Part of JOC-06 — Amines & Diazonium Salts

Preparation of Amines — Gabriel and Hofmann

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Two methods produce pure primary amines without over-alkylation.

Gabriel phthalimide synthesis: Phthalimide + KOH -> K-phthalimide; + RX (SN2) -> N-alkylphthalimide; + N2H4 (Ing-Manske) or NaOH -> RNH2. Only primary amines are possible. Critical limitation: cannot make arylamines (ArX doesn't undergo SN2). CAN make benzylamine (benzyl halide is SN2-reactive). This Gabriel-can't-make-aniline-but-can-make-benzylamine distinction is a JEE favourite.

Hofmann bromamide degradation: RCONH2 + Br2 + NaOH -> RNH2 + Na2CO3. The amine has one fewer carbon than the amide. Mechanism involves 1,2-alkyl migration (R moves from C to N via nitrene intermediate). Works for both aliphatic and aromatic amides — benzamide gives aniline. This is an advantage over Gabriel.

Other methods: reduction of nitrobenzene (Sn/HCl, H2/Pd) is the standard route to aniline. Nitrile reduction (RCN + LiAlH4 -> RCH2NH2) gives 1° amines. Direct alkylation (NH3 + RX) gives uncontrolled mixtures of all amine classes — poor synthetic method.

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