486-84-0

Basic information

• Product Name: HARMANE
• Synonyms: METHYLCARBOLINE;METHYL-4-CARBOLINE;TIMTEC-BB SBB003735;1-Methyl-9H-beta-carboline;1-Methyl-9H-pyrid(3,4-b)indole;1-Methyl-9H-β-carboline;1-Methyl-beta-carboline;1-Methylnorharman
• CAS NO: 486-84-0
• Molecular Formula: C₁₂H₁₀N₂
• Molecular Weight: 182.22
• EINECS: 207-642-2
• Product Categories: Heterocyclic Compounds;Indole Derivatives;Mutagenesis Research Chemicals
• Mol File: 486-84-0.mol
• Article Data: 61

Chemical Properties

• Melting Point: 235-238 °C(lit.)
• Boiling Point: 305.62°C (rough estimate)
• Flash Point: 176.2°C
• Appearance: /
• Density: 1.1485 (rough estimate)
• Vapor Pressure: 7.61E-06mmHg at 25°C
• Refractive Index: 1.6266 (estimate)
• Storage Temp.: Store at RT
• Solubility: methanol: soluble50mg/ml
• PKA: 7.37, 14.6(at 25℃)
• Water Solubility: 1523g/L(20 oC)
• Merck: 13,4630
• BRN: 143898
• CAS DataBase Reference: HARMANE(CAS DataBase Reference)
• NIST Chemistry Reference: HARMANE(486-84-0)
• EPA Substance Registry System: HARMANE(486-84-0)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 20/21-36/37/38
• Safety Statements: 22-24/25-36-26
• RIDADR: 1544
• WGK Germany: 3
• RTECS: UV0280000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 486-84-0(Hazardous Substances Data)

Usage

Description

Harmane, also known as β-carboline alkaloid, is a potent tremor-producing neurotoxin and a major representative of heterocyclic aromatic amines. It is formed in meat from precursors such as creatine, creatinine, amino acids, and sugars during high-temperature heating. Harmane has been isolated from various plant sources and is a specific, reversible inhibitor of monoamine oxidase A. It is an off-white solid and has been linked to elevated blood concentration in essential tremor and late-life neurological diseases.

Uses

Used in Trace Level Determination:
Harmane is used as a trace level determinant by planar chromatography coupled with tandem mass spectrometry for its analysis.
Used in DNA Interaction Studies:
Harmane is utilized in studying the interactions of norharman and harman with DNA, which can provide insights into its biological effects and potential applications.
Used in Analysis of Cyclodextrins:
Harmane serves as a matrix for the analysis of cyclodextrins, which are important in various chemical and pharmaceutical applications.
Used in Sulfated Oligosaccharides Analysis:
In combination with DHB as a co-matrix, harmane is used for the analysis of sulfated oligosaccharides, which have potential applications in the development of new drugs and therapies.
Used in Pharmaceutical Industry:
Harmane, due to its inhibitory effects on monoamine oxidase A, can be explored for its potential use in the development of pharmaceuticals targeting neurological disorders and other conditions related to monoamine oxidase A activity.
Used in Toxicology and Environmental Studies:
As a potent neurotoxin and a member of heterocyclic aromatic amines, harmane can be studied in toxicology and environmental research to understand its effects on human health and the environment, as well as to develop methods for its detection and mitigation.

Synthesis Reference(s)

The Journal of Organic Chemistry, 37, p. 1429, 1972 DOI: 10.1021/jo00974a030Tetrahedron, 49, p. 3325, 1993 DOI: 10.1016/S0040-4020(01)90161-9

Biological Activity

Proposed as the endogenous ligand for imidazoline binding sites. Binds to I 1 -sites in rat kidney with an IC 50 of 31 nM, and I 2 -sites with a K i of 49 nM. In vivo, produces a dose-dependent hypotension that is reversed by efaroxan (2-(2-Ethyl-2,3-dihydro-2-benzofuranyl)-4,5-dihydro-1H-imidazole hydrochloride ). Also a potent inhibitor of monoamine oxidases A and B (I 50 values are 0.5 and 5 μ M respectively).

Biochem/physiol Actions

I1 imidazoline binding site agonist.

InChI:InChI=1/C12H10N2/c1-8-12-10(6-7-13-8)9-4-2-3-5-11(9)14-12/h2-7,14H,1H3

Synthetic route

tryptamine (61-54-1) + acetaldehyde (75-07-0) → harmane (486-84-0)

Conditions	Yield
With acid	88.7%
Stage #1: tryptamine; acetaldehyde With piperidine; methanesulfonic acid at 100℃; for 4h; Sealed tube; Stage #2: With triethylamine In water Stage #3: With palladium on activated charcoal at 180℃; for 5h; Reagent/catalyst; Temperature; Inert atmosphere;	80.2%
Yield given;

eleagnine (2506-10-7) → harmane (486-84-0)

Conditions	Yield
With C21H21ClIrNO2 In tetrahydrofuran; 2,2,2-trifluoroethanol for 20h; Inert atmosphere;	93%
With [bis(acetoxy)iodo]benzene In N,N-dimethyl-formamide at 20℃; for 1h;	84%
With 1,8-diazabicyclo[5.4.0]undec-7-ene; copper(ll) bromide In dimethyl sulfoxide at 25℃; for 24h; Green chemistry;	81%

1-methyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylic acid (5470-37-1, 40678-46-4, 42438-72-2, 96149-76-7, 98718-62-8, 114497-71-1, 143396-05-8) → harmane (486-84-0)

Conditions	Yield
With tetrasodium cobalt(II) 4,4',4'',4'''-tetrasulphophthalocyanine In water; ethyl acetate at 20℃; for 24h; Irradiation; Green chemistry;	87%
With ammonium persulfate; silver nitrate In water; acetonitrile at 80℃;	56%
Multi-step reaction with 2 steps 1: acetic acid; water / 0.33 h / 100 °C 2: sodium hydroxide; sodium hydrogensulfite View Scheme
With manganese(IV) oxide; sulfuric acid

(3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (191279-37-5) → harmane (486-84-0)

Conditions	Yield
With copper dichloride In N,N-dimethyl-formamide at 130℃; for 1h;	84%
With N-chloro-succinimide; triethylamine In N,N-dimethyl-formamide at 20℃; for 0.5h;	82%
With iron(III) chloride In N,N-dimethyl-formamide at 130℃; for 1h; Catalytic behavior; Green chemistry;	82%

1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole trifluoroacetate → harmane (486-84-0)

Conditions	Yield
With 2 mol-% Pd/C; lithium carbonate In ethanol at 150℃; for 0.166667h; Sealed tube; Microwave irradiation;	93%
With lithium carbonate; silver carbonate In N,N-dimethyl-formamide for 1h; Reflux;	34%

1-methyl-4,9-dihydro-3H-β-carboline (525-41-7) → harmane (486-84-0)

Conditions	Yield
With potassium permanganate In acetone at 20℃;	92%
With C21H21ClIrNO2 In tetrahydrofuran; 2,2,2-trifluoroethanol for 20h; Inert atmosphere;	81%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In dimethyl sulfoxide at 125℃; for 10h;	76%

C14H15NO2 → harmane (486-84-0)

Conditions	Yield
With ammonium acetate In acetic acid; N,N-dimethyl-formamide at 120℃; for 7h;	90 mg

C13H16N2O2 → harmane (486-84-0)

Conditions	Yield
Stage #1: C13H16N2O2 With manganese(IV) oxide In water at 100℃; for 0.0833333h; Stage #2: With sulfuric acid In water at 100℃; for 1h;

N-Acetyltryptamine (1016-47-3) → harmane (486-84-0)

Conditions	Yield
Stage #1: N-Acetyltryptamine With trifluoromethylsulfonic anhydride; Triphenylphosphine oxide In chlorobenzene at 20 - 130℃; Stage #2: With manganese(IV) oxide In chlorobenzene at 130℃; for 4h;	82%
Stage #1: N-Acetyltryptamine With trifluoromethylsulfonic anhydride; Triphenylphosphine oxide In chlorobenzene Stage #2: With manganese(IV) oxide In chlorobenzene	80%
With trichlorophosphate In toluene; acetonitrile for 3h; Reflux;

1-methyl-2-tosyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (5159-20-6) → harmane (486-84-0)

Conditions	Yield
With oxygen; sodium hydroxide In water; dimethyl sulfoxide at 125℃; for 5h;	82%
Stage #1: 1-methyl-2-tosyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole In tetrahydrofuran at -78℃; for 2h; Stage #2: With oxygen In tetrahydrofuran at 20℃;	74%

1-methyl-6,7,8,9-tetrahydro-5H-pyrido[3,4-b]indole (31965-09-0) → harmane (486-84-0)

Conditions	Yield
With palladium on activated carbon In diphenylether at 210℃; for 0.66h; Inert atmosphere;	91%
With palladium on activated charcoal; diphenylether; biphenyl

(+/-)-Calligonine hydrochloride (6678-82-6) → harmane (486-84-0)

Conditions	Yield
With 5 mol% Pd/C; lithium carbonate In ethanol at 150℃; for 0.1h; Sealed tube; Microwave irradiation;	92%

6-bromo-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole hydrochloride → harmane (486-84-0)

Conditions	Yield
With 5 mol% Pd/C; lithium carbonate In ethanol at 150℃; for 0.75h; Sealed tube; Microwave irradiation;	75%

3-azido-2-methyl-4-phenylpyridine → harmane (486-84-0)

Conditions	Yield
In 5,5-dimethyl-1,3-cyclohexadiene for 10h; Reflux;	45%

tert.-butylhydroperoxide (75-91-2) + betacarboline (244-63-3) → harmane (486-84-0)

Conditions	Yield
With iron(II) sulfate In sulfuric acid; water; acetic acid at 0℃; for 2h;	75%

6-chloro-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole hydrochloride → harmane (486-84-0)

Conditions	Yield
With 5 mol% Pd/C; lithium carbonate In ethanol at 150℃; for 0.1h; Sealed tube; Microwave irradiation;	60%

N,N-dimethyl acetamide (127-19-5) + 1-(phenylsulfonyl)-3-vinyl-1H-indole (82980-12-9) → harmane (486-84-0)

Conditions	Yield
Stage #1: 3-ethenyl-1-phenylsulfonyl-1H-indole With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: N,N-dimethyl acetamide In tetrahydrofuran at -78 - -10℃; Stage #3: With hydroxylamine hydrochloride; sodium acetate In 1,2-dichloro-benzene for 8h; Heating;	46%

N,N-dimethyl acetamide (127-19-5) + (E)-1-(Phenylsulfonyl)-3-(β-methoxyvinyl)indole (110128-40-0) → harmane (486-84-0)

Conditions	Yield
Stage #1: (E)-1-(Phenylsulfonyl)-3-(β-methoxyvinyl)indole With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: N,N-dimethyl acetamide In tetrahydrofuran at -78 - -10℃; Stage #3: With hydroxylamine hydrochloride; sodium acetate In 1,2-dichloro-benzene for 8h; Heating;	53%

N,N-dimethyl acetamide (127-19-5) + (E)-3-(2-nitrovinyl)-1-(phenylsulfonyl)-1H-indole (211738-25-9) → harmane (486-84-0)

Conditions	Yield
Stage #1: (E)-3-(2-nitrovinyl)-1-(phenylsulfonyl)-1H-indole With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1h; Stage #2: N,N-dimethyl acetamide In tetrahydrofuran at -78 - -10℃; Stage #3: With hydroxylamine hydrochloride; sodium acetate In 1,2-dichloro-benzene for 8h; Heating;	45%

L-Tryptophan (73-22-3) → harmane (486-84-0)

Conditions	Yield
With sulfuric acid; acetaldehyde Oxydieren der Reaktionsloesung mit Kaliumdichromat;
With acetic anhydride; zinc(II) chloride Oxydieren des entstandenen Oels mit Chromschwefelsaeure;
Multi-step reaction with 2 steps 1: acetic acid / 3 h / Reflux 2: acetic acid; potassium dichromate / water / 0.33 h / 100 °C View Scheme

2,2-dimethyl-N-(2-(3-fluoro-2-methyl-4-pyridyl)phenyl)propanamide → harmane (486-84-0)

Conditions	Yield
With pyridine hydrochloride at 210℃; for 0.25h;	84%

tryptamine (61-54-1) → harmane (486-84-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sulfuric acid / water / 0.5 h / 20 °C 1.2: 7 h / Reflux 2.1: maleic acid; palladium on activated charcoal / water / 8 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: sulfuric acid / water / 7 h / Reflux 2: maleic acid; palladium on activated charcoal / water / 8 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: 1,2-dichloro-ethane / 0.05 h / 110 °C / Sealed tube; Microwave irradiation 2: lithium carbonate; 2 mol-% Pd/C / ethanol / 0.17 h / 150 °C / Sealed tube; Microwave irradiation View Scheme

harman-3-carboxylic acid (22329-38-0) → harmane (486-84-0)

Conditions	Yield
With copper In quinoline at 240℃; for 1h;
With sodium hydrogensulfite; sodium hydroxide

C15H15N3O → harmane (486-84-0) + C14H16N2O

Conditions	Yield
With sodium cyanoborohydride In tetrahydrofuran; methanol at 65℃; Inert atmosphere;	A n/a B 20%

trimethylaluminum (75-24-1) + 1-Chlor-9H-pyrido<3,4-b>indol (102337-43-9) → harmane (486-84-0)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane; hexane for 3h; Heating;	66%

methyl 5-acetyl-4-[(β-carbolin-1-yl)methyl]-1,4-dihydropyridine-3-carboxylate (668987-16-4) → harmane (486-84-0) + 5-(1'-hydroxyethyl) nicotinic acid methyl ester (38940-64-6) + methyl 4-[(β-carbolin-1-yl)methyl]-5-(1-hydroxyethyl)-1,4-dihydropyridine-3-carboxylate (52811-49-1)

Conditions	Yield
With sodium tetrahydroborate In methanol at 20℃; for 0.25h;

1-(phenylsulfonyl)indole-3-carbaldehyde (80360-20-9) → harmane (486-84-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 63 percent / AcONa; AcOH 2.1: LDA / tetrahydrofuran / 1 h / -78 °C 2.2: tetrahydrofuran / -78 - -10 °C 2.3: 45 percent / NH2OH*HCl; AcONa / 1,2-dichloro-benzene / 8 h / Heating View Scheme
Multi-step reaction with 2 steps 1.1: 65 percent / t-BuOK / tetrahydrofuran 2.1: LDA / tetrahydrofuran / 1 h / -78 °C 2.2: tetrahydrofuran / -78 - -10 °C 2.3: 46 percent / NH2OH*HCl; AcONa / 1,2-dichloro-benzene / 8 h / Heating View Scheme
Multi-step reaction with 2 steps 1.1: 77 percent / t-BuOK / tetrahydrofuran 2.1: LDA / tetrahydrofuran / 1 h / -78 °C 2.2: tetrahydrofuran / -78 - -10 °C 2.3: 53 percent / NH2OH*HCl; AcONa / 1,2-dichloro-benzene / 8 h / Heating View Scheme

acetaldehyde (75-07-0) + L-Tryptophan (73-22-3) → harmane (486-84-0)

Conditions	Yield
With hydrogenchloride; iron(III) chloride In N,N-dimethyl-formamide at 130℃; for 1h; Catalytic behavior; Pictet-Spengler Synthesis; Green chemistry;	78%
Stage #1: acetaldehyde; L-Tryptophan Acidic conditions; Stage #2: With potassium dichromate
With potassium dichromate

Harman-2-oxide (2506-09-4) → harmane (486-84-0)

Conditions	Yield
With acetic acid; zinc for 2h; Reduction;	87%

Upstream product

• 2506-10-7 eleagnine 
• 31965-09-0 1-methyl-6,7,8,9-tetrahydro-5H-pyrido[3,4-b]indole 
• 487-03-6 harmol 
• 54-12-6 Trp 
• 56-41-7 L-alanin 
• 73-22-3 L-Tryptophan 
• 105-57-7 diethyl acetal 
• 144-62-7 oxalic acid 
• 71-36-3 butan-1-ol 
• 108-24-7 acetic anhydride 
• 5435-44-9 (E)-3-Ureido-but-2-enoic acid ethyl ester 
• 522-87-2 yohimbinic acid 
• 483-05-6 17α-hydroxy-20α-yohimban-16α-carboxylic acid 
• 146-48-5 Yohimbine 

Downstream Products

• 63885-36-9 1-methyl-2-(3-trimethylammonio-propyl)-9H-β-carbolinium; dibromide 
• 63885-34-7 1-methyl-2-(10-trimethylammonio-decyl)-9H-β-carbolinium; dibromide 
• 20127-62-2 (E)-1-(2-phenylvinyl)-9H-pyrido[3,4-b]indole 
• 2506-10-7 eleagnine 
• 102207-02-3 8-nitro-1-methyl-9H-pyrido[3,4-b]indole 
• 38314-91-9 6-nitro-1-methyl-9H-pyrido[3,4-b]indole 
• 96405-71-9 3-Benzyl-3H-indolo[3,2,1-de][1,5]naphthyridine-5,6-dione 
• 139332-26-6 2-Amino-1-methyl-9H-pyrido<3,4-b>indolium mesitylenesulfonate 
• 87604-37-3 2-(9H-β-Carbolin-1-yl)-1-phenyl-ethanol 
• 91487-11-5 1-<2-(3,4-dimethoxyphenyl)vinyl>-β-carboline 
• 68267-34-5 4-(9H-β-carbolin-1-yl)-1,3-diphenyl-butan-1-one 
• 6801-22-5 melinonine F 
• 244-63-3 betacarboline 
• 18813-71-3 6-bromo-1-methyl-9H-pyrido[3,4-b]indole 

Relevant articles and documents

Indole alkaloids from two species of Ophiorrhiza

Extraction of the aerial parts of Ophiorrhiza rosacea Ridley (Rubiaceae) has yielded harman-2-oxide (1). Extraction of the aerial parts of O. kunstleri King yielded the alkaloids palicoside (3) and 3,14-didehydro-19-methylnormalindine (8). The structures

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Visible light mediated selective oxidation of alcohols and oxidative dehydrogenation of N-heterocycles using scalable and reusable La-doped NiWO4nanoparticles

Visible light-mediated selective and efficient oxidation of various primary/secondary benzyl alcohols to aldehydes/ketones and oxidative dehydrogenation (ODH) of partially saturated heterocycles using a scalable and reusable heterogeneous photoredox catalyst in aqueous medium are described. A systematic study led to a selective synthesis of aldehydes under an argon atmosphere while the ODH of partially saturated heterocycles under an oxygen atmosphere resulted in very good to excellent yields. The methodology is atom economical and exhibits excellent tolerance towards various functional groups, and broad substrate scope. Furthermore, a one-pot procedure was developed for the sequential oxidation of benzyl alcohols and heteroaryl carbinols followed by the Pictet-Spengler cyclization and then aromatization to obtain the β-carbolines in high isolated yields. This methodology was found to be suitable for scale up and reusability. To the best of our knowledge, this is the first report on the oxidation of structurally diverse aryl carbinols and ODH of partially saturated N-heterocycles using a recyclable and heterogeneous photoredox catalyst under environmentally friendly conditions.

Synthesis method of heterocyclic amine risky substance 1-methyl-9H-pyridine [2,3-b] indole

The invention provides a synthesis method of a Maillard reaction heterocyclic amine risk substance 1-methyl-9H-pyridine [2,3-b] indole. The synthesis method comprises the following steps: taking tryptamine as a raw material and organic acid as an additive, condensing with acetaldehyde in an amine alkaline organic solvent, and carrying out dehydrogenation aromatization to obtain the 1-methyl-9H-pyridine [2,3-b] indole. The preparation method has the advantages that the preparation process is simple and efficient, the post-treatment is simple, and a complicated column separation process is not needed. The yield of the obtained heterocyclic amine risky substances is 80% or above, and the production requirements of scientific research work on the heterocyclic amine compounds can be well met. The structural formula of the 1-methyl-9H-pyridine [2,3-b] indole is as shown in a formula (I) which is described in the specification;