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D. Pajtás et al.
Paper
Synthesis
reached pH 1, the precipitate was collected by filtration, and washed
with H2O (250 mL) to give 7 as yellow crystals; yield: 9.68 g (31.9
mmol, 91%); mp 116–119 °C.
1H NMR (CDCl3): δ = 7.83 (m, 2 H, 2′,6′-H), 7.54 (m, 3 H, 3′,5′-H, 4′-H),
7.48 (d, J = 7.9 Hz, 1 H, 5-H), 7.25 (t, J = 7.9 Hz, 1 H, 6-H), 6.89 (d, J = 7.9
Hz, 1 H, 7-H), 6.77 (s, 1 H, 3-H), 4.45 (s, 1 H, NH), 3.28 (m, 2 H, 1′′H),
1.74 (pent, J = 7.2 Hz, 2 H, 2′′-H), 1.51 (s, J = 7.2 Hz, 2 H, 3′′-H), 1.02 (t,
J = 7.2 Hz, 2 H, 4′′-H).
IR (ATR): 3443, 3063, 2858, 2768, 1948, 1639, 1573, 1472, 1425, 1333,
1226, 1145, 1044, 978, 858, 756, 700, 580 cm–1
.
13C NMR (CDCl3): δ = 178.8 (C-4), 162.4 (C-2), 144.8 (C-8a), 138.1 (C-
8), 132.3 (C-1′), 131.4 (C-4′), 129.2 (C-3′,5′), 126.2 (C-2′,6′), 125.6 (C-
6), 123.8 (C-4a), 112.9 (C-7), 111.7 (C-5), 108.0 (C-3), 43.5 (C-1′′, 31.5
(C-2′′), 20.4 (C-3′′), 13.9 (C-4′′).
1H NMR (CDCl3): δ = 13.61 (s, 1 H, OH), 7.96 (d, J = 15.4 Hz, 1 H, β-H),
7.90 (dd, J = 8.0, 1.1 Hz, 1 H, 5-H), 7.76 (dd, J = 7.8, 0.9 Hz, 1 H, 7-H),
7.65 (m, 3 H, 2,6-H, α-H), 7.45 (m, 3 H, 3,5-H, 4-H), 6.86 (t, J = 7.9 Hz,
1 H, 6-H).
13C NMR (CDCl3): δ = 193.3 (C=O), 160.0 (C-2′), 146.6 (C-β),139.4 (C-
4′), 134.3 (C-1), 131.3 (C-4), 129.1 (C-3,5),128.8 (C-2,6, C-6′), 120.8 (C-
1′), 119.5 (C-α), 119.4 (C-5′), 112.3 (C-3′).
MS: m/z = 293 [M+∙], 250 (100%), 148, 107, 65.
Anal. Calcd for C19H19NO2: C, 77.79; H, 6.53; N, 4.77. Found: C, 77.75;
H, 6.50; N, 4.73.
MS: m/z = 302 [M+∙], 304 [M+∙ + 2], 303 [M + H+∙, 100%], 305 [M + H+∙
2], 287, 285, 227, 225, 200, 198, 165, 145, 143, 131, 119, 103, 92, 77,
63, 51.
+
8-[(4-Methoxyphenyl)amino]flavone (13d)
Eluent: toluene–EtOAc (8:1); yield: 148 mg (65%); mp 170.0–
172.0 °C.
Anal. Calcd for C15H11BrO2: C, 59.43; H, 3.66. Found: C, 59.31; H, 3.56.
IR (ATR): 3424, 3298, 3004, 2951, 2830, 2320, 2062, 1633, 1582, 1509,
1379, 1244, 1042, 896, 826, 770, 687, 546, 508, 453 cm–1
.
8-Bromoflavone (6)
To a solution of 7 (9.68 g, 31.9 mmol) in DMSO (60 mL) was added I2
(650 mg, 2.55 mmol) and the mixture was mildly refluxed for 15 min.
The mixture was poured into 10% aq Na2SO3 (300 mL) and stirred. The
solid product 6 was collected by filtration and recrystallized from
hexane–acetone (5:1); yield: 8.46 g (28.1 mmol, 88%); white solid;
mp 181.0–182.0 °C.
1H NMR (CDCl3): δ = 7.85 (m, 2 H, 2′,6′-H), 7.60 (dd, J = 7.4, 1.8 Hz, 1 H,
5-H), 7.52 (m, 3 H, 3′,5′-H, 4′-H), 7.21 (m, 4 H, 6-H, 7-H, 2′′,6′′-H), 6.94
(d, J = 8.8 Hz, 2 H, 3′′,5′′-H), 6.79 (s, 1 H, 3-H), 6.16 (s, 1 H, NH), 3.83 (s,
3 H, OCH3).
13C NMR (CDCl3): δ = 178.6 (C-4), 162.6 (C-2), 156.7 (C-4′′), 145.5 (C-
8a), 135.9 (C-1′′), 133.8 (C-8), 132.1 (C-1′), 131.5 (C-4′), 129.1 (C-3′,5′),
126.3 (C-2′,6′), 125.2 (C-6), 124.6 (C-2′,6′), 124.4 (C-4a), 116.1 (C-7),
115.0 (C-3′′,5′′), 114.4 (C-5), 108.0 (C-3), 55.6 (OCH3).
IR (ATR): 3444, 3070, 2309, 1959, 1646, 1472, 1370, 1236, 1103, 1068,
1021, 916, 853, 771, 689, 627, 518, 503, 451, 418 cm–1
.
1H NMR (CDCl3): δ = 8.14 (m, 3 H, 5-H, 2′,6′-H), 8.01 (d, J = 7.9 Hz, 1 H,
7-H), 7.62 (m, 3 H, 3′,5′-H, 4′-H), 7.43 (t, J = 7.9 Hz, 1 H, 6-H), 7.15 (s, 1
H, 3-H).
13C NMR (CDCl3): δ = 176.6 (C-4), 162.4 (C-2), 152.0 (C-8a), 137.4 (C-
7), 132.1 (C-4′), 130.7 (C-1′), 129.2 (C-3′,5′), 126.4 (C-5), 126.3 (C-
2′,6′), 124.7 (C-4a), 124.5 (C-6), 111.5 (C-8), 106.9 (C-3).
MS: m/z = 343 [M+∙, 100%], 328, 226, 170, 142, 120, 77.
Anal. Calcd for C22H17NO3: C, 76.95; H, 4.99; N, 4.08. Found: C, 76.85;
H, 4.94; N, 4.03.
8-Morpholinoflavone (13f)
Eluent: toluene–EtOAc (4:1); yield: 96 mg (47%); mp 200.0–202.0 °C.
MS: m/z = 300 [M+∙], 302 [M+∙ + 2, 100%], 274, 272, 200, 198, 172, 170,
137, 135, 119, 102, 82, 63.
IR (ATR): 3433, 3059, 2972, 2846, 2830, 2753, 1638, 1576, 1485, 1447,
1376, 1240, 1113, 983, 855, 775, 749, 689, 629, 532, 501, 458, 438
cm–1
.
Anal. Calcd for C15H9BrO2: C, 59.83; H, 3.01. Found: C, 59.78; H, 2.98.
1H NMR (DMSO-d6): δ = 8.06 (m, 2 H, 2′,6′-H), 7.65 (m, 4 H, 5-H, 3′,5′-
H, 4′-H), 7.41 (m, 2 H, 6-H, 7-H), 7.09 (s, 1 H, 3-H), 3.90 (m, 2 H, 3′′,5′′-
H), 3.17 (m, 2 H, 2′′,6′′-H).
13C NMR (DMSO-d6): δ = 177.5 (C-4), 161.9 (C-2), 149.0 (C-8a), 141.9
(C-8), 131.8 (C-4′), 131.4 (C-1′), 129.3 (C-3′,5′), 126.1 (C-2′,6′), 125.4
(C-6), 124.3 (C-4a), 122.5 (C-7), 117.7 (C-5), 106.7 (C-3), 66.4 (C-
3′′,5′′), 51.4 (C-2′′,6′′).
8-Alkyl-/Arylaminoflavones 13a–f; General Procedure
To a mixture of 8-bromoflavone (6; 200 mg, 0.66 mmol), NaOt-Bu (88
mg, 0.92 mmol), BINAP (32 mg, 0.050 mmol), and amine 12a–f (0.80
mmol) in anhydrous toluene (6 mL) in a dried flask was added
Pd2(dba)3 (30 mg, 0.032 mmol) under N2. The reaction mixture was
stirred and refluxed at 110 °C for 3 h in an oil bath. The crude reaction
mixture was filtered on silica gel eluting with pure acetone. To the fil-
trate was added a small amount of silica gel and the solvent was re-
moved under reduced pressure. The residue was purified by column
chromatography to give the pure cross-coupled product 13a–f as yel-
low solids.
MS: m/z = 307 [M+∙, 100%], 276, 249, 231, 165, 147, 119, 92.
Anal. Calcd for C19H17NO3: C, 74.25; H, 5.58; N, 4.56. Found: C, 74.18;
H, 5.50; N, 4.50.
(3-Bromo-2-hydroxyphenyl)-3-hydroxy-3-phenylprop-2-en-1-
one (15)
Only representative examples are given below, the vast majority of
the characterizations are presented in the Supporting Information.
This compound was obtained as a by-product from the reaction of
amines and 8-bromoflavone (6) in a varying yield of 10–30%; eluent:
toluene–EtOAc (8:1); yellow crystals; mp 136.0–138.5 °C.
8-(Butylamino)flavone (13a)
Eluent: toluene–EtOAc (8:1); yield: 99 mg (51%); mp 91.5–93.5 °C.
IR (ATR): 3442, 3057, 2923, 2852, 1609, 1576, 1479, 1320, 1240, 1178,
IR (ATR): 3444, 3061, 2961, 2931, 2857, 1904, 1815, 1638, 1590, 1483,
1099, 1057, 884, 756, 706, 681, 623 cm–1
.
1452, 1375, 1309, 1212, 1149, 1043, 878, 771, 738, 687, 536, 501 cm–1
.
1H NMR (CDCl3): δ = 15.34 (s, 1 H, β-OH), 12.87 (1 H, s, 2′-OH), 7.94 (d,
J = 7.6 Hz, 2 H, 2,6-H), 7.74 (m, 3 H, 3,5-H, 4-H), 7.50 (m, 2 H, 4′-H, 6′-
H), 6.83 (m, 2 H, 5′-H, α-H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 97–102