Ch. 18 Orgo 2: Aromatic Substitution Reactions Overview

Electrophilic Aromatic Substitution (EAS)

• Aromatic protons are replaced by electrophiles.

• The aromatic ring acts as the nucleophile, preserving aromaticity.

Halogenation

• Bromination Mechanism

• Step 1: Aromatic ring attacks electrophile, forming sigma complex.

• Step 2: Deprotonation leads to rearomatization.

• FeBr3 or AlBr3 can activate Br2 for bromination.

Sulfonation

• SO3 is used as the electrophile, with H2SO4 as the catalyst.

• Mechanism involves nucleophilic attack, sigma complex formation, and two proton transfers.

• Sulfonation is reversible, depending on concentration.

Nitration

• HNO3 serves as the electrophile with H2SO4 catalyst; nitronium ion (NO2+) is the active species.

• Mechanism follows nucleophilic attack and sigma complex formation.

Friedel-Crafts Reactions

• Alkylation: Alkyl halides act as electrophiles; AlCl3 is the catalyst.

• Susceptible to rearrangement, especially for 1° halides.

• Acylation: An acylium ion is the active electrophile; it avoids rearrangement.

Directing Effects

• Activating groups (e.g., CH3, OCH3) are ortho-para directors, while deactivating groups (e.g., NO2) are meta directors.

• Halogens are exceptions: they withdraw electrons but are ortho-para directors due to resonance.

Multiple Substituents

• Directing effects of substituents must be considered during EAS.

• Steric effects influence regioselectivity, especially in disubstituted rings.

Nucleophilic Aromatic Substitution (NAS)

• Requires a strong electron-withdrawing group.

• Mechanism forms a Meisenheimer complex, which is not stable when substituents are in meta positions.

Elimination-Addition Mechanism

• Can occur under high temperatures to create benzyne intermediates.

Key Considerations

• Certain conditions inhibit nitration on amino-substituted rings.

• The sequence of reactions is critical, particularly with regard to activating and deactivating influences.

Halogenation Mechanism

• Step 1: Aromatic ring attacks the electrophile (Br2 activated by FeBr3 or AlBr3), forming a sigma complex.

• Step 2: Deprotonation occurs, leading to rearomatization of the ring.

Sulfonation Mechanism

• SO3 acts as an electrophile in the presence of H2SO4.

• Nucleophilic attack by the aromatic ring leads to the formation of a sigma complex.

• Two proton transfers occur, with sulfonation being a reversible reaction.

Nitration Mechanism

• Involves HNO3 as an electrophile with H2SO4 as the catalyst, yielding the nitronium ion (NO2+).

• The aromatic ring undergoes a nucleophilic attack, resulting in a sigma complex formation evaluated for rearrangement.

Friedel-Crafts Alkylation Mechanism

• Alkyl halides act as the electrophile, and AlCl3 catalyzes the reaction.

• The aromatic nucleus attacks the alkyl halide to form a sigma complex, followed by rearomatization that could lead to instability and rearrangement for 1° halides.

Friedel-Crafts Acylation Mechanism

• The acylium ion serves as the active electrophile to prevent rearrangement.

• Similar to alkylation, the mechanism involves nucleophilic attack and formation of a sigma complex, followed by rearomatization.

Nucleophilic Aromatic Substitution (NAS) Mechanism

• A strong electron-withdrawing group is necessary for reaction.

• The mechanism forms a Meisenheimer complex (intermediate), typically unstable when substituents are in meta positions.

Elimination-Addition Mechanism

• Occurs under high temperatures, creating benzyne intermediates.

• The elimination of a leaving group followed by the addition of a nucleophile takes place in this process.

General Notes on Mechanisms

• The position and order of substituents significantly affect the reaction pathways and regioselectivity, especially concerning activating and deactivating influences in electrophilic aromatic substitutions.

• Special conditions apply when dealing with amino-substituted rings, particularly making nitration challenging.