| Identification | More | [Name]
Tetramethylpyrazine | [CAS]
1124-11-4 | [Synonyms]
2,3,5,6-TETRAMETHYL-1,4-PYRAZINE
2,3,5,6-TETRAMETHYLPYRAZINE
2,3,5,6-TETRAMETHYLPYRAZINES
FEMA 3237
FEMA NUMBER 3237
TETRAMETHYLPYRAZINE
TETRAPYRAZINE
BS Factor
Ligustrazine
Pyrazine,tetramethyl-
Tetramethylpyrazin
tetramethyl-pyrazin
2 3 5 6-TETRAMETHYLPYRAZINE 98+%
Ligustrazine（tetramethylprazine）
Ligustrazine（tetramethylpyrazine）
2,3,5,6-TETRAMETHYLPYRAZINE WITH GC
2,3,5,6-TETRAMETHYL PYRAZINE, NATURAL
2,3,5,6-TETRAMETHYLPYRAZINE, SYNTHETIC
2,3,5,6-Tetramethylpyrazine，Ligustrazine | [EINECS(EC#)]
214-391-2 | [Molecular Formula]
C8H12N2 | [MDL Number]
MFCD00006146 | [Molecular Weight]
136.19 | [MOL File]
1124-11-4.mol |
| Chemical Properties | Back Directory | [Appearance]
white crystals or powder | [Melting point ]
77-80 °C(lit.)
| [Boiling point ]
190 °C(lit.)
| [density ]
1.08
| [FEMA ]
3237 | [refractive index ]
1.5880 (estimate) | [Fp ]
128-130°C/200mm | [storage temp. ]
Sealed in dry,Room Temperature | [solubility ]
4g/l | [form ]
neat | [pka]
3.20±0.10(Predicted) | [color ]
White to Off-White | [Odor]
at 10.00 % in dipropylene glycol. nutty musty chocolate coffee cocoa brown lard burnt | [Stability:]
Stable. Incompatible with strong acids, strong oxidizing agents. | [Odor Type]
nutty | [Water Solubility ]
Soluble in water (4 g/L at 20°C). | [JECFA Number]
780 | [BRN ]
113100 | [InChIKey]
FINHMKGKINIASC-UHFFFAOYSA-N | [LogP]
1.56 | [CAS DataBase Reference]
1124-11-4(CAS DataBase Reference) | [NIST Chemistry Reference]
Pyrazine, tetramethyl-(1124-11-4) | [EPA Substance Registry System]
1124-11-4(EPA Substance) |
| Safety Data | Back Directory | [Hazard Codes ]
Xn,Xi | [Risk Statements ]
R22:Harmful if swallowed.
R37/38:Irritating to respiratory system and skin .
R41:Risk of serious damage to eyes.
R36/37/38:Irritating to eyes, respiratory system and skin . | [Safety Statements ]
S26:In case of contact with eyes, rinse immediately with plenty of water and seek medical advice .
S39:Wear eye/face protection .
S24/25:Avoid contact with skin and eyes .
S37/39:Wear suitable gloves and eye/face protection .
S36:Wear suitable protective clothing . | [WGK Germany ]
3
| [RTECS ]
UQ3905000
| [TSCA ]
Yes | [HS Code ]
29339990 | [Safety Profile]
Poison by intravenous and intraperitoneal routes. Moderately toxic by ingestion. When heated to decomposition it emits toxic fumes of NOx. |
| Questions And Answer | Back Directory | [Description]
Tetramethylpyrazine (TMP) is a kind of alkaloids identified in Ligusticum wallichii FRANCH. It has various kinds of medical applications. It has long been used in China for the treatment of cardiovascular problems. It also has antiinflammatory and analgesic effect. It can be used for the treatment of diabetic peripheral neuropathy. Through effectively penetrating across the blood-brain barrier, it can exert its neuroprotection function which is useful for the treatment of ischemic brain injury. Moreover, it can eliminate superoxide anion and decreases nitric oxide production in human polymorphonuclear leukocytes.
| [Chemical Characteristic]
White crystal or powder. With aroma of beef and heated lard and fermented soybean flavor. It smells chocolate flavor when diluted to 20mg/kg. Boiling point is 190℃. Melting point is between 84 and 86℃. Soluble in ethanol, most non-volatile oils and propylene glycol, slightly soluble in water.
Natural products exist in guava, roast beef, cocoa, coffee, shrimp and so on.
| [Uses]
- Permissible edible flavors, mainly used to prepare meat, cocoa, peanut, nut, coffee, chocolate flavor and so on;
- For medicine production;
- Used as flavoring agents, sweeteners for alcoholic beverages, flavor and enriching supplement for cigarettes.
| [Preparation]
- Butanedione monoxime generated by butanone and ethyl nitrite condensation is reduced and cyclized to produce methylpyrazine. The cyclization reaction product is subjected to steam distillation and the distillate is cooled,crystallized and filtered to generate crude tetramethylpyrazine which is refined with water recrystallization and activated carbon to decolor. Ethanol solution with 15% to 20% hydrogen chloride can be added into acetone to prepare hydrochloride salt.
- Condensed by 2,3-butanedione and 2,3-butanediamine.
| [References]
TH Tsai, CC Liang. International Journal of Pharmaceutics, 216. 1-2 (2001)
WU, Zhi-youg, et al. Chinese Journal of Experimental Traditional Medical Formulae 14 (2012): 085.
Ozaki, Yukihiro. Chemical and pharmaceutical bulletin 40.4 (1992): 954-956.
Kao, Tsung-Kuei, et al. Neurochemistry international 48.3 (2006): 166-176.
Zhang, Zhaohui, et al. Life sciences 72.22 (2003): 2465-2472.
|
| Hazard Information | Back Directory | [Chemical Properties]
2,3,5,6-Tetramethylpyrazine has musty, fermented, coffee odor | [Chemical Properties]
white crystals or powder | [Physical properties]
Appearance: colorless needle crystal. Solubility: soluble in hot water, petroleum
ether, chloroform, dilute hydrochloric acid, slightly soluble in ether, insoluble in
cold water. Melting point: 77–80? °C. Boiling point: 190? °C. Flash point: 128–
130? °C/200? mm. Ligustrazine has a particular odor, moisture absorption, and
sublimation. | [Occurrence]
Reported found in French fried potato, bell pepper, wheat bread, emmental cheese, Swiss cheese, Camembert cheese, Gruyere cheese, boiled and cooked beef, grilled and roasted beef, fried beef, cooked lamb and mutton, lamb and mutton liver, grilled and roasted uncured pork, beer, black tea, green tea. Also reported present in cocoa products, coffee, dairy products, oatmeal, galbanum oil, roasted peanuts, soybean, beans, mushroom, trassi, coriander seed, rice bran, trassi, sukiyaki, soy sauce, malt, licorice, dried bonito, wild rice, shrimp, crab, clam, scallop, filberts, rum, sake, wine, whiskey, burley tobacco and soy products. | [History]
Ligusticum walliichi has a long medicinal history in China and is used in the treatment of headache, promoting blood and Qi circulation, curing chills and alleviating
pain”. Clinically, it is mainly used for the treatment of cardiovascular and cerebrovascular diseases. Ligustrazine (2,3,5,6-tetramethylpyrazine) is the main active
ingredient of Ligusticum walliich. It was first isolated in 1962 .
In recent years, studies have found that ligustrazine can inhibit the activity of the
cerebral cortex and medullary respiratory center, excite vasomotors, induce the
expansion of peripheral blood vessels, promote the blood flow of the coronary artery
and lower limbs, and reduce blood pressure. Ligustrazine can also paralyze the
nerve center and has sedative and analgesic effects.
Studies have suggested that ligustrazine has a variety of new effects, including
improving leptomeningeal and peripheral microcirculation and increasing cerebral
blood flow, and its effect is better than that of papaverine. Ligustrazine can also
protect against experimental cerebral ischemia and alleviate brain edema and the
deposition of fibrin in microvessels. Ligustrazine is also used in the treatment of
pulmonary heart disease, heart failure, dilated heart disease, portal hypertension,
type II diabetes mellitus, tumor and coronary heart disease, and restenosis after
stent implantation . | [Definition]
ChEBI: A member of the class of pyrazines that is pyrazine in which all four hydrogens have been replaced by methyl groups. An alkaloid extracted from Chuanxiong (Ligusticum wallichii). | [Indications]
Ligustrazine is used for occlusive vascular diseases, cerebral thrombosis, vasculitis,
coronary heart disease, angina pectoris, and others | [Aroma threshold values]
Detection: 1 to 10 ppm. Aroma characteristics at 1.0%: slightly musty, nutty, cocoa-like with a vanilla undernote | [Taste threshold values]
Taste characteristics at 10 ppm: weak, nutty, musty cocoa and chocolate-like with dry coffee nuances. | [General Description]
2,3,5,6-Tetramethylpyrazine has been isolated from Ephedra sinica. It is useful in the treatment of several disorders such as asthma, heart failure, rhinitis and urinary incontinence. It is a flavor ingredient of tobacco. It forms cocrystal with 4-hydroxybenzoic acid which exhibits supramolecular synthon polymorphism. | [Pharmacology]
Traditional Chinese medicine has some advantages in comprehensive treatment
under multisite, multitarget conditions and overall regulation. Ligustrazine can
inhibit phosphodiesterase activity and inhibit platelet aggregation. It has the typical
characteristics of a calcium antagonist and can adjust the release of various vasoactive substances against the vasoconstrictive action of the sympathetic nerve, improve
microcirculation, reduce red blood cell aggregation, shorten the erythrocyte electrophoresis time, and thereby reduce blood viscosity .
Ligustrazine can inhibit the proliferation of vascular endothelial cells induced by
vascular endothelial growth factor, which may be one of the mechanisms by which
angiogenesis is inhibited. The mechanism by which ligustrazine inhibits the proliferation of vascular endothelial cells may be through calcium ion retardation, inhibition of cell adhesion molecules, or through the antagonistic or synergistic effects of
some growth factors involved in the proliferation and angiogenesis of vascular
endothelial cells
Studies have shown that ligustrazine plays a role in resistance to ischemiareperfusion injury and antiapoptotic effects via the phosphatidylinositol 3- kinase/
protein kinase B (PI3K/Akt) pathway. The phosphorylation of endothelial nitric oxide
synthase (eNOS) and generation of nitric oxide (NO) are important downstream effectors, which significantly enhance the myocardial protective effects of ligustrazine.
one of the mechanisms of resistance to fibrosis . | [Clinical Use]
The main clinical formulation of ligustrazine is ligustrazine hydrochloride injection.
Ligustrazine hydrochloride injection was used to prevent restenosis following coronary stent implantation and to treat acute coronary syndrome and ischemic stroke.
Ligustrazine hydrochloride injection is helpful in alleviating pulmonary hypertension in patients with pulmonary heart disease. The therapeutic effect of ligustrazine
hydrochloride injection on severe cholestatic liver cirrhosis caused by chronic heart
failure of rheumatic heart disease is remarkable. In addition, ligustrazine is widely
used in the treatment of vertigo syndrome, vertebrobasilar insufficiency, tension
headache, and so on. It has a good symptomatic-treatment effect .
Ligustrazine is also reported for the treatment of children with viral myocarditis,
chronic renal failure, hepatic fibrosis, portal hypertension, tumors, and diabetic
nephropathy. Ligustrazine can relieve symptoms rapidly, and its effect is stable and
lasting. It has good clinical promotion value . |
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