PAPER
Synthesis of Isoflavones from 2 -Hydroxychalcones
2495
Examination of the Protecting Group of the 2′-Hydroxy Group
of the Chalcone 1h
H, J = 8.3 Hz), 7.43 (t, 1 H, J = 7.3 Hz), 6.99 (d, 1 H, J = 8.6 Hz),
3.85 (s, 3 H).
2 -Acetoxychalcone 1h-Ac and 2 -Benzoyloxychalcone 1h-Bz
were prepared from 1h using Ac2O/pyridine and BzCl/K2CO3 in
DMF, respectively. 2 -Methoxymethoxychalcone 1h-MOM was
prepared by an aldol condensation of p-anisaldehyde with 2 -meth-
oxymethoxyacetophenone which was obtained by the reaction of 2 -
hydroxyacetophenone with chloromethyl methyl ether in the pres-
ence of N,N-diisopropylethylamine in CH2Cl2. The HTIB oxidative
rearrangement of 2 -O-protected 1h was conducted in a similar way
as shown above and the product composition was analyzed by
HPLC. Each product was separated by preparative TLC and deter-
mined in the usual way. Results are shown in Table 2.
MS (70 eV): m/z (%) = 252 (M+, 100), 237 (29), 209 (14), 132 (56),
117 (20), 89 (35).
Anal. Calcd for C25H24O6: C, 76.18; H, 4.79. Found: C, 76.09; H,
4.98.
Oxidative Rearrangement of Chalcones 1 into Acetals 2 Using
PSDIB/TsOH; General Procedure
To a stirred suspension of PSDIB (0.38 mmol) and TsOH (0.77
mmol) in CH2Cl2 (4 mL) and MeOH (6 mL), was added chalcone 1
(0.13 mmol) and the reaction mixture was stirred for 24 h at r.t.
Then to the mixture, was added aq NaHCO3 (5% w/v, 2 mL) and the
mixture was allowed to stir for 10 min. The resulting precipitate was
filtered off and the filtrate was extracted with EtOAc, washed with
brine, dried, and evaporated to give a yellow oil containing mainly
the crude acetal. In the optimization study shown in Table 5, the
yields of acetals were estimated by 1H NMR spectroscopy.
Time Dependence of the Reactions on Equivalency of HTIB in
MeOH
To a methanolic solution (3 mL) of 1h-Bz (40 mg, 0.11 mmol) and
naphthalene (3 mg, 0.02 mmol) as an internal standard, was added
a minimum solution of HTIB (53 mg, 0.14 mmol) in MeOH and the
mixture was stirred at r.t. Since HTIB is known to be decomposed
by the action of naphthalene by an electron-transfer mechanism,13
a
Oxidative Rearrangement of 2 -Benzoyloxychalcones 1-Bz into
Isoflavones 3 Using PSDIB/TsOH; General Procedure
slightly excess HTIB was used. An aliquot (0.01 mL) of the mixture
was taken and the composition was analyzed by HPLC after usual
workup of the aliquot. Results are shown in Figure 1. Amount of
HTIB altered and the reactions were followed again by the same
way as above.
To a stirred suspension of PSDIB (0.34 mmol) and TsOH (0.67
mmol) in CH2Cl2 (8 mL) and MeOH (12 mL), was added 2 -benzoy-
loxychalcones 1-Bz (0.11 mmol) and the reaction mixture was
stirred for 24 h at r.t. Then to the mixture, was added aq NaOH (60
mg, 1.5 mmol) containing MeOH and the mixture was filtered. Af-
ter the filtrate was allowed to stir for 24 h, the formation of pale yel-
low crystalline material developed. Filtration and washing with
small amount of MeOH gave 3 as colorless to pale yellow needles.
Examination of Equivalency of TsOH on the DIB-Oxidative Re-
arrangement of 2 -Benzoyloxychalcone 1h-Bz in MeOH
Five sets of the reaction mixture containing 1h-Bz (10 mg, 0.028
mmol), DIB (18 mg, 0.056 mmol, 2 equiv), and naphthalene (1.0
mg, 7.8 10–3 mmol) in MeOH were prepared. Then 5.28 mg (1
equiv), 10.6 mg (2 equiv), 15.8 mg (3 equiv), and 21.1 mg (4 equiv)
of TsOH H2O were added each into four sets of the reaction mixture
and no TsOH H2O was added into one set of the reaction mixture.
An aliquot (0.01 mL) of the mixture was taken at an interval of 1 h
and the product composition was analyzed by HPLC after the usual
workup of the aliquot. No reaction took place without TsOH and the
reactivity was enhanced depending on the amount of TsOH em-
ployed. Results are summarized in Table 3.
Isoflavone 3i
Yield: 11 mg (61%);11 mp 163–165 °C (from MeOH) (Lit.18 mp 164
°C).
1H NMR (CDCl3): = 8.22 (d, 1 H, J = 9.0 Hz), 7.93 (s, 1 H), 7.51
(d, 2 H, J = 8.8 Hz), 7.00 (dd, 1 H, J = 2.2, 8.9 Hz), 6.98 (d, 2 H,
J = 8.8 Hz), 6.86 (d, 1 H, J = 2.2 Hz), 3.92 (s, 3 H), 3.85 (s, 3 H).
MS (70 eV): m/z (%) = 282 (M+, 67), 267 (9.7), 150 (17), 132 (100),
117 (23), 107 (12), 89 (29), 79 (11).
Isoflavone 3j
Yield: 18 mg (77%);11 mp 120–123 °C (from MeOH) (Lit.19 mp
124–126 °C).
Oxidative Rearrangements of Chalcones 1 into Acetals 2; Rep-
resentative Procedure
To a solution of 1b (15 mg, 0.064 mmol) in CH2Cl2 (1 mL)–MeOH
(3 mL), was added a minimum solution of DIB (30 mg, 0.095
mmol) and TsOH (21 mg, 0.13 mmol) in MeOH and the mixture
was stirred for 8 h at r.t. Then an aqueous solution (5%, 1 mL) of
Na2SO3 was added to decompose the unreacted HTIB. The mixture
was extracted with CH2Cl2 and the organic layer was dried
(Na2SO4). Concentration of the extract gave 2 with sufficient purity
1H NMR (CDCl3): = 7.84 (s, 1 H), 7.55 (t, 1 H, J = 8.3 Hz), 7.49
(d, 2 H, J = 8.8 Hz), 7.02 (d, 1 H, J = 8.3 Hz), 6.95 (d, 2 H, J = 8.8
Hz), 6.82 (d, 1 H, J = 8.3 Hz), 3.98 (s, 3 H), 3.84 (s, 3 H).
MS (70 eV): m/z (%) = 282 (M+, 100), 265 (13), 253 (23), 236 (49),
174 (17), 141 (13), 132 (46), 117 (29), 107 (45), 89 (43).
Isoflavone 3k16
Yield: 14 mg (64%);11 mp 242–246 °C (from MeOH).
1H NMR (CDCl3): = 7.86 (s, 1 H), 7.61–7.64 (m, 4 H), 7.27–7.45
(m, 13 H), 7.15-7.21 (m, 4 H), 6.56 (d, 2 H, J = 2.4 Hz), 5.23 (s, 2
H), 5.14 (s, 2 H), 5.07 (s, 2 H), 4.73 (s, 2 H), 3.88 (s, 3 H).
1
(by H NMR) and the pure material was obtained by preparative
TLC, if necessary. Results are shown in Table 4.
One-Pot Synthesis of the Isoflavone 3h
To a methanolic solution (3–4 mL) of 1h-Bz (50 mg, 0.14 mmol),
was added a mixture of DIB (45 mg, 0.14 mmol) and TsOH H2O
(53 mg, 0.28 mmol) in MeOH at r.t. The mixture was allowed to stir
for 2 h. Then, a H2O–MeOH solution [7.0 mL, containing 35 mg
(0.91 mmol) of NaOH]8 of NaOH was added and stirred for 5 h at
r.t. The reaction mixture was extracted with CH2Cl2 and the com-
bined organic layers were dried (Na2SO4). Concentration of the ex-
tract in vacuo gave a brown oil (114.5 mg). The mixture was
subjected to a silica gel flash column chromatography to remove
PhI and to afford 3h as colorless needles; yield: 35 mg ( 100%); mp
138–139 °C (from MeOH) (Lit.17 mp 138–139 °C).
MS (20 eV): m/z (%) = 710 (24), 493 (9.9), 465 (6.2), 379 (6.1), 343
(6.7), 207 (5.0), 181 (8.3), 105 (10), 91 (100), 70 (7.8).
Anal. Calcd for C44H35O7I·H2O: C, 64.40; H, 4.54. Found: C, 64.58;
H, 4.40.
Isoflavone 3l16
Yield: 12 mg (56%);11 mp 147–148 °C (from MeOH).
1H NMR (CDCl3): = 7.82 (s, 1 H), 7.78 (d, 2 H, J = 7.2 Hz), 7.53
(d, 2 H, J = 7.2 Hz), 7.33–7.49 (m, 13 H), 7.04 (d, 2 H, J = 8.8 Hz),
6.75 (s, 1 H), 5.27 (s, 2 H), 5.11 (s, 2 H), 5.07 (s, 2 H).
1H NMR (CDCl3): = 8.32 (dd, 1 H, J = 1.5, 7.9 Hz), 8.00 (s, 1 H),
7.68 (td, 1 H, J = 1.5, 7.8 Hz), 7.52 (d, 2 H, J = 8.6 Hz), 7.48 (d, 1
Synthesis 2002, No. 17, 2490–2496 ISSN 0039-7881 © Thieme Stuttgart · New York