D. Garbicz, et al.
Biomedicine&Pharmacotherapy123(2020)109781
was protected with an ethyl group according to [39], compounds (1)
and (3) were synthesized according to literature procedures [26] and
[27] respectively. Molecule (6) was prepared according to modified
literature procedures: [27,33].
heated at 90 °C for 2 h under argon, then dissolved in 150 mL of ethyl
acetate and washed with 0.25 M hydrochloric acid (2 × 25 mL) and
water to neutral pH. Then, the solvent and the remaining water were
removed in vacuo and the crude product was purified by crystallization
from methanol or ethanol with the additive of charcoal. After hot fil-
tration, a pure stilbene was obtained.
2.1.1. Synthesis of (5a) and (6)
9-nitrobenzo[b]naphtho[1,2-f]oxepine (4), Yield 29 %, product was
crystallized from methanol, 1H NMR (500 MHz, CDCl3): δ 7.04 (d, 1H,
J = 11.5 Hz, CH=), 7.35 (d, 1H, J = 8.5 Hz, Ph-NO2), 7.42 (d, 1H,
J = 9.0 Hz, Napht), 7.48 (ddd, 1H, J = 8.0, J = 7.0, J = 1.5 Hz,
Napht), 7.57 (ddd, 1H, J = 8.0, J = 7.0,J = 1.5 Hz, Napht), 7.64 (d,
1H, J = 11.5 Hz, CH=), 7.83–7.85 (m, 1 H), 7.886 (d, 1H, J = 9.0 Hz,
Napht), 8.00 (dd, 1H, J = 2.5 Hz, J = 8.5 Hz, Ar-NO2), 8.05 (dd, 1H,
J = 8.5 Hz, J = 1.0 Hz), 8.08 (d, 1H, J = 2.5 Hz, Ar-NO2). 13C NMR
(125 MHz, CDCl3): δ 117.0, 120.3, 121.1, 123.3, 123.4, 125.7, 127.5,
128.8, 129.2, 129.3, 130.1, 131.5, 131.6, 131.9, 137.9, 148.7, 156.0,
157.7. FTIR (νmax/cm-1) 3101, 3074, 3037, 1615, 1591, 1522, 1483,
1438, 1400, 1341, 1320, 1227, 1207, 1191, 1149, 1129, 1078, 1062,
925, 896, 858, 850, 821, 808, 794, 760, 737, 725, 690, 670, 635. HRMS
(ESI): C18H11NO3Na+,calcd. m/z 312.0637- found 312.0638.
3-ethoxy-4-hydroxy-2′4′-dinitrostilbene (10) Yield 41 %, the pro-
duct was crystallized from ethanol. 1H NMR (500 MHz, CDCl3): δ 1.50
(t, 3H, J = 7.0 Hz, CH3), 4.19 (q, 2H, J = 7.0 Hz, CH2O), 5.92 (s, 1H,
OH), 6.95 (d, 1H, J = 8.0 Hz, Ar-3-CH3CH2O-4-OH), 7.07–7.09 (m, 2H,
Ar-3-CH3CH2O-4-OH), 7.23 (d, 1H, J = 16.0 Hz, CH=), 7.45 (d, 1H,
J = 16.0 Hz, CH=), 7.95 (d, 1H, J = 9.0 Hz, Ar-2,4-NO2), 8.38 (ddd,
1H, J = 0.5 Hz, J = 2.5, J = 9.0 Hz, Ar-2,4-NO2), 8.78 (d, 1H,
J = 2.5 Hz, Ar-2,4-NO2). 13C NMR (125 MHz, CDCl3): δ 14.9, 64.9,
109.7, 114.9, 118.6, 120.9, 122.8, 127.1, 128.3, 128.5, 138.5, 139.2,
145.9, 146.4, 147.3, 147.9. FTIR (νmax/cm-1) 3493, 3116, 2988, 2944,
2887, 1625, 1601, 1586, 1555, 1513, 1474, 1443, 1432, 1401, 1381,
1342, 1327, 1303, 1291, 1275, 1261, 1238, 1218, 1194, 1170, 1141,
1126, 1061, 1043, 973, 967, 962, 937, 920, 904, 852, 834, 826, 813,
737, 727, 713, 682. HRMS (ESI) : C16H14N2O6Na+, calcd. m/z
353.0749 -found 353.0748.
To a well-stirred and cooled to 0 °C suspension of zinc powder
(9.40 g, 143.8 mmol) in anhydrous THF (100.0 mL), titanium tetra-
chloride (13.62 g, 7.86 mL, 71.8 mmol) was added dropwise. The mix-
ture was stirred at 0 °C for 0.5 h and then p-methoxybenzaldehyde
(59.8 mmol) or solution of 3,4,5-trimethoxybenzaldehyde (59.8 mmol)
in THF (25 ml) was slowly added. The suspension was refluxed for 24 h
under argon, then cooled to 0 °C and diluted with cold water (200 mL).
Zinc dust and precipitated stilbene were filtered off, washed with dis-
tilled water (2 × 50 mL) and methanol (2 × 25 mL) and dried under
vacuume. After recrystallization and hot filtration, pure stilbene was
obtained.
(E)-4,4′-dimethoxystilbene (5a), Yield 68 %, product was crystal-
lized from toluene/ethyl acetate. 1H NMR (CDCl3, 500 MHz): δ 3.83 (s,
6H, CH3O), 6.88–6.91 (m, 4H, Ar), 6.93 (s, 2H, CH = CH), 7.41–7.44
(m, 4H, Ar). 13C NMR (CDCl3, 125 MHz): δ 55.5, 114.3, 126.3, 127.6,
130.6, 159.2. FTIR (νmax/ cm−1): 3069, 3017, 2955, 2937, 2911, 2838,
2051, 1987, 1894, 1832, 1606, 1575, 1511, 1464, 1447, 1440, 1425,
1306, 1269, 1244, 1214, 1177, 1152, 1110, 1027, 967, 955, 832, 824,
815, 744, 728, 640. HRMS (ESI): C16H16O2Na+, calcd m/z 263.1048 ;
found m/z 263.1049.
(E)-3,3′,4,4′,5,5′-hexamethoxystilbene (6), Yield 81 %, product was
crystallized from toluene. 1H NMR (CDCl3, 500 MHz): δ 3.87 (s, 6H,
CH3O), 3.91 (s, 12H, CH3O), 6.73 (s, 4H, Ar), 6.93 (s, 2H, CH = CH).
13C NMR (CDCl3, 125 MHz): δ 56.2, 61.1, 103.6, 128.2, 133.0, 138.0,
153.5. FTIR (νmax/ cm−1): 3006, 2976, 2941, 2833, 1583, 1508, 1464,
1418, 1350, 1316, 1263, 1248, 1231, 1187, 1119, 993, 966, 919, 830,
782, 675, 651. HRMS (ESI): C20H24O6Na+, calcd m/z 383.1471; found
m/z 383.1470.
2.1.2. Synthesis of (5)
2.1.4. Synthesis of (7, 8, 9)
To a stirred mixture of 2,4-dinitrotoluene (2.19 g, 12 mmol), alde-
hyde (12 mmol) and toluene (20 ml) under argon, dry piperidine
(1.09 ml, 0.937 g, 11.0 mmol) was added. After 3 h of heating at 90 °C,
the solvent was distilled off on a rotary evaporator. Then ethyl acetate
(150 mL) was added to the residue, and the resulting mixture was
washed with 0.5 M hydrochloric acid (2 × 40 mL) and water to neutral
pH. Next, the solvent and the remaining water were removed in vacuo
and the crude product was purified by crystallization from methanol or
ethanol with the additive of charcoal. After hot filtration, pure stilbene
was obtained.
3-hydroxy-2′,4′-dinitrostilbene (7), Yield 22 %, product was crys-
tallized from ethanol, 1H NMR (500 MHz, DMSO-D6, 30 °C): δ 6.80
(ddd, 1H, J = 8.0 Hz, J = 2.5 Hz, J = 1.0 Hz, Ar-3-OH), 7.05–7.09 (m,
2H, Ar-3-OH), 7.24 (t, 1H, J = 8.0 Hz, Ar-3-OH), 7.43 (d, 1H,
J = 16.5 Hz, CH=), 7.51 (d, 1H, J = 16.5 Hz, CH=), 8.26 (d, 1H,
J = 8.5 Hz, Ar-2,4-NO2), 8.48 (ddd, 1H, J = 8.5 Hz, J = 2.5 Hz,
J = 0.5 Hz, Ar-2,4-NO2), 8.74 (d, 1H, J = 2.5 Hz, Ar-2,4-NO2), 9.56 (s,
1H, OH). 13C NMR (125 MHz, DMSO-D6, 30 °C): δ 113.6, 116.7, 118.7,
120.2, 120.9, 127.1, 129.2, 129.9, 136.9, 137.5, 137.6, 145.8, 147.2,
157.7. FTIR (νmax/cm-1): 3429, 3094, 2356, 1627, 1594, 1580, 1515,
1344, 1290, 1254, 1211, 1168, 1153, 1125, 1091, 1064, 997, 978, 950,
922, 905, 876, 849, 833, 770, 755, 741, 727, 700, 678, 654, 605, 580.
HRMS (ESI): C14H10N2O5Na+, calcd. m/z 309.0487- found 309.0489.
4-hydroxy-2′,4′-dinitrostilbene (8), Yield 14 %, the product was
crystallized from a small amount of methanol. 1H NMR (500 MHz,
was prepared according to literature procedures [27]: 7-methoxy-1,2,3-
tris(4-methoxyphenyl)-1,2,3,4-tetrahydronaphthalene (5). White solid,
yield: 432 mg (90 %), m.p. 139−140 °C (EtOH). 1H NMR (500 MHz,
CDCl3, 298 K): δ (ppm): the ring: 3.06 (1H, AB spin system, dd 2J =
-16.5 Hz, 3J = 4.5 Hz, H4), 3.18 (1H, AB spin system, dd, 3J = 11.5 Hz,
H4′), 4.18 (1H, d, 3J =10.5 Hz, H1), 3.15 (1H, dd, 3J =11 Hz, H2), 3.33
(1H, ddd, H3); A ring: 6.75 (2H, d, 3J = 8.5 Hz, H2,H6), 6.66 (2H, d,
H3,H5), 3.74 (3H, s, OCH3); B ring 6.68 (2H, d, 3J = 8.5 Hz, H2, H6),
6.52 (2H, d, H3, H5), 3.65 (3H, s, OCH3); C ring: 6.98 (2H, d,
3J = 8.5 Hz, 1 H2, H6), 6.64 (2H, d, H3, H5), 3.70 (3H, s, OCH3); D
ring 7.07(1H, d, 3J =8.5 Hz, H5), 6.34 (1H, d, 4J = 2.5 Hz, H8), 6.72
(1H, dd, H6), 3.63 (3H, s, OCH3). 13C NMR (125 MHz, CDCl3, 298 K): δ
(ppm): the ring: 55.02(C1), 55.53(C2), 46.35(C3), 39.65(C4); A ring:
137.58(C1), 130.19(C2,C6), 113.45(C3,C5), 157.64 (C4), 55.09(OCH3);
B ring: 135.18(C1), 129.26(C2,C6), 113.03 (C3,C5), 157.18(C4) 54.91
(OCH3);
C ring: 136.82(C1), 128.52 (C2,C6), 113.33 (C3,C5),
157.45(C4),55.06 (OCH3); D ring 129.37 (C4a), 129.06 (C5), 112.07
(C6), 157.75 (C7), 114.86 (C8), 141.45 (C8a), 55.20(OCH3). HRMS
(ESI): C32H32O4Na+, calcd m/z 503.2198; found m/z 503.2195.
2.1.3. Synthesis of (4, 10)
A mixture of aromatic aldehyde (12 mmol) and 2.19 g (12 mmol) of
2,4-dinitrotoluene was ground in a mortar and then placed in a thick-
walled glass test tube with a Teflon closure and 1.09 mL (0.937 g,
11.0 mmol) of piperidine was added. The contents of the vessel were
DMSO-D6): δ 6.83 (d, 2H, J = 9.0 Hz, Ar-4-OH), 7.27 (d, 1H,
J = 16.0 Hz, CH=), 7.50–7.55 (m, 3H, Ar-4-OH and CH=), 8.21 (d,
1H, J = 9.0 Hz, Ar-2,4-NO2), 8.43 (dd, 1H, J = 9.0 Hz, J = 2.5 Hz, Ar-
2,4-NO2), 8.70 (d, 1H, J = 2.5 Hz, Ar-2,4-NO2), 9.94 (s, 1H, OH). 13C
3