Facile synthesis of 3-substituted indoles containing highly polarized double bonds

Article abstract of DOI:10.1016/j.crci.2016.09.004

In this paper, an effective procedure is described for the synthesis of novel indoles containing highly polarized double bonds. The strategy involves the preparation of (indolylmethyl)malononitriles via the one-pot three-component reaction of an aldehyde,

Full text of DOI:10.1016/j.crci.2016.09.004

C. R. Chimie xxx (2016) 1e5
Contents lists available at ScienceDirect
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Full paper/M eꢀ moire
Facile synthesis of 3-substituted indoles containing highly
polarized double bonds
*
Mehdi Omidi, Mohammad Ali Amrollahi
Department of Chemistry, Yazd University, P.O. Box 89195e741, Yazd, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
In this paper, an effective procedure is described for the synthesis of novel indoles con-
taining highly polarized double bonds. The strategy involves the preparation of (indo-
lylmethyl)malononitriles via the one-pot three-component reaction of an aldehyde,
Received 20 June 2016
Accepted 15 September 2016
Available online xxxx
2
malononitrile and indole in the presence of Zn(OAc) /NaOAc under silent and ultrasonic
conditions. The reaction further proceeds through oxidative elimination under solvent-free
Keywords:
conditions in the presence of Ca(OCl)
short reaction times.
2
to furnish indolylacrylonitriles in high yields and
Ca(OCl)
2
One-pot
©
2016 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Oxidative elimination
Indolylacrylonitriles
3-Substituted indoles
1
. Introduction
irradiation [14e17]. In continuation of our previous work
on the development of new and simple synthetic meth-
odologies [18,19], initially, (indolylmethyl)malononitriles
were synthesized by the reaction of aldehydes, malononi-
The indole nucleus has been found as an essential
element in medicinal and agricultural chemistry with sig-
nificant biological activities [1e3]. 3-Substituted indoles
are prominent structural motifs found in numerous natural
products or therapeutic agents with diverse pharmaceu-
tical activities [4e6]. The development of simple proced-
ures for the synthesis of compounds with biological
benefits is the driving force for the discovery and design of
new bioactive compounds. Three-component reactions of
indoles, aldehydes, and malononitrile were used as a sim-
ple procedure to produce 3-substituted indole derivatives
trile, and indole in the presence of Zn(OAc)
at 60 C under silent and ultrasound irradiation conditions
(Scheme 1).
2
/NaOAc in EtOH
ꢀ
It is desirable to develop an efficient and cost-effective
method for the oxidative elimination of the synthesized
(indolylmethyl)malononitriles to produce indoles contain-
ing highly polarized double bonds. Therefore, oxohalogen
derivatives have been employed as versatile reagents in
organic synthesis activities owing to their mild oxidative
and halogenating properties [20e25]. In the present study,
[7e13]. Ultrasound irradiation has been also considered as
a clean and useful protocol in organic synthesis during the
last three decades. In comparison with silent methods, the
procedure is more convenient. A large number of organic
reactions can be carried out in higher yields, a shorter re-
action time, and milder conditions under ultrasound
2
among these derivatives, Ca(OCl) was selected as an
oxidant preferred over other available oxidizing agents
because it is cheap, operationally safe, environmentally
friendly, and easy to handle and work up. In the next step,
oxidative elimination of (indolylmethyl)malononitrile de-
rivatives was investigated in the presence of Ca(OCl)
2
at
room temperature (Scheme 2).
*
Corresponding author.
E-mail address: mamrollahi@yazd.ac.ir (M.A. Amrollahi).
http://dx.doi.org/10.1016/j.crci.2016.09.004
631-0748/© 2016 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.
1
Please cite this article in press as: M. Omidi, M.A. Amrollahi, Facile synthesis of 3-substituted indoles containing highly polarized
double bonds, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/j.crci.2016.09.004

2
M. Omidi, M.A. Amrollahi / C. R. Chimie xxx (2016) 1e5
2
Scheme 1. Synthesis of (indolylmethyl)malononitriles catalyzed by Zn(OAc) /NaOAc.
Table 1
Optimization study for the one-pot synthesis of (indolylmethyl)malono-
a
nitrile.
Scheme 2. Oxidative elimination of (indolylmethyl)malononitrile in the
presence of Ca(OCl) .
2
2
. Results and discussion
For the preparation of (indolylmethyl)malononitrile
ꢀ
Entry Catalyst (mol %)
Solvent
T ( C) Time
Yield
(%)
(h)
derivatives, the one-pot three-component reaction of
benzaldehyde, malononitrile, and indole was investigated
as a model reaction. To find the best catalyst, several Lewis
1
2
3
4
5
6
7
8
9
10
ZrOCl
CuCl (10)
FeCl $6H
Zn(OAc) (10)
2
$8H
2
O (10)
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
60
60
60
60
60
60
60
60
60
60
60
9
9
9
9
9
9
7
7
7
9
9
30
45
20
60
75
75
80
85
85
70
72
3
2
O (10)
acids such as ZrOCl
The highest yield was achieved with Zn(OAc)
2
, CuCl, FeCl
3
and Zn(OAc)
2
were used.
. The for-
2
Zn(OAc)
Zn(OAc)
Zn(OAc)
Zn(OAc)
Zn(OAc)
Zn(OAc)
Zn(OAc)
2
2
2
2
2
2
2
(15)
(20)
2
mation of the product was more facile and proceeded in a
shorter time when the reaction was performed in the
/NaOAc (15/5)
/NaOAc (15/10) EtOH
/NaOAc (15/15) EtOH
presence of Zn(OAc)
of 15/10 mol % of Zn(OAc)
2
/NaOAc. The results show that the use
/NaOAc in EtOH is sufficient.
/NaOAc (15/10)
/NaOAc (10/15) EtOH:H
1:1)
Zn(OAc)2/NaOAc (15/10) EtOH
Zn(OAc) /NaOAc (15/10) EtOH
NaOAc (10) EtOH
Zn(OAc) /NaOAc (15/10) EtOH
2
H O
2
11
2
O
Greater amounts of the catalyst had no significant influence
on the reaction yield. To find the optimum temperature, the
(
1
1
2
3
reflux
rt
60
9
9
9
25
5
30
reaction was conducted with 15/10 mol % of Zn(OAc)
2
/
2
ꢀ
NaOAc at room temperature, at 60 C, and at reflux tem-
perature, which resulted in the isolation of the product in a
trace amount, 85% and 25% yields, respectively. In addition,
14
15
b
2
60
20 min 88
a
Reaction conditions: aldehyde (1 mmol), malononitrile (1 mmol), and
CH
2
Cl
2
, MeCN and AcOEt were also tested as solvents. In all
indole(1 mmol).
b
Sonication.
these cases, the product was formed in lower yields.
Solvent-free conditions at different temperatures did not
accelerate the reaction. Thus, the reaction was optimally
conducted in the presence of 15/10 mol % of Zn(OAc)
2
/
ꢀ
2 2
ZrOCl , NaOCl and Ca(OCl) in different solvents at reflux
NaOAc at 60 C in EtOH. To study the effect of ultrasound,
the reactions were carried out under silent and ultrasonic
irradiation conditions. Ultrasound irradiation accelerated
such reactions. The results are summarized in Table 1.
temperature. The progress of the reaction was monitored
by thin-layer chromatography (TLC). The formation of the
product was more facile and proceeded in a shorter time
when the reaction was performed in the presence of
Ca(OCl) under solvent-free conditions at room tempera-
2
ture (Table 3).
To examine the generality of the procedure, the oxida-
tive elimination of various (indolylmethyl)malononitriles
2
and Ca(OCl) was checked under optimized reaction con-
(
Indolylmethyl)malononitrile derivatives were synthe-
sized under the optimized conditions. It can be observed
that the process tolerates both electron-donating and
electron-withdrawing substituents in the substrates. In all
the cases, the reactions proceeded efficiently in EtOH under
mild conditions to afford the corresponding products in
1
ditions. The results are summarized in Table 4.
high yields. All the products were characterized by IR, H
13
The structure of the indolylacrylonitrile derivatives was
and C NMR spectra, and elemental analysis.
1
13
investigated by spectroscopic studies such as IR, H and
C
The (indolylphenylmethyl)malononitrile was subjected
to oxidation using Ca(OCl) to produce indolylphenylacry-
2
lonitrile with an excellent yield. The initial studies were
carried out by treating (indolylphenylmethyl)malononitrile
2 3 2 3
with oxidant agents such as CoCl /KClO , CaCl /KClO
NMR and elemental (CHN) analyses. The indolylacryloni-
trile derivatives were established on the basis of the
1
chemical shift of olefin singlet for vinyl proton in H NMR.
Although the mechanism of these reactions has not yet
been established experimentally, the formation of the
Please cite this article in press as: M. Omidi, M.A. Amrollahi, Facile synthesis of 3-substituted indoles containing highly polarized
double bonds, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/j.crci.2016.09.004

M. Omidi, M.A. Amrollahi / C. R. Chimie xxx (2016) 1e5
3
Table 2
Zn(OAc)
2
/NaOAc promoted one-pot synthesis of (indolylmethyl)malononitriles.a
ꢀ
Entry
R
Time thermal (h)/
Sonication (min)
Yield(%) thermal/
Sonication
mp ( C)
Ref.
1
2
3
4
5
6
7
8
9
H
9/15
6/15
4/11
6/15
6/15
6/15
6/15
9/20
11/25
11/22
10/20
10/20
85/88
85/90
90/85
85/80
87/90
85/90
70/75
80/85
86/90
55/60
70/75
85/90
82e84
81e83
[11]
[16]
[7]
[10]
[11]
[16]
[10]
[9]
3-NO
4-NO
4-F
4-Cl
2,4-diCl
4-Br
2
2
190e192
116e118
78e80
169e171
98e100
165e167
179e181
94e96
4-CN
4-OH
4-OMe
4-Me
4-ipr
10
11
12
[9]
[7]
[9]
120e122
125e127
a
ꢀ
ꢀ
Reaction conditions: aldehyde (1 mmol), malononitrile (1 mmol), indole(1 mmol), and Zn(OAc)
2
/NaOAc (15/10 mol %) at 60 C or u.s./60 C in EtOH.
Table 3
3. Conclusion
a
Optimization study for the synthesis of indolylphenylacrylonitrile.
In summary, a remarkable and expedient technique is
reported for rapid synthesis of 3-substituted indoles con-
taining highly polarized double bonds from easily acces-
sible starting materials. Ultrasound accelerated a one-pot
three-component reaction of an aldehyde, malononitrile,
and indole. This method can be of choice for the prepara-
tion of a variety of (indolylmethyl)malononitrile derivatives
some of which take a long reaction time to be made
through silent approaches. It is also shown for the first time
how oxidative elimination of (indolylmethyl)malononitrile
promoted by calcium hypochlorite is able to yield indoly-
lacrylonitrile, not previously described, in excellent yields,
in short reaction times, and under solvent-free conditions.
Entry Oxidative agent (g)
Solvent
Temp Time (h) Yield
%)
(
1
2
3
4
5
6
7
8
9
1
1
1
1
1
CoCl
CaCl
ZrOCl
NaOCl (0.20)
NaOCl (0.20)
NaOCl (020)
NaOCl (0.20)
Ca(OCl)
Ca(OCl)
Ca(OCl)
Ca(OCl)
Ca(OCl)
Ca(OCl)
Ca(OCl)
2
/KClO
/KClO
$8H
3
(0.0.20/0.10)
(0.20/).10)
O (0.0.20)
H
H
H
H
2
O
2
O
2
O
2
O
Reflux 24
Reflux 24
Reflux 24
Reflux 24
Reflux 24
Reflux 24
e
2
3
e
2
2
e
20
20
50
75
50
55
70
85
EtOH
EtOAc
n-Hexane Reflux 24
4. Experimental
2
2
2
2
2
2
2
(0.20)
(0.20)
(0.20)
(0.20)
(0.20)
(0.10)
(0.17)
H
2
O
Reflux 24
Reflux 24
Reflux 24
All the chemicals were of reagent grades and were used
EtOH
EtOAc
n-Hexane Reflux 2.5
e
e
e
1
13
as received without further purification. H and C NMR
0
1
2
3
4
ꢀ
spectra were recorded at 25 C at a 300 MHz or 400 MHz
rt
rt
rt
20 min 95
20 min 75
20 min 92
(Bruker Avance) instrument using TMS as the internal
standard. The chemical shifts were given in parts per
million (ppm). The IR spectroscopy of the samples as KBr
pellets was carried out on a Bruker Eqinox 55 FT-IR spec-
a
Reaction conditions: 2-((indolyl)(phenyl)methyl)malononitrile
(0.20 g), Solvent-free, and rt.
(
1 mmol), Ca(OCl)
2
ꢁ1
trometer in the 400e4000 cm region. Sonication was
performed in a Shanghai Branson-CQX ultrasonic cleaner
(with a frequency of 25 kHz and a nominal power of
250 W). A reaction flask was placed in an ultrasonic bath,
where the surface of the reactants was slightly lower than
the level of the water. The reaction temperature was
controlled by adding or removing water from the ultrasonic
bath. The melting points were determined by Büchi
melting point B-540 B.V.CHI apparatus in open capillaries.
They were uncorrected. All the reactions and the purity of
product can be rationalized as outlined in Scheme 3. The
Knoevenagel product (1) can be generated in a reaction
between benzaldehyde and malononitrile in the presence
of Zn(OAc)2/NaOAc. Michael addition of indole on com-
2
þ
pound 1 can be enhanced by Zn of Zn(OAc)
vation of olefinic compound 1 to form 3-substituted indole
. Finally, oxidative elimination of 2 in the presence of
Ca(OCl)2 resulted in 3-(Indolyl)-3-phenylacrylonitrile (3).
2
upon acti-
2
Please cite this article in press as: M. Omidi, M.A. Amrollahi, Facile synthesis of 3-substituted indoles containing highly polarized
double bonds, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/j.crci.2016.09.004

4
M. Omidi, M.A. Amrollahi / C. R. Chimie xxx (2016) 1e5
Table 4
4.1.2. Ultrasound irradiation
Oxidative elimination of (indolylmethyl)malononitriles by Ca(OCl)
2
.a
A solution of an appropriate aldehyde (1 mmol), malo-
2
nonitrile (1 mmol), indole (1 mmol), and Zn(OAc) /NaOAc (15/
10 mol %) in EtOH (5 mL) was sonicated in a sonic bath for an
appropriate period of time until the initial materials were no
longer detectable by TLC. After the completion of the reaction,
the solvent was evaporated, and the crude mixture was so-
lidified from a mixture of ethanol and water and then filtered.
A pure product was obtained by recrystallization in ethanol.
ꢀ
Entry
R
Yield (%)
mp ( C)
4.2. General procedure for the synthesis of indolylacrylonitrile
1
2
3
4
5
6
H
98
96
98
93
90
n.r
73e75
105e107
120e122
79e81
95e97
d
3-NO
4-NO
4-Br
4-Me
4-OH
2
2
-((Indolyl)(aryl)methyl)malononitrile (1 mmol) and
2
Ca(OCl) (0.20 g) were added to a mortar. The mixture was
ground using the mortar and pestle at room temperature
for 20 min. After the completion of the reaction, to isolate
2
a
2 2
the catalyst, the mixture was dissolved in hot CH Cl and
Reaction conditions: 2-((indolyl)(aryl)methyl)malononitrile (1 mmol),
(0.20 g), Solvent-free, and rt.
Ca(OCl)
2
filtered. The solvent of the resulting filtrate was evaporated,
and a pure product was obtained by recrystallization from
ethanol. The authenticity of the products was established
the products were monitored using thin-layer chromatog-
raphy (TLC) on aluminum-backed plates coated with Merck
Kieselgel 60 F254 silica gel and by watching the spots under
ultraviolet light.
1
13
by the data of IR, H NMR, C NMR and elemental analyses.
4.3. Selected spectroscopic data
4
.3.1. 2-((Indolyl)(phenyl)methyl)malononitrile
4
.1. General procedure for the synthesis of (indolylmethyl)
ꢀ
White crystals; mp 82e84 C. IR (KBr): ꢀꢁ ¼ 3346, 3031,
malononitriles
ꢁ
1
1
2
882, 2258, 1620, 1458, 746 cm
; H NMR (300 MHz,
CDCl
H), 7.32 (d, J ¼ 8.1 Hz, 1H), 7.26 (t, J ¼ 7.8 Hz, 1H), 7.10 (t,
J ¼ 7.5 Hz, 1H), 4.95 (d, J ¼ 6.3 Hz, 1H), 4.46 (d, J ¼ 6.3 Hz,
3
):
d
¼ 8.29 (s, 1H), 7.48e7.43 (m, 2H), 7.43e7.40 (m,
4
.1.1. Silent conditions
Aldehyde (1 mmol), malononitrile (1 mmol), indole
5
(
(
2
1 mmol), Zn(OAc) /NaOAc (15/10 mol %) and EtOH
5 mL) were placed in a round-bottom flask that was
1
3
1
H) ppm; C NMR (100 MHz, DMSO-d
128.6, 128.0, 127.7, 125.8, 122.7, 121.6, 118.8, 118.5, 114.1,
13.8, 112.3, 111.6, 42.4, 28.6 ppm (Table 2, entry 1).
6
):
d
¼ 139.2, 136.1,
ꢀ
heated at 60 C. The progress of the reaction was fol-
lowed by TLC. After the completion of the reaction, the
solvent was evaporated, the crude mixture was solidified
from a mixture of ethanol and water, and it was filtered.
A pure product was obtained by recrystallization in
ethanol.
1
4.3.2. 2-((Indolyl)(4-nitrophenyl)methyl)malononitrile
ꢀ
Yellow crystals; mp 190e192 C. IR (KBr): ꢀꢁ ¼ 3378,
ꢁ
1 1
3054, 2890, 2258,1607, 1528, 1421, 1351, 744 cm ; H NMR
Scheme 3. The proposed mechanism for the synthesis of indolylacrylonitrile.
Please cite this article in press as: M. Omidi, M.A. Amrollahi, Facile synthesis of 3-substituted indoles containing highly polarized
double bonds, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/j.crci.2016.09.004

M. Omidi, M.A. Amrollahi / C. R. Chimie xxx (2016) 1e5
5
(
2
1
400 MHz,DMSO-d
6
):
H), 7.80 (d, J ¼ 8.8 Hz, 2H), 7.61 (s, 1H), 7.48 (d, J ¼ 8.0 Hz,
H), 7.40 (d, J ¼ 8.0 Hz, 1H), 7.11 (t, J ¼ 6.8 Hz,1H), 6.97 (t,
d
¼ 11.33 (s, 1H), 8.26 (d, J ¼ 8.8 Hz,
ppm; 13C NMR (100 MHz, DMSO-d
137.2, 136.3, 135.4, 130.7, 126.2, 125.1, 124.6, 123.4, 122.0,
120.4, 115.8, 115.3, 113.2, 111.9 ppm; Anal. calcd for
C H N O : C 70.58; H 3.83; N 14.53%. Found: C 70.8; H
17 11 3 2
3.6; N 14.4% (Table 4, entry 2).
6
):
d
¼ 164.9, 147.7, 137.8,
J ¼ 7.2 Hz,1H), 5.99 (d, J ¼ 9.2 Hz,1H), 5.51 (d, J ¼ 9.2 Hz,1H)
13
ppm; C NMR (100 MHz, DMSO-d
29.4, 125.6, 123.9, 123.1, 121.8, 119.1, 118.3, 113.6, 113.4,
11.7, 111.2, 41.7, 28.0 ppm (Table 2, entry 3).
6
):
d
¼ 147.0, 146.6, 136.0,
1
1
4.3.8. 3-(Indolyl)-3-(p-tolyl)acrylonitrile
ꢀ
White crystals; mp 95e97 C. IR (KBr): ꢀꢁ ¼ 3380, 3050,
ꢁ1
1
2
d
240, 1632, 1490, 760 cm
; H NMR (300 MHz, CDCl ):
3
4
.3.3. 2-((Indolyl)(4-fluorophenyl)methyl)malononitrile
ꢀ
¼ 9.85 (s, 1H), 7.87 (d, J ¼ 8.0 Hz, 1H), 7.78 (s, 1H), 7.62 (m,
White crystals; mp 116e118 C. IR (KBr): ꢀꢁ ¼ 3428,
ꢁ
1
1
2
H), 7.55 (d, J ¼ 7.5 Hz, 2H), 7.47 (d, J ¼ 8.0 Hz, 1H), 7.40 (d,
3
054, 2883, 2257, 1605, 1426, 751 cm
;
H NMR
13
J ¼ 7.5 Hz, 2H), 5.12 (s, 1H), 2.27 (s, 3H) ppm; C NMR
(
400 MHz, DMSO-d
6
):
d
¼ 11.25 (s, 1H), 7.57 (m, 3H), 7.45
(
1
1
1
100 MHz, DMSO-d
29.8, 128.8, 125.6, 123.1, 121.6, 120.3, 116.3, 115.6, 113.1,
12.1, 20.5 ppm; Anal. calcd for C18 : C 83.69; H 5.46; N
0.84%. Found: C 83.7; H 5.6; N 11.1% (Table 4, entry 5).
6
)
d
¼ 168.0, 137.1, 136.3, 134.4, 131.9,
(
d, J ¼ 7.6 Hz,1H), 7.40 (d, J ¼ 7.6 Hz, 1H), 7.22 (m, 2H), 7.10
(
t, J ¼ 7.6 Hz, 1H), 6.96 (t, J ¼ 7.2 Hz, 1H), 5.84 (d, J ¼ 9.2 Hz,
13
14 2
H N
1
H), 5.27 (d, J ¼ 9.2 Hz, 1H) ppm; C NMR (100 MHz,
DMSO-d
18.9, 118.4, 115.5, 113.9, 113.7, 112.1, 111.6, 41.5, 28.7 ppm
Table 2, entry 3).
6
):
d
¼ 160.3, 136.0, 135.4, 130.1, 125.8, 122.6, 121.7,
1
(
Acknowledgements
4
.3.4. 2-((Indolyl)(4-hydroxyphenyl)methyl)malononitrile
The authors thank the Research Council of Yazd Uni-
versity for financial support.
ꢀ
Yellow crystals; mp 179e181 C. IR (KBr): ꢀꢁ ¼ 3353,
ꢁ
1
1
2
899, 2226, 1566, 1445, 744 cm
; H NMR (400 MHz,
DMSO-d
6
):
d
¼ 11.17 (s, 1H), 7.89 (d, J ¼ 8.8 Hz, 1H), 7.42 (d,
Appendix A. Supplementary data
J ¼ 8.0 Hz, 1H), 7.28 (d, J ¼ 8.4 Hz, 2H), 7.19 (s, 1H), 7.09 (t,
J ¼ 7.2 Hz, 1H), 6.9 (t, J ¼ 8.5 Hz, 1H), 6.68 (d, J ¼ 8.4 Hz, 2H),
Supplementary data related to this article can be found
at http://dx.doi.org/10.1016/j.crci.2016.09.004.
5
.70 (d, J ¼ 9.2 Hz, 1H), 5.10 (d, J ¼ 9.2 Hz, 1H), 3.40 (broad,
1
H) ppm; 13C NMR (100 MHz, DMSO-d
6
):
30.0, 129.1, 122.7, 121.5, 120.8118.7, 118.6, 118.2, 116.5,
15.2, 115.0, 114.1, 112.7, 111.3 ppm; Anal. calcd for
O: C 75.25; H 4.56; N 14.63%. Found: C 75.1; H 4.6;
N 14.4% (Table 2, entry 9).
d
¼ 160.4, 133.8,
1
1
C
References
H
18 13
N
3
[1] J. Hajicek, Czech. Chem. Commun. 72 (2007) 821.
[2] M.A. Metwally, S. Shaaban, B.F. Abdel-Wahab, G.A. El-Hiti, Curr. Org.
Chem. 13 (2009) 1475.
[
[
3] A. Casapullo, G. Bifulco, I. R. Bruno, J. Nat. Prod. 63 (200) 447.
4] M.P. L eꢀ z eꢀ , M.L. Borgne, P. Marchand, D. Loquet, M. Kogler, G.L. Baut,
4
.3.5. 2-((Indolyl)(p-tolyl)methyl)malononitrile
A. Palusczak, R.W. Hartmann, J. Enzyme Inhib. Med. Chem. 19 (2004) 549.
ꢀ
Pale yellow crystals; mp 120e122 C. IR (KBr): ꢀꢁ ¼ 3350,
[
[
[
5] J. Deng, T. Sanchez, N. Neamati, J.M. Briggs, J. Med. Chem. 49 (2006)
ꢁ
1 1
3
035, 2883, 2225,1588,1459, 745 cm ; H NMR (400 MHz,
1684.
6] R. Contractor, I.J. Samudio, Z. Estrov, D. Harris, J.A. McCubrey,
DMSO-d
6
)
d
¼ 11.22 (s, 1H), 7.87 (d, J ¼ 7.8 Hz, 1H), 7.47 (d,
S.H. Safe, M. Andreeff, M. Konopleva, Cancer Res. 65 (2005) 2890.
J ¼ 7.8 Hz, 1H), 7.44 (s, 1H), 7.41 (d, J ¼ 8.0 Hz, 2H), 7.17 (d,
7] Y. Qu, F. Ke, L. Zhou, Z. Li, H. Xiang, D. Wu, X. Zhou, Chem. Commun.
J ¼ 8.0 Hz, 2H), 7.10e6.96 (m, 2H), 5.82 (d, J ¼ 9.2 Hz, 1H),
47 (2011) 3912.
13
ꢀ
5
.17 (d, J ¼ 9.2 Hz,1H), 2.27 (s, 3H) ppm; C NMR (100 MHz,
[8] D. Anselmo, E.C. Escudero-Adan, M. Martínez Belmonte, A.W. Kleij,
Eur. J. Inorg. Chem. 29 (2012) 4694.
DMSO-d
1
2
6
):
d
¼ 137.0, 136.2, 130.6, 130.1, 129.1, 127.9, 125.8,
[
9] L. Wang, M. Huang, X. Zhu, Y. Wan, Appl. Catal. A. Gen. 454 (2013) 160.
22.6, 121.6, 118.5, 114.1, 113.8, 112.4, 111.6, 42.1, 28.7,
[10] S. Chandrasekhar, V. Patro, G.P.K. Reddy, R. Gr eꢀ e, Tetrahedron Lett.
0.5 ppm (Table 2, entry 11).
53 (2012) 6223.
[
11] N. Singh, B.K. Allam, D.S. Raghuvanshi, K.N. Singh, Adv. Synth. Catal.
3
55 (2013) 1840.
4
.3.6. 3-(Indolyl)-3-phenylacrylonitrile
[12] U.C. Rajesh, J. Wang, S. Prescott, T. Tsuzuki, D.S. Rawat, ACS. Sustain.
Chem. Eng. 3 (2014) 9.
[13] U.C. Rajesh, R. Kholiya, A. Thakur, D.S. Rawat, Tetrahedron Lett. 56
ꢀ
White crystals; mp 73e75 C. IR (KBr): ꢀꢁ ¼ 3400, 3030,
ꢁ1
1
2
d
259, 1621, 1493, 743 cm ; H NMR (300 MHz, CDCl ):
3
(2015) 1790.
¼ 8.40 (s, 1H), 7.73 (s, 1H), 7.62 (m, 2H), 7.48e7.41 (m, 5H),
[14] Y. Hu, Y. Zou, H. Wu, D. Shi, Ultrason. Sonochem 19 (2012) 264.
[15] J. Noei, A.R. Khosropour, Ultrason. Sonochem 16 (2009) 711.
[16] Y. Zou, H. Wu, Y. Hu, H. Liu, X. Zhao, H. Ji, D. Shi, Ultrason. Sonochem
7
.26 (t, J ¼ 7.8 Hz,1H), 7.14 (t, J ¼ 7.5 Hz,1H), 5.12 (s,1H) ppm;
13
C NMR (100 MHz, DMSO-d
31.9, 129.8, 128.8, 125.6, 123.1, 121.6, 120.3, 116.3, 115.6, 113.1,
12.1 ppm; Anal. calcd for C17 : C 83.58; H 4.95; N
1.47%. Found: C 83.7; H 4.6; N 11.4% (Table 4, entry 1).
6
)
d
¼ 168.0, 137.1, 136.3, 134.4,
1
8 (2011) 708.
17] S. Puri1, B. Kaur, A. Parmar, H. Kumar, Curr. Org. Chem. 17 (2013) 1790.
[18] S. Rahimi, M.A. Amrollahi, Z. Kheilkordi, C. R. Chimie 18 (2015) 558.
1
1
1
[
12 2
H N
[
[
19] H. Emtiazi, M.A. Amrollahi, Helv. Chimi. Acta 96 (2013) 2196.
20] C.E. McDonald, L.E. Nice, A.W. Shaw, N.B. Nestor, Tetrahedron Lett.
34 (1993) 2744.
4
.3.7. 3-(Indolyl)-3-(3-nitrophenyl)acrylonitrile
[21] S.O. Nwaukwa, P.M. Keehn, Tetrahedron Lett. 23 (1982) 35.
ꢀ
[22] V. Pace, F. Martínez, M. Fern aꢀ ndez, J.V. Sinisterra, A.R. Alc ꢀa ntara,
Yellow crystals; mp 105e107 C. IR (KBr): ꢀꢁ ¼ 3374,
Adv. Synth. Catal. 351 (2009) 3199.
ꢁ
1
1
3
062, 2251, 1620, 1583, 1527, 1352, 745 cm
; H NMR
[
[
23] M.P. VanBrunt, R.O. Ambenge, S.M. Weinreb, J. Org. Chem. 68 (2003)
3323.
24] V. Pace, L. Castoldi, M.J. Hern ꢀa iz, A.R. Alc ꢀa ntara, W. Holzer, Tetra-
(
400 MHz, DMSO-d
6
):
d
¼ 12.92 (s, 1H), 8.51 (d, J ¼ 8.0 Hz,
1
H), 8.42 (s, 1H), 8.35 (s, 1H), 8.04 (d, J ¼ 8.0 Hz, 1H), 7.88 (t,
hedron Lett. (2013) (in press), http://dx.doi.org/10.1016/j.tetlet.
J ¼ 8.0 Hz,1H), 7.58 (d, J ¼ 8.0 Hz,1H), 7.23 (t, J ¼ 7.6 Hz,1H),
2013.05.118.
7.04 (t, J ¼ 7.6 Hz, 1H), 6.57 (d, J ¼ 8.0 Hz, 1H), 5.88 (s, 1H)
[25] V. Pace, L. Castoldi, W. Holzer, Tetrahedron Lett. 53 (2012) 967.
Please cite this article in press as: M. Omidi, M.A. Amrollahi, Facile synthesis of 3-substituted indoles containing highly polarized
double bonds, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/j.crci.2016.09.004