A facile synthesis of 1,2,3-triazolyl indole hybrids via SbCl3-catalysed Michael addition of indoles to 1,2,3-triazolyl chalcones

Article abstract of DOI:10.1007/s12039-012-0281-x

An efficient, facile and environmentally benign synthesis of a library of 1,2,3-triazolyl chalcone hybrids (3a-u) has been accomplished by grinding the reactants at room temperature in excellent yields in very short reaction time. Subsequently, SbCl₃ catalysed Michael addition of indoles to the chalcones afford 1,2,3-triazolyl indole hybrids (5a-l) in excellent yields. Indian Academy of Sciences.

Full text of DOI:10.1007/s12039-012-0281-x

c
J. Chem. Sci. Vol. 124, No. 4, July 2012, pp. 941–950. ꢀ Indian Academy of Sciences.
A facile synthesis of 1,2,3-triazolyl indole hybrids via SbCl3-catalysed
Michael addition of indoles to 1,2,3-triazolyl chalcones
POOVAN SHANMUGAVELAN, MURUGAN SATHISHKUMAR,
SANGARAIAH NAGARAJAN and ALAGUSUNDARAM PONNUSWAMY∗
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625 021, India
e-mail: ramradkrish@yahoo.co.in
MS received 17 December 2011; revised 29 February 2012; accepted 6 March 2012
Abstract. An efficient, facile and environmentally benign synthesis of a library of 1,2,3-triazolyl chalcone
hybrids (3a–u) has been accomplished by grinding the reactants at room temperature in excellent yields in
very short reaction time. Subsequently, SbCl3 catalysed Michael addition of indoles to the chalcones afford
1,2,3-triazolyl indole hybrids (5a–l) in excellent yields.
Keywords. Environmentally benign; 1,2,3-triazolyl chalcone; Michael addition; SbCl3 catalysed;
1,2,3-triazolyl indole.
1. Introduction
2. Experimental
Chalcones represent an important group of natural pro- All chemicals, reagents and solvents were of com-
ducts belonging to the flavonoids family.1,2 Compounds mercially high purity grade purchased from Avra
with the backbone of chalcones possess interesting Synthesis Pvt. Ltd. and Merck Pvt. Ltd. India. 1H NMR
biological activities such as cytotoxic,3 antimalarial,4 and 13C NMR spectra were recorded in CDCl3 on
antileishmanial,5 antiinflammatory,6 antiHIV,7 antifun- Bruker Avance 300 MHz spectrometer and the chem-
gal8 and tyrosine kinase inhibitors.9
ical shifts are reported as δ values in parts per mil-
On the other hand, 1,2,3-triazoles have received lion (ppm) relative to tetramethylsilane, with coupling
1
much attention due to their interesting pharmacologi- constant (J) values in Hertz (Hz). In H NMR, the
cal activity profile such as antibiotic, antifungal, ante- abbreviation of splitting refers as s=singlet, d=doublet,
helmintic,10 anticancer activity,11 and antiHIV.12 They t=triplet, q=quartet, m=multiplet, dd=doublet of dou-
also serve as potential chemotherapeutic agents for blet and bs=broad singlet. 13C NMR data are reported
various diseases.13
with the solvent peak (CDCl3 = 77.00 MHz) as the
Indole derivatives continue to receive much attention internal standard. Elemental analyses of all the com-
in organic synthesis because of their biological activi- pounds were performed which were in agreement with
ties.14,15 Among them, 3-substituted indoles are impor- the calculated values within 0.4%.
tant building blocks for the synthesis of biologically
active compounds and natural products.16
Keeping in view of the potential importance of the
above said individual bioactive compounds, it was
2.1 Synthesis of 4-acetyl-1-benzyl-5-methyl-1,2,3-
triazole (1)17
envisaged that synthesis of molecules containing two of
the above said moieties in a single framework is worth
the attempt. In this regard, we report here for the first
time the synthesis of the hybrid molecules containing
the triazole–enone and triazole–indole skeletons.
A mixture of benzyl azide (3.00 g, 1.0 equiv), acetyl
acetone (2.25 g, 1.0 equiv), potassium carbonate
(6.23 g, 2.0 equiv) and absolute ethanol (95%, 15 ml)
was taken in a round bottomed flask equipped with
stirrer. The reaction mixture was stirred at 75◦C for
30 min. The progress of the reaction was monitored
by TLC. After the completion of the reaction, the
solvent was removed under vacuum and to the resi-
dual mass, excess of ice-water was added and neutra-
lized with 10% HCl (20 ml). The product was extracted
∗For correspondence
941

942
Poovan Shanmugavelan et al.
with diethyl ether (20 ml) and the extract was dried The triazolyl indole hybrids (5) which precipitated as
over anhydrous sodium sulphate. Evaporation of the solids were filtered recrystallized from ethanol. Yield:
solvent gave the crude product, which was purified 95–98%.
by column chromatography using petroleum ether:
ethylacetate (98:3) as eluent and recrystallized from
absolute ethanol. Yield: 3.97g (82%), Mp. 148◦C.
2.3a 1-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-3-(1H-
indol-3-yl)-3-phenylpropan-1-one (5a): Yield: 0.37 g
(96%), colourless solid, mp.138–139◦C. 1H NMR
spectrum (CDCl3, 300 MHz), δ, ppm, 2.32 s (3H, CH3),
3.88 dd (1H, CH2, J = 7.8 and 16.2 Hz), 4.01 dd (1H,
CH2, J = 7.5 and 16.2 Hz), 5.09 t (1H, CH, J =
7.8 Hz), 5.53 s (2H, N-CH2), 6.97–7.50 m (14H, ArH),
8.02 s (1H, NH). 13C NMR spectrum (CDCl3, 75 MHz),
δ, ppm, 9.08, 38.23, 46.29, 51.66, 110.94, 119.34,
119.49, 119.61, 121.55, 122.03, 126.11, 126.94, 127.26,
128.29, 128.58, 129.12, 134.00, 136.61, 137.09, 143.93,
144.51, 194.85. Found, %: C 77.09, H 5.76, N 13.31.
C27H24N4O. Calculated, %: C 77.12, H 5.75, N 13.32.
The analytical data of all the synthesized compounds
are presented in the supplementary information.
2.2 General procedure for the synthesis of 1,2,3-triazolyl
chalcone hybrids (3)
A mixture of 4-acetyl-1-benzyl-5-methyl-1,2,3-triazole,
1 (0.2 g, 1.0 equiv) and aromatic/heteroaromatic alde-
hydes, 2 (1.0 equiv) and 50% aqueous sodium hydrox-
ide solution (1 ml) was ground for 4–7 min at room
temperature and poured onto excess of crushed ice and
neutralized with dilute hydrochloric acid. The chalcone
derivatives (3) which precipitated as solids were filtered
and recrystallized from ethanol. Yield: 97–99%.
2.2a (E)-1-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-
3-phenylprop-2-en-1-one (3a): Yield 0.27 g (97%),
white solid, mp.157–158◦C. 1H NMR spectrum (CDCl3,
300 MHz), δ, ppm: 2.55 s (3H, CH3); 5.57 s (2H,
N-CH2), 7.20–7.72 m (10H, ArH), 7.87 d (1H, =CH, J =
15.9 Hz), 8.05 d (1H, =CH, J = 15.9 Hz). 13C NMR
spectrum (CDCl3, 75 MHz), δ, ppm: 9.31, 51.75, 123.16,
127.25, 128.60, 128.71, 128.85, 129.14, 130.41,
134.07, 135.09, 137.95, 143.53, 144.36, 184.40. Found,
%: C 75.27, H 5.65, N 13.84. C19H17N3O. Calculated,
%: C 75.23, H 5.65, N 13.85.
3. Results and discussion
Traditionally, chalcones could be obtained via Claisen–
Schmidt condensation carried out in acidic or basic
media under homogeneous conditions, with many
drawbacks, such as catalyst recovery and waste disposal
problems.18 As a potential alternative, heterogeneous
catalysts have also been used for Claisen–Schmidt con-
densation, including Lewis acids,19 Bronsted acids,20
solid acids,21 and solid bases.22 In addition, ionic liq-
uids23 and microwave24 have also been tried to enhance
the yields of the chalcones. But all these reported meth-
ods make use of organic solvents during condensation
and during isolation of products by way of extraction.
2.3 General procedure for the synthesis of 1,2,3-triazolyl
indole hybrids (5)
To a solution of 1-benzyl-5-methyl-1,2,3-triazol-4-yl-3- These organic solvents have been considered to be haz-
arylprop-2-en-1-one, 3 (0.2 g, 1.0 equiv) and indole/2- ardous to human health and the environment due to their
methylindole, 4 (1.0 equiv) in CH3CN (3–5ml) was volatile nature. Hence, development of organic reac-
added SbCl3 (10 mol%) and the mixture was refluxed tions under solvent-free conditions being eco-friendly
for 3–4 h. After completion of reaction as indicated has attained much importance. In particular, organic
by TLC, the catalyst was filtered and the filtrate was reactions in water medium are of current interest.
concentrated under reduced pressure to give the crude
To the best of our knowledge, though there are very
product, which was triturated with petroleum ether. few reports on triazolyl chalcone synthesis in organic
O
CH3
N
CH3
CH3
O
50% NaOH
N
N
H
N
N
i) EtOH, ref lux
ii) grinding, rt
iii) H2O, grinding, rt
N
O
3a
2a
1
Scheme 1. Reaction optimization for the synthesis of 1,2,3-triazolyl chalcone hybrid (3a).

An efficient antimony chloride catalysed synthesis of 1,2,3-triazolyl indole hybrid
943
O
H
R3
R3
R1
N3
R2
CH3
N
R2
2
CH3
CH3
O
K2CO3
R1
N
N
N
N
50 % aq.NaOH
EtOH
N
O
O
O
grinding,
4-7 minutes
rt
ref, 30 min
1
3
o = R1=R3=Cl, R2=H
h = R1=Cl, R2=R3=H
i = R1=Br, R2=R3=H
j = R1=CH3, R2=R3=H
k = R1=OCH3, R2=R3=H
l = R1=NO2, R2=R3=H
m = R1=R3=H, R2=Br
n = R1=R3=H, R2=OCH3
a = R1=R2=R3=H
p = R1=R3=OCH3, R2=H
q = R1=H, R2=R3=OCH3
r = cinnamaldehyde
s = furfuraldehyde
t = 5-methylfurfuraldehyde
u = thiophene-3-aldehyde
b = R1=R2=H, R3=Cl
c = R1=R2=H, R3=Br
d = R1=R2=H, R3=F
e = R1=R2=H, R3=CH3
f = R1=R2=H, R3=OCH3
g = R1=R2=H, R3=NO2
Scheme 2. Synthesis of 1,2,3-triazolyl chalcone hybrids (3a–u).
solvents,25 perusal of literature suggests the lack of affording the 1,2,3-triazolyl chalcone hybrid (3a) in
any report on the synthesis of 1,2,3-triazolyl chalcone 97% yield. On the other hand, grinding the heteroge-
hybrids in water which forms the first part of the present nous reaction mixture in minimum amount of water at
study. Here, it is notable that the yield of the hybrids in room temperature gave identical yield of 3a in compara-
the organic solvent viz. ethanol and in water medium is ble reaction time, i.e., 4 min. The later protocol avoiding
comparable.
the organic solvent viz. ethanol is greener.
At the outset, a mixture of 1,2,3-triazolylketone (1a,
The broad scope of the above said protocol involv-
1.0 equiv), benzaldehyde (2a, 1.1 equiv) and 50% ing water as media was established via the synthesis
NaOH in ethanol (5 ml) was stirred at room tempera- of a library of 1,2,3-triazolyl chalcone hybrids (3a–u,
ture (scheme 1). The reaction was completed in 5 min scheme 2) in excellent yields (97–99%, table 1).
Table 1. Synthesis of 1,2,3-triazolyl chalcone hybrids (3a–u).
1,2,3-triazolyl
Solvent (ethanol)
Water (grinding)
Aldehydes
(2a–u)
chalcones
(3a–u)
Time
(min)
Yield
(%)
Time
(min)
Yield
(%)
Entry
1
CH3
2a
2b
3
2
97
97
4
4
97
98
N
N
N
O
3a
3b
Cl
CH3
2
3
4
N
N
N
O
Br
CH3
2c
2
2
98
99
4
4
98
98
N
N
N
3c
O
F
CH3
2d
N
N
N
O
3d

944
Poovan Shanmugavelan et al.
Table 1. (continued)
1,2,3-triazolyl
chalcones
Solvent (ethanol) Water (grinding)
Aldehydes
Entry (2a–u)
Time
(min)
Yield
(%)
Time
(min)
Yield
(%)
(3a–u)
CH3
CH3
5
6
2e
2f
3
3
98
96
5
4
99
97
N
N
3e
3f
N
O
OCH3
CH3
N
N
N
O
NO2
CH3
7
2g
4
98
6
97
N
N
3g
N
O
CH3
8
2h
2i
4
4
4
98
97
97
7
7
7
98
98
97
Cl
N
N
N
O
3h
CH3
9
Br
N
N
N
O
3i
CH3
10
2j
CH3
N
N
N
O
3j
CH3
11
12
13
14
2k
2l
3
4
3
3
98
98
98
97
7
7
6
6
97
97
98
97
OCH3
N
N
N
O
3k
3l
CH3
NO2
Br
N
N
N
O
CH3
2m
2n
N
N
N
O
3m
OCH3
CH3
N
N
N
O
3n

An efficient antimony chloride catalysed synthesis of 1,2,3-triazolyl indole hybrid
945
Table 1. (continued)
1,2,3-triazolyl
Solvent (ethanol) Water (grinding)
Aldehydes
Entry (2a–u)
chalcones
(3a–u)
Time
(min)
Yield
(%)
Time
(min)
Yield
(%)
Cl
CH3
15
16
2o
2p
4
4
98
97
7
7
98
97
Cl
N
N
3o
N
O
OCH3
CH3
OCH3
N
N
3p
N
O
OCH3
OCH3
CH3
17
18
19
2q
2r
2s
4
4
2
96
97
98
7
7
5
97
97
98
N
N
3q
N
O
CH3
N
N
N
O
3r
O
CH3
N
N
N
O
3s
H3C
O
20
21
2t
2
2
97
97
5
5
97
97
CH3
N
N
N
3t
O
S
CH3
N
2u
N
N
O
3u
The X-ray crystal structure of compounds, 3a26 and Among the various approaches for preparing three-
3d27 proved their structures unequivocally.
substituted indoles,30,31 Michael addition32,33 of indoles
to electron-deficient olefins or α,β-unsaturated ketones
being direct method is very elegant. This conjugate
addition is facilitated in the presence of various cata-
lysts,34 protic30 and/or Lewis acid.31 As the strong acid
catalysed Michael addition is associated with the side
3.1 Micheal addition of indoles to 1,2,3-triazolyl
chalcone hybrids
Three substituted indoles exhibit numerous biological reactions resulting in dimerization and polymerization,
activities28 and are also used as building blocks for the utility of efficient catalysts in the conjugate addition has
synthesis of natural products and therapeutic agents.29 attained importance.

946
Poovan Shanmugavelan et al.
NH
CH3
N
N
O
N
N
H
N
Catalysts
N
O
N
CH3CN
reflux
CH3
3a
5a
4
Scheme 3. Catalyst screening in the synthesis of 1,2,3-triazolyl indole hybrid (5a).
Table 2. Catalyst screening in the synthesis of 1,2,3-triazolyl
indole hybrid (5a).
Reaction condition
Entry
Catalyst
Reaction time (h)
Yield (%)
1
2
3
4
5
FeCl3
AlCl3
SbCl3
SnCl3
PTSA
10
12
3
>12
>12
70
60
96
–
–
NH
CH3
N
N
O
R1
R
H
SbCl3
N
N
N
O
R1
N
N
CH3CN
reflux, 3-4 hr
CH3
R
5
4
3
R
a = H; b = 4-CH3; c = 4-NO2; d = 4-Br; e = 2,4-di-Cl; f = furan-2
R1 = H, CH3
Scheme 4. Synthesis of 1,2,3-triazolyl indole hybrids (5a–l).
Here, we report for the first tme the synthesis of
Further, to establish the broad scope of the catalyst,
hybrid compounds containing 1,2,3-triazole and indole synthesis of a series of 1,2,3-triazole-indole hybrids
skeleton via. SbCl3 catalysed conjugate addition of (5) has been accomplished via the Michael addition
indoles to 1,2,3-triazolyl chalcones, the details of which of indole/2-methylindole (4) with 1,2,3-triazolyl chal-
are presented vide infra.
cones (3) in the presence of SbCl3(10 mol%) in CH3CN
In the preliminary study, for the purpose of screening (scheme 4). Generally, after completion of the reac-
of the catalyst, FeCl3 (10 mol%) was used as catalyst tion as indicated by TLC, the catalyst was filtered and
in the Michael addition of indole (4, 1.0 equiv) to the the filtrate concentrated under reduced pressure to give
chalcone (3a, 1.0 equiv) which gave the product (5a) the crude product, which on triturating with petroleum
in 60% yield in 10 h (scheme 3). The reaction was then ether afford the 1,2,3-triazolyl indole hybrids (5a–l)
performed by varying the catalysts (table 2, entry 1–5). as solids in excellent yields (95–98%, table 3). The
This screening study indicated that SbCl3 (table 2, entry products were recrystallized from ethanol.
3) is the best catalyst affording 96% of 5a in short
reaction time (3 h).
The synthesized compounds were characterized by
NMR (1D and 2D), IR and mass spectral techniques.

An efficient antimony chloride catalysed synthesis of 1,2,3-triazolyl indole hybrid
947
Table 3. Synthesis of 1,2,3-triazolyl indole hybrids (5a–l).
Chalcone
Indole
(4)
1,2,3-triazolyl indole hybrid Time Yield
Entry
(3)
(5a–l)
(h)
(%)
NH
H
N
N
N
1
3a
3
96
N
O
CH3
5a
NH
H
N
N
N
N
4
2
3
5
3c
3e
3g
3o
3.5
95
98
95
95
O
O
O
CH3
Br
5b
5c
5d
5e
NH
H
N
N
N
N
3
CH3
CH3
NH
H
N
N
N
N
3.5
CH3
NO2
NH
Cl
H
N
N
N
N
4
O
CH3
Cl
NH
O
H
N
N
N
N
6
7
3s
4
97
97
O
CH3
5f
NH
H
N
N
N
N
CH3
3a
3.5
CH3
O
CH3
5g

948
Poovan Shanmugavelan et al.
Table 3. (continued)
Chalcone
Indole
(4)
1,2,3-triazolyl indole hybrid Time Yield
Entry
(3)
(5a–l)
(h)
(%)
NH
CH3
H
N
N
N
N
10
3c
3.5
96
CH3
CH3
CH3
CH3
CH3
O
CH3
Br
5h
NH
CH3
H
N
N
N
N
8
3e
3g
3o
3s
3
3.5
4
98
95
95
95
O
CH3
CH3
NH
5i
H
N
N
N
N
CH3
9
O
O
O
CH3
NO2
5j
5k
5l
NH
CH
H
N
N
N
N
Cl3
11
12
CH3
Cl
NH
CH3
H
N
N
N
N
4
O
CH3
3.88, dd,
J=7.5 & 16.2 Hz,
1H
8.06, d, 1H,
NH
8.02, s, 1H
4.01, dd,
J=7.5 & 16.2 Hz,
J=16.2 Hz
143.93
H
H
1H
122.89 134.86
143.42
N
H
N
38.23
N
N
144.20
46.29
H
5.09, t,
J=7.8 Hz, 1H
H
194.85
184.24
O
133.92
7.71, m, 2H
H
N
H
N
143.93
136.61
51.61
H
5.55, s, 2H
5.46, s, 2H
H
137.91
7.87, d, 2H,
J=16.2 Hz
51.66
137.09
127.15
O
H
CH3
2.37, s, 3H
9.08
134.00
H
H
H
7.19, d, 2H,
J=7.2 Hz
H
2.54, s, 3H
(3a)
(5a)
Figure 1. Selected 1H and 13C NMR chemical shift values.

An efficient antimony chloride catalysed synthesis of 1,2,3-triazolyl indole hybrid
949
Selected 1H and 13C NMR chemical shift values of rep- 12. Alvarez R, Velazquez S, San-Felix A, Aquaro S, De
Clerq E, Perno C F, Karlsson A, Balzarini J and
Camarasa M J 1994 J. Med. Chem. 37 4194
13. Wang S, Wang Q, Wang Y, Liu L, Weng X, Zhang
resentative compounds 3a and 5a are presented vide
infra (figure 1).
G L X and Zhou X 2008 Bioorg. Med. Chem. Lett. 18
6505
4. Conclusion
14. (a) Aubry C, Patel A, Mahale S, Chaudhuri B, Marechal
J D, Sutcliffe M J and Jenkins P R 2005 Tetrahedron.
Lett. 46 1423; (b) Marugan J J, Manthey C, Anaclerio B,
Lafrance L, Lu T, Markotan T, Leonard K. A, Crysler C,
Eisennagel S, Dasgupta M and Tomczuk B 2005 J. Med.
In conclusion, we have reported for the first time a
facile, rapid, mild and environmentally benign, green
protocol for the synthesis of a library of 1,2,3-triazolyl
chalcone hybrids by just grinding the reactants and
SbCl3 catalysed synthesis of a series of 1,2,3-triazolyl
indole hybrids via Michael addition in excellent yields.
Chem. 48 926; (c) Fukuyama, T and Chen X Q 1994
J. Am. Chem. Soc. 116 3125
15. (a) Zhang H C, Ye H, Moretto A F, Brumfield K K and
Maryanoff B E 2000 Org. Lett. 2 89; (b) Faul M M,
Winneroski L L and Krumrich C A 1998 J. Org. Chem.
63 6053; (c) Tani M, Matsumoto S, Aida Y, Arikawa S,
Nakane A, Yokoyama Y and Murakami Y 1994 Chem.
Pharm. Bull. 42 443
16. (a) Gribble G W 2000 J. Chem. Soc. Perkin Trans. 1
1045; (b) Moore R E, Cheuk C, Yan X Q, Patterson
G M L, Bonjouklian R, Smitka T A, Mynderse J S,
Foster, R S, Jones N D, Swartzendruber, J K and Deeter,
J B 1987 J. Org. Chem. 52 1036; (c) Moore R E,
Cheuk C, Patterson G M L 1984 J. Am. Chem. Soc. 106
6456
17. Kamalraj V R, Senthil S and Kannan P 2008 J. Mol.
Struct. 892 210
18. Dhar D N 1981 New York: Wiley
19. (a) Iranpoor N, Kazemi F, Iranpoor N and Kazemi E
1998 Tetrahedron. 54 9475; (b) Narender T and Reddy
K P 2007 Tetrahedron. Lett. 48 3177
Supplementary information
The supplementary information can be seen in
www.ias.ac.in/chemsci.
Acknowledgements
The authors thank Intensification of Research in High
Priority Areas (IRHPA), the Department of Science
and Technology (DST), India for providing 300 MHz
NMR instrument for recording the NMR spectra for
the compounds synthesized and the University Grants
Commission (UGC), India for giving financial support.
20. Szell T and Sohar I 1969 Can. J. Chem. 47 1254
21. (a) Drexler M T and Amiridis J 2003 J. Catal. 214
136; (b) Choudary B M, Ranganath K V, Yadav, J
and Kantam M L 2005 Tetrahedron Lett. 46 1369; (c)
Saravanamurugan S, Palanichamy M, Arabindoo B and
Murugesan V 2004 J. Mol. Catal. A: Chem. 218 101
22. (a) Daskiewicz J B, Comte G, Barron D, Pietro A D and
Thomasson F 1999 Tetrahedron Lett. 40 7095; (b) Sebti
S, Solhy A, Smahi A, Kossir A and Oumimoun H 2002
Catal. Commun. 3 335; (c) Wang X and Cheng S 2006
Catal. Commun. 7 689
References
1. Nowakowska Z 2007 Eur. J. Med. Chem. 42 125
2. Akihisa T, Tokuda H, Hasegawa D, Ukiya M, Kimura Y
and Enjo F 2006 J. Nat. Pro. 69 38
3. Modzelewska A, Pettit C, Achanta G, Davidson N E,
Huang, P and Khan S R 2006 Bioorg. Med. Chem. 14
3491
4. Dominguez J N, Leon C, Rodrigues J, Gamboa de
Dominguez N, Gut J and Rosenthal P J 2005 J. Med.
Chem. 48 3654
23. (a) Yang S D, Wu L Y, Yan ZY, Pan Z L and Liang
Y M 2007 J. Mol. Catal. A: Chem. 268 107; (b) Dong
F, Jian C, Hao F Z, Kai G and Liang L Z 2008 Catal.
Commun. 9 1924; (c) Pilar F and Antonio G 2004 J. Mol.
Catal., A: Chem. 214 137; (d) Shen J H, Wang H, Liu
H C, Sun Y and Liu Z M 2008 J. Mol. Catal. A: Chem.
280 24
5. Nielsen S F, Christensen S B, Cruciani G, Kharazmi A
and Liljefors T 1998 J. Med. Chem. 41 4819
6. Yang H M, Shin H R, Cho S H, Bang S C, Song G Y and
Ju J H 2007 Bioorg. Med. Chem. 15 104
7. Cheenpracha S, Karalai C, Ponglimanont C,
Subhadhirasakul S and Tewtrakul S 2006 Bioorg. Med.
Chem. 14 1710
8. Svetaz L, Tapia A, Lopez S N, Furlan R L F, Petenatti E
and Pioli R 2004 J. Agri. Food Chem. 52 3297
9. Nerya R, Musa S, Khatib S, Tamir and Vaya J 2004
Phytochemistry 65 1389
10. (a) Aufort M, Herscovici J, Bouhours P, Moreau N and
Girard C 2008 Bioorg. Med. Chem. Lett. 18 1195; (b)
Wang X L, Wan K and Zhou C H 2010 Eur. J. Med.
Chem. 45 4631; (c) Odlo K, Hentzen J, Chabert J F D,
Ducki S, Gani, O A B S M, Sylte I, Skrede M, Florenes
V A and Hansen T V 2008 Bioorg. Med. Chem. 16 4829
11. Li W T, Wu W H, Tang C H, Tai R and Chen S T 2011
Combinatorial. Sci. 13 72
24. Gupta R, Gupta A K, Paul S and Kachroo P L 1995
Indian J. Chem. 34 61
25. (a) Funiss B S, Hannford A J, Smith P W G Tatchell
A R 2004 Vogel’s Textbook of practical organic chem-
istry, fifth edition 19 1032; (b) Guantai, Kanyile Ncokazi
E M, Timothy E J, Jiri Gut, Rosenthal, P J, Smith, P J
and Kelly Chibale 2010 Bioorg. Med. Chem. 18 8243;
(c) Ahmed Kamal S, Prabhakar M, Janaki Ramaiah
P, Venkat Reddy, Ratna Reddy A, Mallareddy Nagula
Shankaraiah T, Lakshmi Narayan Reddy S, Pushpavalli
N C and Manika Pal Bhadra V L 2011 Eur. J. Med.
Chem. 46 3820

950
Poovan Shanmugavelan et al.
26. Fun
H
K, Hemamalini M, Shanmugavelan P, 32. Noland W E, Christensen G M, Sauer G L and Dutton
Ponnuswamy A and Jagatheesan R 2011 Acta Cryst.
E67 o2707
27. Fun K, Hemamalini M, Shanmugavelan P,
Ponnuswamy A and Jagatheesan R 2011 Acta Cryst.
E67 o2776
28. Sundberg R J 1996 The Chemistry of Indoles, New York:
Academic Press 113
G G S 1955 J. Am. Chem. Soc. 77 456
33. (a) Harrington P and Kerr M A 1998 Can. J. Chem.
76 1256; (b) Loh T P and Wei L L 1998 Synlett (9)
975; (c) Loh T P, Pei J and Lin M 1996 Chem. Com-
mun. (20) 2315; (d) Yadav J S, Abraham S, Reddy BVS
and Sabitha G 2001 Synthesis. (14) 2165; (e) Bandini
M, Cozzi PG, Giacomini M, Melchiorre P, Selva S and
Umani-Ronchi A 2002 J. Org. Chem. 67 3700
H
29. (a) Saxton J E 1997 Nat. Prod. Rep. 14 559; (b) Toyota
M and Ihara N 1998 Nat. Prod. Rep. 15 327
34. (a) Tahir R, Banert K, Solhy A and Sebti S 2006 J. Mol.
Catal. A Chem. 246 39; (b) Ko S K Lin C C, Tu Z
J, Wang Y F, Wang C C and Yao, C F 2006 Tetrahe-
dron Lett. 47 487; (c) Bandini M, Cozzi P G, Giacomini
M, Melchiorre P and Selva S 2002 J. Org. Chem. 67
3700; (d) Ji S J and Wang S Y 2005 Sonochem. 12 339;
(e) Srivastava N and Banik B K 2003 J. Org. Chem.
68 2109; (f) Ekbote S S, Panda, A G, Bhor M D and
Bhanage B M 2009 Catal. Commun. 10 1569; (g) Li D P,
Guo Y C, Ding Y and Xiao W J 2006 Chem. Commun.
37 799
30. (a) Szmuszkovicz J 1957 J. Am. Chem. Soc. 79 2819;
(b) Iqbal Z, Jackson A H, Rao and K R N 1988 Tetra-
hedron Lett. 29 2577; (c) Tahir R, Banert K, Solhy A,
Sebt S. 2006 J. Mol. Catal. A. 39 246; (d) Zhou W, Xu
L W, Yang L, Zhao P Q and Xia C G 2006 Eur. J. Org.
Chem. (23) 5225
31. (a) Zhan Z P and Lang K 2005 Synlett (10) 1551; Yadav
J S, Reddy B V S, Baishya G, Reddy K V and Narsaiah
A V 2005 Tetrahedron 61 9541; (b) Zhan Z P, Yang R F
and Lang K 2005 Tetrahedron Lett. 46 3859