Gabriel synthesis

The Gabriel synthesis is a chemical reaction that transforms primary alkyl halides into primary amines. Traditionally, the reaction uses potassium phthalimide. The reaction is named after the German chemist Siegmund Gabriel, who first posited the synthesis with the aid of his partner, James Dornbush. The Gabriel reaction has been generalized to include the alkylation of sulfonamides and imides, followed by deprotection, to obtain amines (see Alternative Gabriel reagents). The alkylation of ammonia is often an unselective and inefficient route to amines. In the Gabriel method, phthalimide anion is employed as a surrogate of H2N−. In this method, the sodium or potassium salt of phthalimide is N-alkylated with a primary alkyl halide to give the corresponding N-alkylphthalimide. Upon workup by acidic hydrolysis the primary amine is liberated as the amine salt. Alternatively the workup may be via the Ing–Manske procedure, involving reaction with hydrazine. This method produces a precipitate of phthalhydrazide (C6H4(CO)2N2H2) along with the primary amine: