Gabriel Phthalimide Synthesis

The Gabriel phthalimide synthesis solves ammonolysis's over-alkylation problem by

protecting the nitrogen inside a ring until the very last step, so it can never react

more than once:

1. Phthalimide is treated with ethanolic $\text{KOH}$ to form potassium phthalimide, deprotonating the acidic $\text{N}-\text{H}$ (acidic because the resulting anion is stabilised by delocalisation into both flanking carbonyl groups).
2. Potassium phthalimide is heated with a haloalkane, $\text{R}-\text{X}$; the phthalimide nitrogen, now a good nucleophile, displaces the halide in a clean $S_N2$ substitution to give $N$-alkylphthalimide. Because nitrogen is locked inside the ring with no $\text{N}-\text{H}$ left, it CANNOT react with a second equivalent of $\text{R}-\text{X}$ -- over-alkylation is structurally impossible.
3. The $N$-alkylphthalimide is hydrolysed (boiling aqueous $\text{NaOH}$ or $\text{HCl}$, or more efficiently treated with hydrazine, $\text{N}_2\text{H}_4$, in the Ing-Manske modification) to release the free primary amine, $\text{R}-\text{NH}_2$, and phthalhydrazide (or phthalic acid/its salt) as a by-product.

The overall result is a primary amine of guaranteed purity, with no secondary or

tertiary amine contaminating it -- the single biggest advantage of this method over

plain ammonolysis.

The key limitation: this method cannot be used to prepare an AROMATIC primary amine

such as aniline directly, because step 2 requires the haloalkane to undergo nucleophilic …