Proceeding of the International Conference
on Mathematics and Sciences (ICOMSc) 2011
ISBN978-602-19142-0-5
COMPARISON OF AlCl3 AND ZSM-5
CATALYSTS FOR REACTION
OF ISATIN AND INDOLE
Arif Fadlan, Ariefta Henda Kurniatullah, Didik Prasetyoko
Chemistry Department, Faculty of Mathematics and Natural Sciences,
Institut Teknologi Sepuluh Nopember, Surabaya, Indonesia
[email protected]
Abstract. Indole derivatives such as trisindoline, show antibiotic and anticancer activity,
and are a potential source of drugs lead compounds. A single type of acid catalyst,
Bronsted acids or Lewis acids has been used for synthesis of trisindoline and no
publication reported using double type of this catalyst. ZSM-5, a double type acid
catalyst, was prepared and characterized using XRD, IR spectroscopy and pyridine
adsorption techniques for its acidity, and applied for the reaction of indole and isatin.
Based on the thin layer chromatography and infrared spectroscopy techniques, the
reaction of indole and isatin catalyzed by ZSM-5 has resulted a product other than
trisindoline, while catalysis by AlCl3 has produced trisindoline and other product.
Keywords: indole, trisindoline, ZSM-5.
1
Introduction
3,3'-Bis(indole-3-yl)oxindole (1), one of bis(indolyl)methane compounds, firstly
isolated from bacterial-sea cultures Vibrio sp obtained from fresh marine sponges Hyrtios
altum which live in the Okinawa sea of Japan [1]. Trisindoline (1) then also succesfully
isolated from the Vibrio parahaemolictus Bio 240 living in the North Sea and from
Escherichia coli that expressing mutant enzyme [2, 3]. Trisindoline (1) shows antibiotic
activity againts E. coli, Bacillus subtilis, and Staphylococcus aureus [4]. Further studies
showed that trisindoline (1) has an anticancer activity against human uterine sarcoma cell
lines (MES-SA and MES-SA/DX5), colorectal adenocarcinoma cell line (HCT 15), lung
(A-549), CNS (SK-N-SH), breast (MCF-7), liver (Hep-2), and prostate (DU-145) [5].
Therefore, the study of trisindoline (1) syntheses have received an increasing attention
due to its promising application in modern pharma-ceutical chemistry.
HN
N
H
O
(1)
OC 05
N
H
COMPARISON OF AlCl3 AND ZSM-5 CATALYSTS
Several methods using a single type of acid catalyst, Bronsted acids or Lewis
Acids, such as copper(II) bromide and silver(I) carbonate [1], ceric ammonium(IV)
nitrate combined with ultrasonic wave [6], silica-sulfuric acid [7], boron trifluoride and
sulfuric acid [8, 9], and FeCl3 have been reported in the literature for the synthesis of
trisindoline (1). To the best of our knowledge, there are no publication reported about
trisindoline (1) synthesis using double type of acid catalyst, i.e. Bronsted acid and Lewis
acid. This paper reported the use of a double type of Lewis acid and Bronsted acid
catalyst, ZSM-5, in the reaction of isatin and indole, compared to a single type Lewis acid
catalyst, AlCl3.
2
Experimental
Materials
The mesoporous ZSM-5 was prepared according to the method reported by Eimer
et al. [10] using sodium aluminat (NaAlO2, Al2O3 50-56%, Sigma Aldrich). The seeding
gel was obtained by stirring 2.0 g of NaAlO2 with 45.0 mL of tetraethyl ortho silicate
(TEOS, reagent grade 98 % Aldrich) followed by addition of 20.1 mL of tetra propyl
alumunium hydroxide (TPAOH, ≥ 99%, Merck) and 40.0 mL of distilled water. This
mixture was stirred for 15 h at room temperature and aged at 80 °C for 24 h before
addition of 19.1 g of cetyl trimethyl ammonium bromide (CTAB). The overall gel was
then stirred for 30 min to obtain homogenicity, allowed to stand for 3 h, centifuged, and
finally the solid was separated by filtration, washed with distilled water and dried, firstly
for 24 h at 60 oC and subsequently for 1 h at 550 oC with nitrogen flow, and then followed
by calcination in air for 6 h. The H-form samples were ion-exchanged using aqueous
solution of CH3COONH3 (0,5 M) at 60 oC for 3 h, followed by calcination at 550 oC for
10 h. A commercially available AlCl3 catalyst was used for comparative study.
Characterization
Powder X-ray diffraction (XRD) for crystallinity and phase content determination
of the solid materials was carried out using a JEOL JDX-3530 X-ray Diffractometer with
the Cu K (=1.5405 Å) radiation as the diffracted monochromatic beam at 40 kV and 30
mA. The pattern was scanned in the 2 ranges from 5o to 50o at a step size 0.010o and step
time 1s. The acidity of the samples was monitored by Fourier Transform Infrared (FTIR)
spectroscopy technique using pyridine as a probe molecule. The wafer of the sample (1012 mg) was locked in the cell equipped with CaF2 windows and evacuated at 400 oC
under nitrogen condition for 4 h. Then pyridine was adsorbed at room temperature,
followed by evacuation at 150 oC for 3 h. Infrared spectra of the sample were recorded at
room temperature in the region of 1700–1400 cm-1 on a Shimadzu FTIR 8400S.
2
COMPARISON OF AlCl3 AND ZSM-5 CATALYSTS
Synthesis of Trisindoline
The reaction of isatin (0.14 g, 1.0 mmol) and indole (0.23 g, 2.0 mmol) was
carried out in the presence of catalysts (5 %mol) using acetonitrile as solvent following to
the method reported earlier [5]. The reaction mixture stirred continuously for 2 h at room
temperature in a 50 mL round-bottomed flask and monitored by TLC. After complete
conversion as indicated by TLC, NaHCO3 was added to the reaction mixture followed by
filtering the reaction mixture and the catalyst washed thoroughly with acetonitrile. The
combined washings and the filtrate were extracted using ethyl acetate (3x30 mL) and
Na2SO4.5H2O was added to the organic phase. The product was identified by TLC and
infrared spectroscopy.
3
Results and discussion
Characterization of the catalyst
The XRD pattern of ZSM-5 in Figure 1. showed typical reflections of the MFI
structure as indicated by peaks at 2θ 7.8, 8.8, 23.0, 23.8 o [11, 12]. The humps at 2θ 10-40
and little peaks at 2θ 5-10, 20-25, and 42-50 indicate that ZSM-5 is in amorphous phase
with low crystallinity.
Figure 1. Powder X-ray diffraction pattern of ZSM-5
The acidity of ZSM-5 was investigated by FTIR measurements using pyridine
adsorption (Figure 2.). The IR spectrum shows peaks around 1449-1452 cm-1 that
correspond to pyridine coordinated to Lewis acid sites and peaks at 1540-1545 cm-1
correlate to pyridine bound to Brønsted acid sites. The peak around 1490 cm-1 is assigned
to both Lewis acid and Brønsted acid sites [13, 14]. As a result, the catalyst contains both
Lewis acid and Brønsted acid sites.
3
COMPARISON OF AlCl3 AND ZSM-5 CATALYSTS
Figure 2. FTIR spectrum for ZSM-5, coordinated pyridine bands
Catalytic activity
Trisindoline was obtained when indole was reacted with isatin in the presence of
AlCl3 catalyst in acetonitrile as the solvent, while another compound is yielded when
reaction carried out using ZSM-5 as catalyst, as indicated by TLC analysis (Figure 3.).
The retardation factor (Rf) of each spot in the samples is listed in Table 1. The reaction is
illustrated in Scheme 1.
1 = trisindoline
2 = crude product reaction using AlCl3
3 = crude product reaction using ZSM-5
4 = crude product reaction using no catalyst
5 = indole
6 = isatin
eluen = n-hexana : ethyl acetate (1:1)
Figure 3. TLC analysis
4
COMPARISON OF AlCl3 AND ZSM-5 CATALYSTS
The most significant vibration modes of the N-H, -CONH-, and C=O groups
from IR analysis are listed in the Table 2. Further study shows different intensity of 3217
Table 1. The retardation factor (Rf) of each spot in the samples
Spot
Sample
1
Isatin Indole Trisindoline Other compound
0.45
-
2
0.54
0.87
0.42
0.21
3
0.53
0.86
-
0.22
4
0.51
0.85
-
0.21
5
-
0.84
-
-
6
0.52
-
-
-
HN
O
AlCl3/ZSM-5
O
+
2
MeCN, rt
N
H
N
H
N
H
O
(1)
N
H
Scheme 1. ZSM-5/AlCl3 catalyzed reaction of isatin and indole
Table 2. Vibration modes of IR spectra
Sample N-H (cm-1) -CONH- (cm-1)
1
2
3
4
5
6
3429
3406
3444
3402
3402
-
3325
3217-3198
3217-3198
3194
3194
C=O (cm-1)
1708
1732, 1620
1732, 1620
1732, 1620
1732-1620
cm-1 wavenumber compared to 3198 cm-1 in the IR spectrum of crude product resulted
from reaction catalyzed by AlCl3 and ZSM- 5 (Figure 4., Table 3). Generally, the IR
spectra of sample 2, 3, 4, and 6 have similar peak pattern in 3217-3194 cm-1 wavenumber.
The highest ratio of intensity of this two wavenumber (3217/3194) is 97 % for sample 2,
almost similar with sample 3 with 90 %, while only 73 % for sample 6, and the lowest is
for sample 4 with only 70 %. It can be concluded that sample 4 contains more unreacted
5
COMPARISON OF AlCl3 AND ZSM-5 CATALYSTS
isatin and a peak at 3217 cm-1 would growing up and shifted to the left, as for trisindoline
peak. No trisindoline resulted from the reaction using ZSM-5 as catalyst indicates that the
reaction takes place mainly due to the act of Al ion in the surface on Lewis acid catalyst,
AlCl3 , and not in the tunnel of Si-(OH)-Al where Brønsted acid sites come from, ZSM-5
[15, 16].
(1)
(2)
(3)
(4)
(5)
(6)
Figure 4. IR spectra of the samples in the region 3000-3500 cm-1
Table 3. The ratio of intensity 3217/3194 cm-1
Sampel
∂/∂o
% Intensitas
1
-
-
2
0,97
97
3
0,90
90
4
0,70
70
5
-
-
6
0,73
73
6
COMPARISON OF AlCl3 AND ZSM-5 CATALYSTS
4
Conclusion
AlCl3 is a better catalyst than ZSM-5 in the synthesis of bis(indolyl)methanes
compounds such as trisindoline. The low yield of trisindoline from the reaction using
ZSM-5 as catalyst indicates that the reaction occurs at the outer surface.
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