Background and overview[1]
2,5-Dimethoxyphenylethylamine is the main raw material for the synthesis of 5-hydroxytryptamine (5-HT) compounds. Its main synthesis method consists of 2,5-dimethoxybenzaldehyde and nitrate. 2,5-dimethoxy-β-nitrostyrene is prepared by reacting with methane, and is prepared by reduction. 2,5-Dimethoxystyrene derivatives can be used as tyrosine-activating enzyme inhibitors in cancer treatment. Current synthesis of 2,5-dimethoxy-β-nitrostyrene (II). The method uses benzene and ethanol as solvents, methylamine and piperidine as catalysts, uses nitromethane as both reactant and solvent, and uses ammonium acetate as catalyst, which shortens the reaction time and improves the yield.
Preparation[1]
The preparation of 2,5-dimethoxyphenylethylamine is as follows:
1) 2,5-dimethoxy-β-nitrostyrene (Ⅰ)
Put 3.32g (0.02mol) of 2,5-dimethoxybenzaldehyde, 0.5g of ammonium acetate and 4mL of nitromethane into the reaction bottle, heat to 85°C with stirring, and keep warm for 30 minutes. Pour the reactant into cold water, cool, yellow crystals will precipitate, filter, and wash with 70% ethanol to obtain (Ⅰ) 3.7g (yield 90%), mp119~120℃ (document [3] mp118~119℃) .
2) 2,5-Dimethoxyphenylethylamine hydrochloride (II)
Add 4.18g of (Ⅰ) into a 250mL three-necked flask, add 20mL of 95% ethanol, stir, heat to 40℃, add 35mL of concentrated hydrochloric acid and 40mL of water; add 25g of zinc powder in batches at 65℃, and add a small amount After the zinc powder, add a small amount of metallic mercury to keep the temperature between 65 and 70°C; after adding the zinc powder, cool to 50°C and add 10 mL of hydrochloric acid and maintain 50 to 55°C for 3 hours; cool, add sodium carbonate to adjust the pH to 8 to 9, and use normal Extract with butanol, and distill the extract under reduced pressure to remove n-butanol. The reactant turns into a dark brown slurry weighing 6.5g. Salt formation: Add methanol hydrochloric acid solution to the slurry reactant, evaporate most of the methanol, and cool and crystallize to obtain light brown crystal II, 2.52g (yield 60%), mp136~138℃ (mp139℃).
Main reference materials
[1] New synthesis process of 2, 5-dimethoxyphenylethylamine hydrochloride
