Chapter 22: Amines

Summary

• The advantage of this method is that over alkylation is avoided (see previous page)
• Reaction of phthalimide with KOH removes the N-H proton giving an imide ion, a good nucleophile.
• Nucleophilic substitution by the imide ion on the alkyl halide generates an intermediate, N-alkyl phthalimide.
• Hydrolysis or hydrazinolysis liberates a primary alkyl amine.
• Aryl amines cannot be prepared via this method since aryl halides do not undergo simple nucleophilic substitution.

• Alkylation of Ammonia
• Substitution reactions of Alkyl Halides

 

MECHANISM OF THE GABRIEL SYNTHESIS
Step 1: An acid/base reaction. Deprotonation of the imide N-H proton by the base, hydroxide. This proton is more acidic than a simple amine due to the resonance stabilization by the two adjacent C=O groups. This generates a strong nucleophile, the -ve N.
Step 2: The N nucleophile attacks the electrophilic C of the alkyl halide displacing the bromide and creating the new C-N bond. This product can be compared to an N-alkyl amide.
Step 3: The imide can be cleaved via a mechanism analogous to that of amides. Hydrolysis creates the dicarboxylic acid and the required amine.