Lecture Notes on Aromatic Substitution Reactions

Overview

• Topics Covered:
  • Ortho, Para, and Meta Directors
  • Activating and Deactivating Groups
  • Electrophilic vs. Nucleophilic Aromatic Substitution
  • Reactivity Ranking
  • Important Reactions for Tests
  • Synthesis and Mechanism Problems

Key Concepts

Ortho, Para, and Meta Directors

• Ortho (1,2) and Para (1,4) Directors:
  • Typically activating groups
  • Have lone pairs on the first atom connected to the ring (e.g., NH2, OH groups)
• Meta (1,3) Directors:
  • Typically deactivating groups
  • First atom attached to the ring is often partially positive

Activating vs. Deactivating Groups

• Activating Groups:
  • Donate electron density to the benzene ring
  • Make the ring more nucleophilic
• Deactivating Groups:
  • Withdraw electron density
  • Make the benzene ring less reactive towards electrophilic substitution

Electrophilic Aromatic Substitution (EAS)

• Involves replacing a hydrogen atom with an electrophile
• Benzene ring acts as a nucleophile
• Activating groups enhance reactivity towards EAS

Nucleophilic Aromatic Substitution (NAS)

• Involves replacing a leaving group (e.g., Br) with a nucleophile
• Electron withdrawing groups enhance reactivity towards NAS

Reaction Mechanisms

• EAS Mechanism: Electrophile replaces hydrogen
• NAS Mechanism: Nucleophile replaces a leaving group

Important Reactions

Electrophilic Aromatic Substitution Reactions

• Nitration: Replace H with NO2 using HNO3, H2SO4
• Bromination: Use Br2 and a Lewis acid catalyst
• Chlorination and Iodination: Similar to bromination
• Sulfonation: Add SO3H using SO3 and H2SO4
• Friedel-Crafts Alkylation and Acylation:
  • Alkylation: Attach alkyl groups
  • Acylation: Introduce acyl groups (can lead to rearrangements)

Nucleophilic Aromatic Substitution

• Addition-Elimination Mechanism:
  • Occurs with presence of electron-withdrawing groups
  • e.g., Convert Ar-Br to Ar-OH using OH- with NO2 present
• Benzyne Intermediate Mechanism:
  • Involves strong bases like NH2-
  • Forms a triple bond intermediate

Synthesis Strategies

• Choosing the Order of Reagents: Important for directing positions
• Protecting Groups: Sometimes needed to prevent unwanted reactions
• Examples:
  • Creating specific substitutions on benzene rings
  • Making functional groups like esters, ethers, and amides

Mechanism Problems

• Proposed mechanisms for specific reactions
• Understanding resonance structures and reaction intermediates
• Example: Formation via Friedel-Crafts reactions and others

Conclusion

• Mastery of aromatic substitution involves understanding directing effects, reactivity, and mechanism details
• Practice with synthesis and mechanism questions to reinforce learning