Synthesis of a novel piperidine-functionalized poly(ethylene glycol) bridged dicationic ionic liquid and its application in one-pot synthesis of substituted 2-amino-2-chromenes and 3,4-dihydropyrano[3,2-c]chromenes in aqueous media

Article abstract of DOI:10.1007/s00706-013-1066-8

A novel piperidine-functionalized poly(ethylene glycol) bridged dicationic ionic liquid was prepared and identified. It was used as a recyclable catalyst for the synthesis of substituted 2-amino-2-chromenes and 3,4-dihydropyrano[3,2- c]chromenes with exce

Full text of DOI:10.1007/s00706-013-1066-8

Monatsh Chem (2013) 144:1871–1876
DOI 10.1007/s00706-013-1066-8
ORIGINAL PAPER
Synthesis of a novel piperidine-functionalized poly(ethylene glycol)
bridged dicationic ionic liquid and its application in one-pot
synthesis of substituted 2-amino-2-chromenes
and 3,4-dihydropyrano[3,2-c]chromenes in aqueous media
Yinglei Wang
Zuliang Liu
•
Jun Luo
•
Tantan Xing
•
Received: 16 October 2012 / Accepted: 17 July 2013 / Published online: 16 August 2013
Ó Springer-Verlag Wien 2013
Abstract A novel piperidine-functionalized poly(ethyl-
ene glycol) bridged dicationic ionic liquid was prepared
and identified. It was used as a recyclable catalyst for the
synthesis of substituted 2-amino-2-chromenes and 3,4-di-
hydropyrano[3,2-c]chromenes with excellent yieldsthrough a
one-pot three-component reaction of aromatic aldehydes,
malononitrile, and activated phenols in aqueous media. This
environmentally benign protocol was found to be fairly effi-
cientandofferwidesubstrateflexibility.The basicionicliquid
could be reused several times without any obvious loss of
catalytic activity.
starting materials in one-pot operations, and these reactions
avoid the isolation and purification of intermediates and
diminish waste generation [1–4]. Water is the most widely
available and nontoxic reaction medium, which makes it an
ideal solvent for green chemistry protocols [5–9]. There-
fore, the development of MCRs in water or an aqueous
medium is an active research area.
2-Amino-2-chromenes and 3,4-dihydropyrano[3,2-c]-
chromenes comprise an important class of heterocycles due
to their biological and pharmacological properties, and are
widely used in cosmetics and pigments [10], are potential
biodegradable agrochemicals [11–13], and are employed in
pharmaceuticals [14–16]. The conventional straightforward
synthesis of this heterocyclic system involves multicompo-
nent reactions of an aromatic aldehyde, malononitrile, and
activated phenol in the presence of a basic catalyst in organic
solvent. Recently, several modified catalysts have been
employed to accomplish this transformation such as tetra-
butylammonium bromide (TBAB) [17], hexadecyltrimeth-
ylammonium bromide (HTMAB) [18], DABCO [19], DBU
[20], diammonium hydrogenphosphate (DAHP) [21],
4-(dimethylamino)pyridine (DMAP) [22], CuO nanoparti-
cles [23], Ru(II) complexes bearing tertiary phosphine
ligands [24], a (2-aminomethyl)phenol moiety supported
on HAp-encapsulated-c-Fe O (c-Fe O @HApSi-(CH ) -
Keywords Poly(ethylene glycol) ꢀ
Functionalized ionic liquid ꢀ
Multicomponent condensation ꢀ Chromenes ꢀ
Aqueous media ꢀ Recycability
Introduction
Multicomponent reactions (MCRs), involving domino
processes with at least three components, have emerged as
a powerful strategy in synthetic organic chemistry. Com-
pared with conventional multistep linear synthetic
protocols, MCRs exhibit high levels of efficiency and
diversity because they offer rapid and convergent con-
struction of complex molecular skeletons from simple
2
3
2
3
2 3
AMP) [25], sodium dodecyl sulfate (SDS) [26], a hetero-
polyacid (HPA) [27, 28], and high-surface-area MgO [29].
At the same time, several methods of promoting this reaction
have been reported, including the use of microwave irradi-
ation [30–36], ultrasonic irradiation [37], and grinding [38,
39]. However, some of these methods suffer from one or
more drawbacks, such as the use of volatile organic solvents,
a long reaction time, unsatisfactory yields, the need for
special equipment, difficulties in recycling the catalyst, and a
laborious workup procedure.
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-013-1066-8) contains supplementary
material, which is available to authorized users.
Y. Wang ꢀ J. Luo (&) ꢀ T. Xing ꢀ Z. Liu
School of Chemical Engineering, Nanjing University of Science
and Technology, Nanjing 210094, China
e-mail: luojun@njust.edu.cn
123

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Y. Wang et al.
Ionic liquids (ILs) are considered to be among of the
bridged dicationic ionic liquid PEG800-DPIL(Cl) and
applied it as an efficient and recyclable catalyst in a three-
component condensation that was performed to prepare
2-amino-2-chromenes and 3,4-dihydropyrano[3,2-c]chrom-
enes in an aqueous medium. That work is described in this
paper.
most promising novel reaction media due to their unique
properties, such as their negligible volatility, high thermal
and chemical stability, wide liquid range, excellent solu-
bility, and ease of recovery and reuse [40–44]. Moreover,
functionalized ionic liquids (FILs)—so-called task-specific
ionic liquids (TSILs), which incorporate additional groups
into the cation and/or anion—have attracted increasing
attention from researchers in various fields due to their
adjustable physical and chemical properties [45–48]. FILs
have been used as alternative green solvents as well as
reagents and/or catalysts in synthetic organic chemistry.
Among them, basic ionic liquids exhibit unique advantages
over traditional bases owing to their adjustable basicity and
solubility, which gives them high catalytic efficiency and
makes them easy to recover. Indeed, basic ionic liquids
Results and discussion
The synthetic route to piperidine-functionalized poly(eth-
ylene glycol)-bridged dicationic ionic liquid is illustrated in
Scheme 1. It was readily prepared through a convergence-
style procedure from commercially available starting
materials and reagents in good yields [64]. PEG800
-
DPIL(Cl) has good thermal stability and does not decom-
pose below about 250 °C. In addition, the solubility of
PEG800-DPIL(Cl) was determined at room temperature. In
general, it is immiscible with heptane, cyclohexane, diethyl
ether, toluene, and ethyl acetate, and miscible with
dichloromethane, acetone, isopropanol, methanol, ethanol,
N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO),
and water.
0
0
such as N,N,N ,N -tetramethylguanidinium trifluoroacetate
(
TMGT) [49], 1-butyl-3-methylimidazolium hydroxide
(
[Bmim][OH]) [50, 51], (N,N-dimethylaminoethyl)benzyl-
?
dimethylammonium chloride ([PhCH Me N CH CH N
2
2
2
2
-
Me ][Cl ]) [52], 3-hydroxypropanaminium acetate (HPAA)
2
[
53], triethylenetetraammonium trifluoroacetate ([TETA]
TFA]) [54], and 2-hydroxyethylammonium formate [55]
[
have been successfully used as catalysts for the synthesis
of 2-amino-2-chromenes and/or 3,4-dihydropyrano[3,2-c]-
chromenes.
PEG800-DPIL(Cl) was then used to catalyze a one-pot
three-component condensation that was performed to pre-
pare 2-amino-2-chromenes and 3,4-dihydropyrano[3,2-
c]chromenes from aromatic aldehydes, malononitrile, and
activated phenols in water. Firstly, to evaluate the catalytic
efficiency of this catalyst, benzaldehyde, malononitrile, and
1-naphthol were selected as model substrates for the
preparation of 2-amino-2-chromenes. Selected results from
our screening experiments are summarized in Table 1.
When PEG800-DPIL(Cl) was used as both catalyst and
solvent, the yield was only 72 %, possibly because the high
Due to the wide-ranging applications of these hetero-
cyclic compounds and the advantages of basic ionic
liquids, the further development of catalysts that are
recyclable simply and efficiently is a desirable goal. In our
continuous research on the synthesis and applications of
poly(ethylene glycol)-bridged dicationic acidic ionic liq-
uids in synthetic organic chemistry [56, 57], we prepared a
novel piperidine-functionalized poly(ethylene glycol)-
Scheme 1
1
23

Synthesis of chromene derivatives by PEG800-DPIL(Cl) in water
1873
Table 1 Optimization of the reaction conditions
NH2
CN
OH
O
CHO
CN
CN
PEG800-DPIL(Cl)
+
+
H O
2
a
Entry
Amount of catalyst/%
Temp./°C
Solvent
Time/min
Yield/%
1
2
3
4
5
6
7
8
9
10
–
100
100
100
100
100
100
100
80
–
20
20
20
20
20
20
20
30
20
72
–
H
H
H
H
H
H
H
H
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
1
45
78
90
90
91
81
87
3
5
7
10
5
5
90
3
Reaction conditions: 2 mmol benzaldehyde, 2 mmol malononitrile, 2 mmol 1-naphthol, 2 cm water
a
Isolated yield
viscosity of the ionic liquid blocked the mass transfer
Table 1, entry 1). However, none of the desired product
100
90
90
89
(
87
86
was detected when the reaction was carried out in water
under reflux for 20 min in the absence of PEG800-DPIL(Cl)
8
6
4
2
0
0
0
0
0
(
Table 1, entry 2). The reaction was subsequently carried
out in the presence of various amounts of catalyst in water.
The results indicated that the optimal amount of catalyst
was 5 mol% (Table 1, entries 3–7). Adding more catalyst
did not improve the results at all. Furthermore, low tem-
peratures decelerated the reaction and led to lower yields
(
Table 1, entries 8, 9).
The recyclability of the catalyst was also investigated
using the above model reaction. After separating out the
product by filtration, the filtrate containing the catalyst was
reused for the next run without further purification. Fresh
starting materials of benzaldehyde, malononitrile, and
1
2
3
4
5
Run
2
Fig. 1 The reusability of the PEG800-DPIL(Cl)/H O system
1
-naphthol in the appropriate stoichiometric ratio were
charged into the filtrate and stirred under the same condi-
tions. The results are depicted in Fig. 1. It is apparent that
the reaction system could be reused five times without
suffering any significant decrease in yield.
times were required and lower yields were obtained than
those bearing electron-withdrawing groups (such as halide,
nitro) (Table 2, entries 6–14). It is worth noting that ortho
and meta substituents did not significantly hamper the
condensation reaction (Table 2, entries 6–8 and entries
11–13). Furthermore, the activity of 2-naphthol was lower
than that of 1-naphthol owing to an electronic effect
(Table 2, entries 16–18).
Using the optimized reaction conditions, the scope and
efficiency of the reaction for the synthesis of a wide variety
of 2-amino-2-chromenes with various aromatic aldehydes
were explored. The results are summarized in Table 2. The
substituents of the aromatic aldehyde and the position of
the hydroxyl on the naphthol dramatically influence the
reaction. When aromatic aldehydes bearing electron-
donating groups (such as methyl, hydroxy, methoxy)
The generality and versatility of this basic ionic liquid
was further investigated by utilizing it in a one-pot con-
densation of an aromatic aldehyde, malononitrile, and
4-hydroxycoumarin to prepare 3,4-dihydropyrano[3,2-
(
Table 2, entries 2–5) were employed, longer reaction
123

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Y. Wang et al.
Table 2 Synthesis of 2-amino-2-chromene derivatives by PEG800-DPIL(Cl) in water
NH2
OH
CN
O
R
CHO
CN
CN
PEG800-DPIL(Cl)
or
R
+
+
or
H O, 100 °C
2
R
CN
OH
NH2
O
a
Entry
R
Naphthol
Time/min
Yield/%
M.p./°C
Lit. m.p./°C
1
2
3
4
5
6
7
8
9
H
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
1-Naphthol
2-Naphthol
2-Naphthol
2-Naphthol
20
30
25
30
40
12
10
8
90
86
86
88
85
92
92
94
95
94
93
95
96
94
89
84
81
86
215–216
207–208
249–250
189–190
214–215
248–249
228–229
247–248
243–244
231–233
207–209
219–220
213–214
223–224
167–169
291–292
273–275
222–223
215–217 [19]
206–207 [50]
250–252 [32]
190–192 [52]
215–218 [32]
248–250 [38]
228–230 [18]
245–248 [19]
241–243 [19]
232–233 [50]
208–210 [32]
217–219 [19]
210–212 [58]
222–224 [18]
169–171 [52]
290–292 [59]
270–272 [38]
222–224 [38]
4-CH
3
4-OH
4-CH
3
O
3-CH
2-Cl
3-Cl
4-Cl
4-Br
4-F
3
O-4-OH
10
12
10
8
10
11
12
13
14
15
16
17
18
2-NO
3-NO
4-NO
2
2
2
8
2,4-Cl
2
15
20
30
40
20
2-Furyl
H
4-CH
4-Cl
3
3
Reaction conditions: 2 mmol aromatic aldehyde, 2 mmol malononitrile, 2 mmol 1-naphthol, 0.1 mmol PEG800-DPIL(Cl), 2 cm water, 100 °C
a
Isolated yield
c]chromenes in aqueous media under reflux. As can be seen
from Table 3, aromatic aldehydes with electron-donating
as well as electron-withdrawing groups were transformed
into the corresponding products in good to excellent yields
within 10–20 min. The electronic and steric effects are in
accord with the above condensations.
friendly, requires only mild reaction conditions and short
reaction times, produces high yields, has a simple work-up
procedure, and exhibits good reusability.
Experimental
In summary, a novel piperidine-functionalized poly
(
ethylene glycol)-bridged dicationic ionic liquid was suc-
All of the reagents and solvents were purchased from
commercial suppliers and used without further purification.
The synthesis of piperidine-functionalized poly(ethylene
glycol)-bridged dicationic ionic liquid PEG800-DPIL(Cl)
was described previously [64].
cessfully prepared and used as an efficient and recyclable
catalyst for the synthesis of substituted 2-amino-2-chrom-
enes and 3,4-dihydropyrano[3,2-c]chromenes via one-pot
three-component condensations of aromatic aldehydes,
malononitrile, and activated phenols in water. Advanta-
geously, this novel catalytic system is environmentally
All melting points were determined on a digital melting-
1 13
point apparatus. H NMR and C NMR were recorded on
1
23

Synthesis of chromene derivatives by PEG800-DPIL(Cl) in water
1875
Table 3 Synthesis of 3,4-dihydropyrano[3,2-c]chromene derivatives by PEG800-DPIL(Cl) in water
NH2
OH
CN
CHO
CN
CN
O
O
PEG800-DPIL(Cl)
R
+
+
H O, 100 °C
2
O
O
O
R
a
Entry
R
Time/min
Yield/%
M.p./°C
Lit. m.p./°C
1
2
3
4
5
6
7
8
9
H
15
20
15
20
25
30
8
91
88
86
89
85
87
93
93
94
95
94
93
94
96
93
94
265–266
249–251
266–267
233–234
250–251
223–224
274–275
248–249
264–265
255–257
264–265
253–255
265–266
277–278
244–246
243–244
265–267 [60]
250–251 [23]
266–267 [20]
233–236 [23]
252–253 [62]
224–225 [20]
273–274 [55]
246–248 [26]
263–265 [21]
254–256 [63]
263–264 [23]
254–256 [51]
263–265 [29]
278–280 [61]
245–247 [55]
243–244 [63]
3
4-CH
3
4-OH
4-CH
3-CH
3
O
3
O-4-OH
4-NMe
2-Cl
3-Cl
4-Cl
4-Br
4-F
2
8
6
10
11
12
13
14
15
16
6
8
2-NO
3-NO
4-NO
2
2
2
8
6
6
2,4-Cl
3,4-Cl
2
15
15
2
Reaction conditions: 2 mmol aromatic aldehyde, 2 mmol malononitrile, 2 mmol 4-hydroxycoumarin, 0.1 mmol PEG800-DPIL(Cl), 2 cm water,
1
a
00 °C
Isolated yield
a Bruker (Rheinstetten, Germany) Avance III 500, and
tetramethylsilane (TMS) was used as internal standard.
Mass spectra were taken on an Agilent (Santa Clara, CA,
USA) liquid chromatography–mass spectrometry (LC-MS)
products are known and the data used to identify them were
found to be in accord with those reported in literature. The
solution of PEG800-DPIL(Cl) in water was reused in the
next reaction without any treatment.
1
100 series instrument in the electrospray ionization
Acknowledgments This project was financially sponsored and
supported by the National Natural Science Foundation of China (No.
(
positive electrospray ionization (ESI)) mode. IR spectra
were recorded from KBr disks with a Shimadzu (Kyoto,
Japan) IRPrestige-21 FT-IR spectrometer.
2
1002050), the Doctoral Fund of the Ministry of Education of China
for New Teachers (No. 200802881029), the Zijin Star Project and the
Excellence Initiative Project of NUST.
General procedure for the synthesis of 2-amino-2-
chromenes or 3,4-dihydropyrano[3,2-c]chromenes
and recycling of the catalyst
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