Molecules 2009, 14
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5,8-Dihydroxy-7H-benzo[c]xanthen-7-one (5): An oven-dried 50-mL round bottom flask equipped
with a stir bar was charged at room temperature (rt) with benzophenone 4 (27.3 mg, 0.08417 mmol,
1 equiv), followed by CH2Cl2 (3.0 mL), giving a bright yellow solution. Then BBr3 (337 μL, 1.0 M in
CH2Cl2, 0.337 mmol, 4 equiv) was added via syringe. This instantly generated a deep red,
homogeneous solution. After 8 h at rt, the reaction mixture was cooled to 0 °C and then H2O (2 mL)
was added via syringe, resulting in an orange biphasic mixture. This was warmed to rt, diluted with
CH2Cl2 (20 mL), poured into a separatory funnel and then the organic layer was washed with H2O (2 x
20 mL), brine (1 x 20 mL), dried over MgSO4, filtered and concentrated in vacuo to afford an orange
solid that was purified by column chromatography (hexanes-EtOAc 3:2) to afford the
1
tetrahydroxybenzophenone as an orange solid (16 mg, 0.0540 mmol, 64%); H-NMR (acetone-d6): δ
8.67 (s, 1H, exchangeable with D2O), 8.57 (s, 1H, exchangeable with D2O), 8.44 (d, J = 8.0 Hz, 1H),
8.20 (d, J = 8.0 Hz, 1H), 7.71 (t, J = 8.0 Hz, 1 H), 7.62 (t, J = 8.0 Hz, 1 H), 7.18 (t, J = 8.0 Hz, 1 H),
13
6.78 (s, 1 H), 6.55 (d, J = 8.0 Hz, 2 H); C-NMR (acetone-d6): δ 202.3, 156.3, 145.5, 132.0, 130.9,
130.2, 127.1, 126.7 (overlap of two C), 124.8, 123.1, 115.9, 115.4, 108.1, 107.9.
A pressure tube equipped with a stir bar was charged with the tetrahydroxybenzophenone (18.9 mg,
0.0638 mmol), H2O (1.6 mL) and DMF (1.0 mL). The resulting homogeneous orange solution was
cooled to 0 °C, sealed and then warmed to 180 °C. After 16 h at this temperature, a yellow solid
precipitated. The mixture was cooled to 0 °C, opened, diluted with EtOAc (10 mL), and poured into a
separatory funnel. The organic layer was washed with H2O (2 x 10 mL) and brine (1 x 10 mL), dried
over MgSO4, filtered and concentrated in vacuo to afford a yellow solid that was purified by column
chromatography (hexanes-EtOAc 9:1) to afford the xanthone 5 as a yellow solid (17 mg, 0.0638 mmol,
95% yield); 1H-NMR (DMSO-d6): δ 12.72 (s, 1 H, exchangeable with D2O), 8.60 (d, J = 8.0 Hz, 1 H),
8.27 (d, J = 8.0 Hz, IH), 7.81 (dt, J = 8.0 Hz, 2H), 7.73 (t, J = 8.0 Hz, IH), 7.34 (s, 1 H), 7.26 (d, J =
8.0 Hz, IH) 6.82 (d, J = 8.0 Hz, IH); 13C-NMR (DMSO-d6) δ 181.5, 161.0, 155.8, 150.5, 147.8, 137.0,
130.2, 129.5, 128.4, 124.6, 123.3, 123.1, 116.8, 110.4, 109.0, 107.9, 98.8.
1-Methoxy-7-hydroxyxanthone (2): To a mixture (87.2 mg) of 3 and inseparable 2,6-dimethoxy-
benzaldehye in ice-cold methanol (2 mL), a solution of KOH (89.2 mg, 1.6 mmol) in methanol (1 mL)
was added dropwise over 2 min. The reaction mixture was refluxed overnight, cooled to 0 °C, then
acidified with 10% HCl. After extracting with EtOAc (2x), the combined organic layers were dried
over MgSO4, filtered, concentrated in vacuo, and purified by column chromatography (3% MeOH in
CH2Cl2) to afford 43 mg of 2 that crystallized from MeOH as yellow needles, m.p. 238-240 °C (lit.
[11] 238-240 °C). All spectra were identical with those previously reported [11].
Euxanthone (1): To a stirred suspension of 2 (48 mg, 0.198 mmol) in CH2Cl2 (2 mL) at –78 °C was
rapidly added BBr3 (149 mg, 0.595 mmol, 0.595 mL of 1.0 M solution in CH2Cl2). The reaction
mixture was slowly allowed to warm to rt, stirred for 36 hours, cooled to 0 °C, then quenched with
water. CH2Cl2 was removed in vacuo, and the aqueous layer was extracted with EtOAc (2x). The
combined organic layers were washed with water and brine and dried over MgSO4, filtered,
concentrated in vacuo, and purified by column chromatography (15% EtOAc in hexanes) to afford
23.5 mg (56% yield) of 1 as yellow needles, m.p. 236-238 °C (lit. [12] 236-238 °C).