Background and overview[1]
2,4,5-Trimethoxybenzaldehyde is mainly used in the preparation of asarone. α-Asarone mainly exists in the volatile oils of plants such as Acorus calamus, a natural product. It has sedative, prolonged hypnosis and antibacterial effects. It is clinically used for the treatment of chronic bronchitis, epilepsy, coma and other mental diseases. Since the 1960s, extensive research has been conducted at home and abroad on the extraction, synthesis, pharmacology, toxicology and clinical practice of α-asarone monomer, the active ingredient of the Calamus plant, and significant progress has been made.
Preparation[1]
A synthesis method of 2,4,5-trimethoxybenzaldehyde, which method includes the following steps:
Step 1. Add 4.42g of 1,2,4-trimethoxybenzene and 10ml of DMF to the reaction bottle in sequence, take an ice-water bath, control the temperature to 10°C, and add dropwise a DMF solution containing 1.47g of phosphorus oxychloride into the solution. After the dropwise addition is completed, the mixture is heated to 60°C and stirred for 1 hour;
Step 2, control the reaction by TLC. If the reaction is complete, pour the reaction solution into 30 ml of cold water, add 30% potassium hydroxide solution dropwise to adjust pH=7, lower the temperature by 5°C, crystallize for 30 minutes, filter and wash, to obtain 2,4,5-trimethoxybenzaldehyde.
Apply[2]
2,4,5-Trimethoxybenzaldehyde is mainly used in the preparation of asarone. Using 2,4,5-trimethoxybenzaldehyde as the raw material, the adduct of the Grid addition reaction with ethyl magnesium bromide is concentrated and eliminated, and the recrystallization method is used to obtain asarone crystals, which are characterized by: : Put 75g of the adduct produced by 2,4,5-trimethoxybenzaldehyde on a rotary evaporator, recover THF at 46°C, cool to room temperature, add 375mL of ethyl acetate, and stir for 5 hours at 22°C. Add 75 ml acetic anhydride and stir for 60 minutes, then add 350 ml distilled water and stir quickly for 10 seconds. Separate the water layer, wash the ester layer with sodium carbonate solution to pH=9~10, then wash with saturated brine, dry over anhydrous sodium sulfate overnight, and filter. Concentrate, then add 15mL of 70% ethanol and shake well, cool to room temperature, add a small amount of seed crystals, place in the freezer of the refrigerator overnight, filter, then transfer the solid to a 250mL dry one-neck flask, add 25mL of 80% ethanol, heat to dissolve, and crystallize at room temperature , filtered, dried for 5 hours (vacuum 46°C), weighed 48.8 grams, and the yield was 61.31%. (GC-MS detection content is 99.21%).
Main reference materials
[1] CN201810279852.7 A synthesis method of pharmaceutical intermediate 2,4,5-trimethoxybenzoic acid
[2] Synthesis method of CN200710049565.9α-asarone
