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Y. C¸ etinkaya et al.
Arch. Pharm. Chem. Life Sci. 2012, 345, 323–334
water (2 ꢆ 20 mL), and brine (20 mL). Then it was dried over
Na2SO4 and the solvents were evaporated. The residue was sub-
jected to column chromatography on silica gel (SiO2, 110 g) and
eluted using EtOAc/hexane (1:9) to give dibromide 12 (47 mg,
5%), monobromide 10 (299 mg, 38%) and monobromide 11
(409 mg, 52%), respectively.
obtained maximum reducing power in three different
assays.
Experimental section
General information
1-Bromo-5-(3,4-dimethoxybenzyl)-2,3,4-
All chemicals and solvents are commercially available and were
used after distillation or treatment with drying agents. Melting
points were determined on a capillary melting apparatus (BUCHI
530) and are uncorrected. IR spectra were obtained from
solutions in 0.1 mm cells with a Perkin-Elmer spectropho-
tometer. The 1H- and 13C-NMR spectra were recorded on a 200
(50) and 400 (100)-MHz Varian spectrometer; d in ppm, Me4Si as
the internal standard. Elemental analyses were performed on a
Leco CHNS-932 apparatus. All column chromatography was per-
formed on silica gel (60-mesh, Merck). PLC is preparative thick-
layer chromatography: 1 mm of silica gel 60 PF (Merck) on glass
plates.
trimethoxybenzene (10)
Liquid as pale yellow. 1H-NMR (400 MHz, CDCl3) d (ppm): 7.00
(bs, aromatic, 1H), 6.79 (d, A part of AB-system, J ¼ 8.1 Hz, aromatic,
1H), 6.73 (s, aromatic, 1H), 6.71 (dd, B part of AB-system, J ¼ 8.2,
1.83 Hz, aromatic, 1H), 3.91 (s, OCH3, 3H), 3.87 (s, OCH3, 3H), 3.85
(s, OCH3, 6H), 3.83 (s, CH2, 2H), 3.76 (s, OCH3, 3H). 13C-NMR
(100 MHz, CDCl3) d 151.55 (C), 149.91 (C), 149.14 (C), 147.73
(C), 133.04 (C), 132.20 (C), 127.93 (CH), 127.59 (C), 121.06 (CH),
112.52 (CH), 111.51 (CH), 111.47 (C), 61.19 (OCH3), 61.15 (OCH3),
61.04 (OCH3), 56.12 (OCH3), 56.10 (OCH3), 35.44 (-CH2–).
IR (CH2Cl2, cmꢁ1) 2928, 2850, 1590, 1513, 1460, 1418, 1403,
1292, 1236, 1139, 1082, 1037, 1006, 962. Anal. Calcd. for
(C18H21BrO5): C 54.42; H 5.33 Found C 54.47; H 5.34.
The compounds 6–8 were synthesized according to [36].
Synthesis of 1-(3,4-dimethoxybenzyl)-2,3,4-
trimethoxybenzene (9)
1-(2-Bromo-4,5-dimethoxybenzyl)-2,3,4-
trimethoxybenzene (11)
To
a
solution of the ketone
6
(2.1 g, 6.3 mmol) in
Amorphous as pale yellow. Mp 75–778C. 1H-NMR (400 MHz,
CDCl3) d (ppm): 7.03 (s, aromatic, 1H), 6.68 (d, A part of
AB-system, J ¼ 8.6 Hz, aromatic, 1H), 6.63 (s, aromatic, 1H),
6.58 (d, B part of AB-system, J ¼ 8.6 Hz, aromatic, 1H), 3.97
(s, CH2, 2H), 3.87 (s, OCH3, 3H), 3.85 (s, OCH3, 3H), 3.832
(s, OCH3, 3H), 3.828 (s, OCH3, 3H), 3.75 (s, OCH3, 3H).
13C-NMR (100 MHz, CDCl3) d 152.62 (C), 152.04 (C), 148.58 (C),
148.15 (C), 132.56 (C), 126.19 (C), 124.31 (CH), 115.67 (CH), 114.71
(C), 113.86 (CH), 113.77 (C), 107.34 (CH), 60.97 (OCH3), 60.95
(OCH3), 56.36, (OCH3), 56.15 (2 OCH3), 35.44 (CH2). IR (CH2Cl2,
cmꢁ1) 3072, 3008, 2937, 2834, 2602, 2021, 1723, 1601, 1510,
1491, 1467, 1443, 1428, 1415, 1385, 1343, 1329, 1257, 1228,
1200, 1193, 1170, 1095, 1036, 972, 937, 905. Anal. Calcd. for
(C18H21BrO5): C 54.42; H 5.33 Found C 54.50; H 5.36.
OHCH2CH2OH (4.0 mL) were added KOH (227 mg, 5.9 mmol)
and hydrazine hydrate (0.6 mL, 619 mg, 12 mmol), consecu-
tively, at RT and under N2(g). After the mixture was heated to
1108C and stirred at this temperature for 1 h, it was stirred at
1908C for 3 d. The mixture was cooled to RT, acidified with HCl
(10%), and extracted with ethyl acetate (EtOAc) (3 ꢆ 40 mL). The
combined organic phases were dried over Na2SO4 and the solvent
was evaporated. The residue with EtOAc/hexane (3:7) was
filtrated from silica gel column (SiO2, 80 g) and 9 (83%, 1.67 g)
was obtained and crystallized from methanol as white crystals
in the refrigerator at 48C. Mp 58–608C. 1H-NMR (400 MHz, CDCl3)
d (ppm): 6.79 (d, A part of AB-system, J ¼ 8.1 Hz, aromatic, 1H),
6.78 (d, A part of AB-system, J ¼ 8.5 Hz, aromatic, 1H), 6.75
(d, J ¼ 1.7 Hz, aromatic, 1H), 6.72 (dd, B part of AB-system,
J ¼ 8.1, 1.8 Hz aromatic, 1H), 6.60 (d, B part of AB-system,
J ¼ 8.5 Hz, aromatic, 1H), 3.88 (s, OCH3, 3H), 3.87 (s, OCH3,
3H), 3.85 (s, CH2, 2H), 3.84 (s, OCH3, 6H), 3.77 (s, OCH3, 3H).
13C-NMR (100 MHz, CDCl3) d 152.5 (C), 152.0 (C), 149.1 (C),
147.5 (C), 142.6 (C), 134.3 (C), 127.7 (C), 124.5 (CH), 120.9 (CH),
112.5 (CH), 111.4 (CH), 107.4 (CH), 61.0 (OCH3), 60.9 (OCH3), 56.2
1-Bromo-5-(2-bromo-4,5-dimethoxybenzyl)-2,3,4-
trimethoxybenzene (12)
Pale yellow crystals from CH2Cl2/hexane. Mp 97–1008C. 1H-NMR
(400 MHz, CDCl3) d (ppm): 7.03 (s, aromatic, 1H), 6.87 (s, aromatic,
1H), 6.64 (s, aromatic, 1H), 3.95 (s, CH2, 2H), 3.91 (s, OCH3, 3H),
3.88 (s, OCH3, 3H), 3.86 (s, OCH3, 3H), 3.84 (s, OCH3, 3H), 3.78
(s, OCH3, 3H).
(OCH3), 56.1 (OCH3), 56.0 (OCH3), 35.5 (CH2). IR (CH2Cl2, cmꢁ1
)
2991, 2940, 2836, 1601, 1513, 1494, 1465, 1442, 1417, 1311,
1275, 1260, 1204, 1164, 1136, 1100, 1094, 1027, 917. Anal.
Calcd. for (C18H22O5): C 67.91; H 6.97. Found C 67.97; H 6.99.
(C18H22O5): C 67.91 MS m/z (CI, methane) 318.1 (Mþ).
13C-NMR (100 MHz, CDCl3) d 151.56 (C), 150.00 (C), 148.67 (C),
148.44 (C), 147.64 (C), 131.31 (C), 130.75 (CH), 127.57 (CH), 115.78
(CH), 114.85 (CH), 113.94 (CH), 111.55 (C), 61.21, 61.00, 56.37,
56.26 (OCH3), 35.35 (CH2). IR (CH2Cl2, cmꢁ1) 3074, 2957, 2052,
2010, 1935, 1715, 1610, 1592, 1522. Anal. Calcd. for (C18H21BrO5):
C 45.40; H 4.23 Found C 45.58; H 4.22.
Standard procedure for bromination with LiBr/CAN
Bromination of 1-(3,4-dimethoxybenzyl)-2,3,4-
trimethoxybenzene (9) with LiBr/CAN (1 equiv.)
1-(3,4-Dimethoxybenzyl)-2,3,4-trimethoxybenzene (9)
with different equivalents (2.1 and 6.0.) of LiBr/CAN
To a solution of 6 (630 mg, 1.98 mmol) and LiBr (172 mg,
1,98 mmol) in CH3CN (15 mL) was added a solution of CAN
(1.086 g, 1.98 mmol) in CH3CN (15 mL) dropwise at RT and
under N2 over 10 min. After the solution was stirred at RT
and under N2 for 3 d, water (15 mL) was added and the mixture
was extracted with EtOAc (3 ꢆ 40 mL). The combined organic
phases were washed with solutions (5%, 2 ꢆ 20 mL) of NaHCO3,
Only dibromide 12 (287 mg, 95%) was obtained when the
reaction of
6 (200 mg, 0,6 mmol, 1.0 equiv.) with LiBr
(114 mg, 1.32 mmol, 2.1 equiv.) and CAN (724 mg, 1.32 mmol,
2.1 equiv.) was performed according to the standard procedure
described above. The reaction of 6 (200 mg, 0.6 mmol, 1.0 equiv.)
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