Green synthesis of quinolines via A3-coupling by using graphene oxide-supported Br?nsted acidic ionic liquid

Article abstract of DOI:10.1007/s11164-020-04099-7

Abstract: Graphene oxide-supported Bronsted acidic ionic liquid ([GrBenzImi]SO₃H) has been prepared by covalent grafting of benzimidazole unit in the matrix of graphene oxide followed by reaction with 1,4-butane sultone and hydrochloric acid. [GrBenzImi]SO₃H has been characterized by various techniques including Fourier transform infrared spectroscopy (FTIR), FT-Raman (FT-Raman spectroscopy), CP-MAS ¹³C NMR spectroscopy, thermogravimetric analysis, energy-dispersive X-ray analysis, Brunauer–Emmett–Teller surface area, X-ray diffraction, and transmission electron microscopy. [GrBenzImi]SO₃H was successfully employed as heterogeneous catalyst in A³-coupling reaction of aryl aldehydes, anilines and phenylacetylene for the synthesis of 2,4-disubstituted quinolines using water/ethanol system (1:1) as green medium. [GrBenzImi]SO₃H could be recycled six times without significant loss in the yield of product. Graphic abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s11164-020-04099-7

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-020-04099-7
Green synthesis of quinolines via A3‑coupling by using
graphene oxide‑supported Brønsted acidic ionic liquid
Shivanand Gajare1 · Audumbar Patil1 · Shankar Hangirgekar1 ·
Sushilkumar Dhanmane2 · Gajanan Rashinkar1
Received: 19 October 2019 / Accepted: 5 February 2020
© Springer Nature B.V. 2020
Abstract
Graphene oxide-supported Bronsted acidic ionic liquid ([GrBenzImi]SO3H) has
been prepared by covalent grafting of benzimidazole unit in the matrix of gra-
phene oxide followed by reaction with 1,4-butane sultone and hydrochloric acid.
[GrBenzImi]SO3H has been characterized by various techniques including Fourier
transform infrared spectroscopy (FTIR), FT-Raman (FT-Raman spectroscopy), CP-
MAS 13C NMR spectroscopy, thermogravimetric analysis, energy-dispersive X-ray
analysis, Brunauer–Emmett–Teller surface area, X-ray difraction, and transmission
electron microscopy. [GrBenzImi]SO3H was successfully employed as heterogene-
ous catalyst in A3-coupling reaction of aryl aldehydes, anilines and phenylacetylene
for the synthesis of 2,4-disubstituted quinolines using water/ethanol system (1:1) as
green medium. [GrBenzImi]SO3H could be recycled six times without signifcant
loss in the yield of product.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-020-04099-7) contains supplementary material, which is available to authorized users.
*
Gajanan Rashinkar
gsr_chem@unishivaji.ac.in
Sushilkumar Dhanmane
Sushorganic@gmail.com
1
2
Department of Chemistry, Shivaji University, Kolhapur, MS 416004, India
Department of Chemistry, Fergusson College, Pune, MS 411004, India
Vol.:(0123456789)
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S. Gajare et al.
Graphic abstract
Keywords Bronsted acidic ionic liquid · Graphene oxide · A3-coupling ·
2,4-disubstituted quinolines · Reusability
Introduction
Advent of green chemistry principles has spurred extensive interest in developing
environmentally benign processes using Brønsted acidic ionic liquids (BAILs) in
organic synthesis [1–4]. BAILs circumvent the environmental and personal toxic-
ity concern that are associated with traditional Brønsted acids and ofer high ther-
mal stability as well as high acidity accompanied by negligible release of haz-
ardous gases. In addition, their excellent catalytic performance, non-hygroscopic
nature, easy separation from reaction medium makes their utilization economi-
cally feasible [5–7]. Owing to these properties BAILs have been exploited for
various organic transformations such as aza-Michael reaction, Beckmann rear-
rangement, Pechmann reaction, Mannich reaction, Koch carbonylation, Prin’s
reaction, Hantzsch reaction [8]. In recent years, great attention has been dedi-
cated to the development of supported BAILs as they ofer signifcant advantages
such as high reactivity and facile reusability over homogeneous BAILs. In addi-
tion, they can be applied in continuous fxed bed reactors. Owing to these advan-
tages, supported BAILs have been employed in the pharmaceuticals, polymers,
1 3

Green synthesis of quinolines via A3-coupling by using…
biodiesel as well as in oil refning and petroleum industries [9–12]. A careful
insight into heterogeneous BAILs revels that their catalytic performance depends
on the nature of support material [13]. In view of this, various supports such as
silica, alumina, zeolites and polystyrene type polymers have been employed for
the preparation of supported BAILs [14]. However, despite considerable progress,
there is still scope to develop novel supported BAILs especially using nanomate-
rials as a support.
Nanostructure materials have emerged as attractive supports in the synthesis
of heterogeneous catalysts. They ofer extraordinary features such as nanosize,
large surface-to-volume ratio, and ease of surface functionalization [15]. In the
recent years, graphene oxide (GO) has emerged as one of the most promising
two-dimensional (2D) nanomaterial that has been widely applied in wide areas
including cancer therapy, photocatalysis, organic synthesis, electrochemistry, tis-
sue engineering, imaging, diagnostics, etc. [16–19]. GO possesses unique features
such as large surface area, ultrahigh electrical conductivity, excellent mechanical
properties, high chemical stability, surface functionalizability, amphiphilicity, fu-
orescence quenching capacity, surface-enhanced Raman scattering (SERS) prop-
erty, and amazing aqueous processability. Due to these fascinating properties, GO
has emerged as unparallel 2D support in the preparation of heterogeneous cata-
lysts [20]. The recent applications of GO-supported ionic liquid catalysts in the
realm of catalysis have demonstrated their tremendous potential in the develop-
ment of economical, efcient and environmentally benign processes [21].
The efcacious catalytic construction of bio-relevant heterocyclic architectures
is still a fascinating endeavor for chemists intending to explore new chemical
spaces and to develop more sustainable organic synthesis [22]. Quinolines are
privileged heterocyclic scafolds with wide range of pharmacological properties
such as anticancer, antimalarial, antimicrobial, antitubercular, anti-infammatory,
antioxidant, anticonvulsant, and antihypertensive activities [23]. Owing to the
wide array of biological activities, methodology of their synthesis has attracted
signifcant attention in the last decade. In line with their increasing relevance,
numerous bespoke classical strategies such as classical Skraup [24], Doeb-
ner–Miller [25], Friedlander [26], Pftzinger reactions [27], Conrad–Limpach
[28], and Combes synthesis [29] have been explored for their synthesis. However,
many of these methods sufer from limitations such as expensive reagents or cata-
lysts, strong acidic conditions, long reaction times, high temperatures and envi-
ronmentally unfriendly solvents. In recent years, A3-coupling reaction between
aromatic aldehyde, anilines, and terminal alkynes has been established as a con-
venient method for synthesis of quinolines [30–32]. However, despite impressive
progress, a thrust toward developing a green procedure using a more efcient het-
erogeneous catalyst is a subject of immense research in organic synthesis.
Based on aforementioned facts and in continuation of our studies related to het-
erogeneous catalysis [33, 34], herein we report an eco-friendly, efcient, and versa-
tile approach for the synthesis of 2,4-disubstituted quinolines using graphene oxide-
supported Brønsted acidic ionic liquid as a catalyst.
1 3

S. Gajare et al.
Experimental section
General remarks
All reactions were carried out under air atmosphere in dried glassware. FTIR spectra
were measured with a PerkinElmer one FTIR spectrophotometer. The samples were
examined as KBr discs (~5% w/w). Raman spectroscopy was done using a Bruker:
RFS 27 spectrometer. The thermogravimetric analysis (TGA) curves were obtained
using instrument SDT Q600 V20.9 Build 20 in the presence of static air at linear
heating rate of 10 °C/min from 25 to 1000 °C. Elemental analyses were performed
in a PerkinElmer 2400, Series II, CHNS/O analyzer and using an energy‐dispersive
X‐ray spectroscopic facility (Hitachi S 4800, Japan). 1H NMR and 13C NMR spectra
1
were recorded with a Bruker Avance (300 MHz for H NMR and 75 MHz for 13C
NMR) spectrometer using CDCl3 solvent and tetramethylsilane as an internal stand-
ard. Chemical shifts are expressed in parts per million (ppm) and coupling constants
are expressed in hertz (Hz). The CP‐MAS 13C NMR spectrum was recorded with a
JEOL‐ECX400 type FT‐NMR spectrometer. Mass spectra were recorded with a Shi-
madzu QP2010 gas chromatography–mass spectrometry (GC–MS). The materials
were analyzed by TEM using a PHILIPS CM 200 model with 20–200 kV accelerat-
ing voltages. Melting points were determined using MEL‐TEMP capillary melting
point apparatus and are uncorrected. BET (Brunauer–Emmet–Teller) Quantachrome
Nova Win surface area analyzer was used for surface area and pore size measure-
ments by N2 adsorption–desorption analysis. X-ray powder difraction (XRD) was
taken using a Bruker D2 Phaser. Graphite (1) and all other chemicals were obtained
from local suppliers and used without further purifcation. Graphite oxide (2) and
graphene oxide (GO) (3) were synthesized following the literature procedure [35,
36] and reported in our previous work [37].
Preparation of 3‑chloropropyl graphene oxide (4)
A mixture of 3 (8.0 g) and (3-chloropropyl)triethoxysilane (10.8 mL, 45 mmol) in
xylene (50 mL) was refuxed in an oil bath. After 24 h, the mixture was cooled, and
the residue was separated by centrifugation, washed with THF (3×5 mL), and dried
under vacuum at room temperature to aford 3-chloropropyl graphene oxide (4).
IR (KBr, thin flm): υ=3437, 2945, 2885, 2375, 1698, 1426, 995, 792, 682 cm−1;
Raman: υ=3036, 2129, 1974, 1597, 1293 cm−1; Loading: 0.12 mmol of functional
group per gram of 4.
Preparation of [GrBenzImi] (6)
A mixture of 4 (8.0 g) and sodium salt of benzimidazole (5) (2 g, 15 mmol) in ben-
zene (50 mL) was heated at 80 °C in an oil bath. After 24 h, the solid was separated
by centrifugation, washed with benzene (3×50 mL), MeOH (3×50 mL), CH2Cl2
(3×50 mL), and dried under vacuum at 50 °C for 24 h to aford [GrBenzImi] (6).
1 3

Green synthesis of quinolines via A3-coupling by using…
IR (KBr, thin flm): υ=3410, 2922, 2856, 1670, 1565, 1405, 1322, 1097, 1023,
467 cm−1. Raman: υ=3064, 2714, 2117, 1594, 1296 cm−1. Elemental analysis
observed: %C 68.57, %H 0.25, % N 5.59. Loading: 0.47 mmol functional group per
gram of 6.
Preparation of [GrBenzImi]SO3H (7)
A mixture of 6 (10.0 g) and 1,4-butane sultone (2.5 g, 18 mmol) in toluene (50 mL)
was heated at 100 °C in an oil bath for 6 h. Afterward, the mixture was treated with
conc. HCl (3 mmol, 36% w/w) and allow to stand at room temperature for 24 h, and
washed with the diethyl ether (3×50 mL) and dried under vacuum at 50 °C for 24 h
to aford [GrBenzImi]SO3H (7).
FTIR (KBr, thin flm): υ=3410, 2922, 2856, 1670, 1565, 1188, 1034 cm−1;
Raman: υ=3064, 2774, 2136, 1599, 1294 cm−1. Elemental analysis observed: %C
68.57, % O 19.43, % Si 2.87, % N 5.59, % Cl 2.91, % S 0.38 and % H 0.25. Loading
of SO3H: 0.12 mmol functional group per gram of 7.
General method for synthesis of 2,4‑disubstituted quinolines
A mixture of aryl aldehyde (1 mmol), aniline (1 mmol), phenylacetylene (1 mmol),
and [GrBenzImi]SO3H (7) (50 mg) in water/ethanol (1;1) solvent system (3 mL)
was stirred at 80 °C. After completion of the reaction as monitored by the TLC, the
reaction mixture was centrifuged to remove 7. Evaporation of solvent in vacuo fol-
lowed by column chromatography over silica gel using petroleum ether/ethyl acetate
aforded pure products.
Results and discussion
The preparation of graphene oxide‐supported Bronsted acidic ionic liquid phase cat-
alyst is outlined in Scheme 1. Initially, purifed graphite (1) was oxidized to graph-
ite oxide (2) following modifed Hummers and Ofeman’s method [35, 36]. The
ultrasound-mediated exfoliation of 2 using hydrazine hydrate in aqueous medium
aforded graphene oxide (GO) (3) [37] which on further treatment with (3‐chloro-
propyl)triethoxysilane aforded 3-chloropropyl graphene oxide (4). The synthetically
fertile chloro group in 4 allowed introduction of ionic liquid-like group in the GO
matrix through quaternization with sodium salt of benzimidazole (5) to yield precur-
sor acronymed as [GrBenzImi] (6). Finally, the acid treatment of 6 with 1,4-butane
sultone and hydrochloric acid aforded the desired GO-supported Bronsted acidic
ionic liquid acronymed as [GrBenzImi]SO3H (7).
Fourier transform infrared (FTIR), FT‐Raman, and cross-polarization magic
angle spinning (CP‐MAS) 13C NMR spectroscopy were used to monitor the reac-
tions involved in the preparation of [GrBenzImi]SO3H (7). The FTIR spectrum
of 3-chloropropyl graphene oxide (4) displayed peaks at 3437 (O–H stretching),
2885 (C–H stretching), 995 (Si–O stretching) and 682 cm−1 (C–Cl stretching)
1 3

S. Gajare et al.
O
O
H
O
HO
OH
OH
98% H2SO4,
NaNO3
O
O
KMnO4
O
OH
O
Graphite (1)
HO
HO
))))
O
O
O
Graphite oxide (2)
N2H4.H2O,
4h, 100 oC
O
OH
HO
COOH
COOH
OH
HOOC
O
OH
O
OH
O
OH
OH
OH
OH
O
=
HO
O
HOOC
O
HO
COOH
COOH
OH
OH
O
Graphene oxide (GO) (3)
Graphene oxide (GO) (3)
OEt
Xylene, 110 o
24h
C
EtO Si
OEt
Cl
COOH
COOH
OH
HOOC
O
O
O
O
Si
Cl
HO
3
O
O
HOOC
COOH
COOH
3-Chloropropyl graphene oxide (4)
N
+
Na
Benzene, reflux, 24 h
N
Sodium salt of benzimidazole (5)
COOH
COOH
O
S
O
O
COOH
COOH
HOOC
O
HOOC
O
OH
O
OH
O
N
N
O
Si
O
Si
3
N
N
3
SO3H
O
HO
4
O
Toluene,100oC, 6h, HCl
HO
O
O
O
O
HOOC
Cl
HOOC
COOH
COOH
COOH
COOH
[GrBenzImi] (6)
[GrBenzImi]SO3H (7)
Scheme 1 Preparation of [GrBenzImi]SO3H (7)
[38, 39] (Fig. 1c). The quaternization of 4 with sodium salt of benzimidazole (5)
was monitored by FTIR spectroscopy. The vanishing of C–Cl stretching peak at
682 cm−1 and appearance of bands at 1565 (C=N stretching of benzimidazolium
ring), 1670 (C=C stretching of benzimidazolium) and 2922 cm−1 (C–H stretching
1 3

Green synthesis of quinolines via A3-coupling by using…
Fig. 1 FTIR spectra of (a) Graphite oxide (2); (b) Graphene oxide (3); (c) 3-Chloropropyl graphene
oxide (4); (d) [GrBenzImi] (6); (e) [GrBenzImi]SO3H (7); (f) Reused [GrBenzImi]SO3H (7)
of benzimidazolium) demonstrated successful formation of 6 via quaternization
(Fig. 1d). The formation of [GrBenzImi]SO3H (7) was confrmed on the basis
of characteristic peaks at 1188 cm−1 (asymmetric stretching of S=O of sulfonate
group) and 1034 cm−1 (symmetric stretching of S=O of sulfonate group) (Fig. 1e)
[40, 41]. Another promising technique to study structural defects and structural
modifcations in graphene-based material is Raman spectroscopy. The Raman
analysis of [GrBenzImi] (6) (Fig. 2a) and [GrBenzImi]SO3H (7) (Fig. 2b) dis-
played two major characteristic bands, assigned as D and G bands. The D band
results from vibrations due to the structural imperfections that are caused by the
attachment of oxygenated groups on the sp3-hybridized graphitic sheet carbons
basal plane and disordered lattices, while the G band arises due to vibration of
the sp2-hybridized carbon atoms in graphene lattices and the frst-order scatter-
ing from the doubly degenerate E2g phonon modes of graphite as well as bond
stretching of sp2 carbon pairs in both rings and chains of graphene skeleton. The
D and G band peaks in 6 were observed at 1296 cm−1 and 1594 cm−1, respec-
tively. The D and G band peaks for 7 were displayed at 1296 cm−1 and 1599 cm−1
indicating that position of the D band is almost the same before and after the
chemical modifcations but G band shows slight redshift due to increasing strain
by sulfonic group attached on the surface of graphene oxide [42, 43]. In addition,
7 shows higher intensity of D band (0.014) than G band (0.012) due to intro-
duction of benzimidazolium group in the GO matrix revealing the formation of
7 [44]. Finally, the CP-MAS 13C NMR of 7 displayed signals at δ 193 (C=O
groups of graphene), 169 (O=C–O), 101 (O–C–O), 130 (graphitic sp2–C), 70
(C–OH), 62 (epoxide), 153 (s, benzimidazolium C2), 152 (s, benzimidazolium
1 3

S. Gajare et al.
Fig. 2 a Raman spectra of [GrBenzImi]Cl (6). b Raman spectra of [GrBenzImi]SO3H (7). c Raman spec-
tra of reused [GrBenzImi]SO3H (7)
C4), 120 (s, benzimidazolium C5), 49 (s, 1C, =N–CH2CH2–CH2), 28 (s, 1C,
=N–CH2CH2–CH2), 8 (s, 1C, –CH2Si) confrming the formation of 7.
Thermogravimetric analysis (TGA) was employed to study of thermal stability
of [GrBenzImi]SO3H (7) over the temperature range of 25–1000 °C at heating
rate of 10 °C/min (Fig. 3). The TGA curve displayed three major weight losses.
The initial weight loss of 1.7% below 200 °C is due to release of physically
adsorbed water. The second key weight loss of 38.7% up to 535 °C is attributed to
loss of labile oxygen-containing groups such as CO and CO2 [45] as well as lib-
eration of SO3H group [46] and surface-bound organic scafolds from GO surface
[47]. The major weight loss of 49.2% up to 754 °C ascribed to complete combus-
tion of GO and carbon skeleton.
The elemental mapping by energy-dispersive X-ray spectroscopic analysis
(EDX) of [GrBenzImi]SO3H (7) revealed carbon and oxygen as the major ele-
ments which are attributed to GO skeleton whereas displayed minor peaks for
silicon and sulfur. The presence of sulfur in its respective energy position at
2.2–2.3 keV also supports the formation of 7 [48]. Further, the quantifcation of
1 3

Green synthesis of quinolines via A3-coupling by using…
Fig. 3 TGA curve of [GrBenzImi]SO3H (7)
SO3H group in 7 was performed by employing volumetric titration analysis [49]
and was found to be 0.12 mmol per gram of 7.
The surface area and textural properties of GO (3) and [GrBenzImi]SO3H (7)
were analyzed by Brunauer–Emmett–Teller (BET) using nitrogen. The 7 showed
BET surface area of 49.72 m2/g with the average pore diameter of 19 Å. The surface
area, pore volume, and pore size of 7 were signifcantly lower than that of pristine
GO (3) (77 m2/g, 23 Å) indicating loss of micropores due to substantial grafting of
organic moieties on the matrix of graphene oxide [50].
The evidence for retention of crystal structure of GO (3) (Fig. 4a) in [GrBenzImi]
SO3H (7) (Fig. 4b) was further investigated by X-ray difraction (XRD). The difrac-
tograms of GO (3) and 7 displayed two main characteristic peaks at 2θ values 26.0°
and 43.3° which are attributed to (002) and (101) refections of graphitized carbon.
Thus XRD analysis revealed that the structure of pristine GO was retained in 7 even
after multi-step functionalization [51]. In addition, the peak range of 2θ=13°–16°,
which is due to the presence of benzimidazolium groups on the graphene oxide
sheets was also observed [52].
The surface morphology of GO (3) and [GrBenzImi]SO3H (7) were studied by
transmission electron microscopy (TEM). The TEM image of 7 (Fig. 5a–c) and pris-
tine GO (3) (Fig. 5f) displayed agglomerated, wrinkled and folded sheet-like struc-
ture which is inconsistent with graphene oxide structure and crumpling features with
twisted nanosheets in disordered phase [53]. The GO nanosheets carry immobilized
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S. Gajare et al.
Fig. 4 a XRD of graphene oxide (GO) (3). b XRD of [GrBenzImi]SO3H (7)
Fig. 5 TEM images of a–c [GrBenzImi]SO3H (7) with SEAD pattern; d, e reused [GrBenzImi]SO3H
(7); f TEM image of graphene oxide (GO) (3)
spherical dense spots which are attributed to the presence of benzimidazolium group
and SO3H group. The selected area electron difraction (SAED) pattern exhibit dif-
fused ring pattern that persuades amorphous nature of GO nanosheets [54].
In order to optimize the reaction conditions, a model reaction between benzal-
dehyde (8a; 1 mmol), aniline (9a; 1 mmol), and phenyl acetylene (10; 1.0 mmol)
in the presence of [GrBenzImi]SO3H (7) was carried out at 80 °C for the synthesis
of 2,4-disubstituted quinolines (Scheme 2). Initially, the efect of various solvents
1 3

Green synthesis of quinolines via A3-coupling by using…
CHO
NH2
[GrBenzImi]SO3H (7)
+
+
N
80 ºC, H2O:EtOH (1:1)
11a
8a
9a
10
Scheme 2 [GrBenzImi]SO3H (7) catalyzed synthesis of 2,4-disubstituted quinolines
Table 1 Optimization of solvent in synthesis of 2,4-disubstituted quinolines
CHO
NH2
[GrBenzImi]SO3H (7)
+
+
N
80 ºC , solvent
11a
8a
9a
10
Entry
Solvent
Time (min)
Yielda (%)
1
2
3
4
5
6
7
8
Water
DCM
THF
Acetonitrile
Ethanol
Methanol
Toluene
Water/ethanol (1:1)
20
25
20
20
15
15
25
18
55
76
78
72
92
86
68
93
Reaction condition: benzaldehyde (1 mmol), aniline (1 mmol), phenyl acetylene (1 mmol), solvent
(3 mL)
aIsolated yields after chromatography
on the model reaction was investigated in the presence of 7 at 80 °C (Table 1).
The reaction aforded poor yield of 11a in water (Table 1, entry 1), whereas better
yields were obtained in polar aprotic solvents such as dichloromethane (DCM),
tetrahydrofuran (THF) and acetonitrile (Table 1, entries 2–4). Further, moderate
yield of 11a was obtained in nonpolar solvent such as toluene (Table 1, entry 7).
Moreover, better yields were achieved in polar protic solvents like methanol and
ethanol (Table 1, entries 5–6). Among all the screened solvents, combination of
water and ethanol (1:1) system furnished the highest yield 11a (Table 1, entry 8).
Therefore, water/ethanol (1:1) system was chosen as the solvent for further stud-
ies. Initially a control reaction was carried out by using GO (3) and [GrBenzImi]
(6). The reaction could not be initiated by using 3 and 6 in spite of using high
1 3

S. Gajare et al.
quantities (up to 200 mg) indicating that they were inefective as catalysts for the
projected reaction (Table 2, entry 1–2). Next, the efect of catalyst loading was
investigated on the model reaction. In the presence 10 mg (0.0029 mmol) and
20 mg (0.0058 mmol) of 7, low amount of corresponding product viz. 2,4-diphe-
nyl quinoline (11a) was formed even after prolonged reaction time (Table 2,
entry 3-4). Gratifyingly, when the amount of catalyst was increased from 30 mg
(0.0087 mmol) to 50 mg (0.014 mmol), the yield of 11a was elevated up to 93%
(Table 2, entry 5–7). However, no substantial alteration has been occurred in the
yield of product and reaction time using quantities beyond 50 mg up to 200 mg
(Table 2, entries 8–10). Thus, 50 mg of 7 was selected as optimal catalyst loading
for further studies. In addition, the efect of surfactant sodium dodecylsulfate was
also studied on model reaction, and there were no substantial changes in reaction
time and yield. (Table 2, entry 11).
With the optimal reaction conditions in hands, the scope and generality of
the methodology were illustrated for A3-coupling reaction using variety of aryl
Table 2 Optimization of catalyst loading in synthesis of 2,4-disubstituted quinolines
CHO
NH2
[GrBenzImi]SO3H (7)
+
+
N
80 ºC, H2O:EtOH (1:1)
11a
8a
9a
10
Entry
Catalyst
Amount of catalyst
(mg)
Time (min)
Yielda (%)
1
2
3
4
5
6
7
8
GO (3)
200
200
10
20
30
40
50
100
150
200
(50+30)
1440
1440
25
20
16
15
18
14
–
–
[GrBenzImi] (6)
[GrBenzImi]SO3H (7)
52
78
88
91
93
92
93
93
92
7
7
7
7
7
9
10
11
7
12
12
18
7
7+SDS
Reaction condition: benzaldehyde (1 mmol), aniline (1 mmol), phenyl acetylene (1 mmol), Water/ethanol
(3 mL) at 80 °C
aIsolated yields after chromatography
1 3

Green synthesis of quinolines via A3-coupling by using…
aldehydes (8), substituted anilines (9) and phenylacetylene (10). The results are
summarized in Table 3. In all the cases, reactions proceeded smoothly afording
the desired 2,4-disubstituted quinolines in good to excellent yields. It is worth men-
tioning that electronic efect of substituents in anilines has infuence on the yields
of products. Anilines with electron-donating substituents such as 4-methoxy ani-
line (Table 3, entry 9c), and 4-methyl aniline (Table 3, entry 9g) reacted more ef-
ciently than anilines with electron-withdrawing substituents such as 4-chloro aniline
(Table 3, entry 9b) and 4-nitro aniline (Table 3, entry 9f).
A plausible mechanism of [GrBenzImi]SO3H (7) catalyzed synthesis of 2,4-dis-
ubstituted quinolines is outlined in Scheme 3. Initially, 7 activates the carbonyl
group of aldehyde through hydrogen bonding which facilitated Knoevenagel con-
densation with aniline afording aldimine intermediate (A) via removal of water
molecule. Further, addition of phenylacetylene to A forms the propargylamine inter-
mediate (B) which undergoes cyclization to form the dihydroquinoline intermediate
(C). Finally, C is subsequently oxidized by O2 in air to give the desired 2, 4-disubsti-
tuted quinoline (D) [55–57].
The hot fltration test was carried out to confrm heterogeneous nature of
[GrBenzImi]SO3H (7) by using the model reaction. In this test, a mixture of 7
(50 mg), benzaldehyde (8a; 1 mmol) aniline (9a; 1 mmol) and phenylacetylene (10;
1 mmol) in water/ethanol (1:1) (3 mL) was heated at 80 °C. The 7 was separated
from the hot reaction mixture when 50% conversion was accomplished (GC). The
reaction was continued with the fltrate for further 8 h. There was no increase in the
yield of the product beyond 50% even after 8 h confrming the heterogeneous nature
of 7.
From the green chemistry point of view, the reusability is one of the signifcant
facets of heterogeneous catalyst to determine efcient recovery and reuse of the cat-
alyst with their dynamic life span. Thus, the recovery and reusability of [GrBenzImi]
SO3H (7) investigated by employing model reaction (Fig. 6). In brief, after reac-
tion was completed, the 7 was isolated from reaction mixture by centrifugation. The
recovered 7 was washed several times with water/ethanol solvent system, dried in
vacuum at room temperature and used directly for the next cycle. The recovered cat-
alyst could be reused for six times without signifcant decrease in the yield of the
products. Further, the stability of recycled catalyst 7 was studied by FTIR spectros-
copy, FT-Raman spectroscopy, EDX and TEM analysis. It is noteworthy to mention
that, the FTIR (Fig. 1f) and FT-Raman (Fig. 2c) spectra of reused 7 still retain the
prominent peak pattern of the 7. The EDX mapping of 7 after six catalytic cycles
confrmed the integrity of the recycled catalyst. Moreover, TEM analysis of fresh
(Fig. 5a–c) and reused 7 (Fig. 5d, e) designates that morphology is preserved even
after six successive runs. The results of FTIR, FT-Raman, EDX and TEM analysis
of fresh and reused 7 confrmed that the structural rigidity and main characteris-
tics of complex remain conserved, demonstrating stability of 7 after six consecutive
runs.
To demonstrate the importance of [GrBenzImi]SO3H (7) in comparison with
other reported traditional methods, we have summarized previous report for synthe-
sis of quinolines in Tables 4 and 5. The comparison of results (Table 5.) clearly
1 3

S. Gajare et al.
Table 3 [GrBenzImi]SO3H (7) catalyzed synthesis of 2,4-disubstituted quinolines
CHO
NH2
R,
[GrBenzImi]SO3H (7)
+
+
N
R
80 ºC, H2O:EtOH (1:1)
R
R,
10
11a-l
8a-l
9a-l
Entry
Aldehydes
(8)
Anilines
Phenyl
Product
(11)
Time
(Min)
Yielda
(%)
(9)
acetylene (10)
CHO
NH2
a
18
93
N
CHO
NH2
b
c
Cl
15
25
78
90
N
Cl
CHO
NH2
H3CO
N
OCH3
CHO
CHO
NH2
d
e
22
88
I
N
I
NH2
Br
20
20
83
80
N
Br
CHO
NH2
f
O2N
N
NO2
1 3

Green synthesis of quinolines via A3-coupling by using…
Table 3 (continued)
Entry
Aldehydes
Anilines
(9)
Phenyl
Product
(11)
Time
(Min)
Yielda
(%)
(8)
acetylene (10)
CHO
CHO
NH2
g
H3C
22
20
89
N
CH3
NH2
h
88
90
N
CH3
CH3
CHO
NH2
i
18
N
Br
Br
CHO
NH2
j
15
87
N
Cl
Cl
CHO
NH2
k
l
17
26
89
82
N
NO2
NO2
CHO
NH2
N
F
F
Reaction condition: benzaldehyde (1 mmol), aniline (1 mmol), phenyl acetylene (1 mmol), solvent water/
ethanol (1:1) (3 mL); [GrBenzImi]SO3H (7) (50 mg)
aIsolated yields after chromatography
persuades that 7 is a superior catalyst in terms of catalyst loading and reaction time
as compared to the reported catalyst.
1 3

S. Gajare et al.
COOH
COOH
HOOC
O
OH
O
O
O
Si
3 N
N
4
SO H
3
HO
O
O
O
HOOC
Cl
+
COOH
COOH
H
H2N
..
-H2O
COOH
COOH
N
N
(A)
HOOC
O
OH
(D)
O
O
Si
O
3
N N
4
SO3H
HO
O
O
H
HOOC
Cl
COOH
COOH
-H2
..
HN
N
H
(C)
COOH
(B)
COOH
OH
HOOC
O
O
O
O
Si
3
N
N
SO H
4
HO
3
O
O
HOOC
Cl
COOH
COOH
Scheme 3 Plausible mechanism for the synthesis of 2,4-disubstituted quinolines using [GrBenzImi]
SO3H (7)
Fig. 6 Reusability of [GrBenzImi]SO3H (7) in the synthesis 2,4-disubstituted quinolines
1 3

Green synthesis of quinolines via A3-coupling by using…
1 3

S. Gajare et al.
Table 5 Comparison of this work with literature results for synthesis of 2,4-disubstituted quinolines cata-
lyzed by various catalysts
Entry
Catalyst
Solvent
Temperature
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
NbCl5
Nano AMA
FeCl3
Fe(OTf)3 (5%)
1 wt% CeO2–TiO2
BF3∙E2O
Yb(Pfb)3
Yb(Pfb)3
AgNTf2/HOTf
InCl3
In/HCl
I2
AuCl3/CuBr
AlCl3
ZnCl2
Acetonitrile
Acetonitrile
1,2-Dichloroethane
Solvent free
None
Toluene
Toluene
CH2Cl2
Toluene
Toluene
Water
MeNO2
Methanol
None
Refux
Refux
Refux
100 °C
80 °C
Refux
Refux
35 °C
80 °C
Refux
Refux
Refux
rt
1440
45
720
180
90
74
90
93
71
95
88
82
10
90
90
72
61
240
1440
2880
1440
1440
1080
720
23,280
2880
2880
18
9
10
11
12
13
14
15
16
55
110 °C
110 °C
80 °C
Trace
Trace
93
None
Present work [GrBen- Water/EtOH (1:1)
zImi] SO3H (7)
Conclusion
In conclusion, we have reported a graphene oxide‐supported Bronsted acidic
ionic liquid [GrBenzImi]SO3H (7) catalyst. The catalyst 7 was thoroughly char-
acterized by FTIR, FT-Raman, CP-MAS 13C NMR spectroscopy, XRD, TEM,
TGA, EDX and BET analysis. [GrBenzImi]SO3H was successfully employed as
a heterogeneous catalyst with outstanding activity in A3-coupling reaction of aryl
aldehydes, anilines, and phenylacetylene for the synthesis of 2,4-disubstituted
quinolines. The protocol ofers several striking advantages such as good yields,
simple workup procedure, short reaction time, use of environmentally benign sol-
vent and efcient recyclability of the catalyst.
Acknowledgements We gratefully acknowledge Indian Institute of Bombay (IITB), North-Eastern Hill
University Shillong (NEHU), Indian Institute of Technology, Madras (IITM) for providing spectral facili-
ties and Shivaji University Kolhapur for providing fnancial assistance and Golden Jubilee Research Fel-
lowship (GJRF).
Compliance with ethical standards
Confict of interest The authors declare that they have no confict of interest.
1 3

Green synthesis of quinolines via A3-coupling by using…
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