Delepine reaction
Encyclopedia
The Delépine reaction is the organic synthesis
of primary amine
s (4) by reaction of a benzyl
or alkyl halide
s (1) with hexamethylenetetramine (2) followed by acid hydrolysis
of the quaternary ammonium salt (3). It is named after the French chemist Stéphane Marcel Delépine (1871–1965).
Advantages of this reaction are selective access to the primary amine without side reactions from easily accessible reactants with short reaction times and relatively mild reaction conditions.
An example is the synthesis of 2-bromoallylamine from 2,3-dibromopropene.
halide or alkyl halide 1 reacts with hexamethylenetetramine to a quaternary ammonium salt 3, each time just alkylating one nitrogen atom. By reflux
ing in concentrated ethanolic hydrochloric acid
solution this salt is converted to the primary amine together with formaldehyde
(as the acetal
with ethanol
) and ammonium chloride
.
Organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
of primary amine
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
s (4) by reaction of a benzyl
Benzyl
In organic chemistry, benzyl is the term used to describe the substituent or molecular fragment possessing the structure C6H5CH2-. Benzyl features a benzene ring attached to a CH2 group.-Nomenclature:...
or alkyl halide
Halide
A halide is a binary compound, of which one part is a halogen atom and the other part is an element or radical that is less electronegative than the halogen, to make a fluoride, chloride, bromide, iodide, or astatide compound. Many salts are halides...
s (1) with hexamethylenetetramine (2) followed by acid hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
of the quaternary ammonium salt (3). It is named after the French chemist Stéphane Marcel Delépine (1871–1965).
Advantages of this reaction are selective access to the primary amine without side reactions from easily accessible reactants with short reaction times and relatively mild reaction conditions.
An example is the synthesis of 2-bromoallylamine from 2,3-dibromopropene.
Reaction mechanism
The benzylBenzyl
In organic chemistry, benzyl is the term used to describe the substituent or molecular fragment possessing the structure C6H5CH2-. Benzyl features a benzene ring attached to a CH2 group.-Nomenclature:...
halide or alkyl halide 1 reacts with hexamethylenetetramine to a quaternary ammonium salt 3, each time just alkylating one nitrogen atom. By reflux
Reflux
Reflux is a technique involving the condensation of vapors and the return of this condensate to the system from which it originated. It is used in industrial and laboratory distillations...
ing in concentrated ethanolic hydrochloric acid
Hydrochloric acid
Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....
solution this salt is converted to the primary amine together with formaldehyde
Formaldehyde
Formaldehyde is an organic compound with the formula CH2O. It is the simplest aldehyde, hence its systematic name methanal.Formaldehyde is a colorless gas with a characteristic pungent odor. It is an important precursor to many other chemical compounds, especially for polymers...
(as the acetal
Acetal
An acetal is a molecule with two single-bonded oxygen atoms attached to the same carbon atom.Traditional usages distinguish ketals from acetals...
with ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
) and ammonium chloride
Ammonium chloride
Ammonium chloride NH4Cl is an inorganic compound with the formula NH4Cl. It is a white crystalline salt that is highly soluble in water. Solutions of ammonium chloride are mildly acidic. Sal ammoniac is a name of natural, mineralogical form of ammonium chloride...
.