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How does the Gabriel synthesis prevent repeated alkylation when making primary amines?
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amine
Examples of different types of amines.
The Gabriel synthesis prevents repeated alkylation by using phthalimide as a "blocking" agent to ensure that only one alkyl group is introduced to the nitrogen atom.1
In this process, the acidic hydrogen atom of phthalimide is removed by a base, such as potassium hydroxide, to form a salt. While phthalimide itself is not reactive, its resulting anion reacts with alkyl halides only once. Because the nitrogen atom in the intermediate alkylphthalimide is no longer nucleophilic enough to undergo further alkylation, the reaction is effectively limited to a single substitution. Finally, hydrolysis of the alkylphthalimide releases the desired primary amine.1