[6-Hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-YL](4-methoxyphenyl)methanone → 2-(4-Hydroxyphenyl)-3-(4-Hydroxybenzoyl)-6-Hydroxybenzo[b]thiophene

Participants

Reaction Conditions

Reaction Steps

A 250 mL, 3 neck, flask fitted with a thermometer, condenser, and stopper is charged 2-(4-hydroxyphenyl)-3-(4-methoxybenzoyl)-6-hydroxybenzo[b]thiophene (3.0 g, 7.97 mmol) and pyridine hydrochloride (18.5 g, 160 mmol). The contents are heated to 185-190° C. and held at this temperature for 90 minutes. The hot mixture is then poured into 250 mL of ice/water. A yellow solid formed with this addition. The material is extracted into 250 mL of ethyl acetate. The aqueous is then back-extracted with 100 mL of ethyl acetate. The combined organics are washed with 150 mL 1N hydrochloric acid and 150 mL brine. The solvent is removed in vacuo giving a viscous oil. To the oil is added 10 mL of 1:1 methylene chloride/hexanes which induced crystallization. The slurry is cooled to 0° C. and stirred at this temperature for 1 hour. The product is collected by vacuum filtration and washed with 25 mL of 4:1 hexanes/methylene chloride. Drying the solid at 100° C. for 5 hours afforded 2.5 g (86.2%) of a dark yellow solid containing approximately 3% monomethoxy starting material. An analytical sample is obtained by chromatography on silica gel (15:1 methylene chloride:methanol). mp 135° C. (dec); 1H NMR (300.1 MHz, DMSO-d6) δ 6.67 (d, 2H), 6.71 (d, 2H), 6.85 (dd, 1H), 7.17 (d, 2H), 7.25 (d, 1H), 7.32 (d, 1H), 7.57 (d, 2H), 9.73 (br s, 2H), 10.41 (br s, 1H); 13C NMR (75.5 MHz, DMSO-d6) d 107.1, 115.1, 115.4, 115.6, 123.4, 123.9, 128.4, 129.7, 129.9, 132.1, 132.4, 139.2, 140.0, 155.4, 157.8, 162.5, 192.4; MS (FD+) m/e 362 (100), 363 (24), 364 (7); HRMS m/e calc'd for C2H15O4S (M+1): 363.069106, found 363.06990.

Provenance & Evidence