The Gabriel synthesis uses phthalimide, a base, an alkyl halide, and hydrazine to make a 1° amine in a two-step process. First phthalimide is alkylated with an alkyl halide via an SN2 reaction, forming N-alkylphthalimide. Next, hydrazine attacks a carbonyl group of N-alkylphthalimide, resulting in the ring opening, followed by a proton transfer, and intramolecular attack of the other carbonyl by hydrazine’s terminal nitrogen to form a tetrahedral intermediate. A final proton transfer and breakdown of the tetrahedral intermediate gives the desired 1° amine and a cyclic phthalhydrazide by-product.
- Reagents: Acid, Base or Hydrazine/Solvent (e.g. MeOH)
- Reactant: Alkyl Halide, Phthalimide or Potassium Phthalimide
- Product: 1° Amine
- Type of Reaction: SN2, Nucleophilic Addition of Hydrazine
Mechanism
Top Citations
Original Paper
Related Reactions
- Delépine Reaction
- Eschweiler-Clarke Reaction
- Staudinger Reaction
- Synthesis of Primary Amines
Related Compounds
- Phthalidamide (CAS85-41-6)
- Hydrazine (CAS 302-01-2)
- Acid
- Base
