In organic chemistry, a hemiaminal (also carbinolamine) is a functional group or type of chemical compound that has a hydroxyl group and an amine attached to the same carbon atom: . R can be hydrogen or an alkyl group. Hemiaminals are intermediates in imine formation from an amine and a carbonyl by alkylimino-de-oxo-bisubstitution.
Classification according to amine precursor
Hemiaminals form from the reaction of an amine and a ketone or aldehyde. The hemiaminal is sometimes isolable, but often they spontaneously dehydrate to give imines.
Addition of ammonia
The
formed by the addition of
ammonia to aldehydes have long been studied.
[Justus Liebig "Ueber die Producte der Oxydation des Alkohols" Annalen der Pharmacie 1835, Volume 14, pp 133–167. ] Compounds containing both a primary
amino group and a
hydroxyl group bonded to the same
carbon atom are rarely stable ("The hemiaminal derived is, except in very special cases... not observed"),
as they tend to dehydrate to form
which polymerise to hexamethylenetetramine. A rare stable example is the adduct of
ammonia and hexafluoroacetone, .
[.]
The C-substituted derivatives are obtained by reaction of aldehydes and ammonia:
- 3 RCHO + 3 NH3 -> (RCHNH)3 + 3 H2O
Addition of primary amines
N-substituted derivatives are somewhat stable. They are invoked but rarely observed as intermediates in the
Mannich reaction. These N,N',N''-trisubstituted hexahydro-1,3,5-triazines arise from the condensation of the
amine and formaldehyde as illustrated by the route to 1,3,5-trimethyl-1,3,5-triazacyclohexane:
- 3 CH2O + 3 H2NMe -> (CH2NMe)3 + 3 H2O
Although adducts generated from primary amines or ammonia are usually unstable, the hemiaminals have been trapped in a cavity.
Addition of secondary amines: carbinolamines (hemiaminals) and bisaminomethanes
One of the simplest reactions entails condensation of formaldehyde and dimethylamine. This reaction produces first the carbinolamine (a hemiaminal) and bis(dimethylamino)methane ():
- Me2NH + CH2O -> Me2NCH2OH
- Me2NH + Me2NCH2OH -> Me2NCH2NMe2 + H2O
The reaction of formaldehyde with carbazole, which is weakly basic, proceed similarly:[ Carbazol-9-yl-methanol Milata Viktor, Kada Rudolf, Lokaj Ján Molbank 2004, M354 open access publication [1] ]
Again, this carbinol converts readily to the methylene-linked bis(carbazole).
Hemiaminal ethers
Hemiaminal ethers have the following structure: R‴-C(NR'
2)(OR")-R⁗. The
are examples of cyclic hemiaminal ethers.
Methanolamine.svg|methanolamine, an intermediate in the reaction of ammonia with formaldehyde
OC(NHCH2OH)2.png|Bis(hydroxymethyl)urea is a commercially useful hemiaminal
CF3-stabilizedHemiaminal.svg|An unusual example of an isolable, acyclic hemiaminal: the adduct of ammonia and hexafluoroacetone
Hemiaminal ether aldehyde.png| Hemiaminal ether derived from an aldehyde
Hemiaminal ether ketone.png| Hemiaminal ether derived from a ketone
Bredereck's reagent.svg|Tert-Butoxybis(dimethylamino)methane
Use in total synthesis
Hemiaminal formation is a key step in an asymmetric
total synthesis of
saxitoxin:
In this reaction step the
alkene group is first oxidized to an intermediate
acyloin by action of osmium(III) chloride,
oxone (sacrificial catalyst) and
sodium carbonate (base).
See also
