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: Template:Chem2. 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.
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
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, Template:Chem2.[5]
The C-substituted derivatives are obtained by reaction of aldehydes and ammonia:[6]
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:
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 (Template:Chem2):[8][9]
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
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methanolamine, an intermediate in the reaction of ammonia with formaldehyde
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Bis(hydroxymethyl)urea is a commercially useful hemiaminal
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An unusual example of an isolable, acyclic hemiaminal: the adduct of ammonia and hexafluoroacetone
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Hemiaminal ether derived from an aldehyde
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Hemiaminal ether derived from a ketone
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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
References
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- ↑ Justus Liebig "Ueber die Producte der Oxydation des Alkohols" Annalen der Pharmacie 1835, Volume 14, pp 133–167. Script error: No such module "doi".
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- ↑ Carbazol-9-yl-methanol Milata Viktora, Kada Rudolfa, Lokaj J¨¢nb Molbank 2004, M354 open access publication [1] Template:Webarchive
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