1698
Paolo Bovicelli etal
General procedure for the bromination
of flavanones
6,8-Dibromo-5,7,4¢-trihydroxyflavanone (17)
We used 250 mg (0.92 mmol) naringenin, 204 mg (2 mmol)
NaBr and 1.48 g (1.2 mmol) oxone. After 30 min, a non-crys-
tallizable yellow solid separated. The filtered product
To a 0.01 M solution of the appropriate flavanone and NaBr
(1 equivalent for every bromine atom to be introduced in
the substrate) in a 1:1 mixture of acetone and water, oxone
was added in small portions until consumption of the sub-
strate (usually 1.4 eq.); the course of the reaction was mon-
itored by thin-layer chromatography (TLC) (hexane/EtOAc
1:1). Na2S2O3 was added to reduce the excess of oxone,
until no reaction of a NaI solution occurred. The mixture
was then extracted twice with EtOAc. The organic extracts
were washed with a saturated aqueous NaCl solution, dried
over anhydrous Na2SO4 and the solvent evaporated in
vacuum.
1
(336 mg, 85%) was shown to be pure by NMR analysis. H-
NMR (acetone-d6) d(ppm): 2.95 (1H, dd, J = 12.2, 17.1 Hz),
3.33 (1H, dd, J = 3.4, 17.1 Hz), 5.66 (1H, dd, J = 3.4, 12.7 Hz),
6.91 (2H, d, J=8.8Hz), 7.43 (2H, d, J=8.8Hz), 13.01 (1H, s).
13C-NMR (acetone-d6) d(ppm): 80.6, 90.1, 91.1, 103.8, 116.3,
128.9, 130.0, 158.9, 159.2, 160.1, 160.2, 197.4. Anal. calcd for
C15H10Br2O5: C, 41.89; H, 2.34. Found: C, 41.65; H, 2.15.
Typical procedure for the oxidation of
flavanones to flavones
The appropriate flavanone (0.45 mmol) was dissolved in
DMSO (1 mL) and the solution heated to 100°C. To the warm
solution were added catalytic amounts of I2 (10 mg,
0.05 mmol) and concentrated H2SO4 (1 drop), and the reac-
tion was monitored by TLC (hexane/EtOAc). When the sub-
strate was completely consumed, the mixture was quenched
with ice and a 0.1 M aqueous solution of Na2S2O3 added to
destroy the I2 residue. The mixture was extracted with EtOAc
(3 × 10 mL) and the reunited organic phases washed with a
saturated aqueous NaCl solution (2 × 5 mL). The organic
solution was then dried over anhydrous Na2SO4 and the sol-
vent evaporated under vacuum. Products that did not need
any further chromatographic purification were obtained in
good yields (73% to > 95%, Table 1).
6,8-Dibromo-5-methoxyflavanone (2)
We used 250 mg (1 mmol) 5-methoxyflavanone, 204 mg
(2 mmol) NaBr and 1.85 g (1.5 mmol) oxone, and the reaction
was complete in 30 min. After flash chromatography (hexane/
EtOAc 8:2), 410 mg (90%) of product were obtained as
brown oil. 1H-NMR (CDCl3) d(ppm): 3.02 (1H, d, J = 4.5 Hz),
3.06 (1H, d, J = 11.3 Hz), 3.90 (3H, s), 5.56 (1H, dd, J = 4.5,
11.3 Hz), 7.43 (5H, m), 7.92 (1H, s). 13C-NMR (CDCl3)
d(ppm): 44.9, 61.7, 79.3, 107.4, 110.7, 117.1, 125.8, 128.8,
128.9, 137.7, 137.6, 141.2, 156.7, 158.1, 188.6. Anal. calcd
for C16H12Br2O3: C, 46.64; H, 2.94. Found: C, 46.40; H, 2.82.
6-Bromoflavanone (10)
The product was obtained by the above procedure from fla-
vone in 96% yield. Physical data were in accordance with that
reported in literature (Ramadas & Krupadanam 2004).
Data for compounds 6 (Moon et al 2005), 8 (Shen et al
1993), 9 (Rho et al 2002), 11 (Marder et al 1996) and 13
(Khan & Goswami 2005) were in accordance with that
reported in literature.
8-Bromo-5,7,4¢-trimethoxyflavanone (12)
6,8-Dibromo-5-methoxyflavone (3)
185 mg (0.45 mmol) of 6,8-bromo-5-methoxyflavanone gave
135 mg (73%) of product as a brown oil. H-NMR (CDCl3)
d(ppm): 3.98 (3H, s), 6.81 (1H, s), 7.54–7.57 (3H, m), 7.97–
8.02 (2H, m), 8.11 (1H, s). 13C-NMR (CDCl3) d(ppm): 62.0,
105.7, 107.4, 108.3, 114.6, 129.2, 132.0, 132.7, 139.5, 155.8,
161.9, 176.2. Anal. calcd for C16H10Br2O3: C, 46.86; H, 2.46.
Found: C, 46.50; H, 2.2.
We used 200 mg (0.64 mmol) naringenin trimethyl ether,
144 mg (1.4 mmol) NaBr and 1.23 g (1 mmol) oxone. After
45 min the mixture was extracted as usual and the product
purified by flash chromatography (hexane/EtOAc 8:2) to
yield a yellow–brown oil. 1H-NMR (CDCl3) d(ppm): 2.93
(1H, d, J = 4.0 Hz), 2.99 (1H, d, J = 11.3 Hz), 3.81 (3H, s),
3.94 (3H, s), 3.96 (3H, s), 5.48 (1H, dd, J = 4.0, 11.3 Hz), 6.15
(1H, s), 6.93 (1H, d, J = 8.8 Hz), 7.42 (1H, d, J = 8.8 Hz). 13C-
NMR (CDCl3) d(ppm): 44.9, 55.3, 56.2, 56.4, 78.8, 89.4,
91.7, 106.4, 114.1, 127.3, 130.5, 159.8, 160.1, 161.6, 161.9,
189.1. Anal. calcd for C18H17BrO5: C, 54.98; H, 4.36. Found:
C, 54.65; H, 4.25.
1
6,8-Bromo-5,7,4¢-trihydroxyflavone (18)
300 mg of 17 (0.7 mmol) gave 275 mg (92%) of a yellow
solid that was difficult to manipulate because of its low
Table 1 Oxidation of flavanones to flavones
Substrate
Time (min)
Product
Yield (%)
6-OMe-flavone (1)
6,8-Br-5-OMe-flavanone (2)
Flavanone (5)
Naringenin (7)
6-Br-flavanone (10)
8-Br-5,7,4′-OMe-flavanone (12)
6,8-Br-5,7,4′-OH-flavanone (17)
20
40
15
90
30
50
60
6-OMe-flavone (9)
6,8-Br-5-OMe-flavone (3)
Flavone (6)
Apigenin (8)
6-Br-flavone (11)
8-Br-5,7,4′-OMe-flavone (13)
6,8-Br-5,7,4′-OH-flavone (18)
92
73
95
95
90
90
92