Nitration and Sulfonation of Benzene

Nitration of Benzene

• Reaction of aromatic rings with concentrated nitric acid (HNO3) and sulfuric acid (H2SO4) produces the nitronium ion (NO2+), the electrophile.
• Sulfuric acid serves as a catalyst, enhancing reaction speed and allowing for lower temperature conditions.
• Example: Nitration leads to amino-substituted products, essential for dye and pharmaceutical synthesis.

Reduction of the Nitro Group

• Nitro groups (NO2) can be reduced to amino groups (NH2) using metals like zinc, tin, or iron in the presence of aqueous hydrochloric acid (HCl).
• Aromatic nitration is primarily conducted in labs, not naturally occurring.

Sulfonation of Benzene

• Aromatic rings undergo sulfonation via fuming sulfuric acid, which contains approximately 7% SO3 mixed with H2SO4.
• The electrophile in this reaction is HSO3, and it introduces a sulfonic acid group (—SO3H) to the aromatic system.
• This process is crucial for synthesizing antibiotics from the sulfa drug family.

Desulfonation Reaction

• Sulfonic acid groups can be removed by heating with dilute sulfuric acid, often with steam providing both heat and water.

Nitration of Toluene

• Toluene nitrates 25 times faster than benzene due to the activating effect of the methyl group.
• The primary products formed are ortho and para substituted derivatives.

Friedel–Crafts Alkylation and Acylation

• Friedel–Crafts alkylation involves adding an alkyl group (R) to benzene through alkyl chloride and aluminum chloride (AlCl3) as a catalyst.
• Friedel–Crafts acylation introduces an acyl group (R-C=O) via the reaction of aromatic compounds with acyl chloride (RCOCl) and AlCl3.
• Example: Benzene reacts with acetyl chloride to produce acetophenone.

Limitations of Friedel–Crafts

• Effective on benzene and its activated derivatives, but fails on strongly deactivated aromatic rings (NO2, CN, SO3H, COR).
• Carbocation rearrangements may occur, and alkylbenzene products can lead to multiple substitutions (polyalkylation).

Clemmensen Reduction

• Converts acylbenzenes to alkylbenzenes using aqueous HCl and amalgamated zinc.

Substituent Effects in Electrophilic Aromatic Substitution

• Substituents can either activate or deactivate aromatic rings, affecting reactivity compared to benzene.
• Significant reactivity differences: -OH makes a ring 1000 times more reactive, while -NO2 makes it over 10 million times less reactive.
• Substituents affect reaction orientation; ortho and para positions favored with activating groups, while meta positions favored with deactivating groups.

Effects of Multiple Substituents

• Combined effects dictate reactivity. Activating groups typically dominate over deactivating groups.
• Activators direct substitutions to ortho and para positions; deactivators generally direct to meta positions, except halogens which are ortho/para directing.

Oxidation and Reduction of Aromatic Compounds

• Benzene typically does not react with strong oxidizing agents like KMnO4; however, alkyl groups can be oxidized to carboxylic acids (CO2H).
• Example: Ethylbenzene oxidized to benzoic acid.

Alkyl Group Stabilization

• Alkyl groups act as activating substituents and direct to ortho/para positions via inductive effects, enhancing electron density on the ring.

Review of Electrophilic Aromatic Substitution (EAS)

• The aromatic ring acts as a nucleophile that attacks an electrophile, forming a carbocation intermediate.
• Electron-donating groups (like -OH and alkyl groups) increase reaction speed by stabilizing the carbocation, while electron-withdrawing groups (like -NO2 and -SO3H) slow it down.

Nucleophilic Aromatic Substitution (NAS)

• NAS features a nucleophile attacking an electron-poor aromatic ring (instead of an electrophile in EAS).
• The reaction rates increase with electron-withdrawing groups, which stabilize the intermediate formed during substitution.
• The position of nucleophile attack is determined by the leaving group, contrasting with the multiple orientations in EAS.

This quiz covers the nitration and sulfonation processes of benzene, including the formation of important electrophiles and the reduction of nitro groups. Understand the role of catalysts and reactions that are pivotal for dye and pharmaceutical synthesis. Perfect for students of organic chemistry.