Hemiaminal
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.

Classification according to amine precursor
Addition of ammonia

The adducts formed by the addition of ammonia to aldehydes have long been studied.[2] Compounds containing both a primary amino group and a hydroxyl group bonded to the same carbon atom are rare. They are invoked but rarely observed as intermediates in the reaction of ammonia and aldehydes and ketones. One example of this rare functionality is the adduct of ammonia and hexafluoroacetone, (CF3)2C(OH)NH2.[3]
The C-substituted derivatives are obtained by reaction of aldehydes and ammonia:[4]
- 3 RCHO + 3 NH3 → (RCHNH)3 + 3 H2O
Addition of primary amines
N-substituted derivatives are somewhat stable. 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.[5]
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):[6][7]
- Me2NH + CH2O → Me2NCH2OH
- Me2NH + Me2NCH2OH → Me2NCH2NMe2 + H2O
The reaction of formaldehyde with carbazole, which is weakly basic, proceed similarly:[8]
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
Use in total synthesis
Hemiaminal formation is a key step in an asymmetric total synthesis of saxitoxin:[9]
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
- Urbansky, Edward T. (2000). "Carbinolamines and Geminal Diols in Aqueous Environmental Organic Chemistry". Journal of Chemical Education. 77 (12): 1644. Bibcode:2000JChEd..77.1644U. doi:10.1021/ed077p1644.
- Justus Liebig "Ueber die Producte der Oxydation des Alkohols" Annalen der Pharmacie 1835, Volume 14, pp 133–167. doi:10.1002/jlac.18350140202
- W. J. Middleton, H. D. Carlson (1970). "Hexafluoroacetone imine". Org. Syntheses. 50: 81–3. doi:10.15227/orgsyn.050.0081..
- Nielsen, Arnold T.; Atkins, Ronald L.; Moore, Donald W.; Scott, Robert; Mallory, Daniel; LaBerge, Jeanne M. (1973). "Structure and Chemistry of the Aldehyde Ammonias. 1-Amino-1-Alkanols, 2,4,6-Trialkyl-1,3,5-Hexahydrotriazines, and N,N-Dialkylidene-1,1-Diaminoalkanes". J. Org. Chem. 38 (19): 3288–3295. doi:10.1021/jo00959a010.
- Iwasawa, T.; Hooley, R. J.; Rebek, J. (2007). "Stabilization of Labile Carbonyl Addition Intermediates by a Synthetic Receptor". Science. 317 (5837): 493–496. Bibcode:2007Sci...317..493I. doi:10.1126/science.1143272. PMID 17656719. S2CID 37292853.
- Hellmann Heinrich, Günter Opitz (1960). Aminoalkylierung. Weinheim.
- Rogers, F. E.; Rapiejko, R. J. (1974). "Thermochemistry of Carbonyl Addition Reactions. II. Enthalpy of Addition of Dimethylamine to Formaldehyde". The Journal of Physical Chemistry. 78 (6): 599–603. doi:10.1021/j100599a008.
- Carbazol-9-yl-methanol Milata Viktora, Kada Rudolfa, Lokaj J¨¢nb Molbank 2004, M354 open access publication Archived 2018-09-26 at the Wayback Machine
- Fleming, James J.; McReynolds, Matthew D.; Du Bois, J. (2007). "(+)-Saxitoxin: A First and Second Generation Stereoselective Synthesis". Journal of the American Chemical Society. 129 (32): 9964–9975. doi:10.1021/ja071501o. PMID 17658800.
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