6814
Y. Zhang et al. / Bioorg. Med. Chem. Lett. 21 (2011) 6811–6815
(3 mmol), xylene (15 mL) and selenium dioxide (6 mmol) was refluxed at
7.43 (dd, J = 14.0, 6.6 Hz, 3H, Ar-H), 7.37 (t, J = 7.3 Hz, 3H, Ar-H), 6.91 (d,
J = 7.8 Hz, 1H, Ar-H), 6.89 (dd, J = 5.3, 1.5 Hz, 1H, Ar-H), 6.86 (s, 1H, C@CH), 6.82
(d, J = 2.1 Hz, 1H, Ar-H), 6.65 (d, J = 7.9 Hz, 1H, Ar-H), 6.17 (t, J = 7.9 Hz, 1H, Ar-
H), 6.09 (d, J = 7.4 Hz, 1H, Ar-H), 5.32 (s, 2H, NH2), 5.27 (s, 2H, CH2), 5.23 (s, 2H,
CH2); 13C NMR (DMSO-d6, 125 MHz) d 162.58, 160.42, 157.87, 157.14, 153.79,
149.04, 145.17, 136.67, 135.81, 134.31, 129.44, 129.19, 129.01, 128.64, 128.45,
117.57, 116.55, 115.35, 109.89, 102.85, 98.03, 95.65, 72.07, 70.60; MS (m/z)
477 (M+1)+; Compound 5f1: Yields 70%; mp: 210.2–211.3 °C; 1H NMR (DMSO-
d6, 500 MHz) d 9.82 (s, 1H, OH), 8.89 (s, 1H, N@CH), 8.85 (d, J = 9.0 Hz, 1H, Ar-
H), 7.49 (d, J = 7.3 Hz, 2H, Ar-H), 7.45–7.39 (m, 4H, Ar-H), 7.36 (t, J = 7.2 Hz, 1H,
Ar-H), 7.14 (s, 1H, Ar-H), 7.09 (d, J = 9.0 Hz, 1H, Ar-H), 6.87 (d, J = 8.6 Hz, 2H, Ar-
H), 6.77 (s, 1H, C@CH), 5.26 (s, 2H, CH2); 13C NMR (DMSO-d6, 125 MHz) d
161.47, 160.16, 158.12, 154.79, 153.81, 153.42, 136.42, 136.38, 128.59, 128.17,
128.14, 127.95, 127.89, 126.57, 123.71, 116.01, 114.63, 113.42, 113.00, 112.78,
111.34, 110.58, 102.07, 101.84, 69.98, 18.17; MS (m/z) 372 (M+1)+; Compound
5f2: Yields 68%; mp: 231.5–233.1 °C; 1H NMR (DMSO-d6, 500 MHz) d 9.58 (s,
1H, OH), 8.98 (s, 1H, N@CH), 7.57–7.26 (m, 10H, Ar-H), 6.85 (s, 1H Ar-H), 6.80
(s, 1H Ar-H), 6.69 (d, J = 8.5 Hz, 2H Ar-H), 6.61 (d, J = 8.5 Hz, 2H Ar-H), 6.50 (s,
1H, C@CH), 5.26 (s, 2H, CH2), 5.20 (s, 2H, CH2); 13C NMR (DMSO-d6, 125 MHz) d
162.79, 160.38, 157.91, 157.69, 157.21, 154.81, 149.27, 141.80, 136.73, 135.94,
129.53, 129.25, 129.12, 128.75, 128.57, 123.58, 116.31, 109.28, 102.86, 98.08,
95.71, 72.12, 70.71; MS (m/z) 478 (M+1)+; Compound 5g1: Yields 83%; mp:
194.8–196.5 °C; 1H NMR (500 MHz, CDCl3) d 8.89 (s, 1H, OH), 8.36 (d, J = 8.9 Hz,
1H, Ar-H), 7.50–7.41 (m, 4H, Ar-H), 7.36 (m, 3H, Ar-H, N@CH), 7.10 (d,
J = 8.8 Hz, 1H, Ar-H), 7.06–6.93 (m, 4H, Ar-H), 6.77 (s, 1H, C@CH), 5.20 (s, 2H,
CH2); 13C NMR (DMSO-d6, 125 MHz) d 161.51, 160.54, 155.76, 151.87, 145.95,
137.24, 136.38, 129.25, 128.60, 128.17, 127.99, 127.95, 120.04, 119.63, 116.76,
114.42, 112.99, 110.69, 102.11, 70.01; MS (m/z) 370 (Mꢀ1)+; Compound 5g2:
Yields 83%; mp: 249.7–250.9 °C; 1H NMR (DMSO-d6, 500 MHz) d 9.11 (s, 1H,
OH), 7.50 (dd, J = 12.5, 7.4 Hz, 4H, Ar-H), 7.44 (t, J = 7.5 Hz, 2H, Ar-H), 7.41–7.37
(m, 2H, Ar-H), 7.34 (t, J = 7.3 Hz, 2H, Ar-H), 6.99 (s, 1H, N@CH), 6.90–6.78 (m,
3H, Ar-H), 6.67–6.21 (m, 4H, Ar-H and C@CH), 5.27 (s, 2H, CH2), 5.24 (s, 2H,
CH2); 13C NMR (DMSO-d6, 125 MHz) d 162.24, 160.08, 157.33, 156.65, 151.97,
148.31, 144.08, 136.73, 136.27, 135.44, 128.96, 128.77, 128.68, 128.63, 128.26,
128.08, 119.69, 118.72, 116.44, 114.51, 110.32, 102.38, 97.65, 95.27, 71.62,
70.23; MS (m/z) 478 (M+1)+; Compound 5h1: Yields 73%; mp: 208.3–209.3 °C;
1H NMR (DMSO-d6, 500 MHz) d 8.42 (s, 1H, N@CH), 8.36 (d, J = 9.0 Hz, 1H, Ar-
H), 7.49 (s, 1H, Ar-H), 7.47 (s, 1H, Ar-H), 7.41 (t, J = 7.4 Hz, 2H, Ar-H), 7.35 (t,
J = 7.2 Hz, 1H, Ar-H), 7.10 (d, J = 2.2 Hz, 1H, Ar-H), 7.05 (dd, J = 9.0, 2.2 Hz, 1H,
Ar-H), 6.52 (s, 1H, C@CH), 5.23 (s, 2H, CH2); 13C NMR (DMSO-d6, 125 MHz) d
161.86, 160.59, 155.88, 146.84, 144.72, 136.68, 128.99, 128.58, 128.50, 128.35,
113.37, 112.57, 110.46, 102.44, 70.37; MS (m/z) 296 (M+1)+; Compound 5h2:
Yields 75%; mp: 210.4–211.3 °C; 1H NMR (DMSO-d6, 500 MHz) d 11.72 (s, 1H,
OH), 8.66 (s, 1H, N@CH), 7.47 (s, 4H, Ar-H), 7.39 (dd, J = 15.5, 7.3 Hz, 6H, Ar-H),
6.78 (d, J = 9.8 Hz, 2H, Ar-H), 6.26 (s, 1H, C@CH), 5.26 (s, 2H, CH2), 5.23 (s, 2H,
CH2); 13C NMR (DMSO-d6, 125 MHz) d 162.25, 159.57, 157.17, 156.67, 147.33,
145.48, 136.23, 135.87, 128.66, 128.29, 128.24, 128.11, 127.88, 108.06, 102.28,
97.92, 95.27, 71.12, 70.21; MS (m/z) 402 (M+1)+; Compound 6: Yields 93%; mp:
229.4–231.3 °C; 1H NMR (DMSO-d6, 500 MHz) d13.32 (s, 1H, NH), 9.14 (d,
J = 8.8 Hz, 1H, Ar-H), 7.85 (d, J = 7.8 Hz, 1H, Ar-H), 7.62 (d, J = 7.8 Hz, 1H, Ar-H),
7.51 (d, J = 7.1 Hz, 2H, Ar-H), 7.42 (t, J = 7.3 Hz, 2H, Ar-H), 7.37 (d, J = 7.2 Hz, 2H,
Ar-H), 7.31 (t, J = 7.4 Hz, 1H, Ar-H), 7.16 (d, J = 12.9 Hz, 2H, Ar-H), 6.92 (s, 1H,
C@CH), 5.27 (s, 2H, CH2); 13C NMR (DMSO-d6, 125 MHz) d 161.68, 160.07,
155.89, 146.86, 143.80, 141.49, 136.34, 134.20, 129.82, 128.63, 128.22, 128.02,
124.62, 122.68, 120.10, 113.22, 112.06, 111.94, 110.24, 102.11, 70.07; MS (m/z)
369 (M+1)+.
150 °C for 20 h and then the solvent was removed by vacuum distillation. The
gum obtained was purified by silica column chromatography with petroleum
ether–ethyl acetate (v/v = 5:1) as the eluent. Upon recrystallization, yellow
crystals of compound 4 were obtained. The mixture of compound 4 (1 mmol)
and different primarily amines (1.1 mmol) or hydrazinium (1.1 mmol) was
refluxed in ethanol for 5 h. After cooling to room temperature, crystals of
compound 5 were obtained. The mixture of compound 4 (1 mmol) and o-
diaminobenzene (1 mmol) was refluxed in DMF for 6 h, and crystals of
compound
6 were obtained when the reaction solution cooling to room
temperature. In addition, the treatment of compound 5e1 and hot DMF also
offer compound 6; (b) Experimental: Melting points were determined on a
WRS-IA apparatus without correction. 1H NMR and 13C NMR spectra were
recorded on a BRUKER AVANCE 500 spectrometer in DMSO-d or CDCl3. Mass
spectra were recorded on BRUKER ESQUIRE HCT spectrometer. Compound 5a1:
Yields 69%; mp: 150.2–150.8 °C; 1H NMR (DMSO-d6, 500 MHz) d 8.39 (s, 1H,
N@CH), 8.13 (s, 2H, NH2), 7.82 (s, 1H, Ar-H), 7.48 (d, J = 7.4 Hz, 2H, Ar-H), 7.41
(t, J = 7.4 Hz, 2H, Ar-H), 7.35 (t, J = 7.2 Hz, 1H, Ar-H), 7.08–6.99 (m, 2H, Ar-H),
6.22 (s, 1H, C@CH), 5.22 (s, 2H, CH2); 13C NMR (DMSO-d6, 125 MHz) d 161.15,
160.73, 155.56, 146.95, 136.43, 131.09, 128.59, 128.16, 127.95, 127.62, 112.68,
110.71, 106.18, 101.96, 69.94, 54.95; MS (m/z) 295 (M+1)+; Compound 5a2:
Yields 67%; mp: 214–215.7 °C; 1H NMR (DMSO-d6, 500 MHz) d 8.46 (s, 1H,
N@CH), 7.63 (s, 2H, Ar-H), 7.47 (d, J = 7.3 Hz, 2H, Ar-H), 7.43–7.30 (m, 2H, Ar-
H), 7.30–7.07 (m, 5H, Ar-H), 6.87 (s, 1H, Ar-H), 6.31 (s, 1H, C@CH), 5.35 (s, 2H,
CH2), 5.24 (s, 2H, CH2), 3.99 (s, 2H, NH2); 13C NMR (DMSO-d6, 125 MHz) d
160.22, 159.34, 156.36, 154.11, 149.35, 140.69, 136.76, 136.61, 134.17, 129.11,
128.97, 128.65, 128.62, 128.50, 128.25, 128.00, 126.26, 109.88, 103.27, 95.92,
71.16, 70.54; MS (m/z) 401 (M+1)+; Compound 5b1: Yields 83%; mp: 205.3–
206.3 °C; 1H NMR (DMSO-d6, 500 MHz) d11.21 (s, 1H, NH), 8.52 (d, J = 8.9 Hz,
1H, Ar-H), 8.02 (s, 1H, N@CH), 7.49 (d, J = 7.3 Hz, 2H, Ar-H), 7.42 (t, J = 7.4 Hz,
2H, Ar-H), 7.38–7.29 (m, 3H, Ar-H), 7.18 (d, J = 7.7 Hz, 2H, Ar-H), 7.14 (dd,
J = 9.0, 2.5 Hz, 1H, Ar-H), 7.10 (d, J = 2.5 Hz, 1H, Ar-H), 6.91 (t, J = 7.3 Hz, 1H, Ar-
H), 6.46 (s, 1H, C@CH), 5.25 (s, 2H, CH2); 13C NMR (DMSO-d6, 125 MHz) d
161.25, 160.54, 155.59, 145.98, 143.87, 136.42, 131.70, 129.49, 128.59, 128.14,
127.89, 127.50, 120.94, 113.12, 112.87, 110.49, 108.06, 102.24, 69.96; MS (m/z)
371 (M+1)+; Compound 5b2: Yields 83%; mp:242.0–243.5 °C; 1H NMR (DMSO-
d6, 500 MHz) d 10.99 (s, 1H, NH), 8.75 (s, 1H, N@CH), 7.47 (s, 1H, Ar-H), 7.46 (s,
1H, Ar-H), 7.45 (d, J = 7.6 Hz, 1H, Ar-H), 7.43 (s, 1H, Ar-H), 7.42 (s, 1H, Ar-H),
7.40 (s, 1H, Ar-H), 7.38 (d, J = 3.1 Hz, 1H, Ar-H), 7.36 (s, 1H, Ar-H), 7.35–7.35 (m,
1H, Ar-H), 7.35 (d, J = 7.1 Hz, 1H, Ar-H), 7.33–7.26 (m, 3H, Ar-H), 7.14 (d,
J = 7.7 Hz, 1H, Ar-H), 6.86 (t, J = 7.3 Hz, 1H, Ar-H), 6.72 (d, J = 7.3 Hz, 1H, Ar-H),
6.66 (d, J = 8.3 Hz, 1H, Ar-H), 6.53 (s, 1H, C@CH), 5.41 (s, 2H, CH2), 5.17 (s, 2H,
CH2); 13C NMR (DMSO-d6, 125 MHz) d 161.68, 159.90, 157.20, 156.96, 147.77,
144.34, 136.32, 136.23, 133.47, 129.41, 128.69, 128.61, 128.24, 128.07, 128.03,
127.32, 120.42, 112.91, 104.08, 102.79, 98.26, 95.34, 70.42, 70.11; MS (m/z)
477 (M+1)+; Compound 5c1: Yields 80%; mp: 255.2–257.0 °C; 1H NMR (DMSO-
d6, 500 MHz) d 11.84 (s, 1H, NH), 8.43 (d, J = 8.7 Hz, 1H, Ar-H), 8.21 (s, 1H,
N@CH), 8.19 (d, J = 5.9 Hz, 2H, Ar-H), 7.49 (d, J = 7.5 Hz, 2H, Ar-H), 7.42 (t,
J = 7.3 Hz, 2H, Ar-H), 7.37 (d, J = 7.3 Hz, 1H, Ar-H), 7.29 (d, J = 8.8 Hz, 2H, Ar-H),
7.14 (d, J = 10.0 Hz, 2H, Ar-H), 6.61 (s, 1H, C@CH), 5.26 (s, 2H, CH2); 13C NMR
(DMSO-d6, 125 MHz) d 161.80, 160.72, 155.99, 149.89, 145.57, 140.56, 137.34,
136.76, 129.00, 128.56, 128.30, 127.79, 126.55, 113.48, 113.05, 110.83, 110.62,
102.67, 70.38; MS (m/z) 414 (Mꢀ1)+; Compound 5c2: Yields 82%; mp:226.7–
227.9 °C; 1H NMR (DMSO-d6, 500 MHz) d 11.62 (s, 1H, NH), 8.81 (s, 1H, N@CH),
8.18 (d, J = 9.1 Hz, 2H, Ar-H), 7.46 (s, 2H, Ar-H), 7.45–7.37 (m, 5H, Ar-H), 7.38–
7.28 (m, 5H, Ar-H), 6.75 (d, J = 1.9 Hz, 1H, Ar-H), 6.69 (d, J = 1.7 Hz, 1H, Ar-H),
6.53 (s, 1H, C@CH), 5.39 (s, 2H, CH2), 5.19 (s, 2H, CH2); 13C NMR (DMSO-d6,
125 MHz) d 162.33, 160.17, 157.38, 157.16, 150.33, 147.28, 139.98, 139.68,
136.53, 129.04, 129.00, 128.65, 128.62, 128.46, 128.02, 127.71, 126.57, 112.60,
107.05, 102.96, 98.61, 95.67, 70.95, 70.52; MS (m/z) 522 (M+1)+; Compound
5d1: Yields 88%; mp:295.2–297.0 °C; 1H NMR (DMSO-d6, 500 MHz) d 11.90 (s,
1H, NH), 9.02 (s, 1H, Ar-H), 8.87 (s, 1H, N@CH), 8.42 (d, J = 9.5 Hz, 1H, Ar-H),
8.21 (d, J = 8.5 Hz, 1H, Ar-H), 8.12 (d, J = 9.8 Hz, 1H, Ar-H), 7.49 (d, J = 7.7 Hz,
2H, Ar-H), 7.42 (t, J = 7.4 Hz, 2H, Ar-H), 7.37 (d, J = 7.6 Hz, 1H, Ar-H), 7.15 (d,
J = 9.6 Hz, 2H, Ar-H), 6.73 (s, 1H, C@CH), 5.26 (s, 2H, CH2); 13C NMR (DMSO-d6,
125 MHz) d 162.09, 160.55, 156.04, 145.16, 143.98, 138.93, 136.70, 130.42,
129.01, 128.60, 128.33, 127.11, 123.19, 117.85, 113.69, 110.74, 102.77, 70.46;
MS (m/z) 461 (M+1)+; Compound 5d2: Yields 87%; mp: 236.8–238.8 °C; 1H
NMR (DMSO-d6, 500 MHz) d 11.62 (s, 1H, NH), 9.16 (s, 1H, N@CH), 8.36 (d,
J = 9.3 Hz, 1H, Ar-H), 8.03 (d, J = 9.5 Hz, 1H, Ar-H), 7.95 (s, 1H, Ar-H), 7.49–7.44
(m, 4H, Ar-H), 7.42 (s, 1H, Ar-H), 7.37 (d, J = 7.0 Hz, 1H, Ar-H), 7.30 (s, 1H, Ar-H),
7.28 (s, 1H, Ar-H), 7.26 (d, J = 1.0 Hz, 1H, Ar-H), 7.20 (d, J = 7.4 Hz, 1H, Ar-H),
6.79 (d, J = 2.2 Hz, 1H, Ar-H), 6.77 (d, J = 2.0 Hz, 1H, Ar-H), 6.50 (s, 1H, C@CH),
5.30 (s, 2H, CH2), 5.22 (s, 2H, CH2); 13C NMR (DMSO-d6, 125 MHz) d 162.83,
162.70, 160.07, 157.37, 156.98, 147.89, 147.33, 146.77, 139.22, 138.73, 136.53,
136.31, 130.13, 129.01, 128.98, 128.67, 128.46, 128.25, 128.02, 123.29, 119.99,
117.59, 109.00, 102.73, 98.38, 95.64, 71.51, 70.59; MS (m/z) 565 (Mꢀ1)+;
Compound 5e1: Yields 85%; mp: 152.6–153.8 °C; 1H NMR (DMSO-d6, 500 MHz)
d 8.96 (s, 1H, N@CH), 8.66 (d, J = 8.9 Hz, 1H, Ar-H), 7.49 (d, J = 7.6 Hz, 2H, Ar-H),
7.41 (t, J = 7.3 Hz, 2H, Ar-H), 7.35 (t, J = 7.2 Hz, 2H, Ar-H), 7.14–7.04 (m, 3H, Ar-
H), 6.97 (s, 1H, C@CH), 6.78 (d, J = 8.1 Hz, 1H, Ar-H), 6.59 (t, J = 7.5 Hz, 1H, Ar-
H), 5.42 (s, 2H, NH2), 5.25 (s, 2H, CH2); 13C NMR (DMSO-d6, 125 MHz) d 161.81,
160.97, 156.09, 151.95, 146.48, 145.72, 136.74, 134.40, 130.15, 128.99, 128.56,
128.33, 128.04, 118.05, 116.54, 115.84, 113.55, 113.40, 111.21, 102.46, 70.36;
MS (m/z) 371 (M+1)+; Compound 5e2: Yields 85%; mp: 194.0–194.7 °C; 1H
NMR (DMSO-d6, 500 MHz) d 9.04 (s, 1H, N@CH), 7.51 (d, J = 5.4 Hz, 4H, Ar-H),
13. (a) Pan, Y. M.; Zhu, J. C.; Wang, H. S.; Zhang, X. P.; Zhang, Y.; He, C. H.; Ji, X. W.;
Li H. Y. Food Chem. 2007, 103, 913; (b) General procedure for evaluation of
DPPH radical activity: Each sample solution (0.1 mL) in DMF at different
concentrations was added to the solution [3.9 mL, 0.004% (w/v)] of DPPHÅ in
ethanol. The reaction mixture was incubated at 37 °C. The scavenging activity
on DPPHÅ was determined by measuring the absorbance at 517 nm after
30 min. All tests were performed in triplicate and mean were centred. The
scavenging activity was expressed as a percentage of scavenging activity on
DPPHÅ: SC% = [(Acontrol –Atest)/Acontrol)] ꢁ 100%, where Acontrol is the absorbance
of the control (DPPHÅ solution without test sample) and Atest is the absorbance
of the test sample (DPPHÅ solution plus scavenger). The control contains all
reagents except the scavenger.
14. (a) Pan,Y. M.; He, C. H.; Wang, H. S.; Ji, X. W.; Wang, K.; Liu, P. Z.; Food Chem.
2010, 121, 497; (b) General procedure for evaluation of ABTS radical activity:
Stock solution of ABTS (2 mM) was prepared by dissolving in phosphate
buffered saline (PBS, 50 ml) and the pH of the solution should be 7.4. ABTSÅ+
was produced by reacting of stock solution (50 ml) with K2S2O8 water solution
(200 ml, 70 mM). The mixture was left to stand in the dark at room
temperature for 15–16 h before use. For the evaluation of antioxidant
activity, the ABTSÅ+ solution was diluted with PBS to obtain the absorbency
of 0.700 0.030 at 734 nm. Compounds 5–6 solution (0.1 ml) at different
concentration were mixed with ABTSÅ+ solution (1.9 ml), then absorbance was
read at ambient temperature after 3 min. PBS solution was used as a blank
sample. All tests were performed in triplicate and mean were centred. The
radical scavenging activity of the sample was expressed as
SC% = [(Acontrol ꢀ Atest)/Acontrol] ꢁ 100%, where Acontrol is the absorbance of the
control (ABTSÅ+ solution without test sample) and Atest is the absorbance of the
test sample (ABTSÅ+ solution plus extracts).
15. (a) Guo T.; Wei, L.; Sun, J.; Hou, C. L.; Fan, L.; Food Chem. 2011, 127, 1634; (b)
General procedure for evaluation of hydroxyl radical activity: The following