Alkanolamine

In organic chemistry, alkanolamines (amino alcohols) are organic compounds that contain both hydroxyl (−OH) and amino (−NH2, −NHR, and −NR2) functional groups on an alkane backbone. Alkanolamines' bifunctionality and physicochemical characteristics lead to their use in many applications, such as textiles, cosmetics, agricultural chemical intermediates, drugs, and metal working fluids. Alkanolamines are present in many approved drugs and thousands of natural products. Two amino acids are alkanolamines, formally speaking: serine and hydroxyproline.

Alkanolamines usually have high-solubility in water due to the hydrogen bonding ability of both the hydroxyl group and the amino group. Alkanoamines have also shown a broad toxicity for a variety of organisms, including parasites, insect larvae and eggs, and microbes. Studies have also shown that the antimicrobial effect of alkanolamines increases in higher pH's. Most alkanolamines are colorless.

1-Aminoalcohols

1-Aminoalcohols are better known as hemiaminals. Methanolamine is the simplest member. 1-Aminoalcohols tend to be labile, readily converting to more highly condensed derivatives or hydrolyzing to the amine and carbonyl.

2-Aminoalcohols

Routes

2-Aminoalcohols are often generated by the reaction of amines with epoxides:

C2H4O + R−NH2 → RNHC2H4OH

Hydrogenation or reduction of amino acids gives a large family of chiral 2-aminoalcohols:

RCH(NH2)CO2H + 2 H2 → RCH(NH2)CH2OH + H2O

Examples include prolinol (from proline), valinol (from valine), tyrosinol (from tyrosine). Some 2-aminoalcohols are produced by the Sharpless asymmetric amino hydroxylation.

Uses and examples

Simple alkanolamines are used as solvents, synthetic intermediates, and high-boiling bases.

2-Aminoalcohols have been used as synthetic building blocks and chiral auxiliaries.Amino ethanols have been proven to be vital precursors for chiral morpholines and piperazines. Key members: ethanolamine, dimethylethanolamine, N-methylethanolamine, Aminomethyl propanol. Two popular drugs, often called alkanolamine beta blockers, are members of this structural class: propranolol, pindolol. 2-Aminoalcohols can also be found in the direct action subgroup of adrenergic drugs such as epinephrine, isoproterenol, phenylephrine and isoetarine.

Other medicinally useful derivative of ethanolamine: Isoetarine, veratridine, veratrine, epinephrine (adrenaline), norepinephrine (noradrenaline), atropine.

1,3- to 1,7-amino alcohols

Two examples of longer aminoalcohols include Heptaminol, a cardiac stimulant, and propanolamines.

1,3-Aminoalcohols are present in several bioactive molecules, such as Sedinone, Dumetorine, and Hygroline. 1,3-Aminoalcohols have been synthesized through a couple methods. Similar to 2-aminoalcohols, 1,3 aminoalcohols can be formed through ring openings, such as an azo-ring opening and addition. 1,3-aminoalcohols can also be synthesized through an azo-aldol condensation or an intermolecular C-H activation.

1,4 and 1,5-aminoalcohols have been synthesized through the reduction of cyclic amides. Catalyzed alkylation of primary amines with 1,4-butanediol is another synthetic route for 1,4-aminoalcohols. Larger amino alcohol (1,5 - and up) synthesis is comparatively underdeveloped. Electrochemical ring-openings can produce 1,3 to 1,7-aminoalcohols.

References

  1. ↑ Davis, John W.; Carpenter, Constance L. (1997), "Environmental Assessment of the Alkanolamines", in Ware, George W. (ed.), Reviews of Environmental Contamination and Toxicology, vol. 149, New York, NY: Springer New York, pp. 87–137, doi:10.1007/978-1-4612-2272-9_2, ISBN 978-1-4612-7482-7, PMID 8956559, retrieved 2025-03-19
  2. ↑ Laskar, Ranjini; Dutta, Subhabrata; Spies, Jan C.; Mukherjee, Poulami; Rentería-Gómez, Ángel; Thielemann, Rebecca E.; Daniliuc, Constantin G.; Gutierrez, Osvaldo; Glorius, Frank (2024-04-17). "γ-Amino Alcohols via Energy Transfer Enabled Brook Rearrangement". Journal of the American Chemical Society. 146 (15): 10899–10907. Bibcode:2024JAChS.14610899L. doi:10.1021/jacs.4c01667. ISSN 0002-7863. PMC 11027157. PMID 38569596.
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  7. ↑ Yan, Xu; Feng, Wei; Ng, Jiong Xu; Li, Jiaxin; Liu, Ying; Zhang, Bo; Shao, Pan-Lin; Zhao, Yu (2025). "Recent advances in catalytic enantioselective synthesis of vicinal amino alcohols". Chemical Society Reviews. 54 (17): 7966–8018. doi:10.1039/D4CS00966E. PMID 40711534.
  8. ↑ Bodkin, Jennifer A.; McLeod, Malcolm D. (2002). "The Sharpless asymmetric aminohydroxylation". Journal of the Chemical Society, Perkin Transactions 1 (24): 2733–2746. doi:10.1039/B111276G.
  9. ↑ Herranz, E.; Sharpless, K. B. (1983). "Osmium-Catalyzed Vicinal Oxyamination of Olefins by Chloramine-T: cis-2-(p-Toluenesulfonamido)cyclohexanol and 2-Methyl-3-(p-Toluenesulfonamido)-2-Pentanol". Org. Synth. 61: 85. doi:10.15227/orgsyn.061.0085.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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  12. ↑ "Pindolol Uses, Side Effects & Warnings". Drugs.com. Retrieved 2025-03-28.
  13. ↑ Wong, Gavin W. K.; Boyda, Heidi N.; Wright, James M. (2014-11-27). "Blood pressure lowering efficacy of partial agonist beta blocker monotherapy for primary hypertension". The Cochrane Database of Systematic Reviews. 2014 (11) CD007450. doi:10.1002/14651858.CD007450.pub2. ISSN 1469-493X. PMC 6486122. PMID 25427719.
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