Master Organic Chemistry Reaction Guide

The Gabriel synthesis of amines

Description: The Gabriel synthesis is a method for making primary amines through an SN2 reaction of a phthalimide with an alkyl halide followed by cleavage with hydrazine (NH2NH2).

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Real-Life Example:
Org. Synth. 1947, 27, 12
DOI Link: 10.15227/orgsyn.027.0012

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6 thoughts on “The Gabriel synthesis of amines

    1. Great question! For uncomplicated molecules without a lot of different functional groups, they both work.

      From a practical standpoint, N3- tends to get more use.

      N3- tends to be a better nucleophile (faster rxn) than potassium phthalimide. Also, reduction of N3 to NH2 can be done many different ways (Pd-C/H2, LiAlH4, etc) and only blows off N2, whereas cleavage of the phthalimide necessitates getting rid of the byproduct.

      For your purposes though – either one is probably fine!

      1. Hi James,

        Which functional groups will not tolerate either/both of these transformations (i.e. azide SN2 & Gabriel rxn)?


        1. That’s kind of a broad question. With the Gabriel you’d want to avoid any unprotected aldehydes/ketones for a variety of reasons, particularly the deprotection step. That’s just a start.

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