4-methyl-2-(methylsulfanyl) pyrimidine is an organic compound with the molecular formula C6H8N2S and CAS 14001-63-9. It typically appears as a yellow or dark brown liquid. Low solubility in water, but soluble in organic solvents such as ethanol, ether, and dimethyl sulfoxide. It is a non-volatile compound with low vapor pressure, stable at room temperature, and not easily affected by oxidants or light in the air. It is an important intermediate for many drug molecules, such as angiotensin II receptor antagonists, anti-tumor drugs, antiviral drugs, etc.
Can be used as a reagent or catalyst for some chemical reactions, such as Suzuki reaction, Heck reaction, Sonogashira reaction, etc. It can be used for research and application in the fields of electrochemistry such as electrolytes, electrochemical catalysis, and electrode surface modification. It can also be used in other fields such as materials science, polymer chemistry, catalyst design, etc. Due to its important intermediates and wide range of applications, it is a very useful compound.
|
Chemical Formula |
C6H8N2S |
|
Exact Mass |
140 |
|
Molecular Weight |
140 |
|
m/z |
140 (100.0%), 141 (6.5%), 142 (4.5%) |
|
Elemental Analysis |
C, 51.40; H, 5.75; N, 19.98; S, 22.87 |
|
|
|
4-Methyl-2- (methylsulfonyl) pyrimidine is an important organic compound with potential applications in the fields of medicine, pesticides, and materials science.
CN201710955247.2 discloses a concave convex rod soil based adsorbent material for solidifying chromium in river sediment. Material A was prepared by modifying a mixture of 2-fluoropyrimidin-3-boronic acid pinal ester, phenylpropargyl sulfide, N-methyl-N-phenylthiourea, and 4-methylbenzenesulfonic acid octadecyl ester after cleaning with attapulgite soil; Substance A was modified with a mixture of NbCl4, AlCl3, Co (NO3) 2, and Mg (NO3) 2 to prepare substance B; Substance B was modified with a mixture of 1-benzoyl-3-phenylthiourea, 3-carbaldehyde benzothiophene, and 4-methyl-2-methylthiopyrimidine to prepare substance C.
The substance C modified with a mixture of (3-bromopropoxy) tert butyldimethylsilane, methylene disulfonate, and thiochloroformat-S-isopropylamine is the attapulgite based adsorbent material used to solidify chromium in river sediment.4-methyl-2-methylthiopyrimidine can be used to prepare C-terminal Src kinase (CSK) inhibitors with the following structure.The key regulatory factor of TCR signaling cascade reaction is CSK, which is a tyrosine protein kinase, also known as C-terminal Src kinase. CSK has a structural domain architecture related to Src, including SH3 domain, SH2 domain, and catalytic domain. CSK phosphorylation is located at the C-terminal tail of the Src family kinases (SFKs) tyrosine residues.
CSK is an LCK inhibitory kinase. In lymphocytes, CSK inhibits T cell activation by phosphorylating LCK at tyrosine 505. To inhibit LCK, CSK is recruited to the plasma membrane by binding to transmembrane proteins or adaptor proteins located near the membrane. CSK inhibits signal transduction through various surface receptors, including TCR.In the selection process of developing T cells in the thymus, LCK, a member of the SRC kinase family, plays a crucial role in T cell receptor signaling and is also important for T cell receptor signaling in naive and effector T cells. Mice lacking LCK exhibit complete loss of T cell development. LCK is constitutively associated with the cytoplasmic domains of CD4 and CD8.
And is considered a kinase primarily responsive to phosphorylation of T cell receptor ITAM (an activation motif based on immune receptor tyrosine). There is evidence to suggest that the binding of helper receptors to peptide MHC complexes that bind to T cell receptors enhances the recruitment of LCK to participating T cell receptors, leading to more effective phosphorylation of T cell receptor ITAM.
Only activated LCK can phosphorylate ITAM in the relevant T cell receptor signaling chain. The complete activation of LCK catalytic activity requires autophosphorylation on the activation ring in the kinase domain. Phosphorylation of carboxyl tyrosine by C-terminal Src kinase (CSK) restores LCK to its inactive state.
In summary, CSK and LCK play important roles in regulating immune responses. Co clustering TCR and LCK or separating CSK from the membrane can trigger TCR phosphorylation. Therefore, selective CSK inhibitors will enhance TCR phosphorylation and improve the efficacy of weak tumor antigens, and can overcome the inhibitory activity of checkpoint blockade.
4-methyl-2-methylthiopyrimidine is an organic intermediate that can be prepared by reacting 4-methylpyrimidin-2-thiol hydrochloride with iodomethane. There are literature reports that it can be used to prepare concave convex rod soil based adsorbent materials and C-terminal Src kinase (CSK) inhibitors for solidifying chromium in river sediment.
4-methyl-2-(methylsulfanyl) pyrimidine can be synthesized by the following synthetic route:
- 2-Methyl-4-cyanopyridine reacts with methylmercaptan to generate 2-methyl-4-methylthiopyridine.
- Carrying out Knoevenagel condensation reaction of 2-methyl-4-methylthiopyridine and methylacetone under alkaline conditions to generate 4-methyl-2-(methylthio)pyridine-5-carboxylic acid.
- Reducing 4-methyl-2-(methylthio)pyridine-5-carboxylic acid to 4-methyl-2-(methylthio)pyridine through hydrogenation reduction reaction of hydrogen and Pd/C catalyst.
- Finally, it is produced by reacting 4-methyl-2-(methylthio)pyridine and potassium cyanide in methanol.
Step 1:
2-methyl-4-cyanopyridine + methylmercaptan → 2-methyl-4-methylthiopyridine
Step 2:
2-methyl-4-methylthiopyridine + methylacetone + base → 4-methyl-2-(methylthio)pyridine-5-carboxylic acid
Step 3:
4-methyl-2-(methylthio)pyridine-5-carboxylic acid + H2/Pd-C → 4-methyl-2-(methylthio)pyridine
Step 4:
4-Methyl-2-(methylthio)pyridine + KCN + CH3OH → C6H8N2S
The following is a method for synthesizing 4-methyl-2-(methylsulfanyl) pyrimidine commonly used in laboratories:
1. Synthesis of 4-Methyl-2-(trifluoromethyl)pyrimidine: react 2,4-dichloro-6-picoline with trifluoroacetylformamide to obtain 4-Methyl-2-(trifluoromethyl)pyrimidine.
2. Synthesis of product: react 4-Methyl-2-(trifluoromethyl)pyrimidine with thiol, extract with acetone and water mixture to obtain product.
This method requires the use of some basic techniques and equipment of organic synthetic chemistry, such as desiccant, inert atmosphere, solvent distillation, and column chromatography. At the same time, it is necessary to pay attention to safe operation, especially the use and handling of organic chlorine compounds should pay attention to protective measures.
Key Chemical Reactivity Features
Alkaline hydrolysis:
Under alkaline conditions, it will be hydrolyzed into 4-METHYL-2-PYRIMIDINOL and methyl mercaptan.
Reactivity:
It can undergo a series of reactions, such as oxidation, hydrogenation, alkylation, arylation and dehydration.
Nucleophilic addition:
Due to its α-methylthio and 2,4-diposition electron cloud enrichment characteristics, it can undergo nucleophilic addition reactions, such as Michael addition And imino alcoholization reaction, etc.
Catalytic properties:
It can also be used as a catalyst for some reactions, such as ethanol dehydration, aldehyde oxidation and aromatization, etc.
In summary, it has some important reactivity properties, and has a wide range of applications in the fields of pharmaceuticals, pesticides, chemistry and electrochemistry.
Safety Operating Procedures
Personal Protection: During operation, wear laboratory coats, chemical protective gloves, and goggles to prevent skin and eye contact.
Ventilation Requirements: All operations should be conducted in a fume hood or local exhaust system to ensure air circulation.
Emergency Handling: In case of leakage, cover with a damp cloth and clean it up. Do not sweep with brooms or compressed air. Clean contaminated clothing separately and prohibit mixing with other clothing.
Waste Management: Wastes should be classified and collected, handed over to institutions with hazardous waste handling qualifications for processing, and fill out the "Hazardous Waste Transfer Manifest".
synthetic formulation
In an argon atmosphere, 4-methylpyrimidin-2-thiol hydrochloride (13.78g, 84.7mmol) was added to a solution of NaOH (7.46g, 186.4mmol) in water (120mL), followed by dropwise addition of iodomethane (13.23g, 93.2mmol). Stir at room temperature for 2 hours, then extract with CH2Cl2 (2x).
The organic phase was dried over Na2SO4 and concentrated to dryness. The crude product obtained was purified by silica gel chromatography using a mixture of hexane EtOAc with increased polarity as the eluent, resulting in 10.26g of the desired compound (yield: 86%).
Add 4-methylpyrimidin-2-thiol hydrochloride (13.78g, 84.7mmol) to a solution of NaOH (7.46g, 186.4mmol) in water (120ml), followed by dropwise addition of iodomethane (13.23g, 93.2mmol) under argon atmosphere.
Stir at room temperature for 2 hours. Extract (x2) with CH2Cl2. Dry the organic phase over Na2SO4 and concentrate to dryness. The crude product obtained was purified by silica gel chromatography using an increasing polarity hexane EtOAc mixture as the eluent, yielding 10.26g of the desired compound (yield: 86%).
Stability
Physical Stability
4-methyl-2-(methylsulfanyl) pyrimidine is a dark brown liquid at room temperature and has specific physical parameters: the boiling point is 78-80°C (under 1 mmHg conditions), the density is 1.007 g/mL (at 25°C), the refractive index is n20/D 1.572, and the flash point is 220°F (approximately 104°C). These data indicate that the physical properties of this substance are stable under normal storage conditions (such as sealing and avoiding light), and it is not prone to decomposition or phase change.
Chemical Stability
Under the recommended storage conditions (2-8°C), the chemical properties of 4-methyl-2-methoxy pyrimidine are stable and do not react with components in the air. However, it should be noted that it may be sensitive to strong oxidants, strong acids, or strong bases, and contact with such substances may lead to decomposition or the generation of harmful products. Therefore, when storing, it should be kept away from oxidizing or corrosive chemicals and ensure good container sealing.
Storage Conditions
To maintain stability, this substance should be stored refrigerated (2-8°C) and protected from direct sunlight. During long-term storage, it is recommended to regularly check the container seal to prevent moisture absorption or contamination. If transportation is required, use shock-resistant and leak-proof packaging and mark with the warning sign "Flammable Liquid".
Safety
Health Hazards
4-Methyl-2-methoxy pyrimidine poses potential health hazards, specifically:
Eye Damage: Direct contact may cause severe eye damage (H318), and immediate rinsing with plenty of water and seeking medical attention is required.Skin Irritation: Contact may cause skin irritation (H315), and chemical protective gloves (such as nitrile rubber material) should be worn during operation.Respiratory Irritation: Inhalation of dust or vapor may cause respiratory irritation (H335), and operations should be conducted in a fume hood or local exhaust system.
Environmental Hazards
The environmental impact of this substance has not been clearly classified, but based on its chemical properties, it should be avoided from being directly discharged into water bodies or soil. Wastes should be handed over to professional institutions for handling to prevent ecological pollution. The data on its biodegradability is limited, but it is presumed that the degradation rate in natural environments is slow, and it should be managed with caution.
FAQ
This compound primarily serves as an organic synthesis intermediate, particularly for producing pharmaceuticals and agrochemicals. The methylthio group and methyl-substituted pyrimidine ring in its structure are key pharmacophores or structural units, often used for further derivatization-such as converting the methylthio group to more reactive methylsulfonyl or methylsulfonyl groups via oxidation.
It should be preserved in fully sealed containers and kept away from direct light within a cool and dry storage environment at a constant temperature of 2 to 8 degrees Celsius. The methylthio group contained in this substance tends to be gradually oxidized when exposed to ambient air and sunlight, which may lead to the decline of product quality. For long-term preservation, regular purity detection is highly recommended, and nuclear magnetic resonance hydrogen spectroscopy can be adopted as an effective detection method. In addition, direct contact with strong oxidizing substances must be strictly avoided during storage and use.
The pyrimidine ring is an electron-deficient aromatic system that can undergo nucleophilic substitution reactions under specific conditions. The methylthio group (-SMe) is a key functional group: on the one hand, the sulfur atom has lone pairs of electrons, which can act as a mild Lewis base or ligand; on the other hand, the C-S bond is easily broken or transformed, especially through oxidation or transition metal-catalyzed coupling reactions for functional group exchange.
Yes. This chemical compound generally emits a pungent and disagreeable odor characteristic of sulfur-containing substances, which is analogous to the unpleasant scent of rotten cabbage or strong garlic. Given its irritating olfactory property and potential health hazards, all relevant experimental handling and operational procedures must be strictly performed inside a fully ventilated laboratory fume hood. Meanwhile, researchers are required to wear complete standard personal protective equipment including chemical-resistant gloves, protective goggles and dedicated lab coats throughout the whole process. Such standardized protective measures are essential to effectively prevent accidental inhalation of harmful volatile vapors and avert direct skin or mucous membrane contact with this substance, so as to fully ensure personal experimental safety and maintain a secure laboratory working environment.
Hot Tags: 4-METHYL-2-(METHYLSULFANYL) PYRIMIDINE CAS 14001-63-9, suppliers, manufacturers, factory, wholesale, buy, price, bulk, for sale, Methyltrialkylammonium Chloride, 6 Nitro 1 diazo 2 naphthol 4 sulfonic Acid, 3 Bromobenzotrifluoride CAS 401 78 5, Tetramethyl orthosilicate, 2 6 Pyridinedicarboxylic acid, Methylamine hydrochloride powder