2-Methoxybenzene-1,4-diol → 2-Methoxy-1,4-benzoquinone

참여 물질

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To a vigorously stirred solution of NaIO4 (15.4 g, 72.2 mmol, Baker) in water (500 mL), there was added solid 2-methoxyhydroquinone (37, 3.20 g, 22.8 mmol) in portions. The reaction immediately became dark orange. The reaction was allowed to stir for 1 h at it and was extracted with CH2Cl2 (3×75 mL). The extract was washed with half saturated brine (1×75 mL), filtered through cotton and the solvent removed in vacuo to yield 17 as an orange solid (3.02 g, 96%) which was of sufficient purity (TLC analysis, 10% EtOAc, 90% CHCl3) for further reaction. The crude 17 was combined with 2,4-hexadiene (10 g, isomeric mixture, Aldrich, used as received), toluene (30 mL) and hydroquinone (300 mg, Mallinkrodt). The reaction mixture was heated under N2 in a 60° C. oil bath for 17.5 h, with the contents being stirred magnetically. A pale orange, near homogeneous solution was present. The reaction was allowed to cool to rt, the contents filtered and the solvent removed in vacuo to give a brown oil (5.8 g). TLC analysis (10% EtOAc, 90% CHCl3) showed no remaining 17. Without purification, the oil was dissolved in MeOH (270 mL), Et3N (1.5 mL) added, and the resulting dark solution was allowed to vigorously stir under O2 for 40 min at rt (Note: Further reaction time may improve the final yield). TLC analysis (10% EtOAc, 90% CHCl3) showed the major Diels-Alder adduct to be consumed, with a major higher Rf spot being formed. The reaction mixture was acidified with 10% HCl (100 mL), diluted with H2O (200 mL) and the MeOH removed in vacuo to give an orange suspension. The suspension was extracted with CHCl3 (3×75 mL). The extract was washed with saturated NaHCO3 (3×75 mL), and H2O (1×200 mL), filtered through cotton, and the solvent removed in vacuo to give an orange tacky solid (5.9 g). This was passed through a silica gel column in the dark with CHCl3 elution (the product is slightly photosensitive in solution). The initial orange band was collected to give an orange solid (3.0 g). Crystallization from 95% EtOH yielded 38 as orange plates (2.22 g, 45% from 37, pure by TLC and 1H NMR); mp 110.0°-111.5° C. (EtOH); 1H NMR (CDCl3) δ1.19 (s, 3H), 1.21 (s, 3H), 3.40 (m, 2H), 3.81 (s, 3H), 5.78 (m, 2H), 5.88 (s, 1H). Note: Further reaction of this compound with O2 in Et3N/MeOH failed to produce the subsequent aromatic compound.

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