# Hemiaminal

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)(NR$_2$)−. 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, (CF$_3$)$_2$C(OH)NH$_2$.
The C-substituted derivatives are obtained by reaction of aldehydes and ammonia:
    ${\ce {3 RCHO + 3 NH3 -> (RCHNH)3 + 3 H2O}}$

### 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:
    ${\ce {3 CH2O + 3 H2NMe -> (CH2NMe)3 + 3 H2O}}$
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 = CH$_3$):
    ${\ce {Me2NH + CH2O -> Me2NCH2OH}}$
    ${\ce {Me2NH + Me2NCH2OH -> Me2NCH2NMe2 + H2O}}$
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).