Phthalimide, potassium salt Gabriel synthesis

Alkylation of phthalimide The Gabriel synthesis (Section 22 8) The potassium salt of phthalimide reacts with alkyl hal ides to give N alkylphthalimide deriva fives Hydrolysis or hydrazinolysis of this derivative yields a primary alkylamine... 

Gabriel synthesis (Section 22 8) Method for the synthesis of primary alkylamines in which a key step is the formation of a carbon-nitrogen bond by alkylation of the potassium salt of phthalimide... 

Gabriel synthesis is used for the preparation of primary amines. Phthalimide on treatment with ethanolic potassium hydroxide forms potassium salt of phthalimide which on heating with allqrl halide followed by alkaline hydrolysis produces the corresponding primary amine. Aromatic primary amines cannot be prepared by this method because aryl halides do not undergo nucleophilic substitution with the anion formed by phthalimide. 

The reaction with ammonia or amines, which undoubtedly proceeds by the SNAr mechanism, is catalyzed by copper8" and nickel105 salts, though these are normally used only with rather unreactive halides.106 This reaction, with phase transfer catalysis, has been used to synthesize triarylamines.107 Copper ion catalysts (especially cuprous oxide or iodide) also permit the Gabriel synthesis (0-58) to be applied to aromatic substrates. Aryl bromides or iodides are refluxed with potassium phthalimide and Cu 0 or Cul in dimethylacetamide to give N-aryl phthalimides, which can be hydrolyzed to primary aryl amines.108... 

An alternative reagent equivalent for the amide anion synthon is the potassium salt of phthalimide which can only react with one molecular proportion of alkyl halide. The resulting JV-alkylphthalimide is then cleaved to the primary amine (the Gabriel synthesis). The preliminary preparation of potassium phthalimide (from a solution of phthalimide in absolute ethanol and potassium hydroxide in 75% ethanol) may be avoided in some cases by boiling phthalimide with the halide in the presence of anhydrous potassium carbonate. The cleavage of the JV-substituted phthalimide is best effected by reaction with hydrazine hydrate and then heating the reaction mixture with hydrochloric acid. The insoluble phthalylhydrazide is filtered off, leaving the amine hydrochloride in solution from which the amine may be liberated and isolated in the appropriate manner. 

A method that achieves the same end result as that of alkylation of ammonia but which avoids the formation of secondary and tertiary amines as byproducts is the Gabriel synthesis. Alkyl halides are converted to primary alkylamines without contamination by secondary or tertiary amines. The key reagent is the potassium salt of phthalimide, prepared by the reaction... 

Gabriel amine synthesis Synthesis of primary amines by alkylation of the potassium salt of phthalimide, followed by displacement of the amine by hydrazine, (p. 915)... 

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