alkanolamine
{{Short description|Organic compounds with hydroxyl and amino groups on an alkane backbone}}
In organic chemistry, alkanolamines (amino alcohols) are organic compounds that contain both hydroxyl ({{chem2|\sOH}}) and amino ({{chem2|\sNH2}}, {{chem2|\sNHR}}, and {{chem2|\sNR2}}) functional groups on an alkane backbone. Alkanolamine's bifunctionality and physicochemical characteristics lead to its use in many applications, such as textiles, cosmetics, agricultural chemical intermediates, drugs, and metal working fluids.{{Citation |last1=Davis |first1=John W. |title=Environmental Assessment of the Alkanolamines |date=1997 |journal=Reviews of Environmental Contamination and Toxicology |volume=149 |pages=87–137 |editor-last=Ware |editor-first=George W. |url=https://link.springer.com/chapter/10.1007/978-1-4612-2272-9_2 |access-date=2025-03-19 |place=New York, NY |publisher=Springer New York |doi=10.1007/978-1-4612-2272-9_2 |isbn=978-1-4612-7482-7 |last2=Carpenter |first2=Constance L.|pmid=8956559 |url-access=subscription }}{{Cite journal |last1=Laskar |first1=Ranjini |last2=Dutta |first2=Subhabrata |last3=Spies |first3=Jan C. |last4=Mukherjee |first4=Poulami |last5=Rentería-Gómez |first5=Ángel |last6=Thielemann |first6=Rebecca E. |last7=Daniliuc |first7=Constantin G. |last8=Gutierrez |first8=Osvaldo |last9=Glorius |first9=Frank |date=2024-04-17 |title=γ-Amino Alcohols via Energy Transfer Enabled Brook Rearrangement |journal=Journal of the American Chemical Society |language=en |volume=146 |issue=15 |pages=10899–10907 |doi=10.1021/jacs.4c01667 |issn=0002-7863 |pmc=11027157 |pmid=38569596|bibcode=2024JAChS.14610899L }} Many aminoalcohols derivatives also have chemotherapeutic properties. {{Cite journal |last=Ager |first=David J. |last2=Prakash |first2=Indra |last3=Schaad |first3=David R. |date=1996-01-01 |title=1,2-Amino Alcohols and Their Heterocyclic Derivatives as Chiral Auxiliaries in Asymmetric Synthesis |url=https://pubs.acs.org/doi/10.1021/cr9500038 |journal=Chemical Reviews |language=en |volume=96 |issue=2 |pages=835–876 |doi=10.1021/cr9500038 |issn=0009-2665|url-access=subscription }}
Methanolamine.svg|Methanolamine, from the reaction of ammonia with formaldehyde
Ethanolamine.svg|Ethanolamine
2-amino-2-methyl-1-propanol.svg|2-Amino-2-methyl-1-propanol is a precursor to oxazolines
valinol.svg|Valinol is derived from the amino acid valine
Sphingosine structure.svg|Sphingosine is a component of some cell membranes.
Alkanolamines usually have high-solubility in water due to the hydrogen bonding ability of both the hydroxyl group and the amino group.{{Cite web |title=Amino Alcohols - Alfa Chemistry |url=https://www.alfa-chemistry.com/products/amino-alcohols-94.htm#:~:text=Most%20amino%20alcohols%20are%20highly,at%20normal%20temperature%20and%20pressure. |access-date=2025-03-28 |website=www.alfa-chemistry.com}} 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. {{Cite journal |last1=Sandin |first1=M |last2=Allenmark |first2=S |last3=Edebo |first3=L |date=March 1990 |title=Selective toxicity of alkanolamines |journal=Antimicrobial Agents and Chemotherapy |language=en |volume=34 |issue=3 |pages=491–493 |doi=10.1128/AAC.34.3.491 |pmid=2334165 |pmc=171625 |issn=0066-4804}} 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
2-Aminoalcohols, or 1,2-aminoalcohols are an important class of organic compounds. 2-Aminoalcohols have been used in target molecule synthesis, chiral auxiliaries, and as ligands. This is because 2-aminoalcohols are able to create another stereogenic center. 2-Aminoalcohols are often generated by the reaction of amines with epoxides:
:{{chem2|C2H4O + R\sNH2 -> RNHC2H4OH}}
2-Aminoalcohols can also be synthesized from cyclic systems containing an oxygen and a nitrogen. One popular method to synthesizing 2-aminoalcohols is the Sharpless asymmetric amino hydroxylation.{{Cite journal |last=Sun |first=Jiawei |last2=Wang |first2=Shuanghu |last3=Harper |first3=Kaid C. |last4=Kawamata |first4=Yu |last5=Baran |first5=Phil S. |date=January 2025 |title=Stereoselective amino alcohol synthesis via chemoselective electrocatalytic radical cross-couplings |url=https://www.nature.com/articles/s41557-024-01695-7 |journal=Nature Chemistry |language=en |volume=17 |issue=1 |pages=44–53 |doi=10.1038/s41557-024-01695-7 |issn=1755-4349|url-access=subscription }}
Simple alkanolamines are used as solvents, synthetic intermediates, and high-boiling bases.{{Ullmann|author1=Martin Ernst |author2=Johann-Peter Melder |author3=Franz Ingo Berger |author4=Christian Koch|title=Ethanolamines and Propanolamines|year=2022|publisher=Wiley-VCH|location=Weinheim|doi=10.1002/14356007.a10_001.pub2 }}
Hydrogenation or hydride reduction of amino acids gives the corresponding 2-aminoalcohols. Examples include prolinol (from proline), valinol (from valine), tyrosinol (from tyrosine).
Key members: ethanolamine, dimethylethanolamine, N-methylethanolamine, Aminomethyl propanol. Two popular drugs, often called alkanolamine beta blockers, are members of this structural class: propranolol, pindolol.{{Cite web |title=Propranolol Monograph for Professionals |url=https://www.drugs.com/monograph/propranolol.html |access-date=2025-03-28 |website=Drugs.com |language=en}}{{Cite web |title=Pindolol Uses, Side Effects & Warnings |url=https://www.drugs.com/mtm/pindolol.html |access-date=2025-03-28 |website=Drugs.com |language=en}}{{Cite journal |last1=Wong |first1=Gavin W. K. |last2=Boyda |first2=Heidi N. |last3=Wright |first3=James M. |date=2014-11-27 |title=Blood pressure lowering efficacy of partial agonist beta blocker monotherapy for primary hypertension |journal=The Cochrane Database of Systematic Reviews |volume=2014 |issue=11 |pages=CD007450 |doi=10.1002/14651858.CD007450.pub2 |issn=1469-493X |pmc=6486122 |pmid=25427719}} 2-Aminoalcohols can also be found in the direct action subgroup of adrenergic drugs such as epinephrine, isoproterenol, phenylephrine and isoetarine.Vardanyan, R. S.; Hruby, V. J. (2006-01-01), Vardanyan, R. S.; Hruby, V. J. (eds.), "11 - Adrenergic (Sympathomimetic) Drugs", Synthesis of Essential Drugs, Amsterdam: Elsevier, pp. 143–159, {{ISBN|978-0-444-52166-8}}, retrieved 2025-03-28 Isoetarine is yet another medicinally useful derivative of ethanolamine.{{Citation needed|date=November 2023}}
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.{{Cite journal |last=Wang |first=Wei |last2=Hu |first2=Yi |last3=Lin |first3=Ruiqi |last4=Wu |first4=Heng |last5=Tong |first5=Qi |last6=Wang |first6=Liansheng |last7=Xiao |first7=Zufeng |last8=Zhu |first8=Lei |date=2020 |title=Progress on the Synthesis of 1,3-Amino Alcohol |url=http://sioc-journal.cn/Jwk_yjhx/CN/10.6023/cjoc201911011 |journal=Chinese Journal of Organic Chemistry |language=en |volume=40 |issue=5 |pages=1129 |doi=10.6023/cjoc201911011 |issn=0253-2786}} 1,3-Aminoalcohols have be synthesize 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.{{Cite journal |last=Xiao |first=Zhen |last2=Li |first2=Juanjuan |last3=Yue |first3=Qiang |last4=Zhang |first4=Qian |last5=Li |first5=Dong |date=2018 |title=An efficient and atom-economical route to N -aryl amino alcohols from primary amines |url=https://xlink.rsc.org/?DOI=C8RA07355D |journal=RSC Advances |language=en |volume=8 |issue=60 |pages=34304–34308 |doi=10.1039/C8RA07355D |issn=2046-2069 |pmc=9086943 |pmid=35548644}} 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. Recently, electrochemical ring-openings have shown robustness and versatility in producing 1,3 to 1,7-aminoalcohols. {{Cite journal |last=Fang |first=Xinyue |last2=Hu |first2=Xinwei |last3=Li |first3=Quan-Xin |last4=Ni |first4=Shao-Fei |last5=Ruan |first5=Zhixiong |date=2025 |title=Paired Electro-Synthesis of Remote Amino Alcohols with/in H2O |url=https://onlinelibrary.wiley.com/doi/10.1002/anie.202418277 |journal=Angewandte Chemie International Edition |language=en |volume=64 |issue=6 |pages=e202418277 |doi=10.1002/anie.202418277 |issn=1521-3773}}
Natural Products & Drugs
Alkanolamines are present in biomolecules and building blocks leading them to be present in most proteins and peptides. There are 88 approved drugs and more than 3600 natural products that contain aminoalcohols. Two amino acids are alkanolamines, formally speaking: serine and hydroxyproline.
- Veratridine and veratrine
- Tropane alkaloids such as atropine
- hormones and neurotransmitters epinephrine (adrenaline) and norepinephrine (noradrenaline)
The electrochemical ring-opening synthesis has show compatibility with natural aliphatic amino acids, including serine. Amino ethanols have been proven to be vital precursors for chiral morpholines and piperazines.
References
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