Background and overview[1]
4-(4-Methoxyphenyl)-2-butanone can be used to prepare 4-p-hydroxyphenyl-2-butanone, also known as raspberry ketone, Raspberry ketone, raspberry ketone, was discovered by Nomura et al. in Japan in 1918. It was confirmed as the main aroma substance in raspberries in 1957. Raspberry ketone is an aromatic substance approved by the American Flavor Manufacturers Association (FEMA). It is a safe edible spice jointly recognized by the Council of Europe (COE) and its FEMA number is 2588.
4-(4-Methoxyphenyl)-2-butanone can be prepared from p-methoxybenzaldehyde through a four-step reaction.
Preparation[1]
(1) Preparation of p-methoxybenzyl alcohol: p-methoxybenzaldehyde (formula 6), reducing reagent and solvent A, perform a reduction reaction, then add water and solvent B, separate the organic layer and the aqueous layer Extract with solvent B, combine the organic phases, dry, filter and concentrate to obtain p-methoxybenzyl alcohol (formula 2);
(2) Preparation of p-methoxybenzyl chloride: Dissolve p-methoxybenzyl alcohol in solvent C, add halogenating reagent dropwise, perform halogenation reaction, stir, separate the organic layer, and use solvent C for the aqueous layer Extract, combine the organic phases, dry, filter, and concentrate to obtain p-methoxybenzyl chloride (formula 3);
Preparation of (3) 4-(4-methoxyphenyl)-2-butanone: Dissolve metallic sodium in solvent D, add ethyl acetoacetate, and then add p-methoxybenzyl chloride for substitution React and stir to obtain a solution containing 2-acetyl-3-(4-methoxyphenyl) ethyl propionate (Formula 4); then base A is added dropwise to a solution containing 2-acetyl-3-(4 -Methoxyphenyl)ethyl propionate solution, heat and stir to carry out hydrolysis reaction; then add acid A, heat and stir to carry out decarboxylation reaction, cool, concentrate, extract with solvent E, dry, filter, concentrate, and distill under reduced pressure. Obtain 4-(4-methoxyphenyl)-2-butanone (formula 5);
Apply[1]
4-(4-Methoxyphenyl)-2-butanone can be used to prepare 4-p-hydroxyphenyl-2-butanone: 4-(4-methoxyphenyl)-2-butanone , demethylation reagent, solvent F and acid B are placed in a reaction bottle, perform a demethylation reaction, then concentrate, add water, extract with solvent G, combine the organic phases, dry, concentrate, and then recrystallize after acid and alkali treatment. 4-p-hydroxyphenyl-2-butanone (formula 1) is obtained.
Main reference materials
[1] [Chinese invention] CN201811252782.2 A preparation method of 4-p-hydroxyphenyl-2-butanone
