An Efficient Synthesis of Pyrrolidinone Derivatives in the Presence of 1,1′-Butylenebis(3-sulfo-3 H -imidazol-1-ium) Chloride

Article abstract of DOI:10.1071/CH18246

The catalytic efficiency of 1,1′-butylenebis(3-sulfo-3H-imidazol-1-ium) chloride as a sulfonic acid-functionalized ionic liquid was demonstrated for the synthesis of pyrrolidinone derivatives under mild conditions. The electronic effect of substituents on aniline derivatives was investigated. Further, a study on the structure-activity relationship of ionic liquids containing sulfonic groups for the synthesis of ethyl-2-(4-chlorophenyl)-4-hydroxy-5-oxo-1-(p-tolyl)-2,5-dihydro-1H-pyrrole-3-carboxylate was performed under optimal conditions. The results showed that the catalytic properties of ionic liquids containing two sulfonic or imidazole moieties with carbon spacers was superior to ionic liquids having one sulfonic or imidazole moiety with no carbon spacer.

Full text of DOI:10.1071/CH18246

CSIRO PUBLISHING
Aust. J. Chem.
Full Paper
https://doi.org/10.1071/CH18246
An Efficient Synthesis of Pyrrolidinone Derivatives in the
Presence of 1,19-Butylenebis(3-sulfo-3H-imidazol-1-ium)
Chloride
A D
,
A
B
Nader Ghaffari Khaligh,
Kim Foong Chong, Taraneh Mihankhah,
C
A
A
Salam Titinchi, Mohd Rafie Johan, and Juan Joon Ching
A
Nanotechnology and Catalysis Research Center, 3rd Floor, Block A, Institute of
Postgraduate Studies, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Environmental Research Laboratory, Department of Water and Environmental
B
Engineering, School of Civil Engineering, Iran University of Science and Technology,
16765-163, Tehran, Iran.
C
Department of Chemistry, University of the Western Cape, Cape Town 7530, South
Africa.
D
Corresponding author. Email: ngkhaligh@gmail.com
The catalytic efficiency of 1,10-butylenebis(3-sulfo-3H-imidazol-1-ium) chloride as a sulfonic acid-functionalized ionic
liquid was demonstrated for the synthesis of pyrrolidinone derivatives under mild conditions. The electronic effect of
substituents on aniline derivatives was investigated. Further, a study on the structure–activity relationship of ionic liquids
containing sulfonic groups for the synthesis of ethyl-2-(4-chlorophenyl)-4-hydroxy-5-oxo-1-(p-tolyl)-2,5-dihydro-1H-
pyrrole-3-carboxylate was performed under optimal conditions. The results showed that the catalytic properties of ionic
liquids containing two sulfonic or imidazole moieties with carbon spacers was superior to ionic liquids having one sulfonic
or imidazole moiety with no carbon spacer.
Manuscript received: 25 May 2018.
Manuscript accepted: 7 July 2018.
Published online:
31 July 2018.
Introduction
conditions. Also, in continuing our investigation on the influ-
ence of IL structure on catalytic efficiency,[28] the cation effect
of some mono- and di-cationic ionic liquids was investigated for
the synthesis of ethyl-2-(4-chlorophenyl)-4-hydroxy-5-oxo-1-
(p-tolyl)-2,5-dihydro-1H-pyrrole-3-carboxylate (2a).
Ionic liquids (ILs) have become alternative solvents, catalysts,
and extracting agents owing to environmental considerations
including low vapour pressure, thermal and chemical stability,
high ionic conductivity, tunable polarity, designable properties,
and potential reusability.[1–3] Immiscibility of ILs with some
organic solvents is another valuable property for organic syn-
thesis. This property allows the simple separation of the desired
products and catalysts in different phases, which avoids tedious
and expensive work-up procedures along with the consumption
of high volumes of toxic and volatile organic solvents.[4,5]
2-Pyrrolidinones are found in many pharmaceuticals and in
active natural products. Theyhave achieved much attention owing
to their wide spectrum of biological and pharmaceutical activities
and their applications in medicinal chemistry and drug design-
ing.[6–14] Therefore, a variety of synthetic protocols have been
reported for the preparation of substituted pyrrolidinones.[15–23]
The ILs containing the SO3H functional group on the
imidazole ring are well known to exhibit catalytic activity for
multicomponent reactions.[24–26] Very recently, 1,10-butylene-
bis(3-sulfo-3H-imidazol-1-ium) chloride ([BBSI]Cl) was syn-
thesized and its dual solvent–catalytic activity was studied
for the synthesis of xanthenes under mild conditions.[27] Herein,
we describe the synthesis of 2-pyrrolidinone derivatives in
the presence of [BBSI]Cl as an efficient catalyst under mild
Results and Discussion
Synthesis of Pyrrolidinone Derivatives in the Presence of
[BBSI]Cl
Initially, the reaction of 4-chlorobenzaldehyde (1a), aniline,
and diethyl acetylenedicarboxylate as the model reaction was
studiedinthe absenceofcatalystandsolvent atroom temperature.
The model reactants were ground using a planetary ball mill to
afford the desired product in trace yield after 4 h at room tem-
perature, confirming the need for solvent and/or catalyst for this
reaction (Table 1, entry 1). Then, the model reaction was per-
formed in green solventssuch as H2O and C2H5OH in the absence
of a catalyst at room temperature for 4 h, which afforded 2a in 20
and 26 % yield respectively (Table 1, entries 2 and 3). A higher
yield was observed in ethanol because the model reactants were
considerably more soluble in ethanol than in water. 2a was
obtained in 79% yield when 0.5 mol-% of [BBSI]Cl was added to
the model reactants in ethanol and the mixture was stirred for 1 h
at room temperature (Table 1, entry 4). A significant
Journal compilation ꢀ CSIRO 2018
www.publish.csiro.au/journals/ajc

B
N. G. Khaligh et al.
Table 1. Optimization of the synthesis of ethyl-1-phenyl-2-(4-chlorophenyl)-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylate
(2a) under a variety of reaction conditions
Reaction conditions: 4-chlorobenzaldehyde (1a) (2.0 mmol), aniline (2.0 mmol), diethyl acetylenedicarboxylate (2.0 mmol), room temperature.
The bold entry in the table indicates optimized conditions
Entry
Loading of [BBSI]Cl [mol-%]
Solvent (2 mL)
Reaction time [min]
Yield [%]A
1
2
3
4
5
6
7
0.0
0.0
0.0
0.5
1.0
1.0
1.0
–
240
240
240
60
TraceB
20
H2O
EtOH (96 %)
EtOH (96 %)
EtOH (96 %)
EtOH (96 %)
EtOH (96 %)
26
79
60
89
30
88
10
66
AIsolated yield.
BMonitored by GC-MS.
R3
O
O
Table 2. Synthesis of pyrrolidinones in the presence of [BBSI]Cl under
optimized reaction conditions
OH
O
[BBSI]Cl (1 mol-%)
EtOH, r.t., 30 min
O
O
2
ϩ
NH2
ϩ
R
R1
H
Reaction conditions: aryl aldehyde (1) (2.0 mmol),), aniline (2.0 mmol),
diethyl acetylenedicarboxylate (2.0 mmol), [BBSI]Cl (1.0 mol-%), ethanol
(96 %) (2 mL), reaction time (30 min), room temperature
R1
O
O
O
N
R2
2 (a–s)
R3
R3
R3 ϭ Me or Et
1 (a–s)
Entry Aldehyde 1
Product Yield
[%]A
Melting point [8C]
Scheme 1. Synthesis of pyrrolidinone derivatives in the presence of
2
Found
Reported (ref.)
[BBSI]Cl under optimal conditions.
1
4-Cl–C6H4–
C6H5–
a
b
c
d
e
f
88
86
84
94
82
81
96
88
91
82
77
81
86
82
84
–
188–190 190–192 [29]
174–176 174–176 [29]
180–182 179–181 [31]
170–172 172–174 [30]
140–142 138–140 [29]
240–242 243–245 [31]
180–182 181–183 [31]
190–192 190–193 [31]
175–177 178–180 [30]
200–202 204–207 [31]
190–192 193–195 [30]
190–191 190–192 [29]B
178–179 180–182 [21]C
2
improvement was observed on increasing the catalyst loading
(Table 1, entry 5), and decreasing the reaction time to 30 min
reduced the yield very slightly but further reduction of the reac-
tion time led to a lower yield of 2a (Table 1, entries 6 and 7).
The scope of the synthesis of pyrrolidinone derivatives via
this protocol was evaluated utilizing a variety of aldehydes 1a–s,
aniline derivatives, and diethyl acetylenedicarboxylate under
the optimized conditions (Scheme 1).
3
4-CH3–C6H4–
4-CF3–C6H4–
4-CH3O–C6H4–
4-HO–C6H4–
4-NO2–C6H4–
4-Br–C6H4–
2-NO2–C6H5–
2-Cl–C6H4–
2-CH3O–C6H4–
C6H5–
4
5
6
7
g
h
i
8
9
10
11
12
13
14
15
16
j
Pyrrolidinones 2a–n containing a broad range of substituents
were prepared in good to excellent yield, as shown in Table 2.
The aryl aldehydes bearing electron-withdrawing or electron-
donating substituents gave the desired pyrrolidinones in good to
excellent yields. Aldehydes bearing electron-withdrawing sub-
stituents afforded higher yields of pyrrolidinones than those
with electron-donating substituents at the same position
(Table 2, entries 4 and 8 versus 5).
k
l
C6H5–
m
n
o
p
4-CH3–C6H4–
3,4[OCH2O]C6H3–
4-[(CH3)2N]–C6H4–
186–188C
–
170–172 170–172 [29]
–
–
AIsolated yield.
BAniline derivative ¼ benzylamine.
CDimethyl acetylenedicarboxylate.
The electrophilic properties of the carbonyl group are
enhanced for the aryl aldehydes containing electron-withdrawing
substituents such as nitro (–NO2) in the para-position whereas
electron-donating groups such as methoxy (–OCH3) in the same
position clearly decrease the electrophilicity of the carbonyl
group. We performed the reaction with methyl acetylene dicar-
boxylate and the desired products were obtained in high
yield under the same conditions (Table 2, entries 13, 14). As
shown in Table 2, the acid-sensitive aldehydes such as 4- and 2-
methoxybenzaldehyde and 3,4-(methylenedioxy)benzaldehyde
afforded the desired products in good yield without decomposi-
tion and isomerization under the optimized reaction conditions
(Table 2, entries 5, 11 and 15). The desired product 2p was
not obtained when 4-(dimethylamino)benzaldehyde (1p) was
utilized as the aryl aldehyde under the same conditions and the
aryl aldehyde spot along with a few other spots was observed on
TLC. The nucleophilic nature of the carbonyl carbon of 1p
may be reduced owing to the strong electron inductive effect
of the dimethylamino group and also the quinonoid structure
of 1p may be stabilized in the presence of the IL through
hydrogen-bond and ionic interactions, which decrease the reac-
tivity of the carbonyl carbon of 1p (Scheme 2).[32,33] It seems
that the main chemical reaction involves the protonation of 1p
by [BBSI]Cl, and the conversion of part of the keto form (I) into
the enolic and zwitterion tautomers (II and III),[34] which may
be responsible for the inactivation of 1p in the present multi-
component reaction.
The effect of electron-donating and electron-withdrawing
substituents in the para-position of aniline derivatives was
studied for the reaction of 4-trifluorobenzaldeyde, diethyl acet-
ylenedicarboxylate, and various anilines under the optimal
conditions (Table 3). The results demonstrated that the elec-
tron-withdrawing groups deactivated the amino group and led to
a decrease in product yield and reaction rate (Table 3, entry 2),
whereas the electron-donating groups activated the amino group
and afforded a high yield of the desired products under the
optimal reaction conditions (Table 3, entries 3 and 4).

Pyrrolidinone Synthesis Using New Ionic Liquid
C
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
O
S
O
O
S
O
S
N
N
O
O
S
N
N
O
N
N
O
O
S
N
N
O
O
S
O
S
N
N
N
N
O
S
N
N
O
N
O
N
O
O
O
H
O
H
H
O
H
H
H
O
O
O
H
O
H
H
H
H
H
H
H
H
H
N
O
O
H3C
H3C
O
H3C
H3C
O
H3C
N
H3C
N
N
H
H
H
H
CH3
CH3
III
I
II
Scheme 2. Possible stability of the quinonoid structure of 1m in the presence of [BBSI]Cl under optimal conditions.
Table 3. The electronic effect of substituents on para-position of anilines on yield and reaction time of the synthesis of pyrrolidinones in the presence
of [BBSI]Cl under optimized reaction conditions
Reaction conditions: 4-trifluorobenzaldehyde (1d) (2.0 mmol),), aniline derivative (2.0 mmol), diethyl acetylenedicarboxylate (2.0 mmol), [BBSI]Cl
(1.0 mol-%), ethanol (96 %) (2 mL), reaction time (30 min), room temperature
Entry
Benzaldehyde
Aniline
Product 2
Yield [%]A
Melting point [8C]
Reported (ref.)
Found
1
2
3
4
4-CF3–C6H4–
4-CF3–C6H4–
4-CF3–C6H4–
4-CF3–C6H4–
C6H5–NH2
d
q
r
s
94
52B
170–172
170–172
172–173
165–167
172–174 [30]
175–177 [30]
176–178 [30]
162–164 [30]
4-NO2–C6H4–
4-CH3–C6H4–
4-CH3O–C6H4–
82
83
AIsolated yield.
BReaction time 4 h.
Cl
Cl
O
N
N
O
O
S
N
S
ϭ
N
O
O
H
H
O
H
H
O
Acidic sites of [BBSI]Cl
H2O
Ar
O
O
O
HO
OEt
Ar
H
N
NH2
OEt
EtO
O
H2O
OEt
II
I
O
O
Et
O
EtO
O
Ar
NH
III
EtOH
EtO
O
O
O
OH
EtO
Ar
H
Ar
O
O
N
N
IV
Scheme 3. Proposed mechanism for the synthesis of pyrrolidinone derivatives in the presence of [BBSI]Cl.
In addition, the reaction of 4-chlorobenzaldehyde (1a),
aniline, and diethyl acetylenedicarboxylate was performed in
1-butyl-3-methylimidazolium chloride (2 mol-%), methanesulfo-
nic acid (2 mol-%), and a mixture of 1-butyl-3-methylimidazolium
chloride (2 mol-%) and methanesulfonic acid under the optimized
reaction conditions, which afforded 2a in trace, 23, and 48 % yield
respectively. These results reveal that the performance of [BBSI]
Cl is dependent on the covalent attachment of the sulfonic acid
moiety to the imidazole ring and acidic hydrogen plays a more
important role than do the C2–H of the alkyl imidazolium cation.
A proposed mechanism is illustrated in Scheme 3 on the basis
of previous work.[35] In the first step, the aryl aldehyde is

D
N. G. Khaligh et al.
Table 4. The comparative study of present versus previously reported methodologies for the synthesis of the ethyl-1,2-diphenyl-4-hydroxy-5-oxo-
2,5-dihydro-1H-pyrrole-3-carboxylate (2b)
Entry Catalyst
Catalyst loading (mol-%) Solvent
Temp. Reaction time
Yield
(%)
Recyclable Ref.
[8C]
1
2
3
4
5
6
7
–
–
Ethanol/H2O (1 : 1 v/v) r.t.B
15 h
87
–
[38]
Citric acid monohydrate 200
Citric acid monohydrate 200
Ethanol
Ethanol (US 100WC)
r.t.
40
r.t.
10 h
85
No
No
No
No
No
Yes
[31]
20 min
48 h
90
[31]
p-Toluenesulfonic acid
Lactic acid (solvent)
Glacial acetic acid
[BBSI]Cl
20
Ethanol
62
[22]
1 mL (1140)
1 mL (1746)
1.0
Lactic acid (85 % w/w) 30
2 h
60A
24A
86
[30]
Glacial acetic acid
Ethanol (96 %)
30
2 h
[30]
r.t.
30 min
Present
work
A4-Methyl benzaldehyde.
Br.t. ¼ room temperature.
CUltrasound irradiation, 100 W power.
activated by [BBSI]Cl through hydrogen-bond formation
between the carbonyl group and the C-2 hydrogen atom and
the acidic hydrogen of the sulfonic groups of the IL cation.
Aniline and aryl aldehyde activated in this way gave imine I. It
seems that [BBSI]Cl can also serve as dehydrating agent to
facilitate the formation of imine I.[36,37] The intermediate II is
formed through the addition of water and diethyl acetylenedi-
carboxylate. Next, a Michael addition of imine I and intermedi-
ate II leads to intermediate III, followed by an intermolecular
cyclization. An ethanol molecule is eliminated to afford the final
product.
Table 5. Comparison of results obtained for the synthesis of ethyl-2-1-
phenyl-(4-chlorophenyl)-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-3-
carboxylate (2a) in the presence of some sulfonic-functionalized ionic
liquids containing a mono- and di-cationic nucleus with [BBSI]Cl
Reaction conditions: 4-chlorobenzaldehyde (1a) (2.0 mmol), aniline
(2.0 mmol), diethyl acetylenedicarboxylate (2.0 mmol), ionic liquid con-
taining sulfonic acid (1.0 mol-% mL), reaction time (30 min), room tem-
perature. [PiS]Cl, sulfonic acid-functionalized piperizanium chloride; [PzS]
Cl, sulfonic acid-functionalized pyrazinium chloride; [PzPS]Cl, sulfonic
acid-functionalized pyrazinium propyl chloride; [DSI]Cl, sulfonic acid-
functionalized imidazolium chloride
This protocol was carried out on a large scale with 20 mmol
of the model reactants in the presence of 0.2 mmol of [BBSI]Cl
in 20 mL ethanol and 2a was isolated in 82 % yield after 1 h at
room temperature.
Entry IL as solvent–catalyst
Abbreviation Yield [%]
1
[PiS]Cl
66
HO3S NH NH SO3H
Cl
Cl
To show the advantages of the present protocol, a compari-
son of present and previously reported methods is given in
Table 4, which shows the catalytic efficiency of [BBIS]Cl
relative to the reported solvent–catalysts in terms of catalyst
loading, product yields, reaction times, and recyclability.
Then, the catalytic activity of mono- and di-cationic ILs
containing mono- and di-sulfonic groups along with a chloride
counter-anion was explored in catalyzing the reaction of aniline
and diethyl acetylenedicarboxylate with 4-chlorobenzaldehyde
to afford 2a under the aforementioned optimized conditions
(Table 5). The sulfonic acid-functionalized pyrazinium, piper-
azinium, benzimidazolium, and imidazolium ILs were synthe-
sized according to the literature.[39–42]
2
[PzS]Cl
61
HN
Cl
N
SO3H
Cl
3
4
5
[PzPS]Cl
[DSI]Cl
72
77
80
HN
Cl
N
Cl
SO3H
N
SO3H
N
Cl
HO3S
SO3H
[DSBI]Cl
N
As shown in Table 5, the structure–activity relationship
plays an important role on the catalytic efficiency of these ILs
derived from pyrazinium, piperazinium, benzimidazolium, and
imidazolium cations containing chloride as the counter-anion as
previously reported.[28] The best result was obtained with
[BBSI]Cl whereas pyrazinium and piperazinium ILs displayed
a lower catalytic activity in the model reaction. The sulfonic
acid-functionalized piperizanium chloride ([PiS]Cl) and sulfon-
ic acid-functionalized pyrazinium chloride ([PzS]Cl) showed
moderate catalytic activity, which can be ascribed to the
presence of two sulfonic groups per IL molecule (Table 5, entry
1). Based on the catalytic activity of sulfonic acid-functiona-
lized pyrazinium propyl chloride ([PzPS]Cl) and [PzS]Cl, it
seems that a carbon spacer between the pyrazinium cation
and sulfonic group can be an important factor in the catalytic
activity of ILs (Table 5, entries 2 and 3). In general, the presence
N
Cl
SO3H
6
[BBSI]Cl
89
HO3S
N
N
N
N
SO3H
Cl
Cl
and number of C-2 hydrogens per imidazole-based IL for
sulfonic acid-functionalized imidazolium chloride ([DSI]Cl)
along with a four-carbon spacer between two imidazolium
moieties for [BBSI]Cl increased its catalytic efficiency (Table 5,
entries 4–6).

Pyrrolidinone Synthesis Using New Ionic Liquid
E
Reusability of [BBSI]Cl
Physical and Spectral Data of New and Some Known Products
Ethyl-1-phenyl-2-(4-chlorophenyl)-4-hydroxy-5-oxo-
2,5-dihydro-1H-pyrrole-3-carboxylate (2a)
The ILs can be often removed with water from the organic
products using a simple workup. This procedure cannot be
performed when precious metal catalysts are used in the reac-
tion; in these cases, the organic products can be extracted with
non-polar organic solvents and the remaining IL can be con-
centrated and then directly recharged with new reactants for
another run. In the present protocol, after completion of the
reaction, the solvent was removed under reduced pressure and
the desired pyrrolidinones were readily extracted using ethyl
acetate or diethyl ether owing to the insolubility of [BBSI]Cl in
these organic solvents. The residue was recharged with new
model reactants for another run. The desired product was
obtained in an average of 82 % yield for three subsequent runs.
The recycled [BBSI]Cl showed almost constant catalytic
activity even after three consecutive runs. Furthermore, 1H
NMR analysis of recycled [BBSI]Cl after the third run showed
no significant change under the present workup conditions. In
order to investigate leaching of IL catalyst into the product, 1H
NMR analysis of 2a was carried out after the second and third
run and no IL was observed in the pure product (Fig. 1).
n
max (KBr)/cmꢀ1 3300, 1715, 1690, 1660, 1495, 1370, 1310,
1255, 1210, 1135, 760, 520. dH (400 MHz, CDCl3) 1.20 (t, J 7.0,
3H), 4.20 (q, J 7.0, 2H), 5.72 (s, 1H), 7.11–7.17 (m, 3H), 7.22–
7.30 (m, 4H), 7.43 (d, J 8.0, 2H), 9.04 (br s, 1H). dC (100 MHz,
CDCl3) 13.6, 60.5, 61.1, 112.5, 122.0, 125.8, 128.6, 128.7,
128.9, 133.4, 134.1, 135.8, 156.3, 162.4, 164.6. Anal. Calc.
for C19H16ClNO4: C 63.78, H 4.51, N 3.91; found: C 63.73, H
4.49, N 3.86 %.
Ethyl-1-phenyl-4-hydroxy-5-oxo-2-(4-
trifluoromethylphenyl)-2,5-dihydro-1H-pyrrole-3-
carboxylate (2d)
n
max (KBr)/cmꢀ1 3300, 2985, 1725, 1690, 1595, 1500, 1445,
1425, 1375, 1330, 1260, 1165, 1120, 1020 cmꢀ1. dH (400 MHz,
CDCl3) 1.19 (t, J 7.2, 3H), 4.20 (q, J 7.2, 2H), 5.81 (s, 1H), 7.12
(t, J 7.6, 1H), 7.30 (t, J 7.6, 2H), 7.38 (d, J 8.0, 2H), 7.47 (d, J 8.0,
2H), 7.53 (d, J 8.0, 2H), 9.10 (br s, 1H). dC (100 MHz, CDCl3)
14.2, 60.2, 60.4, 112.0, 122.7, 124.3 (1JC–F 244.7), 125.5, 125.7,
125.9, 128.6 (2JC–F 27), 129.0, 129.2 (3JC–F 8), 136.4, 142.0,
152.5, 162.3, 164.2. Anal. Calc. for C20H16F3NO4: C 61.38, H
4.12, N 3.58; found: C, 61.42, H 4.16, N 3.53 %.
Experimental
General
Unless specified, all chemicals were of analytical grade and
purchased from Merck, Aldrich, and Fluka chemical companies
and used without further purification. Products were charac-
terized by their physical constants and FT-IR, NMR, and ele-
mental analysis. The purity determination of the substrates and
reaction monitoring were carried out by TLC using silica gel SIL
G/UV 254 plates. Purity determination of the products was
accomplished by gas chromatography–mass spectrometry (GC-
MS) on an Agilent 6890GC/5973MSD analysis instrument
under 70-eV conditions. The Fourier-transform (FT)-IR spectra
were recorded on a PerkinElmer 781 spectrophotometer using
KBr pellets for solid and neat for liquid samples in the range
4000–400 cmꢀ1. In all cases, the 1H and 13C NMR spectra were
recorded on a Bruker Avance 400-MHz instrument. All chem-
ical shifts are quoted in parts per million (ppm) relative to TMS
using deuterated solvent. Microanalyses were performed on a
PerkinElmer 240-B microanalyser. Melting points were recor-
ded on a Bu¨chi B-545 apparatus in open capillary tubes.
Methyl-1-phenyl-2-p-tolyl-4-hydroxy-5-oxo-2,5-
dihydro-1H-pyrrole-3-carboxylate (2n)
n
max (KBr)/cmꢀ1 3310, 1718, 1685, 1660, 1490, 1372, 1315,
1251, 1211, 1130, 765, 522 cmꢀ1. dH (400 MHz, CDCl3) 2.28 (s,
3H), 3.74 (s, 3H), 5.73 (s, 1H), 7.08–7.22 (m, 5H), 7.25–7.30 (m,
2H), 7.49 (d, J 7.8, 2H), 9.04 (br s, 1H). dC (100 MHz, CDCl3)
21.2, 52.3, 61.7, 113.5, 122.1, 125.6, 127.3, 128.9, 129.4, 131.7,
136.2, 138.6, 157.5, 163.5, 165.2. Anal. Calc. for C19H17NO4: C
70.58, H 5.30, N 4.33; found: C 70.55, H 5.28, N 4.30 %.
Ethyl-1-(4-nitrophenyl)-4-hydroxy-5-oxo-2-(4-
trifluoromethylphenyl)-2,5-dihydro-1H-pyrrole-3-
carboxylate (2q)
n
max (KBr)/cmꢀ1 3320, 2995, 1740, 1690, 1600, 1515, 1450,
1425, 1365, 1330, 1265, 1220, 1190, 1165, 1120, 1070,
1020 cmꢀ1. dH (600 MHz, CDCl3) 1.22 (t, J 7.2, 3H), 4.23 (q, J
7.2, 2H), 5.88 (s, 1H), 7.40 (d, J 8.0, 2H), 7.57 (d, J 8.0, 2H), 7.76
(d, J 9.2, 2H), 8.14 (d, J 9.2, 2H), 9.15 (br s, 1H). dC (150 MHz,
CDCl3) 14.0, 60.5, 61.9, 113.5, 120.6, 123.5 (1JC–F 265), 126.0
(3JC–F 4), 127.8, 130.9, 131.3 (2JC–F 32), 138.7, 141.6, 144.4,
155.8, 163.0, 164.5. Anal. Calc. for C20H15F3N2O6: C 55.05, H
3.46, N 6.42; found: C 55.03, H 3.42, N 6.38 %.
Typical Procedure for the Synthesis of Pyrrolidinones 2a–s
A mixture of the aryl aldehyde (2.0 mmol), aniline derivative
(2.0 mmol), diethyl acetylenedicarboxylate (2.0 mmol, 340 mg),
and[BBSI]Clcatalyst(1.0mmol-%,9.1mg)wasstirredinethanol
(96 %, 2 mL) for 30 min. After completion of the reaction
(monitored by TLC), the crude products were extracted with
EtOAc (3 ꢁ 10 mL). Then, the extracted organic phases were
collected and dried over anhydrous Na2SO4, and the solvent was
removed under vacuum rotary evaporation and the product puri-
fied by flash chromatography or recrystallized from hot ethanol to
get the pure products. All the known products have spectral and
physicaldataconsistent withthosereported inthe literature aswell
as samples prepared from previously reported methods.
Ethyl-1-p-tolyl-4-hydroxy-5-oxo-2-(4-
trifluoromethylphenyl)-2,5-dihydro-1H-pyrrole-3-
carboxylate (2r)
n
max (KBr)/cmꢀ1 3305, 2985, 1730, 1690, 1660, 1515, 1445,
1420, 1370, 1325, 1255, 1215, 1170, 1145, 1110, 1065,
1020 cmꢀ1. dH (400 MHz, CDCl3) 1.19 (t, J 7.2, 3H), 2.26 (s,
3H), 4.20 (q, J 7.2, 2H), 5.77 (s, 1H), 7.09 (d, J 8.4, 2H), 7.34 (d,
J 8.4, 2H), 7.37 (d, J 8.0, 2H), 7.53 (d, J 8.0, 2H), 9.11 (br s, 1H).
dC (100 MHz, CDCl3) 13.8, 20.7, 61.0, 61.2, 112.3, 122.1, 123.8
(1JC–F 270.8), 125.5, 125.6 (3JC–F 4), 127.9, 129.5, 130.0, 130.4
(2JC–F 32), 133.2, 136.0, 139.5, 156.6, 162.5, 164.6. Anal. Calc.
for C21H18F3NO4: C 62.22, H 4.48, N 3.46; found: C 62.19, H
4.42, N 3.38 %.
Recycling Catalyst
After extraction of the product, the volatiles were removed
under vacuum and the remaining IL was collected, dried, and
reused for the next run.

F
N. G. Khaligh et al.
The second run
060718
07/06/2018 Second Run 2a 1H
11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
Chemical shift [ppm]
0
The third run
060718
07/06/2018 Third Run 2a 1H
11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
Chemical shift [ppm]
0
Fig. 1. 1H NMR of 2a after the second and third run of the reaction under optimized reaction conditions.
Ethyl-1-(4-methoxyphenyl)-4-hydroxy-5-oxo-2-(4-
trifluoromethylphenyl)-2,5-dihydro-1H-pyrrole-3-
carboxylate (2s)
123.6, 124.0 (1JC–F 269), 125.6 (3JC–F 7), 128.4, 128.5, 128.7,
129.0, 129.2 (2JC–F 27), 142.2, 153.8, 157.4, 162.4, 164.2. Anal.
Calc. for C21H18F3NO5: C 59.86, H 4.31, N 3.32; found: C
58.82, H 4.25, N 3.29 %.
n
max (KBr)/cmꢀ1 3300, 1715, 1690, 1660, 1495, 1370, 1310,
1255, 1210, 1135, 760, 520 cmꢀ1. dH (400 MHz, CDCl3) 1.14 (t,
J 7.2, 3H), 3.69 (s, 3H), 4.15 (q, J 7.2, 2H), 5.72 (s, 1H), 6.77 (d, J
9.2, 2H), 7.28 (t, J 9.2, 2H), 7.33 (d, J 8.4, 2H), 7.50 (d, J 8.4,
2H). dC (100 MHz, CDCl3) 14.4, 55.6, 60.2, 61.0, 111.8, 114.4,
Conclusion
In summary, the efficient catalytic properties of [BBSI]Cl were
proved for the synthesis of pyrrolidinone derivatives under mild

Pyrrolidinone Synthesis Using New Ionic Liquid
G
conditions. The current protocol has advantages such as being a
simple experimental and sustainable procedure, good to excel-
lent yield of the desired products within short reaction times, and
recyclability of the IL. Its application for a one-pot multicom-
ponent reaction has highlighted the importance of task-specific
ILs (TSILs) as an efficient catalyst in organic chemistry, and we
hope that owing to its broad substrate scope and mild nature, the
present method can find applications in academic and industrial
processes.
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Conflicts of interest
The authors declare no conflicts of interest.
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Acknowledgements
This work was supported by a High-Impact Research Grant (no. RP025A/B/
C-14AET) for Scientific Research from the University of Malaya, Malaysia.
The authors are grateful to staff members in the Analytical and Testing
Centre of Iran University of Science and Technology and the University of
Malaya for partial support.
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