Host/guest inclusion system of surfactants with β-cyclodextrin as a viable catalyst for one-pot synthesis of mono- and bis (indolyl)methylmalononitriles in H2O

Article abstract of DOI:10.3906/kim-1709-11

In this study, encapsulation processes of cetyltrimethylammonium bromide (CTAB) or sodium dodecyl sulfate (SDS) monomers into the cavity of β-cyclodextrin (β-CD) were applied to synthesize mono- and bis (indolyl)methylmalononitrile derivatives by a one-po

Full text of DOI:10.3906/kim-1709-11

Turk J Chem
Turkish Journal of Chemistry
(2018) 42: 988 – 996
© TÜBİTAK
http://journals.tubitak.gov.tr/chem/
doi:10.3906/kim-1709-11
Research Article
Host/guest inclusion system of surfactants with β-cyclodextrin as a viable
catalyst for one-pot synthesis of mono- and bis (indolyl)methylmalononitriles in
H2 O
Fatemeh MIRHASHEMI, Mohammad Ali AMROLLAHI∗,
Department of Chemistry, Faculty of Science, Yazd University, Yazd, Iran
Received: 08.09.2017
•
Accepted/Published Online: 02.04.2018
•
Final Version: 03.08.2018
Abstract: In this study, encapsulation processes of cetyltrimethylammonium bromide (CTAB) or sodium dodecyl
sulfate (SDS) monomers into the cavity of β -cyclodextrin (β -CD) were applied to synthesize mono- and bis (in-
dolyl)methylmalononitrile derivatives by a one-pot three-component reaction of an aldehyde, malononitrile, and indole
in an aqueous solution. These two inclusion complexes proved to be superior to CTAB or SDS individually, as cationic
or anionic surfactants, respectively, for accessing high yields of pure products within shorter reaction times. In addition,
simple isolation of products and mild reaction conditions are the other advantages of this green procedure.
Key words: Conductance, β -cyclodextrin, encapsulation, inclusion complexes, surfactants
1. Introduction
The insolubility of most organic substances in water and the distribution or deactivation of many active
substrates, reagents, and catalysts by water molecules are the two significant limitations of organic reactions
1
in aqueous media. To overcome these constraints, there are some strategies that facilitate the use of water
2−4
as a solvent for a wide variety of organic reactions. In this regard, the use of organic co-solvents,
water-
5−9
10−12
13−16
stable Lewis acids,
surfactants,
or Brønsted/Lewis acid-surfactant-combined catalysts
is the most
important recently reported strategy. Host/guest inclusion catalysts (ICs) have also been of considerable interest
for preparing organic compounds in water. Such ICs can be defined as supramolecules consisting of two or more
distinct species, which are capable of self-assembling through noncovalent interactions without any loss in
17
their chemical identity. The stability of host/guest complexes is achieved through intermolecular interactions,
such as hydrogen bonds, established between the interacting species. The minimum condition required for
the formation of an inclusion compound is the geometric compatibility between the host and guest molecules
18
following the principles of molecular recognition. Therefore, the size and conformation of the guest must be
appropriate enough to be included in the host cavity. β -Cyclodextrin β -CD lies in the class of encapsulation
supramolecular host compounds, which is important in the development of host/guest systems. β -CD is a
19
cyclic oligosaccharide formed by α-D-glucose units linked through glycosidic α-1,4 bonds. Topologically, β -
CD is usually characterized as a doughnut or a wreath-shaped truncated cone, combining the hydrophilic and
hydrophobic region. β -CD forms ICs with smaller molecules that fit into its 6-6.4 Å cavity. The hydrophobic
20,21
cavity of β -CD allows this molecule to encapsulate a variety of nonpolar molecules of a suitable size.
∗Correspondence: mamrollahi@yazd.ac.ir
988
This work is licensed under a Creative Commons Attribution 4.0 International License.

MIRHASHEMI and AMROLLAHI/Turk J Chem
Surfactants also have distinctly separate hydrophilic and hydrophobic parts and commonly show self-assembly,
22
resulting in different structures such as micelles as well as vesicles. Current investigations in surfactant science
are driven by the requirements that design surfactants possess enhanced physicochemical properties, specific
23−25
applications in modern technologies, and new utilization in complex systems.
Hence, investigations of
the host/guest relationship of β -CD and surfactants in complex systems are important because they make it
possible to design new surfactants and corresponding supramolecules for specific applications. These complexes
are of interest for scientific research, and they exist in aqueous solutions in comparison with classical catharses.
Since indole derivatives have been widely found in biologically active compounds, various research groups have
26
turned their attention to access this class of heterocyclic compounds. In continuation of our previous work on
27
the development of new synthetic methodologies, herein we report a convenient, practical, green, and efficient
reaction for the synthesis of (indolyl)methylmalononitrile derivatives via a one-pot three-component reaction of
an aldehyde, a malononitrile, and an indole in H2 O using inclusion compounds of β -CD and CTAB or SDS.
The main goal of this study was to investigate the formation of ICs of CTAB and SDS with β -CD in aqueous
media and then to compare their inclusion efficiency with respect to the surfactants individually.
2. Results and discussion
In our initial study, the conductivity of CTAB and SDS in an experimental solution was measured to get
information about the transport property of ICs as well as the stoichiometry of the complexes. CTAB and
SDS are charged structures and have considerable conductivity in aqueous solutions. By adding β -CD to the
solution of CTAB or SDS, the conductivity of the solution was decreased, which is due to the inclusion of the
hydrophobic part of CTAB or SDS molecules one by one into the nonpolar cavity of β -CD. A decrease in the
solution conductivity by adding β -CD was attributed to the formation of ICs between CTAB or SDS and β -CD
molecules. After a certain concentration of β -CD, no change was observed in the conductivity, indicating that
the stoichiometry of the inclusion complex of β -CD with CTAB or SDS in this concentration range was almost
a 1:1 molar ratio. This points out that CTAB or SDS is in a complex situation. The conductivity values of
each IC are tabulated in Table 1.
The FT-IR spectra of β -CD, β -CD/SDS, and SDS as well as β -CD, β -CD/CTAB, and CTAB were
recorded. The peak at 3371 cm−1 was attributed to the stretching mode of OH in β -CD. After complexion of
β -CD with CTAB or SDS, the peak at 3371 shifted to ∼3360 cm−1 . This was probably caused by the effect
of the ion-dipolar interaction of β -CD with CTAB or SDS when the hydrophobic part of CTAB or SDS was
inside the cavity of β -CD.
The catalytic activity of these two IC systems was investigated for the synthesis of 3-substituted indole
derivatives via three-component reactions of aldehyde, malononitrile, and indole. In order to optimize the
reaction conditions and to achieve the highest yield, the model reaction of benzaldehyde, malononitrile, and
indole was initially carried out under different conditions in the aqueous solution of β -CD/CTAB or β -CD/SDS.
The results are summarized in Table 2. The reaction was first performed in H2 O in the absence of CTBA and
SDS at room temperature. According to the data obtained, no reaction occurred (Table 2, Entry 1). Similar
reactions were then attempted in the presence of CTAB or SDS, as cationic and anionic surfactants, in the
pre-cmc and post-cmc regions. However, it was noticed that no reaction would occur when the concentration
of CTAB was less than the cmc1 (Table 2, Entry, 2), while the formation of the product was more facile and
proceeded with a high yield in the presence of CTBA or SDS at their cmc1 concentrations (Table 2, Entries
3, 10). At this stage, the higher reaction loading of the surfactant had no significant influence on the reaction
989

MIRHASHEMI and AMROLLAHI/Turk J Chem
Table 1. Conductance values of CTAB and SDS with the corresponding concentration of β -CD in an aqueous medium
at 20.0 ꢀ 0.2 ◦ C.
β-CD (mM) Cond. (mS cm−1
)
0
0.238 ꢀ 0.002
0.233 ꢀ 0.003
0.195 ꢀ 0.002
0.175 ꢀ 0.001
0.170 ꢀ 0.002
0.171 ꢀ 0.001
0.170 ꢀ 0.002
0.687ꢀ 0.001
0.657 ꢀ 0.002
0.558 ꢀ 0.003
0.398 ꢀ 0.002
0.245ꢀ 0.002
0.255ꢀ 0.001
0.250ꢀ 0.002
0.2
0.5
0.8
1
2
3
0
2
5
7
a)
CTAB
b)
SDS
8
9
10
a)
Concentration of CTAB is 1 mM (cmc1).
Concentration of SDS is 8.2 mM (cmc1).
b)
time and yield. When the reaction was performed in an aqueous solution of β -CD/CTAB (1 mM:2 mM) or
β -CD/SDS (1 mM:1.5 mM) micelles mixed system, the formation of the product was more facile and proceeded
in a shorter time (Table 2, Entries 8, 13). To find the optimum reaction temperature, the model reaction was
carried out in a solution of β -CD/CTAB (1 mM:2 mM) mixed system at 25, 60, and 80 ◦ C, which resulted in
the isolation of the product yields of 55%, 90%, and 70%, respectively. In order to evaluate the efficiency of ICs,
the reuse of β -CD/CTAB or β -CD/SDS mixed system in the model reaction was investigated. The inclusion
complexes of β -CD/CTAB or β -CD/SDS could be easily recovered by filtration, and the new substrates were
added for the next cycle. The recycled experimental solution of β -CD/CTAB or β -CD/SDS was efficient
enough to turn the condensation reaction of the aldehyde, malononitrile, and indole into the corresponding
(indolylmethyl)malononitrile even after three consecutive times with an activity loss of about 15%–20%.
According to the obtained results, the catalytic effect of the inclusion complexes of β -CD/CTAB or
β -CD/SDS in this three-component reaction can be explained as follows. Aldehydes, malononitrile, and indole,
which are expected to produce (indolylmethyl)malononitrile derivatives, are hydrophobic molecules in water.
In the inclusion compounds of β -CD/CTAB or β -CD/SDS, the hydrophobic moieties escape from the wider
and narrower edges of β -CD, which encircle the micelle hydrophobic core of CTAB or SDS inside the β -CD
cave where the reactions take place more easily.
Mono- and bis (indolyl)methylmalononitrile derivatives were synthesized under the optimized conditions.
As it was observed, the process could tolerate both electron-donating and electron-withdrawing substituents
in the substrates. In all cases, reactions proceed efficiently in H2 O under mild conditions to afford the corre-
sponding products in high yields. The results are summarized in Table 3. All the products were characterized
1
13
by mp, and IR, H NMR, and C NMR spectra.
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MIRHASHEMI and AMROLLAHI/Turk J Chem
Table 2. Optimization traits for the one-pot synthesis of indolylmethylmalononitrile and bis (indolyl) methylmalononi-
a)
trile in aqueous solution
.
Yield (%) b)
Entry
Aqueous solution (conc.)
Time (h)
4a
0
4b
1
-----
7
0
0
2
CTAB (0.5 mM)
7
0
3
CTAB (1 mM) cmc1
7
85
85
20
30
30
25
90
20
20
20
5
5
4
CTAB (2 mM) cmc2
7
5
5
β-CD (1 mM )
7
0
6
CTAB/β-CD 1:1 (1 mM:1 mM)
CTAB/β-CD 1:1 (2 mM:2 mM)
CTAB/β-CD 1:2 (1 mM:2 mM)
CTAB/β-CD 2:1 (2 mM:1 mM)
SDS (8.2 mM) cmc1
7
5
7
7
5
8
7
0
9
2
5
10
11
12
13
14
12
12
12
3.5
12
75
35
35
87
30
SDS/β-CD 1:1 (8.2 mM:8.2 mM)
SDS/β-CD 1.25:1 (10.3 mM:8.2 mM)
SDS/β-CD 1.5:1 (12.3 mM:8.2 mM)
SDS/β-CD 1:1.5 (8.2 mM:12.3 mM)
10
a)
b)
Reaction conditions: aldehyde (1 mmol), malononitrile (1 mmol), indole (1–2 mmol). Isolated yield.
This one-pot three-component reaction involves Knoevenagel condensation and Michael addition occur-
ring in a sequence. These processes take place in β -CD/CTAB or β -CD/SDS inclusion complexes, which have
highly effective catalytic behavior in terms of their host/guest interactions. The formation of the products can
be rationalized by the initial Knoevenagel reaction between aromatic aldehydes and malononitrile. Afterwards,
Michael addition reaction between Knoevenagel adduct and indole gives the desired (indolyl)methylmalononitrile
derivatives. Dehydrogenation of (indolyl)methylmalononitrile in a solution with β -CD/SDS resulted in (in-
dolyl)methylenemalononitriles. Bis (indolyl)methylmalononitriles was obtained by the second conjugate addi-
tion of indole with (indolyl)methylenemalononitriles.
To study the wide capability of the β -CD/CTAB catalytic system, we further investigated the reaction
of malononitrile with benzaldehyde to yield the corresponding 2-benzylidenemalononitrile via Knoevenagel
condensation reaction. The reaction was carried out in aqueous solution of β -CD, CTAB, β -CD/CTAB, SDS,
and β -CD/SDS. It was shown that CTAB and SDS, as cationic and anionic surfactants respectively, accelerate
this reaction, but the inclusion complexes of β -CD/CTAB or β -CD/SDS were not more effective in this reaction.
The results are summarized in Table 4.
991

MIRHASHEMI and AMROLLAHI/Turk J Chem
Table 3. Synthesis of indolylmethylmalononitrile and bis (indolyl)methylmalononitriles derivatives in the presence of
inclusion complexes.
CTAB/β-CD 2:1
SDS/β-CD 1.5:1
(12 mM:8.2 mM)
4b
(2 mM:1 mM)
Ref.
Ref.
Entry
R
4a
Time (min)
Yield (%) a)
Time (min)
210
Yield (%) a)
1
2
3
4
5
6
7
8
C6H5
110
80
90
87
80
90
80
85
95
90
[27]
87
85
80
90
80
85
95
90
[32]
[32]
[26]
[26]
[32]
[26]
[26]
[32]
4-ClC6H4
4-MeOC6H4
4-MeC6H4
4-HOC6H4
4-iprC6H4
4-O2NC6H4
4-FC6H4
[27]
[28]
[28]
[29]
[29]
[30]
[31]
150
120
100
120
100
45
210
200
210
200
140
80
140
a)
Isolated yield
a)
Table 4. Optimization traits for the synthesis of 2-benzylidenemalononitrilein in an aqueous solution
.
Entry Aqueous solution
Time (min)
Yield (%) b)
1
2
3
4
5
6
7
8
-
240
10
10
10
10
5
85
87
50
30
90
90
20
95
CTAB (1 mM) cmc1
β-CD (0.5 mM)
CTAB/β-CD 1:1 (1 mM:1 mM)
CTAB/β-CD 2:1 (2 mM:1 mM)
SDS (8.2 mM)
SDS/β-CD 1:1 (8.2 mM:8.2 mM)
SDS/β-CD 1.5:1 (12.3 mM:8.2 mM)
5
5
a)
b)
Reaction conditions: benzaldehyde (1 mmol), malononitrile (1 mmol),
Isolated yield
992

MIRHASHEMI and AMROLLAHI/Turk J Chem
3. Experimental
All the organic materials were purchased commercially from Sigma-Aldrich and Merck and used without further
purification. The inclusion compounds were characterized by FT-IR and their conductivity in experimental
solutions. The conductance measurements were carried out in a Systronic-308 conductivity meter using a
dip-type immersion conductivity cell, CD-10, having a cell constant of approximately (0.1 ꢀ 0.001) cm−1
.
The measurements were completed in a water bath maintained within a temperature range of 20.0 ꢀ 0.2 ◦ C.
1
13
The synthesized products were characterized by mp, and IR, H NMR, and C NMR spectra. The melting
points were determined by Büchi melting point B-540 B.V.CHI apparatus in open capillaries. The points were
uncorrected. The FT-IR spectroscopy of the samples as KBr pellets was carried out on a Bruker Eqinox 55
1
13
FT-IR spectrometer in the 400–4000 cm−1 region. H and C NMR spectra were recorded at 25 ◦ C and on
a 400 MHz or 500 MHz (Bruker Avance) instrument using TMS as the internal standard. The chemical shifts
were given in parts per million (ppm). All the reactions and the purity of the products were monitored using
thin-layer chromatography (TLC) on aluminum-backed plates coated with Merck Kieselgel 60 F254 silica gel
and by watching the spots under ultraviolet light.
3.1. General procedure for the synthesis of the indolylmethylmalononitrile derivatives
Aldehyde (1 mmol), malononitrile (1 mmol, 0.07 g), and indole (1 mmol, 0.12 g) were added to a magnetically
stirred soln. of β -CD/CTAB (1 mM:2 mM) in H2 O (5 mL). The mixture was then stirred at 60 ◦ C for a given
time. The progress of the reaction was followed by TLC. After completion of the reaction, the precipitated
products were filtrated off and washed with hot H2 O. The crude products were purified by recrystallization in
EtOH. The results are summarized in Table 3.
3.2. General procedure for the synthesis of the bis (indolyl)methylmalononitrile derivatives
Aldehyde (1 mmol), malononitrile (1 mmol, 0.07 g), and indole (2 mmol, 0.24 g) were added to a magnetically
stirred soln. of β -CD/SDS (1 mM:1.2 mM) in H2 O (5 mL). The mixture was then stirred at 60 ◦ C for a given
time. The progress of the reaction was followed by TLC. After completion of the reaction, the precipitated
products were filtrated off and washed with hot H2 O. The crude products were purified by recrystallization in
EtOH. The results are summarized in Table 3.
3.3. Selected data
3.3.1. 2-((Indolyl)(phenyl)methyl)malononitrile (Table 3, 4a, Entry 1)
White crystals, mp 75–77 ◦ C. IR: 3346 (NH stretching), 3031(=CH stretching), 2898 (CH stretching), 2258
1
(C≡ N), 1620, 1458 (C=C). H NMR (400 MHz, CDCl3): 4.46 (d, J = 6.3 Hz, 1 H, CH), 4.95 (d, J = 6.4
Hz, 1 H, CH), 7.10–7.26 (m, 2 H, ArH), 7.35–7.55 (m, 6 H, ArH), 7.70–7.75 (m, 2 H, ArH), 8.89 (s, 1 H, NH).
13
C NMR (100 MHz, DMSO-d6): 28.6, 42.4, 111.6, 112.3, 113.8, 114.1, 118.5, 118.8, 121.6, 122.7, 125.8, 127.7,
128.0, 128.6, 136.1, 139.2.
3.3.2. 2-((Indolyl)(4-chlorophenyl)methyl)malononitrile (Table 3, 4a, Entry 2)
White crystals, mp 74–75 ◦ C. IR: 3380 (NH stretching), 3047 (=CH stretching), 2890 (CH stretching), 2260
1
(C≡ N), 1600, 1480 (C=C). H NMR (400 MHz, DMSO-d6): 4.95 (d, J = 8.1 Hz, 1 H, CH), 5.22 (d, J =
13
8.1 Hz, 1 H, CH), 7.15 (t, J = 6.9 Hz, 1 H, ArH), 7.40–7.60 (m, 8 H, ArH), 9.25 (s, 1 H, NH). C NMR (100
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MIRHASHEMI and AMROLLAHI/Turk J Chem
MHz, DMSO-d6): 27.7, 41.5, 110.8, 112.1, 113.4, 115.5, 118.9, 121.7, 122.6, 125.0 125.8, 128.2, 130.1, 135.4,
136.0, 143.3.
3.3.3. 2-((Indolyl)(p-tolyl)methyl)malononitrile (Table 3, 4a, Entry 4)
Pale yellow crystals, mp 117–119 ◦ C. IR: 3350 (NH stretching), 3035 (=CH stretching), 2883 (CH stretching),
1
2225 (C≡ N), 1588, 1459 (C=C). H NMR (400 MHz, DMSO-d6): 2.27 (s, 3 H, CH3), 5.17 (d, J = 9.2 Hz,
1 H, CH), 5.82 (d, J = 9.2 Hz, 1 H, CH), 6.90–7.05 (m, 2 H, ArH), 7.20 (d, J = 8.0 Hz, 2 H, ArH), 7.41 (d,
13
J = 8.0 Hz, 2 H, ArH), 7.55–7.70 (m, 3 H, ArH), 10.80 (s, 1 H, NH). C NMR (100 MHz, DMSO-d6): 20.5,
28.7, 42.1, 111.6, 112.4, 113.8, 118.5, 121.6, 122.6, 125.8, 127.9, 129.1, 130.1, 130.6, 136.2, 139.5, 143.1.
3.3.4. 2-((Indolyl)(4-hydroxyphenyl)methyl)malononitrile (Table 3, 4a, Entry 5)
Yellow crystals, mp 172–174 ◦ C. IR: 3386, (OH and NH stretching), 3055 (=CH stretching), 2910 (CH
1
stretching), 2226 (C≡ N), 15610, 1445 (C=C). H NMR (400 MHz, DMSO-d6): 3.40 (s, 1H, OH), 5.10
(d, J = 9.2 Hz, 1 H, CH), 5.70 (d, J = 9.1 Hz, 1 H, CH), 6.68 (d, J = 8.4 Hz, 2 H, ArH), 6.90–715 (m, 3 H,
13
ArH), 7.30 (d, J = 8.4 Hz, 2 H, ArH), 7.52–7.85 (m, 2 H, ArH), 10.17 (s, 1 H, NH). C NMR (100 MHz,
DMSO-d6): 23.3, 40.5, 112.7, 114.1, 115.0, 115.2, 116.5, 118.2, 118.6, 118.7, 120.8, 121.5, 122.7, 129.1, 133.8,
140.4.
3.3.5. 2-((Indolyl)(4-nitrophenyl)methyl)malononitrile (Table 3, 4a, Entry 7)
Yellow crystals, mp 200–201 ◦ C. IR: 3378 (NH stretching), 3054 (=CH stretching), 2890 (CH stretching), 2248
1
(C≡ N), 1607, 1471 (C=C). H NMR (400 MHz, DMSO-d6): 5.51 (d, J = 9.2 Hz, 1 H, CH), 5.99 (d, J =
9.2 Hz, 1 H, CH), 6.95–7.15 (m, 2 H, ArH), 7.40–7.60 (m, 3 H, ArH), 7.80 (d, J = 8.8 Hz, 2 H, ArH), 8.10 (d,
13
J = 8.8 Hz, 2 H, ArH), 10.33 (s, 1 H, NH). C NMR (100 MHz, DMSO-d6): 28.1, 41.7, 111.2, 111.7, 113.4,
113.6, 118.3, 119.1, 121.1, 123.8, 123.9, 125.6, 129.4, 136.0, 142.6, 145.0.
3.3.6. 2-((Indolyl)(4-fluorophenyl)methyl)malononitrile (Table 3, 4a, Entry 8)
White crystals, mp 113–114 ◦ C. IR: 3360 (NH stretching), 3034 (=CH stretching), 2883 (CH stretching), 2267
1
(C≡ N), 1605, 1466 (C=C). H NMR (400 MHz, DMSO-d6): 5.27 (d, J = 9.2 Hz, 1 H, CH), 5.84 (d, J = 9.2
13
Hz, 1 H, CH), 7.00–7.20 (m, 4 H, ArH), 7.40–7.60 (m, 5 H, ArH), 10.25 (s, 1 H, NH). C NMR (100 MHz,
DMSO-d6): 28.7, 41.5, 111.6, 112.1, 113.7, 113.9, 114.7, 115.5, 118.9, 121.7, 122.6, 125.8, 130.1, 135.4, 136.0
143.3.
3.3.7. 2-(Di(1H-indol-3-yl)(phenyl)methyl)malononitrile (Table 3, 4b, Entry 1)
Red crystals, mp 89–91 ◦ C. IR: 3398 (NH stretching), 3030 (=CH stretching), 2950 (CH stretching), 2190 (C≡
1
N), 1610, 1470 (C=C). H NMR (500 MHz, CDCl3): 5.85 (s, 1 H, CH), 6.95 (s, 2 H, CH), 7.05–7.15 (m, 4 H,
13
ArH), 7.30–7.50 (m, 7 H, ArH), 7.55–7.65 (m, 2 H, ArH), 9.58 (s, 2 H, NH). C NMR (125 MHz, CDCl3):
30.6, 45.7, 111.4, 112.6, 119.5, 120.3, 121.5, 122.3, 124.0, 126.5, 127.5, 128.6, 129.1, 135.9, 137.1, 148.4.
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MIRHASHEMI and AMROLLAHI/Turk J Chem
3.3.8. 2-((4-Chlorophenyl)di(1H-indol-3-yl)methyl)malononitrile (Table 3, 4b, Entry 2)
Light red crystals, mp 90–91 ◦ C. IR: 3401 (NH stretching), 3052 (=CH stretching), 2923 (CH stretching), 2245
1
(C≡ N), 1616, 1465 (C=C). H NMR (500 MHz, CDCl3): 5.89 (s, 1 H, CH), 6.96 (s, 2 H, CH), 705–7.30 (m,
13
8 H, ArH), 7.50 (d, J = 8.1 Hz, 2 H, ArH), 7.75 (d, J = 8.0 Hz, 2 H, ArH), 9.60 (s, 2 H, NH). C NMR
(125 MHz, CDCl3): 37.6, 48.5, 109.8, 110.7, 115.8, 118.4, 120.0, 121.4, 122.6, 125.5, 128.3, 130.0, 131.8, 138.0,
147.0, 149.1.
3.3.9. 2-(Di(1H-indol-3-yl)(p-tolyl)methyl)malononitrile (Table 3, 4b, Entry 4)
Red crystals, mp 174–176 ◦ C. IR: 3380 (NH stretching), 3030 (=CH stretching), 2923 (CH stretching), 2267
1
(C≡ N), 1610, 1475 (C=C). H NMR (500 MHz, CDCl3): 2.54 (s, 3 H, CH3), 5.32 (s, 1 H, CH), 6.80 (s, 2
H, CH), 7.15–7.30 (m, 8 H, ArH), 7.40 (d, J = 7.3 Hz, 2 H, ArH), 7.49 (d, J = 7.5 Hz, 2 H, ArH), 8.93 (s, 2
13
H, NH); C NMR (125 MHz, CDCl3): 21.4, 37.8, 55.7, 112.6, 113.4, 119.6, 120.1, 120.9, 122.3, 124.0, 126.5,
127.5, 128.6, 129.1, 137.1, 144.4.
3.3.10. 2-((4-Hydroxyphenyl)di(1H-indol-3-yl)methelyl)malononitrile (Table 3, 4b, Entry 5)
Red crystals, mp 126–128 ◦ C. IR: 3407 (OH and NH stretching), 3055 (=CH stretching), 2922 (CH stretching),
1
2220 (C≡ N), 1611, 1455 (C=C). H NMR (500 MHz, CDCl3): 5.30 (s, 1 H, OH), 5.65 (s, 1 H, CH), 6.90 (s,
2 H, CH), 7.00 (d, J = 8.2 Hz, 2 H, ArH), 7.20–7.35 (m, 4 H, ArH), 7.50 (d, J = 8.1 Hz, 2 H, ArH), 7.55–7.70
13
(m, 4 H, ArH), 9.90 (s, 2 H, NH). C NMR (125 MHz, CDCl3): 32.0, 49.0, 111.0, 111.6, 119.5, 122.1, 123.0,
125.8, 128.2, 129.0, 129.5, 132.6, 136.5, 138.0, 143.2, 147.5.
3.3.11. 2-(Di(1H-indol-3-yl)(4-nitrophenyl)methelyl)malononitrile (Table 3, 4b, Entry 7)
Yellow crystals, mp 160–162 ◦ C. IR: 3412 (NH stretching), 3052 (=CH stretching), 2923 (CH stretching), 2257
1
(C≡ N), 1610, 1456 (C=C). H NMR (500 MHz, CDCl3): 5.93 (s, 1 H, CH), 6.94 (s, 2 H, CH), 7.10–7.34
13
(m, 8 H, ArH), 7.56 (d, J = 8.3 Hz, 2 H, ArH), 7.86 (d, J = 8.2 Hz, 2 H, ArH), 9.30 (s, 2 H, NH). C NMR
(125 MHz, CDCl3): 36.0, 48.9, 111.0, 112.0, 113.2, 119.7, 120.1, 122.0, 123.7, 124.0, 128.0, 130.5, 133.4, 138.5,
148.0, 149.7.
3.3.12. 2-((4-Fluorophenyl)di(1H-indol-3-yl)methyl)malononitrile (Table 3, 4b, Entry 8)
Red crystals, mp 132–135 ◦ C. IR: 3403 (NH stretching), 3072 (=CH stretching), 2928 (CH stretching), 2215
1
(C≡ N), 1601, 1476 (C=C). H NMR (500 MHz, CDCl3): 5.75 (s, 1 H, CH), 6.97 (s, 2 H, CH), 7.15–7.30
13
(m, 8 H, ArH), 7.45–7.70 (m, 4 H, ArH), 9.80 (s, 2 H, NH) C NMR (125 MHz, CDCl3): 39.9, 48.0, 110.0,
111.2, 116.0, 119.0, 120.6, 121.2, 123.7, 126.2, 128.4, 130.0, 136.7, 138.0, 147.5, 150.1.
4. Conclusion
In this paper, we have reported a remarkable and expedient technique for the rapid synthesis of mono- and bis
(indolyl)methylmalononitriles by one-pot three-component condensation of aldehyde, malononitrile, and indole.
ICs of β -CD/CTAB or β -CD/SDS proved to accelerate this reaction. The proposed method can be used to
prepare a wide variety of (indolyl)methylmalononitrile derivatives, some of which would need toxic conditions
and a long reaction time to be made via other established methods.
995

MIRHASHEMI and AMROLLAHI/Turk J Chem
Acknowledgment
The authors thank the Research Council of Yazd University for its financial support.
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