688 JOURNAL OF CHEMICAL RESEARCH 2014
for another 4 h. After completion of the reaction, H2O (100 mL) was
added and the mixture was stirred for another 1 h and extracted with
dichloromethane (50 mL×2). The organic layers were combined
and washed sequentially with H2O (100 mL×2), saturated sodium
bicarbonate (100 mL×2) and H2O (100 mL×1). Then the extracts
were dried over anhydrous magnesium sulfate and evaporated in
vacuo to give a solid. The residue was recrystallised from ethanol to
give compound 3 (3.5 g), yield 90%, white crystals, m.p. 81–82 °C
(lit.22 80–81 °C) 1H NMR (500 MHz, DMSO‑d6) (δ, ppm): 2.60 (s, 3H,
COCH3), 3.81 (s, 3H, OCH3), 3.85 (s, 3H, OCH3), 5.92 (s, 1H, ArH),
6.05 (s, 1H, ArH), 14.02 (s, 1H, OH). IR νmax (KBr/cm−1): 3461 (OH),
1619 (C=O).
Method (b2): Compound 4 (2.5 g, 0.015 mol), K2CO3 (1.7 g, 0.01 mol),
and DMC (7.5 mL, 0.09 mol) in DMSO (20 mL) were heated at 120 °C
until TLC showed that compound 4 had disappeared. Then the
mixture was cooled to room temperature and H2O (30 mL) was added.
The reaction mixture was neutralised to pH 3–4 with 10% aqueous
HCl and the precipitate was filtered and recrystallised from methanol
to give compound 3 (2.0 g), yield 69%, white crystals, m.p. 81–82 °C
(lit.22 80–81 °C) 1H NMR (500 MHz, DMSO‑d6) (δ, ppm): 2.60 (s, 3H,
COCH3), 3.81 (s, 3H, OCH3), 3.85 (s, 3H, OCH3), 5.92 (s, 1H, ArH),
6.05 (s, 1H, ArH), 14.02 (s, 1H, OH). IR νmax (KBr/cm−1): 3461 (OH),
1619 (C=O).
1H, ArH), 6.09 (d, 1H, ArH), 3.81 (s, 3H, OCH3), 3.82 (s, 3H, OCH3),
3.86 (s, 3H, OCH3).
4′,5,7-Trihydroxyflavanone (1): Method (e): A mixture of compound
6 (6.28 g, 0.02 mol) and excess pyridine hydrochloride (22.8 g,
0.20 mol) was heated at 180–190 °C for 7 h under an N2 atmosphere.
Then the mixture was cooled to room temperature and ethanol (25 mL)
and H2O (80 mL) were added. The reaction mixture was stirred for
another 10 min. The precipitate was filtered off, washed with ethanol
and recrystallised from ethanol to give compound 1 (4.84 g); yield
1
89%, yellow crystals, m.p. 253–254 °C (lit.26 247–250 °C) H NMR
(500 MHz, DMSO‑d6) (δ, ppm): 12.15 (s, 1H, CH), 10.80 (s, 1H, ArH),
9.60 (s, 1H, ArH), 7.73–7.64 (m, 4H, ArH), 5.87 (s, 2H, OH), 5.48–5.37
(m, 1H, OH), 3.27 (dd, J=17.2, 12.9 Hz, 1H, CH2), 2.66 (dd, J=17.0,
3.0 Hz, 1H, CH2).
Method (b3): A mixture of compound 4 (3.36 g, 0.02 mol) and
4‑hydroxybenzaldehyde (2.7 g, 0.022 mol) was dissolved in ethanol
(20 mL), and 15% aqueous HCl 15 mL was added dropwise. The
solution was vigorously stirred for 72 h at room temperature. The
precipitate was washed with water and the crude product was purified
by a silica‑gel column chromatography with petroleum ether and
EtOAc (8:1) as eluent to give the desired title compound (2.45 g); yield
1
45%, yellow crystals, m.p. 253–254 °C (lit.26 247–250 °C) H NMR
(500 MHz, DMSO‑d6) (δ, ppm): 12.15 (s, 1H, CH), 10.80 (s, 1H, ArH),
9.60 (s, 1H, ArH), 7.73–7.64 (m, 4H, ArH), 5.87 (s, 2H, OH), 5.48–5.37
(m, 1H, OH), 3.27 (dd, J=17.2, 12.9 Hz, 1H, CH2), 2.66 (dd, J=17.0,
3.0 Hz, 1H, CH2).
2,4,6-Trihydroxyacetophenone (4): m‑Trihydroxybenzene (2.5 g,
0.02 mol) and acetic anhydride 4.5 mL (0.045 mol) were dissolved
in ethyl acetate (10 mL), and BF3–Et2O 4 mL (0.032 mol) was added
dropwise. The reaction mixture was heated at 75 °C for 15 h. Then,
H2O (20 mL) was added and the reaction mixture was extracted with
ethyl acetate. After evaporation of the solvent, the crude products were
purified by a silica‑gel column chromatography with petroleum ether
and CH2Cl2 (3:1) as eluent to give the desired compound 4 (2.25 g);
2,5-Dihydroxyacetophenone (7): 1,4‑Dihydroxybenzene (5.5 g,
0.05 mol) and dichloroethane (10 mL) were placed in a dry round‑
bottomed flask, then Ac2O (10 mL, 0.1 mol) was slowly added.
The solution was stirred for 4 h at 100 °C until TLC showed that
1,4‑dihydroxybenzene had disappeared. BF3–Et2O (9 mL, 0.07 mol)
was then added dropwise and the reaction mixture was heated to
120 °C and stirred for another 2–3 h. H2O (40 mL) was then added and
the reaction mixture was extracted with ethyl acetate (50 mL×2). The
combined extracts were washed sequentially with H2O (100 mL×2),
saturated sodium bicarbonate (100 mL×2) and H2O (100 mL×1) and
then dried with anhydrous sodium sulfate overnight. Removal of the
solvent in vacuo to give a solid residue, which was recrystallised from
ethanol to give compound 7 as yellow crystals (7.0 g), yield: 92%, m.p.
195–198 °C (lit.27 197–199 °C) 1H NMR (500 MHz, DMSO‑d6) (δ,
ppm): 2.6 (s, 3H, CH3), 6.9 (s, 1H, OH), 7.2–7.3 (m, 3H, ArH), 11.8 (s,
1H, OH).
1
yield 67%, yellow crystals, m.p. 222–223 °C (lit.23 221 °C) H NMR
(500 MHz, DMSO‑d6): 12.23 (s, 2H, OH), 10.38 (s, 1H, OH), 5.79 (s,
2H, ArH), 2.50 (s, 3H, COCH3). IR νmax (KBr/cm−1): 3201 (OH), 1616
(C=O).
2′-Hydroxy-4,4′,6′-trimethoxychalcone (5): A mixture of compound
3 (0.98 g, 0.005 mol), anisaldehyde (0.85 g, 0.006 mol) and methanol
(35 mL) was placed in a dry round‑bottomed flask. Sodium hydroxide
(4 g, 0.10 mol) was slowly added and the solution was stirred for
approximately 72 h at room temperature. The progress of the reaction
was monitored by TLC. After completion of the reaction, the reaction
mixture was neutralised to pH 3–4 with 10% aqueous HCl. The
precipitate was filtered off, washed with water and recrystallised
from ethanol to give compound 5 (1.3 g) as yellow crystals; yield 83%,
m.p. 114–115 °C (lit.24 113–114 °C) 1H NMR (500 MHz, DMSO‑d6) (δ,
ppm): 14.40 (s, 1H, OH), 7.83–7.77 (m, 2H, ArH), 7.57 (d, J=8.5 Hz,
2H, ArH), 6.93 (d, J=8.5 Hz, 2H, ArH), 6.11 (s, 1H, CH), 5.97 (s, 1H,
CH), 3.82 (s, 3H, OCH3), 3.84 (s, 3H, OCH3), 3.86 (s, 3H, OCH3). IR
νmax (KBr/cm−1): 3648 (OH), 1622 (C=O), 1580 (C=C).
Synthesis of 9A, 9B, 9C; general procedure
Method (c2): A mixture of compound 7 (0.02 mol) and compound 8
(0.022 mol) were dissolved in methanol (20 mL), and 40% aqueous
KOH (100 mL) was added dropwise at approximately 0 °C. The
solution was vigorously stirred for 72 h at room temperature. Then the
reaction mixture was neutralised to pH 5 with 37% aqueous HCl. The
precipitate was filtered off, washed with water and recrystallised from
ethanol to give compound 9.
6-Hydroxyflavanone (9A): White solid (4.3 g), yield: 89%, m.p.
214–215 °C (lit.28 213–214 °C) 1H NMR (500 MHz, DMSO‑d6) (δ,
ppm): 7.49–7.31 (m, 5H, ArH), 7.09–6.51 (m, 3H, ArH), 5.43 (dd, 1H,
CH), 4.96 (s, 1H, OH), 3.07 (dd, 1H, CH2), 2.87 (dd, 1H, CH2).
6-Hydroxy-4′-methoxyflavanone (9B): Light white solid (4.75 g),
yield: 88%, m.p. 142–144 °C (lit.29 138 °C) 1H NMR (500 MHz,
DMSO‑d6) (δ, ppm): 7.42–6.93 (m, 7H, ArH), 5.38 (dd, 1H, CH), 5.18
(s, 1H, OH), 3.84 (s, 3H, CH3), 3.06 (dd, 1H, CH2), 2.86 (dd, 1H, CH2).
6-Hydroxy-3′,4′-dimethoxyflavanone (9C): Light white solid
(5.52 g), yield: 92%, m.p. 284–285.5 °C 1H NMR (500 MHz,
DMSO‑d6) (δ, ppm): 7.33–6.90 (m, 6H, ArH), 5.36 (dd, 1H, CH), 5.02
(s, 1H, OH), 3.93 (d, 6H, CH3), 3.09 (dd, 1H, CH2), 2.87 (dd, 1H, CH2).
4′,5,7-Trimethoxyflavanone (6): Method (d): Compound 5 (2 g,
0.006 mol) and ethanol (10 mL) was placed in a dry round‑bottomed
flask, then 15% aqueous HCl (10 mL) was slowly added and the
solution was stirred for 48 h at room temperature. The precipitate was
filtered off and solvent was removed in vacuo. The crude material
was recrystallised from H2O to give compound 6 (1.37 g); yield
1
73%; almost white crystals, m.p. 122–123 °C (lit.25 124 °C) H NMR
(500 MHz, DMSO‑d6) (δ, ppm): 7.70 (d, 2H, ArH), 7.01 (d, 2H, ArH),
6.14 (s, 1H, CH2), 6.12 (d, 1H, ArH), 6.09 (d, 1H, ArH), 3.81 (s, 3H,
OCH3), 3.82 (s, 3H, OCH3), 3.86 (s, 3H, OCH3).
Method (c2): A mixture of compound 3 (0.02 mol) and anisaldehyde
(0.022 mol) was dissolved in methanol (20 mL), and 40% aqueous
KOH 100 mL was added dropwise at approximately 0 °C. The
solution was vigorously stirred for 72 h at room temperature. Then the
reaction mixture was neutralised to pH 5 with 37% aqueous HCl. The
precipitate was filtered off, washed with water and recrystallised from
ethanol to give compound 6 (5.7 g); yield 91%; almost white crystals,
m.p. 122–123 °C (lit.25 124 °C) 1H NMR (500 MHz, DMSO‑d6) (δ,
ppm): 7.70 (d, 2H, ArH), 7.01 (d, 2H, ArH), 6.14 (s, 1H, CH2), 6.12 (d,
Synthesis of 10B, 10C; general procedure
Method (e): A mixture of compound 9 (0.02 mol) and excess pyridine
hydrochloride (22.8 g, 0.20 mol) was heated at 180–190 °C for 7 h
under a nitrogen atmosphere. Then the mixture was cooled to room
temperature and ethanol (25 mL) and H2O (80 mL) were added. The
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