Methyl3-hydroxy-4-methoxybenzoate

Off-white to beige crystalline powder

To a suspension of 3-hydroxy-4- (methyloxy) benzoic acid (25g, 149 mmol. ) in methanol (200 mL) was added concentrated sulfuric acid (1 mL) and the mixture was brought to reflux over 18 hours. The resulting homogeneous solution was cooled to room temperature, concentrated in vacuo and the residual oil taken into ethyl acetate (300 mL). The solution was washed once with water, saturated aqueous sodium hydrogencarbonate then brine and dried over anhydrous magnesium sulfate. Filtration and concentration gave methyl 3- hydroxy-4- (methyloxy) benzoate (27g, 100percent yield) as an OIL.H NMR (400 MHz, CDC13): 7.59 (dd, 1H), 7.57 (d, 1H), 6.85 (d, 1H), 5.72 (s, 1H), 3.93 (s, 3H), 3. 87 (s, 3H).To a suspension of 3-hydroxy-4- (methyloxy) benzoic acid (25g, 149 mmol. ) in methanol (200 mL) was added concentrated sulfuric acid (1 mL) and the mixture was brought to reflux over 18 hours. The resulting homogeneous solution was cooled to room temperature, concentrated in vacuo and the residual oil taken into ethyl acetate (300 mL). The solution was washed once with water, saturated aqueous sodium hydrogencarbonate then brine and dried over anhydrous magnesium sulfate. Filtration and concentration gave methyl 3- hydroxy-4- (methyloxy) benzoate (27g, 100percent yield) as an OIL.H NMR (400 MHz, CDC13): 7.59 (dd, 1H), 7.57 (d, 1H), 6.85 (d, 1H), 5.72 (s, 1H), 3.93 (s, 3H), 3. 87 (s, 3H).To a stirred solution of 3-hydroxy-4-methoxy benzoic acid (4.00 g, 23.7 mmol) (commercially available) in methanol, was added sulfuric acid (catalytic amount) and the reaction mixture was heated at 65-70 A mixture of 3-hydroxy-4-methoxy benzoic acid 4 (40 g, 0.2378 mol) and methanolic HCl (400 mL) was stirred and heated to 50-55°C for 4 hr. The methanolic HCl was removed by vacuum distillation and the residue was diluted with water 100 mL. The aqueous mixture was extracted with ethyl acetate 2 × 200 mL. The combined organic layers were washed with water and solvent was distilled under vacuum to get light brown compound 5. Which was taken in situ for next step without isolation (38.2 g, yield 88.22percent, purity 98-99percent); m.p. 70-71°C; To a stirred solution of 3-hydroxy-4-methoxybenzoic acid 19 (1.68 g, 10 mmol) in 15 mL MeOH under ice-cooling, was added SOClb) Preparation of Methyl-2-hydroxy-3-methoxy benzoate; The solid obtained in step a), was refluxed with 10percent methanolic hydrochloric acid solution (250 ml) for 6 hours. The reaction mass was quenched into chilled water (1 It) and repeatedly extracted with methylene chloride (250 ml). The combined methylene To a dry 100 mL three-necked flask, 10 g of 3-hydroxy-4-methoxybenzoic acid, 110 ml of methanol, and 360 uL of concentrated sulfuric acid were successively added, and the mixture was heated to 65 ° C, and reacted under magnetic stirring overnight. The progress of the reaction was judged by thin layer chromatography, and the developing solvent was ethyl acetate: dichloromethane = 1:1. After completion of the reaction, the product was collected, and the product was transferred to a round-bottomed flask to remove methanol under reduced pressure. The residue was extracted with ethyl acetate (25 mL), and neutralized with 15 mL of saturated sodium hydrogencarbonate. Ethyl acetate was evaporated to give a solid product, methyl 3-hydroxy-4-methoxybenzoic acid, 9.06 g, yield: 83.6percent.Isovanillic acid (50 g, 0.3 mol), MeOH (500 ml), and thionyl chloride (23.6 ml) were introduced into a reaction vessel, and the mixture was heated at reflux for 2 hours. After cooling, the mixture was neutralized with a 25percent NaOH aqueous solution, and water (250 ml) and activated carbon (2.5 g) were added thereto. After the mixture was stirred at room temperature, insoluble matter was filtrated. The filtrate was concentrated and extracted with AcOEt (350 ml). After the organic layer was separated, it was concentrated by distilling off the solvent to give oily Compound (18a) (54 g) . Compound (18a): 3 - hydroxy -4 - methoxybenzaldehyde (10g, 65.7mmol) is dissolved in formic acid (9.1g, 197 . 1mmol) in, solution is cooled to 0 °C, the 35percent hydrogen peroxide (22.3g, 230mmol) slow instillment like in the above solution, keep the 4 °C reaction overnight. Filtering the solid material after completion of the reaction, ice water after washing, drying to obtain solid material. The solid is dissolved in methanol (50 ml) in, slowly adding concentrated sulfuric acid (98percent, 3.2 ml, 59 . 1mmol), heating to reflux, the solvent is removed to obtain the crude product, 10percent methanol aqueous solution by recrystallization to obtain 3 - hydroxy -4 - methoxybenzoic acid methyl ester (II) (9.6g), yield 80percent.General procedure: The reaction of 3, 4, 5-trimethoxybenzaldehyde (0.01mol)withH2O2(0.04 mol) and methanolwas carried out in 100 mL round bottomflask.The reaction mixture was reflux for 24 h. After completion of the reaction, the reaction mixture pour in distilled water; the aqueous solutionwas the extracted with ethyl acetate (3 × 20 mL) and brine solution toget clear ethyl acetate layer. The organic layerwas driedwith anhydrous sodiumsulfate. It was filtered and vaporized to dryness at reduced pressureto obtained corresponding methyl etster.FIGURES 8A-8C are illustrations of the hydroxylation of arenes mediated by 4, 5-dichlorophthaloyl peroxide. To examine the scope of the hydroxylation reaction mediated by 4, 5-dichlorophthaloyl peroxide (2), two general sets of reaction conditions were developed. The oxidations are carried out using either 1.3 equivalents of 4, 5-dichlorophthaloyl peroxide (2) at 50 °C or 2.5 equivalents heated to 75 °C. Operationally the reaction proceeds without the need for special exclusion of air and the use of commercial grade HFIP is sufficient. Thermogravimetric analysis indicates that 4, 5-dichlorophthaloyl peroxide has a point of decomposition at 135 °C. Therefore, all reactions reported are conducted at or below 75 °C. While we have not encountered exothermic reactions, appropriate precautions must be used similar to those for all experiments using peroxides. Isolated yields are given below each entry. The yield in parentheses refers to the starting material recovered. The minor regioisomeric positions are labeled with the respective carbon atom number and, after the major isomer, listed sequentially. Reaction conducted at 0°C. Prior to the addition of 4, 5-dichlorophthaloyl peroxide (2) p-toluenesulfonic acid monohydrate (1.0 equiv.) was added to the solution of 3(y).

Molecular Weight:182.17
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:182.05790880
Monoisotopic Mass:182.05790880
Topological Polar Surface Area:55.8
Heavy Atom Count:13
Complexity:181
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes