Background and overview[1][2]
Phenolic compounds are an important class of organic chemical raw materials. Phenol is one of the important derivatives of propylene and is mainly used in the production of phenolic resin, caprolactam, bisphenol A, etc. In addition, phenolic compounds play a major role in the life activities of the human body and plants, such as antioxidant and antiviral. 2-Methyl-4-methoxyphenol is a phenolic derivative and can be used as a pharmaceutical synthesis intermediate.
Preparation[1]
Method 1: Weigh 50g of ceric ammonium nitrate and dissolve it in 4L of water, use 25wt% sodium carbonate aqueous solution as the precipitant, adjust the system pH = 10, centrifuge the resulting precipitate, wash until neutral, dry, and roast at 500°C 3h, cerium dioxide is obtained. Sieve the 14-25 mesh catalyst from the ceria molding screen and fill it into a reaction tube with an inner diameter of 7mm, and fill it with a 15cm bed. Under normal pressure, a methanol solution of 10wt% ecological oil is used as the raw material, and the acetic acid content of the ecological oil is: 19.77 %, the acetone content is: 12.06%, the methanol content is 6.22%, the raw material feed rate is 0.03mL·min-1, nitrogen is the carrier gas, the flow rate is 30mL·min-1 , react at 350℃ for 12h. After the reaction is completed, an extraction agent is added to the system for extraction and the product is collected by rotary evaporation. The extraction agent is methylene chloride. The product composition is determined by mass spectrometry and quantified by chromatography. The conversion based on acetone was 70% and the overall selectivity for 2-methyl-4-methoxyphenol compounds was 85%.
Method 2:
The specific steps are as follows: Add ethyl chloroformate (5 mL) dropwise to cooled 2-hydroxy-5-methoxy-benzaldehyde (624 μL, 5.0 mmol) and triethylamine (832 μL, 6.0 mmol) in THF (5 mL). 571 μL, 6.0 mmol) solution for 30 min, and the mixture was stirred at 0°C for 30 min. The precipitate was filtered off, and the filtrate was added dropwise to a solution of ice-cold NaBH4 (756 mg, 20 mmol) in water (7.5 mL) over 45 minutes. The resulting mixture was stirred at room temperature for 90 minutes, then diluted with water, acidified to pH<2 with 2M HCl and extracted with diethyl ether. The organic phase was dried (MgSO4) and evaporated. When 90% of the ether evaporates, the precipitate formed is filtered off. The filtrate is 2-methyl-4-methoxyphenol.
Apply[2]
2-Methyl-4-methoxyphenol can be used as a pharmaceutical synthesis intermediate. If the following reaction occurs:
Place 2-methyl-4-methoxyphenol (1.62g, 6.61mmol) dicyclohexyl-(2′,4′,6′-triisopropyl-biphenyl-2-yl)-phosphine (94 mg, 0.20 mmol), diacetonitrile palladium (II) chloride (17 mg, 0.066 mmol), cesium carbonate (4.31 g, 13.2 mmol) and propionitrile (40 mL) were stirred under reflux under nitrogen flow. Ethynyl-trimethyl-silane (2.04 mL, 13.2 mmol) was added via syringe and the mixture was stirred at reflux for a further 2 hours. After cooling and diluting with water, the mixture was extracted with CH2Cl2 and filtered through a phase separator. The organic phase was evaporated and the residue was purified by column chromatography (mobile phase: CH2Cl2-isohexane 1:3) to give the title compound (312 mg, 19%).
Main reference materials
[1](CN106431844) A ceria catalyzed ecological oil to prepare phenolsCompound methods
[2](WO2009124968)NOVELESTROGENRECEPTORLIGANDS
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