452
Y. Akbaba et al.
Arch. Pharm. Chem. Life Sci. 2013, 346, 447–454
The organic phase was washed with solutions of NaHCO3
(5%, 2 ꢁ 40 mL), H2O (2 ꢁ 40 mL), and brine (40 mL), then dried
over Na2SO4. Evaporation of the solvent afforded 15 (0.090 g,
16% yield), 16 (0.054 g, 8% yield) and (2-bromo-4,5-dimethoxy-
phenyl)(4,5-dimethoxy-2-methylphenyl)methanone (17) (0.213 g,
38% yield).
114.08 (CH), 113.64 (C), 19.43 (CH3). Anal. calcd. for C14H11O5Br: C
49.58, H 3.27; found: C 49.56, H 3.27.
(3-Bromo-4,5-dihydroxy-2-methylphenyl)(2-bromo-4,5-
dihydroxyphenyl)methanone (20)
O-Demethylation of 16 (0.50 g, 1.05 mmol) with BBr3 gave 20
(0.41 g, 94% yield). Solidified. Yellow solid. Mp 183–1858C. IR
(acetone, cmꢂ1): 3339, 1698, 1640, 1590, 1501, 1419, 1361,
1283, 1097. 1H NMR (400 MHz, acetone-d6): d 8.87 (bs, OH,
1H),8.71 (bs, OH, 1H), 8.60 (bs, OH,1H), 8.54 (bs, OH, 1H), 7.10
(s, 1H), 6.94 (s, 1H), 6.82 (s, 1H), 2.45 (s, CH3, 3H). 13C NMR
(100 MHz, acetone-d6): d 195.07 (CO), 148.64 (C), 146.26 (C),
144.65 (C), 142.44 (C), 132.91 (C), 130.87 (C), 120.16 (CH),
117.78 (CH), 116.90 (CH), 116.82 (C), 114.65 (C), 110.00 (C),
19.43 (CH3). Anal. calcd. for C14H10O5Br2: C 40.22, H 2.41; found
C 40.34, H 2.54.
(2-Bromo-4,5-dimethoxyphenyl)(4,5-dimethoxy-2-
methylphenyl)methanone (17)
Recrystallized from EtOAc/hexane. Yellow crystals. Mp 152–
1538C. IR (CH2Cl2, cmꢂ1): 3058, 3003, 2961, 2936, 2844, 1656,
1596, 1567, 1518, 1505, 1464, 1441, 1375, 1344, 1263, 1207,
1162, 1112, 1040, 1028, 1008. 1H NMR (200 MHz, CDCl3):
d 7.03 (s, 1H), 6.92 (s, 1H), 6.90 (s, 1H), 6.72 (s, 1H), 3.91
(s, OCH3, 3H), 3.90 (s, OCH3, 3H), 3.82 (s, OCH3, 3H), 3.72
(s, OCH3, 3H), 2.43 (CH3, 3H). 13C NMR (50 MHz, CDCl3):
d 197.94 (CO), 154.04 (C), 153.08 (C), 150.33 (C), 148.43 (C),
136.26 (CH), 135.87 (C), 131.04 (C), 118.08 (CH), 117.07 (C),
116.48 (CH), 114.90 (CH), 113.62 (C), 58.27 (OCH3), 58.20
(2 OCH3), 57.92 (OCH3), 22.90 (CH3). Anal. calcd. for C18H19O5Br:
C 54.70, H 4.85; found: C 54.68, H 4.81.
(2-Bromo-4,5-dihydroxyphenyl)(4,5-dihydroxy-2-
methylphenyl)methanone (21)
Demethylation reaction of 17 (0.41 g, 1.04 mmol) with BBr3
afforded bromophenol 21 (0.33 g, 94% yield). Solidified.
Brownish solid. Mp 221–2238C. IR (acetone, cmꢂ1): 3426, 2974,
1631, 1591, 1513, 1497, 1454, 1418, 1366, 1287, 1214, 1183,
1155. 1H NMR (400 MHz, acetone-d6): d 8.76 (bs, 1H, OH), d 8.52
(bs, 2H, OH), d 8.06 (bs, 1H, OH), d 7.09 (s, 1H), 6.86 (s, 1H), 6.84 (s,
1H), 6.78 (s, 1H), 2.40 (CH3, 3H). 13C NMR (100 MHz, acetone-d6): d
195.36 (CO), 149.08 (C), 147.78 (C), 144.65 (C), 142.23 (C), 134.13
(CH), 133.13 (CH), 128.65 (C), 119.74 (CH), 119.68 (CH), 118.86 (C),
116.73 (CH), 109.09 (C), 20.27 (CH3). Anal. calcd. for C14H11O5Br: C
49.58, H 3.27; found: C 49.58, H 3.29.
Synthesis of (4,5-dihydroxy-2-methylphenyl)(3,4-
dihydroxyphenyl)methanone (18)
General procedure for O-demethylation of arylmethyl ethers: To
a stirred solution of diarylmethanone 14 (0.40 g, 1.01 mmol)
in CH2Cl2 (10 mL) at 08C was added a solution of BBr3
(0.65 mL) in CH2Cl2 (7 mL) dropwise under N2(g) for 5–10 min.
The reaction mixture was stirred at the same temperature for 2 h
and then at room temperature for 1 day under N2. The reaction
was monitored by TLC and after completion, methanol (40 mL)
was slowly added for 15 min to the mixture at 08C. The solvent
was evaporated, water (45 mL) and EtOAc (50 mL) were added to
the residue. The organic layer was separated and the water phase
was extracted with EtOAc (2 ꢁ 30 mL). The combined organic
layers were dried over Na2SO4 and the solvent was evaporated. An
oily (4,5-dihydroxy-2-methylphenyl)(3,4-dihydroxyphenyl)metha-
none (18) was obtained (0.24 g, 91% yield). IR (acetone, cmꢂ1):
3247, 2975, 2930, 1695, 1633, 1587, 1518, 1441, 1354, 1293,
1217, 1192, 1155, 1119, 1080, 971. 1H NMR (400 MHz, acetone-
d6): d 8.37 (bs, 4H, OH), 7.31 (s, 1H), 7.30 (d, J ¼ 2.2 Hz, 1H), 7.17
(dd, J ¼ 8.2, 2.2 Hz, 1H), 6.90 (d, J ¼ 8.2 Hz, 1H), 6.81 (s, 1H), 6.76
(s, 1H), 2.09 (s, 3H). 13C NMR (100 MHz, acetone-d6): d 195.61 (CO),
150.10 (C), 146.95 (C), 144.92 (C), 142.06 (C), 131.17 (C), 130.75 (C),
129.26 (C), 123.89 (CH), 117.88 (CH), 116.75 (CH), 116.58 (CH),
114.91 (CH), 18.82 (CH3). Anal. calcd. for C14H12O5: C 64.61, H
4.65; found: C 64.60, H 4.64.
X-ray diffraction analysis
For the crystal structure determination, the single-crystal of the
complex [Ru(Ph2PNHCH2-C4H3S)(h6-benzene)Cl2] was used for
data collection on a four-circle Rigaku R-AXIS RAPID-S diffrac-
tometer (equipped with a two-dimensional area IP detector). The
˚
graphite-monochromatized Mo Ka radiation (l ¼ 0.71073 A) and
oscillation scans technique with Dv ¼ 58 for one image were
used for data collection. The lattice parameters were determined
by the least-squares methods on the basis of all reflections with
F2 > 2s(F2). H atoms were positioned geometrically and refined
using a riding model. Integration of the intensities, correction
for Lorentz and polarization effects and cell refinement was
performed using CrystalClear (Rigaku/MSC Inc., 2005) software
[35]. The structures were solved by direct methods using SHELXS-
97 and refined by a full-matrix least-squares procedure using the
program SHELXL-97 [36]. The final difference Fourier maps
showed no peaks of chemical significance. Crystal data for mono-
bromide 15: C18H19O5Br, crystal system, space group: mono-
clinic, P21/c; (no:14); unit cell dimensions: a ¼ 12.2185(2),
(3-Bromo-4,5-dihydroxy-2-methylphenyl)(3,4-
dihydroxyphenyl)methanone (19)
˚
The procedure described for 18 was applied to 15 (0.41 g,
1.04 mmol) to give bromopehol 19 (0.32 g, 91%). Solidified.
Yellow solid. Mp 208–2108C. IR (acetone, cmꢂ1): 3386, 3254,
2974, 1628, 1587, 1518, 1480, 1421, 1359, 1294, 1217, 1117,
1077, 1029. 1H NMR (400 MHz, acetone-d6): d 8.74 (bs,2H, OH),
d 8.41 (bs, 1H, OH), d 8.32 (bs, 1H, OH), d 7.31 (d, J ¼ 2.2 Hz, 1H), d
7.18 (dd, J ¼ 8.3 Hz, J ¼ 2.2 Hz, 1H), d 6.91 (d, J ¼ 8.3 Hz, 1H),
6.79 (s, 1H), 2.20 (CH3, 3H). 13C NMR (100 MHz, acetone-d6): d
195.09 (CO), 150.68 (C), 145.11 (C), 144.54 (C), 142.68 (C), 132.17
(C), 130.48 (C), 127.51 (C), 124.15 (CH), 116.64 (CH), 115.14 (CH),
b ¼ 7.3752(1), c ¼ 20.2548(4) A, b ¼ 105.93(2)8; volume:
3
3
˚
1755.17(5) A ; Z ¼ 4; calculated density: 1.496 g/cm ; absorption
coefficient: 2.366 mmꢂ1; F(000): 808; u-range for data collection
2.3–30.678; refinement method: full-matrix least-square on F2;
data/parameters: 3229/218; goodness-of-fit on F2: 1.391; final R
indices [I > 2s(I)]: R1 ¼ 0.0853, wR2 ¼ 0.1457; largest diff. peak
and hole: 0.341 and ꢂ0.418 e Aꢂ3; CCDC-873395. Crystal data for
˚
dibromide 16: C18H18Br2O5, crystal system, space group: triclinic,
P-1; (no:2); unit cell dimensions: a ¼ 8.8103(2), b ¼ 9.9903(3),
˚
c ¼ 11.5582(5) A, a ¼ 86.13(3), b ¼ 87.44(3), g ¼ 68.88(2)8;
ß 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.archpharm.com