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E. Fındık et al. / European Journal of Medicinal Chemistry 46 (2011) 4618e4624
temperature at 140 ꢂC for 3 h. When the reaction was complete, the
mixture was cooled, diluted with ethyl acetate, and treated with
HCl solution (5%) to compose the catalyst. Then, the mixture was
washed with saturated NaHCO3 solution and water until rinsing
was neutral. The organic layer was dried over anhydrous Na2SO4.
The solvent was evaporated, and the crude products were purified
by column chromatography (on a silica gel column) using n-
hexane/EtOAc (9:1) as eluent. The products were crystallized from
n-hexane/EtOAc (9:1).
cmꢀ1): 3473, 3403, 3369, 3243, 2967, 2956, 2929, 2869, 1600, 1521,
1477, 1278, 1122, 1027, 966, 800, 761, 632. Anal. Calcd for
(C16H18O4): C, 70.02; H, 6.61. Found: C, 69.78; H, 6.44. GC/MS (m/z):
274 (Mþ, 30%), 245 (100%, eCH2CH3), 213 (13%, eOCH3), 77 (10%,
C6H5). UVeVis:
l (log ε) 239 (1.24), 280 (1.19).
5.1.6. 4-(1-(4-Hydroxy-3-methoxyphenyl)propyl)benzen-1,2-diol
(11)
Colorless crystals, Yield (55%), M.p. 127e129 ꢂC 1H NMR
(400 MHz, d6-DMSO, ppm):
d
¼ 8.66 (s, 2H, eOH), 8.59 (s,1H, eOH),
5.1.2. 4-(1-(2-Hydroxyphenyl)propyl)-2-methoxyphenol (7)
Colorless crystals, Yield (25%), M.p. 99e101 ꢂC 1H NMR
6.73 (s, 1H), 6.64 (d, J ¼ 8.0 Hz, 1H, A part of AB system), 6.60e6.58
(m, 3H, ArH), 6.49 (dd, J ¼ 8.0, 1.6 Hz, 1H, B part of AB system), 3.70
(s, 3H, eOCH3), 3.46 (t, J ¼ 7.6 Hz, 1H), 1.89e1.82 (m, 2H), 0.77 (t,
(400 MHz, CDCl3, ppm):
d
¼ 7.28 (d, J ¼ 8.0 Hz, 1H), 7.12 (dt, J ¼ 7.5,
1.6 Hz, 1H), 6.95 (t, J ¼ 7.5 Hz, 1H), 6.87 (d, J ¼ 8.0 Hz, 1H), 6.80 (dd,
J ¼ 8.0, 1.6 Hz, 1H), 6.76 (bd, J ¼ 8.0 Hz, 1H), 6.73 (d, J ¼ 1.6 Hz, 1H),
5.56 (s, 1H, eOH), 4.85 (s, 1H, eOH), 4.00 (t, J ¼ 7.6 Hz, 1H), 3.82 (s,
3H, eOCH3), 2.06 (m, 2H), 0.94 (t, J ¼ 7.6 Hz, 3H, eCH3). 13C NMR
J ¼ 7.2 Hz, 3H, eCH3). 13C NMR (100 MHz, d6-DMSO, ppm):
¼ 147.7,
d
145.3, 144.9, 143.6, 137.2, 137.1, 119.9, 118.5, 115.7, 115.7, 115.4, 112.4,
56.1, 51.8, 28.8, 13.2. IR (KCl, cmꢀ1): 3440, 3361, 3253, 2958, 2931,
2873, 1602, 1513, 1427, 1353, 1268, 1027, 794, 779, 557. Anal. Calcd
for (C16H18O4): C, 70.02; H, 6.61. Found: C, 70.25; H, 6.55. GC/MS (m/
z): 274 (Mþ, 20%), 245 (100%, eCH2CH3), 213 (5%, eOCH3), 77 (5%,
(100 MHz, CDCl3, ppm):
d
¼ 153.6, 146.7, 144.1, 135.9, 131.2, 127.8,
127.3, 120.8, 120.5, 116.1, 114.3, 110.6, 55.8, 46.1, 27.7, 12.6. IR (KCl,
cmꢀ1): 3469, 3378, 3012, 2973, 2954, 2929, 2869, 1515, 1502, 1457,
1378, 1276, 1255, 1226, 1149, 1130, 1037, 796, 757, 638, 553. Anal.
Calcd for C16H18O3: C, 74.39; H, 7.02. Found: C, 73.97; H, 6.92. GC/MS
(m/z): 258 (Mþ, 20%), 229 (100%, eCH2CH3), 197 (15%, eOCH3), 77
C6H5). UVeVis:
l (log ε) 239 (1.24), 280 (1.19).
5.1.7. 4-(1-(4-Hydroxy-3-methoxyphenyl)propyl)benzene-1,3-diol
(12)
(10%, C6H5). UVeVis:
l
(log ε) 239 (1.79), 242 (1.70), 278 (2.17).
Colorless crystals, Yield (65%), M.p. 88e90 ꢂC 1H NMR (400 MHz,
d6-DMSO, ppm):
d
¼ 9.02 (s,1H, eOH), 8.93 (s,1H, eOH), 8.60 (s,1H,
5.1.3. 4-(1-(2-Hydroxy-3-ethoxyphenyl)propyl)-2-methoxyphenol
eOH), 6.87 (dd, J ¼ 8.4, 2.8 Hz, 1H), 6.74 (s, 1H), 6.63e6.57 (m, 2H),
6.22 (s, 1H), 6.13 (d, J ¼ 8.4 Hz, 1H), 3.93 (t, J ¼ 8.0 Hz, 1H), 3.69 (s,
(8)
Colorless crystals, Yield 40%, M.p.162e164 ꢂC 1H NMR (400 MHz,
3H, eOCH3), 1.89e1.81 (m, 2H), 0.77 (t, J ¼ 5.6 Hz, 3H, eCH3). 13
C
d6-DMSO, ppm):
d
¼ 8.66 (s,1H, eOH), 8.16 (s,1H, eOH), 6.82 (s,1H),
NMR (100 MHz, d6-DMSO, ppm):
d
¼ 156.3, 155.7, 147.5, 144.7, 137.2,
6.77 (dd, J ¼ 7.2, 1.6 Hz, 1H), 6.73e6.67 (m, 4H), 4.15 (t, J ¼ 8.0 Hz,
1H), 4.02e3.94 (m, 2H, -OCH2CH3), 3.71 (s, 3H, eOCH3), 1.97e1.90
(m, 2H), 1.32 (t, J ¼ 7.2 Hz, 3H, eOCH2CH3), 0.82 (t, J ¼ 7.2 Hz, 3H,
128.1, 122.8, 120.3, 115.5, 112.7, 106.5, 102.8, 56.0, 44.0, 28.2, 13.3. IR
(KCl, cmꢀ1): 3444, 3396, 3288, 2964, 2954, 2931, 2871, 1743, 1617,
1604, 1513, 1446, 1432, 1375, 1251, 1199, 1128, 1031, 971, 842, 813,
640, 557. Anal. Calcd for (C16H18O4): C, 70.02; H, 6.61. Found: C,
69.80; H, 6.65. GC/MS (m/z): 274 (Mþ, 30%), 245 (100%, eCH2CH3),
eCH3). 13C NMR (100 MHz, d6-DMSO, ppm):
d
¼ 147.6, 146.7, 144.9,
144.2, 136.5, 132.5, 120.4, 119.6, 119.1, 115.5, 112.7, 110.5, 64.4, 56.1,
44.6, 27.9, 15.1, 13.3. IR (KCl, cmꢀ1): 3432, 2962, 2931, 2867, 1610,
1511, 1469, 1251, 1203, 1126, 1052, 806, 754, 559. Anal. Calcd for
(C18H22O4): C, 71.50; H, 7.33. Found: C, 70.98; H, 7.27. GC/MS (m/z):
302 (Mþ, 20%), 273 (100%, eCH2CH3), 243 (5%, eCH2CH3), 213 (10%,
213 (15%, eOCH3), 77 (10%, C6H5). UVeVis:
l (log ε) 239 (1.83), 240
(1.85), 243 (1.82), 282 (2.11).
5.2. Antioxidant activity
eOCH3), 77 (5%, C6H5). UVeVis:
l (log ε) 240 (1.32), 281 (1.31).
5.2.1. DPPH radical scavenging activity
5.1.4. 4-(1-(2-Hydroxy-3-isopropylphenyl)propyl)-2-
methoxyphenol (9)
The free radical scavenging activities of phenolic compounds
were measured by 1,1-diphenyl-2-picrylhydrazil (DPPH) using the
method of Blois [48]. Briefly, 0.1 mM solution of DPPH in ethanol was
prepared and 1 mL of this solution was added to 3 mL of ethanolic
Colorless crystals, Yield (64%), M.p. 75e77 ꢂC 1H NMR (400 MHz,
d6-DMSO, ppm):
d
¼ 8.65 (s, 1H, eOH), 8.05 (s, 1H, eOH), 6.99 (d,
J ¼ 7.6 Hz, 1H), 6.95 (d, J ¼ 7.2 Hz, 1H), 6.84 (s, 1H), 6.76 (t, J ¼ 7.6 Hz,
1H), 6.67 (s, 2H), 4.22 (t, J ¼ 7.6 Hz, 1H), 3.71 (s, 3H, eOCH3),
3.34e3.25 (h, J ¼ 6.8 Hz, 1H, eCH(CH3)2), 1.97e1.85 (m, 2H), 1.13 (t,
J ¼ 7.2 Hz, 6H), 0.83 (t, J ¼ 6.8 Hz, 3H, eCH3). 13C NMR (100 MHz, d6-
phenolic compounds at different concentrations (10e40 mg/mL).
The mixture was shaken vigorously and allowed to be kept stand at
room temperature for 30 min. Then the absorbance was measured at
517 nm in a spectrophotometer. The radical scavenging activities of
the samples were expressed in terms of IC50 (concentration required
DMSO, ppm):
d
¼ 151.4, 147.6, 144.9, 136.4, 135.6, 133.3, 124.9, 123.4,
120.5, 120.2, 115.6, 112.9, 56.1, 44.4, 28.5, 26.5, 23.6, 23.3, 13.2. IR
(KCl, cmꢀ1): 3390, 3255, 2964, 2929, 2867, 2836, 1598, 1523, 1459,
1446, 1274, 1257, 1207, 1184, 1128, 1035, 782, 746, 565. Anal. Calcd
for (C19H24O3): C, 75.92; H, 8.05. Found: C, 75.62; H, 7.75. GC/MS (m/
z): 300 (Mþ, % 20), 271 (100%, eCH2CH3), 239 (5%, eOCH3), 197
for a 50% decrease in absorbance of DPPH radical). A lower IC50
value indicates greater antioxidant activity.
(mM)
5.2.2. ABTSþ radical scavenging activity
Radical scavenging activity was evaluated according to the
protocol of Nenadis, Wang, Tsimidou & Zhang [49] which was
appropriately adjusted. To quench the ABTSþ, a blue-green chro-
mophore was used with a characteristic absorption at 734 nm; an
antioxidant is added to a pre-formed ABTS radical solution, and after
a fixed time period, the remaining ABTSþ is quantified spectropho-
tometrically at 734 nm. The ABTSþ was produced by reacting ABTS
(2 mM) in water with potassium persulfate (2.45 mM, K2S2O8),
stored in the dark at room temperature for 12 h. Then, to ABTSþ
solution (0.5 mL) was added solution of the synthesized compounds
(10%, eCH(CH3)2), 77 (5%, C6H5). UVeVis:
l (log ε) 239 (2.08), 242
(1.76), 277 (2.07).
5.1.5. 3-(1-(4-Hydroxy-3-methoxyphenyl)propyl)benzen-1,2-diol
(10)
Colorless crystals, Yield (35%), M.p. 103e105 ꢂC 1H NMR (d6-
DMSO, ppm): 9.21 (s, 1H, eOH); 8.63 (s, 1H, eOH); 8.06 (s, 1H,
eOH); 6.79 (s, 1H); 6.64e6.52 (m, 5H); 4.10 (t, J ¼ 7.6 Hz, 1H); 3.70
(s, 3H, eOCH3); 1.97e1.86 (m, 2H); 0.80 (t, J ¼ 7.2 Hz, 3H, eCH3); 13
C
NMR (d6-DMSO, ppm):
d
147.6, 145.2, 144.8, 143.2, 136.6, 132.8,
(7e12) in ethanol at various concentrations (1.5 mL, 10e30
mg/mL).
120.42, 119.0, 118.2, 115.5, 113.0, 112.8, 56.1, 44.6, 28.0, 13.3. IR (KCl,
After the solution was mixed for 30 min, the absorbance was