Ruthenium-exchanged FAU-Y zeolite catalyzed improvement in the synthesis of 6H-indolo[2,3-b]quinolines

Article abstract of DOI:10.1016/j.molcata.2011.05.010

Ruthenium-exchanged FAU-Y zeolite (RuY) was used as a recyclable catalyst for preparation of 6H-indolo[2,3-b]quinolines from the reaction of indole-3-carbaldehyde with aryl amines in refluxing dioxane. Under the above mentioned conditions, reasonable yields of the desired products with different substituents on the quinoline ring were obtained.

Full text of DOI:10.1016/j.molcata.2011.05.010

Journal of Molecular Catalysis A: Chemical 344 (2011) 128–131
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Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Ruthenium-exchanged FAU-Y zeolite catalyzed improvement in the synthesis of
6H-indolo[2,3-b]quinolines
Alireza Khorshidi∗, Khalil Tabatabaeian
Department of Chemistry, Faculty of Sciences, University of Guilan, P.O. Box 41335-1914, Rasht, Guilan, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Ruthenium-exchanged FAU-Y zeolite (RuY) was used as a recyclable catalyst for preparation of 6H-
indolo[2,3-b]quinolines from the reaction of indole-3-carbaldehyde with aryl amines in refluxing
dioxane. Under the above mentioned conditions, reasonable yields of the desired products with different
substituents on the quinoline ring were obtained.
Received 27 January 2011
Received in revised form 16 April 2011
Accepted 15 May 2011
Available online 23 May 2011
© 2011 Elsevier B.V. All rights reserved.
Keywords:
Ruthenium-exchanged zeolite
6H-Indolo[2,3-b]quinoline
Catalyst
Table 1
1. Introduction
Effect of catalyst on the yield of 6H-indolo[2,3-b]quinoline.
Entrya
Catalyst
Loadingb
Yieldc (%)
The development of new efficient synthetic methods lead-
ing to indole derivatives continues to receive much attention
in organic synthesis because of their biological activities [1,2].
Various indole derivatives occur in many pharmacologically and
biologically active compounds [3]. Among them, 6H-indolo[2,3-
b]quinoline is the precursor to cryptotakieine (neocryptolepine)
alkaloid [4–7], one of the major metabolites out of thirteen alkaloids
isolated from Cryptolepis sanguinolenta [8,9], which proved to be an
effective DNA intercalator [10–12]. Various methyl derivatives of
such systems display biological properties such as antimuscarinic,
antibacterial, antiviral, antimicotic and antihyperglycemic [13–15].
We have recently reported the preparation of oxindoles form
electrophilic substitution reaction of indoles with isatin-derived
imines under ruthenium catalysis [16]. During preparation of the
aldimine precursor from indole-3-carbaldehyde and aniline for a
similar reaction, we observed that a trace amount of an unknown
side product was formed. Meanwhile, Parameswaran et al. reported
the preparation of 6H-indolo[2,3-b]quinolines from the reaction
of indole-3-carbaldehyde with aryl amines in the presence of a
catalytic amount of iodine [17]. Characterization of the afore-
mentioned side product revealed its 6H-indolo[2,3-b]quinoline
structure. This prompted us to evaluate the catalytic potential of
ruthenium towards preparation of 6H-indolo[2,3-b]quinolines. Lit-
erature survey showed that the reported methods on this type of
1
2
3
4
5
6
7
8
No catalyst
RuY
RuY
RuY
HY
NaY
Ru-NaY
Ru-AlMCM-41
0
0
40
65
65
38
0
0.05
0.1
0.25
0.1
0.1
0.1
0.1
58
45
a
The reaction was carried out according to general experimental procedure. Con-
ditions: dioxane, 4 h, reflux.
b
g of catalyst per mmol of aldehyde.
Isolated yields.
c
synthesis have drawbacks such as multi step procedure, long reac-
tion times, unsatisfactory yields and use of toxic solvents [17–19].
Ruthenium species, on the other hand, are well known to catalyze
a variety of organic transformations [20]. In continuation of our
recent work on indole derivatives and catalytic reactivity of ruthe-
nium [21–25], we now describe an improvement in the synthesis
of 6H-indolo[2,3-b]quinolines, using ruthenium-exchanged FAU-Y
zeolite (RuY) as a recyclable heterogeneous catalyst (Scheme 1).
∗
Corresponding author. Tel.: +98 911 339 7159; fax: +98 131 322 0066.
E-mail address: rucatalyst@yahoo.com (A. Khorshidi).
Scheme 1. RuY catalyzed synthesis of 6H-indolo[2,3-b]quinolines.
1381-1169/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2011.05.010

A. Khorshidi, K. Tabatabaeian / Journal of Molecular Catalysis A: Chemical 344 (2011) 128–131
129
Table 2
Effect of solvents on the yield of 6H-indolo[2,3-b]quinoline.
Entrya
Solvent
Temperatureb(◦C)
Yieldc (%)
1
2
3
4
5
1,2-Dichloroethane
THF
Dioxane
Dioxane
C2H5OH
84
66
RT
105
78
35
5
0
65
36
a
The reaction was carried out according to general experimental procedure (0.1 g
RuY, 4 h).
b
Reflux conditions.
Isolated yields.
c
2. Results and discussion
First of all, using indole-3-carbaldehyde and aniline as sub-
strates, the reaction conditions were optimized with respect to
catalyst-type and loading, choice of solvent and temperature. The
effect of catalyst-type and loading on the yield of product is sum-
marized in Table 1.
Table 3
RuY catalyzed synthesis of 6H-indolo[2,3-b]quinolines.
Entrya Amine
Productb
Time (h) Yieldc
1
2
Aniline
4
6
65
55
o-Toluidine
Scheme 2. Proposed mechanistic pathway for the RuY catalyzed formation of 6H-
indolo[2,3-b]quinoline.
As it is shown, in the absence of catalyst, no formation of
the desired product was observed (entry 1), and the optimum
loading was found to be 0.1 g RuY per mmol of the aldehyde
substrate (entry 3). In order to further explore the role of differ-
ent acid sites (Lewis and Bronsted) in the reaction, a comparison
was also made between NaY, ruthenium-exchanged NaY (Ru-NaY)
and ruthenium-exchanged mesoporous AlMCM-41 (Ru-AlMCM-
41). In situ DRIFT (pyridine adsorption) measurements were used to
determine the acidity of the catalysts. Correlation between DRIFT
signals and coordination site of pyridine (Lewis or Bronsted acid
sites which are responsible for the catalytic activity of zeolites) is
well reported [26–28]. As it is shown in Table 1, the yield of product
increases in the order NaY < HY < Ru-NaY < RuY, which is the same
order of the increasing Lewis acid site density of the catalysts. Ru3+
ion-exchanged HY zeolite showed better activity than the parent
HY zeolite owing to its higher Lewis acidity. Mesoporous AlMCM-41
(Si/Al ratio of 39) when ion-exchanged with Ru3+, however, showed
lower activity (entry 8). This may be due to lower cation exchange
capacity of the AlMCM-41 [29]. Higher activity of microporous RuY,
on the other hand, may be attributed to its lower Si/Al ratio and
higher external surface acid sites.
3
m-Toluidine
6
50
4
5
p-Toluidine
6
6
55
53
3-Bromoaniline
6
7
3-Aminopyridine
8
5
39
68
␣-Naphthylamine
Solvent screening experiments showed that the yields were sol-
vent dependent (Table 2, entries 1–5) and the best solvent was
found to be refluxing dioxane (105 ◦C, entry 4).
With the optimized conditions in hand (Scheme 1), an array
of anilines was used to explore generality of the reaction. Typical
results are shown in Table 3. Treatment of indole-3-carbaldehyde
(1 mmol) with aniline (1 mmol) in refluxing dioxane (5 mL) in the
presence of Ru3+ exchanged FAU-Y zeolite (RuY, 0.1 g, activated at
8
␤-Naphthylamine
5
73
a
The reaction was carried out according to general experimental procedure (0.1 g
RuY, dioxane, reflux).
b
Identified by comparison with authentic samples [11,17,19].
Isolated yield.
c

130
A. Khorshidi, K. Tabatabaeian / Journal of Molecular Catalysis A: Chemical 344 (2011) 128–131
Table 4
lite). All other materials were purchased from Merck and used
without further purification.
Reaction of indole-3-carbaldehyde and aniline in presence of the recycled catalyst
in successive runs.
Runa
Catalyst:aldehyde ratio
Time (h)
Yieldb (%)
4.3. General procedure for the RuY catalyzed formation of
6H-indolo[2,3-b]quinolines
1
2
3
4
5
0.1 g:1 mmol
4
4
4
4
4
65
63
63
61
60
”
”
”
”
Indole-3-carbaldehyde (1 mmol) and RuY (0.1 g) were added to a
solution of arylamine (1 mmol) in dioxane (10 mL) and the mixture
was refluxed for the appropriate time (Table 3). After completion of
the reaction (as indicated by TLC), the mixture was filtered and the
catalyst washed thoroughly with dioxane, then filtered and dried.
The combined washings and filtrate were concentrated in vacuum.
The crude product was purified by preparative TLC (n-hexane/ethyl
acetate: 10/4). The recovered catalyst was reactivated at 550 ◦C.
a
Conditions: RuY, dioxane, reflux.
Isolated yields.
b
550 ◦C for 3 h) after 4 h, gave 6H-indolo[2,3-b]quinoline in 65% iso-
lated yield. With regard to the amine moiety, the present protocol is
noteworthy because naphthyl amines, as well as other substituted
anilines participated in the reaction.
4.4. Selected spectroscopic data for 6H-indolo[2,3-b]quinoline
Although the precise mechanism of the reaction awaits further
studies, the following proposed mechanistic pathway (Scheme 2)
rationalizes the formation of a quinoline ring on an indole back-
bone.
In order to evaluate reusability of the solid catalyst, the reaction
of indole-3-carbaldehyde and aniline was carried out in presence
of the recycled catalyst (see Section 4) in successive runs. These
results are shown in Table 4.
Yellow solid, m.p. 343–345 ◦C, IR (KBr): ꢀ (cm−1); 3144, 1616,
1460, 1405, 1230; 1H NMR (400 MHz, DMSO-d6, 25 ◦C): ı = 11.70
(s, 1H, NH), 9.05 (s, 1H), 8.27 (d, J = 7.8 Hz, 1H), 8.11 (d, J = 8.1 Hz,
1H), 7.98 (d, J = 8.4 Hz, 1H), 7.72 (m, 1H), 7.45–7.58 (m, 3H), 7.27
(m, 1H) ppm. 13C NMR (100 MHz, DMSO-d6, 25◦C): ı = 153.36,
146.80, 141.95, 130.31, 129.13, 128.68, 128.00, 127.45, 124.15,
123.20, 122.28, 120.76, 120.14, 118.38, 111.39 ppm. Anal. Calcd for
As it is shown, only 5% loss of efficiency in terms of the product
yield was observed after five runs, which promises minimization
of the waste.
C
15H10N2: C, 82.55; H, 4.62; N, 12.84; found: C, 82.51; H, 4.60; N,
12.84.
Acknowledgements
3. Conclusion
The authors are grateful to the Research Council of University of
Guilan for partial support of this study. A. Khorshidi is thankful to
Dr. M. A. Faramarzi for his generous support.
In conclusion, we have developed a convenient method for
preparation of indoloquinolines. Highlights of the present work are:
i) Application of RuY as a heterogeneous catalyst resulted in more
efficiency in terms of reaction time, temperature and yield.
ii) Reusability of the solid acid catalyst is also, noticeable.
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