Sulfuric Acid → Methyl 4-hydroxy-2-methoxybenzoate

Participants

Reaction Conditions

Reaction Steps

To a 250 mL Erlenmeyer flask was added methyl 4-amino-2-methoxybenzoate (7.5 g, 41.4 mmol) and a 25% solution of sulfuric acid (40 mL, 188 mmol). The solution was cooled to 0° C. and a saturated solution of sodium nitrite (4.29 g, 62.2 mmol) was added drop wise. The orange mixture was stirred for 15 minutes. The resulting diazonium solution was then very slowly poured into a 1 L flask containing 500 mL of 3% sulfuric acid. The solution was stirred for 5 minutes then transferred to a separatory funnel. The reaction mixture was diluted with 150 mL of DCM, extracted, dried over magnesium sulfate and concentrated. to a red solid. The resulting solid was triturated with hexane to give 5.71 grams of the desired phenol as a red powder (73% yield). The LC/MS data was obtained on a Shimadzu analytical LC/MICROMASS® Platform LC (ESI+) at 220 nm using the following set of conditions: Waters Sunfire 5 μm C18, 4.6×30 mm column, with a gradient of 0-100% B (B=90% HPLC grade methanol/0.1% trifluoroacetic acid/10% HPLC grade water), (A=90% HPLC grade water/0.1% trifluoroacetic acid/10% HPLC grade methanol), in 2 minutes with a 1 minute hold at a rate of 4 mL/minute. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.67-3.72 (m, 3H), 3.74 (s, 3H), 6.39 (dd, J=8.66, 2.13 Hz, 1H), 6.45 (d, J=2.13 Hz, 1H), 7.59 (d, J=8.66 Hz, 1H). LCMS Rt=1.070 min., m/z 183.09 (M+H), 96% purity.

Provenance & Evidence