Preparation method of 5-hydroxy-2-methoxy-benzaldehyde_Kain Industrial Additive

Overview^[1]

5-Hydroxy-2-methoxy-benzaldehyde is a phenolic structure. The synthesis method of phenolic compounds includes the following steps: in the presence of a cuprous catalyst and ammonia water, an arylboronic acid compound and MOH are Substitution reaction yields phenolic compounds.

Preparation method^[1-2]

Method 1,

Preparation of 2-methoxy 5-hydroxybenzaldehyde

Add 0.0144g cuprous oxide (0.1mmol) and 0.192mL (2.5mmol) NH₃-H₂O into a round-bottomed flask equipped with a magnetic stirrer. ), 0.180g (1mmol) of 3-aldehyde-4-methoxyphenylboronic acid, 0.2g (5mmol) of sodium hydroxide, 2mL of water. At 15°C, open system, reaction time is 24 hours. After the reaction is completed, add hydrochloric acid to adjust the pH value to 2-3, and extract with ethyl acetate three times, 10 mL each time. The combined organic phase is concentrated, separated and purified to obtain 120 mg of 2-methoxy 5-hydroxybenzaldehyde. The rate is 79%.

Product 2-methoxy 5-hydroxybenzaldehyde: ¹H NMR (CDCl₃, 600MHz) δ10.4 (s, 1H), 7.36 (d , 1H, J=2.8Hz), 7.12 (dd, 1H, J=2.8, 8.9Hz), 6.91 (d, 1H, J=8.9Hz), 5.73 (s, 1H), 3.88 (s, 3H).¹³C NMR (CDCl₃, 150MHz) δ190.1, 156.6, 149.8, 125.0, 123.6, 113.7, 113.4, 56.1.ESI-MS[M-H]^– m/z 151.5.

Method 2:

At 0°C, slowly add concentrated H₂SO₄ (40mL) to 2,5-dimethoxybenzaldehyde (3.32g, 20mmol) middle. The solution was heated at 55°C and stirred for 46 hours. The reaction was quenched with water and the product was extracted first with Et₂O and then with aqueous NaOH. The solution was acidified with aqueous HCl and extracted with Et₂O. The solution was dried with MgSO₄ and concentrated by evaporation. The crude product was subjected to SiO₂ column chromatography (CHCl₃/MeOH), followed by precipitation from MeOH/H₂O to obtain the product. Light brown solid, yield 0.9 g, 29%. ¹H NMR (CDCl₃): δ3.87 (s, 3H, -OCH3), 6.57 (s, 1H, -OH) , 6.89 (d, J = 9.2Hz, 1H), 7.13 (dd, Ja = 9.2Hz, Jb = 3.1Hz, 1H), 7.37 (d, J = 3.1Hz, 1H), 10.38 (s, 1H, -CHO ). ¹³CNMR (CDCl₃, 125MHz): δ190.53,156.58,149.95, 124.82,123.96,113.71,113.31,56.14.

Main reference materials

[1] [Chinese invention] CN201110063336.9 A method for synthesizing phenolic compounds

[2] Suzuki Y , Hashimoto K , Tajima K . Synthesis of Regioregular Poly(/r, p/r, -phenylenevinylene)s by Horner Reaction and Their Regioregularity Characterization[J]. Macromolecules, 2007, 40(18) :6521-6528.