51-41-2

Basic information

• Product Name: Norepinephrine
• Synonyms: (-)-alpha-(aminomethyl)protocatechuylalcohol;(-)-noradrec;4-(2-amino-1-hydroxyethyl)-2-benzenedio(r)-;adrenor;aktamin;arterenolfreebase(noradrenaline);d-(-)-noradrenaline;l-1-(3,4-dihydroxyphenyl)-2-aminoethanol
• CAS NO: 51-41-2
• Molecular Formula: C₈H₁₁NO₃
• Molecular Weight: 169.18
• EINECS: 205-750-4
• Product Categories: chiral
• Mol File: 51-41-2.mol

Chemical Properties

• Melting Point: 220-230°C
• Boiling Point: 298.46°C (rough estimate)
• Flash Point: 221.5 °C
• Appearance: off-white to tan/crystalline
• Density: 1.2435 (rough estimate)
• Vapor Pressure: 7.51E-07mmHg at 25°C
• Refractive Index: 1.5100 (estimate)
• Storage Temp.: 2-8°C
• PKA: 8.64(at 25℃)
• Water Solubility: Soluble in alkali and dilute hydrochloric acid. Slightly soluble in water, ethanol and diethyl ether.
• Sensitive: Air & Light Sensitive
• Stability: Stable, but may be light-sensitive. Incompatible with acids, bases, oxidizing agents. Store at -20C.
• Merck: 14,6695
• BRN: 4231961
• CAS DataBase Reference: Norepinephrine(CAS DataBase Reference)
• NIST Chemistry Reference: Norepinephrine(51-41-2)
• EPA Substance Registry System: Norepinephrine(51-41-2)

Safety Data

• Hazard Codes: T+,C,F
• Statements: 26/27/28-34-11-28
• Safety Statements: 28-36/37-45-36/37/39-26-16-20
• RIDADR: UN 2811 6.1/PG 2
• WGK Germany: 3
• RTECS: DN5950000
• F: 8-10-23
• HazardClass: 6.1
• PackingGroup: II
• Hazardous Substances Data: 51-41-2(Hazardous Substances Data)

Usage

Uses

Used in Vascular Active Drug Resistance to Shock:
Norepinephrine is used as a vasoconstrictor for treating hypotensive crises and shock, as its α-activity raises blood pressure.
Used in Cardiac Arrest Treatment:
Norepinephrine is used as an adjunct treatment in cardiac arrest for stimulating the heart, due to its β1-adrenoceptor activity.
Used as an Adrenergic Neurotransmitter:
Norepinephrine is used as an adrenergic neurotransmitter, playing a role in the sympathetic nervous system.
Used in Increasing Cardiac Constriction and Blood Pressure Elevation:
Norepinephrine is used for increasing cardiac constriction and for the necessary elevation of blood pressure after a sharp decline, which can result from surgical intervention or trauma.

World Health Organization (WHO)

Vasoconstrictor agents have been in use for many years to prolong duration of action of local anaesthetics, particularly in dentistry. Combination products containing epinephrine or levarterenol in concentrations of 1:80,000 or less remain widely available. See also WHO comment for epinephrine.

Biological Functions

Most central noradrenergic neurons are located in the nucleus locus ceruleus of the pons and in neurons of the reticular formation. Fibers from these nuclei innervate a large number of cortical, subcortical, and spinomedullary fields. Many functions have been ascribed to the central noradrenergic neurons, including a role in affective disorders (see Chapter 33), in learning and memory, and in sleep–wake cycle regulation.The mammalian CNS contains both α- and β-adrenoceptors.

Hazard

May cause local tissue necrosis, headache, bradycardia, hypertension; poison; teratogen; mutagen.

Pharmacology

Norepinephrine is the primary neurotransmitter produced and released by adrenergic neurons, and in literature it is also described as and called () noradrenaline or levarterenol. This vasopressor catecholamine reduces both the resistance and capacity of blood vessels by stimulating α-adrenoreceptors and having a direct cardiostimulatory effect, which is accomplished by activation of β1-adrenoreceptors. Norepinephrine exhibits significantly less activity than epinephrine as a drug for widening blood vessels through the activation of β2-adrenoreceptors. Elevation of both stylistic and diastolic blood pressure is a typical reaction to intravenous introduction of norepinephrine.

Safety Profile

Poison by ingestion, intraperitoneal, subcutaneous, and intravenous routes. An experimental teratogen. Experimental reproductive effects. Human mutation data reported. A sympathomimetic vasopressor. When heated to decomposition it emits toxic fumes of NOx.

Synthesis

Norepinephrine, L-1-(3,4-dihydroxyphenyl)-2-aminoethanol (11.1.4), is synthesized by two methods starting from 3,4-dihydroxybenzaldehyde. According to the first method, the indicated aldehyde is transformed into the cyanohydrin (11.1.3) by reaction with hydrogen cyanide, which is then reduced into norepinephrine (11.1.5). The second method consists of the condensation of diacetate of the same aldehyde with nitromethane, which forms (3,4-diacetoxyphenyl)-2-nitroethanol (11.1.5). Then the nitro group is reduced and the product (11.1.6) is hydrolyzed into the desired norepinephrine (11.1.4) [4,9,13,14].

Purification Methods

Recrystallise adrenor from EtOH and store it in the dark under N2. [pKa, Lewis Brit J Pharmacol Chemother 9 488 1954, UV: Bergstr.m et al. Acta Physiol Scand 20 101 1950, Fluorescence: Bowman et al. Science NY 122 32 1955, Tullar J Am Chem Soc 70 2067 1948.] The L-tartrate salt monohydrate has m 102-104.5o, [] D -11o (c 1.6, H2O), after recrystallisation from H2O or EtOH. [Beilstein 13 III 2382.]

InChI:InChI=1/C8H11NO3/c9-8(12)4-5-1-2-6(10)7(11)3-5/h1-3,8,10-12H,4,9H2

Synthetic route

arterenone (499-61-6) → norepinephrine (51-41-2)

Conditions	Yield
Stage #1: arterenone With (-)-diisopinocampheylboron chloride In tert-butyl methyl ether at -25 - -20℃; for 3h; Inert atmosphere; Stage #2: With hydrogenchloride In tert-butyl methyl ether; water at 25℃; for 1.5h; Catalytic behavior; Reagent/catalyst; Solvent; Temperature; Inert atmosphere;	70.3%

R-(+)-2,2'-dinitrobiphenyl-6,6'-dicarbonsaeure-di-N,N'-1-(3,4-dihydroxyphenyl)-1-hydroxy-2-amido-ethan (104819-57-0, 104873-30-5, 104873-31-6) → norepinephrine (51-41-2)

Conditions	Yield
With hydrogenchloride; hydrogen; palladium on activated charcoal In ethanol for 6h; Ambient temperature;	51.4%

Norepinephrine (138-65-8) → norepinephrine (51-41-2)

Conditions	Yield
With MANDELIC ACID
With (R)-methoxyphenylacetic acid
With L-Tartaric acid

glycine (56-40-6) + 3,4-dihydroxybenzaldehyde (139-85-5) → norepinephrine (51-41-2) + D-noradrenaline (149-95-1)

Conditions	Yield
With pyridoxal 5'-phosphate In dimethyl sulfoxide at 20℃; for 89h; Enzymatic reaction; Title compound not separated from byproducts.;

1-(3,4-dihydroxyphenyl)-1-oxo-2-amino-ethan-hydrochlorid (5090-29-9) → norepinephrine (51-41-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 61.4 percent / NaHCO3 / benzene; H2O / 30 h 2: NaBH4 / methanol / 24 h 3: 51.4 percent / H2, conc HCl / Pd/C / ethanol / 6 h / Ambient temperature View Scheme

R-(+)-2,2'-dinitrobiphenyl-6,6'-dicarbonsaeure-di-N,N'-1-(3,4-dihydroxyphenyl)-1-oxo-2-amido-ethan (104819-55-8, 104873-27-0, 104873-28-1) → norepinephrine (51-41-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaBH4 / methanol / 24 h 2: 51.4 percent / H2, conc HCl / Pd/C / ethanol / 6 h / Ambient temperature View Scheme

L-tyrosine (60-18-4) → norepinephrine (51-41-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: tetrahydrobiopterin; oxygen; tyrosine hydroxylase / Enzymatic reaction 2: aromatic L-amino acid decarboxylase / Enzymatic reaction 3: oxygen; dopamine β-hydroxylase; ascorbic acid / Enzymatic reaction View Scheme

levodopa (59-92-7) → norepinephrine (51-41-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: aromatic L-amino acid decarboxylase / Enzymatic reaction 2: oxygen; dopamine β-hydroxylase; ascorbic acid / Enzymatic reaction View Scheme

dopamine (51-61-6) → norepinephrine (51-41-2)

Conditions	Yield
With dopamine β-hydroxylase; oxygen; ascorbic acid Enzymatic reaction;

C14H21N4O3(1+)*Cl(1-) → norepinephrine (51-41-2)

Conditions	Yield
With hydrogenchloride In water at 20℃; for 10h;	6.8 g

2-chloro-3',4'-dihydroxyacetophenone (99-40-1) → norepinephrine (51-41-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: (R)-α,α-diphenylprolinol; sodium tetrahydroborate; chloro-trimethyl-silane / tetrahydrofuran / 24 h / 10 - 30 °C / Inert atmosphere 2: N,N-dimethyl-formamide / 18 h / 85 °C 3: hydrogenchloride / water / 10 h / 20 °C View Scheme

C8H9ClO3 → norepinephrine (51-41-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 18 h / 85 °C 2: hydrogenchloride / water / 10 h / 20 °C View Scheme

Norepinephrine (138-65-8) → norepinephrine (51-41-2) + D-noradrenaline (149-95-1)

Conditions	Yield
With phase-transitioned bovine serum albumin film-coated capillary column In methanol pH=8; Resolution of racemate;

L-Tartaric acid (87-69-4) + norepinephrine (51-41-2) → C8H11NO3*C4H6O6*H2O

Conditions	Yield
With water In ethanol at 20℃; for 12h;	96.7%

formaldehyd (50-00-0) + norepinephrine (51-41-2) → 1,2,3,4-tetrahydro-4,6,7-isoquinolinetriol hydrochloride (41462-32-2)

Conditions	Yield
With hydrogenchloride at 24℃; for 24h;	92%

norepinephrine (51-41-2) + 3-<<4-<(tert-butyldimethylsilyl)oxy>phenyl>acetyl>thiazolidine-2-thione (130120-90-0) → 2-[4-(tert-Butyl-dimethyl-silanyloxy)-phenyl]-N-[(R)-2-(3,4-dihydroxy-phenyl)-2-hydroxy-ethyl]-acetamide (130097-10-8)

Conditions	Yield
In N,N-dimethyl-formamide at 25℃;	82%

norepinephrine (51-41-2) + 1-(2-Thioxo-thiazolidin-3-yl)-hexadecan-1-one (74058-64-3) → N-hexadecanoyl-L-noradrenaline (74064-89-4, 94475-55-5)

Conditions	Yield
In tetrahydrofuran; ethanol for 5h; Ambient temperature;	51%

2-(2-methoxyphenoxy)-ethyl methanesulphonate (122853-43-4) + norepinephrine (51-41-2) + trifluoroacetic acid (76-05-1) → (R)-4-(1-hydroxy-2-((2-(2-methoxyphenoxy)ethyl)amino)ethyl)benzene-1,2-diol trifluoroacetate

Conditions	Yield
Stage #1: 2-(2-methoxyphenoxy)-ethyl methanesulphonate; norepinephrine In dimethyl sulfoxide at 70℃; for 6h; Inert atmosphere; Stage #2: trifluoroacetic acid In methanol; water; dimethyl sulfoxide	46%

norepinephrine (51-41-2) + 3-methoxy-4-(3-phenylpropoxy)phenethyl methanesulfonate + trifluoroacetic acid (76-05-1) → (R)-4-(1-hydroxy-2-((3-methoxy-4-(3-phenylpropoxy)phenethyl)amino)ethyl)benzene-1,2-diol trifluoroacetate

Conditions	Yield
Stage #1: norepinephrine; 3-methoxy-4-(3-phenylpropoxy)phenethyl methanesulfonate In dimethyl sulfoxide at 70℃; for 6h; Inert atmosphere; Stage #2: trifluoroacetic acid In methanol; water; dimethyl sulfoxide Inert atmosphere;	38%

nicotinic anhydride (16837-38-0) + norepinephrine (51-41-2) → N-nicotinoylnorepinephrine

Conditions	Yield
In tetrahydrofuran; methanol at 20℃; for 20h;	37%

norepinephrine (51-41-2) + N-{4-[4-(4-oxopiperidin-1-yl)phenylsulfamoyl]phenyl}acetamide (373359-53-6) → N-(4-{[4-(4-{[(2R)-2-(3,4-dihydroxyphenyl)-2-hydroxyethyl]amino}-1-piperidinyl)anilino]sulfonyl}phenyl)acetamide

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol under 258.574 - 1034.3 Torr;	15%

norepinephrine (51-41-2) + 5-azidopentan-2-one (84702-73-8) → 1-(R)-(3.4-dihydroxyphenyl)-2-(1-methyl-4-azidobutylamino)ethanol oxalate salt (186303-33-3)

Conditions	Yield
	15%

norepinephrine (51-41-2) + acetic anhydride (108-24-7) → 4-[bis-(1H-5,6-diacetoxyindol-2-yl)methyl]-1,2-diacetoxybenzene + 3,4-diacetoxybenzaldehyde (67727-64-4) + 5,6-diacetoxyindole (15069-79-1) + 1-acetyl-3,5,6-triacetoxyindole

Conditions	Yield
Stage #1: norepinephrine With sodium periodate; phosphate buffer In water for 0.0833333h; pH=7.4; Stage #2: acetic anhydride With pyridine	A 7% B 1% C 1% D 3%

C18H32O4 (5503-03-7) + norepinephrine (51-41-2) → C26H41NO8 (1036406-97-9)

Conditions	Yield
With oxygen; tris hydrochloride In water; dimethyl sulfoxide at 25℃; for 15h; pH=8.0; regioselective reaction;	6%

C18H30O3 + norepinephrine (51-41-2) → C26H39NO7 (1036407-01-8)

Conditions	Yield
With oxygen; tris hydrochloride In water; dimethyl sulfoxide at 25℃; for 15h; pH=8.0; regioselective reaction;	2%

10-oxo-cis-12-octadecenoic acid (155168-72-2) + norepinephrine (51-41-2) → C26H41NO7 (1036407-00-7)

Conditions	Yield
With oxygen; tris hydrochloride In water; dimethyl sulfoxide at 25℃; for 15h; pH=8.0;	2%

3-pyridinecarbonyl chloride (10400-19-8) + norepinephrine (51-41-2) → N-nicotinoylnorepinephrine

Conditions	Yield
With pyridine

norepinephrine (51-41-2) → (R)-2-acetylamino-1-(3,4-dimethoxy-phenyl)-ethanol (26630-36-4)

Conditions	Yield
durch Acetylierung und Umsetzung des Reaktionsprodukts mit Diazomethan;

norepinephrine (51-41-2) → noradrenochrome (490-89-1)

Conditions	Yield
With methanol; silver(l) oxide

norepinephrine (51-41-2) + chloroformic acid ethyl ester (541-41-3) → ((R)-3,4,β-trihydroxy-phenethyl)-carbamic acid ethyl ester (99161-02-1, 103565-71-5)

norepinephrine (51-41-2) + acetic anhydride (108-24-7) → (R)-2-acetylamino-1-(3,4-diacetoxy-phenyl)-ethanol (28371-32-6)

norepinephrine (51-41-2) + salicylaldehyde (90-02-8) → (R)-N-salicylidenenorepinephrine (73428-22-5)

Conditions	Yield
With ethanol
In methanol

norepinephrine (51-41-2) + 6-oxoheptanoic acid p-methylanilide (83086-06-0) → 6-[(E)-(R)-2-(3,4-Dihydroxy-phenyl)-2-hydroxy-ethylimino]-heptanoic acid p-tolylamide (90900-18-8)

Conditions	Yield
With 3 A molecular sieve In N,N-dimethyl-formamide at 75℃; for 24h;

norepinephrine (51-41-2) + 6-oxo-N-<4-(trifluoromethyl)phenyl>heptanamide (84417-40-3) → 6-[(E)-(R)-2-(3,4-Dihydroxy-phenyl)-2-hydroxy-ethylimino]-heptanoic acid (4-trifluoromethyl-phenyl)-amide (90900-17-7) + 6-[(R)-2-(3,4-Dihydroxy-phenyl)-2-hydroxy-ethylamino]-hept-6-enoic acid (4-trifluoromethyl-phenyl)-amide

Conditions	Yield
With 3 A molecular sieve In N,N-dimethyl-formamide at 75℃; for 24h; Title compound not separated from byproducts;

norepinephrine (51-41-2) + homovanillic acid (130097-16-4) → 2-[4-(tert-Butyl-dimethyl-silanyloxy)-3-methoxy-phenyl]-N-[(R)-2-(3,4-dihydroxy-phenyl)-2-hydroxy-ethyl]-acetamide

Conditions	Yield
In N,N-dimethyl-formamide at 25℃;

norepinephrine (51-41-2) + acetaldehyde (75-07-0) → trans-1,2,3,4-tetrahydro-1-methyl-4,6,7-isoquinolinetriol hydrochloride (85507-49-9) + cis-1,2,3,4-tetrahydro-1-methyl-4,6,7-isoquinolinetriol hydrochloride (85507-48-8)

Conditions	Yield
With hydrogenchloride for 36h; Product distribution; with formaldehyde, var. pH;
With hydrogenchloride for 36h; Yield given. Yields of byproduct given;

norepinephrine (51-41-2) + 4-diethylaminodiazobenzene-4'-isothiocyanate (204763-28-0) → 1-[4-(4-Diethylamino-phenylazo)-phenyl]-3-[(R)-2-(3,4-dihydroxy-phenyl)-2-hydroxy-ethyl]-thiourea

Conditions	Yield
With acetic acid; triethylamine In acetone Addition; Heating;

norepinephrine (51-41-2) → (R)-3',4'-dihydroxyphenylglycol + (R)-3',4'-dihydroxymandelic acid

Conditions	Yield
With Krebs solution; monoamine oxidase in lung of rat Kinetics; Further Variations:; Catalysts; Deamination;

norepinephrine (51-41-2) + water (7732-18-5) + ethylenediamine (107-15-3) + air → 1,2,3,4-tetrahydropyrazino[2,3-g]quinoxaline (28857-14-9)

Conditions	Yield
pH 11;

Upstream product

• 138-65-8 Norepinephrine 
• 104819-57-0 R-(+)-2,2'-dinitrobiphenyl-6,6'-dicarbonsaeure-di-N,N'-1-(3,4-dihydroxyphenyl)-1-hydroxy-2-amido-ethan 
• 56-40-6 glycine 
• 139-85-5 3,4-dihydroxybenzaldehyde 
• 5090-29-9 1-(3,4-dihydroxyphenyl)-1-oxo-2-amino-ethan-hydrochlorid 
• 104819-55-8 R-(+)-2,2'-dinitrobiphenyl-6,6'-dicarbonsaeure-di-N,N'-1-(3,4-dihydroxyphenyl)-1-oxo-2-amido-ethan 
• 60-18-4 L-tyrosine 
• 59-92-7 levodopa 
• 51-61-6 dopamine 
• 499-61-6 arterenone 
• 99-40-1 2-chloro-3',4'-dihydroxyacetophenone 

Downstream Products

• 26630-36-4 (R)-2-acetylamino-1-(3,4-dimethoxy-phenyl)-ethanol 
• 490-89-1 noradrenochrome 
• 41462-32-2 1,2,3,4-tetrahydro-4,6,7-isoquinolinetriol hydrochloride 
• 90900-18-8 6-[(E)-(R)-2-(3,4-Dihydroxy-phenyl)-2-hydroxy-ethylimino]-heptanoic acid p-tolylamide 
• 90900-17-7 6-[(E)-(R)-2-(3,4-Dihydroxy-phenyl)-2-hydroxy-ethylimino]-heptanoic acid (4-trifluoromethyl-phenyl)-amide 
• 74064-89-4 N-hexadecanoyl-L-noradrenaline 
• 67896-55-3 norepinephrine o-quinone 
• 61693-05-8 (R)-(-)-2-amino-1-(3,4-dimethoxyphenyl)ethanol 
• 67727-64-4 3,4-diacetoxybenzaldehyde 
• 15069-79-1 5,6-diacetoxyindole 
• 54837-87-5 ((R)-β-hydroxy-3,4-dimethoxy-phenethyl)-carbamic acid ethyl ester 
• 125251-66-3 1-(3,4 dihydroxyphenyl)-2-(4-(4-hydroxyphenyl)butylamino)ethanol hydrochloride 
• 186303-19-5 1-(R)-(3,4-dihydroxyphenyl)-2-(1-methyl-4-methoxybutylamino)ethanol oxalate salt 
• 186303-25-3 1-(R)-(3,4-dihydroxyphenyl)-2(1-methyl-4-methylthiobutylamino)ethanol oxalate salt 

Relevant articles and documents

In-situ and one-step preparation of protein film in capillary column for open tubular capillary electrochromatography enantioseparation

In this work, the phase-transitioned BSA (PTB) film using the mild and fast fabrication process adhered to the capillary inner wall uniformly, and the fabricated PTB film-coated capillary column was applied to realize open tubular capillary electrochromatography (OT-CEC) enantioseparation. The enantioseparation ability of PTB film-coated capillary was evaluated with eight pairs of chiral analytes including drugs and neurotransmitters, all achieving good resolution and symmetrical peak shape. For three consecutive runs, the relative standard deviations (RSD) of migration time for intra-day, inter-day, and column-to-column repeatability were in the range of 0.3%–3.5%, 0.2%–4.9% and 2.1%–7.7%, respectively. Moreover, the PTB film-coated capillary column ran continuously over 300 times with high separation efficiency. Therefore, the coating method based on BSA self-assembly supramolecular film can be extended to the preparation of other proteinaceous capillary columns.

Method for asymmetrically synthesizing norepinephrine bitartrate

The invention discloses a preparation method for asymmetrically synthesizing norepinephrine bitartrate. The method is characterized by comprising the following steps: by using chloroacetyl catechol asa raw material, asymmetrically reducing carbonyl in the chloroacetyl catechol into hydroxyl, reacting with urotropine, hydrolyzing with hydrochloric acid to obtain R-norepinephrine, salifying rnorepinephrine and Ltartaric acid are salified to obtain norepinephrine bitartrate, wherein the total yield is larger than or equal to 86%, the ee value is larger than or equal to 95%, and the purity is larger than or equal to 99.6%. The method overcomes the defects in the prior art, and has the advantages that asymmetric reduction is adopted, so that the yield of norepinephrine bitartrate is increased,three wastes and the cost are reduced, and the method is suitable for industrial production.

Method for synthesizing noradrenaline

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A Method for Synthesizing a Catecholamine Using Plasma Polymerization

The present invention relates to a method for manufacturing a catecholamine-based compound using a plasma polymerization method and, more specifically, to a method for artificially synthesizing a unimolecular compound capable of having various catecholamines, i.e. a hydroxyl group (-OH) as a ortho-group of a benzene ring and various alkylamines as a para-group, from a catecholamine precursor material such as phenol, aniline, etc, using a dry plasma polymerization method.COPYRIGHT KIPO 2015

Synthesis of aromatic 1,2-amino alcohols utilizing a bienzymatic dynamic kinetic asymmetric transformation

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Pharmaceutical formula

The present invention concerns a pharmacological vehicle or carrier system, which makes possible administration of the active ingredient with a high absorption thereof in the blood circulation of the patient treated therewith, in particular also in the case of oral administration. The pharmacological vehicle system according to the invention comprises ultrafine particles of a reaction product of a reactive derivative of an at least dibasic inorganic acid or an alkane-carboxylic acid having 2 or 3 carboxyl groups and optionally one or two hydroxy groups, wherein one bond of the dibasic inorganic acid or one carboxy group of the alkane-carboxylic acid is bonded to a pharmacological active ingredient containing a hydroxy group, SH group and/or a primary or secondary amino group having a ractive hydrogen atom on this group, and the other bond is bonded to the free hydroxy group of a glycerolipid having at least one free hydroxy group on the glycerol. The invention further concerns these reaction products and a process for the preparation of ultrafine particles of these reaction products.

Ligand Exchange Chromatography of Amino Alcohols. Use of Schiff Bases in Enantiomer Resolution

A new method for enantiomeric resolution of primary amino alcohols by HPLC is described involving derivatization to the salicylaldehyde Schiff base followed by ligand exchange chromatography (LEC) with chiral L-proline-bonded stationary phases.All of the α-amino alcohols with a hydroxyl substituent on the asymmetric carbon examined were resolved, including catecholamines and other β-hydroxyphenethylamines.The copper(II) ion employed in LEC serves to stabilize the Schiff base, whereas the derivative permits complexation in a manner favorable for resolution and enhanced detection.A possible structure for the mixed complex responsible for separation is suggested.From this structure, a correlation between elution order and configuration is proposed.