329-65-7

Basic information

• Product Name: DL-Adrenalin
• Synonyms: dl-adrenalin;DL-ADRENALINE;DL-EPINEPHRINE;(+/-)-EPINEPHRINE;(+/-)-ADRENALIN;4-[1-HYDROXY-2-(METHYLAMINO)ETHYL]-1,2-BENZENEDIOL;4-(1-HYDROXY-2-METHYLAMINO-ETHYL)-BENZENE-1,2-DIOL;1-(3,4-dihydroxyphenyl)-2-(methylamino)ethanol
• CAS NO: 329-65-7
• Molecular Formula: C₉H₁₃NO₃
• Molecular Weight: 183.2
• EINECS: 206-347-6
• Product Categories: Standards - 13C & 2H for GC-Mass Spectrometry;Amines;Aromatics;Neurochemicals
• Mol File: 329-65-7.mol
• Article Data: 11

Chemical Properties

• Melting Point: 197 °C (dec.)(lit.)
• Boiling Point: 316.88°C (rough estimate)
• Flash Point: 207.9 °C
• Appearance: odorless light brown or nearly white crystals
• Density: 1.1967 (rough estimate)
• Refractive Index: 1.4760 (estimate)
• Storage Temp.: 2-8°C
• PKA: 9.60±0.10(Predicted)
• Water Solubility: Sparingly soluble
• Sensitive: Light Sensitive
• Merck: 14,3619
• CAS DataBase Reference: DL-Adrenalin(CAS DataBase Reference)
• NIST Chemistry Reference: DL-Adrenalin(329-65-7)
• EPA Substance Registry System: DL-Adrenalin(329-65-7)

Safety Data

• Hazard Codes: T
• Statements: 24-36/37/38
• Safety Statements: 26-36/37-45
• RIDADR: UN 2811 6.1/PG 2
• WGK Germany: 3
• RTECS: DO2975000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 329-65-7(Hazardous Substances Data)

Usage

Chemical Properties

Solid

Uses

Different sources of media describe the Uses of 329-65-7 differently. You can refer to the following data:
1. DL-Adrenaline is a hormone and a neurotransmitter secreted by the medulla of the adrenal glands. In medicine DL-Adrenaline is used chiefly as a stimulant in cardiac arrest, as a vasoconstrictor in shock, and as a bronchodilator and antispasmodic in bronch
2. A hormone and neurotransmitter

Definition

ChEBI: A catecholamine in which the aminoethyl side-chain is hydroxy-substituted at C-1 and methylated on nitrogen.

Brand name

Vaponefrin (Fisons).

General Description

Odorless light brown or nearly white crystals.

Air & Water Reactions

Slightly water soluble .

Reactivity Profile

Light sensitive. Incompatible with heat, air, iron salts, and alkalis. . An aminoalcohol. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides. Incompatible with heat, air, iron salts, and alkalis. .

Health Hazard

SYMPTOMS: Pallor, tremor, anxiety, nervousness, rapid, forceful pulse, rise in blood pressure and temperature, rapid breathing, dilation of the pupils.

Fire Hazard

Flash point data for DL-Adrenalin are not available, however, DL-Adrenalin is probably combustible.

InChI:InChI=1/C9H13NO3/c1-10-5-9(13)6-2-3-7(11)8(12)4-6/h2-4,9-13H,5H2,1H3

Synthetic route

(S)-4-[1-hydroxy-2-(methylamino)ethyl]pyrocatechol (150-05-0) → Epinephrine (329-65-7)

Conditions	Yield
With salicylaldehyde; acetic acid at 90℃; for 4h; Temperature; Reagent/catalyst;	92.7%
With hydrogenchloride In water at 80℃; for 1h;	91.5%

1-(3,4-dihydroxyphenyl)-1-oxo-2-methylamino-ethan-hydrochlorid (62-13-5) → Epinephrine (329-65-7)

Conditions	Yield
With hydrogen; palladium(II) hydroxide In methanol; water at 10 - 40℃; under 150.015 Torr; for 16h;	64%
Multi-step reaction with 3 steps 1: 73 percent / NaHCO3 / benzene; H2O / 30 h 2: 71 percent / NaBH4 / methanol / 24 h 3: 54.6 percent / H2, conc HCl / Pd/C / ethanol / 6 h / Ambient temperature View Scheme

R,S-2,2'-dinitrobiphenyl-6,6'-dicarbonsaeure-di-N,N'-1-(3,4-dihydroxyphenyl)-1-hydroxy-methylamido-ethan (104819-58-1, 104873-32-7, 104873-33-8) → Epinephrine (329-65-7)

Conditions	Yield
With hydrogenchloride; hydrogen; palladium on activated charcoal In ethanol for 6h; Ambient temperature;	54.6%

2-(benzyl-methyl-amino)-1-(3,4-dihydroxy-phenyl)-ethanone (36467-25-1) → Epinephrine (329-65-7)

Conditions	Yield
Stage #1: 2-(benzyl-methyl-amino)-1-(3,4-dihydroxy-phenyl)-ethanone With hydrogenchloride; hydrogen; palladium 10% on activated carbon In methanol; water at 40℃; for 30 - 35h; pH=1.0 - 2.4; Stage #2: With ammonia In water at 10 - 15℃; pH=8.5;
With hydrogenchloride; palladium Hydrogenation;

adrenalone (99-45-6) → Epinephrine (329-65-7)

Conditions	Yield
With sodium hydroxide; nickel Hydrogenation;
With water; palladium Hydrogenation;
With sodium hydroxide; nickel Hydrogenation;
With sodium amalgam; ethanol

benzene-1,2-diol (120-80-9) + N-methylaminoacetaldehyde diethyl acetal (20677-73-0) → Epinephrine (329-65-7)

Conditions	Yield
With hydrogenchloride at 100℃; das Hydrochlorid entsteht im Rohr;
With hydrogenchloride at 100℃; das Hydrochlorid entsteht im Rohr;

(-)-epinephrine (51-43-4, 150-05-0, 329-65-7, 6912-68-1) → Epinephrine (329-65-7)

Conditions	Yield
With hydrogenchloride at 30.1℃; Rate constant;

3-methyl-5-<3.4-methylenedioxy-phenyl>-oxazolidone-(2) → Epinephrine (329-65-7)

Conditions	Yield
With hydrogenchloride

dl-adrenaline → Epinephrine (329-65-7)

Conditions	Yield
With D-tartaric acid dextrorotatory methylaminomethyl-<3.4-dioxy-phenyl>-carbinol;

synephrine tartrate (67-04-9, 136-37-8, 136-38-9, 2410-00-6, 3459-11-8, 7418-89-5, 13998-28-2, 16589-24-5, 21254-60-4, 41787-41-1) + sodium chloride + oxygen → Epinephrine (329-65-7)

Conditions	Yield
mit UV-Licht.Irradiation;

ω-methylamino-3.4-dioxy-acetophenone hydrochloride → Epinephrine (329-65-7)

Conditions	Yield
With water; hydrogen; palladium dichloride durch elektrolytische Reduktion an einer Palladiumkathode;

R,S-2,2'-dinitrobiphenyl-6,6'-dicarbonsaeure-di-N,N'-1-(3,4-dihydroxyphenyl)-1-oxo-2-methylamido-ethan (104819-56-9, 104873-29-2, 104874-56-8) → Epinephrine (329-65-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 71 percent / NaBH4 / methanol / 24 h 2: 54.6 percent / H2, conc HCl / Pd/C / ethanol / 6 h / Ambient temperature View Scheme

C9H12NO3 (115780-42-2) → Epinephrine (329-65-7) + adrenaline o-quinone (672-73-1, 162706-73-2)

Conditions	Yield
With tert-butoxy radical; acetic acid In acetonitrile Kinetics; Inert atmosphere;

C24H21NO5 → Epinephrine (329-65-7)

Conditions	Yield
With hydrazine hydrate In ethanol at 20℃; for 45h; Reflux;

2-chloro-3',4'-dihydroxyacetophenone (99-40-1) → Epinephrine (329-65-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: acetonitrile; water / 3 h / 0 - 40 °C / Large scale 1.2: 1.5 h / 5 - 25 °C / Large scale 2.1: hydrogen; palladium(II) hydroxide / water; methanol / 16 h / 10 - 40 °C / 150.01 Torr View Scheme

norepinephrine (51-41-2) + S-Adenosyl-L-methionine (14031-35-7, 17176-17-9, 29908-03-0, 75044-81-4, 78548-84-2, 79647-17-9, 91279-78-6) → Epinephrine (329-65-7) + S-(5'-adenosyl)-L-homocysteine (979-92-0)

Conditions	Yield
With human phenylethanolamine N-methyltransferase In dimethyl sulfoxide at 25 - 100℃; for 0.583333h; Catalytic behavior; Enzymatic reaction;

Epinephrine (329-65-7) → 6-Nitro-adrenalin (25696-27-9)

Conditions	Yield
With phosphate buffer pH 7.4; sodium nitrite Ambient temperature;	100%
With hydrogenchloride; sodium nitrite

methanol (67-56-1) + Epinephrine (329-65-7) → 4-(1-methoxy-2-methylamino-ethyl)-pyrocatechol; hydrochloride (74571-90-7)

Conditions	Yield
With hydrogenchloride for 0.25h;	98%

Epinephrine (329-65-7) + O,O‐diethyl 2-iodoethoxymethylphosphonate → diethyl (2-((2-(3,4-dihydroxyphenyl)-2-hydroxyethyl)(methyl)amino)ethoxy)methylphosphonate

Conditions	Yield
With triethylamine In tetrahydrofuran at 10 - 50℃; for 3h;	86%

Epinephrine (329-65-7) → 4-(1-mercapto-2-methylamino-ethyl)-benzene-1,2-diol

Conditions	Yield
With polymer supported thiol; trifluoroacetic anhydride In dichloromethane at 20℃; for 0.25h;	81%

Epinephrine (329-65-7) → (+/-)-epinine β-sulfonate < (+/-)-N-methyl-2-(3,4-dihydroxyphenyl)ethylammonium-2-sulfonate > (26405-77-6)

Conditions	Yield
With sodium sulfite	68.8%

Epinephrine (329-65-7) → 5,6-dihydroxy-1-methylindole (4821-00-5)

Conditions	Yield
With sodium hydrogencarbonate; tartaric acid; potassium hexacyanoferrate(III) In water for 0.0833333h;	57%

2-chloro-5-nitropyridine (4548-45-2) + Epinephrine (329-65-7) → 5-nitro-2--pyridine

Conditions	Yield
With triethylamine In dimethyl sulfoxide at 100℃; for 1h;	31%
phosphorimetric microdetermination;

formaldehyd (50-00-0) + Epinephrine (329-65-7) → 1,2,3,4-tetrahydro-4,6,7-trihydroxy-2-methylisoquinoline (72812-48-7, 82563-75-5)

Conditions	Yield
In methanol for 1h; Ambient temperature;	23.7%

Epinephrine (329-65-7) + 3-(3-(4-chloro-5-fluoropyrimidin-2-yl)-1-(2-fluorobenzyl)-1H-pyrazol-5-yl)isoxazole (1446358-48-0) → 4-(2-((5-fluoro-2-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl)pyrimidin-4-yl)(methyl)amino)-1-hydroxyethyl)benzene-1,2-diol

Conditions	Yield
With triethylamine In 1,4-dioxane; water at 90℃; for 2h;	14%

formaldehyd (50-00-0) + Epinephrine (329-65-7) → 1,2,3,4-tetrahydro-4,7,8-trihydroxy-2-methylisoquinoline (82334-24-5) + 1,2,3,4-tetrahydro-4,6,7-trihydroxy-2-methylisoquinoline (72812-48-7, 82563-75-5)

Conditions	Yield
With hydrogenchloride; ascorbic acid In water for 1h; Ambient temperature; in Tris-HCl buffer, pH 7.0;	A 8.1% B n/a
In water Product distribution; in acetate buffer, or phosphate buffer, or Tris buffer, or glycine buffer, effect of pH from pH 3 to 10.5; solvent also alcohol;

Epinephrine (329-65-7) → 7-bromo-3-hydroxy-1-methyl-indoline-5,6-dione (5257-04-5)

Conditions	Yield
With water; bromine; sodium acetate; acetic acid

Epinephrine (329-65-7) → 3,4-Dihydroxyphenylacetaldehyde (5707-55-1)

Conditions	Yield
With phosphoric acid

Epinephrine (329-65-7) → 5-methylaminomethyl-5H-dibenzo[a,d]cycloheptene-2,3,7,8-tetraol (481-90-3)

Conditions	Yield
With hydrogenchloride
With hydrogen bromide
With sulfuric acid

Epinephrine (329-65-7) → 4-(1-chloro-2-methylamino-ethyl)-pyrocatechol; hydrochloride (90415-84-2)

Conditions	Yield
With thionyl chloride

Epinephrine (329-65-7) → (+/-)-2-(acetyl-methyl-amino)-1-(3,4-diacetoxy-phenyl)-ethanol (27669-45-0)

Conditions	Yield
With acetyl chloride

Epinephrine (329-65-7) → 3-hydroxy-7-iodo-1-methyl-2,3-dihydro-indole-5,6-dione (5257-03-4)

Conditions	Yield
With hydrogenchloride; potassium iodate; water

Epinephrine (329-65-7) + chloroformic acid ethyl ester (541-41-3) → methyl-(3,4,α-trihydroxy-phenethyl)-carbamic acid ethyl ester

Conditions	Yield
With water

Epinephrine (329-65-7) + acetic anhydride (108-24-7) → N-(3,4-dihydroxy-trans-styryl)-N-methyl-acetamide (99855-33-1)

Conditions	Yield
With methanol

Epinephrine (329-65-7) + acetic anhydride (108-24-7) → 1-acetoxy-2-(acetyl-methyl-amino)-1-(3,4-diacetoxy-phenyl)-ethane (27675-64-5)

Conditions	Yield
With pyridine

Epinephrine (329-65-7) + acetic anhydride (108-24-7) → (+/-)-2-(acetyl-methyl-amino)-1-(3,4-diacetoxy-phenyl)-ethanol (27669-45-0)

Conditions	Yield
With sodium hydrogencarbonate

Epinephrine (329-65-7) + acetyl chloride (75-36-5) → 1,2-diacetoxy-4-(1-chloro-2-methylamino-ethyl)-benzene

Conditions	Yield
With hydrogenchloride; acetic acid

Epinephrine (329-65-7) + acetyl chloride (75-36-5) → (+/-)-2-(acetyl-methyl-amino)-1-(3,4-dihydroxy-phenyl)-ethanol (103565-58-8)

Conditions	Yield
With sodium hydroxide; chloroform

Epinephrine (329-65-7) + methyl iodide (74-88-4) → vanillin (121-33-5)

Conditions	Yield
With sodium hydroxide

2,2,3,3,3-pentafluoropropanoic anhydride (356-42-3) + Epinephrine (329-65-7) → 2,2,3,3,3-Pentafluoro-propionic acid 1-[3,4-bis-(2,2,3,3,3-pentafluoro-propionyloxy)-phenyl]-2-[methyl-(2,2,3,3,3-pentafluoro-propionyl)-amino]-ethyl ester (1995-97-7)

Conditions	Yield
at 60℃; for 0.25h;
With formic acid at 80℃; for 0.583333h;

Upstream product

• 99-45-6 adrenalone 
• 120-80-9 benzene-1,2-diol 
• 20677-73-0 N-methylaminoacetaldehyde diethyl acetal 
• 67-04-9 synephrine tartrate 
• 51-41-2 norepinephrine 
• 14031-35-7 S-Adenosyl-L-methionine 
• 115780-42-2 C₉H₁₂NO₃ 
• 104819-56-9 R,S-2,2'-dinitrobiphenyl-6,6'-dicarbonsaeure-di-N,N'-1-(3,4-dihydroxyphenyl)-1-oxo-2-methylamido-ethan 
• 62-13-5 1-(3,4-dihydroxyphenyl)-1-oxo-2-methylamino-ethan-hydrochlorid 
• 104819-58-1 R,S-2,2'-dinitrobiphenyl-6,6'-dicarbonsaeure-di-N,N'-1-(3,4-dihydroxyphenyl)-1-hydroxy-methylamido-ethan 
• 51-43-4 (-)-epinephrine 
• 36467-25-1 2-(benzyl-methyl-amino)-1-(3,4-dihydroxy-phenyl)-ethanone 
• 150-05-0 (S)-4-[1-hydroxy-2-(methylamino)ethyl]pyrocatechol 
• 99-40-1 2-chloro-3',4'-dihydroxyacetophenone 

Downstream Products

• 5707-55-1 3,4-Dihydroxyphenylacetaldehyde 
• 481-90-3 Adnamin 
• 90415-84-2 4-(1-chloro-2-methylamino-ethyl)-pyrocatechol; hydrochloride 
• 27669-45-0 (+/-)-2-(acetyl-methyl-amino)-1-(3,4-diacetoxy-phenyl)-ethanol 
• 1995-97-7 2,2,3,3,3-Pentafluoro-propionic acid 1-[3,4-bis-(2,2,3,3,3-pentafluoro-propionyloxy)-phenyl]-2-[methyl-(2,2,3,3,3-pentafluoro-propionyl)-amino]-ethyl ester 
• 87697-27-6 tert-butyl [2-(3,4-dihydroxyphenyl)-2-hydroxyethyl](methyl)carbamate 
• 672-73-1 adrenaline o-quinone 
• 50-53-3 2-chloro-N,N-dimethyl-10H-phenothiazine-10-propanamine 
• 4821-00-5 5,6-dihydroxy-1-methylindole 
• 26405-77-6 (+/-)-epinine β-sulfonate < (+/-)-N-methyl-2-(3,4-dihydroxyphenyl)ethylammonium-2-sulfonate > 
• 25696-27-9 6-Nitro-adrenalin 
• 62-32-8 epinine hydrochloride 
• 642-75-1 adrenolutine 
• 54-06-8 adrenochrome 

Relevant articles and documents

Three-Dimensional Proteome-Wide Scale Screening for the 5-Alpha Reductase Inhibitor Finasteride: Identification of a Novel Off-Target

Finasteride, a 5-alpha reductase (5α-R) inhibitor, is a widely used drug for treating androgen-dependent conditions. However, its use is associated with sexual, psychological, and physical complaints, suggesting that other mechanisms, in addition to 5α-R inhibition, may be involved. Here, a multidisciplinary approach has been used to identify potential finasteride off-target proteins. SPILLO-PBSS software suggests an additional inhibitory activity of finasteride on phenylethanolamine N-methyltransferase (PNMT), the limiting enzyme in formation of the stress hormone epinephrine. The interaction of finasteride with PNMT was supported by docking and molecular dynamics analysis and by in vitro assay, confirming the inhibitory nature of the binding. Finally, this inhibition was also confirmed in an in vivo rat model. Literature data indicate that PNMT activity perturbation may be correlated with sexual and psychological side effects. Therefore, results here obtained suggest that the binding of finasteride to PNMT might have a role in producing the side effects exerted by finasteride treatment.

PREPARATION METHOD FOR HIGH PURITY RACEMIC ADRENALINE

A preparation method for a racemic adrenaline as represented by formula II. The method may comprise the following steps: compound 1 is directly racemized in an acidic solution to produce compound 2, the acid solution comprising neither sodium bisulfite nor salicylic acid; and specifically comprises (a), in the acid solution of which the pH is 0.5-1.5, compound 1 is placed under the protection of nitrogen gas and, with the reaction temperature being controlled at 75-95° C., stirred and reacted for 1-3 hours; (b) the reaction solution is controlled at a temperature of 5-20° C., into which an activated carbon is added, under the protection of nitrogen gas, stirred for 20-40 minutes, and filtered, then a filtrate is collected; the filtrate is controlled at a temperature of 5-20° C., the pH thereof is adjusted using ammonia to 8.5-9.5, and is filtered when the pH is stabilized, and a filter cake is washed and dried to produce a high purity racemic adrenaline white powder. The weight yield of the product produced per the preparation method is greater than 90%, the chromatographic purity is greater than 96%, and the ee value approaches zero.

PROCESS FOR THE PREPARATION OF OPTICALLY ENRICHED ADRENALINE

A process for the production of (-)-adrenaline and (-)-adrenaline-L-tartrate is provided. The process provides for a new, efficient and commercially feasible process for the optical resolution of racemic adrenaline. In one aspect, a one pot process for the synthesis of (-)-adrenaline is provided. The process provides a simple and less expensive 5 process that can be used to prepare commercial scale batches of (-)-adrenaline and (-)-adrenaline-L-tartrate of API quality. The process avoids the use of expensive and unpredictable chiral catalysts.