Gabriel synthesis

The Gabriel synthesis, named for the German chemist Siegmund Gabriel, is a chemical reaction that transforms primary alkyl halides into primary amines using potassium phthalimide. [cite journal
title = Ueber eine Darstellung primärer Amine aus den entsprechenden Halogenverbindungen
author = Gabriel, S.
journal = Ber.
date = 1887
volume = 20
issue =
pages = 2224
url = http://gallica.bnf.fr/ark:/12148/bpt6k90711d/f133.chemindefer] [cite journal
title = An Improved Procedure for the Condensation of Potassium Phthalimide with Organic Halides
author = Sheehan, J. C.; Bolhofer, V. A.
journal = J. Am. Chem. Soc.
date = 1950
volume = 72
issue =
pages = 2786
doi = 10.1021/ja01162a527] [cite journal
title = The Gabriel Synthesis of Primary Amines
author = Gibson, M.S.; Bradshaw, R.W.
journal = Angew. Chem. Int. Ed. Engl.
date = 1968
volume = 7
issue =
pages = 919
doi = 10.1002/anie.196809191] [Mitsunobu, O. "Comp. Org. Syn." 1991, "6", 79-85. (Review)]

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. [cite journal
title = Kinetic Evidence for the Occurrence of a Stepwise Mechanism in the Hydrazinolysis of Phthalimide
author = Khan, M. N.
journal = J. Org. Chem.
date = 1995
volume = 60
issue =
pages = 4536
doi = 10.1021/jo00119a035] 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 phtalhydrazide can be unpleasant. For these reasons, other methods for liberating the amine from the phthalimide exist. [cite journal
title = An Exceptionally Mild Deprotection of Phthalimides
author = Osby, J. O.; Martin, M. G.; Ganem, B.
journal = Tetrahedron Lett.
date = 1984
volume = 25
issue = 20| pages = 2093
doi=10.1016/S0040-4039(01)81169-2]

References