Hemiaminal
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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: −C(OH)(NR2)−. 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. Hemiaminals can be viewed as a blend of aminals and geminal diol. They are a special case of amino alcohols.
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 adducts formed by the addition of ammonia to aldehydes have long been studied. Compounds containing both a primary amino group and a hydroxyl group bonded to the same carbon atom are rarely stable ("The hemiaminal [derived from primary amines] is, except in very special cases... not observed"), as they tend to dehydrate to form imines which polymerise to hexamethylenetetramine. A rare stable example is the adduct of ammonia and hexafluoroacetone, (CF3)2C(OH)NH2.
The C-substituted derivatives are obtained by reaction of aldehydes and ammonia:
3 RCHO + 3 NH 3 ⟶ ( RCHNH ) 3 + 3 H 2 O {\displaystyle {\ce {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 CH 2 O + 3 H 2 NMe ⟶ ( CH 2 NMe ) 3 + 3 H 2 O {\displaystyle {\ce {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 (Me = CH3):
Me 2 NH + CH 2 O ⟶ Me 2 NCH 2 OH {\displaystyle {\ce {Me2NH + CH2O -> Me2NCH2OH}}}
Me 2 NH + Me 2 NCH 2 OH ⟶ Me 2 NCH 2 NMe 2 + H 2 O {\displaystyle {\ce {Me2NH + Me2NCH2OH -> Me2NCH2NMe2 + H2O}}}
The reaction of formaldehyde with carbazole, which is weakly basic, proceed similarly:
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 glycosylamines are examples of cyclic hemiaminal ethers.
- Hemiaminals and ethers
- methanolamine, an intermediate in the reaction of ammonia with formaldehyde
- Bis(hydroxymethyl)urea is a commercially useful hemiaminal
- An unusual example of an isolable, acyclic hemiaminal: the adduct of ammonia and hexafluoroacetone
- Hemiaminal ether derived from an aldehyde
- Hemiaminal ether derived from a ketone
- 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).