2,3,5,6-Tetramethylpyrazine

Base Information

• Chemical Name: 2,3,5,6-Tetramethylpyrazine
• CAS No.: 1124-11-4
• Deprecated CAS: 87396-75-6,93615-56-6,93615-56-6
• Molecular Formula: C8H12N2
• Molecular Weight: 136.197
• Hs Code.: 29339990
• European Community (EC) Number: 214-391-2
• NSC Number: 46451,36080
• UNII: V80F4IA5XG
• DSSTox Substance ID: DTXSID6047070
• Nikkaji Number: J39.647H
• Wikipedia: Tetramethylpyrazine
• Wikidata: Q11319317
• Metabolomics Workbench ID: 47401
• ChEMBL ID: CHEMBL303697
• Mol file: 1124-11-4.mol

Synonyms:chuanxiongzine;ligustrazine;Liqustrazine;tetramethyl pyrazine;tetramethylpyrazine;tetramethylpyrazine hydrochloride;TMPZ

Chemical Property of 2,3,5,6-Tetramethylpyrazine

Chemical Property:

• Appearance/Colour: white crystals or powder
• Vapor Pressure: 0.671mmHg at 25°C
• Melting Point: 82-86 °C
• Refractive Index: 1.503
• Boiling Point: 192.7 °C at 760 mmHg
• PKA: 3.20±0.10(Predicted)
• Flash Point: 71.6 °C
• PSA: 25.78000
• Density: 1.08 g/cm³
• LogP: 1.71020
• Storage Temp.: Store below +30°C.
• Solubility.: 4g/l
• Water Solubility.: Soluble in water (4 g/L at 20°C).
• XLogP3: 1.3
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 0
• Exact Mass: 136.100048391
• Heavy Atom Count: 10
• Complexity: 87.8

Purity/Quality:

99% ^*data from raw suppliers

Tetramethylpyrazine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn,Xi
• Hazard Codes: Xn,Xi
• Statements: 22-37/38-41-36/37/38
• Safety Statements: 26-39-24/25-37/39-36

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=C(N=C(C(=N1)C)C)C
• 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. Ligustrazine is an alkaloid derived from chuanxiong (Ligusticum chuanxiong Hort; L. wallichii). Ligusticum wallichii Franchat (or Ligusticum chuanxiong Hort; L. wallichii), a member of the Umbelliferaceae family, is a Chinese medicinal herb that is a common constituent in polypharmaceutical herbal drugs. It has been widely used in Asian countries to increase coronary blood flow and systemic circulation and to relieve stasis.Ligusticum walliichi has the effects of promoting Qi and nourishing blood. Ligusticum walliichi, angelica, and peony were used as medicinal herbs, and thecommonly used Yangxue Siwu decoction was proposed for clinical practice. The combination of gypsum and Ligusticum walliichi can clear lung heat and eliminate cough and asthma. It is a common drug for clearing away heat and toxic substances and purging fire. The compatibility of Ligusticum walliichi and Radix Linderae can regulate the blood and Qi and treat women’s headaches and colds and retrograde and other related pains.Ligusticum walliichi is warm, acrid, and bitter. It can regulate the blood and conduct Qi, which is commonly used in oral administration. Ligusticum walliichi is used to treat apoplexy, headache, cold pain, the upper reaches of the wind, tears clogging of nose by cold, and so on. At present, the study of Chuanxiong in China and abroad has occurred at the molecular level . 2,3,5,6-Tetramethylpyrazine is an alkaloid that has been found in L. wallichii and has diverse biological activities. It reduces kainate-induced increases in production of reactive oxygen species (ROS) and cytotoxicity in primary rat hippocampal neurons when used at a concentration of 5 μM. 2,3,5,6-Tetramethylpyrazine (0.1 mM) induces vasodilation in precontracted isolated and endothelium-denuded rat tail artery strips and reduces blood pressure in anesthetized rats. It decreases infarct volume, caspase-3 activation, and hypoxia-inducible factor-1α (HIF-1α) levels in a rat model of focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) when administered at a dose of 20 mg/kg.
• 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. etramethylpyrazine is an anti-inflammatory compound isolated from the fermented food natto. Tetramethylpyrazine demonstrated in vivo nootropic activity in rats. 2,3,5,6-Tetramethylpyrazine may be used as an analytical reference standard for the quantification of the analyte in Ephedrae herba and Ephedra sinica Stapf using different chromatography techniques. Usually used in research and treatment of multiple disorders.
• 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/200mm. Ligustrazine has a particular odor, moisture absorption, and sublimation.
• Indications: Ligustrazine is used for occlusive vascular diseases, cerebral thrombosis, vasculitis, coronary heart disease, angina pectoris, and others
• 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 .

Technology Process of 2,3,5,6-Tetramethylpyrazine

There total 65 articles about 2,3,5,6-Tetramethylpyrazine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 73.9%

4-Chloro-3-methylphenol (59-50-7) → 2,4-dichloro-3-methylphenol (17788-00-0) + 4,6-dichloro-3-methylphenol (1124-07-8)

Guidance literature:

With chloroamine; In water; pH=9.0; Further Variations:; Reagents; pH-values; Product distribution;

DOI:10.1021/es030644h

Reference yield: 59.6%

2-chloro-5-methylphenol (615-74-7) → 3-methyl-2,6-dichlorophenol (13481-70-4) + 4,6-dichloro-3-methylphenol (1124-07-8)

Guidance literature:

With chloroamine; In water; pH=9.0; Further Variations:; Reagents; pH-values; Product distribution;

DOI:10.1021/es030644h

Reference yield:

2-<2-Hydroxy-2-ethyl>-3,5,6-trimethylpyrazine (72725-76-9) → Tetramethylpyrazine (1124-11-4) + 4-dimethylamino-benzaldehyde (100-10-7)

Guidance literature:

In various solvent(s); at 171.5 ℃; Kinetics; in diglyme-d14; isotopic effect;

DOI:10.1021/jo01294a016

upstream raw materials:

pyridine

L-Aspartic acid

acetic anhydride

2-acetamido-3-butanone

Downstream raw materials:

2,3,5,6-tetramethylpyrazine mono N-oxide

2,3,5,6-tetramethylpyrazine-N,N'-dioxide

pyrazine-2,3,5,6-tetracarboxylic acid

2-(3-pentenyl)-3,5,6-trimethylpyrazine

Refernces

• 1、 Fu, Hui-Yin,Ho, Chi-Tang. "Mechanistic Studies of 2-(1-Hydroxyethyl)-2,4,5-trimethyl-3-oxazoline Formation under Low Temperature in 3-Hydroxy-2-butanone/Ammonium Acetate Model Systems". . p. 1878 - 1882. Retrieved 1997.
• 2、 Huang. "Combined effects of a buffer and solvent on tetramethylpyrazine formation in a 3-hydroxy-2-butanone/ammonium hydroxide system". . p. 1013 - 1015. Retrieved 1997.
• 3、 Klein,Berkowitz,Hetman. "-". . p. 126. Retrieved 1961.
• 4、 Xu, Jin,Green, Anthony P.,Turner, Nicholas J.. "Chemo-Enzymatic Synthesis of Pyrazines and Pyrroles". . p. 16760 - 16763. Retrieved 2018.
• 5、 Zou, Yu,Zhao, Di,Yan, Chang,Ji, Yanpeng,Liu, Jin,Xu, Jinyi,Lai, Yisheng,Tian, Jide,Zhang, Yihua,Huang, Zhangjian. "Novel Ligustrazine-Based Analogs of Piperlongumine Potently Suppress Proliferation and Metastasis of Colorectal Cancer Cells in Vitro and in Vivo". . p. 1821 - 1832. Retrieved 2018.
• 6、 -. "A preparation method of Rhizoma Chuanxiong hydrochlorothizide". Paragraph 0044-0049; 0053-0058; 0062-0067; 0071-0076. . Retrieved 2017/07/04.