CsxH3-xPW12O40 heteropoly salts catalyzed quinoline synthesis via Friedl?nder reaction

Article abstract of DOI:10.1016/j.cclet.2010.09.036

Various type of cesium partially substituted phosphotungstate, Cs _xH_3-xPW₁₂O₄₀ (x = 1.0, 2.0 and 2.5), were synthesized and their catalytic activities were investigated in the synthesis of quinoline. It was show

Full text of DOI:10.1016/j.cclet.2010.09.036

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Chinese Chemical Letters 22 (2011) 288–291
www.elsevier.com/locate/cclet
CsxH3ÀxPW12O40 heteropoly salts catalyzed quinoline synthesis
¨
via Friedlander reaction
a
a,b
Ezzat Rafiee a,b, , Fereshte Khajooei Nejad , Mohammad Joshaghani
*
a Faculty of Chemistry, Razi University, Kermanshah 67149, Iran
b Kermanshah Oil Refining Company, Kermanshah, Iran
Received 17 June 2010
Available online 22 December 2010
Abstract
Various type of cesium partially substituted phosphotungstate, CsxH3ÀxPW12O40 (x = 1.0, 2.0 and 2.5), were synthesized and
their catalytic activities were investigated in the synthesis of quinoline. It was shown that catalytic activities of these catalysts
correlated to surface acidity and total number of acidic sites. Finally, a series of quinoline derivatives were synthesized with
¨
Cs2.5H0.5PW12O40 via the Friedlander reaction in high to excellent yields and the plausible mechanism was proposed. Simple
experiment, catalyst reusability, short reaction time and preclusion of toxic solvent are the advantages of this method.
# 2010 Published by Elsevier B.V. on behalf of Chinese Chemical Society.
¨
Keywords: Quinoline; Friedlander reaction; Cesium Keggin salts; Acidity
Quinoline is a well-known structural unit in several natural compounds (cincona alkaloids) and synthetic analogues
with interesting biological activities [1]. The biological activity of quinoline derivatives has been found to possess
¨
antiasthmatic, antibacterial and antihypertensive properties [2]. The Friedlander reaction is a well-known, simple, and
most straightforward protocol for preparing quinolines and related bicyclic compounds. It is a condensation reaction
followed by a cyclodehydration between an aromatic 2-aminoaldehyde or ketone and an aldehyde or ketone with an a-
methylene functionality under acidic or basic conditions [3]. Several solid acid catalysts have been used in the
¨
Friedlander reaction including Ag3PW12O40 [4], sulfamic acid [5], HClO4–SiO2 [6], amberlyst-15 [7], dodecylpho-
sphonic acid [8] and o-benzenedisulfonimide [9]. Although some of these methods have convenient protocols with
good to high yields, the majority of these methods suffer from drawbacks such as the presence of hazardous and toxic
solvents [4,6,7], long reaction times or unsatisfactory yields for some substrates [5,7–9], and use of expensive or non-
commercially available catalysts [9]. Since, quinoline derivatives are useful in drugs and pharmaceuticals, the
development of simple, convenient and high yielding protocols is much needed.
Rapid development of science and technology requires the development of new catalysts and methodologies with
low waste and reusable reaction media for minimized cost and energy. In order to achieve this goal, use of Keggin type
heteropoly compounds (HPCs) as catalyst is preferred technique owing to their versatility and unique properties which
has been demonstrated both by successful industrial applications, and by interesting results in laboratory scale work.
* Corresponding author at: Faculty of Chemistry, Razi University, Kermanshah 67149, Iran.
E-mail addresses: ezzat_rafiee@yahoo.com, e.rafiei@razi.ac.ir (E. Rafiee).
1001-8417/$ – see front matter # 2010 Published by Elsevier B.V. on behalf of Chinese Chemical Society.
doi:10.1016/j.cclet.2010.09.036

[()TD$FIG]
E. Rafiee et al. / Chinese Chemical Letters 22 (2011) 288–291
289
O
O
O
O
OEt
Catalyst (0.2 g)
Solvent-free, 100 oC
+
OEt
N
NH2
Scheme 1. Model reaction.
The structure and composition of HPCs play an important role in catalysis and their catalytic properties can be
controlled in a systematic way by partially exchanging protons of the parent HPCs with large cations, such as Cs+, K+,
+
Rb+, or NH4 [10]. Partial substitution of Cs+ for protons in CsxH3ÀxPW12O40 catalysts improved surface area and
thermal stability compared to parent acids. Also, the surface acidity, and pore width can be controlled by the Cs content
[11]. These compounds are efficient solid acid catalysts for a variety of organic reactions, such as alkylation [10],
esterification [12], condensation [13], and biodiesel fuel preparation [14]. According to our previous investigations
[12,13], herein we want to report the applicability of CsxH3ÀxPW12O40 in the synthesis of quinolines. The reaction of
2-aminoacetophenone (1.0 mmol) and ethylacetoacetate (1.2 mmol) under solvent-free conditions at 100 8C was
selected as the model reaction in all cases (Scheme 1).
Initially, this conversion has been carried out in the presence of 0.2 g of H3PW12O40 (PW12) and its partial
substituted acidic Cs salt catalysts containing Cs1H2PW12O40 (Cs1PW), Cs2H1PW12O40 (Cs2PW), and
Cs2.5H0.5PW12O40 (Cs2.5PW). Potentiometric titration with n-butylamine has been used to estimate the total number
of acid sites and the acidic strength of these catalysts. The n-butylamine is considered a strong base, so its adsorption
could be expected on sites of different acid strength. Taking into account that the initial electrode potential (Ei)
indicates the highest strength of the acid sites and the obtained plateau value (meq amine/g catalyst) indicates the total
number of acid sites that are present in the titrated solid [15]. The strength of the acid sites can be classified according
to the following scale: Ei > 100 mV (very strong sites); 0 < Ei < 100 mV (strong sites); À100 < Ei < 0 mV (weak
sites); and Ei < À100 mV (very weak sites) [15]. All the catalysts exhibit very strong acidic sites as they showed high
Ei values, which are found to vary in the range of 200–700 mV. Fig. 1a shows yield and Ei amount as a function of Cs
content. The maximum acid strength of the sites (bulk Brønsted acidity) changed in following order:
PW12 > Cs1PW > Cs2PW > Cs2.5PW [11]. The Ei values and yields are in the same order except for Cs2.5PW.
In contrast, both catalytic activity and total number of surface acidic sites decreased slightly from x = 0 to x = 2,
although these amounts increased when the Cs content changed from x = 2 to x = 2.5 (Fig. 1b). Consequently, the
dependence of surface acidity and catalytic activity of CsxH3ÀxPW12O40 to Cs content is remarkable. The surface area
and acidity of Cs salt of heteropoly acid (HPA) were influenced largely by the number of substituted Cs+. For Cs2.5PW
surface area is large and catalytic activity of Cs2.5PW was ascribed to its high surface acidity [11].
In order to extent the scope of this system, various activated a-methylene compounds were used as substrates to
¨
undergo Friedlander reaction using Cs2.5PW as the best catalyst. The results are summarized in Table 1. b-Ketoesters
and acyclic b-diketones worked successfully owing to higher reactivity and gave excellent yield of the products (Table
1, entries 1, 2, 4, 5). Dimedone, 4-methylacetophenone and acetophenone provided the corresponding enamine as a
by-product in low yield, while cyclohexanone gave only enamine as a final product (Table 1, entries 3, 6, 8, 9).
[()TD$FIG]
Fig. 1. Yield of the product in the model reaction after 20 min: (a) acidity and (b) total number of acidic sites of the catalysts as a function of cesium
content in CsxH3ÀxPW12O40
.

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E. Rafiee et al. / Chinese Chemical Letters 22 (2011) 288–291
Table 1
Synthesis of quinoline derivatives in the presence of Cs2.5PW.
[TD$INLE]
.
Entry
Ketone
Time (min)
Yield (%)a,b
Conversion (%)
1
2
3
4
5
6
7
8
9
Ethylacetoacetate
Methylacetoacetate
Dimedone
15
25
15
5
91
98
88
83
96
82c
93
85
61
91
98
97
83
96
82
93
94
82
Benzoylacetone
Acetylacetone
20
30
10
15
15
Cyclohexanone
4-Nitro-acetophenone
4-Methylacetophenone
Acetophenone
a
Isolated yield.
Identified by spectroscopic (IR, 1H NMR) analyses.
b
c
Yield of corresponding enamine.
Acetophenone with an electron withdrawing substitute in para position improved the yield in the reaction process
(Table 1, entry 7).
There are two possible reaction mechanisms that are shown in Scheme 2 [16,17]. The results of the reaction of
cyclohexanone with 2-amino acetophenone (Table 1, entry 6) confirmed that mechanism b is the possible one, which
enamine was formed as an intermediate. Proton conductivity of HPAs as acid catalysts is completely essential to
¨
activate carbonyl compound. In the Friedlander synthesis, a crossed-aldol reaction takes place initially, creating an
amino ketone. This intermediate subsequently condenses with itself, and produced the ring with concomitant
formation of the carbon–nitrogen double bond.
The results after reusing of Cs2.5PW for three times in model reaction indicate that Cs2.5PW is a reusable catalyst
and yield of product was 76% after fourth run. Conversion was approximately constant, but selectivity of the reaction
has been slightly decreased (81% after fourth run), it is because of formation of side product.
CsxH3ÀxPW12O40 (x = 1.0, 2.0 and 2.5) compounds were active catalysts for the reaction of 2-aminoacetophenone
and ethylacetoacetate under solvent-free conditions. Among these acidic Cs salts, Cs2.5PW was most active. This is
due to the largest amount of acid sites on the surface (surface acidity). Thus, various activated a-methylene
[()TD$FIG]
H
HO
O
R2
R1
O
OH
O
(a)
R2
R2
R2
H+
+
R1
R1
R1
NH2
NH2
O
R2
R1
R2
R1
OH
R2
R1
-H2O
-H2O
N
N
O
NH2
R2
H
O
O
R2
R1
Scheme 2. Proposed mechanism.
O
(b)
R2
R1
+
N
R1
N
NH2
H

E. Rafiee et al. / Chinese Chemical Letters 22 (2011) 288–291
291
¨
compounds were used as substrate to undergo Friedlander reaction using Cs2.5PW as catalyst. The catalyst could be
easily recovered and reused without a considerable change in its catalytic activity. Also, the plausible mechanism was
proposed according to enamine which was formed as an intermediate.
1. Experimental
For the potentiometric titration, 0.05 g of solid was preheated and suspended in acetonitrile (90 ml) and stirred for
3 h. The suspension was titrated with a 0.05 mol/L solution of n-butylamine in acetonitrile. The potential variation was
measured with a Hanna 302 pH meter using a double junction electrode.
1.1. Preparation of CsxH3ÀxPW12O40
The acidic salts of CsxH3ÀxPW12O40 were prepared by the literature method [11]. The required amount of aqueous
cesium carbonate has been added to aqueous solution of PW12 with stirring. An appropriate amount of the aqueous
solution of Cs2CO3 (0.10 mol/L) was added drop wise to the aqueous solution of PW12 (0.08 mol/L) at room
temperature with vigorous stirring. The Cs content was adjusted by the amount of Cs2CO3 solution added. The
resulting white colloidal solutions of Cs salts were left overnight in the oven at 40 8C to slowly evaporate to dryness.
Cesium content in CsxH3ÀxPW12O40 catalysts was confirmed by inductively coupled plasma (ICP) atomic emission
spectroscopy on a Spectro Ciros CCd spectrometer. The primary Keggin structures of these catalysts were identified by
comparing their FTIR absorption bands to those of bulk PW12 as reported elsewhere [18].
¨
1.2. General procedure for Friedlander reaction
A mixture of 2-amino acetophenone (1.0 mmol), a-methylene carbonyl compound (1.2 mmol) and catalyst (0.2 g)
were added to a pyrex tube fitted with a ground glass joint. These compounds were ground together using a glass rod at
100 8C. After reaction completion, as indicated by TLC, the reaction mixture was cooled and diluted with CH3CN
(5 mL) and filtered. The catalyst was recovered from residue. The filtrate was concentrated and product was purified
by column chromatography on silica gel using ethylacetate/hexane as eluent. Recovered catalyst was washed with
CH3CN (3 Â 10 mL) and reused.
Acknowledgments
The authors thank the Razi University Research Council and Kermanshah Oil Refining Company for support of this
work.
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