Novel Schiff base's complex as a green catalyst for the synthesis of diindolylmethanes under ultrasonics irradiation

Article abstract of DOI:10.1134/S1070363213120293

A facile and convenient protocol was developed for the synthesis of diindolylmethanes in short reaction time and high yields using newly synthesized complex as an efficient recyclable heterogeneous catalyst. All synthesized compounds were characterized by

Full text of DOI:10.1134/S1070363213120293

ISSN 1070-3632, Russian Journal of General Chemistry, 2013, Vol. 83, No. 12, pp. 2370–2374. © Pleiades Publishing, Ltd., 2013.
Novel Schiff Base’s Complex as a Green Catalyst
for the Synthesis of Diindolylmethanes
1
under Ultrasonics Irradiation
a
b
a
M. Nikpassand , L. Zare Fekri , and Sh. Sharafi
a
Department of Chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran
email: nikpassand@iaurasht.ac.ir
b
Department of Chemistry, Payame Noor University, PO Box 19395-3697 Tehran, Iran
Received July 22, 2013
Abstract—A facile and convenient protocol was developed for the synthesis of diindolylmethanes in short
reaction time and high yields using newly synthesized complex as an efficient recyclable heterogeneous
catalyst. All synthesized compounds were characterized by IR, NMR spectra and elemental analysis.
DOI: 10.1134/S1070363213120293
INTRODUCTION
EXPERIMENTAL
It is well known that diindolylmethanes (DIMs) and
related compounds exhibit a wide range of biological
activities like antibacterial and antitumor properties
Materials and measurements. For the ultrasonic
activation ultrasound apparatus astra 3D (9.5 dm ,
5 kHz frequency, input power with heating 305W,
3
4
[1]. Diindolylmethanes are the most active crucial
number of transducers, 2) from TECNO-GAZ was
used. Melting points were measured on an Electro-
thermal 9100 apparatus. IR spectra were recorded on a
substances for promoting beneficial estrogen meta-
bolism in women and men [2]. DIMs increase the
body’s natural metabolism of hormones and promote
the formation of good estrogen (2-hydroxyestrogen).
This indole antioxidant is patented for alleviating
symptoms of Fibromyalgia [3]. Due to the potent
biological activity exhibited by various indole derive-
atives, there is a continuous demand for new synthetic
methods in this area. Several synthetic methods for the
preparation of DIMs have been reported by using
catalysts like trichloro-1,3,5-triazine [4], Zeolite [5],
Zeokarb-225 [6], iodine [7], aminosulfonic acid [8],
1
13
Shimadzo IR-470 spectrometer. H and C NMR
spectra were registered on a 500 MHz Bruker DRX-
5
00 in CDCl or DMSO-d as solvent and TMS as
3 6
internal reference. Chemicals were purchased from
Merck and Fluka. Elemental analyses were done on a
Carlo-Erba EA1110CNNO-S analyzer and compared
with the calculated values. All solvents before use
were dried and distilled according to standard
procedures.
1
2-tungstophosphoric acid supported on zirconia [9],
Preparation of catalyst. A solution of synthesized
Schiff base (2 mmol) and copper acetate (1 mmol) in
EtOH (10 mL) were refluxed for the required time.
The progress of reaction was controlled by TLC. After
completion of the reaction, the mixture was filtered to
separate the catalyst.
oxalic acid [10], diphosphooctadecatungstic acid [11],
aluminum oxide [12], and phosphated zirconia [13].
Most of these methods possess various disadvantages
such as long reaction time, use of expensive Lewis
acids, severe reaction conditions, excess of toxic or
organic solvents, low yield, and cumbersome product
isolation procedure. Therefore, it is necessary develop
to further an efficient and convenient method for the
synthesis of these significant scaffolds.
General procedure for the synthesis of diindol-
ylmethanes. A solution of aldehyde (1 mmol), indole
derivatives (2 mmol), and synthesized complex III
(
0.05 g) in EtOH (10 mL) were placed into an open
Herein, we report our preliminary results on the
synthesis of diindolylmethanes catalyzed by syn-
thesized Schiff base’s complex.
vessel of Pyrex glass, and the mixture was irradiated in
a water bath at 60°C by ultrasound (45 kHz) for the
required reaction time. The progress of the reaction
was monitored by TLC. When the irradiation was
1
The text was submitted by the authors in English.
2
370

NOVEL SCHIFF BASE’S COMPLEX AS A GREEN CATALYST
2371
OH
CHO
NO2
CHO
OH
NO2
NH2
NaNO , HCl
2
H C
N=N
H C
3
3
NaOH
CH3
I
N
N
CHO
H C
3
NO2
N
NO2
N=N
H
H C
N=N
OH
H C
OH + N
3
3
N
NH2
H
II
I
CH3
N
NO2
N=N
N
N
H
+
Cu(OAc)2
III
H C
OH
3
II
CH3
+2
N
NO2
N
O
N
H
H C
N=N
3
Cu
II
O
N
N=N
O N
CH3
2
OAc−
H
N
2
N
H C
3
III
Fig. 1. Synthesis of complex III.
stopped, the complex was filtered to separate from the
product. The crystalline products were obtained in high
yields.
In continuation of our studies on the synthesis of
heterocyclic and pharmaceutical compounds by mild
and practical protocols [14, 15], herein we report on
NH
CHO
+
III
N
H
N
H
IV
Fig. 2. Synthesis of diindolylmethanes using synthesized complex III.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 12 2013

2
372
NIKPASSAND et al.
Table 1. The effect of complex III amount on the synthesis
of IVa under ultrasonic irradiation
Run Catalyst amount (mmol)
no. per 1 mmol of substrate
Time, min
Yield, %
1
2
3
4
–
450
60
5
–
0.025
0.050
0.100
66
92
93
Recoveribility of complex
Fig. 3. Synthesis of IVa.
5
our experimental results on the synthesis of diindolyl-
methanes using different substituted aldehydes and
indole derivatives in the presence of a new synthesized
Schiff base’s complex under ultrasound irradiation
indole under ultrasonic irradiation as a model reaction
(Fig. 2).
We have studied the effect of catalyst amount on
the model reaction and the results are listed in Table 1.
(
Fig. 1).
Initially, a new Schiff base II was synthesized by
refluxing azo-linked salicylaldehyde I with 5-methyl-
-aminopyrazole in EtOH. Then, we used this new
5
0 mg of complex is sufficient to promote the reaction
to completion and 0.025 g of catalyst was not enough.
Higher amounts of catalyst did not lead to significant
change in the reaction yields. To generalize the
procedure we have prepared a number of known and
unknown diindolylmethanes following the ecofriendly
methodology. The results are summarized in Table 2.
3
Schiff base II for the preparation of our complex III
by refluxing two equivalents of Schiff base II with
Cu(OAc) as described in Fig. 1.
2
In continuation of our studies, we applied the
synthesized complex III as an effective and green
catalyst to the condensation of benzaldehyde and
Apart from the mild condition of the process and its
excellent results, the simplicity of product isolation,
replacement of small amount of catalyst and the
Table 2. Synthesis of simple diindolylmethanes using new complex III under ultrasonic irradiation
a,b
Run no.
Aldehyde
Benzaldehyde
Indole
indole
indole
indole
indole
indole
indole
indole
indole
indole
indole
indole
indole
Product
IVa
IVb
IVc
IVd
IVe
IVf
Time, min
Yield, %
mp, °C
108–110
76–77
c
c
1
2
3
4
5
6
7
8
9
5 (120)
92 (81)
89
2-Cl-benzaldehyde
3-Cl-benzaldehyde
4-Cl-benzaldehyde
8
7
5
9
5
3
8
9
7
5
6
91
84–86
95
78–80
2-NO
3-NO
4-NO
2
2
2
-benzaldehyde
-benzaldehyde
-benzaldehyde
92
111–112
265–266
235–237
185–186
86–87
95
IVg
IVh
IVi
98
4-OCH
3
-benzaldehyde
96
2-OH-benzaldehyde
4-OH-benzaldehyde
Indole-3-carbaldehyde
87
1
1
1
0
1
2
IVj
89
122–123
161–163
308–309
IVk
IVl
97
Furfural
95
a
b
Isolated yield. The products were characterized by comparison of their spectroscopic data with those of samples synthesized by
c
published procedures. Classical reaction was carried out using indol (2 mmol), benzaldehyde (1 mmol), and complex III in EtOH
(10 mL) under reflux condition.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 12 2013

NOVEL SCHIFF BASE’S COMPLEX AS A GREEN CATALYST
2373
Table 3. Comparison of the newly developed procedure with the previously reported methods
Method
number
Amount of
catalyst
catalyst
Conditions
Time, min Yield, %
1
2
3
4
5
6
7
8
Trichloro-1,3,5-triazine [4]
10%
0.25 mol %
0.5 g
rt
15
30
92
12-Tungstophosphoric acid supported on zirconia [9]
Zeolite [5]
60°C
90
80
95
96
96
72
93
rt
rt
120
450
40
Zeokarb-225 [6]
0.5 g
Oxalic acid [10]
10 mmol
0.7 mol %
0.2 mmol
1.5 mmol
80°C
Diphosphooctadecatungstic acid [11]
Iodine [7]
Solvent free, 110°C
rt, solvent free
Ultrasonic irradiation,
40
10
Aminosulfonic acid [8]
30
3
0–38°C
9
Aluminum oxide [12]
Phosphated zirconia [13]
Present complex
0.5 g
20 wt %
0.05 g
Microwave, 450W
Solvent free
5
20
5
97
93
92
1
1
0
1
Ultrasonic irradiation
possibility to recycle synthesized complex offer a
significant advantage. After the reaction was
completed, the catalyst could be easily filtered in hot
EtOH to separate from product. After further treatment
DMSO-d ), δ, ppm: 2.25 s (3H), 2.69 s (3H), 6.26 s
6
(1H), 7.08 br (1H), 7.60 br (1H), 7.92 br (1H), 8.08 br
(1H), 8.21 br (2H), 9.10 s (1H), 12.62 s (1H), 14.13 s
1
3
(1H). C NMR (125 MHz, DMSO-d ), δ, ppm: 17.89,
6
including washing with CHCl and activation at 60°C,
23.50, 95.81, 117.29, 118.97, 120.12, 127.04, 127.65,
129.92, 130.01, 139.10, 141.07, 146.05, 148.51,
154.21, 155.12, 157.46, 161.72. IR (KBr), ν, cm :
3
the recycled catalyst has been examined in the next
run. Studies on the synthesis of IVa as model substrate
showed that the recovered catalyst could be
successively recycled in subsequent reactions without
any decrease of yields (Fig. 3).
–
1
3274(OH), 3191, 2991, 1614 (CO), 1519 (NO ), 1434,
2
1342 (NO ), 1288. Calculated, %: C 59.35; H 4.82; N
2
23.49. C H N O . Found, %: C 59.43; H 4.76; N 23.55.
18
16
6
3
Complex II. Brown solid; mp: >300°C; Calculated,
: C 33.46; H 2.56; N 13.42. C H Ac CuN O .
Found, %: C 33.38; H 2.70; N 13.51.
To investigate the efficiency of this method, the
comparison between this procedure and some of
previously reported reactions was carried out. The
results are shown in Table 3, Figs. 5 and 4.
%
36 32
2
12
8
CONCLUSIONS
2
-{(E)-[3-Methyl-1H-pyrazol-5-ylimino]methyl}-
In conclusion, this protocol under ultrasonic
irradiation provides a green, fast and practical method
for the preparation of diindolylmethanes in short
4
-[(2-methyl-4-nitrophenyl) diazenyl]phenol (II).
Yellow solid; mp: 215°C; H NMR (500 MHz,
1
Described method no.
Described method no.
Fig. 4. Comparison of reaction time between the new
Fig. 5. Comparison of reaction yield between the new
method and reported methods in the case of benzaldehyde.
method and reported methods in the case of benzaldehyde.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 12 2013

2
374
NIKPASSAND et al.
reaction times and excellent yields. The simplicity,
high atom economy, easy execution and work up,
productivity, together with the use of inexpensive
material and environmentally friendly procedure are
the remarkable features of this process.
7. Magesh, C.J., Nagarajan, R., Karthik, M., and Perumal, P.T.,
Catalyst. Applied Catalysis, 2004, vol. 266, pp. 1–10.
8. Michnovicz, J.J., Bradlowin, H.L., Huang, M.J., Osawa, T.,
Ho, C.T., and Rosen, R.T., Food Phytochemicals for
Cancer Prevention 1 ,Washington, DC, 1994.
9
. Nadkarni, S.V., Gawande, M.B., Jayaram, R.V., and
Nagarkar, J.M., Catal. Commun., 2008, vol. 9, pp. 1728–
1733.
ACKNOWLEDGMENTS
We are grateful the Research Committee of Islamic
Azad University of Rasht Branch for partial support
given to this study.
1
1
1
1
0. Nikpassand, M., Mamaghani, M., Tabatabaeian, K., and
Kupaei Abiazi, M., Molecular Diversity, 2009, p. 389.
1. Nikpassand, M., Mamaghani, M., and Tabatabaeian, K.,
REFERENCES
Molecules, 2009, vol. 14, pp. 1468–1476.
1
2
3
4
. Drasar, B.S., Human Intestinal Flora, Hill Academic
Press: New York, 1974, 2nd ed..
. Heravi, M., Bakhtiari, K., Fatehi, A., and Bamoharram, F.F.,
Catal. Commun., 2008, vol. 9, pp. 289–292.
. Ji, S.J., Wang, S.Y., Zhang, Y., and Loh, T.P.,
Tetrahedron, 2004, vol. 60, pp. 2051–2055.
. Karthik, M., Tripathi, A.K., Gupta, N.M., Palanichamy, M.,
and Murugesan, V., Catal. Commun., 2004, vol. 5,
pp. 371–375.
2. Nikpassand, M., Zare, L., and Saberi, M., Monat. fur
Chemie, 2012, pp. 143, pp. 289–293.
3. Sadaphal, S.A., Kategaonkar, A.H., Labade, V.B., and
Shingare, M.S., Chin. Chem. Lett., 2010, vol. 21,
pp. 39–42.
1
4. Satam, J.R., Parghi, K.D., and Jayaram, R.V., Catal.
Commun., 2008, vol. 9, pp. 1071–1078.
15. Sharma, G.V.M., Reddy, J.J., Lakshmi, P.S., and
Krishna, P.R., Tetrahedron Lett., 2004, vol. 45, pp. 7729–
5
6
. Kokare, N.D., Sangshetti, J.N., and Shinde, D.B., Chin.
Chem. Lett., 2008, vol. 19, pp. 1186–1189.
. Li, J.T., Dai, H.G., Xu, W.Z., and Li, T.S., Ultrason.
Sonochem., 2006, vol. 13, pp. 24–27.
7
732.
16. Zeligs, M.A., J. Medicinal Food, 1998, vol. 1, pp. 67–
82.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 12 2013