◦
saturated brine (20 mL) before drying (MgSO4) and evaporation
in vacuo. The crude product was purified by preparative thin layer
chromatography (petrol–EtOAc 2:1) to give 2e¢ as a white solid
(0.09 g, 78%). 1H NMR (400 MHz, CDCl3, TMS): d 7.12 (t, 1H,
J = 8.4 Hz, 4-H), 6.61 (d, 2H, J = 8.4 Hz, 3,5-H), 3.81 (s, 6H,
CH3O), 2.33 (s, 3H, CH3CO); MS (ESI, m/z): 219 [M + Na+]; data
consistent with the literature.22
heated at 50 C for 0.5 h. Then H2O (20 mL) and Na2S2O3 was
added and the reaction mixture was poured into 5% hydrochloric
acid (10 mL). The solution was extracted with EtOAc (2 ¥ 15 mL)
and the combined organic phase was washed with saturated
sodium bicarbonate solution (20 mL) and saturated brine (20 mL),
dried over MgSO4 and evaporated in vacuo. The crude product was
purified by preparative thin layer chromatography (petrol–EtOAc
2:1) to give 10 as a white solid (0.11 g, 61%). 1H NMR (600 MHz,
CDCl3, TMS): d 7.76 (d, 1H, J = 8.8 Hz, 5-H), 7.22 (s, 2H, 2¢,6¢-
H), 7.01 (d, 1H, J = 8.8 Hz, 6-H), 6.69 (s, 1H, 3-H), 4.04 (s, 3H,
7-CH3O), 3.99 (s, 6H, 3¢,5¢-CH3O); MS (ESI, m/z): 367 [M + Na+];
data consistent with the literature.17
2¢-Fluoro-3,3¢,5-trimethoxybiphenyl-4-ol (8a)
IR (KBr) nmax/cm-1 3420, 3003, 2937, 2844, 2360, 1611, 1219, 1116;
1H NMR (400 MHz, CDCl3, TMS): d 7.10 (m, 1H, 5¢-H), 6.99 (m,
1H, 6¢-H), 6.93 (m, 1H, 4¢-H), 6.78 (s, 2H, 2,6-H), 5.57 (s, 1H,
4-OH), 3.92 (s, 6H, 3,5-CH3O), 3.93 (s, 3H, 3¢-CH3O); 13C NMR
(100 MHz, CDCl3, TMS): d 150.8 (C-2¢), 148.4 (C-3¢), 147.0 (C-
3/C-5), 134.8 (C-4), 130.1 (C-1¢), 126.7 (C-1), 123.8 (C-5¢), 121.9
(C-6¢), 112.0 (C-4¢), 106.2 (C-2/C-6), 56.4 (3,5-CH3O); MS (ESI,
m/z): 301 [M + Na+], 277 [M - H-]; HRMS (ESI, m/z) Calcd. for
C15H15FO4Na+ 301.0847, found 301.0853.
3-Benzyloxy-3¢,4¢,5¢-trimethoxybiphenyl-4-carbaldehyde (11)
To a solution of 2-benzyloxy-4-bromobenzaldehyde (5.24 g,
18.00 mmol) and 3,4,5-trimethoxyphenylboronic acid (2.54 g,
12.00 mmol) in DMF (20 mL), was added anhydrous K2CO3
(3.32 g, 24.00 mmol) and Pd(OAc)2 (0.08 g, 0.36 mmol). The
reaction mixture was strirred at 110 ◦C for 5 h, then cooled to room
temperature and poured into water, filtered and recrystallized with
ethyl acetate to afford 11 as a colorless solid (3.27 g, 72%). IR
(KBr) nmax/cm-1 3432, 2921, 2852, 2361, 1678, 1604, 1132, 1004;
1H NMR (400 MHz, CDCl3, TMS): d 10.57 (s, 1H, CHO), 7.90 (d,
1H, J = 8.0 Hz, 5-H), 7.36-7.48 (m, 5H, benzyl-H), 7.21 (d, 1H,
J = 8.1 Hz, 6-H), 7.15 (s, 1H, 2-H), 6.70 (s, 2H, 2¢,6¢-H), 5.29 (s,
2H, CH2Obenzyl), 3.91 (s, 6H, 3¢,5¢-CH3O), 3.90 (s, 3H, 4¢-CH3O);
13C NMR (100 MHz, CDCl3, TMS): d 189.24 (CO), 161.2 (C-3),
153.6 (C-3¢/C-5¢), 149.0 (C-1), 138.9 (C-4¢), 135.9 (C-1¢), 136.2,
128.8, 128.3, 127.3 (C-benzyl), 129.0 (C-5), 124.1 (C-4), 120.0 (C-
6), 112.0 (C-2), 104.8 (C-2¢/C-6¢), 70.8 (CH2Obenzyl), 61.0 (4¢-
CH3O), 56.4 (3¢,5¢-CH3O); MS (ESI, m/z): 401 [M + Na+], 779
[2M + Na+]; HRMS (ESI, m/z) Calcd. for C23H22O5Na+ 401.1365,
found 401.1361.
2-Fluoro-3¢,5¢-dimethoxybiphenyl-3,4¢-diol (8a¢)
IR (KBr) nmax/cm-1 3407, 2924, 2852, 2360, 1614, 1216, 1115; 1H
NMR (400 MHz, CDCl3, TMS): d 7.07 (m, 1H, 6-H), 6.99 (m, 2H,
4,5-H), 6.77 (s, 2H, 2¢,6¢-H), 3.93 (s, 6H, 3¢,5¢-CH3O); 13C NMR
(100 MHz, CDCl3, TMS): d 149.5 (C-2), 147.0 (C-3¢/C-5¢), 144.2
(C-3), 134.9 (C-4¢), 129.7 (C-1), 126.5 (C-1¢), 124.4 (C-5), 121.6 (C-
6), 115.8 (C-4), 106.1 (C-2¢/C-6¢), 56.4 (3¢, 5¢-CH3O); MS (ESI,
m/z): 287 [M + Na+], 263 [M - H-]; HRMS (ESI, m/z) Calcd. for
C14H23FO4Na+ 287.0690, found 287.0701.
3¢,5¢-Dimethoxybiphenyl-3,4¢-diol (8b)
IR (KBr) nmax/cm-1 3419, 2924, 2852, 1712, 1613, 1217, 1114; 1H
NMR (400 MHz, CDCl3, TMS): d 7.29 (m, 1H, 5-H), 7.12 (m,
1H, 2-H), 7.02 (m, 1H, 6-H), 6.79 (s, 2H, 2¢,6¢-H), 6.78 (m, 1H, 4-
H), 3.95 (s, 6H, 3¢,5¢-CH3O); 13C NMR (100 MHz, CDCl3, TMS):
d 156.7 (C-3), 147.3 (C-3¢/C-5¢), 143.3 (C-1), 134.7 (C-4¢), 132.4
(C-1¢), 129.9 (C-5), 119.6 (C-6), 114.0 (C-4), 113.8 (C-2), 104.2 (C-
2¢/C-6¢), 56.4 (3¢, 5¢-CH3O); MS (ESI, m/z): 269 [M + Na+], 245
[M - H-]; HRMS (ESI, m/z) Calcd. for C14H14O4Na+ 269.0784,
found 269.0789.
3-Benzyloxy-3¢,4¢,5¢-trimethoxybiphenyl-4-ol (12)
m-CPBA (85%, 8.63 g, 42.50 mmol) was added in portions to a
suspension of 11 (3.22 g, 8.50 mmol) and anhydrous Na2HPO4
(1.57 g, 11.05 mmol) in CH2Cl2 (50 mL) in an ice–water bath
and the mixture was stirred at room temperature for 1 h. The
resulting mixture was refluxed overnight, then cooled and filtered.
The filter cake was washed with CH2Cl2 (3 ¥ 30 mL). Evaporation
of the solvent in vacuo gave a residue that was directly used in
the next reaction. KOH (0.52 g, 9.35 mmol) in H2O (10 mL)
was added to the crude formate in MeOH (20 mL) and stirred
for 2 h at room temperature. The mixture was concentrated and
acidified with hydrochloric acid (5 mL of a 2 M solution). The
aqueous layer was extracted with CHCl3 (3 ¥ 20 mL), washed
with H2O (2 ¥ 20 mL) and brine (20 mL), dried over anhydrous
Na2SO4, and concentrated. The residue was purified by column
chromatography (n-hexane–EtOAc 3:1) to give 12 (2.43 g, 78%) as
a light yellow solid. IR (KBr) nmax/cm-1 3538, 2957, 2937, 2360,
1581, 1498, 1261, 1131, 1003; 1H NMR (400 MHz, CDCl3, TMS):
d 7.36-7.46 (m, 5H, benzyl-H), 6.99 (m, 1H, 2-H), 7.06-7.08 (m,
2H, 5,6-H), 6.65 (s, 2H, 2¢,6¢-H), 5.66 (s, 1H, OH), 5.19 (s, 2H,
CH2Obenzyl), 3.90 (s, 6H, 3¢,5¢-CH3O), 3.87 (s, 3H, 4¢-CH3O);
13C NMR (100 MHz, CDCl3, TMS): d 153.4 (C-3¢/C-5¢), 145.9
(C-3), 145.6 (C-4), 137.2 (C-1), 137.1 (C-4¢), 133.9 (C-1¢), 136.4,
3,4¢-Dihydroxy-3¢,5¢-dimethoxybiphenyl-4-carbaldehyde (8c)
IR (KBr) nmax/cm-1 3451, 2925, 2852, 2359, 1645, 1210, 1107; 1H
NMR (400 MHz, CDCl3, TMS): d 11.12 (s, 1H, CHO), 9.90 (s, 1H,
3-OH), 7.58 (d, 1H, J = 8.0 Hz, 5-H), 7.20 (dd, 1H, J = 8.0 Hz,
1.5 Hz, 6-H), 7.17 (d, 1H, J = 1.5 Hz, 2-H), 6.85 (s, 2H, 2¢,6¢-H),
5.64 (s, 1H, 4¢-OH), 3.96 (s, 6H, 3¢,5¢-CH3O); 13C NMR (100 MHz,
CDCl3, TMS): d 195.8 (CHO), 162.0 (C-3), 150.0 (C-1), 147.5 (C-
3¢/C-5¢), 134.0 (C-4¢), 130.8 (C-1¢), 121.0 (C-4), 119.4 (C-5), 118.5
(C-6), 115.3 (C-2), 104.5 (C-2¢/C-6¢), 56.5 (3¢, 5¢-CH3O); MS (ESI,
m/z): 275 [M + H+], 273 [M - H-]; HRMS (ESI, m/z) Calcd. for
C15H14O5H+ 275.0914, found 275.0908.
8,4¢-Dihydroxy-7,3¢,5¢-trimethoxyflavone (10)
MgI2 (0.60 g, 2.15 mmol) in dry ether (15 mL) was added to a
solution of 9 (0.20 g, 0.54 mmol) in CH2Cl2 (10 mL). The solvent
was removed under reduced pressure and the residual solid was
5088 | Org. Biomol. Chem., 2009, 7, 5084–5090
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