Hydrogen Bromide → 4-(4-Chlorophenoxy)phenol

Participants

Reaction Steps

A 1 liter 3-necked flask is equipped with a mechanical stirrer, a Dean-Stark trap carrying a reflux condenser, and a heating mantle, and is charged with 4-methoxyphenol (35.9 grams, 0.29 mol), 85 percent KOH (19.1 grams, 0.29 mol ,and p-xylene (350 ml). The mixture is heated at reflux for 1 hour, removing the water of reaction azeotropically. Then it is cooled, and 1-chloro-4-iodobenzene (69 grams, 0.29 mol), copper powder (2.9 grams, 46 mmol), and cuprous chloride (2.9 grams, 29 mmol) are added, and the mixture is heated at reflux for 20 hours. Workup consists of diluting the cooled mixture with Et2O (200 ml), filtration through a medium-fritted funnel, and concentration of the filtrate to leave a deep dark oily residue. This crude material, consisting primarily of 4-(4-chlorophenoxy)anisole, is treated with glacial acetic acid (275 ml) and 48 percent HBr (105 ml), then the mixture is heated at reflux for 24 hours. Workup consists of partitioning the mixture between H2O (1.2 l) and CH2CL2 (0.5 l), washing the organic phase with H2O (0.5 l), and concentration to leave a deep dark oily residue. This residue is taken up in ethanol (0.5 l) and treated with activated carbon (Norit; ca. 50 grams). Filtration through celite, and concentration of the filtrate gave the crude title compound as a thick, red oil. Further purification of the product is achieved by chromatography on a column packed with flash-grade silica gel (6"×2" i.d.), eluting with CH2CL2, to give after concentration a pinkish solid, which is subsequently recrystallized from hexane-EtOAc to give 31.4 grams (49 percent yield) of pure 4-(4-chlorophenoxy)phenol as off-white prisms, m.p. 85° C. to 86° C.

Provenance & Evidence