C. Praveen et al. / Bioorg. Med. Chem. Lett. 20 (2010) 7292–7296
7295
Table 6
Hydrogen peroxide radical scavenging activity of bis(indolyl)methanes (6a–6k)
S. No.
Sample
Time (min)
Abs (20 min)
Abs (0 min)
%
Abs (10 min)
%
%
Abs (30 min)
%
Abs (40 min)
%
1
2
3
4
5
6
7
8
9
10
11
12
13
BHT
6a
6b
6c
6d
6e
6f
6g
6h
6i
0.072
0.514
0.126
0.162
0.144
0.153
0.063
0.108
0.387
0.135
0.117
0.360
0.9022
92
43
86
82
84
83
93
88
57
85
87
60
0.126
0.586
0.135
0.171
0.153
0.162
0.144
0.135
0.514
0.180
0.153
0.487
86
35
85
81
83
82
84
85
43
80
83
45
0.153
0.712
0.234
0.234
0.180
0.171
0.162
0.216
0.550
0.162
0.225
0.541
83
21
74
74
80
81
82
76
39
82
75
45
0.162
0.799
0.252
0.261
0.243
0.180
0.207
0.243
0.631
0.225
0.270
0.586
82
20
72
71
73
80
77
73
30
75
70
35
0.180
0.757
0.279
0.315
0.288
0.189
0.261
0.270
0.712
0.315
0.369
0.685
80
16
69
65
68
79
71
70
21
65
59
24
6j
6k
Control
12. (a) Bradfield, C. A.; Bjeldanes, L. F. J. Toxicol. Health 1987, 21, 311; (b)
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4-benzoic 6k groups were much lower. Other compounds exhibited
comparable inhibition values with that of the standard, BHT.
In summary, a safe and practical synthesis of substituted quin-
olines and bis(indolyl)methanes was achieved under solvent free
condition. Operational simplicity, low catalyst loading, wide sub-
strate scope, were screened for their antimicrobial activities. Most
good yield and short reaction time are the significant advantages
from synthetic viewpoint. All the compounds of the compounds
were identified to be active, with an efficacy comparable to those
of the standard drugs. Most of the bis(indolyl)methanes showed
good antioxidant potential. Further studies on the activity of these
compounds in an expanded panel of organisms and in vivo efficacy
models will be reported in due course.
13. Zeligs, M. A. J. Med. Food 1998, 1, 67.
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64, 2369; (b) Praveen, C.; Sagayaraj, Y. W.; Perumal, P. T. Tetrahedron Lett. 2009,
50, 644; (c) Praveen, C.; Kiruthiga, P.; Perumal, P. T. Synlett 2009, 1990; (d)
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Muralidharan, D.; Perumal, P. T. Synthesis 2004, 63; (j) Shanthi, G.;
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Acknowledgment
One of the authors C.P. thanks CSIR, New Delhi for the research
fellowship.
17. For reactions involving Zn(OTf)2 as catalyst, see: (a) Chiacchio, U.; Rescifina, A.;
Saita, M. G.; Iannazzo, D.; Romeo, G.; Mates, J.; Tejero, T.; Merino, P. J. Org.
Chem. 2005, 70, 8991; (b) Murakata, M.; Tsutsui, H.; Hoshino, O. Org. Lett. 2001,
3, 299; (c) Ishimaru, K.; Kojima, T. J. Org. Chem. 2003, 68, 4959; (d) Zhu, X.;
Ganesan, A. J. Org. Chem. 2002, 67, 2705.
References and notes
18. Representative procedure for the Zn(OTf)2 catalyzed synthesis of quinoline (3i)
under microwave condition: 20-aminobenzophenone (1.0 mmol), 3-
bromophenylacetylene (1.5 mmol) and Zn(OTf)2 (1 mol %) was stirred for
5 min for uniform mixing and was then transferred to a glass tube and inserted
in an alumina bath (100 g, 60 G254, Fischer scientific bath (6.8 cm diameter))
and was irradiated in a domestic microwave oven (BPL, India) at 450 W for
10 min. The temperature of the alumina bath (90 °C) was measured after 1 min
of the reaction. On completion, the reaction mixture was directly charged on a
small silica gel column and eluted with a mixture of EtOAc/hexane to afford the
pure quinoline product (3i) as yellow liquid; IR (film): 701, 773, 793, 878, 1073,
1. (a) Michael, J. P. Nat. Prod. Rep. 2007, 24, 223; (b) Michael, J. P. Nat. Prod. Rep.
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4. Bergstrom, F. W. Chem. Rev. 1944, 35, 153.
5. Cheng, C.-C.; Yan, S.-J. Org. React. 1982, 28, 37.
1545, 1588, 3062 cmꢀ1
7.44–7.58 (m, 7H), 7.70–7.73 (s, 1H),7.75 (s, 1H), 7.90 (dd, J = 0.75, 8.11 Hz,
1H), 8.09 (dt, J = 0.72, 7.8 Hz, 1H), 8.21–8.24 (m, 1H), 8.38 (t, J = 1.7 Hz, 1H). 13
.
1H NMR (500 MHz, CDCl3) dH 7.36 (t, J = 7.8 Hz, 1H),
C
NMR (125 MHz, CDCl3): dC 118.9, 123.0, 125.6, 125.8, 126.0, 126.6, 128.4,
128.6, 129.4, 129.6, 130.11, 130.2, 130.5, 132.1, 138.1, 141.5, 148.6, 149.42,
155.0. MS (ESI): m/z = 360 [M+H]+, 362 [M+H]+.2 Anal. Calcd for C21H14BrN: C,
70.02; H, 3.92; N, 3.89. Found: C, 70.41; H, 4.00; N, 3.75. This procedure was
followed for all the substrates.
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2002, 4, 2605; (b) Yamashita, M.; Yamada, K.-i.; Tomioka, K. Adv. Synth. Catal.
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3653; (c) Xiao, F.; Chen, Y.; Liu, Y.; Wang, J. Tetrahedron 2008, 64, 2755; (d)
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7079.
20. Representative procedure for the Zn(OTf)2 catalyzed synthesis of
bis(indolyl)methane (6i) under microwave condition: 2-Phenylindole (4)
(1.0 mmol), aldehyde (5i) (0.55 mmol) and Zn(OTf)2 (1 mol %) was stirred for
5 min for uniform mixing and was then transferred to a glass tube and inserted
in an alumina bath (100 g, 60 G254, Fischer scientific bath (6.8 cm diameter))
and was irradiated in a domestic microwave oven (BPL, India) at 450 W for
10 min. The temperature of the alumina bath (90 °C) was measured after 1 min
of the reaction. On completion, the reaction mixture was directly charged on a
small silica gel column and eluted with a mixture of EtOAc/hexane to afford the
pure bis(indolyl)methane (6i) product as a pale yellow solid; mp 278–280 °C;
Rf = 0.23 (AcOEt/petroleum ether 20%). IR (KBr): 3401, 1483, 1457, 1340, 1233,
.
743 cmꢀ1 1H NMR (500 MHz, DMSO-d6) dH 1.26 (t, 3H, J = 7.6 Hz, –NCH2CH3),
11. Shiri, M.; Zolfigol, M. A.; Kruger, H. G.; Tanbakouchian, Z. Chem. Rev. 2010, 110,
2250.
4.33 (q, 2H, J = 6.8 Hz, –NCH2CH3), 6.17 (s, 1H, –CH-Ar), 6.58 (t, 2H, J = 8.4 Hz,