms.
  • Haloarenes are aromatic compounds in which one or more hydrogen atoms have been replaced by halogen atoms.
  • The key difference between haloalkanes and haloarenes lies in the nature of the carbon-halogen bond and the type of compound they are derived from.
  • Haloalkanes are derived from alkanes, while haloarenes are derived from aromatic compounds.

Slide 12: Reactivity of Haloalkanes vs Haloarenes

  • Haloalkanes are generally more reactive than haloarenes due to the presence of sp3 hybridized carbon atoms in their structure.
  • The carbon-halogen bond in haloalkanes is polarized, making it susceptible to nucleophilic attack.
  • In contrast, haloarenes have a partially delocalized electron cloud due to the presence of the aromatic ring, which reduces the reactivity of the carbon-halogen bond.
  • Haloarenes are less reactive towards nucleophilic substitution reactions, but they can undergo electrophilic substitution reactions.

Slide 13: Comparison of Electrophilic Substitution in Benzene and Halogenated Benzene

  • Benzene undergoes electrophilic substitution reactions due to its high electron density and aromaticity.
  • The electrophile attacks and substitutes a hydrogen atom on the benzene ring.
  • In haloarenes, the presence of halogen atoms further influences the reactivity and position of electrophilic substitution.
  • The presence of halogen atoms in halogenated benzene can either facilitate or hinder further electrophilic substitution, depending on the position and number of halogen atoms.

Slide 14: Ortho, Meta, and Para Substitution in Halogenated Benzene

  • In halogenated benzene, the electrophilic substitution can occur in different positions of the benzene ring.
  • When a single halogen atom is present, substitution can occur at three different positions: ortho, meta, and para.
  • Ortho substitution refers to the substitution at positions adjacent to the halogen atom.
  • Meta substitution refers to the substitution at positions separated by one carbon atom from the halogen atom.
  • Para substitution refers to the substitution at positions opposite to the halogen atom.

Slide 15: Influence of Halogen Substituents on Reactivity

  • The nature and position of the halogen substituent in haloarenes can significantly influence the reactivity of the compound.
  • Electron-withdrawing groups, such as fluorine or chlorine, increase the reactivity of the benzene ring towards electrophilic substitution.
  • Electron-donating groups, such as methyl or methoxy, decrease the reactivity of the benzene ring towards electrophilic substitution.
  • The position of the halogen substituent can also affect the reactivity; ortho and para substituents generally increase the reactivity, while meta substituents decrease it.

Slide 16: Examples of Electrophilic Substitution in Haloarenes

  • Let’s look at some examples of electrophilic substitution reactions in haloarenes:
    • Nitration of chlorobenzene:
      • Chlorobenzene reacts with nitric acid in the presence of sulfuric acid as a catalyst to form nitrochlorobenzene.
    • Friedel-Crafts alkylation of bromobenzene:
      • Bromobenzene reacts with an alkyl halide in the presence of a Lewis acid catalyst, such as AlCl3, to form an alkylated benzene derivative.
    • Friedel-Crafts acylation of iodobenzene:
      • Iodobenzene reacts with an acyl halide in the presence of a Lewis acid catalyst to form an aromatic ketone.

Slide 17: Nitration of Chlorobenzene

  • Nitration of chlorobenzene is an example of electrophilic substitution in a haloarene.
  • The reaction involves the substitution of a hydrogen atom on the benzene ring with a nitro (-NO2) group.
  • The reaction is carried out in the presence of concentrated nitric acid and sulfuric acid as a catalyst.
  • The nitro group is an electron-withdrawing group, which increases the reactivity of the benzene ring towards electrophilic substitution.

Slide 18: Friedel-Crafts Alkylation of Bromobenzene

  • Friedel-Crafts alkylation is another example of electrophilic substitution in haloarenes.
  • Bromobenzene reacts with an alkyl halide in the presence of a Lewis acid catalyst, such as AlCl3.
  • The reaction leads to the substitution of a hydrogen atom on the benzene ring with an alkyl group.
  • The alkyl group can be a simple alkyl chain, such as methyl or ethyl.

Slide 19: Friedel-Crafts Acylation of Iodobenzene

  • Friedel-Crafts acylation is a variation of electrophilic substitution in haloarenes.
  • Iodobenzene reacts with an acyl halide in the presence of a Lewis acid catalyst.
  • The acyl group (-COR) replaces a hydrogen atom on the benzene ring, resulting in the formation of an aromatic ketone.
  • This reaction is important for the synthesis of various aromatic compounds, including pharmaceuticals and natural products.

Slide 20: Summary

  • Haloarenes are aromatic compounds in which one or more hydrogen atoms have been replaced by halogen atoms.
  • They can undergo electrophilic substitution reactions, allowing the introduction of various functional groups onto the benzene ring.
  • The reactivity of haloarenes is influenced by the nature and position of the halogen substituent.
  • Examples of electrophilic substitution reactions in haloarenes include nitration, Friedel-Crafts alkylation, and Friedel-Crafts acylation.

Slide 21: Reaction Mechanism for Nitration of Chlorobenzene

  • Step 1: Formation of the electrophile (nitronium ion) from concentrated nitric acid and sulfuric acid
  • Step 2: Attack of the chlorobenzene on the nitronium ion
  • Step 3: Regeneration of the catalyst and formation of nitrochlorobenzene
  • Example equation:
    • Chlorobenzene + HNO3 -> Nitrochlorobenzene + H2SO4

Slide 22: Factors Affecting Nitration of Haloarenes

  • Temperature: Higher temperatures increase the rate of the reaction.
  • Concentration of nitric acid: Higher concentration increases the rate of the reaction.
  • Nature of the substituent: Electron-donating groups increase the rate, while electron-withdrawing groups decrease the rate.
  • Position of the substituent: Ortho and para substituents increase the rate, while meta substituents decrease the rate.

Slide 23: Friedel-Crafts Alkylation Mechanism

  • Step 1: Formation of a complex between the Lewis acid catalyst (e.g., AlCl3) and the alkyl halide
  • Step 2: Reaction of the complex with the benzene ring
  • Step 3: Regeneration of the catalyst and formation of the alkylated product
  • Example equation:
    • Bromobenzene + CH3Cl -> Toluene + AlCl3

Slide 24: Factors Affecting Friedel-Crafts Alkylation

  • Nature of the alkyl halide: Primary alkyl halides are preferred.
  • Temperature: Higher temperatures increase the rate of the reaction.
  • Concentration of the Lewis acid catalyst: Higher concentration increases the rate of the reaction.
  • Nature of the substituent: Electron-donating groups increase the rate, while electron-withdrawing groups decrease the rate.

Slide 25: Friedel-Crafts Acylation Mechanism

  • Step 1: Formation of a complex between the Lewis acid catalyst (e.g., AlCl3) and the acyl halide
  • Step 2: Reaction of the complex with the benzene ring
  • Step 3: Regeneration of the catalyst and formation of the acylated product
  • Example equation:
    • Iodobenzene + CH3COCl -> Acetophenone + AlCl3

Slide 26: Factors Affecting Friedel-Crafts Acylation

  • Nature of the acyl halide: Acid chlorides (acyl chlorides) are commonly used.
  • Temperature: Higher temperatures increase the rate of the reaction.
  • Concentration of the Lewis acid catalyst: Higher concentration increases the rate of the reaction.
  • Nature of the substituent: Electron-donating groups increase the rate, while electron-withdrawing groups decrease the rate.

Slide 27: Importance of Haloarenes in Pharmaceuticals

  • Many pharmaceuticals contain haloarene functional groups.
  • The introduction of the halogen atom can modify the biological activity and pharmacological properties of the compounds.
  • Chlorobenzene derivatives, such as chlorpromazine and prochlorperazine, are used as antipsychotic drugs.
  • Fluorobenzene derivatives, such as fluoxetine (Prozac), are used as antidepressants.
  • Iodobenzene derivatives, such as diiodohydroxyquinoline, have antiseptic properties.

Slide 28: Environmental Impact of Haloarenes

  • Haloarenes, particularly those containing chlorine or bromine atoms, can persist in the environment and cause pollution.
  • Some haloarenes are classified as persistent organic pollutants (POPs) and are regulated due to their toxic and bioaccumulative nature.
  • Polychlorinated biphenyls (PCBs), which are derived from halobenzenes, were widely used in electrical equipment and have been found to have adverse effects on human health and the environment.

Slide 29: Quiz Question: Which of the following compounds can be prepared through electrophilic substitution reactions?

  • A) N-Chlorobenzamide
  • B) N-Bromomethylbenzamine
  • C) N-Iodoethylaniline
  • D) N-Methylbenzylamine

Slide 30: Summary

  • Haloarenes can be prepared through electrophilic substitution reactions on the benzene ring.
  • Nitration, Friedel-Crafts alkylation, and Friedel-Crafts acylation are common examples of electrophilic substitution reactions in haloarenes.
  • The reactivity of these reactions is influenced by factors such as temperature, concentration, and the nature of substituents.
  • Haloarenes find applications in pharmaceuticals, but also pose environmental concerns due to their persistence and potential toxicity.