The Gabriel synthesis is a chemical reaction that tranforms primary alkyl halides into primary amines using potassium phthalimide.

The sodium or potassium salt of the product reacts with a primary alkyl halide to form an alkyl phthalic imide. The reaction fails with secondary alkyl halides.

Upon workup by acidic hydrolysis the primary amine is liberated as the amine salt. Alternatively the workup may be via the Ing-Manske procedure, involving reaction with aqueous or ethanolic hydrazine at reflux. This produces a precipitate of phthalhydrazide along with the primary amine. The first technique often produces bad yields or side products; separation of phalhydrazide can be unpleasant. For these reasons, other methods for liberating the amine from the phthalimide exist.

References

1. Gabriel, S. Ber. 1887, 20, 2224.
2. Sheehan, J. C.; Bolhofer, V. A. J. Am. Chem. Soc. 1950, 72, 2786.
3. Gibson, M.S.; Bradshaw, R.W. Angew. Chem. Int. Ed. Engl. 1968, 7, 919.
4. Mitsunobu, O. Comp. Org. Syn. 1991, 6, 79-85. (Review)
5. Khan, M. N. J. Org. Chem. 1995, 60, 4536.
6. Osby, J. O.; Martin, M. G.; Ganem, B. Tetrahedron Lett. 1984, 2093.

Organic reactions

Gabriel-Synthese | Gabriel-synthese