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Related Reactions
Eschweiler-Clarke Reaction
Gabriel Synthesis
Staudinger Reaction
Synthesis of primary amines

DelÚpine Reaction

The DelÚpine Reaction allows the synthesis of primary amines from alkyl halides by the reaction with hexamethylentetramine (urotropine) and subsequent acidic hydrolysis of the resulting quartenary ammonium salt.

Mechanism of the DelÚpine Reaction

An SN2 reaction leads to the hexamethylentetramine salt. In chloroform, the starting materials are soluble wheareas the products crystallize out. It is usually not possible to purify the salt:

Hexamethylenetetramine is formed in nearly quantitative yield from the condensation of ammonia and formaldehyde.

The compound is rather stable, although dihetero-substituted methylene groups are usually highly reactive. In neutral, aqueous solution, urotropine remains stable even at elevated temperatures. Urotropine decomposes in dilute aqueous acid, and the derived ammonium salts also decompose to form the amine hydrochloride and formaldehyde (and formaldehyde diethylacetal):

During acidic hydrolysis or ethanolysis, semiaminals are formed first; these further decompose to yield formaldehyde or the diethylacetal, ammonium salt and the amine hydrochloride:

For a review of the uses of hexamethylenetetramine, a versatile reagent in organic synthesis, please refer to Blažević (Synthesis, 1979, 161-176. DOI).

Recent Literature

A Convenient Route to 3-Pyrroline Utilizing the DelÚpine Reaction
S. Brandńnge, B. Rodriquez, Synthesis, 1988, 347-348.

Reactions of alkyl (halomethyl)furancarboxylates with hexamethylenetetramine
I. M. Lapina, L. M. Pevzner, A. A. Potekhin, Russ. J. Gen. Chem., 2006, 1304-1309.