Gabriel synthesis

The Gabriel synthesis is a name reaction in organic chemistry, which was named after its discoverer Siegmund Gabriel ( 1851-1924 ). It is a chemical method for the selective preparation of primary amines by splitting phthalimides. A historically interesting variant of this synthesis is the 1889 was synthetic preparation of α -amino acids.

Overview reaction

Potassium phthalimide to react with an alkyl halide to N- alkylphthalimide, which reacts in a number of reaction steps to a primary amine.

Mechanism

In the first step of potassium phthalimide reacts with an alkyl halide (here with bromine) to N- alkyl phthalimide. The next step is added to N- alkylphthalimide hydrazine. In this so-called Ing- Manske variant create a cyclic phthalhydrazide and a primary amine. This hydrazinolysis is carried out for several hours in boiling ethanol. This step under mild conditions usually no side reactions. In addition to the hydrazinolysis amine synthesis may also be carried out by hydrolysis, which proceeds only very slowly, however, or under severe conditions. The aminolysis runs better because of the adjacent lone pairs in hydrazine, since the nucleophilicity is larger ( α - effect).

Variants

Saponification

In addition to the hydrazinolysis saponification is another method for the preparation of primary amines. The first reaction step proceeds identical. In the second reaction step, the N- alkyl phthalimide to react with a caustic solution to a Phthalsäureanion and an alkylamine.

Reaction with Brommalonsäureester

When used in place of haloalkanes as Brommalonsäureester substrate α -amino acids are available. The first part of the reaction mechanism resembles that of the saponification, except that R is replaced with malonic acid. The following figure shows the further reaction step ( saponification) of the α - amino acid glycine to Aminmalonsäureester.

N- Phthalimidomalonsäureester can be alkylated with a variety of alkyl halides or α, β -unsaturated carbonyl compounds, so that different α - amino acids can be illustrated.

Practical significance

The Gabriel Synthesis is a pure laboratory procedures. Due to the formation of stoichiometric amounts of several waste materials the atom economy of the Gabriel synthesis is so bad that no one realized a technical synthesis of primary amines based on this reaction.