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Chapter 15 Notes: Reactions of Aromatic Compounds

Electrophilic Aromatic Substitution (EAS) – Five Reactions

  • Reactions Involved:
    1. Halogenation
    2. Nitration
    3. Sulfonation
    4. Friedel-Crafts Alkylation
    5. Friedel-Crafts Acylation
  • General Characteristics:
    • Electrophilic aromatic substitution reactions involve the introduction of an electrophile to the aromatic system.
    • Strong electrophilic reactivity is key for these reactions to proceed.
    • Common electrophiles include $E^+$ (e.g., halogens, nitrating agents).

Mechanism of Halogenation of Benzene

  • Electrophiles Used: $X = Cl^+$ or $Br^+$
  • Mechanism Steps:
    • Step 1: Formation of the arenium ion – A slow step which is the rate-determining, where a weak base $E$ is involved.
    • Step 2: Fast reaction following the generation of the arenium ion leads to aromaticity being restored.
  • Catalysts Used: $FeX3$ (e.g., $FeCl3$, $FeBr_3$) acts as a catalyst for the reaction.

Nitration Mechanism

  • Nitration likewise forms an arenium ion as an intermediate.
  • Reversible reaction; the -$SO_3H$ group can act as a protecting group, demonstrating protection in synthetic applications.
  • Key Considerations: Observations about equilibria influence how strongly acidic conditions shift product formation.

Sulfonation Mechanism

  • Similar to nitration, where the -$SO_3H$ group can be involved in displacing other substituents in electrophilic aromatic substitutions.

Friedel-Crafts Alkylation Mechanism

  • Limitations of Friedel-Crafts Reactions:

    1. Presence of strong electron-withdrawing groups (EWGs) like $-NO2$, $-SO3H$, or $-C=O$ can destabilize the arenium ion.
    2. Avoid basic nitrogen groups in reagents (e.g., -NR2) to prevent interference.
    3. Aryl or vinyl halides cannot serve as electrophiles due to repulsive $ ext{π}$ electron interactions.

  • Rearrangements:

    • Friedel-Crafts alkylations may lead to rearrangements while acylations do not permit such rearrangements (no hydride shifts).
    • Reaction conditions should be carefully controlled to manage stability and yield.

Effects of Substituents on EAS

  • Electron-Withdrawing Groups (EWGs):
    • Destabilize the arenium ion; increase the activation energy ($E_a$) and lower reaction rates.
  • Electron-Donating Groups (EDGs):
    • Stabilize the arenium ion; decrease $E_a$ and increase reaction rates.
  • The directing effects of functiom groups in substituted benzenes favor ortho and para substitution when an EDG is present.

Substituent Effects in Multisubstituted Benzenes

  • Most activated groups (EDGs) dictate the director pathways for new substitutions.
  • Sterics and electronic effects will influence observances of where substitutions occur within the molecular structure.

Potassium Permanganate (KMnO4) Application

  • KMnO4 can oxidatively cleave the benzylic carbon to install a carboxylic acid.
  • Additional side reactions such as the oxidation of alcohols may occur, leading to competition in reaction pathways.

Nucleophilic Aromatic Substitution (SNAr)

  • Utilizes an addition-elimination mechanism where a powerful EWG must be ortho or para to the leaving group in the benzene.
    • A meta position cannot stabilize the intermediate formed in the addition step (Meisenheimer complex).

Benzyne Formation

  • Benzyne formation occurs through an elimination-addition pathway.
  • Key historical insights include JD Roberts’ experiments in 1952 involving radioactively labeled carbon-14 in benzene.
  • Donald Cram's work on trapping benzyne in molecular containers led to Nobel Prize recognition in 1987.

Birch Reduction Overview

  • Process description:
    • Involves dissolving metal reductions conducted at low temperatures (-60°C) in liquid ammonia with alkali metals acting as reductants.
  • Birch reduction alters benzene to yield products through the formation of radical anions, changing saturation states on nearby carbons.

Substituent Effects during Birch Reduction

  • EWG promote reactions at the carbon they are attached to (ipso position) leading to faster reaction rates (lower $E_a$).
  • Conversely, EDGs promote reactions at adjacent carbons (ortho position) and generally yield slower reaction rates (higher $E_a$).