Green synthesis of polyhydroquinolines catalyzed by silica-supported ionic liquid Si–[SbSipim][PF6]

Article abstract of DOI:10.1002/jccs.201800301

Silica-supported ionic liquid Si–[SbSipim][PF₆] as a catalyst was used first in the synthesis of polyhydroquinolines. The catalyst exhibits high catalytic activity in the reaction, and can be easily recovered and reused without significant loss

Full text of DOI:10.1002/jccs.201800301

Received: 1 August 2018
Revised: 28 January 2019
Accepted: 14 March 2019
DOI: 10.1002/jccs.201800301
A R T I C L E
Green synthesis of polyhydroquinolines catalyzed by
silica-supported ionic liquid Si–[SbSipim][PF6]
Hui Ying Liao | Li Qin Kang | Shan Shan Zhang | Jia Hui Yan
School of Chemical and Environmental
Silica-supported ionic liquid Si–[SbSipim][PF ] as a catalyst was used first in the
Engineering, Shanghai Institute of Technology,
Shanghai, China
6
synthesis of polyhydroquinolines. The catalyst exhibits high catalytic activity in
the reaction, and can be easily recovered and reused without significant loss of its
activity for six runs. This green method offers several advantages, including high
yield, short reaction time, simple work-up procedure, ease of separation, and recy-
clability of the catalyst.
Correspondence
Li Qin Kang, School of Chemical and
Environmental Engineering, Shanghai Institute of
Technology, 100 Haiquan Road, Shanghai, China.
Email: klq@sit.edu.cn
Jia Hui Yan, School of Chemical and
Environmental Engineering, Shanghai Institute of
Technology, 100 Haiquan Road, Shanghai, China.
Email: yjh@sit.edu.cn
KEYWORDS
ionic liquid, multicomponent reaction, recyclable, silica-supported
Funding information
Science and Technology Foundation of Shanghai
Institute of Technology
1
| INTRODUCTION
under green conditions is still the need of the day. As a part
of our program to explore the potential applications of func-
Polyhydroquinolines and their derivatives are an important
class of organic heterocyclic compounds due to their appli-
cations in pharmaceutical and chemical industries. They are
very well known for their wide range of biological activities
tional ionic liquids, we now report silica-supported ionic liq-
uid (Si–[SbSipim][PF ]) as the catalyst for the synthesis of
6
polyhydroquinolines. To the best of our knowledge, the use
of silica-supported ionic liquid for the synthesis of poly-
hydroquinolines has not been studied yet.
[
1]
including antiulcer, antihypertensive, analgesic, and hyp-
[
2]
notic. They are also very well known for the most impor-
tant classes of drugs for the treatment of angina pectoris,
2
| RESULTS AND DISCUSSION
[3,4]
hypertension, and other cardiovascular diseases.
The
Hantzsch reaction for the synthesis of polyhydroquinolines
involves one-pot condensation of an aldehyde with
[25]
In continuation of our work
on the development of useful
synthetic methodologies, we observed that poly-
hydroquinolines can conveniently be synthesized by a mul-
ticomponent reaction of an aldehyde, ethyl acetoacetate,
, 5-dimethyl-1, 3-cyclohexanedione, and AcONH in the
4
presence of Silica-supported ionic liquid Si–[SbSipim][PF6]
in ethanol under reflux with 8 mol% of Si–[SbSipim][PF6]
β-ketoester and NH in AcOH or in alcohol under reflux for
3
[
5–11]
several hours.
This reaction has subsequently been pro-
moted by employing different catalysts, such as nano-CuO,
5
[
12,13]
[14]
[15]
ZnO,
acid,
nano-Fe O @SiO ,
Ni nanoparticles,
lewis
3
4
2
[
16]
[17,18]
[19]
Mg(ClO ) or Yb(OTf) ,
and ionic liquid.
4
2
3
In recent years, supported ionic liquid catalysts (SILCs) have
(
Scheme 1). The acid exchange capacity of Si–[SbSipim]
PF ] measured by potentiometric titration with NaOH was
[20,21]
been an attractive research area.
This reaction has sub-
[
6
sequently been carried out by employing different catalysts
1
.0 mmol/g. The sulfonic acid-functional ionic liquid had
[22]
such as silica-supported acids,
silica-functionalized sul-
been bound to a surface of silica by covalent bonds and
avoided any loss of ionic liquid after the reaction. Ther-
mogravimetric (TG) experiments were carried out in N at a
[23]
fonic acid coated with ionic liquid,
and ionic liquid-
However, the synthesis of
polyhydroquinolines using efficient and reusable catalysts
[24]
supported nanoporous silica.
2
scan rate of 100 mL/min. The heating rate employed was
©
2019 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J Chin Chem Soc. 2019;1–5.
http://www.jccs.wiley-vch.de
1

2
LIAO ET AL.
O
2
TABLE 1 Effect of catalysts and solvents on model reaction
O
1
Ar
H
O
O
Ar
O
Yield
b
Si-[SbSipim][PF6]
Entrya
ꢀ
Solvent
Solvent-free
Acetonitrile
Water
T ( C)
Reflux
Reflux
Reflux
Reflux
60
Catalyst (g)
Time (hr)
(%)
25
65
18
86
78
40
86
74
86
O
3
O
1
2
3
4
5
6
7
8
9
0.5
0.5
0.5
0.5
0.5
0.5
0.4
0.3
0.6
2
2
2
2
2
2
2
2
2
O
O
N
H
NH4OAc
4
5a-5i
-
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Si [SbSipim][PF6]
OH
PF6-
OMe
O
SO H
3
30
Si
O
N
N
Reflux
Reflux
Reflux
SCHEME 1 Green one-pot route for the synthesis of polyhydroquinolines
a
Reaction conditions: benzaldehyde (5.0 mmol), 5, 5-dimethyl-1,
-ethylacetoacetate (5.0 mmol), ammonium acetate (5.0 mmol), and Si–
3
[SbSipim][PF
6
] (0.4 g) as catalysts.
ꢀ
b
1
0 C/min. We investigated the thermostability of Si–
Isolated yield.
[
SbSipim][PF ] via Thermogravimetric analysis (TGA) mea-
6
surement. The TGA curve measured for the catalyst revealed
the weight loss process with a thermal decomposition tem-
compounds to afford the corresponding products in excellent
yields (Table 2).
ꢀ
perature (T) in the 0–700 C range (Figure 1). As shown in
The recyclability of the Si–[SbSipim][PF ] was investi-
ꢀ
6
Figure 1, a mass loss begins at 250 C, which is attributed to
gated through the syntheses of 5a as modeling reaction.
After completion of the reaction, monitored by TLC, the cat-
alyst was filtered and washed with ethanol, dried and reused
five times. The average chemical yield for six consecutive
runs was 86% to 83%. The yield did not drop significantly
until the eighth consecutive runs, which clearly demonstrates
the practical recyclability of this catalyst (Figure 2).
the dehydration of Si–[SbSipim][PF ]. Therefore, Si–
6
[
2
SbSipim][PF ] retained a high thermostability before
50 C. This provides the basis for our later catalytic
6
ꢀ
experiments.
The catalytic Si–[SbSipim][PF ] has been systemati-
6
cally studied in the rapid and efficient preparation of poly-
hydroquinolines through a multicomponent reaction. A
four-component coupling reaction of benzaldehyde,
The mechanism for the formation of poly-
hydroquinolines in the presence of [SbSipim][PF ] was
6
5, 5-dimethyl-1,3-cyclohexanedione, ethyl acetoacetate, and
hypothesized, which can act as an acid catalyst. As can be
ammonium acetate as a modeling reaction was examined. As
can be seen from the results in Table 1, the use of benzalde-
hyde (5 mmol), 5,5-dimethyl-1,3-cyclohexanedione (5 mmol),
ethyl acetoacetate (5 mmol), and ammonium acetate (5 mmol)
seen, the interaction between [SbSipim][PF ] and lone pair
6
electrons of oxygen in the carbonyl bond causes the forma-
tion of corresponding Knoevenagel product 5 as well as
enamine product 6. In the following, Michael addition and
cyclohydration to furnish the desired products 7 occurred
in the presence of Si–[SbSipim][PF ] (0.4 g) in ethanol under
6
reflux was the best condition. Aromatic aldehydes with vari-
ous substituents carrying either electron-donating or electron-
withdrawing groups reacted successfully with 1, 3-dicarbonyl
between 5 and 6 under [SbSipim][PF ] (Scheme 2).
6
6
TABLE 2 Formation of polyhydroquinolines using Si–[SbSipim][PF ]
ionic liquid as a catalyst
1
1
1
1
1
1
1
7.0
6.5
6.0
5.5
5.0
4.5
4.0
ꢀ
b
M.p./( C)
Found
Yield
t/hr /%
a
Product
R
Reported
[
26]
5
5
5
5
a
b
c
C
6
H
5
2
2
2
1
1
2
1
1
1
86
88
87
86
84
85
84
85
80
228.9–229.0 228–229
210.8–211.0 210–212
203.7–204.2 201–204
179.1–179.4 177–178
294.9–295.3 297–298
258.5–258.8 260–262
230.5–230.9 230–232
217.7–217.9 216–218
201.4–201.5 201–204
[27]
2-Cl-C
3-Br-C
3-NO
4-CH
4-OCH
4-N(CH
2,4-diCl-C
α-Naphthyl
6 4
H
[
[
[
[
28]
29]
30]
26]
6 4
H
d
2
5e
3
-C
6
H
4
5
5
5
5
f
3
-C
6
H
4
[29]
g
h
i
3 2 6 4
) -C H
[
[
26]
31]
6 3
H
0
100
200
300
400
500
600
700
800
a
Reaction conditions: aldehyde (5.0 mmol), 5, 5-dimethyl-1, 3-ethylacetoacetate
] (0.4 g), etha-
T (°C)
FIGURE 1 TGA of Si–[SbSipim][PF
(
5.0 mmol), ammonium acetate (5.0 mmol), and Si–[SbSipim][PF
6
nol as a solvent, reflux.
b
6
]
Isolated yield.

LIAO ET AL.
3
3
1
.2.2 | Ethyl 4-(3-brominephenyl)-2,7,7-trimethyl-5-oxo-
,4,5,6,7,8-hexahydroquin-oline-3-carboxylate (5c)
1
Yellow solid; H NMR (500 MHz, CDCl ) δ: 0.98 (s，3H),
3
1
(
(
7
.11 (s，3H)，1.21–1.24 (t，J = 7.25 Hz, 3H)，2.17–2.27
m，3H)，2.35–2.41 (m，4H)，4.07–4.10 (m，2H)，5.04
s，1H)，5.82 (s，1H)，7.07–7.10 (t，J = 7.75 Hz, 1H),
.24–7.26 (d, 1H)，7.28 (d, 1H)，and 7.42 (s, 1H).
3
1
.2.3 | Ethyl 4-(3-nitrophenyl)-2,7,7-trimethyl-5-oxo-
,4,5,6,7,8-hexahydroquin-oline-3-carboxylate (5d)
1
Yellow solid; H NMR (500 MHz, CDCl ) δ: 0.957 (s，
3
3H)，1.12 (s，3H)，1.20–1.23 (t，J = 2 Hz, 3H)，
2.15–2.30 (m，4H)，2.42–2.44 (m，3H)，4.06–4.10 (m，
2H)，5.17 (s，1H)，5.86 (s，1H)，7.38–7.41 (t，
J = 8 Hz, 1H)，7.74–7.76 (d，1H)，7.99–8.01 (d，1H)，
and 8.12 (s, 1H).
6
FIGURE 2 Recycling of Si–[SbSipim][PF ]
3
1
.2.4 | Ethyl 4-(4-methylphenyl)-2,7,7-trimethyl-5-oxo-
,4,5,6,7,8-hexahydroquin-oline-3-carboxylate (5e)
3
| EXPERIMENTAL
.1 | Chemicals and instrumentation
1
Yellow solid; H NMR (CDCl , 500 MHz) δ: 0.97 (s，
3
3
2
2
H)，1.09 (s，3H)，1.22–1.25 (t，J = 7.25 Hz, 3H)，
.16–2.27 (m，6H)，2.33–2.38 (m，4H)，4.08–4.09 (m，
H)，5.03 (s，1H)，5.86 (s，1H)，7.01–7.03 (d，2H)，
3
Melting points were measured on a WRS-IB digital melting
1
point instrument. H NMR was recorded on an AVANG
and 7.19–7.21 (d，2H).
500 MHz spectrometer with TMS as an internal standard.
The ionic liquid Si–[SbSipim][PF6] was synthesized
according to the procedure reported in previous literature.
3.2.5
| Ethyl 4-(4-methoxylphenyl)-2,7,7-trimethyl-5-oxo-
[
32]
1,4,5,6,7,8-hexahydroquin-oline-3-carboxylate (5f)
1
Yellow solid; H NMR (500 MHz, CDCl ) δ: 0.96
3
(
2
s, 3H)，1.09 (s，3H)，1.21–1.24 (t，3H，J = 7.25 Hz),
.16–2.26 (q，3H)，2.33–2.38 (m，4H)，3.78 (s, 3H),
3
.2 | General procedure for the synthesis of 5a–5i
The aldehyde (5 mmol), ethyl acetoacetate (5 mmol),
cyclohexane-1,3-dione (5 mmol), AcONH (5 mmol), Si–
4.06–4.10 (m，2H)，5.01 (s，1H)，5.77 (s，1H),
6.79–6.75 (d，2H)，and 7.24–7.23 (d，2H).
4
3
[SbSipim][PF ] (0.4 g), and ethanol (5 cm ) were added to a
6
3
5
.2.6 | Ethyl 4-(4-N, N -dimethylphenyl)-2,7,7-trimethyl-
-oxo-1,4,5,6,7,8-hexahydroquin-oline-3-carboxylate (5g)
5
0 mL round-bottom flask equipped with a magnetic stirring
bar connected to a water-cooled condenser. The mixture was
stirred at reflux for a certain period of time to complete the
reaction (oil bath, monitored by TLC). After the reaction, the
hot mixture was filtered to separate the catalyst. The catalyst
was recovered by washing with ethanol and drying. The fil-
trate was cooled to ambient temperature and the resulting
solid crude product was filtered and then recrystallized from
1
Yellow solid; H NMR (500 MHz, CDCl ) δ: 0.99 (s,
3
3
H)，1.09 (s, 3H)，1.23–1.26 (t，J = 7 Hz, 3H), 2.16–2.26
(m, 3H)，2.32–2.38 (m, 4H)，2.89 (s, 6H)，4.06–4.10 (m,
2
7
H)，4.97 (s, 1H)，5.79 (s, 1H)，6.61–6.62 (m, 2H)，and
.17–7.18 (d, 2H).
3
1
.2.7 | Ethyl 4-(2, 4- dichlorophenyl)-2,7,7-trimethyl-5-oxo-
,4,5,6,7,8-hexahydroquin-oline-3-carboxylate (5h)
95% ethanol to obtain pure product polyhydroquinolines. All
1
compounds were characterized by the H NMR spectra were
listed in the Supporting Information. Melting points are
found to be almost identical with those that reported in the
literature elsewhere.
1
Yellow solid; H NMR (500 MHz, CDCl ) δ: 0.97 (s,
3
3
3
H)，1.09 (s, 3H)，1.19–1.21 (t, 3H)，2.12–2.24 (m,
H)，2.35 (m, 4H)，4.04–4.08 (m, 2H)，5.35 (s, 1H), 5.98
(s, 1H)，7.11–7.13 (d, 1H)，7.28 (s, 1H)，and 7.34–7.35
(
d, 1H).
3
1
.2.1 | Ethyl 4-(2-chlorophenyl)-2,7,7-trimethyl-5-oxo-
,4,5,6,7,8-hexahydroquin-oline-3-carboxylate (5b)
3
.2.8 | Ethyl 4-(α-naphthyl)-2,7,7-trimethyl-5-oxo-
1
Yellow solid; H NMR (500 MHz, CDCl ) δ: 0.98 (s, 3H),
1,4,5,6,7,8-hexahydroquin-oline-3-carboxylate (5i)
3
1
1
3
5
.09 (s, 3H), 1.18–1.21 (t, J = 7 Hz, 3H), 2.16–2.23 (m,
H), 2.33–2.36 (m, 4H), 4.02–4.10 (m, 2H), 5.40 (s, 1H),
.82 (s, 1H), 7.03–7.06 (t, J = 7.5 Hz, 1H), 7.12–7.15 (t,
Yellow solid; H NMR (500 MHz, CDCl ) δ: 0.90 (s,
6H)，1.08
(m, 2H)，2.32–2.36 (m，1H)，2.41 (s，3H)，3.77–3.94
(m, 2H)，5.84 (s，1H)，5.93 (s，1H)，7.33–7.36 (t, J = 7.5
3
(s，3H)，2.09–2.10
(m，1H)，2.18–2.23
J = 7.25 Hz, 1H), 7.25–7.26 (d, 1H), and 7.40–7.42 (d, 1H).

4
LIAO ET AL.
O
O
3
H O
2
O
AcOH
NH OAc
Ar
4
O
O
O
4
O
O
H O
2
H N
2
6
OH HN
O
Ar
O
O
O
Si
SO H
3
Ar
N
H
O
-
OH
O
PF
6
5
OMe
Si
7
SO H
SO H
3
3
N
NH
O
O
Ar
O
Si
SO3H
OH
Si
O
O
H
Ar
2
O
OH
O
1
Si
SO3H
SCHEME 2 Proposed mechanism for the formation of polyhydroquinolines
[
[
4] B. Friedrich, M. W. E. Horst, Angew. Chem. 1981, 93, 755.
Hz, 1H)，7.42–7.45 (m，2H)，7.55–7.58 (t，J = 7.5 Hz,
5] V. A. Chebanov, V. E. Saraev, S. M. Desenko, V. N. Chernenko,
S. V. Shishkina, O. V. Shishkin, K. M. Kobzar, C. O. Kappe, Org. Lett.
2007, 9, 1691.
1H)，7.63–7.64 (d, 1H)，7.75–7.76 (d, 1H), and 8.82–8.88
(s, 1H).
[
6] D. Alessandro, M. Alessandro, S. Simona, B. Valerio, J. Org. Chem. 2002,
67, 6979.
[
[
7] D. J. Ramon, M. Yus, Angew. Chem. Int. Ed. 2005, 44, 1602.
8] B. Groenendaal, E. Ruijter, R. V. A. Orru, Chem. Commun. 2008, 43,
4
| CONCLUSIONS
5
474.
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, 1787.
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Med. Chem. Lett. 2008, 18, 60.
In summary, we have developed a convenient, efficient
method for the synthesis of polyhydroquinolines via Si–
6
[
[
SbSipim][PF ] as a highly efficient catalyst in alcohol
6
under reflux. The catalytic system can combine the
advantages of homogeneous and heterogeneous catalysts.
The attractive features of this method are simple proce-
dure, ease of separation, and recyclability of the
catalyst.
[
12] M. L. Kantam, T. Ramani, L. Chakrapani, B. M. Choudary, Catal.
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[
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[
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We are grateful to the Science and Technology Foundation
of Shanghai Institute of Technology for financial support.
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[
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Li Qin Kang https://orcid.org/0000-0003-4932-4017
[
[
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SUPPORTING INFORMATION
1
Additional supporting information may be found online in
the Supporting Information section at the end of this article.
2
5
How to cite this article: Liao HY, Kang LQ,
Zhang SS, Yan JH. Green synthesis of poly-
hydroquinolines catalyzed by silica-supported ionic
1
2
liquid Si–[SbSipim][PF ]. J Chin Chem Soc. 2019;
6
2
1–5. https://doi.org/10.1002/jccs.201800301
2