1835-14-9

1-(4-Hydroxy-3-methoxyphenyl)-1-propanone is a derivative of Guaiacol, a precursor to various flavorants, such as eugenol and vanillin.

Preparation by Fries rearrangement of 2-methoxyphenyl propionate, (b.p.20 140–143°)
with aluminium chloride in nitrobenzene, first at 60–80° for 1 h, then at r.t. overnight, at 60° for 1 h or at 50° for 5 h (44%) ;
with aluminium chloride (2 mol) in nitromethane at r.t. for 24 h (65%)
with aluminium chloride in carbon disulfide
with titanium tetrachloride (2 mol) in nitromethane at r.t. for 24 h (62%)
with stannic chloride (2 mol) in nitromethane at r.t. for 24 h (69%)
with antimony pentachloride (2 mol) in nitromethane at r.t. for 24 h (28%) with formation of important tars.

The Journal of Organic Chemistry, 15, p. 227, 1950 DOI: 10.1021/jo01148a001

The general procedure for the synthesis of 3-methoxy-4-hydroxypropiophenone from (2-methoxyphenyl) propionate is as follows: powdered anhydrous aluminum chloride (3.0 g, 22.5 mmol) was dissolved in anhydrous nitrobenzene (10 mL) at 100 °C. After cooling to room temperature, 2-methoxyphenyl propionate (2.0 g, 11.1 mmol) was quickly added. The reaction mixture was heated at 60 °C for 1.5 h and subsequently cooled to room temperature. A 3N NaOH solution was added to the reaction mixture and stirred for 15 minutes. The suspension was filtered and the solid was washed with water. The filtrate was washed twice with dichloromethane (CH2Cl2) and then acidified with 3N HCl. The acidified aqueous phase was extracted with dichloromethane and the organic phases were combined. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (eluent: petroleum ether/ethyl acetate = 10/1 to 5/1) to afford the target compound 3-methoxy-4-hydroxypropiophenone (874 mg, 44% yield) as a yellow oil.

[1] Patent: WO2013/97773, 2013, A1. Location in patent: Paragraph 0154
[2] Journal of the Chemical Society, 1930, p. 280,291
[3] Journal of the American Chemical Society, 1948, vol. 70, p. 60,62