chapter 15 Ochem

Organic Chemistry: Reactions of Aromatic Compounds

Electrophilic Aromatic Substitution

• Electrophilic Aromatic Substitution (EAS) is a fundamental reaction mechanism for aromatic compounds.

  • General representation:

  • $E-A + H$

  • Where $E-A$ represents the electrophilic reactant and $H$ represents the hydrogen atom that is substituted.

Common Electrophilic Aromatic Substitutions

1. Halogenation (Section 15.3)

   • Reactants: $X<em>2$ (e.g. $Cl</em>2$, $Br<em>2$) and $FeX</em>3$ (where $X = Cl, Br$)

2. Nitration (Section 15.4)

   • Reactants: $HNO<em>3$ and $H</em>2SO<em>4$ to generate $NO</em>2$

3. Sulfonation (Section 15.5)

   • Reactants: $SO<em>3$ and $H</em>2SO_4$

4. Friedel-Crafts Alkylation (Section 15.6)

   • Reactants: $RCl$ or $RCOCl$ and $AlCl_3$

5. Friedel-Crafts Acylation (Section 15.6)

   • Reactants: $RCOCl$ and $AlCl_3$

Mechanism of Alkenes vs. Arenes

• Alkenes undergo electrophilic addition:

  • Step 1: Alkene + Electrophile (e.g. $HBr$)

  • Step 2: Carbocation formation and addition product formation.

• Arenes undergo electrophilic substitution:

  • Step 1: Electrophile reacts with arenes leading to an arenium ion (a delocalized cyclohexadienyl cation).

  • Step 2: Elimination of $H-A$ to reform the aromatic structure.

Energy Profile for Electrophilic Aromatic Substitution

• Reaction Coordinate:

  • Describes the change in free energy during the EAS process.

  • Illustrated with activated states (H) and energy differences between reactants and products.

Intermediate Formation in EAS

• Sigma Complex:

  • Formation of the arenium ion intermediary, which is a crucial step and has significant energy barriers.

  • The difference in stability between the sigma complex and the starting material dictates the reactivity of various aromatic compounds.

Mechanism of Electrophilic Halogenation

1. $FeCl<em>3 + Cl</em>2 <br>ightarrow [Cl<em>2FeCl</em>3]$

2. Intermediate forms arsenium ion, it undergoes substitution leading to chlorobenzene or bromobenzene as products.

Mechanism of Electrophilic Nitration

1. Mixing $HNO<em>3 + H</em>2SO<em>4 ightarrow$ generates the nitronium ion ($NO</em>2^+$).

2. Arene reacts with this ion to form the arenium ion.

3. Deprotonation reestablishes the aromatic character and produces nitrated products such as nitrobenzene.

Mechanism of Friedel-Crafts Reactions

Friedel-Crafts Alkylation

1. Alkyl halide reacts with $AlCl_3$ to form the carbocation.

2. The carbocation attacks the aromatic ring to form an alkylated product.

Friedel-Crafts Acylation

1. Acylium ions are formed similar to the alkylation mechanism but yield ketone derivatives.

   • Acylium ions demonstrate resonance stability but can rearrange to produce different products (e.g. secondary carbocation).

Effects of Substituents on EAS

• Ortho-para directors amplify reactivity towards electrophilic attack: e.g., alkyl groups (+I effect).

• Meta directors (deactivating groups) hinder attack, leading to placement in the meta position.

  • Substituents can influence electronic density and resonance stabilization, which can dictate the regioselectivity of substitutions.

Directing Groups Examples

1. Ortho-para Directors: Strongly activating (e.g., -NH₂, -OH).

2. Meta Directors: Moderately deactivating (e.g., -NO₂, -CF₃).

3. Weakly Activating: Alkyl groups and phenyl groups.

Competitive Resonance Effects

• Resonance stability of intermediates can dictate pathways during substitution reactions, affecting overall yields and products.

Rearrangements and Inhibitions

• Cations can rearrange during Friedel-Crafts alkylation, which can lead to different product distributions.

• Certain groups can deactivate aromatic rings, inhibiting Friedel-Crafts reactions.

Summary of Reaction Mechanisms

• Mechanistic pathways (SNAr, EAS, Friedel-Crafts, Birch reduction) highlight the diverse transformations aromatic compounds can undergo, which are influenced by electronic factors and sterics.

Conjugation and Stability

• Conjugated systems are generally more stable than their non-conjugated counterparts, affecting mechanisms such as E1, E2 eliminations favoring conjugated products.

Key Reactions to Study

1. Formation of nitrobenzene from benzene.

2. The reduction mechanisms to convert carbonyls back to benzenoid systems.

3. The Diels-Alder cycloaddition to form fused cyclic systems.

Synthesis Examples

• Types of synthetic pathways involving aromatic compounds, including alkylation, acylation, and nitration, portray the complexity and versatility of reactions involving aromaticity in organic synthesis.

Conclusion

• A thorough understanding of electrophilic aromatic substitutions and the structure-activity relationships of substituents allows for strategic manipulation of aromatic compounds in synthetic chemistry.

Note: This guide captures essential mechanisms, experimental conditions, and substituent effects vital for mastering reactions of aromatic compounds in organic chemistry.