Reactions of Isoquinoline

Reactions of Isoquinoline include electrophilic substitution, nucleophilic substitution, oxidation, and reduction important in medicinal chemistry.

Reactions of Isoquinoline

1. Electrophilic Aromatic Substitution (EAS)

   • Preferred at benzene ring positions:
     • Especially C-5 and C-8 (similar to quinoline).
   • EAS is harder on the pyridine ring (C-1 to C-4).
   • Examples:
     • Nitration: HNO₃/H₂SO₄ → 5-nitroisoquinoline
     • Bromination: Br₂/FeBr₃ → 5-bromoisoquinoline
     • Sulfonation: Concentrated H₂SO₄ → 5-sulfono derivative

2. Nucleophilic Substitution (NAS)

   • C-1 and C-3 are activated for nucleophilic attack when a leaving group (e.g., Cl) is present.
   • Example:
     • 1-chloroisoquinoline +  NH₃  →  1-aminoisoquinoline

3. Reduction

   • Catalytic hydrogenation:
     • Full: → tetrahydroisoquinoline or octahydroisoquinoline
     • Partial: with hydride → 1,2-dihydroisoquinoline

4. N-Oxidation

   • m-CPBA or H₂O₂ oxidizes nitrogen → isoquinoline N-oxide.

5. Chichibabin Reaction

   • Reacts with NaNH₂ to give 2-aminoisoquinoline (via benzyne-like intermediate at C-2).

6. Pomeranz–Fritsch Synthesis (important synthetic route):

   • Benzaldehyde + aminoacetaldehyde derivatives → cyclization → isoquinoline.

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