8
B. Jiang et al.
Arch. Pharm. Chem. Life Sci. 2012, 000, 1–10
56.2, 56.1, 56.0 ꢀ 2, 40.4, 39.7. HRMS for C26H26O679Br281Br2
[MþH]þ: Calcd., 753.8422; found, 753.8416.
General procedure for synthesis of demethylate
compounds
Compounds 22, 24, 26, 28, 31, 33, 35, 38, 40, 44, 47, and 49
(2 mmol) were dissolved in 10 mL dry CH2Cl2, then 8 mL BBr3
(1 mol/L in CH2Cl2) was added dropwise while stirring in ice bath.
The reaction mixture was stirred for a further 4 h at room
temperature. Then the solution was poured into ice-cold water
and extracted with EtOAc (3 ꢀ 60 mL). The organic extract
was dried over anhydrous Na2SO4, and evaporated in vacuo.
The residue was purified by silica gel column chromatography
(CHCl3/MeOH, 15:1) to afford the corresponding demethylate
compounds.
General procedure for synthesis of compounds 44, 46, 47,
and 49
The preparations of compounds 44, 46, 47, and 49 were according
to the general procedure for synthesis of compounds 22, 24, and 26.
2,3-Dibromo-1-(2-(3,4-dimethoxybenzyl)-4,5-dimethoxy-
benzyl)-4,5-dimethoxybenzene 44
Yield 32%, white solid. m.p. 151–1528C. 1H-NMR (500 MHz,
CDCl3) d: 6.76 (s, 1H, ArH), 6.71 (d, J ¼ 7.94 Hz, 1H, ArH), 6.60
(s, 1H, ArH), 6.57 (d, J ¼ 7.94 Hz, 1H, ArH), 6.56 (s, 1H, ArH), 6.22 (s,
1H, ArH), 3.97 (s, 2H, ArCH2Ar), 3.87 (s, 3H, OCH3), 3.82 (s, 3H,
OCH3), 3.81 (s, 3H, OCH3), 3.80 (s, 3H, OCH3), 3.79 (s, 2H, ArCH2Ar),
3.77 (s, 3H, OCH3), 3.56 (s, 3H, OCH3): 13C-NMR (125 MHz, CDCl3)
d: 152.2, 148.4, 147.8, 147.7, 147.3, 146.0, 137.7, 133.0, 131.9,
129.3, 121.6, 120.4, 117.5, 114.1, 114.0, 113.1, 112.0, 111.2,
60.5, 56.1, 56.0, 55.9, 55.8, 55.7, 40.5, 38.5. HRMS for
C20H16O679Br81Br [MþH]þ: Calcd., 596.0232; found, 596.0205.
5-(2-(3-Bromo-4,5-dihydroxybenzyl)-4,5-dihydroxy-
benzyl)-3-bromobenzene-1,2-diol 23
Yield 80%, pale solid. 1H-NMR (500 MHz, DMSO-d6) d: 9.61
(s, 2H, OH ꢀ 2), 8.86 (s, 2H, OH ꢀ 2), 8.65 s, 2H, OH ꢀ 2), 6.58
(s, 2H, ArH ꢀ 2), 6.55 (s, 2H, ArH ꢀ 2), 6.46 (s, 2H, ArH ꢀ 2), 3.55
(s, 4H, ArCH2Ar ꢀ 2); 13C-NMR (125 MHz, DMSO-d6) d: 146.1, 143.4,
140.8, 133.2, 129.2, 122.3, 117.5, 114.5, 109.6, 35.9. HRMS for
C20H16O679Br81Br [MþH]þ: Calcd., 511.9293; found, 511.9253.
2,3-Dibromo-1-(2-(3-bromo-4,5-dimethoxybenzyl)-4,5-
dimethoxybenzyl)-4,5-dimethoxybenzene 46
4-(2-(2-Bromo-4,5-dihydroxybenzyl)-4,5-
Yield 31%, white solid. m.p. 126–1278C. 1H-NMR (500 MHz,
CDCl3) d: 6.77 (s, 1H, ArH), 6.69 (s, 1H, ArH), 6.62 (s, 1H, ArH),
6.50 (s, 1H, ArH), 6.14 (s, 1H, ArH), 3.95 (s, 2H, ArCH2Ar), 3.90 (s,
3H, OCH3), 3.84 (s, 3H, OCH3), 3.79 (s, 2H, ArCH2Ar), 3.78 (s, 3H,
OCH3), 3.75 (s, 3H, OCH3), 3.74 (s, 3H, OCH3), 3.55 (s, 3H, OCH3):
13C-NMR (125 MHz, CDCl3) d: 153.2, 152.2, 147.9, 147.8, 145.9,
144.5, 137.5, 137.3, 130.8, 129.4, 124.1, 121.5, 117.4, 117.3,
114.3 ꢀ 2, 112.8, 112.1, 60.5, 60.4, 56.1 ꢀ 2, 56.0, 55.9, 40.7,
38.6. HRMS for C26H27O679Br281Br [MþH]þ: Calcd., 673.9337;
found, 673.9359.
dihydroxybenzyl)-5-bromobenzene-1,2-diol 25
Yield 88%, brownish solid. 1H-NMR (500 MHz, DMSO-d6) d: 9.16
(s, 2H, OH ꢀ 2), 9.07 (s, 2H, OH ꢀ 2), 8.62 (s, 2H, OH ꢀ 2), 6.91
(s, 2H, ArH ꢀ 2), 6.41 (s, 2H, ArH ꢀ 2), 6.35 (s, 2H, ArH ꢀ 2), 3.58
(s, 4H, ArCH2Ar ꢀ 2): 13C-NMR (125 MHz, DMSO-d6) d: 145.0,
144.7, 143.4, 130.1, 128.4, 118.8, 117.4, 117.0, 111.6, 36.8.
HRMS for C20H16O679Br81Br [MþH]þ: Calcd., 511.9293; found,
511.9254.
5-(2-(2,3-Dibromo-4,5-dihydroxybenzyl)-4,5-dihydroxy-
benzyl)-3,4-dibromobenzene-1,2-diol 27
Bis(2-(2,3-dibromo-4,5-dimethoxybenzyl)-4,5-dimethoxy-
Yield 88%, brownish solid. 1H-NMR (500 MHz, DMSO-d6) d: 9.88
(s, 2H, OH ꢀ 2), 9.38 (s, 2H, OH ꢀ 2), 8.68 (s, 2H, OH ꢀ 2), 6.50 (s,
2H, ArH ꢀ 2), 6.36 (s, 2H, ArH ꢀ 2), 3.68 (s, 4H, ArCH2Ar ꢀ 2):
13C-NMR (125 MHz, DMSO-d6) d: 145.2, 143.6, 142.9, 131.7, 128.1,
117.1, 115.9, 114.9, 113.3, 48.6. HRMS for C20H14O679Br281Br2
[MþH]þ: Calcd., 669.7483; found, 669.7458.
phenyl)methane 47
Yield 30%, white solid. m.p. 161–1628C. 1H-NMR (500 MHz,
CDCl3) d: 6.55 (s, 2H, ArH ꢀ 2), 6.52 (d, 2H, ArH ꢀ 2), 6.34 (s,
2H, ArH ꢀ 2), 3.87 (s, 4H, ArCH2Ar ꢀ 2), 3.79 (s, 12H, OCH3 ꢀ 4),
3.75 (s, 6H, OCH3 ꢀ 2), 3.63 (s, 2H, ArCH2Ar), 3.61 (s, 6H,
OCH3 ꢀ 2): 13C-NMR (125 MHz, CDCl3) d: 152.4, 147.8, 147.6,
146.2, 137.3, 130.9, 129.3, 121.8, 117.7, 113.8, 113.5, 113.1,
60.5, 56.1, 56.0, 40.6, 35.6, 30.8. HRMS for C35H36O879Br281Br2
[MþH]þ: Calcd., 903.9103; found, 903.9070.
4-(2,3-Dibromo-4,5-dihydroxybenzyl)-5-(2-bromo-4,5-
dihydroxybenzyl)benzene-1,2-diol 29
Yield 78%, brownish solid. 1H-NMR (500 MHz, DMSO-d6) d: 9.87
(s, 1H, OH), 9.37 (s, 1H, OH), 9.17 (s, 1H, OH), 9.07 (s, 1H, OH), 8.65
(s, 1H, OH), 8.64 (s, 1H, OH), 6.91 (s, 1H, ArH), 6.48 (s, 1H, ArH), 6.42
(s, 1H, ArH), 6.36 (s, 1H, ArH), 6.35 (s, 1H, ArH), 3.69 (s, 2H,
ArCH2Ar), 3.57 (s, 2H, ArCH2Ar): 13C-NMR (125 MHz, DMSO-d6)
d: 145.1, 145.0, 144.7, 143.5, 143.4, 142.8, 131.8, 129.9, 128.6,
127.9, 118.8, 117.4, 117.1, 117.0, 115.8, 114.9, 113.2, 111.6, 39.4,
36.8. HRMS for C20H15O679Br281Br [MþH]þ: Calcd., 589.8398;
found, 589.8417.
2,3-Dibromo-1-(2-(3-bromo-2-(2,3-dibromo-4,5-
dimethoxybenzyl)-4,5-dimethoxybenzyl)-4,5-
dimethoxybenzyl)-4,5-dimethoxybenzene 49
Yield 46%, white solid. m.p. 102–1038C. 1H-NMR (500 MHz,
CDCl3) d: 6.49 (s, 1H, ArH), 6.48 (s, 1H, ArH), 6.45 (s, 1H, ArH),
6.32 (s, 1H, ArH), 6.15 (s, 1H, ArH), 4.17 (s, 2H, ArCH2Ar), 3.86
(s, 3H, OCH3), 3.81 (s, 3H, OCH3), 3.78 (s, 2H, ArCH2Ar), 3.77 (s, 6H,
OCH3 ꢀ 2), 3.74 (s, 6H, OCH3 ꢀ 2), 3.65 (s, 3H, OCH3), 3.64 (s, 2H,
ArCH2Ar), 3.53 (s, 3H, OCH3): 13C-NMR (125 MHz, CDCl3) d: 152.5,
152.4, 152.2, 147.8, 146.2, 137.0, 136.5, 135.6, 129.9, 129.8,
129.5, 122.8, 121.9, 121.7, 117.7, 117.5, 113.8, 113.7, 113.4,
113.1, 111.8, 60.5 ꢀ 2, 60.4 ꢀ 2, 56.2 ꢀ 2, 56.0 ꢀ 2, 40.7, 40.2,
37.1. HRMS for C35H36O879Br381Br2 [MþH]þ: Calcd., 978.8327;
found, 978.8346.
5-(2-(2,3-Dibromo-4,5-dihydroxybenzyl)-3,6-dibromo-4,5-
dihydroxybenzyl)-3,4-dibromobenzene-1,2-diol 32
Yield 73%, yellowish solid. 1H-NMR (500 MHz, DMSO-d6) d: 9.79
(s, 2H, OH ꢀ 2), 9.71 (s, 2H, OH ꢀ 2), 9.42 (s, 2H, OH ꢀ 2), 6.14
(s, 2H, ArH ꢀ 2), 3.83 (s, 4H, ArCH2Ar ꢀ 2): 13C-NMR (125 MHz,
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