PAPER
Synthesis of Neoflavonoid Antioxidants Based on Montmorillonite K-10 Catalysis
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crude product was subjected to column chromatography (silica,
Et2O–CH2Cl2, 1:1) to give 4 (2.4 g, 84%) as a light brown solid; mp
259–260 °C (lit.24 mp 256–258 °C).
J = 2.4 Hz, 1 H), 6.25 (d, J = 2.4 Hz, 1 H), 6.72 (d, J = 8.5 Hz, 2
H), 6.96 (d, J = 8.5 Hz, 2 H), 8.19 (s, OH, 1 H), 8.53 (s, OH, 1 H),
8.67 (s, OH, 1 H).
1H NMR [(CD3)2CO–DMSO]: = 4.03 (s, 3 H), 5.84 (s, 1 H), 6.48
(s, OH, 2 H). 6.49 (d, J = 2.3 Hz, 2 H), 7.13 (d, J = 8.7 Hz, 2 H),
7.50 (d, J = 8.7 Hz, 2 H).
13C NMR [(CD3)2CO]: = 33.3, 37.0, 95.0, 98.4, 104.1, 115.0,
127.5, 132.9, 153.3, 155.0, 155.9, 157.7, 167.0.
5,7-Dihydroxy-4-(4-methoxyphenyl)-chroman-2-one (8)
To a mixture of 4-methoxycinnamic acid (2.5 g, 14.0 mmol) in
CH2Cl2 (50 mL) was introduced SOCl2 (1.2 mL, 1.2 equiv) into the
solution dropwise at r.t. and the reaction mixture was refluxed for 2
h. The resulting solution was cooled, followed by removal of the
solvent in vacuo. To the solid was added phloroglucinol (2.6 g, 16.0
mmol), K-10 (5.0 g) in nitrobenzene (20 mL, anhyd) and the solu-
tion was stirred at r.t. for 12 h. The resulting mixture was filtered
and the filtrate was concentrated in vacuo. The crude product was
subjected to column chromatography (silica, Et2O–CH2Cl2, 1:1) to
give 8 (3.6 g, 89%) as a white solid; mp 150–151 °C (lit.13 mp 147–
148 °C).
5,7-Dihydroxy-4-(3,4-dihydroxyphenyl)-chroman-2-one (5)
A mixture of 3,4-dihydroxycinnamic acid (1.5 g, 8.3 mmol) and
SOCl2 (1.0 mL, 1.6 equiv) in dioxane (30 mL, anhyd) was heated to
reflux for 2 h followed by removal of the solvent in vacuo. To the
residue was added phloroglucinol (1.2 g, 9.5 mmol), K-10 (5.0 g) in
nitrobenzene (15 mL, anhyd) at r.t. and the solution was stirred 12
h. The suspension was directly filtered and the solvent was removed
in vacuo. The residue was subjected to column chromatography
(silica, EtOAc–Et2O–CH2Cl2, 1:1:1) to obtain the crude product,
which was recrystallized with EtOAc–hexane to afford 5 (2.2 g,
90%) as white solid; mp 74–75 °C.
1H NMR [(CD3)2CO]: = 2.84 (dd, J = 15.7, 2.0 Hz, 1 H), 3.05 (dd,
J = 15.7, 6.6 Hz, 1 H), 4.43 (dd, J = 6.6, 2.0 Hz, 1 H), 6.11 (d,
J = 2.3 Hz, 1 H), 6.25 (d, J = 2.3 Hz, 1 H), 6.48 (dd, J = 8.1, 2.3 Hz,
1 H), 6.58 (d, J = 2.3 Hz, 1 H), 6.69 (d, J = 8.1 Hz, 1 H), 7.78 (s,
OH, 1 H), 7.83 (s, OH, 1 H), 8.63 (s, OH, 1H), 8.77 (s, OH, 1 H).
1H NMR [(CD3)2CO]: = 2.87 (dd, J = 15.7, 1.9 Hz, 1 H), 3.10 (dd,
J = 15.7, 6.7 Hz, 1 H), 3.72 (s, 3 H), 4.53 (dd, J = 6.7, 1.9 Hz, 1 H),
6.12 (d, J = 2.2 Hz, 1 H), 6.23 (d, J = 2.2 Hz, 1 H), 6.80 (d, J = 8.8
Hz, 2 H), 7.04 (d, J = 8.8 Hz, 2 H), 8.57 (s, OH, 1 H), 8.71 (s, OH,
1 H).
13C NMR [(CD3)2CO]: = 35.0, 38.6, 96.5, 100.0, 105.7, 115.2,
116.5, 119.4, 135.4, 145.1, 146.3, 154.8, 156.7, 159.2, 168.6.
13C NMR [(CD3)2CO]: = 32.3, 36.0, 64.0, 94.1, 97.6, 103.0, 112.6,
126.5, 133.0, 152.3, 154.0, 156.7, 157.3, 166.2.
HPLC: Rt = 10.59 min (100%).
9-Hydroxy-4,8-(4-methoxyphenyl)-dichroman-2,6-dione (9)
To a solution of 4-methoxycinnamic acid (1.0 g, 5.6 mmol) in
CH2Cl2 (50 mL) was introduced SOCl2 (0.5 mL, 1.2 equiv) into the
solution dropwise at r.t. and the reaction mixture was refluxed for 2
h. The resulting solution was cooled, followed by removal of the
solvent in vacuo. To the residue was added 8 (1.6 g, 5.6 mmol), K-
10 (3.0 g) in nitrobenzene (15 mL, anhyd) and the solution was
stirred at r.t. for 12 h. The resulting suspension was filtered and the
filtrate was concentrated in vacuo. The crude product was subjected
to column chromatography (silica, EtOAc–Et2O–CH2Cl2, 1:1:1) to
afford 9 (1.9 g, 77%) as pale yellow solid; mp 265–266 °C.
1H NMR [(CD3)2CO]: = 3.06–3.29 (m, 4 H), 3.72 (s, 3 H), 3.73 (s,
3 H), 4.65 (d, J = 5.2 Hz, 1 H), 4.67 (d, J = 5.3 Hz, 1 H), 6.52 (s, 1
H), 6.83 (d, J = 8.6 Hz, 4 H), 7.06 (d, J = 8.6 Hz, 2 H), 7.12 (d,
J = 8.6 Hz, 2 H), 9.46 (s, 1 H).
13C NMR [(CD3)2CO]: = 33.3, 33.4, 36.3, 36.5, 54.2, 54.2, 99.0,
105.1, 109.2, 113.6, 113.8, 127.3, 127.5, 133.2, 149.3, 151.8,154.1,
158.4, 165.9, 166.3.
HRMS (m/z): calcd for C15H12O6, 288.0634; found, 288.0625.
5,7-Dihydroxy-4-(3,4-dimethoxyphenyl)-chroman-2-one (6)
To a solution of 3,4-dimethoxycinnamic acid (3.0 g, 14.4 mmol) in
CH2Cl2 (50 mL) was added SOCl2 (1.4 mL, 1.3 equiv) dropwise at
r.t. and the solution was refluxed for 2 h. The solvent was removed
and to the residue was added phloroglucinol (2.6 g, 15.9 mmol), K-
10 (5.0 g) in nitrobenzene (25 mL, anhyd) at r.t. and the solution
was stirred for 12 h. The suspension was directly filtered and the
solvent was removed in vacuo. The solid was subjected to column
chromatography (silica, Et2O–CH2Cl2, 1:1) to provide the crude
product, which was recrystallized with CH2Cl2–hexane to obtain 6
(4.2 g, 92%) as a white solid; mp 183–184 °C.
1H NMR [(CD3)2CO]: = 2.86 (dd, J = 15.7, 2.0 Hz, 1 H), 3.04 (dd,
J = 15.7, 6.6 Hz, 1 H), 3.73 (s, 6 H), 4.44 (dd, J = 6.6, 2.0 Hz, 1 H),
6.15 (d, J = 2.2 Hz, 1H), 6.18 (d, J = 2.2 Hz, 1 H), 6.47 (dd, J = 8.3,
2.0 Hz, 1 H), 6.77 (d, J = 2.0 Hz, 1 H), 6.78 (d, J = 8.3 Hz, 1 H),
7.16 (s, OH, 1 H), 7.28 (s, OH, 1 H).
HPLC: Rt = 2.27 min (96%), 3.19 min (3%).
13C NMR [(CD3)2CO–CDCl3]: = 33.6, 36.9, 55.0, 55.2, 95.6, 99.0,
103.8, 110.1, 111.0, 118.2, 134.1, 147.5, 148.6, 152.7, 154.5, 157.1,
168.2.
HRMS (m/z): calcd for C26H22O7, 446.1366; found, 446.1361.
5,7-Dihydroxy-4-(3,4-dimethoxyphenyl)-3-bromochroman-2-
one (13)
HPLC: Rt = 2.19 min (94%), 3.17 min (5%).
To a mixture of the known21 bromocinnamic acid 12 (1.0 g, 3.5
mmol) in CHCl3 (50 mL) was added SOCl2 (0.4 mL, 1.6 equiv)
dropwise at r.t. and then the solution was refluxed for 2 h. The sol-
vent was removed and to the residue was added phloroglucinol (0.6
g, 3.7 mmol), K-10 (3.0 g) in nitrobenzene (20 mL, anhyd) and the
solution was stirred at r.t. for 12 h. The suspension was directly fil-
tered and the solvent was removed in vacuo. The residue was sub-
jected to column chromatography (silica, Et2O–CH2Cl2, 1:1) to
obtain 13 (1.2 g, 87%) as a white solid; mp 129–130 °C.
HRMS (m/z): calcd for C17 H16O6, 316.0947; found, 316.0950.
5,7-Dihydroxy-4-(4-hydroxyphenyl)-chroman-2-one (7)
A mixture of 4-hydroxycinnamic acid (1.5 g, 9.1 mmol) and SOCl2
(1.1 mL, 1.6 equiv) in dioxane (20 mL, anhyd) was refluxed for 3 h,
followed by removal of the solvent in vacuo. To the residue was
added phloroglucinol (1.7 g, 10.5 mmol), K-10 (3.0 g) in nitroben-
zene (20 mL, anhyd) at r.t. and the solution was stirred for 12 h. The
suspension was directly filtered and the solvent was removed in
vacuo. The residue was subjected to column chromatography (silica
EtOAc–Et2O–CH2Cl2, 1:1:1) to obtain the crude product, which
was recrystallized with CH2Cl2–hexane to afford 7 (2.1 g, 85%) as
pale yellow solid; mp 275–276 °C (lit.13 mp 270 °C).
1H NMR [(CD3)2CO]: = 3.71 (s, 3 H), 3.74 (s, 3 H), 4.73 (d,
J = 2.2 Hz, 1 H), 4.88 (d, J = 2.2 Hz, 1 H), 6.22 (d, J = 2.2 Hz, 1
H), 6.34 (d, J = 2.2 Hz, 1 H), 6.51 (dd, J = 8.3, 2.1 Hz, 1 H), 6.80
(d, J = 8.3 Hz, 1 H), 6.99 (d, J = 2.1 Hz, 1 H), 8.76 (s, 1 H), 8.91 (s,
1 H).
1H NMR [(CD3)2CO]: = 2.78 (dd, J = 15.8, 2.0 Hz, 1 H), 3.23 (dd,
J = 15.8, 6.9 Hz, 1 H), 4.50 (dd, J = 6.9, 2.0 Hz, 1 H), 6.11 (d,
Synthesis 2001, No. 15, 2247–2254 ISSN 0039-7881 © Thieme Stuttgart · New York