2-Methylresorcinol → 8-Methyl-2-phenylchroman-7-ol

Participants

Reaction Steps

Step 1 A suspension of (E)-3-phenylprop-2-en-1-ol (2.22 g, 16.51 mmol) and 2-methylbenzene-1,3-diol (2.05 g, 16.51 mmol) in 1,2-dichloroethane (100 mL) was treated with p-toluenesulfonic acid monohydrate (0.157 g, 0.826 mmol) and the mixture was heated at reflux for 1 h. The mixture was cooled to rt and concentrated, and the residue was subjected to column chromatography (eluting with a gradient from 90:10 to 75:25 hexane-EtOAc) provided a mixture of 4-cinnamyl-2-methylbenzene-1,3-diol and 4,6-dicinnamyl-2-methylbenzene-1,3-diol (2:1, 1.97 g). This material (1.89 g) was dissolved in toluene (60 mL) and treated with p-toluenesulfonic acid monohydrate (299 mg, 1.57 mmol) and heated at reflux for 6 h. The mixture was cooled to rt, diluted with EtOAc (100 mL), washed with NaHCO3 (aq) (2×30 mL), water (30 mL) and brine (30 mL), dried and concentrated. Column chromatography (eluting with a gradient from 95:5 to 70:30 hexane-EtOAc) provided 8-methyl-2-phenylchroman-7-ol as a brown liquid (ca. 85% purity, 672 mg, 17%) used without further purification. 1H NMR (400 MHz, chloroform-d) δ 7.35-7.50 (4 H, m), 7.27-7.35 (1 H, m), 6.79 (1 H, d, J=8.36 Hz), 6.38 (1 H, d, J=8.14 Hz), 5.07 (1 H, dd, J=10.12, 2.42 Hz), 4.64 (1 H, s), 2.83-3.02 (1 H, m), 2.71 (1 H, ddd, J=16.01, 4.90, 3.74 Hz), 2.16-2.27 (1 H, m), 2.14 (3 H, s), 1.86-2.04 (1 H, m). Mass spectrum m/z 241.0 (M+H)+.

Provenance & Evidence