JOURNAL OF CHEMICAL RESEARCH 2014 445
acetate (3:1) as eluent to afford a yellow solid 1.52 g (69%); m.p.
0.30 mmol) in methanol (25 mL). The reaction mixture was stirred
at 65–70 °C, until TLC showed no trace of compound 2. The solvent
was removed under reduced pressure, and the residue was dissolved in
CH2Cl2 and the solution was washed with H2O, dried over MgSO4 and
concentrated to give a crude product which was chromatographed on
silica gel using petroleum ether/ethyl acetate/triethylamine (3:1:0.2)
as eluent to afford a light yellow solid 81 mg (69%); m.p. 148–149 °C;
1H NMR (CDCl3) δ 12.99 (s, 1H, OH‑5), 7.48 (d, J=12.8 Hz, 1H, H‑6′),
7.28 (s, 1H, H‑2′), 6.93 (d, J=8.4 Hz, 1H, H‑5′), 6.60 (1H, s, H‑3), 6.52
(s, 1H, H‑8), 4.01 (s, 3H, OCH3‑4′), 3.93 (s, 3H, OCH3‑3′), 3.91 (s, 3H,
OCH3‑7), 4.12 (s, 2H, CH2), 2.70 (s, 6H, 2NCH3); 13C NMR (CDCl3) δ
181.20, 168.59, 163.08, 160.03, 157.80, 151.63, 148.41, 122.20, 119.34,
110.22, 107.76, 104.21, 103.87, 100.54, 89.54, 56.02, 55.18, 55.15, 48.08,
44.27; MS (EI): m/z 385 [M+]. Anal. calcd for C21H23NO6: C, 65.44; H,
6.02; N, 3.63; found: C, 65.49; H, 6.05; N, 3.59%.
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166–169 °C (lit.17 m.p. 169 °C); H NMR (DMSO‑d6) δ 12.99 (s, 1H,
OH‑5), 7.79 (dd, J=8.2, 2.0 Hz, 1H, H‑6′), 7.65 (s, 1H, H‑2′), 7.20 (d,
J=8.2 Hz, 1H, H‑5′), 7.09 (s, 1H, H‑3), 6.88 (s, 1H, H‑6), 6.44 (s, 1H,
H‑8), 3.96 (s, 3H, OCH3‑4′), 3.94 (s, 3H, OCH3‑3′), 3.92 (s, 3H, OCH3‑
7). MS (EI): m/z 328 [M+]. Anal. calcd for C18H16O6: C, 65.85; H, 4.91;
found: C, 65.92; H, 4.88%.
3′-(N,N-Dimethylaminomethyl)-2′-hydroxy-3,4,4′,6′‑tetramethoxy
chalcone (3): 37% Aqueous formaldehyde solution (13 μL, 0.44 mmol),
concentrated HCl (aq) 5 drops and 33% aqueous dimethylamine
(22 μL, 0.44 mmol) were added to a solution of compound 1 (100 mg,
0.29 mmol) in 2‑propanol (25 mL). The reaction mixture was stirred
at room temperature overnight to give a yellow precipitate which was
filtered off and then chromatographed on silica gel using petroleum
ethyl acetate/methanol (25:1) as eluent to afford light yellow needles
71 mg (61%); m.p. 180–182 °C; 1H NMR (CDCl3) δ 2.30 (s, 6H,
2NCH3), 3.58 (s, 2H, CH2), 3.92 (s, 3H, OCH3‑6′), 3.91 (s, 3H, OCH3‑
4), 3.90 (s, 3H, OCH3‑3), 3.88 (s, 3H, OCH3‑4′), 6.02 (s, 1H, H‑5′), 6.88
(d, J=8.4 Hz, 1H, H‑5), 7.11 (d, J=2.0 Hz, 1H, H‑2), 7.18 (dd, J=8.4,
2.0 Hz, 1H, H‑6), 7.53 (d, J=16 Hz, 1H, H‑β), 7.43 (d, J=15.6 Hz,
1H, H‑α), 14.39 (s, 1H, OH‑2′); MS (EI): m/z 401 [M+]. Anal. calcd
for C22H27NO6: C, 65.82; H, 6.78; N, 3.49; found: C, 65.95; H, 6.81; N,
3.53%.
3′-(N,N-Diethylaminomethyl)-2′-hydroxy-3,4,4′,6′-tetramethoxy
chalcone (4): The same procedure as for 3 was used, 4 was obtained
as a light yellow solid (68%); m.p. 179–182 °C; 1H NMR (CDCl3) δ 1.21
(t, J=6.89 Hz, 6H, 2NCH2CH3), 2.96 (q, J=6.90 Hz, 4H, 2NCH2CH3),
3.92 (s, 3H, OCH3‑6′), 3.90 (s, 3H, OCH3‑4), 3.88 (s, 3H, OCH3‑3),
3.57 (s, 3H, OCH3‑4′), 4.53 (s, 2H, CH2), 6.01 (s, 1H, H‑5′), 6.90 (d,
J=8.4 Hz, 1H, H‑5), 7.13 (d, J=2.4 Hz, 1H, H‑2), 7.23 (dd, J=8.4,
2.0 Hz, 1H, H‑6), 8.10 (d, J=15.6 Hz, 1H, H‑β), 7.89 (d, J=15.6 Hz,
1H, H‑α), 14.41 (s, 1H, OH); MS(EI): m/z 429 [M+]. Anal. calcd for
C24H31NO6: C, 67.11; H, 7.27; N, 3.26; found: C, 67.02; H, 7.21; N,
3.27%.
6-(N,N-Diethylaminomethyl)-5-hydroxy-7,3′,4′-trimethoxy flavone (9):
The same procedure as for 8 was used, 9 was obtained as light
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yellow needles (68%); m.p. 145–146 °C; H NMR (CDCl3) δ 12.98 (s,
1H, OH‑5), 7.52 (d, J=12.8 Hz, 1H, H‑6′), 7.33 (s, 1H, H‑2′), 6.97 (d,
J=8.4 Hz, 1H; H‑5′), 6.59 (s, 1H, H‑3), 6.48 (s, 1H, H‑8), 3.99 (s, 3H,
OCH3‑4′), 3.97 (s, 3H, OCH3‑3′), 3.93 (s, 3H, OCH3‑7), 3.66 (s, 2H,
CH2), 2.63 (q, J=6.90 Hz, 4H, 2NCH2CH3), 1.11 (t, J=14.4 Hz, 6H,
2NCH2CH3); 13C NMR (CDCl3) δ 181.98, 164.11, 163.28, 160.24,
157.06, 152.07, 149.23, 123.84, 119.91, 111.08, 110.43, 108.70, 106.62,
106.07, 89.62, 66.06, 46.82, 43.61, 11.14; MS (EI): m/z 413 [M+]. Anal.
calcd for C23H27NO6: C, 66.81; H, 6.58; N, 3.39; found: C, 66.89; H,
6.61; N, 3.45%.
6-(Pyrrolidin-1-yl)methyl-5-hydroxy-7,3′,4′-trimethoxy flavone (10):
The same procedure as for 8 was used, 10 was obtained as light
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yellow needles (70%); m.p. 192–195 °C; H NMR (CDCl3) δ 12.99 (s,
1H, OH‑5), 7.50 (d, J=8.4 Hz, 1H, H‑6′), 7.36 (s, 1H, H‑2′), 6.92 (d,
J=8.8 Hz, 1H, H‑5′), 6.53 (s, 1H, H‑3), 6.35 (s, 1H, H‑8), 3.91 (s, 3H,
OCH3‑4′), 3.90 (s, 3H, OCH3‑3′), 3.85 (s, 3H, OCH3‑7), 3.89 (s, 2H,
CH2), 2.55–2.57 (m, 4H, H2CNCH2), 1.68–1.71 (m, 4H, H2CCH2); 13C
NMR (CDCl3) δ 182.27, 164.11, 163.64, 160.16, 157.17, 152.21, 149.31,
123.84, 120.06, 111.16, 110.82, 108.76, 106.46, 106.00, 89.69, 56.18,
56.14, 56.12, 54.06, 46.79, 23.48; MS (EI): m/z 411 [M+]. Anal. calcd
for C23H25NO6: C, 67.14; H, 6.12; N, 3.40; found: C, 67.25; H, 6.09; N,
3.42%.
6-(Morpholin-1-yl)methyl-5-hydroxy-7,3′,4′-trimethoxy flavone (11):
The same procedure as for 8 was used, 11 was obtained as a light yellow
solid (73%); m.p. 164–165 °C; 1H NMR (CDCl3) δ 13.10 (s, 1H, OH‑5),
7.53 (d, J=9.6 Hz, 1H, H‑6′), 7.34 (s, 1H, H‑2′), 6.98 (d, J=8.4 Hz, 1H,
H‑5′), 6.60 (s, 1H, H‑3), 6.51 (s, 1H, H‑8), 3.99 (s, 3H, OCH3‑4′), 3.97
(s, 3H, OCH3‑3′), 3.94 (s, 3H, OCH3‑7), 3.68 (s, 2H, CH2), 3.70–3.75
(m, 4H, H2CNCH2), 2.52–2.65 (m, 4H, H2COCH2); 13C NMR (CDCl3)
δ 182.26, 164.30, 163.7, 160.39, 157.19, 152.25, 149.30, 123.73, 120.07,
111.13, 110.71, 108.54, 105.36, 104.91, 89.69, 67.05, 56.13, 53.42, 48.99;
MS (EI): m/z 427 [M+]. Anal. calcd for C23H25NO7: C, 64.63; H, 5.90; N,
3.28; found: C, 64.52; H, 5.89; N, 3.21%.
6-(Piperidin-1-yl)methyl-5-hydroxy-7,3′,4′-trimethoxy flavone (12):
The same procedure as for 8 was used. 11 was obtain as light yellow
solid (75%); m.p. 171–173 °C; 1H NMR (CDCl3) δ 12.99 (s, 1H, OH‑5),
7.54 (d, J=8.8 Hz, 1H, H‑6′), 7.34 (s, 1H, H‑2′), 6.98 (d, J=8.4 Hz, 1H,
H‑5′), 6.60 (s, 1H, H‑3), 6.50 (s, 1H, H‑8), 3.99 (s, 3H, OCH3‑4′), 3.97
(s, 3H, OCH3‑3′), 3.93 (s, 3H, OCH3‑7), 3.67 (s, 2H, CH2), 2.50–2.53
(m, 4H, H2CNCH2), 1.97–1.99 (m, 2H, H2CCH2CH2), 1.46–1.53 (m,
4H, H2CCH2CH2); 13C NMR (CDCl3) δ 182.15, 164.28, 163.50, 160.43,
157.18, 152.17, 149.30, 123.87, 120.02, 111.13, 110.06, 108.72, 105.50,
105.10, 89.63, 56.13, 54.28, 49.55, 25.84, 24.18; MS (EI): m/z 425 [M+].
Anal. calcd for C24H27NO6: C, 67.75; H, 6.40; N, 3.29; found: C, 67.88;
H, 6.42; N, 3.28%.
3′-(Morpholin-1-yl)methyl-2′-hydroxy-3,4,4′,6′-tetramethoxy
chalcone (5): The same procedure as for 3 was used, 5 was obtained
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as a light yellow solid (76%); m.p. 160–163°C; H NMR (CDCl3) δ
2.55–2.58 (m, 4H, H2CNCH2), 3.67 (s, 2H, CH2), 3.70–3.72 (m, 4H,
H2COCH2), 3.93 (s, 3H, OCH3‑6′), 3.91 (s, 3H, OCH3‑4), 3.90 (s, 3H,
OCH3‑3), 3.89 (s, 3H, OCH3‑4′), 6.02 (s, 1H, H‑5′), 6.89 (d, J=8.4 Hz,
1H, H‑5), 7.12 (d, J=1.6 Hz, 1H, H‑2), 7.19 (dd, J=8.4, 2.0 Hz, 1H, H‑6),
7.49 (d, J=15.6 Hz, 1H, H‑β), 7.65 (d, J=15.6 Hz, 1H, H‑α); MS (EI):
m/z 443 [M+]. Anal. calcd for C24H29NO7: C, 65.00; H, 6.59; N, 3.16;
found: C, 65.18; H, 6.56; N, 3.10%.
3′-(Piperidin-1-yl)methyl-2′-hydroxy-3,4,4′,6′-tetramethoxy
chalcone (6): The same procedure as for 3 was used, 6 was obtained
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as a light yellow solid (73%); m.p. 155–157°C; H NMR (CDCl3) δ
1.40–1.51 (m, 6H, H2CCH2CH2), 2.49–2.51 (m, 4H, H2CNCH2), 3.62
(s, 2H, CH2), 3.84 (s, 3H, OCH3‑6′), 3.83 (s, 3H, OCH3‑4), 3.77 (s, 3H,
OCH3‑3), 3.76 (s, 3H, OCH3‑4′), 5.95 (s, 1H, H‑5′), 6.79 (d, J=8.4 Hz,
1H, H‑5), 7.12 (d, J=1.6 Hz, 1H, H‑2), 7.19 (dd, J=8.4, 2.0 Hz, 1H, H‑6),
7.35 (d, J=15.6 Hz, 1H, H‑β), 7.45 (d, J=15.6 Hz, 1H, H‑α); MS (EI):
m/z 441 [M+]. Anal. calcd for C25H31NO6: C, 68.01; H, 7.08; N, 3.17;
found: C, 68.15; H, 7.15; N, 3.20%.
3′-(N-Methylpiperazin-1-yl)methyle-2′-hydroxy-3,4,4′,6′-
tetramethmethoxy chalcone (7): The same procedure as for 3 was used,
7 was obtained as a light yellow solid (62%); m.p. 147–150 °C; 1H NMR
(CDCl3) δ 2.14 (s, 3H, NCH3), 2.32–2.51 (m, 8H, 2NCH2CH2), 3.61 (s,
2H, CH2), 3.85 (s, 3H, OCH3‑6′), 3.83 (s, 3H, OCH3‑4), 3.81 (s, 3H,
OCH3‑3), 3.80 (s, 3H, OCH3‑4′), 6.02 (s, 1H, H‑5′), 6.79 (d, J=8.4 Hz,
1H, H‑5), 7.12 (d, J=1.6 Hz, 1H, H‑2), 7.16 (dd, J=8.4, 2.0 Hz, 1H, H‑6),
7.37 (d, J=15.6 Hz, 1H, H-α), 7.41 (d, J=15.6 Hz, 1H, H‑β); MS (EI):
m/z 456 [M+]. Anal. calcd for C25H32N2O6: C, 65.77; H, 7.07; N, 6.14;
found: C, 65.68; H, 7.06; N, 6.11%.
6-(N-Methylpiperazin-1-yl)methyl-5-hydroxy-7,3′,4′-trimethoxy
flavone (13): The same procedure as for 8 was used, 11 was obtained
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6-(N,N-Dimethylaminomethyl)-5-hydroxy-7,3′,4′-trimethoxy
flavone (8): 37% Aqueous formaldehyde solution (13 μL, 0.45 mmol),
concentrated HCl (aq) five drops and 33% aqueous dimethylamine
(23 μL, 0.45 mmol) were added to a solution of compound 2 (100 mg,
as light yellow needles (72%); m.p. 192–193 °C; H NMR (CDCl3) δ
13.03 (s, 1H, OH‑5), 7.45 (d, J=8.4 Hz, 1H, H‑6′), 7.26 (s, 1H, H‑2′),
6.90 (d, J=8.4 Hz, 1H, H‑5′), 6.52 (s, 1H, H‑3), 6.41 (s, 1H, H‑8), 3.92
(s, 3H, OCH3‑4′), 3.90 (s, 3H, OCH3‑3′), 3.85 (s, 3H, OCH3‑7), 3.63 (s,
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