Jawaharlal Nehru Technological University Hyderabad B.Pharmacy II PHARMACEUTICAL ORGANIC CHEMISTRY-II Previous Question Paper (September-2021 - R17)

Nitration of benzene is an electrophilic aromatic substitution reaction where a hydrogen atom on the benzene ring is replaced by a nitro group (-NO2). The reaction involves heating benzene with a nitrating mixture consisting of concentrated nitric acid (HNO3) and concentrated sulfuric acid (H2SO4).

The sulfuric acid acts as a catalyst and a dehydrating agent, facilitating the formation of the active electrophile, the nitronium ion (NO2+). The overall reaction is:

The mechanism proceeds in three stages: first, the generation of the nitronium ion through the protonation of nitric acid by sulfuric acid followed by the loss of water. Second, the nitronium ion attacks the benzene ring to form a resonance-stabilized carbocation known as the sigma complex or arenium ion. Finally, the loss of a proton from the sp3-hybridized carbon restores the aromaticity of the ring, yielding nitrobenzene.

Friedel-Crafts acylation involves the introduction of an acyl group (RCO-) into the benzene ring using an acyl halide or acid anhydride in the presence of a Lewis acid catalyst, typically anhydrous aluminum chloride (AlCl3). The product is an aromatic ketone.

The mechanism follows these steps:

1. Formation of the acylium ion: The Lewis acid AlCl3 reacts with the acyl chloride (RCOCl) to form a complex, which then dissociates to generate a resonance-stabilized acylium ion (R-C≡O+).
2. Electrophilic attack: The acylium ion acts as a strong electrophile and attacks the pi-electron cloud of the benzene ring to form a non-aromatic resonance-stabilized arenium ion intermediate.
3. Deprotonation: The AlCl4- ion abstracts a proton from the sp3-carbon of the intermediate, restoring the aromatic system and regenerating the AlCl3 catalyst.
4. Complex formation: The final ketone product forms a complex with AlCl3, which is released upon aqueous work-up.

Unlike alkylation, acylation does not undergo rearrangement because the acylium ion is resonance-stabilized, and the product is deactivated toward further substitution, preventing polyacylation.