Synthesis of new low-viscous sulfonic acid-functionalized ionic liquid and its application as a Br?nsted liquid acid catalyst for the one-pot mechanosynthesis of 4H-pyrans through the ball milling process

Article abstract of DOI:10.1016/j.molliq.2019.01.024

In the present study, a new low-viscous sulfonic acid-functionalized ionic liquid (SAIL) viz. 4,4′-trimethylene-N,N′-sulfonic acid-dipiperidinium chloride was synthesized and characterized by FTIR, 1D and 2D NMR, and Mass spectra. Then, some properties of

Full text of DOI:10.1016/j.molliq.2019.01.024

Accepted Manuscript
Synthesis of new low-viscous sulfonic acid-functionalized ionic
liquid and its application as a Brönsted liquid acid catalyst for the
one-pot mechanosynthesis of 4H-pyrans through the ball milling
process
Nader Ghaffari Khaligh, Taraneh Mihankhah, Mohd Rafie Johan
PII:
S0167-7322(18)34719-6
DOI:
Reference:
https://doi.org/10.1016/j.molliq.2019.01.024
MOLLIQ 10255
To appear in:
Journal of Molecular Liquids
Received date:
Revised date:
Accepted date:
13 September 2018
31 December 2018
4 January 2019
Please cite this article as: Nader Ghaffari Khaligh, Taraneh Mihankhah, Mohd Rafie Johan
, Synthesis of new low-viscous sulfonic acid-functionalized ionic liquid and its application
as a Brönsted liquid acid catalyst for the one-pot mechanosynthesis of 4H-pyrans through
the ball milling process. Molliq (2018), https://doi.org/10.1016/j.molliq.2019.01.024
This is a PDF file of an unedited manuscript that has been accepted for publication. As
a service to our customers we are providing this early version of the manuscript. The
manuscript will undergo copyediting, typesetting, and review of the resulting proof before
it is published in its final form. Please note that during the production process errors may
be discovered which could affect the content, and all legal disclaimers that apply to the
journal pertain.

ACCEPTED MANUSCRIPT
Synthesis of new low-viscous sulfonic acid-functionalized ionic liquid and its
application as a Brönsted liquid acid catalyst for the one-pot mechanosynthesis of 4H-
pyrans through the ball milling process
Nader Ghaffari Khaligha,, Taraneh Mihankhahb, Mohd Rafie Johana
a Nanotechnology and Catalysis Research Center,3rd Floor, Block A, Institute of Postgraduate Studies, University of Malaya,50603 Kuala Lumpur, Malaysia
b Environmental Research Laboratory, Department of Water and Environmental Engineering, School of Civil Engineering, Iran University of Science and
Technology, 16765-163, Tehran, Iran
ARTICLE INFO
ABSTRACT
In the present study, a new low-viscous sulfonic acid-functionalized ionic liquid (SAIL) viz.
4,4’-trimethylene-N,N’-sulfonic acid-dipiperidinium chloride was synthesized and characterized
by FTIR, 1D and 2D NMR, and Mass spectra. Then, some properties of new SAIL were
determined including pH, viscosity, density, and solubility in some common solvents. The
catalytic activity of new SAIL was demonstrated for the one-pot mechanosynthesis of
pyrano[4,3-b]pyrans, dihydropyrano[3,2-c]chromene and tetrahydrobenzo[b]pyrans using
planetary ball mill under solvent-free conditions. This current mechanosynthesis methodology
for the synthesis of 4H-pyran-annulated heterocyclic scaffolds displays a combination of the
synthetic virtues of conventional multi-component reaction with ecological benefits and
convenience of a simple mechanocatalytic procedure. New SAIL was easily recycled and reused
several times with no significant loss of activity.
Article history:
Received
Received in revised form
Accepted
Available online
Keywords:
Sulfonic acid-functionalized ionic liquid
Ball mill
Pyrano[4,3-b]pyran
Dihydropyrano[3,2-c]chromene
Tetrahydrobenzo[b]pyran
Metal and solvent-free conditions
1. Introduction
Ionic liquids (ILs) are interesting chemicals in chemistry research due to their diverse properties such as low volatility, thermal and
chemical stability which makes them appropriate catalyst/solvent for the working in both high-temperature and high-vacuum conditions.
ILs can often be separated from the desired organic products using a simple workup which lead to avoid high volumes of toxic and volatile
organic solvents. Their applications are continuing to grow exponentially in all fields of pure and applied chemistry due to their chemical
tenability, which allows different properties of ILs can tailor by an appropriate selection of anion/cation components and functional
groups. ILs are promising media in liquid-liquid extraction processes and electrochemical devices such as batteries, fuel cells, sensors,
and electrochromic windows. Owing to the high spectral transparency and good solvating properties of ILs, they can be suitable solvents
for spectroscopic measurements. ILs have also been applied in the lubricants, plasticizers, organic synthesis, mass spectroscopy,
manufacture nano-materials, and gas absorption [1-5]. Therefore, the design and synthesis of new ionic liquids and investigation of their
applications are attractive and growing [6-14].
Mechanochemistry has been developed as a clean approach to the chemical transformations which minimize using of toxic and volatile
organic solvents and reduce environmental pollution [15]. The milling process as a solid-state process plays a significant role in a solvent-
free organic synthesis which can lead to improvements including the reduced amount of catalyst loading, shorter reaction time, and higher
yield; furthermore, it fits well with the principles of green chemistry [16]. Planetary ball mills have been utilized in laboratories for the
———
 Corresponding author Tel.: +60-03-7967-6267; Fax: +60-03-7967-6956; E-mail: ngkhaligh@gmail.com and also ngkhaligh@um.edu.my

ACCEPTED MANUSCRIPT
2
synthesis of catalysts [17], metal complexes [18], Schiff bases [19,20], C–C bond formation reactions, the protection of the functional
groups, the preparation of the fullerenes, and redox processes [21].
4H-pyran-annulated heterocyclic scaffolds have been received the great attention of chemists both from the academic organizations
and pharmaceutical industries due to a wide array of biological activities, particularly against cancer [22]. Based on the in vitro, in vivo,
and in silico experiments, 4H-pyran scaffolds could be heterocycle candidates with potentially exploitable structures and diverse
biological properties for the development of new cytotoxic and anticancer agents [23]. Fused 4H-pyran derivatives such as pyrano[4,3-
b]pyrans constitute the core of valuable compounds exhibiting a broad spectrum medicinal and pharmacological properties including
antiviral and antileishmanial [24], anticonvulsant and antimicrobial [25], anti-HIV, antituberculosis, antifungal agents [26,27], antitumor
and antioxidant [28]. Therefore, a wide variety of catalysts were developed for the synthesis of these versatile and valuable compounds;
for example: [bmim][BF4] [24], NH4OAc [28], KF/Al2O3 [29], triethyl benzyl ammonium chloride [30], piperidine [31], magnesium oxide
[32], DBU [33], H6P2W18O62.18H2O [34], nano-eggshell/Cu(OH)2 [35], thiourea dioxide [36], 4-(succinimido)-1-butane sulfonic acid
[37], nano CaO [38], 1,1'-Butylenebis(3-methyl-3H-imidazol-1-ium) dihydrogen sulfate {[BBMIm](HSO4)2} [39], electro-catalysis [40]
and alum [41].
However, the aforementioned catalysts and their methodologies have some of drawbacks such as long reaction times, moderate yields,
expensive reagents, use of toxic and volatile organic solvents, and generate a waste containing metals and transition metal. Also, Lewis
acids are not desirable for the synthesis of pharmaceutical products owing to their toxicity [42].
In pursuit of our studies on the preparation of new SAILs and their applications as solvent or/and catalyst in the various organic
transformations [43-46], herein, a new low-viscous sulfonic acid-functionalized ionic liquid (SAIL) was designed and synthesized. The
1
1
1
structure of new SAIL was characterized by FTIR, H NMR, 13C NMR, H,1H-COSY, H,13C-HMBC, and Mass spectra as well as its
physical properties were determined. The Low viscosity, good conductivity, and the presence of two cation centers linked by alkyl spacer
along with two exchangeable anions are the most interesting features of the new SAIL, and related works are underway in our laboratory.
The catalytic efficiency of new SAIL was demonstrated for the synthesis of 4H-pyran-annulated heterocyclic scaffolds using ball milling
process. We are trying our best to investigate more reactions by using this new SAIL as a solvent or/and catalyst.
2. Results and Discussion
2.1. Synthesis of 4,4’-trimethylene-N,N’-sulfonic acid-dipiperidinium chloride [TMDPS] and the characterization of its structure
4,4’-trimethylene-N,N’-sulfonic acid-dipiperidinium chloride [TMDPS] was prepared through the treatment of 4,4’-trimethylene-
dipiperidine [TMDP] with two equivalents of neat chlorosulfonic acid in CH2Cl2 and the mixture was stirred at 50 °C overnight. The
resulting ionic liquid was isolated as a low-viscous pale yellow liquid which its structure was characterized by FTIR, 1H and 13C NMR,
1H,1H-COSY, 1H,13C-HMBC, and Mass spectra.

ACCEPTED MANUSCRIPT
Cl
Cl
Neat ClSO3H
HO3S
SO3H
HN
NH
N
H
N
H
CH2Cl2, 50 oC, overnight
TMDP
TMDPS
Scheme 1. Synthesis of 4,4’-trimethylene-N,N’-sulfonic acid-dipiperidinium chloride [TMDPS].
FTIR spectrum of TMDPS is presented in Fig. 1 (see Fig. 1 in Supplementary Material). The broad absorption centered at range 3391
cm−1 is assigned to hydrogen bonds of the hydroxyl groups and quaternary ammonium probably corresponding to O–H and NH+ stretching
vibration along with the moisture absorbed by TMDPS. The band at 3035 cm−1 probably corresponds to the N+H· · ·O stretching vibration
[47] and the C–H stretching vibrations were observed at 2928 cm−1, and 2851 cm−1 [48,49]. Two well defined IR bands were observed in
the regions 2520 cm−1 and 1622 cm−1 which could be arisen from proton tunneling and Fermi resonance interactions with the
overtones/combinations of hydrogen-bonded OH bending modes in a strongly hydrogen bonded system with >NH+‒O2S‒OH grouping
[50]. The band appeared at the region 2520 cm−1 and 1622 cm–1 were assigned to the NH+ stretching band and NH+ deformation vibration
of quaternary ammonium, respectively [47,51].
The identification of C–N stretching frequency is a difficult task since the mixing of bands is possible in this region; hence, the IR
band at 1455 cm−1 have been designated to C–N stretching modes of vibrations [52]. The asymmetric and symmetric vibrations of SO2
were observed at range 1300-1000 cm−1 [50]. The sharp peaks at 1283 cm−1, 1174 cm−1, and 1044 cm−1 can be assigned to the C–N
stretching vibration of piperidine ring and S–O bend of sulfonic groups, respectively. The S–N stretching vibration was observed in the
region 955 cm−1 and 865 cm−1 as a series of the medium intensity bands [46]. The bands at 734 cm−1 and 581 cm−1 have been designated
to ring deformation out-of-plane-bending. The C–H out-of-plane-bending peak and the C–H in plane-bending were observed at 734 cm−1
[53]. The presence of νS-O(H) as a sharp band and the δNH modes confimed the structure >NH+‒SO2‒OH for TMDPS.
In 1H NMR spectrum of TMDPS, the acidic hydrogen of sulfonic acid moieties gave two broadened singlets centered at 8.74, 8.73
ppm and NH+ appeared as one apparent doublet at 8.48 ppm with a large coupling constant 11.4 Hz. Their chemical shifts indicate that
these hydrogens were less involved in H-bonding in DMSO-d6 (see Fig. 2 in Supplementary Material). According to the analysis of
chemical shifts and coupling constants (vide infra), the piperidinium cation of the TMDPS assumes a chair conformation and the sulfonic
acid groups and protons of NH+ are in the equatorial and the axial position, respectively [54,55]. Signals in 1H NMR spectra were assigned
based on the cross-peaks in 2D measurements (1H,1H-COSY); nevertheless, severe overlapping of several signals prevented their complete
assignment and only a few coupling constants could be accurately measured. In piperidinium ring, chemical shifts for equatorial hydrogens
are found downfield of the axial counterpart owing to shielding or deshielding, respectively, caused by the magnetic anisotropy of ring
bonds for chair conformations [56,57]. Therefore, the equatorial (eq) hydrogens of C-2, C-2’, C-6, and C-6’ were assigned to a well-
resolved doublet at 3.19 ppm with a large coupling constant 12.2 Hz. The resonance of the axial (ax) hydrogen of C-2, C-2’, C-6, and C-
6’ appeared as an apparent quartet at 2.79 ppm with large constant coupling 11.4 and 11.2 Hz due to the geminal and ax-ax couplings to
the C-2(eq) and C-3(ax) hydrogens, respectively. The apparent doublet signal at 1.74 ppm was assigned to the H-eq of C-3, C-3’, C-5,
and C-5’ with large constant coupling 13.4 Hz. A broadened multiplet at 1.50-1.43 ppm was attributed to axial position of C-4 and C-4’

ACCEPTED MANUSCRIPT
4
protons. The H-ax of C-3, C-3’, C-5, and C-5’ along with hydrogens of trimethylene moiety were observed at 1.30-1.22 and 1.18-1.14
ppm.
13C NMR spectrum of TMDPS exhibits one signal for each of 13 carbon atoms regarding molecular symmetry with chemical shifts
43.7 ppm for C-2, C-2’, C-6, C-6’; 28.8 ppm for C-3, C-3’, C-5, C-5’; 35.9 ppm for C-4,C-4’ (see Fig. 3 in Supplementary Material). The
central and lateral carbons of trimethylene moiety were displayed at 33.2 ppm and 23.0 ppm, respectively.
1H,1H-COSY measurement of TMDPS and the analysis of the coupling pattern showed that signal at 8.48 ppm belonged to NH+ protons
which exhibited a correlation with axial and equatorial hydrogens of C2, C2', C6, C6' at 3.19 ppm and 2.79 ppm, and acid hydrogen of
sulfonic acid group at 8,74 ppm and 8.73 ppm, respectively. The acidic protons of N‒SO3H moieties showed a weak correlation with H-
ax and H-eq of C2, C2', C6, C6', H-eq of C3, C3', C5, C5', and NH+ at 3.19 ppm, 2.79 ppm, 1.74 ppm, and 8.48 ppm, respectively (see
Fig. 4 and 5 in Supplementary Material).
The hydrogen signals of CH-2,2’,6,6’(eq) showed the HMBCs correlation with C-α, C-3, and C-2 at δC 28.74, 33.23, and 43.74 ppm
with low, high, and high intensities, respectively. The protons of CH-2,2’,6,6’(ax) exhibited the HMBCs correlation with C-α, C-3, at δC
28.74, and 33.23 ppm with low intensity (see Fig. 6 in Supplementary Material). The HMBC correlations of the hydrogen signals of CH-
3,3’,5,5’(eq) with C-3, C-α, and C-4 were observed at δC 28.74, 33.23, and 35.93 ppm with high, high, and low intensities, respectively.
The protons of CH-4,4’(ax) exhibit the HMBC correlations with C-β, C-3, C-4, and C-2 at δC 23.01, 28.74, 35.93, and 43.74 ppm with
high intensities.
The hydrogens of CH2-α, CH2-β and CH-3,3’,5,5’(ax) displayed the HMBC correlations with all carbons in TMDPS; however, no the
HMBC correlation was observed with Cα and C-2 at ranges 1.30-1.24 ppm and 1.18-1.14 ppm, respectively. The chemical shifts and
the coupling constants are displayed in Table 1 (Scheme 2).
Cl
Cl

'
'
2
2
4
4
'
3
3
HO3S
SO3H
6
6
'
5
N
H
5
N
H


'
Scheme 2. The elucidated structures of TMDPS based on the 2D NMR experiments.
Table 1. The structure data of TMDPS in DMSO-d6.
Atom
δH (ppm)
8.74 and 8.73
8.48
J (Hz)
br s
d, 11.4
δC (ppm)
-
-
‒SO3H
NH+
CH-2, CH-2’, CH-6 and CH-6’(eq)
CH-2, CH-2’,C H-6 and CH-6’(ax)
CH-3, CH-3’, CH-5 and CH-5’(eq)
CH-3, CH-3’, CH-5 and CH-5’(ax)
CH-4 and CH-4’
3.19
2.79
1.74
1.30-1.22
1.50-1.43
1.30-1.22 and 1.18-1.14
1.30-1.22 and 1.18-1.14
d, 12.2
q, 11.4 and 11.2
d, 13.4
m
m
m
m
43.7
43.7
28.74
28.74
35.93
33.28
23.01
CH2-α
CH2-β

ACCEPTED MANUSCRIPT
+
The cations of C13H27N2O6S2 and C13H27N2O6S2Na+ were detected at m/z 371.13 and 393.12 by positive ion mode LC-ESI-MS for
TMDPS.
2.2. The physical properties of TMDPS
TMDPS is a room temperature ionic liquid and showed any signs of crystallization, even well below −4 °C. The density of TMDPS
was determined 1.04 g/mL at 27.00 ± 0.02 °C using a Mettler Toledo DM45 Deltarange Density meter. Density measurement of TMDPS
was conducted at range 25-90 °C and the temperature dependence of the density for TMDPS is graphically depicted in Fig. 7 (See
Supplementary Material). The calibration was performed using doubly distilled and degassed water and dried air at atmospheric pressure.
The viscosity plays a crucial role in a practical and reliable design, analysis, and optimization of processes including mixing,
separations, flow chemistry, heat exchangers, pipelines, and distillation columns [58,59]. In most cases, ILs are viscous and their
viscosities can be even several orders of magnitude higher than those of water and organic solvents. This unfavorable property is one of
the drawbacks to successful applications of ILs in chemical technology and engineering. Therefore, for the future development of ionic
liquid science and consequently greener technologies, research on the discovery of new low-viscous ILs is highly demanded.
The viscosity of TMDPS was measured 14.1 ± 0.2 mPa s (cP) using a Brookfield DV-III Ultra Viscometer at 27.00 ± 0.02 °C under
ambient pressure. The viscosity measurement of TMDPS was performed at range 25-90 °C and the temperature dependence of the
viscosity for TMDPS is graphically depicted in Fig. 8 (see Supplementary Material).
The ionic conductivity (σ) of neat TMDPS was measured 1.82 mS cm−1 using a Mettler Toledo Seven Easy conductivity meter at 25
°C.
The ILs absorb moisture from the atmosphere during storage; therefore, TMDPS was dried before the determination of its total water
content. The total water content of TMDPS was determined 0.22 ± 0.02 wt. %. by Karl Fisher (KF) titration using a Metrohm 831 KF
coulometer in conditions of ambient humidity and temperature. The conditions of temperature, pressure and drying time were 100 °C, 80
mbar and 12 h, respectively.
The several 0.01 molar solutions of TMDPS was prepared in the deionized water, and the pH readings were recorded 2.1 ± 0.1 using
a pH meter F-71, LAQUA-HORIBA Scientific at 27 ± 1°C. The standard deviations were obtained from three replicate determinations
on the different three days.
The new ionic liquid TMDPS was soluble in water, methanol, ethanol, acetonitrile, and acetic acid while was immiscible with ethyl
acetate, n-hexane, and toluene.
2.3. Thermal stability of TMDPS
The thermal behavior of TMDPS is showed as DSC plot at the temperature range 30-500 °C in Figure 9 (See Supplementary Material).
The baseline was shifted in the endothermic direction due to the decreasing heat capacity of the sample. In nitrogen atmosphere, three
endothermic peaks centered around 130 °C, 270 °C, and 310 °C were recorded on the DSC curves of TMDPS and no exothermic peak
was observed. The first endothermic peak from 82.7 °C to 146.1 °C was attributed to liberate of the adsorbed water and the chemically

ACCEPTED MANUSCRIPT
6
bound hydrogen chloride in the TMDPS sample. The DSC profile indicates that the decomposition of TMDPS include two steps which
the first step as main stage occurred at 269.9 °C with heat of decomposition 281.61 J g−1 (124.87 KJ mol−1) and the second stage began at
293.8 °C with heat of decomposition 21.29 J g−1 (9.44 KJ mol−1), while the tailing ended at 312.5 °C.
TGA/DTG curve of TMDPS is presented in Fig. 10 (See Supplementary Material). Four peaks were visible on DTA curve and TMDPS
decomposition goes in three stages according to TGA/DTG curve. DTA curve of TMDPS obtained by analysis in nitrogen atmosphere
shows a broad peak below 150 °C centered at 59.5 °C which were attributed to elimination of inherent moisture and physically adsorbed
water as well as the chemically bound hydrogen chloride in TMDPS. The first onset of temperature decomposition of TMDPS was
observed at 262.05 °C, and its thermal decomposition ended at 262.96 °C which was very compatible to the DSC result. The second and
third stages of decomposition were display at 289.45 °C and 433.59 °C, respectively. The maximum mass loss was 98.54% that was
related to the total decomposition of piperidine and sulfonic acid fragments of TMDPS. At 263-434 °C, the decomposition of TMDPS
was practically completed. The thermal stability of ionic liquids plays very important role when their reactions need to perform at high
temperature. All the preceding results showed that TMDPS is thermally stable even at relatively high temperatures and its thermal stability
could be a consequence of the presence of hydrogen bonds and electrostatic interactions between ‒NH+ and ‒SO3H groups in the TMDPS.
2.4. Synthesis of pyrano[4,3-b]pyrans in the presence of TMDPS
Initially, the optimum reaction conditions were investigated using the condensation of 4-chlorobenzaldehyde (1a), 4-hydroxy-6-
methyl-2-pyrone (A), and malononitrile as a model reaction (Scheme 3).
Cl
Cl
OH
O
Various parameters
+
CN
+
NC
O
CN
H3C
O
O
H3C
O
NH2
H
O
1a
A
2aA
Scheme 3. The study of optimal reaction parameters and conditions.
The model reactants were ground at room temperature using a planetary ball mill in the absence of a catalyst under solvent-free
conditions. The 2-Amino-4-(4-chlorophenyl)-7-methyl-5-oxo-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile (2Aa) was not observed after 4
h (monitored by GC-MS) (Table 2, entry 1). Then, TMDPS was added to the model reactants and the reaction mixture was milled at room
temperature for 4 h. The deionized water was added to the mixture and TMDPS was washed from the grinding jar, then the desired product
was separated by simple filtration. The ionic liquid was recovered through the evaporation of the water and used for the next run. The
residue was washed from the grinding jar with hot ethanol and 2Aa was obtained in 86% yield after crystallization (Table 2, entry 2). No
significant difference in yield was observed when the reaction time was curtailed to 1 h (Table 2, entry 3). The yield dropped to 65%

ACCEPTED MANUSCRIPT
when the reaction time was reduced to 30 min (Table 2, entry 4). Decreasing the SAIL loading to 5 mol% led to only a slight drop in yield
2Aa (Table 1, entries 5 and 6) while more decreasing the SAIL loading to as low as 2 mol% decreased yield to 55% (Table 2, entry 7).
Then, the influence of technical parameters such as revolution per minute (r.p.m.), size and number of ball mill on performing the
model reaction investigated. The results displayed that the r.p.m. has a crucial influence on the yield of the desired product and the best
yield of 2Aa obtained at 600 rpm after 30 min (Table 2, entries 8-12). At entry 8-10, the milling time was screened to find the optimal
milling time while other parameters were kept constant. As shown in Table 2, the decrease of milling time to 30 min led to no drop in
yield of 2Aa. The shorter milling time led to a significant drop in yield of the desired product (Table 2, entry 10).
The size and the number of milling balls were changed while other parameters kept constant. As expected, a higher yield of 2Aa was
observed when experiments were carried out with a larger size and higher number of balls (Table 2, entries 13 and 14). As reported in the
literature, these parameters directly influence the active surface area and the total mass of the milling balls [60].
Table 2. Optimization of the synthesis of pyrano[4,3-b]pyrans under a variety of reaction conditions.a
Entry
1
Loading TMDPS (mol%)
Number of ball mill
Speed (rpm)
300
Ball mill diameter (mm)
Milling time (min)
Yield (%)b
-
c
0
4
4
4
4
4
4
4
4
4
4
4
4
4
2
7
7
7
7
7
7
7
7
7
7
7
7
5
7
240
240
60
30
60
60
60
60
30
20
30
30
30
30
2
3
4
5
20
20
20
10
5
300
300
300
300
86
84
65
84
82
55
92
92
76
88
67
48
46
6
300
7
2
300
8
5
600
9
5
600
10
11
12
13
14
5
5
5
5
600
500
400
600
5
600
a Reaction conditions: 4-chlorobenzaldehyde (1a) (1.0 mmol), 4-hydroxy-6-methyl-2-pyrone (A) (1.0 mmol), malononitrile (1.0 mmol),
room temperature.
b Isolated yield.
c Monitored by GC-MS.
The scope and generality of the present protocol for the preparation of pyrano[4,3-b]pyran derivatives was evaluated through the
condensation of various aldehydes 1(a-o), 4-hydroxy-6-methyl-2-pyrone (A), and malononitrile under optimized reaction conditions
based on entry 9 in Table 2 (Scheme 4).
OH
O
R
CN
R
TMDPS (5 mol%)
O
+
+
O
NC
H
O
Ball mill (600 rpm), r.t., 30 min
CN
H3C
O
H3C
O
NH2
1(a-o)
A
2A(a-o)
Scheme 4. Synthesis of pyrano[4,3-b]pyran derivatives in the presence of TMDPS under optimal conditions.
The aldehydes bearing electron withdrawing and electron donating substituents gave the desired pyrano[4,3-b]pyran in good to
excellent yields (Table 3). Aldehydes bearing electron withdrawing substituents afforded a slightly higher yield of pyrano[4,3-b]pyran
than electron donating substituents at same position probably due to increased carbonyl group electrophilic property (Table 3, entries

ACCEPTED MANUSCRIPT
8
1,5,12,13 vs 3,4,7). The methoxybenzaldehydes as acid sensitive aldehydes also afforded the desired product in good yield with no
decomposition under the optimized reaction conditions (Table 3, entries 7,9,10).
Table 3. The one-pot multicomponent synthesis of pyrano[4,3-b]pyran derivatives in the presence of TMDPS under optimized
reaction conditions.a
Entry
Aldehydes 2(a-o)
Pyrano[4,3-b]pyran 2A(a-o)
Yield (%)b
Melting point (°C)
Found
Reported (ref.)
1
2
3
4
5
6
7
8
4-Cl-C6H4-
C6H5-
2Aa
2Ab
2Ac
2Ad
2Ae
2Af
2Ag
2Ah
2Ai
2Aj
2Ak
2Al
2Am
2An
2Ao
92
85
88
86
92
87
90
89
84
82
90
91
92
89
92
219-221
246-248
226-228
220-222
216-218
212-214
205-207
258-260
242-244
227-229
219-221
217-219
220-222
240-241
245-247
228-230 (61)
236 (61)
218-220 (61)
-
220-222 (61)
-
210-212 (39)
270-272 (62)
4-CH3-C6H4-
4-(CH3)2CH-C6H4-
4-NO2-C6H4-
3,5-Cl2-C6H4-
4-(CH3O)-C6H4-
2-Cl-C6H4-
2-(CH3O)-C6H4-
3,4,5-(CH3O)3-C6H2-
4-Br-C6H4-
4-CF3-C6H4-
4-F-C6H4-
3,5-F2-C6H3-
3,5-(CF3)2-C6H4-
9
-
10
11
12
13
14
15
235-237 (62)
217-219 (39)
-
223-225 (24)
-
-
a Reaction conditions: aldehyde 1(a-o) (1.0 mmol), hydroxy-6-methyl-2-pyrone (A) (1.0 mmol), malononitrile (1.0 mmol), TMDPS (0.05
mmol), four ball mill with diameter 7 mm, revolution rate (600 rpm), room temperature, milling time (30 min).
bIsolated yield.
In continue of the promising catalytic efficiency of TMDPS, we encouraged to evaluate its catalytic performance towards the synthesis
of dihydropyrano[3,2-c]chromene derivatives and tetrahydrobenzo[b]pyrans under the aforementioned optimal reaction conditions. For
this goal, the various aryl aldehydes with electron withdrawing and electron releasing groups 1(a-l) and malononitrile were subjected to
the reaction with 4-hydroxycoumarin (B) and dimedone (C). The dihydropyrano[3,2-c]chromenes (Scheme 5, Table 4) and
tetrahydrobenzo[b]pyran derivatives (Scheme 6, Table 5) were obtained in good to excellent yields at room temperature at 600 rpm under
solvent-free conditions after 30 min milling time.
OH
O
O
R
O
CN
R
TMDPS (5 mol%)
O
+
+
NC
H
O
Ball mill (600 rpm), r.t., 30 min
CN
O
NH2
1(a-l)
B
2B(a-l)
Scheme 5. Synthesis of dihydropyrano[3,2-c]chromene derivatives in the presence of TMDPS under optimal reaction conditions.
Table 4. The one-pot multicomponent synthesis of dihydropyrano[3,2-c]chromene derivatives in the presence of TMDPS under
optimized reaction conditions.a
Entry
Aldehydes 2(a-n)
Dihydropyrano[3,2-c]chromene 2B(a-
Yield (%)b
Melting point (°C)
l)
Found
Reported (ref.)
1
2
3
4
5
6
7
8
4-Cl-C6H4-
C6H5-
2Ba
2Bb
2Bc
2Bd
2Be
2Bf
2Bg
2Bh
2Bi
2Bj
2Bk
2Bl
94
84
87
85
92
88
91
88
96
85
92
92
262-264
254-256
249-251
242-244
259-261
261-263
244-245
266-268
258-259
269-271
228-230
248-250
265-266 (63)
248-250 (63)
254-255 (63)
237-239 (64)
250-252 (64)
265-267 (64)
251-253 (65)
262-265 (66)
257-259 (67)
275-277 (68)
252-254 (69)
252-254 (65)
4-CH3-C6H4-
4-(CH3O)-C6H4-
4-NO2-C6H4-
4-OH-C6H4-
4-(CH3)2CH-C6H4-
2-Cl-C6H4-
2-NO2-C6H4-
3,4,5-(CH3O)3-C6H2-
4-Br-C6H4-
9
10
11
12
4-CF3-C6H4-

ACCEPTED MANUSCRIPT
a Reaction conditions: aldehyde 1(a-l) (1.0 mmol), 4-hydroxycoumarin (B) (1.0 mmol), malononitrile (1.0 mmol), TMDPS (0.05 mmol),
four ball mill with diameter 7 mm, revolution rate (600 rpm), room temperature, milling time (30 min).
bIsolated yield.
OH
O
R
O
CN
R
TMDPS (5 mol%)
+ H3C
H3C
+
NC
H
O
Ball mill (600 rpm), r.t., 30 min
CN
O
NH2
CH3
CH3
1(a-l)
C
2C(a-l)
Scheme 6. Synthesis of tetrahydrobenzo[b]pyran derivatives in the presence of TMDPS under optimal reaction conditions.
Table 5. The one-pot multicomponent synthesis of tetrahydrobenzo[b]pyran derivatives in the presence of TMDPS under
optimized reaction conditions.a
Entry
Aldehydes 2(a-n)
Tetrahydrobenzo[b]pyran 2C(a-l)
Yield (%)b
Melting point (°C)
Found
Reported (ref.)
1
2
3
4
5
6
7
8
4-Cl-C6H4-
C6H5-
2Ca
2Cb
2Cc
2Cd
2Ce
2Cf
2Cg
2Ch
2Ci
2Cj
2Ck
2Cl
96
92
88
85
96
90
90
89
88
85
94
96
214-216
224-226
205-207
197-199
182-184
204-206
178-180
215-217
198-200
200-202
197-199
217-219
215-216 (63)
225-226 (63)
211-212 (63)
200-201 (63)
185-186 (63)
206-208 (70)
177-178 (63)
216-217 (63)
200-201 (63)
208-210 (65)
205-207 (65)
218-219 (63)
4-CH3-C6H4-
4-(CH3O)-C6H4-
4-NO2-C6H4-
4-HO-C6H4-
4-CH3(CH2)4O-C6H4-
2-Cl-C6H4-
2-(CH3O)-C6H4-
3,4,5-(CH3O)3-C6H2-
4-Br-C6H4-
9
10
11
12
4-CF3-C6H4-
a Reaction conditions: aldehyde 1(a-l) (1.0 mmol), dimedone (C) (1.0 mmol), malononitrile (1.0 mmol), TMDPS (0.05 mmol), four ball
mill with diameter 7 mm, revolution rate (600 rpm), room temperature, milling time (30 min).
bIsolated yield.
The results of experiments on the synthesis of pyrano[4,3-b]pyrans, dihydropyrano[3,2-c]chromenes, and tetrahydrobenzo[b]pyrans
exhibits that TMDPS can be an efficient sulfonic acid-functionalized ionic liquid catalyst for the multicomponent reactions.
A possible mechanism is illustrated in scheme 7. Initially, the aldehyde and 1,3-diketone are activated by TMDPS to promote the
reaction. A nucleophilic attack from 1,3-diketone to activated aldehyde provide intermediate (I). TMDPS can act as an efficient
dehydrating agent and help the dehydration of the intermediate (I) [71] which give Knoevenagel intermediate (II). In the next step, the
knoevenagel intermediate (II) reacts with the activated malononitrile by anion part of TMDPS as a Michael acceptor which produces the
intermediate (III). Then, an intramolecular nucleophilic attack from the oxygen atom to nitrile group followed by tautomerization will
give the desired product.
Cl
Cl
Cl
Cl
Cl
Cl
HO3S
SO3H
HO3S
SO3H
HO3S
SO3
N
H
N
H
N
H
N
H
N
H
N
H
H2O
TMDPS
H
H
TMDPS
H
TMDPS
H2O

ACCEPTED MANUSCRIPT
10
TMDPS
TMDPS
H
TMDPS
H
H
H
TMDPS
O
H
O
TMDPS
H2O
O
H
O
H
O
R
H
N
OH
O
H
H
O
R
N
R
O
O
(I)
(II)
O
R
O
O
R
O
R
H
N
N
CN
NH2
NH
O
H
O
N
(III)
H
TMDPS
Scheme 7. A possible mechanism illustrated for the one-pot multicomponent reactions in the presence of TMDPS.
This current method was compared with the methods reported in the literature as shown in Tables 6-8. Each of these methods has its
advantages, while some still have one or more limitations and drawbacks such as tedious procedures in the preparation of catalyst and
separation product/catalyst in the work up step, use of the expensive catalysts or catalysts containing metal/transition metal, conduct the
reactions at high temperature for the long reaction time along with a low yield of products, un-recyclability of catalyst, generate the metal
wastes, a high catalyst loading, etc.
For example, 2Aa, 2Bb, and 2Cd were obtained in 93%, 81%, and 87% yield in the presence of 10 mol% urea at room temperature in
aqueous ethanol after 7 h, 3 h, and 9 h, respectively [65]; whereas, the same products were afforded in 92%, 84%, and 85% yield under
optimized reaction conditions via the current method (Table 6,7, and 8).
The 2Aa was obtained in 77% yield in the presence of 1 mol% of 1,1,3,3-N,N,N’,N’-tetramethylguanidinium trifluoroacetate (TMGT)
at 100 °C within 60 min [66], while the identical product was isolated in 85% yield at room temperature after 30 min by the new
methodology.
Also, the product 2Aa was afforded in 89.2% yield within 10 h in the presence of 120 unit of porcine pancreas lipase at room
temperature [72], whereas the same reaction gave a 90% yield for 2Aa at room temperature in the presence of 10 mol% TMDPS after 30
min milling time under solvent-free conditions.
The commercially available catalysts such as thiourea dioxide (formamidinesulfinic acid) (Table 6, entry 4) and piperidine (Table 6,
entry 5) requires safe handling and storage due to their self-heating, highly flammablility, and toxicity, respectively [31,36]. Furthermore
, the model reactants were ground using mortar and pestle in the presence of NH4OAc (10 mol%) at room temperature for 14 min [28]
which afforded 2Aa in 32% yield. The desired product 2Aa was isolated in 54% yield after workup when the identical reaction was

ACCEPTED MANUSCRIPT
carried out under optimal conditions of the current protocol viz. NH4OAc (5 mol%), room temperature, speed of ball milling (600 rpm),
milling time (30 min).
Table 6. The comparison of the present protocol with other reported strategies for the synthesis of 2-amino-4-phenyl-7-methyl-5-
oxo-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile.
Entry
Catalyst
Catalyst loading (mol%)
Conditions
Time (min)
Yield (%)
Ref.
1
2
3
[BMIM][BF4]
[NH4][OAc]
KF-Al2O3
664
10
80 °C
180
85
94
76a
24
28
29
Solvent-free, grinding, r.t.
EtOH, reflux
10
100 mg per 2.0 mmol 4-
480a
chlorobenzaldehyde
4
Piperidine
1-2 drops per 1.0 mmol
MeOH, reflux
60
79
31
benzaldehyde
5
6
7
8
Thiourea dioxide
4-(Succinimido)-1-butane sulfonic acid
[BBMIm][HSO4]
10
4.2
120.5
10
H2O, 80 °C
Neat, 60 °C
Solvent-free, 60 °C
Solvent-free, 60 °C (Solar
energy)
40
60
35
35
92
88
94
94
36
37
39
61
Succinimide-N-sulfonic acid
9
Urea
TMGT
Porcine pancreas lipase
-
10
1.0
120 U
-
EtOH:H2O (1:1 v/v), r.t.
Solvent-free, 100 °C
i-Propanol, 60 °C
H2O, 80 °C
420
60
600
630
30
81
77
89
65
85
65
66
72
73
10
11
12
13
TMDPS
5
Ball milling, r.t.
This work
a2-Amino-4-(4-chlorophenyl)-7-methyl-5-oxo-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile.
Abbreviative: TMGT = 1,1,3,3-N,N,N’,N’-tetramethylguanidinium trifluoroacetate
The product 2Bf was produced in 88% yield at 100 °C after 34 min in the presence of 6 mg bisferrocene-containing ionic liquid
supported on silica coated Fe3O4 per mmol of reactants [69], while 2Bf was isolated in 88% yield at room temperature after 30 min the
by the current protocol (Table 7, entry 1). In addition, Fe3O4@-SiO2@imidazol-bisFc[HCO3] was prepared through a tedious and multi-
step process and the aggregation can cause the rapid loss of catalytic activity.
The product 2Ba was obtained in 94% yield within 5 min in the presence of 20 mol% of DMAP and ethanol under reflux conditions
[74], whereas the same reaction in the presence of 5 mol% TMDPS gave 94% yield after 30 min milling time at room temperature under
solvent-free conditions (Table 7, entry 7).
In comparison with other catalysts such as DBU [33], urea [65], tetrabutylammonium bromide [75], Diammonium hydrogen phosphate
and S-proline [76], Potassium phthalimide-N-oxyl [77], H6P2W18O62•18H2O [79], and triethylenetetraammonium trifluoroacetate [81]
which were reported in the synthesis of 2Ba, TMDPS shows more catalytic efficiency in terms of reaction time, catalyst loading, use of
solvent, or temperature (Table 7, entries 1,2,6-8, 10,12).
Table 7. The comparison of the present protocol with other reported strategies for the synthesis of 2-amino-4-phenyl-5-oxo-
4H,5H-pyrano[3,2-c]chromene-3-carbonitrile.
Entry
Catalyst
Catalyst loading (mol%)
Conditions
Time (min)
Yield (%)
Ref.
1
2
3
DBU
Urea
10
10
6 mg
H2O, reflux
EtOH:H2O (1:1 v/v), r.t.
Solvent-free, 100 °C
7
360
23
92
91
87
33
65
69
Fe3O4@SiO2@imidazol-
bisFc[HCO3]
Starch solution
DMAP
4
5
6
4 mL per mmol of aldehyde
20
10
Starch solution, 50 °C
EtOH, reflux
H2O, reflux
Solvent-free, 120 °C
EtOH:H2O (1:1 v/v), r.t.
EtOH:H2O (1:1 v/v), reflux 180
H2O, reflux
H2O, 30 °C
EtOH:H2O (1:1 v/v), reflux 30
EtOH, r.t. 90
25
5
45
44
240
95
94a
91
88
81
72
97
93
89
87
70
74
75
Tetrabutylammonium bromide
7
Diammonium hydrogen phosphate
S-proline
Potassium phthalimide-N-oxyl
Zinc ferrite
H6P2W18O62•18H2O
Amberlyst A21
10
10
5
76
8
9
10
11
12
180
77
78
79
80
40 mg per mmol aldehyde
1
30 mg per 1 mmol aryl
aldehyde
12
13
[TETA][TFA]
TMDPS
5
5
EtOH:H2O (1:1 v/v), reflux 20
Ball milling, r.t. 30
86
84
81
This work

ACCEPTED MANUSCRIPT
12
a Aryl aldehyde was 4-chlorobenzaldehyde
Abbreviates: Fe3O4@SiO2@imidazol-bisFc[HCO3] = Nanomagnetic bisferrocene-containing ionic liquid supported on silica coated
Fe3O4; DBU = 1,8-Diazabicyclo[5.4.0]undec-7-ene; DMAP = 4-(dimethylamino)pyridine; [TETA][TFA] = triethylenetetraammonium
trifluoroacetate
In comparison with the reported catalysts such as urea [65], 2,2,2-trifluoroethanol [82], and [BMIM]Br [83] for the synthesis of 2-
amino-7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-benzopyran-3-carbonitrile (2Cb), our protocol showed the comparative
yields at shorter reaction time (Table 8). Furthermore, this current methodology showed superiority to the reported reports such as DMAP
[74], Potassium phthalimide-N-oxyl [77], triethylenetetraammonium trifluoroacetate [81], 2,2,2-trifluoroethanol [82], Phenylboronic acid
[84], Thiamine hydrochloride [86], and [H2-DABCO][H2PO4]2 [87] in term of the reaction temperature.
The reaction catalyzed by 28 mol% taurine (2-aminoethanesulfonic acid) in water afforded 2Cb in 82% yield under reflux conditions
after 65 min [88], while the 2Cb was obtained in 84% yield under optimal conditions by new developed methodology (Table 8, entry 12).
In addition, the 2Cd was afforded in 78% yield in the presence of Amberlyst A21 (30 mg per mmol aldehyde) in ethanol at room
temperature after 90 min [80], and the 2Cd was isolated in 85% yield after 30 min milling time at room temperature using the new
protocol under solvent-free conditions.
Table 8. The comparison of the present protocol with other reported strategies for the synthesis of 2-amino-7,7-dimethyl-5-oxo-
4-phenyl-5,6,7,8-tetrahydro-4H-benzopyran-3-carbonitrile.
Entry
Catalyst
Urea
DMAP
Potassium phthalimide-N-oxyl
Amberlyst A21
[TETA]TFA
Catalyst loading/mol%
10
20
5
30 mg per mmol aldehyde
5
2 mL per mmol of aldehyde
Conditions
EtOH:H2O (1:1 v/v), r.t.
EtOH, reflux
H2O, reflux
EtOH, r.t.
Time/min
360
15a
15
60
Yield/%
91
Ref.
65
74
77
80
81
82
1
2
3
4
5
6
94a
95
87
85
90
EtOH:H2O (1:1 v/v), reflux
2,2,2-trifluoroethanol, reflux
20
300
2,2,2-Trifluoroethanol
7
8
9
10
11
12
[BMIM]Br
Phenylboronic acid
Fructose
Thiamine hydrochloride (VB1)
[H2-DABCO][H2PO4]2
Taurine
25
5
20
10
16
28
EtOH:H2O (1:1 v/v), r.t.
EtOH:H2O (1:1 v/v), reflux
EtOH:H2O (1:2 v/v), 40 °C
EtOH, reflux
EtOH:H2O (2:1 v/v), reflux
H2O, reflux
24-30 h
30
45
15
12
65-96
88
86
90
90
83
84
85
86
87
88
65
82
(2-aminoethanesulfonic acid)
TMDPS
13
5
Ball milling, r.t.
30
92
This work
a Aryl aldehyde was 4-chlorobenzaldehyde
Abbreviates: Fe3O4@Ph-SO3H = magnetic iron oxide supported phenylsulfonic acid; [TETA]TFA = Triethylenetetraammonium
trifluoroacetate; SiO2-Pr-SO3H = silica based sulfonic acid
The feasibility of the present method on gram scaled experiment was investigated through the condensation of 4-chlorobenzaldehyde
(10 mmol), malononitrile (10 mmol), and 4-hydroxycoumarin (10 mmol) using 5 mol% TMDPS at room temperature under optimized
reaction conditions which afforded the desired product, 2-amino-5-oxo-4-phenyl-4,5-dihydropyrano[3,2-c]-chromene-3-carbonitrile
(2Ba) in 81% isolated yield within 30 min, almost identical in all respects with mmol scale entry.
It is well-known that the chemical structure of the cations and anions determined the physical and chemical properties. In addition,
the catalytic activity of ionic liquids is related to the interaction between the functional and acceptor/donner hydrogen bond groups on the
cation or anion moieties of ionic liquids with reactants. The chemists often change the chemical structure of ionic liquids through insert
new functional groups and investigate the modification effects on their physical and chemical properties as well as their catalytic activity
in the model reaction under identical conditions [89]. This process can be one of attempting to understand and reveal how properties

ACCEPTED MANUSCRIPT
relevant to catalytic activity of ionic liquid are encoded by the chemical structure cation and anion. This can allow the chemist to
design and change the structure of cation/anion or functional groups of ILs which lead to new ILs with desired physical and chemical
properties and catalytic activities. Herein, the catalytic efficiency of di-cationic ionic liquids containing di-sulfonic groups along with
−
nonacidic (Cl−) and acidic (HSO4 ) counter anion was compared with new SAIL to the synthesis of 2Aa, 2Ba and 2Ca under
aforementioned optimized conditions (Table 9). The sulfonic acid-functionalized imidazolium ionic liquids were prepared according to
the literature [46].
Table 9. Comparison of the result obtained for the synthesis of 2Aa, 2Ba, and 2Ca in the presence of some sulfonic-functionalized
ionic liquid containing di-cationic nucleus with carbon spacer.a
Entry
IL as solvent-catalyst
Abbreviation
TMDPS
Yield (%)b
2Aa
92
2Ba
2Ca
1
94
96
Cl
Cl
HO3S
N
SO3H
N
H
H
2
3
BBSI-Cl
92
98
93
98
96
98
HO3S
N
N
N
N
N
N
SO3H
SO3H
Cl
Cl
BBSI-HSO4
HO3S
N
N
HSO4
HSO4
a
Reaction conditions: Reaction conditions: 4-chlorobenzaldehyde 1a (1.0 mmol), hydroxy-6-methyl-2-pyrone (A) (1.0 mmol) or
dimedone (B) or dimedone (C), malononitrile (1.0 mmol), IL (0.05 mmol), four ball mill with diameter 7 mm, revolution rate (600 rpm),
room temperature, milling time (30 min), solvent-free conditions.
bIsolated yield.
As shown in Table 9, the best result was obtained with the BBSI-HSO4 while a slightly drop of the catalytic efficiency was observed
with BBSI-Cl and TMDPS. TMDPS and BBSI-Cl showed the same catalytic efficiency; therefore, it seems that the C2-H of imidazole
ring does not play an important role in the promotion of the reaction when the sulfonic acid groups are present (Table 9, entries 1 and 2).
−
Also, the results showed that sulfonic acid-functionalized IL containing acidic anion such as HSO4 is more efficient than that with a non-
acidic anion such as Cl− (Table 9, entries 2 and 3).
2.5. Reusability of TMDPS
On completion of the reaction, the desired products were readily extracted using hot ethyl acetate, and the remained SAIL was
concentrated under reduced pressure. Then, the reaction jar was recharged with new model reactants for another run. During three
subsequent runs, a range 92-90%, 94-90%, and 96-94% yield were obtained for 2Aa, 2Ba, and 2Ca in the presence of TMDPS,
respectively. Furthermore, the chemical structure of TMDPS showed no significant change under the present workup (See Fig. 11 in
Supplementary Material).
Also, the ionic liquid could be separated by washing with deionized water followed by evaporation of water from an aqueous solution
containing TMDPS. The recovered ionic liquid was successfully reused for the subsequent runs without significant loss of catalytic

ACCEPTED MANUSCRIPT
14
activity. Therefore, either the isolation of product or the separation of ionic liquid was practical for the recovering of TMDPS after
reactions.
3. Experiment
3.1. General
Unless specified, all chemicals were analytical grade and purchased from Merck, Aldrich, and Fluka Chemical Companies and used
without further purification. Products were characterized by their physical constant and IR, NMR and elemental analysis. The purity
determination of the substrates and reaction monitoring were accompanied by TLC using silica gel SIL G/UV 254 plates. The FT-IR
spectra were recorded on a Perkin Elmer 781 Spectrophotometer using KBr pellets for solid and neat for liquid samples in the range of
4000-400 cm−1. In all the cases the 1H and 13C NMR spectra were recorded with Bruker Avance III 600 MHz and 400 MHz instruments.
All chemical shifts are quoted in parts per million (ppm) relative to TMS using deuterated solvent. Microanalyses were performed on a
Perkin- Elmer 240-B microanalyzer. Melting points were recorded on a Büchi B-545 apparatus in open capillary tubes. The mass spectra
of the products were recorded using an Agilent 6560 iFunnel Q–TOF LC–MS instrument. Ball-milling was performed in a Retsch PM100
planetary ball mill using a 25 mL stainless steel chamber and two or four stainless steel balls (diameter: 5 or 7 mm) with 300-600
revolution per minute (rpm).
TGA/DTA curves were obtained with the use of a Mettler Toledo TGA/SDTA 851e. All measurements were taken in the Al2O3
crucible with the sample mass 10.02 mg under nitrogen atmosphere (30 mL min−1). Dynamic scans were performed at the heating rate of
10 °C min−1 in the temperature range 30–800 °C.
Differential scanning calorimetry (DSC) curves were obtained with the use of a DSC-Mettler Toledo DSC 822e calorimeter. The
measurements were taken in the aluminum pans with a pierced lid with the sample mass 17.01 mg under a dry nitrogen gas atmosphere
(30 mL min−1). Dynamic scans were performed at a heating rate of 10 °C min−1 in the temperature range 30–500 °C.
3.2. The synthesis of 4,4’-trimethylene-N,N’-sulfonic acid-dipiperidinium chloride [TMDPS]
The neat chlorosulfonic acid (3.0 mL, 40 mmol) was dropwise added to 4,4’-trimethylene-dipiperidine (4.21 g, 20 mmol) in dry CH2Cl2
(20 mL). The reaction mixture was stirred at 50 °C for overnight which led to the formation of two phases. The upper phase was decanted,
and excess of solvent was removed under reduced pressure. The resulting ionic liquid was isolated as a low-viscous pale yellow liquid
which its structure was characterized by FTIR, Mass spectra, 1D and 2D NMRs.
3.3. Typical procedure for the synthesis of pyran-annulated derivatives in the presence of TMDPS
The aldehyde (1.0 mmol), malononitrile (1.0 mmol), active methylene compounds (1.0 mmol) [hydroxy-6-methyl-2-pyrone (A), 4-
hydroxycoumarin (B) or dimedone (C)], TMDPS (5 mol %) were ground vigorously using the planetary ball mill at room temperature
for 30 min. The progress of the reaction was monitored by TLC. On completion of the reaction, the product was extracted by hot ethyl
acetate which after evaporation of the solvent, the solid crude product was purified just by recrystallization from ethanol without tedious
column chromatographic purification. The TMDPS was concentrated under reduced pressure, and the reaction jar was recharged with

ACCEPTED MANUSCRIPT
new reactants for another reaction. The structure of each purified 4H-pyran-annulated heterocyclic scaffolds was confirmed by melting
1
point and spectral studies including FT-IR, H NMR, 13C NMR, and elemental analysis. All the known compounds had physical and
spectroscopic data identical to the literature data.
3.4. Physical and spectral data of new products
2-Amino-4-(4-isopropylphenyl)-7-methyl-5-oxo-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile (2Ad): m.p. 220-222 °C; FT-IR (KBr) νmax
= 3365, 3300, 2200, 1715, 1670, 1640, 1615, 1375, 1265 cm−1; 1HNMR (400 MHz, DMSO-d6) δ = 7.20-7.18 (m, 3H), 7.10 (d, 2H, J =
8.8 Hz), 6.28 (s, 1H), 4.25 (s, 1H), 2.85 (s, 1H), 2.21 (s, 3H), 1.20 (s, 3H), 1.18 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-d6) δ = 163.1,
161.7, 158.5, 158.4, 147.3, 141.3, 127.7, 126.7, 119.8, 101.2, 98.2, 58.3, 36.1, 33.3, 24.1, 24.2, 19.6 ppm; Anal. Calcd. for C19H18N2O3:
C, 70.79; H, 5.63; N, 8.69. Found: C, 70.73; H, 5.68; N, 8.74.
2-Amino-4-(3,5-dichlorophenyl)-7-methyl-5-oxo-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile (2Af): m.p. 212-214 °C; FT-IR (KBr)
νmax = 3404, 3330, 2194, 1708, 1676, 1645, 1615, 1382, 1262 cm−1; 1HNMR (400 MHz, DMSO-d6) δ = 7.46 (t, J =1.8 Hz, 1H), 7.20-
7.18 (m, 2H), 6.98 (s, 2H), 6.30 (s, 1H), 4.46 (s, 1H), 2.28 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-d6) δ = 164.1, 162.0, 160.8, 158.7,
145.7, 134.6, 127.4, 122.5, 117.3,104.0, 98.4, 56.3, 39.5, 19.6 ppm; Anal. Calcd. for C16H10Cl2N2O3: C, 55.04; H, 2.89; N, 8.02. Found:
C, 54.97; H, 2.83; N, 8.04.
2-Amino-4-(2-methoxyphenyl)-7-methyl-5-oxo-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile (2Ai): m.p. 242-244 °C; FT-IR (KBr) νmax
= 3385, 3295, 2195, 1710, 1676, 1640, 1605, 1380, 1260 cm−1; 1HNMR (400 MHz, DMSO-d6) δ = 7.20-7.18 (m, 1H), 7.05-6.98 (m,
2H), 6.92-6.87 (m, 3H), 4.70 (s, 1H), 3.68 (s, 3H), 2.30 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-d6) δ = 164.3, 162.0, 158.8, 158.5,
155.7, 132.6, 130.6, 128.4, 120.5, 118.3, 112.0, 102.9, 98.4, 56.3, 55.7, 35.5, 19.7 ppm; Anal. Calcd. for C17H14N2O4: C, 65.80; H, 4.55;
N, 9.03. Found: C, 65.87; H, 4.61; N, 9.04.
2-Amino-4-(4-trifluoromethyl-phenyl)-7-methyl-5-oxo-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile (2Al): m.p. 217-219 °C; FT-IR
(KBr) νmax = 3395, 3325, 2190, 1685, 1655, 1370, 1325, 1120 cm−1; 1HNMR (400 MHz, DMSO-d6) δ = 7.70 (d, J = 8.4 Hz, 2H), 7.51
(s, 2H), 7.46 (d, J = 8.4 Hz, 2H), 4.58 (s, 1H), 2.91 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-d6) δ = 163.8, 162.4, 159.0, 157.9, 143.8,
2
1
3
134.6 (q, JC-F = 28 Hz), 125.6 (q, JC-F = 273 Hz), 125.1 (q, JC-F = 4 Hz), 118.3, 105.2, 98.4, 55.8, 39.5, 19.8 ppm; Anal. Calcd. for
C17H11F3N2O3: C, 58.63; H, 3.18; N, 8.04. Found: C, 58.67; H, 3.22; N, 7.99.
2-Amino-4-(4-fluorophenyl)-7-methyl-5-oxo-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile (2Am): m.p. 220-222 °C; FT-IR (KBr) νmax
=
1
3398, 3322, 2194, 1688, 1648, 1368, 1329, 1117 cm−1; HNMR (400 MHz, DMSO-d6) δ = 7.25-7.12 (m, 6H), 6.28 (s, 1H), 4.31 (s, 1H),
2.22 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-d6) δ = 163.4, 161.7 (d, 1JC-F = 267 Hz), 158.6, 158.5, 140.2, 129.9 (d, 3JC-F = 7 Hz), 119.8,
115.6, 115.4 (d, 2JC-F = 26 Hz), 100.9, 98.5, 58.2, 36.1, 19.7 ppm; Anal. Calcd. for C16H11FN2O3: C, 64.43; H, 3.72; N, 9.39. Found: C,
64.47; H, 3.68; N, 9.34.
2-Amino-4-(3,5-difluorophenyl)-7-methyl-5-oxo-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile (2An): m.p. 240-242 °C; FT-IR (KBr)
νmax = 3404, 3330, 2194, 1707, 1675, 1644, 1615, 1381, 1261, 1120, 993, 777 cm−1; 1HNMR (400 MHz, DMSO-d6) δ = 7.33 (s, 2H),
7.16-7.08 (m, 1H), 7.01-6.94 (m, 2H), 6.30 (s, 1H), 4.43 (s, 1H), 2.25 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-d6) δ = 163.8, 162.8 (dd,

ACCEPTED MANUSCRIPT
16
3
2
1JC-F = 244.5 and 12.8 Hz), 161.8, 159.2, 158.7, 148.7 (t, JC-F = 8.2 Hz), 119.4, 111.4 (dd, JC-F = 24.0 and 7.5 Hz), 103.0 (t, 2JC-F = 25.5
Hz), 99.9, 98.6, 57.3, 36.5, 19.8 ppm; Anal. Calcd. for C16H10F2N2O3: C, 60.67; H, 3.19; N, 8.86. Found: C, 60.71; H, 3.18; N, 8.81.
2-Amino-4-(3,5-bis(trifluoromethyl)phenyl)-7-methyl-5-oxo-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile (2Ao): m.p. 245-247 °C; FT-
IR (KBr) νmax = 3421, 3339, 3210, 2193, 1720, 1674, 1646, 1611, 1384, 1283, 1172, 1125, 980, 904, 706 cm−1; 1HNMR (400 MHz,
DMSO-d6) δ = 8.02 (s, 1H), 7.96 (s, 2H), 7.41 (s, 2H), 6.32 (s, 1H), 4.72 (s, 1H), 2.25 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-d6) δ =
164.0, 161.9, 159.3, 158.8, 147.3, 130.6 (q, 2JC-F = 32.2 Hz), 129.2, 123.8 (d, 1JC-F = 270.8 Hz), 121.5, 119.4, 99.4, 98.7, 56.8, 36.4, 19.8
ppm; Anal. Calcd. for C18H10F6N2O3: C, 51.94; H, 2.42; N, 6.73. Found: C, 51.89; H, 2.38; N, 6.69.
3.5. Physical and spectral data of known products
2-amino-7-methyl-5-oxo-4-(4-nitrophenyl)-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile (2Ae): m.p. 216-218 °C; FT-IR (KBr) νmax
=
1
3497, 3316, 3158, 2203, 1705, 1678, 1653, 1622, 1595, 1520 cm−1; HNMR (400 MHz, DMSO-d6) δ = 8.15 (d, J = 8.8 Hz, 2H), 7.55 (d,
J = 8.8 Hz, 2H), 7.33 (s, 2H), 6.30 (s, 1H), 4.49 (s, 1H), 2.22 (s, 3H) ppm.
2-amino-7-methyl-5-oxo-4-(4-methoxyphenyl)-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile (2Ag): m.p. 205-207 °C; FT-IR (KBr) νmax
1
= 3455, 3312, 3168, 2186, 1728, 1676, 1646, 1607, 1510 cm−1; HNMR (400 MHz, DMSO-d6) δ = 7.12 (s, 2H), 7.08 (d, J = 8.8 Hz, 2H),
6.84 (d, J = 8.8 Hz, 2H), 6.24 (s, 1H), 4.21 (s, 1H), 3.71 (s, 3H), 2.20 (s, 3H) ppm.
2-amino-7-methyl-5-oxo-4-(3,4,5-trimethoxyphenyl)-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile (2Aj); m.p. 235-237 °C; FT-IR (KBr)
1
νmax = 3118, 1754, 1621, 1565, 1512, 1410, 1230 cm−1; HNMR (400 MHz, DMSO-d6) δ = 7.10 (s, 2H), 6.82 (s, 2H), 6.12 (s, 1H), 4.20
(s, 1H), 3.91 (s, 6H), 3.82 (s , 3H), 2.34 (s, 3H) ppm.
2-Amino-5-oxo-4-(4-trifluoromethyl-phenyl)-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile (2Bl): m.p. 208-210 °C; FT-IR (KBr) νmax
= 3325, 3194, 3072, 2877, 2198, 1716, 1602, 1377, 1112, 765 cm−1; 1H NMR (400 MHz, DMSO-d6) δ = 7.91(d, J = 7.6 Hz), 7.73 (t, J
= 7.0 Hz, 1H), 7.68 (d, J = 8.6 Hz, 2H), 7.47-7.53 (m, 6H), 4.60 (s, 1H) ppm.
2-amino-5-oxo-4-(3,4,5-trimethoxyphenyl)-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile (2Bj): m.p. 208-210 °C; FT-IR (KBr) νmax
= 3123, 1765, 1623, 1535, 1524, 1410, 1230 cm−1; 1H NMR (400 MHz, DMSO-d6) δ = 8.00 (d, J = 8.0 Hz, 1H), 7.75-7.70 (m, 1H), 7.65
(d, J = 7.6 Hz, 1H), 7.45-7.39 (m, 1H), 7.26 (s, 2H), 6.79 (s, 2H), 4.34 (s, 1H), 3.80 (s, 6H), 3.72 (s , 3H) ppm.
2-Amino-7,7-dimethyl-5-oxo-4-(4-pentyloxy-phenyl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (2Cg): m.p. 178-180 °C; FT-IR
1
(KBr) νmax = 3545, 3327, 3215, 2937, 2193, 1683, 1653, 1606, 1508, 1367, 1251, 1211, 1174, 1035, 842 cm−1; H NMR (400 MHz,
CDCl3) δ = 7.13 (d, J = 8.5 Hz, 2H), 6.80 (d, J = 8.5 Hz, 2H), 4.49 (s, 2H), 4.35 (s, 1H), 3.90 (t, J = 7.0 Hz, 2H), 2.44 (s, 2H), 2.19 and
2.24 (AB system, J = 16.5 Hz, 2H), 1.75 (quin, J = 7.0 Hz, 2H), 1.33-1.44 (m, 4H), 1.10 (s, 3H), 1.03 (s, 3H), 0.92 (t, J = 7.0 Hz, 3H)
ppm.
4. Conclusion
In summary, a novel binuclear sulfonic-functionalized ionic liquid was prepared and its structure was characterized by FTIR, 1H and
13C NMR, Mass spectra. The physical properties such as density and viscosity and pH of the aqueous solution of ionic liquid were

ACCEPTED MANUSCRIPT
determined. The catalytic efficiency of TMDPS was demonstrated for a one-pot multicomponent reaction under mild conditions. The
structure-activity relationship (SAR) of the novel binuclear sulfonic-functionalized acid were studied in comparison with some previously
reported sulfonic-functionalized ionic liquids which proved the superiority of binuclear ionic liquids containing sulfonic-functionalized
imidazolium moiety with an acidic counter anion. The current protocol has the advantages such as simple experimental and sustainable
procedure, high yield of the desired products within short reaction times, a broad substrate scope, and recyclability of novel ionic liquid.
The application of TMDPS in the one-pot multicomponent reactions has highlighted the importance of binuclear sulfonic acid-
functionalized ionic liquids as an efficient and recyclable catalyst in organic chemistry, and we hope that our work will encourage further
research in this area with promising results for future applications of TMDPS.
Conflicts of interest
There are no conflicts of interest to declare.
Acknowledgments
The authors are grateful to staff members in the Analytical and Testing Center of Malaya University for partial support.
References
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
A.S. Amarasekara, Chem. Rev.116 (2016) 6133-6183.
D.D. Patel, J.M. Lee, Chem. Rec. 12 (2012) 329-355.
M. Koel, Crit. Rev. Anal Chem. 35 (2005) 177-192.
X. Sun, H. Luo, S. Dai, Chem. Rev. 112 (2012) 2100-2128.
R. koda-Földes, Molecules 19 (2014) 8840-8884.
H. Olivier-Bourbigou, L. Magna, J. Mol. Catal. A Chem. 182–183 (2002) 419-437.
Z.S. Qureshi, K.M. Deshmukh, B.M. Bhanage, Clean Technol. Envir. 16 (2014) 1487-1513.
M. Bielejewski, M. Ghorbani, M.A. Zolfigol, J. Tritt-Goc, S. Noura, M. Narimani, M. Oftadeh, RSC Adv. RSC Adv. 6
(2016) 108896-108907.
[9]
A. Khazaei, M.A. Zolfigol, A.R. Moosavi-Zare, A. Zare, Sientica Iranica Trans. C Chem. Chem. Eng. 17 (2010) 31-36.
M.A. Zolfigol, A. Khazaei, A.R. Moosavi-Zare, A. Zare, H.G. Kruger, Z. Asgari, V. Khakyzadeh, M. Kazem-Rostami,
[10]
J. Org. Chem. 77 (2012) 3640-3645.
[11]
[12]
[13]
[14]
[15]
[16]
[17]
M. Zarei, E. Noroozizadeh, A.R. Moosavi-Zare, M.A. Zolfigol, J. Org. Chem. 83 (2018) 3645-3650.
M.A. Zolfigol, Tetrahedron 57 (2001) 9509-9511.
N.G Khaligh, T. Mihankhah, Mohd Rafie Johan, Polycycl. Arom. Comp. Doi:10.1080/10406638.2018.1538058.
N. G. Khaligh, Res. Chem. Intermed. 44 (2018) 4045-4062.
J.-L. Do, T. Frisꢀiꢀ, ACS Cent. Sci. 3 (2017) 13-19.
M.A.P. Martins, C.P. Frizzo, D.N. Moreira, L. Buriol, P. Machado, Chem. Rev. 109 (2009) 4140-4182
B. Kubias, M.J.G. Fait, R. Schlogl, in Hand book of Heterogeneous Catalysis, ed. Ertl G, Knozinger H, Schuth F,
Weitkamp J, Wiley-VCH, Weinheim, 2nd edn, 2008, pp. 571-583.
[18]
[19]
[20]
A.L. Garay, A. Pichon, S.L. James, Chem. Soc. Rev. 36 (2007) 846-855.
N.G. Khaligh, H.S. Abbo, S.J.J. Titinchi, Res. Chem. Intermed. 43 (2017) 901-910.
N.G. Khaligh, O.C. Ling, T. Mihankhah, M.R. Johan, J.J. Ching, Aust. J. Chem. 2018, DIO: 10.1071/CH18408.

ACCEPTED MANUSCRIPT
18
[21] A. Stolle, T. Szuppa, S.E.S. Leonhardt, B. Ondruschka, Chem. Soc. Rev. 40 (2011) 2317-2329.
[22]
I.V. Magedov, M. Manpadi, M.A. Ogasawara, A.S. Dhawan, S. Rogelj, S. Van slambrouck, W.F.A. Steelant, N.M.
Evdokimov, P.Y. Uglinskii, E.M. Elias, E.J. Knee, P. Tongwa, M. Yu. Antipin, A. Kornienko, J. Med. Chem. 51 (2008) 2561-
2570.
[23]
[24]
D. Kumar, P. Sharma, H. Singh, K. Nepali, G.K. Gupta, S.K. Jaina, F. Ntie-Kang, RSC Adv. 7 (2017) 36977-36999.
X. Fan, D. Feng, Y. Qu, X. Zhang , J. Wang , P.M. Loiseau, G. Andrei , R. Snoeck , E. De Clercq, Bioorg. Med. Chem.
Lett. 20 (2010) 809-813.
M.D. Aytemir, U. Calis, M. Ozalp, Arch. Pharm. 337 (2004) 281-288.
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
[48]
[49]
[50]
1994.
[51]
[52]
[53]
[54]
R.L.T. Parreira, O. Abrahão, S.E. Galembeck. Tetrahedron 57 (2001) 3243-3253.
L. Abrunhosa, M. Costa, F. Areias, A. Venâncio, F. Proenca, J. Ind. Microbiol. Biotechnol. 34 (2007) 787-792.
D. Rajguru, B.S. Keshwal, S. Jain, Med. Chem. Res. 22 (2013) 5934-5939.
X.S. Wang, J.X. Zhou, Z.S. Zeng, Y.-L. Li, D.-Q. Shi, S.-J. Tu, Arkivoc 11 (2006) 107-113.
D.Q. Shi, L.H. Niu, Q.Y. Zhuhang, Chin. J. Org. Chem. 28 (2008) 1633-1636.
E. V. Stoyanov, I.C. Ivanov, D. Heber, Molecules 5 (2000) 19-32.
M. Seifi, H. Sheibani, Catal. Lett. 126 (2008) 275-279.
J.M. Khurana, B. Nand, P. Saluja, Tetrahedron 66 (2010) 5637-5641.
D. Rajguru, B.S. Keshwal, S. Jain, Chin. Chem. Lett. 24 (2013) 1033-1036
E. Mosaddegh, A. Hassankhani, H. Karimi-Maleh, Mater. Sci. Eng., C 46 (2015) 264-269.
M. Ghashang, S.S. Mansoor, K. Aswin, Chin. J. Catal. 35 (2014) 127-133.
N. G. Khaligh, Chin. Chem. Lett. 26 (2015) 26-30.
E. Mosaddegh, A. Hassankhani, Chin. J. Catal. 35 (2014) 351-356.
N.G. Khaligh, Monatsh. Chem. 145 (2014) 1643-1648.
M.N. Elinson, R.F. Nasybullin, G.I. Nikishin, Electrocatalysis 4 (2013) 56-60.
D. Rajguru, B.S. Keshwal, S. Jain, V.W. Bhagwat, Monatsh. Chem. 144 (2013) 1411-1416.
R.N. Rao, M.V.N.K. Talluri, J. Pharmaceut. Biomed. 43 (2007) 1-13.
N.G. Khaligh, Polycycl. Arom. Comp. 36 (2016) 284-294.
N.G. Khaligh, Res. Chem. Intermed. 41 (2015) 5411-5421.
N.G. Khaligh, Chin. J. Catal. 35 (2014) 1497-1503.
N.G. Khaligh, T. Mihankhah, M.R. Johan, J.J. Ching, J. Mol. Liq. 259 (2018) 260-273.
E. Bartoszak-Adamska, Z. Dega-Szafran, A. Komasa, M. Szafran, Vib. Spectrosc. 81 (2015) 13-21.
G.H. Silver, J.L. Wood, Trans. Faraday Soc. 60 (1964) 5-9.
R. Ramasamy, J. Appl. Spec. 80 (2013) 492-498.
N.P.G. Roeges, A Guide to the complete interpretation of infrared spectra of organic structures. Wiley, New York,
R. A. Heacock, Léo Marion, Can. J. Chem. 34 (1956) 1782-1795.
V. Krishnakumar, R. Ramasamy, Indian J. Pure & Appl. Phys. 40 (2002) 252-255.
R. Ramasamy, Arm. J. Phys. 8 (2015) 51-55.
Z. Dega-Szafran, M. Petryna, E. Tykarska, M. Szafran, Molecular structure of 1-piperidinium acid perchlorate studied
by X-ray diffraction and FTIR spectroscopy. J. Mol. Structure 643 (2002) 69-75.
[55] T. Belhocine, S.A. Forsyth, H.Q.N. Gunaratne, M. Nieuwenhuyzen, P. Nockemann, A.V. Puga, K.R. Seddon, G.
Srinivasan, K. Whiston, 3-Methylpiperidinium ionic liquids. Phys. Chem. Chem. Phys., 2015, 17, 10398-10416
[56] E.W. Garbisch, M.G. Griffith, J. Am. Chem. Soc. 90 (1968) 6543-6544.

ACCEPTED MANUSCRIPT
[57]
491.
[58]
[59]
E. L. Eliel, S. H. Wilen and M. P. Doyle, Basic Organic Stereochemistry, Wiley-Interscience, New York, 2001, pp. 436-
V.M.B. Nunes, M.J.V. Lourenco, F.J.V. Santos, C.N. de Castro, J. Chem. Eng. Data 48 (2003) 446-450.
E. Hendriks, G.M. Kontogeorgis, R. Dohrn, J.C. de Hemptine, I.G. Economou, L.F. Zilnik, V. Vesovic, Ind. Eng.
Chem. Res. 49 (2010) 11131-11141.
[60]
[61]
[62]
[63]
[64]
[65]
[66]
[67]
[68]
F. Schneider, A. Stolle, B. Ondruschka, H. Hopf, Org. Process Res. Devel. 13 (2009) 44-48.
N.G. Khaligh, S.B. Abd Hamid, S.J.J. Titinchi, Polycycl. Arom. Comp. 37 (2017) 31-38.
E. Abbaspour-Gilandeh, S.C. Azimi, K. Rad-Moghadam, A.M. Barkchai, Iran. J. Catal. 3 (2013) 91-97.
R.-Y. Guo, Z.-M. An, L.-P. Mo, R.-Z. Wang, H.-X. Liu, S.-X. Wang, Z.-H. Zhang, ACS Comb. Sci. 15 (2013) 557-563.
S.S. Pendalwar, A.V. Chakrawar, A.S. Chavan, S.R. Bhusare, Der Pharma Chemica, 8 (2016) 143-145.
G. Brahmachari, B. Banerjee, ACS Sustainable Chem. Eng. 2 (2014) 411-422.
A. Shaabani, S. Samadi, Z. Badri, A. Rahmati, Catal. Let. 104 (2005) 39-43.
M. Esmaeilpour, J. Javidi, F. Dehghani, F.N. Dodeji, RSC Adv. 5 (2015) 26625-26633.
M. Khoobi, L. Ma’mani, F. Rezazadeh, Z. Zareie, A. Foroumadi, A. Ramazani, A. Shafiee, J. Mol. Catal. A: Chem. 359
(2012) 74-80.
[69]
R. Teimuri-Mofrad, S. Esmati, S. Tahmasebi, M. Gholamhosseini-Nazari, J. Organometal. Chem. 870 (2018) 38-50.
[70]
N. Hazeri, M.T. Maghsoodlou, F. Mir, M. Kangani, H. Saravani, E. Molashahi, Chin. J. Catal. 35 (2014) 391-395.
A.C. Flores, E.A. Flores, E. Hernández, L.V. Castro, A. García, F. Alvarez, F.S. Vázquez, J. Mol. Liquids. 2014, 196,
[71]
249-257.
[72]
X. Chen, W. Zhang, F. Yang, C. Guo, Z. Zhao, D. Ji, F. Zhou, Z. Wang, R. Zhao, L. Wang, Green Chem. Lett. Rev. 10
(2017) 54-58.
A. Shaabani, S. Samadi, A. Rahmati. Syn. Commun. 37 (2007) 491-499.
[73]
[74]
[75]
[76]
[77]
[78]
[79]
[80]
[81]
[82]
[83]
[84]
[85]
[86]
[87]
[88]
[89]
A.T. Khan, M. Lal, S. Ali, M.M. Khan, Tetrahedron Lett. 52 (2011) 5327-5332.
J.M. Khurana, S. Kumar, Tetrahedron Lett. 50 (2009) 4125-4127.
S. Abdolmohammadi, S. Balalaie, Tetrahedron Lett. 48 (2007) 3299-3303.
M.G. Dekamin, M. Eslami, A. Maleki, Tetrahedron 69 (2013) 1074-1085.
P. Das, A. Dutta, A. Bhaumik, C. Mukhopadhyay, Green Chem. 16 (2014) 1426-1435.
M.M. Heravi, B.A. Jani, F. Derikvand, F.F. Bamoharram, H.A. Oskooie, Catal. Commun. 10 (2008) 272-275.
M. Bihani, P.P. Bora, G. Bez, H. Askari, C. R. Chimie 16 (2013) 419-426.
J. Zheng, Y. Li, Mendeleev Commun. 21 (2011) 280-281.
S. Khaksar, A. Rouhollahpour, S.M. Talesh, J. Fluorine Chem. 141 (2012) 11-15.
V. Bhaskar, R. Chowdary, S.R. Dixit, S.D. Joshi, Bioorg. Chem. 84 (2019) 202-210.
S. Nemouchi, R. Boulcina, B.Carboni, A. Debache, C. R. Chimie 15 (2012) 394-397.
S.S. Pourpanah, S.M. Habibi-Khorassani, M. Shahraki, Chin. J. Catal. 36 (2015) 757-763.
D.S. Bhagat, J.L. Wawre, A.R. Yadav, P.G. Pathare, L. Kotai, R.P. Pawar, Eur. Chem. Bull. 6 (2017) 211-214.
F. Shirini, M.S.N. Langarudi, N. Daneshvar, J. Mol. Liq. 234 (2017) 268-278.
F. Shirini, N. Daneshvar, RSC Adv. 6 (2016) 110190-110205.
K. Matuszek, A. Chrobok, F. Coleman, K.R. Seddon, M. Swadźba-Kwaśny, Green Chem 16 (2014) 3463-3471.

ACCEPTED MANUSCRIPT
20
Highlights
 Synthesize of a low-viscous binuclear sulfonic-functionalized ionic liquid (SAIL)
 Measure and determine the physical properties
 Investigate the catalyst activity of new SAIL in the one-pot multicomponent reactions
 The present a new protocol for the synthesis using the planetary ball milling process
 The synthesis and characterization of new pyrano[4,3-b]pyrans