Catalytic performance of a new Br?nsted acidic oligo(ionic liquid) in efficient synthesis of pyrano[3,2-c]quinolines and pyrano[2,3-d]pyrimidines

Article abstract of DOI:10.1016/j.molliq.2017.10.065

An acidic liquid 1,3-ionene was synthesized from co-oligomerization of epichlorohydrin and imidazole followed by subjecting the resulting light oligomer to anion exchange with concentrated sulfuric acid and subsequent sulfonylation with chlorosulfonic acid. The ¹H and ¹³C NMR spectra of the synthesized oligo(ionic liquid) displayed significant chemical shifts on transferring the oligomer from D₂O to DMSO. This observation was interpreted as resulting from a conformational change in the multicationic oligomer. Application of this oligo(ionic liquid) as both solvent and acidic promoter to the synthesis of pyrano[3,2-c]quinolines and pyrano[2,3-d]pyrimidines gave fairly high yields of the products in short reaction times. The oligo(ionic liquid) is virtually stable, as could be stored for several months at room temperature and can be easily recycled several times in the synthesis of pyrano[3,2-c]quinolines and pyrano[2,3-d]pyrimidines at 80 °C without appreciable loss of activity.

Full text of DOI:10.1016/j.molliq.2017.10.065

Accepted Manuscript
Catalytic performance of a new Brønsted acidic oligo(ionic
liquid) in efficient synthesis of pyrano[3,2-c]quinolines and
pyrano[2,3-d]pyrimidines
Zahra Tashrifi, Kurosh Rad-Moghadam, Morteza Mehrdad
PII:
DOI:
Reference:
S0167-7322(17)33285-3
doi:10.1016/j.molliq.2017.10.065
MOLLIQ 8027
To appear in:
Journal of Molecular Liquids
Received date:
Revised date:
Accepted date:
21 July 2017
10 October 2017
13 October 2017
Please cite this article as: Zahra Tashrifi, Kurosh Rad-Moghadam, Morteza Mehrdad ,
Catalytic performance of a new Brønsted acidic oligo(ionic liquid) in efficient synthesis of
pyrano[3,2-c]quinolines and pyrano[2,3-d]pyrimidines. The address for the corresponding
author was captured as affiliation for all authors. Please check if appropriate.
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ACCEPTED MANUSCRIPT
Catalytic performance of a new Brønsted acidic oligo(ionic liquid) in efficient synthesis
of pyrano[3,2-c]quinolines and pyrano[2,3-d]pyrimidines
Zahra Tashrifi, Kurosh Rad-Moghadam* and Morteza Mehrdad
Department of Chemistry, University of Guilan, Rasht PO Box 41335-1914, Iran. E-mail : radmm@guilan.ac.ir
Fax: +98 1333367067
Abstract
An acidic liquid 1,3-ionene was synthesized from co-oligomerization of epichlorohydrin and
imidazole followed by subjecting the resulting light oligomer to anion exchange with
concentrated sulfuric acid and subsequent sulfonylation with chlorosulfonic acid. The 1H- and
13C NMR spectra of the synthesized oligo(ionic liquid) displayed significant chemical shifts
on transferring the oligomer from D2O to DMSO. This observation was interpreted as
resulting from a conformational change in the multicationic oligomer. Application of this
oligo(ionic liquid) as both solvent and acidic promoter to the synthesis of pyrano[3,2-
c]quinolines and pyrano[2,3-d]pyrimidines gave fairly high yields of the products in short
reaction times. The oligo(ionic liquid) is virtually stable, as could be stored for several
months at room temperature and can be easily recycled several times in the synthesis of
pyrano[3,2-c]quinolines and pyrano[2,3-d]pyrimidines at 80 °C without appreciable loss of
activity.
Keywords: Oligo(ionic liquid); Ionene; pyrano[3,2-c]quinolines; pyrano[2,3-d]pyrimidines;
Homogeneous catalysis; Conformational change.
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1. Introduction
Recent decades have been witness to vast developments of ionic liquids (ILs) and so
expansion of their applications from simple solvents to efficient catalysts [1], novel
polymeric electrolytes [2], and surfactants [3]. Much of these advances have been made
possible by modification of chemical and physical properties of ILs through variation of their
cationic and anionic constituents. A much more diversity in physicochemical properties of
ILs is achieved by fabricating them from functionalized [4-6] and multicationic [7]
components. Multicationic ILs usually show a greater range of physical properties and self-
assembling tendency than traditional mono-cationic ILs [8]. These diversity generating
parameters provide flexibility for designing task-specific ILs and tuning their solubility as
such to be easily recoverable from reaction mixtures by biphasic separation. Acidic ionic
liquids are the elaborately functionalized ILs, which recently have attracted more interests
due to their both solid acid and liquid acid advantages.
Synthesis of the first Brønsted acidic IL was reported [9] in 2002 and since then studies on
these acidic liquids has grown up rapidly. Imidazolium-based ILs comprise one of the most
studied classes of ILs. Selection of imidazolium ring as the cationic core of ILs is mainly due
to its stability under oxidative and reductive conditions, low viscosity of imidazolium ILs and
the ease with which it can be diversified [10]. The noncoordinative and ionic nature of
imidazolium ILs make them privileged media for acid catalysis reactions [11]. In these ionic
media, the protic groups gain increased ionic dissociation potential and the substrates serve as
the sole proton acceptors. Among Brønsted-acidic ionic liquids, those bearing SO3H and
SO4H groupings have received much attention because of their high acidity strength and
catalytic efficacy [12].
Here, we describe the synthesis, spectroscopic structural elucidation, and valuable physical
characteristics of a novel sulfuric acid-functionalized oligo(ionic liquid) (OIL). The
synthesized OIL, which is structurally a liquid ionene sulfuric acid (ISA), was successfully
evaluated as both solvent and acid promoter in the three-component probe synthesis of
pyrano[3,2-c]quinolines and pyrano[2,3-d]pyrimidines. Synthesis of these compounds has
long been the subject of numerous studies due to their diverse pharmacological activities
[13,14]. Although several routes have, so far, been reported for synthesis of these compounds
[15], they are commonly synthesized through three-component annulation of a pyran ring
onto appropriate hydroxypyrimidones or hydroxyquinolones [16]. These reactions are not
fisible by themselves, so many methods based on using a vareity of catalysts have been
developed [17]. However, despite the obvious merit of the recent reported methods,
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development of alternative green and efficient approaches are still in demand to avoid
limitations such as use of expensive reagents, long reaction times, and laborious workup
procedures.
2. Experimental Section
2.1 Materials and Instruments
Chemicals were purchased from Merck and Aldrich chemical companies. All the yields refer
1
to the isolated products. The products were identified by H NMR spectroscopy and
comparison of their physical constants and spectral data with those reported in literature. The
synthesized OIL was characterized by its 1H and 13C NMR (400 MHz) spectra recorded on a
Bruker-AVANCE spectrometer. Monitoring of the reaction was performed by TLC on silica
gel (polygram SILG/UV 254) plates. Gel-permeation chromatography (GPC) analysis was
performed on a Shimadzu LC-20A chromatographer (equipped with Waters Ultrahydrogel
Linear column and connected to a RI detector) against polystyrene sulfonate (Na) standards
by using 0.1 M solution of NaNO3 as the mobile phase. The TGA (thermogravimetric
analysis), DTG (differential thermogravimetry), and DSC (differential scanning calorimetry)
studies of the OIL were carried out under He atmosphere on a SETARAM (SETSYS-1760)
thermal analyser. The thermal behaviour of the OIL sample (16 mg) was scanned from 40 °C
to 600 °C at the rate of 20 °C/min under helium gas flow. Area under each peak in the DSC
plot gives an estimate of the enthalpy of the corresponding change which can be calculated
by the following equation.
∆H=
=
= .
The Fourier transform infrared (FT-IR) spectra were taken by using KBr discs on a Perkin-
Elmer Spectrum One apparatus in the range of 400–4000 cm-1. Electrical conductivities were
measured on an Orion 101 conductometer using a platinum conductivity cell (cell constant =
1 cm-1).
2.2 Preparation of the OIL; Oligo(imidazolium hydrogensulfate-1,3-diylpropane-2-
hydrogensulfate-1,3-diyl)
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Imidazole 1 (6 mmol, 0.408 g) and epichlorohydrin 2 (9 mmol, 0.71 mL) were added to
absolute ethanol (12 mL) in a round-bottom flask. The resulting solution was stirred for 5-6 h
at 60 °C and then was concentrated under reduced pressure to obtain a viscous pale yellow
oil. After dilution with dry CH2Cl2 (5 mL), sulfuric acid 98% (6 mmol, 0.33 mL) was added
in a dropwise fashion over a period of 0.5-1 h at 40-50 °C and under a continuous flow of
nitrogen to remove the generated HCl gas. Stirring of the resulting mixture was continued for
the next 24 h at room temperature. The supernatant layer (CH2Cl2) of the resulting biphasic
liquid mixture was decanted and the residual viscous oil was washed with dry CH2Cl2 (3 × 5
mL). To this oily residue was added, while stirring, a solution of chlorosulfonic acid (12
mmol, 0.8 mL) in CH2Cl2 (5 mL) dropwise over a period of 20 min at 0 °C. Afterward, the
resulting mixture was warmed to room temperature and stirring continued for 24 h. The
supernatant CH2Cl2 layer was decanted and the residue was washed three times with dry
CH2Cl2 (3 × 5 mL). Evaporation of the volatiles under reduced pressure gave a pale brown oil
with lower viscosity than the oil obtained before the sulfonation step (Fig. 1, Scheme 1). GPC
analysis of ISA 5 displayed the number averaged molecular weight Mn= 1227 g.mol-1, weight
averaged molecular weight Mw= 1328 g.mol-1, and the polydispersity index PDI= 1.08.
Figure 1. The structure and colour of the synthesized OIL
2.3 General procedure for preparation of pyrano[3,2-c]quinolines 10a-h and
pyrano[2,3-d]pyrimidines 11a-c under catalysis of the OIL
A mixture of an aldehyde 6a-i (1 mmol), malononitrile 7 (1.1 mmol), 4-hydroxyquinolin-2-
one 8/ 6-hydroxy-tetrahydropyrimidin-4-one 9 (1 mmol), and the above synthesized OIL (0.5
mL) was magnetically stirred under solvent-free condition at 80 °C for an appropriate period
of time (according to Table 3). The progress of the reaction was monitored by TLC using n-
hexane and EtOAc (in the ratio of 1:1) as eluent. After completion of the reaction, as
indicated by TLC, the mixture was cooled at room temperature and distilled water (8 mL)
was added while stirring. The solid crude product, which precipitates at this end, was
separated from the aqueous layer by decantation and then recrystallized from hot ethanol
(95%) to give the pure product. The OIL, remains on evaporation of the aqueous solution
4

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under reduced pressure at 50 °C, was washed with ethyl acetate before use in the next cycle
of the same synthesis.
2.4 Selected spectral data for the products
2-Amino-4-phenyl-5-oxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carbonitrile 10a: IR
1
(KBr): υmax (cm-1) 1381, 1589, 1672, 2206 (C≡N), 3180, 3315, 3462. H NMR (400MHz,
DMSO-d6): δH 4.49 (1H, s, 4-H), 7.18-7.22 (3H, m, Ar), 7.27-7.32 (5H, m, Ar), 7.34 (1H, d, J
8.4Hz, 7-H), 7.58 (1H, dt, J 7.6 and 1.4Hz, 8-H), 7.91 (1H, dd, J 8.0 and 1.4Hz, 10-H), 11.78
(1H, s, N-H).
2-Amino-4-(4-nitrophenyl)-5-oxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carbonitrile
10b: IR (KBr) υmax (cm-1): 1348 and 1514 (NO2), 1387, 1632, 1674, 2202 (C≡N), 3335 and
3406 (N-H). 1H NMR (400.13MHz, DMSO-d6): δH 4.69 (1H, s, 4-H), 7.31 (1H, t, J 7.6Hz, 9-
H), 7.34 (1H, d, J 9.2Hz, 7-H), 7.42 (2H, s, NH2), 7.51 (2H, d, J 8.8Hz, 2´- and 6´-H), 7.60
(1H, dt, J 7.8 and 1.2Hz, 8-H), 7.93 (1H, d, J 8.0Hz, 10-H), 8.17 (1H, d, J 8.8Hz, 3´-H and
5´-H), 11.84 (1H, s, N-H).
2-Amino-4-(2-chlorophenyl)-5-oxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carbonitrile
10c: IR (KBr) υmax (cm-1): 1385 (C-O pyran), 1632 (N-H bend), 1674 (C=O), 2195 (C≡N),
1
3180, 3321, 3365 (N-H). H NMR (400.13MHz, DMSO-d6): δH 5.02 (1H, s, 4-H), 7.15 (1H,
m, 6´-H), 7.21-7.25 (2H, m, 4´- and 5´-H), 7.27 (2H, s, NH2), 7.31 (1H, t, J 7.6Hz, 9-H), 7.35
(1H, d, J 8.4Hz, 7-H), 7.39 (1H, m, 3´-H), 7.59 (1H, t, J 7.6Hz, 8-H), 7.92 (1H, d, J 8.0Hz,
10-H), 11.74 (1H, s, N-H).
2-Amino-4-(3-bromophenyl)-5-oxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carbonitrile
10d: IR (KBr) υmax (cm-1): 1383 (C-O pyran), 1624 (N-H bend), 1670 (C=O), 2193 (C≡N),
3163, 3360, 3454 (N-H). 1H NMR (400.13 MHz, DMSO-d6): δH 4.54 (1H, s, 4-H), 7.22 (1H,
dt, J 7.6 and 1.4Hz, 6´-H), 7.27 (1H, t, J 7.6HZ, 5´-H), 7.30 (1H, dt, J 7.6 and 1.2Hz, 9-H),
7.34 (1H, d, J 7.6Hz, 7-H), 7.35 (2H, s, NH2), 7.39-7.43 (2H, m, 2´- and 4´-H), 7.59 (1H, dt, J
7.7 and 1.4Hz, 8-H), 7.91(1H, dd, J 8.0 and 0.8Hz, 10-H), 11.81 (1H, s, N-H).
2-Amino-4-(4-chlorophenyl)-5-oxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carbonitrile
10e: IR (KBr) υmax (cm-1): 1383 (C-O pyran), 1674 (C=O), 2187 (C≡N), 3169, 3286, 3379,
1
3408 (N-H). H NMR (400.13MHz, DMSO-d6): δH 4.52 (1H, s, 4-H), 7.24 (2H, d, J 8.4Hz
5

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2´- and 6´-H), 7.30 (1H, dt, J 8.0 and 1.2Hz, 9-H), 7.32 (2H, s, NH2), 7.34 (1H, d, J 8.4Hz, 7-
H), 7.35 (2H, d, J 8.4Hz, 3´-H and 5´-H), 7.59 (1H, dt, J 7.8 and 1.2Hz, 8-H), 7.91 (1H, dd, J
8.0 and 1.2Hz, 10-H), 11.80 (1H, s, N-H).
2-Amino-4-(4-methoxyphenyl)-5-oxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carbonitrile
10f: IR (KBr) υmax (cm-1): 1379 (C-O pyran), 1632 (N-H bend), 1676 (C=O), 2183 (C≡N),
1
3163, 3246, 3283, 3337 (N-H). H NMR (400.13MHz, DMSO-d6): δH 3.71 (3H, s, OCH3),
4.44 (1H, s, 4-H), 6.84 (2H, d, J 8.8Hz, 3´-H and 5´-H), 7.12 (2H, d, J 8.8Hz, 2´-H and 6´-H),
7.23 (2H, s, NH2), 7.29 (1H, dt, J 7.6 and 1.2Hz, 9-H), 7.33 (1H, d, J 8.0Hz, 7-H), 7.57 (1H,
dt, J 7.8 and 1.6Hz, 8-H), 7.90 (1H, dd, J 8.0 and 0.8Hz, 10-H), 11.57 (1H, s, N-H).
2-Amino-4-(4-methylphenyl)-5-oxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carbonitrile
10g: IR (KBr) υmax (cm-1): 1375 (C-O pyran), 1624 (N-H bend), 1691(C=O), 2189 (C≡N),
3223, 3443 (N-H amine). 1H NMR (400.13MHz, DMSO-d6): δH 2.24 (3H, s, CH3), 4.45 (1H,
s, 4-H), 7.08 (4H, s, Ar-H), 7.23 (2H, s, NH2), 7.29 (1H, dt, J 7.6 and 1.2Hz, 9-H), 7.33 (1H,
d, J 8.0Hz, 7-H), 7.58 (1H, dt, J 7.7 and 1.4Hz, 8-H), 7.90 (1H, dd, J 8.0 and 1.2Hz, 10-H),
11.76 (1H, s, N-H).
2-Amino-4-(thiophene-2-yl)-5-oxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carbonitrile
10h: IR (KBr) υmax (cm-1): 1385 (C-O pyran), 1676 (C=O), 2201 (C≡N), 3182, 3319, 3468
1
(N-H). H NMR (400.13MHz, DMSO-d6): δH 4.86 (1H, s, 4-H), 6.93 (1H, dd, J 5.2 and
3.4Hz, 4´-H), 6.98 (1H, d, J 3.4Hz, 3´-H), 7.29 (1H, dt, J 7.6 and 0.8Hz, 9-H), 7.33 (1H, dd, J
5.2 and 1.2Hz, 5´-H), 7.35 (1H, d, J 8.4Hz, 7-H), 7.40 (2H, s, NH2), 7.58 (1H, dt, J 7.4 and
1.4Hz, 8-H), 7.88 (1H, dd, J 8.0 and 1.0Hz, 10-H), 11.88 (1H, s, N-H). 13C NMR
(100.61MHz, DMSO-d6): δC 32.1 (C-4), 57.9 (C-3), 110.1 and 112.4 (C-4a and C≡N), 115.9,
120.2, 122.2, 122.6, 124.9, 125.1, 127.4, 131.9, 138.2, 149.1, 151.4; 160.0 and 160.9 (C-2
and C-5).
7-Amino-5-(3-nitrophenyl)-4-oxo-4,5-dihydro-3H-pyrano[2,3-d]pyrimidine-6-carbonitrile
11a: IR(KBr): υmax (cm-1) 3429, 3326, 3163, 2921, 2185 (C≡N), 1658, 1600, 1396, 1533,
1346 (NO2). 1H NMR (400MHz, DMSO-d6) δH: 12.80 (1H, s, N-H), 8.18 (1H, s, 2-H), 8.11
(1H, ddd, J 8.4, 2.4 and 0.8Hz, 4ʹ-H), 8.05 (1H, t, J 2.0Hz, 2ʹ-H), 7.72 (1H, dt, J 8.0, 1.4Hz,
13
6ʹ-H), 7.63 (1H, t, J 8.0, 5ʹ-H), 7.33 (2H, s, NH2), 4.67 (1H, s, 5-H). C NMR (100.61MHz,
6

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DMSO-d6) δC: 161.1, 160.3, 159.8, 150.5 (C-2), 148.2, 146.5, 134.9, 130.5, 122.5, 119.8
(C≡N), 102.7 (C-4a), 56.6 (C-6), 36.7 (C-5).
7-Amino-5-(2-chlorophenyl)-4-oxo-4,5-dihydro-3H-pyrano[2,3-d]pyrimidine-6-carbonitrile
1
11b: IR(KBr): υmax(cm-1) 3394, 3326, 2975, 2194 (C≡N), 1658, 1585, 1392. H NMR
(400MHz, DMSO-d6) δH: 12.72 (1H, s, N-H), 8.16 (1H, s, 2-H), 7.38 (1H, dd, J 7.6 and
1.6Hz, 3ʹ-H), 7.28 (1H, dt, J 7.6 and 1.6Hz, 5ʹ-H), 7.23 (1H, dt, J 7.6 and 2.4Hz, 4ʹ-H), 7.18
(1H, dd, J 7.6 and 2.4Hz, 6ʹ-H); 7.16 (2H, s, NH2); 4.91 (1H, s, 5-H). 13C NMR (100.61MHz,
DMSO-d6) δC: 161.0, 160.7, 159.7, 150.2 (C-2); 141.2, 132.7, 130.9, 130, 128.9, 128, 119.7
(C≡N), 102.7 (C-4a), 56.4 (C-6), 34.6 (C-5).
7-Amino-5-(4-chlorophenyl)-4-oxo-4,5-dihydro-3H-pyrano[2,3-d]pyrimidine-6-carbonitrile
1
11c: IR(KBr): υmax(cm-1) 3417, 3309, 3163, 2920, 2190 (C≡N), 1660, 1587, 1386. H NMR
(400MHz, DMSO-d6) δH: 12.75 (1H, s, N-H), 8.15 (1H, s, 2-H), 7.36 (2H, d, J 8.6Hz, Ar),
7.23 (2H, d, J 8.6Hz, Ar), 7.21 (2H, s, NH2), 4.44 (1H, s, 5-H). 13C NMR (100.61MHz,
DMSO-d6) δC: 161.1, 160.1, 159.6, 150.1 (C-2), 143.4, 131.8, 129.8, 128.8, 120 (C≡N),
103.3 (C-4a), 57.2 (C-6), 36.4 (C-5).
3. Results and discussion
As depicted in scheme 1, the reaction of imidazole 1 and epichlorohydrin 2 results in
formation of the ionene 3. Treatment of this ionene with concentrated sulfuric acid in
dichloromethane solution resulted in liberation of gaseous HCl and gave the ionene 4 in
-
which the Cl- counter ions were replaced by HSO4 anions. Subsequent addition of ionene 4
to dichloromethane solution of chlorosulfonic acid was also accompanied with liberation of
gaseous HCl. This observation was taken as a sign of condensation between these two
reacting species, which quantitatively delivered the ionene sulfuric acid (ISA) 5, i.e.
oligo(imidazolium
hydrogensulfate-1,3-diylpropane-2-hydrogensulfate-1,3-diyl).
The
1
13
structure assigned to the synthesized ISA 5 is consistent with its FT-IR, H- and C NMR
spectra. A strong sharp band is seen in the FT-IR spectrum of this ISA at 1175 cm−1,
corresponding to asymmetric stretching vibration of its SO4H groups. The strong broad band
observed at around 2500–3500 cm−1 is relating to O-H stretching vibration of SO4H group
and affirms the presence of this group in the synthesized ISA. Moreover, this spectrum
exhibits a band at 1633 cm-1 due to C=N stretching vibration of the imidazolium rings.
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Cl
O
EtOH Abs.
50-60 °C
HN
N
N
N
Cl
OH
1
2
3
n
H2SO4 98%,
HCl
CH2Cl2, 24 h, r.t.
HCl
HSO4
HSO4
N
N
N
N
ClSO3H
CH2Cl2, 24 h, r.t.
OSO3H
OH
n
n
5
4
Scheme 1. An outline of the steps taken for synthesis of the ISA
5
1
The H NMR spectrum of this ISA in DMSO-d6 (as solvent) displayed a characteristic peak
at 13.95 ppm, which was readily conceived as arising from a portion of the acidic O-SO3H
-
protons of the OIL. The another part of these protons joined with those of HSO4 ions
involved in hydrogen bonding with a trace of H2O impurity of the solvent and appeared at
8.68 ppm. Both of these signals disappeared on exchange of the acidic protons with D2O and
replaced by the signal of HOD at 5.24 ppm. It is noteworthy that the signals of all the C-H
protons remarkably shift to upper fields in D2O (solvent) when are compared with the same
signals in DMSO-d6 (Fig. 2). This shift, which amounts to about 1 ppm, reasonably attests to
a conformational change of the oligomeric chain on going from protic to aprotic polar
-
solvent. In D2O, the HSO4 anions are more strongly solvated than in DMSO, largely by
hydrogen bonding, hence depart from the oligomeric matrix to gain increased entropy,
though, as hydrated anions in solution. As a result, the oligomeric chains are left with several
positive point charges positioned along their backbones. Electrostatic repulsions between
these charges force the multicationic chain to adopt a rod-like conformation. Upon adopting
-
this spatially extended conformation associated with detachment of the HSO4 counter ions,
1
13
the oligomer is partially relieved from steric constraints and hence it’s H- and C-signals
shift to higher fields. On the other hand, due to poor solvation of anions in DMSO-d6, the
-
oligomeric chain remains entirely screened by HSO4 anions and presumably adopts a
1
sterically hindered coil-like conformation in this solvent. For this reason, the H and 13C
nuclei of the oligomer experience a rather increased steric hindrance in DMSO and their
signals shift to lower fields. Like most oligomers, ISA 5 normally consists of chains with
different degrees of polymerization. Moreover, even in a single chain, the monomers owing
8

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to their different positions along the molecule may no longer be equivalent, so are expected to
display signals at slightly different chemical shifts. In D2O solution, the 2-H protons (Hf) of
the chemically nonequivalent imidazolium units give multiple singlets at δ 7.65-7.92 and the
4,5-H protons of these units along with the geminal proton of the OSO3H group are seen at
2
6.45-6.62 ppm. A doublet of AB-quartet (with J = 12 Hz and 3J = 4.6 Hz) which appears at
up-field (δH 2.71 and 2.67) of this spectrum (in D2O) is assigned to the diastereotopic protons
of the terminal methylene (CH2-Cl) groups (Fig. 2). These signals are interesting in that
significantly shift to lower fields (δH 3.52 and 3.47) in DMSO-d6 and their integrated
intensity, with respect to that of the remaining aliphatic protons, gives an estimate of the
degree of polymerization (dp) for ISA 5. Considering that application of excess
epichlorohydrin gives the linear ISA 5 symmetrically capped with CH2-Cl groups, the dp of
this polymer can be calculated by the following equation:
̅
(
)
=
̅
where denotes the number-averaged dp for ISA 5, m refers to the number of aliphatic
protons present in each repeating unit, and n is the total number of the terminal CH2-Cl
protons in each polymeric chain. The two symbols Ii and Ij stand for the integral intensity of
the signals arising from the internal aliphatic protons (+N-CH2 and O-CH appearing at δH
3.24-3.57) and the terminal methylene protons n, respectively. Upon determining the value of
Ii/Ij = 4.8 from 1H NMR spectrum of ISA 5 and substituting it into above equation and given
̅
that for most ISA 5 chains m = 5 and n = 4, we obtain for this OIL. The
oligomeric structure of ISA 5 is also supported by its GPC (gel permeation chromatography)
analysis which displays a unimodal size-distribution with number averaged molecular weight
of Mn= 1227 g.mol-1 and polydispersity index of PDI= 1.08. These values correspond to a
̅
narrow size-distribution of the oligomeric molecules with = 3.37 and are in good
agreement with the result obtained from the 1H NMR study of the OIL. The slight difference
1
̅
between the deduced from the H NMR measurement and that from the GPC analysis
̅
(∆ = 0.27) is due to a minute non-oligomeric condensation products, which are eluted
within a longer time as a unimodal weak peak separate from the main GPC curve.
9

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HgSO4
Hd
He
Hg,f
Hf
Hd
Hd
Hb
Ha
Hd
Hd Hd
Hd
Cl
OSOHc
N
N
HcO3SO
Hd
Cl
He
He
HOD
Hf
Ha,b
Hd
He
In D2O
Hc
Hd
Ha,b
In DMSO
Figure 2. 1H NMR spectra of the ISA
5 in D2O and DMSO
Similar shifts to lower fields were observed for the 13C NMR signals of this OIL on
transferring from D2O to DMSO-d6. The magnitude of this shift is somewhat greater for the
carbon nuclei of the imidazolium rings than that of the aliphatic carbons. Probably, the large
deshields of the imidazolium carbons is somehow attributed to the steric requirements of their
-
proximate HSO4 anions. Moreover, the NMR spectra of the ionenes 3 and 4 show that the
1
13
chemical shifts of H and C nuclei in these oligomers considerably vary by exchanging the
-
counter anion Cl- with HSO4 and sulfonation of the OH groups. Other details regarding the
1H NMR and 13C NMR signals are provided in the supporting information of this article.
Thermal behaviour of the synthesized ISA 5 was studied by thermogravimetric analysis
(TGA) and differential scanning calorimetry (DSC) in the temperatures between 25 to
600 °C (Fig. 3). Three weight loss stages are observed in the TGA of the sample. The first
step in the TG curve, which starts at the onset point of 125 °C corresponds to an
endothermic trace, centring at 155 °C, in the DSC thermograph of the polymer and is
followed by two additional mass loss steps occurring at the ranges (220−280 °C) and (320-
365 °C) of the TG analysis. These two latter steps, where appearing in the DSC curve of
ISA 5 at 250 °C and 345 °C, are likewise endothermic in nature but have the enthalpies
much lower than that of the first step. After these three steps, which are explicitly
recognizable from the differential thermogravimetric (DTG) analysis, the oligomer
undergoes a smooth decomposition at temperatures greater than 365 °C to complete
10

ACCEPTED MANUSCRIPT
weight loss. The DSC trace of the oligomer in the temperature interval of this late
decomposition stage shows an exothermic peak occurring at 514.9 °C (Fig.3).
Figure 3. The thermograms TGA (A), DTG (B), and DSC (C) of the ISA 5
In sharp difference to ISA 5, the ionenes 3 and 4 have shown greater thermal stabilities (Fig.
4). The TGA curve of 3 exhibits only one main decomposition step, starting at the onset point
of 315 °C, whilst those of ionene 4 and ISA 5 consist of two and three main decomposition
steps and the onset points of their early steps occur at 230 °C and 125 °C, respectively.
Noticeably, all of these ionenes (3, 4, and 5) have a common endothermic decomposition
trace in their TGA curves, which gives a peak at around 348 °C. Based on these thermograms
one may suggest that the two early decomposition steps of ISA 5 stem from its HSO4
-
substituents and HSO4 anions.
(%)
(%)
11

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100
90
80
70
60
50
40
30
20
10
0
100
90
80
70
60
50
40
30
20
10
0
0
200
400
600
0
200
400
600
800
TGA curve of Ionene 3 Temprature (°C)
TGA curve of Ionene 4 Temprature (°C)
Figure 4. The TGA curves of the ionenes 3 and 4
Owing to possessing HSO4 groups as both counter anion and substituent, ISA 5 is a Brønsted
acidic OIL. An estimate of the acidic strength that is produced by this liquid oligomer in non-
aqueous media can be calculated by Hammett’s acidity function [18]. This function is
expressed by the following equation:
Ho = pKa(BH+)aq + log ([B] / [BH+])
where pKa(BH+)aq denotes the pKa of an indicator base in aqueous solution and [B]/[BH+]
stands for the molar concentration ratio of the indicator to its conjugate acid in non-aqueous
media. Here, 4-nitroaniline (with pKa = 0.99) was chosen as the indicator base and the value
of [B]/[BH+] was determined by measuring the UV-visible absorbances of 4-nitroaniline at
the maximal absorption wave length (λmax) of 335 nm before and after adding ISA 5 to its
solution in CCl4 (Fig. 5). As Table 1 shows, the data obtained from these evaluations afford
the value of Ho = 0.59 for ~2 g.L-1 of the ISA 5 in CCl4.
Table 1. The absorbances measured at λmax= 335 nm for determining the Hammett’s acidity
[a]
value (H0) of the synthesized ISA
5
in CCl4
Amax
Entry
Acid
[B] (%)
100
[BH+] (%)
Ho
-
-
1.139
0.324
0
1
2
ISA
5
28.44
71.55
0.59
a
The conditions adopted for UV–visible measurements in CCl4: 1.44×10−4 mol/L solution (10 mL) of 4-
nitroaniline (pKa (BH+)aq= 0.99) as the base indicator; ISA 5 (the OIL, 20 mg); 25 °C.
12

ACCEPTED MANUSCRIPT
Figure 5. The UV-visible absorption spectra of 4-nitroaniline in CCl4 (A), and after addition of the
ISA 5 (B)
In Table 2 the acidic strength of ISA 5 was compared with those of some mineral and organic
acids in the Hammett’s scale. As can be seen, the acidic strength of ISA 5 is comparable to
that of 0.25 M H2SO4 (aq) and is far greater than most reported acidic ionic liquids.
Table 2. The Hammett’s acidity values for ISA 5 and some selected acids
a
Acid
H2SO4
CF3SO3H
-13.7 [20]
[Gly]NO3
2.44 [21]
[BMIm]HSO4
0.8 [22]
[HMIm]BF4
1.28 [22]
Ho
0.45 [19]
a
0.25 M aqueous solution.
ISA 5 exhibits significant electric conductivity (EC) in both DMSO and water as a signature
of its ionic character. Figure 6 displays the temperature-dependent plots of the electrical
conductivity owned by ISA 5 in DMSO and water. To assess the conductivity owned by ISA
5 in each of the solutions, we made the following calculation:
( ) ( )
( )
where ( ) stands for the contribution of ISA 5 to EC of its solution at a given temperature
and the symbols and refer to conductivities of the solution and the blank
( )
( )
solvent at the same temperature, respectively. It is evident that ISA 5 makes a larger
contribution to EC of its solution in DMSO than in water. This difference shows that the
oligomeric chains have a restricted mobility in water arising from their extensive hydrogen
bonding with solvent and so greater Stokes radii in water than in DMSO. The greater Stokes
radii of ISA 5 chains in water may also be due to the rod-like shape that they adopt in this
solvent. Upon rising the temperature, the EC of ISA 5 in water increases, however, with a far
lower slope than in DMSO. The sharp effect of temperature on the EC of ISA 5 in DMSO is
13

ACCEPTED MANUSCRIPT
related, inter alia, to removal of less-bound solvent molecules from its chain at higher
temperatures and to remarkable conformational folding of the multicationic chains in this
solvent, making the multicationic ISA more mobile. The increasing mobility of the
conjugated anions at elevated temperatures also heightens the EC of the DMSO solution
whereby it reaches to a maximum at 67 °C. Above this temperature, the conductance curve
follows a fairly constant decreasing trend, presumably, due to aggregation of the polymeric
chains and consequently a decrease in the number of ions per volume of solution.
Figure 6. Plots of conductivity ( ) against temperature for ISA 5 in H2O and DMSO
Based on its acidic and ionic-liquid nature, the ISA 5 is expected to play as an effective
medium especially for the acid demanding reactions. In this view, we planned to examine the
utility of ISA 5 in the synthesis of pyrano[3,2-c]quinolines and pyrano[2,3-d]pyrimidines via
the three-component reaction of 4-hydroxyquinolin-2-one 8/6-hydroxy-tetrahydropyrimidin-
4-one 9 with malononitrile 7 and arylaldehydes. For this purpose, the reaction between 4-
hydroxyquinolin-2-one 8, malononitrile 7, and benzaldehyde 6a in the presence of ISA 5 was
chosen as the model reaction. Initial results of our attempts to find out the optimum
conditions for the trial synthesis of 10a were encouraging in terms of yields and reaction
times. The best results for the model reaction were obtained at 80 °C using 0.5 mL of ISA 5
per 1.1 mmol of malononitrile 7 and 1 mmol of each of the other reactants.
In next phase of this investigation we set out to examining the substrate scope of the method
by employing different substituted aromatic aldehydes (Table 3, Scheme 2). As Table 3
shows, this synthetic method has no appreciable sensitivity to presence of various
substituents and goes almost equally well with electron-rich and electron-deficient as well as
sterically hindered aromatic aldehydes to give the desired products. Beside its role as an
acidic catalyst, ISA 5 also plays as solvent. Hence, all the syntheses underwent smoothly in
homogeneous phase.
14

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OH
OH
NH2
NH2
N
CN
Ar
CN
Ar
O
O
N
H
9
O
N
H
8
O
N
+
Ar-CHO
NC
CN
ISA 5, 80 °C
ISA 5, 80 °C
N
H
O
N
H
O
11a-c
6
7
10a-h
Scheme 2. Three-component one-pot synthesis of pyrano[3,2-c]quinolines 10a-h and pyrano[2,3-
d]pyrimidines 11a-c under catalysis of ISA 5
Table 3. The representative syntheses of pyrano[3,2-c]quinolones 10a-h and pyrano[2,3-
d]pyrimidines 11a-c under catalysis of ISA 5 at 80 °C
Product
Ar
Time (min)
Yield (%)a
MpFound (°C)
Mp Lit. (°C)
>300[14]
>300[14]
10
5
90
92
84
89
88
83
90
83
92
80
85
297-299
>300
10a
10b
10c
10d
10e
10f
Phenyl
4-Nitrophenyl
2-Chlorophenyl
3-Bromophenyl
4-Chlorophenyl
4-Methoxyphenyl
4-Methylphenyl
Thiophen-2-yl
3-Nitrophenyl
2-Chlorophenyl
4-Chlorophenyl
>300[14]
15
10
10
15
10
10
10
20
15
294-296
>300
>300[13a]
>300[14]
297-299
297-300
>300
>300[14]
>300[14]
10g
10h
11a
11b
11c
>300[13a]
273-275[13b]
263-265[13b]
254-256[13b]
>300
291-293
276-278
273-275
a
Isolated yields
A comparison of ISA
model product 10a was presented in Table 4. It is evident from this table that ISA
can be represented as an efficient catalyst for the synthesis of pyrano[3,2 c]quinolin‐4‐
5 and some previously reported catalysts for synthesis of the
5
‐
ones. Although ammonium acetate is a cheap and efficient catalyst for the synthesis of
the model product (entry 4), it cannot be recovered completely from the reaction
mixture, due to decomposition in hot solutions via the loss of ammonia. The other
catalysts either result in lower reaction rate (entry 2) or need a complicated procedure,
including fine filtration, for separation from the products (entry 1).
Table 4. A comparative catalytic efficacy of ISA 5 for synthesis of the model product 10a
Entry
Catalyst
Time
Yield (%)a
Conditions
Ref.
15

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1
(CTA)3[SiW14]-Li+-MMT
10 min
93
Reflux/ H2O
[23]
2
3
4
5
KF-Alumina
DABCO
5 h
78
87
94
90
Reflux/ EtOH
Reflux/ H2O:EtOH (1:1)
Reflux/ EtOH
[24]
[25]
20 min
3 min
10 min
Ammonium acetate
The ISA 5
[14]
80 °C, Solvent-free
This work
aIsolated yields
Solubility of ISA
5 in common solvents would be a matter of interest as it throws light
on choice of a suitable procedure for separation of this OIL from the reaction
mixtures. Table 5 exhibits that ISA is insoluble in common nonpolar solvents, as a
consequence of its ionic and polar groups.
5
Table 5. Solubility of ISA 5 in common selected solvents
Solvent
CH2Cl2
CHCl3
EtOH
At 25 °C
Insoluble
Insoluble
Less soluble
Soluble
Hot a
Insoluble
Insoluble
Soluble
H2O
Soluble
AcOEt
Acetone
DMSO
Insoluble
Insoluble
Soluble
Insoluble
Insoluble
Soluble
a
At 60 °C except for CH2Cl2 (35 °C) and acetone (55 °C).
Reusability and recycling performance of ISA
5 was examined for production of
compound 10a at 80 °C. It was found that the recovered oligo(ionic liquid) could be
reused directly in the next run without appreciable loss of activity even after four times
recycling (Fig. 7).
16

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Time (min)
Yields (%)
100
80
60
40
20
0
90
90
89
89
88
1
2
3
4
5
Runs
Figure 7. The reusability of ISA 5 in synthesis of (10a) at 80 °C
Conclusion
Co-oligomerization of imidazole with epichlorohydrin led to formation of a light 1,3-ionene,
which on sulfonylation with chlorosulfonic acid and subsequent anion exchange with sulfuric
1
acid gave the ionenesulfuric acid ISA 5. The H and 13C NMR spectra of this ionene are
consistent with its oligo(ionic liquid) structure and displayed a conformational change when
ISA 5 was transferred from D2O to DMSO, as a sign of its multicationic nature. The liquid
ISA was proved to be a highly efficient Brønsted acidic promoter for synthesis of
pyrano[3,2-c]quinolines and pyrano[2,3-d]pyrimidines via a simple one-pot protocol under
solvent-free conditions to give fairly high yields in short reaction times. The oligo(ionic
liquid) can be reused several times without sensible loss of activity.
Acknowledgements
The authors are grateful to the Research Council of University of Guilan for support of this
work.
17

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Highlights
A liquid ionene, bearing HSO4 counter anion and substituent, was synthesized► The ionene has a
flexible conformation responding to solvent changes► It seems to take a rod-like conformation and
resists to folding by heating in water► The ionene was applied as a catalyst for synthesis of some
pyran-annulated quinolines and pyrimidines► The ionene has a long-term stability and can be
recycled several times.
20