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)(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.^[1] Hemiaminals can be viewed as a blend of aminals and geminal diol. They are a special case of amino alcohols.

Generic hemiaminal

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.^[2]

Addition of ammonia

Methanolamine, a simple hemiaminal

The adducts formed by the addition of ammonia to aldehydes have long been studied.^[3] 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"),^[4] 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.^[5]

The C-substituted derivatives are obtained by reaction of aldehydes and ammonia:^[6]

${\displaystyle {\ce {3 RCHO + 3 NH3 -> (RCHNH)3 + 3 H2O}}}$

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:

${\displaystyle {\ce {3 CH2O + 3 H2NMe -> (CH2NMe)3 + 3 H2O}}}$

Although adducts generated from primary amines or ammonia are usually unstable, the hemiaminals have been trapped in a cavity.^[7]

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):^[8][9]

${\displaystyle {\ce {Me2NH + CH2O -> Me2NCH2OH}}}$

${\displaystyle {\ce {Me2NH + Me2NCH2OH -> Me2NCH2NMe2 + H2O}}}$

The reaction of formaldehyde with carbazole, which is weakly basic, proceed similarly:^[10]

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:^[11]

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

• Aminal
• Alkanolamine
• Hemiacetal