Introduction of a novel dicationic Br?nsted acidic ionic liquid based on pyrazine and its application in the synthesis of xanthenediones and 3, 4-dihydropyrimidin-2(1H)-ones under solvent-free conditions

Article abstract of DOI:10.1007/s11164-020-04089-9

A novel dicationic Br?nsted acidic ionic liquid based on pyrazine has been prepared and characterized by FTIR, ¹H NMR, ¹³C NMR, MS, thermal gravimetric and differential thermal gravimetric analysis and also Hammett acidity function.

Full text of DOI:10.1007/s11164-020-04089-9

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-020-04089-9
Introduction of a novel dicationic Brönsted acidic ionic
liquid based on pyrazine and its application in the synthesis
of xanthenediones and 3, 4‑dihydropyrimidin‑2(1H)‑ones
under solvent‑free conditions
Seyyed Erfan Sadati Sorkhi1 · Mohammad M. Hashemi1 · Ali Ezabadi2
Received: 19 September 2019 / Accepted: 17 January 2020
© Springer Nature B.V. 2020
Abstract
A novel dicationic Brönsted acidic ionic liquid based on pyrazine has been prepared
1
and characterized by FTIR, H NMR, 13C NMR, MS, thermal gravimetric and dif-
ferential thermal gravimetric analysis and also Hammett acidity function. The pre-
pared dicationic ionic liquid is found to be an efcient and reusable catalyst for the
synthesis of xanthenediones and 3,4-dihydropyrimidin-2(1H)-ones under solvent-
free conditions. The merits of the developed procedure include novelty in terms of
the ionic liquid, easy preparation of the ionic liquid, easy workup, reusability of the
catalyst, high yield, short reaction time and absence of toxic organic solvent.
Keywords Dicationic ionic liquid · Pyrazine · Xanthenediones ·
3,4-Dihydropyrimidin-2(1H)-ones · Solvent-free
Introduction
Ionic liquids (ILs) are organic salts comprised of organic cations in combination
with organic and/or inorganic anions, which exhibit a myriad of remarkable and
interesting properties, such as wide liquid range, negligible vapor pressure, sim-
ple recovery process, high ionic conductivity, broad electrochemical window and
design ability by appropriate modifcations of cations or anions in structures [1,
2]. Recently, many researches have been focusing on the development of a new
subclass of ILs known as dicationic ionic liquids (DILs), which typically con-
sist of two cationic head groups linked by a rigid or fexible spacer, associated
*
Mohammad M. Hashemi
mhashemi@sharif.edu
1
2
Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran
Department of Chemistry, Faculty of Science, Central Tehran Branch, Islamic Azad University,
Tehran, Iran
Vol.:(0123456789)
1 3

S. E. Sadati Sorkhi et al.
with two counteranions [3]. Compared to monocationic ILs, multicationic ones
can have a higher melting point, viscosity, surface tension, thermal stability, wide
liquid range and tenability of chemical and physical properties [4, 5]. Therefore,
they have good potential to be used in a wide range of applications including
solar cells, fuel cells, batteries, lubricants, reaction media, separation technolo-
gies, material preparation, catalysis reactions and, more recently, improving the
isomerization degree of n-pentane and electrolytes for photo-harvesting [6–8].
Structures containing xanthene moiety are well known to have a wide range of
biological and pharmacological activities, such as antibacterial [9], anti-infam-
matory [10] and antiviral [11] activities. They are used as an antagonist for para-
lyzing the action of zoxazolamine [12] and in photodynamic therapy [13]. These
heterocyclic compounds are also used as dyes [14], as pH-sensitive fuorescent
materials for visualization of biomolecules [15] and in laser technologies because
of their valuable spectroscopic properties [16]. In addition, xanthenediones occur
as constituent units in a large number of natural products [17].
Therefore, in recent years, many eforts have been focused on the synthesis of
xanthenediones by one-pot condensation of aldehydes with 5,5-dimethyl-1,3-cy-
clohexanedione in the presence of catalysts such as Brönsted–Lewis acidic ionic
liquids [18], CuO nanoparticles [19], trichloromelamine [20], secondary amine-
based ionic liquid [21], SmI3 [22], 1-butyl-3-methylimidazolium hydrogen sul-
fate [bmim] HSO4 [23], carboxy-functionalized ionic liquid [24], β-cyclodextrin
grafted with butyl sulfonic acid [25], cesium salt for phosphotungstic acid
[26], titanium aminophosphates [27], [Et3NH][HSO4] [28], SbCl3/SiO2 [29],
ZrOCl2·8H2O [30], Fe3O4 nanoparticles [31], InCl3 or P2O5 [32], 3-(N,N-dime-
thyldodecylammonium) propanesulfonic acid hydrogen sulfate ([DDPA][HSO4])
[33], [DABCO](SO3H)2Cl2 [34], imidazol-1-yl-acetic acid [35], [Et3N–SO3H]Cl
[36], natural acidic ionic liquid immobilized on magnetic silica [37], task-specifc
dicationic ionic liquids [38], acetic acid [39], amberlite IR-120H [40], cyclodex-
trin nanosponges [41] and phosphomolybdic acid supported on Schif-base-func-
tionalized graphene oxide nanosheets [42].
Due to our interest in the design, preparation and use of novel ionic liquids for
organic transformations [43–46], herein we report for the frst time the develop-
ment of a new dicationic Brönsted acidic ionic liquid (Fig. 1)-catalyzed synthesis
of xanthenediones and 3,4-dihydropyrimidin-2(1H)-ones under solvent-free con-
ditions (Schemes 1, 2).
Fig. 1 Structure of the dica-
tionic Brönsted ionic liquid
1 3

Introduction of a novel dicationic Brönsted acidic ionic liquid…
Scheme 1 Synthesis of xanthenediones catalyzed by {[SO3H–Pyrazine–SO3H]Cl2}d under solvent-free
conditions
Scheme 2 Synthesis of DHPMs catalyzed by {[SO3H–Pyrazine–SO3H]Cl2} under solvent-free condi-
tions
Experimental section
All reagents and solvents were commercially available and used without fur-
1
ther purifcation. H NMR and 13C NMR in DMSO-d6 were recorded on a Bruker
Avance Ultrashield spectrometer at 500 and 125 MHz, respectively. Chemical shifts
were reported in parts per millions (δ), relative to the internal standard of tetra-
methylsilane (TMS). Thermal analysis (TG–DTA) of the DIL was recorded on a
STA-1500 Rheometric Scientifc TGA. Mass spectrometry (MS) studies were per-
formed using 5957C VL MSD with a triple-axis detector, Agilent Technologies (ion
source: electron impact (IE) 70 eV, ion source temperature: 230 °C, analyzer: Quad-
rupole). FTIR spectrum was taken on a FTIR PerkinElmer Spectrum Version 10.51
with KBr plates. Melting points were recorded on a Mettler Toledo Type FP62 in
open capillary tubes.
Preparation of the catalyst
A round-bottom fask (100 mL) was flled with a solution of pyrazine (3.2 g,
0.04 mol) in chloroform (80 mL) and cooled in an ice bath. Then, with intensive
stirring, chlorosulfonic acid (5.3 mL, 0.08 mol) was added dropwise over a period
of 10 min at 0 °C. After addition, the reaction mixture was removed from the ice
bath and stirred for 4 h at room temperature. A white precipitate formed, which was
fltered, washed with chloroform (3×15 mL) and dried at room temperature in 94%
of yield (Scheme 3).
1 3

S. E. Sadati Sorkhi et al.
Scheme 3 Preparation of {[SO3H–Pyrazine–SO3H]Cl2}
Determination of the structure of the catalyst
For determining the structure of the catalyst, several techniques including FTIR,
1H NMR, 13C NMR, TG/DTA and MS were used.
FTIR
FTIR spectrum of the catalyst is depicted in Fig. 2. The presence of some bonds
reveals the complete transfer of acidic hydrogen from chlorosulfonic acid to two
nitrogen atoms of pyrazinium ring.
The broad peak at 3400–2400 cm−1. This peak is due to the stretching vibration
•
of O–H bond present in SO3H group.
Two peaks at 1617 cm−1 and 1487 cm−1. These two peaks belong to C=N and
•
C=C vibrations, respectively.
Two peaks at 1158 cm−1 and 1228 cm−1. These two peaks belong to O–SO2 sym-
•
metric and asymmetric stretching, respectively, and the other band at 1009 cm−1
is related to N–SO2 stretching.
Fig. 2 FTIR spectrum of {[SO3H–Pyrazine–SO3H]Cl2}
1 3

Introduction of a novel dicationic Brönsted acidic ionic liquid…
1H NMR
Another evidence for determining the structure of the catalyst is extracted from
1
NMR study. The H NMR of the catalyst is shown in Fig. 3. Two singlet signals
are observed in 1H NMR spectrum of the catalyst.
•
•
Signal at 8.66 ppm which is related to four hydrogen atoms of pyrazinium ring.
Signal at 11.95 ppm which is related to two acidic hydrogen atoms of SO3H
groups.
13C NMR
13C NMR of the catalyst is shown in Fig. 4. The spectrum shows only one peak
at 145.08 ppm, which clearly indicates the symmetrical structure of the catalyst.
Fig. 3 1H NMR spectrum of {[SO3H–Pyrazine–SO3H]Cl2}
1 3

S. E. Sadati Sorkhi et al.
Fig. 4 13C NMR spectrum of {[SO3H–Pyrazine–SO3H]Cl2}
Mass spectrum
The mass spectrum of the DIL is shown in Fig. 5. In this spectrum, the molecular
ion appears at 312 m/z. Other ionic peaks are also observed at 277 (M+–Cl), 150
(M+–2SO3H), 115 (M+–2SO3H and Cl) and 80 (M+–2SO3H, 2Cl).
TG/DTA
The behavior of the DIL against heat change was investigated by thermal gravimet-
ric (TG) and diferential thermal gravimetric (DTA) analysis. TG and DTA plots of
DIL showed that the weight losses in one step as well as stability at about 285 °C
(Fig. 6).
In another study, to prove that {[SO3H–Pyrazine–SO3H]Cl2} was correctly synthe-
sized, we decided to do the halogen test. Therefore, we added silver nitrate solution to
the aqueous solution of the dicationic ionic liquid. This addition led to a white solid,
1 3

Introduction of a novel dicationic Brönsted acidic ionic liquid…
Fig. 5 Mass spectrum of {[SO3H–Pyrazine–SO3H]Cl2}
Fig. 6 TG/DTA of {[SO3H–Pyrazine–SO3H]Cl2}
which indicates the formation of silver chloride. This result showed that the DIL con-
tains chloride anions.
Hammett acidity function
The acidity of the synthesized ionic liquid was measured using UV–visible spec-
troscopy by means of 4-nitroaniline as a basic indicator. The UV absorption of
4-nitroaniline solely as well as mixed with the dicationic Brönsted acidic ionic liq-
uid in water is shown in Fig. 7. The maximum absorbance was observed at 380 nm.
Hammett acidity function, H0 can be calculated using the following equation:
(
)
[I]
[IH+]
H0 = pK(I)aq + log
1 3

S. E. Sadati Sorkhi et al.
Fig. 7 Hammett acidity function of the {[SO3H–Pyrazine–SO3H]Cl2}
where pK(I)aq is pKa value of 4-nitroaniline (0.99) and [IH+] and [I] (I represents
indicator) are the molar concentrations of the protonated and unprotonated forms of
the indicator, respectively. The [I]/[IH+] ratio can be determined from absorbance
measured before and after the addition of the ionic liquid. The detailed results are
given in Table 1.
Results and discussion
To achieve the appropriate reaction conditions, the reaction of 4-chlorobenzaldehyde
and 5,5-dimethyl-1,3-cyclohexanedione catalyzed by {[SO3H–Pyrazine–SO3H]Cl2}
was chosen as model reaction, and the reaction was carried out under diferent sets
of conditions with respect to solvents, amounts of catalyst and temperatures.
Initially, the model reaction was investigated in diferent solvents (Table 2,
entries 1–5). The solvents did not improve the yield of the reaction in the presence
of the catalyst. Therefore, we carried out the model reaction under solvent-free
Table 1 Calculation of H0 value
Ionic liquid
Blank
Absorbance [I] (%) [IH+] (%) [I]/[IH+] H0
of {[SO3H–Pyrazine–SO3H]
Cl2} in water at 298 K
1.2
100
0
–
–
{[SO3H–Pyra- 0.34
zine–SO3H]
Cl2}
28.3
71.7
0.39
0.58
Condition for UV–visible spectrum measurement: solvent: H2O,
indicator: 4-nitroaniline, 7.5×10−5 mol L−1; IL: 3×10−3 mol L−1
25 °C
,
1 3

Introduction of a novel dicationic Brönsted acidic ionic liquid…
Table 2 Efect of diferent reaction conditions on {[SO3H–Pyrazine–SO3H]Cl2}-catalyzed synthesis of
xanthenediones
Entry
Solvent
Temperature (°C)
Catalyst
(mol%)
Time (min)
Yielda (%)
1
2
3
4
5
6
7
8
CH2Cl2
EtOAc
Acetone
EtOH
Refux
Refux
Refux
Refux
Refux
100
90
110
100
100
25
25
25
25
25
25
25
25
20
30
–
300
300
300
300
300
15
25
10
25
10
41
42
48
64
52
93
88
78
H2O
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
9
10
11
90
91
Very low
100
15
Reaction conditions: 4-chlorobenzaldehyde (1 mmol); 5,5-dimethyl-1,3-cyclohexanedione (2 mmol); sol-
vent (15 mL)
aIsolated yield
conditions. The result (Table 2, entry 6) indicates that the yield of the reaction
under solvent-free conditions was higher and the reaction time was shorter in
comparison with solvent conditions.
To optimize the reaction temperature, the model reaction was heated at 90 and
110 °C (Table 2, entries 7, 8). The results shown in Table 2 indicate that the
100 °C led to highest yield; therefore, it was selected as the reaction temperature
for all further reactions. Finally, the model reaction was optimized by varying the
amounts of catalysts (20 and 30 mol%) at 100 °C under solvent-free conditions
(Table 2, entries 9 and 10). The results show that 25 mol% of the catalyst is suf-
cient for the best results. To determine the role of the catalyst, the model reaction
was performed in the absence of the catalyst at the same condition, which results
in very low yield of the product (Table 2, entry 11), which indicates the high
catalytic activity of {[SO3H–Pyrazine–SO3H]Cl2} in the synthesis.
To evaluate the scope and the limitations of this method, we extended our
studies to various aldehydes under the optimized conditions. These results are
depicted in Table 3. From the results, we could see that all reactions proceeded
smoothly to aford the corresponding xanthenediones in high to excellent yields
in the short reaction times. Various functional groups present in the aryl alde-
hydes such as halogen, methoxy, hydroxy and nitro groups were tolerated
(Table 3, entries 1–12). Extension of this methodology to heterocyclic aldehyde
was also successful (Table 3, entry 13).
In view of green chemistry, reusability of the catalyst is important. Therefore,
some experiments were run under the same optimal conditions mentioned above
over the {[SO3H–Pyrazine–SO3H]Cl2}. The results showed that the catalyst could
1 3

S. E. Sadati Sorkhi et al.
Table 3 {[SO3H–Pyrazine–SO3H]Cl2}-catalyzed synthesis of xanthenediones
Entry Aldehyde
Product Time (min) Yielda (%) Melting point (°C)
Found
Reported [Ref.]
1
2
3
4
5
6
7
8
9
4-Chlorobenzaldehyde
Benzaldehyde
3a
3b
3c
3d
3e
3f
3g
3h
3i
15
35
35
15
33
30
25
35
20
93
93
95
95
81
80
96
97
91
234–236 230–232 [23]
202–204 204–205 [23]
239–242 240–241 [23]
170–172 170–172 [28]
191–193 192–194 [24]
220–222 223–225 [29]
187–189 189–191 [35]
4-Bromobenzaldehyde
3-Nitrobenzaldehyde
3-Bromobenzaldehyde
3-Hydoxybenzaldehyde
2-Methoxybenzaldehyde
Terephethaldehyde
>300
>300 [34]
4-Hydroxy-3-methoxybenzal-
226–228 226–228 [28]
dehyde
10
11
12
13
4-Hydoxybenzaldehyde
4-Fluorobenzaldehyde
2-Bromobenzaldehyde
2-Thiophenecarbaldehyde
3j
3k
3l
45
40
25
45
87
90
84
77
251–253 247–248 [30]
226–227 226–227 [29]
226–228 226–229 [30]
163–165 164–165 [30]
3m
Reaction conditions: aromatic aldehyde (1 mmol), 5,5-dimethyl-1,3-cyclohexanedione (2 mmol),
{[SO3H–Pyrazine–SO3H]Cl2} (0.25 mmol) at 100 °C under solvent-free conditions
aIsolated yield
Fig. 8 Reusability of the {[SO3H–Pyrazine–SO3H]Cl2} in the reaction of 4-chlorobenzaldehyde and
5,5-dimethyl-1,3-cyclohexanedione under optimized reaction conditions
1 3

Introduction of a novel dicationic Brönsted acidic ionic liquid…
Scheme 4 The suggested mechanistic pathway for formation of xanthenediones in the presence of the
catalyst
Table 4 Comparison of the efciency of various catalysts with {[SO3H–Pyrazine–SO3H]Cl2} in the syn-
thesis of 3a
Entry Catalyst
Amount
of catalyst
(mol%)
Conditions
Time (min) Yield (%)
1
{[SO3H–Pyrazine–SO3H]
25
Solvent-free, 100 °C 10
93 (This work)
Cl2}
2
3
4
5
6
7
[Et3NH][HSO4]
[DDPA][HSO4]
[DDPA][HSO4]
Fe3O4 nanoparticles
[n-Pr2NH2][HSO4]
[Et3–SO3H]Cl
20
10
40
10
50
25
Solvent-free, 100 °C 45
Solvent-free, 100 °C 90
87 [28]
87 [33]
90 [23]
90 [31]
85 [21]
93 [36]
H2O, 100 °C
210
Solvent-free, 100 °C 20
Solvent-free, 80 °C
Solvent-free, 80 °C
10
40
accelerate the reaction three runs without a signifcant loss in its catalytic activity
(Fig. 8).
The mechanism of the reaction starts with facilitating Knoevenagel condensation
due to activating carbonyl group of aldehyde by acidic property of catalyst. In the
following, the catalyst again plays a signifcant role in accelerating the Michael addi-
tion and dehydration (Scheme 4).
A comparative study on the catalytic activity of the introduced catalyst in this
paper with some reported catalysts was carried out using 3a as a model compound
1 3

S. E. Sadati Sorkhi et al.
(Table 4). From this study, {[SO3H–Pyrazine–SO3H]Cl2} can be regarded as a more
powerful catalyst for the synthesis of xanthenediones in terms of the yield and the
reaction time.
Multicomponent reactions (MCRs) are defned as one-pot processes that com-
bine at least three reactants to selectively form single complex compounds as well as
small heterocycles containing essentially all the atoms of the reactants [47]. Among
MCRs, the Biginelli reaction allows for the straight access of multifunctionalized
3,4-dihydropyrimidin-2(1H)-ones (DHPMs) through one-pot cyclocondensation of
an aldehyde, a β-keto ester and urea in the presence of catalytic amount of acid [48,
49]. Molecules containing DHPM core and its derivatives are of immense biologi-
cal importance due to a wide range of pharmaceutical and therapeutic properties
such as antiviral [50], antitumor [51], antibacterial [52, 53], anti-infammatory [54],
anti-HIV agents [55, 56], mitotic kinesin inhibition [57], calcium channel modula-
tion [58, 59], α1a-adrenergic antagonists [60] and A2B adenosine receptor antago-
nists [61]. In the classical Biginelli conditions, low yields and difcult isolation of
the products are the main drawbacks due to strongly acidic conditions [62]. Hence,
many catalytic methods including Brönsted and Lewis acid [63–73], ionic liquids
[74–78], polymer-supported catalyst [79] and nanoparticles [80–84] have been intro-
duced to enhance the efciency of the synthesis of these important heterocycles.
After obtaining acceptable results from xanthenediones synthesis catalyzed by
{[SO3H–Pyrazine–SO3H]Cl2}, we decided to study its efciency in the synthesis of
DHPMs (Scheme 2). In order to obtain the optimized conditions, the model reaction
involving cyclocondensation of 4-chlorobenzaldehyde, ethyl acetoacetate and urea
was examined. As given in Table 5, the best result was obtained when the reaction
was carried out at 120 °C in the presence of 25 mol% of {[SO3H–Pyrazine–SO3H]
Table 5 Efect of diferent reaction conditions on {[SO3H–Pyrazine–SO3H]Cl2}-catalyzed synthesis of
DHPMs
Entry
Solvent
Temperature (°C)
Amount of cata-
lysts (mol%)
Time (min)
Yielda (%)
1
2
3
4
5
6
7
8
H2O
H2O/EtOH
Acetone
EtOAc
CHCl3
Refux
Refux
Refux
Refux
Refux
Refux
120
110
100
120
120
25
25
25
25
15
15
25
25
25
20
15
70
67
110
90
105
55
10
17
40
15
38
42
50
64
68
75
51
92
81
78
85
71
CH3CN
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
9
10
11
Reaction conditions: 4-chlorobenzaldehyde (1 mmol), ethyl acetoacetate (1 mmol), urea (2 mmol), sol-
vent (15 mL)
aIsolated yield
1 3

Introduction of a novel dicationic Brönsted acidic ionic liquid…
Cl2} under solvent-free conditions. After getting the satisfactory reaction condition
in hand, the scope and efciency of this approach were examined with respect to
aldehydes, and the obtained results are shown in Table 6. Fortunately, a variety of
functional groups, such as halo, methoxy, hydroxy and nitro, were all well tolerated
(Table 6, entries 1–10). In addition, heterocyclic aromatic aldehyde aforded the cor-
responding product with high yield (Table 6, entry 11).
A plausible one-pot reaction pathway for the synthesis of DHPMs catalyzed by
{[SO3H–Pyrazine–SO3H]Cl2} is proposed in Scheme 5. Initially, acyl imine inter-
mediate (I) is produced via condensation of aryl aldehyde and urea in the presence
of the catalyst as a Brönsted acidic catalyst. Next, ethyl acetoacetate attacks the (I),
followed by intramolecular cyclization and dehydration reaction under acidic condi-
tion to yield the Biginelli product.
Next, the reusability of {[SO3H–Pyrazine–SO3H]Cl2} was examined in the
reaction of 4-chlorobenzaldehyde, ethyl acetoacetate and urea under optimized
conditions. As shown in Fig. 9, the catalyst could be reused three times without a
signifcant loss in its catalytic activity. In order to show the efcacy of {[SO3H–Pyra-
zine–SO3H]Cl2}, a comparison of the present method and some reported methods is
shown in Table 7. As revealed from this table, the catalyst can be considered as a
more powerful catalyst for the synthesis of DHPMs in terms of the yield and reac-
tion time.
General procedure for the synthesis of xanthenediones under solvent‑free
conditions
To a mixture of aromatic aldehyde (1 mmol) and 5, 5-dimethyl-1, 3-cyclohexanedi-
one (2 mmol), 25 mol% of {[SO3H–Pyrazine–SO3H]Cl2} (0.25 mmol) was added
Table 6 {[SO3H–Pyrazine–SO3H]Cl2}-catalyzed synthesis of DHPMs
Entry Aldehyde
Product Time (min) Yielda (%) Melting point (°C)
Found Reported [Ref.]
1
2
3
4
5
6
7
8
4-Chlorobenzaldehyde
5a
5b
5c
5d
5e
5f
10
10
15
13
17
17
18
15
10
18
15
92
87
88
83
87
89
81
83
82
88
90
213
189
213
230
190
208
217
230
183
212
210
214–215 [73]
199.9–201 [78]
214–215 [73]
211–212 [73]
184–185 [85]
206–208 [86]
214–216 [87]
233.5–234.1 [78]
182–184 [85]
209.9–212 [78]
212–214 [88]
3-Chlorobenzaldehyde
2-Chlorobenzaldehyde
4-Bromobenzaldehyde
3-Bromobenzaldehyde
2-Bromobenzaldehyde
4-Nitrobenzaldehyde
3-Nitrobenzaldehyde
4-Fluorobenzaldehyde
Benzaldehyde
5g
5h
5i
9
10
11
5j
2-Thiophenecarbaldehyde 5k
Reaction conditions: aromatic aldehyde (1 mmol), ethyl acetoacetate (1 mmol), urea (2 mmol) and
{[SO3H–Pyrazine–SO3H]Cl2} (0.25 mmol) at 120 °C under solvent-free conditions
aIsolated yield
1 3

S. E. Sadati Sorkhi et al.
Scheme 5 Plausible mechanism for one-pot synthesis of DHPMs in the presence of the catalyst
Fig. 9 Reusability of the {[SO3H–Pyrazine–SO3H]Cl2} in the reaction of 4-chlorobenzaldehyde, ethyl
acetoacetate and urea under optimized reaction conditions
1 3

Introduction of a novel dicationic Brönsted acidic ionic liquid…
Table 7 Comparison of the efciency of various catalysts with {[SO3H–Pyrazine–SO3H]Cl2} in the syn-
thesis of 5a
Entry Catalyst
Reaction condition Time
Yield (%) References
1
2
3
4
5
{[SO3H–Pyrazine–SO3H]Cl2} (25 mol%) Solvent-free, 120 °C 10 min 92
This work
[89]
[90]
[80]
[78]
Montmorillonite KSF (0.5 g)
Al(HSO4)3 (10 mol%)
Fe3O4 @ CM (20 mg)
Phytic acid (10 mol%)
Solvent-free, 130 °C 48 h
Solvent-free, 130 °C 55 min 90
Water, refux 60 min 95
Solvent-free, 100 °C 3.5 h 86
76
and the reaction mixture was heated at 100 °C with stirring. After completion of
the reaction monitored by thin-layer chromatography (TLC), the reaction mixture
was allowed to cool at room temperature. Water (10 mL) was added and fltered to
separate the catalyst. Then, the obtained solid product was fltered and then recrys-
tallized from ethanol to aford the pure product. The products were identifed by IR,
1H NMR and physical data (M.P.) with those reported in the literature.
General procedure for the synthesis of DHPMs under solvent‑free conditions
To a mixture of aromatic aldehyde (1 mmol), ethyl acetoacetate (1 mmol) and urea
(2 mmol), 25 mol% of {[SO3H–Pyrazine–SO3H]Cl2} (0.25 mmol) was added and
the reaction mixture was heated at 120 °C with stirring. After completion of the
reaction evident from thin-layer chromatography (TLC), the reaction mixture was
allowed to cool at room temperature. Water (10 mL) was added and the obtained
solid product was fltered and then recrystallized from ethanol. The products were
identifed by IR, 1H NMR and physical data (M.P.) with those reported in the litera-
ture. The spectra data for some selected compounds are presented in the following.
Spectra data of some selected compounds
3,4,6,7‑Tetrahydro‑3,3,6,6‑tetramethyl‑9‑(4‑chlorophenyl)‑2H‑xanthene‑1,8(5H,
1
9H)‑dione (3a) H NMR (500 MHz, CDCl3): 7.27 (d, 2H), 7.22 (d, 2H), 4.75 (s,
1H), 2.46 (s, 4H), 2.24 (dd, 4H), 6.12 (s, 6H), 6.27 (s, 6H). IR (KBr): 2956, 1661,
1362, 1198, 1007 cm−1.
3,4,6,7‑Tetrahydro‑3,3,6,6‑tetramethyl‑9‑(3‑hydroxyphenyl)‑2H‑xanthene‑1,8(5H,
1
9H)‑dione (3f) H NMR (500 MHz, DMSO-d6): δ 9.18 (s, 1H), 6.96 (t, 1H), 6.62
(s, 1H), 6.53 (d, 2H), 6.46 (d, 1H), 4.42 (s, 1H), 2.49 (s, 4H), 2.16 (dd, 4H), 1.04
(s, 6H), 0.90 (s, 6H). IR (KBr): 3330, 2962, 1658, 1598, 1453, 1362, 1255, 1199,
1143 cm−1.
3,4,6,7‑Tetrahydro‑3,3,6,6‑tetramethyl‑9‑(2‑thienyl)‑2H‑xanthene‑1,8(5H, 9H)‑dione
1
(3m) H NMR (500 MHz, DMSO-d6): δ 7.21 (q, 1H), 6.82 (q, 1H), 6.75 (d, 2H),
4.85 (s, 1H), 2.49 (m, 4H), 2.22 (dd, 2H), 1.03 (s, 6H), 0.953 (s, 6H). IR (KBr):
2957, 2872, 1664, 1360, 1164, 1003 cm−1.
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S. E. Sadati Sorkhi et al.
5‑Eth1oxycarbonyl‑6‑methyl‑4‑(4‑chlorophenyl)‑3,4‑dihydropyrimidine‑2(1H)‑one
(5a) H NMR (500 MHz, DMSO-d6): δ 9.23 (s, 1H), 7.76 (s, 1H), 7.38 (d, 2H),
7.23 (d, 2H), 5.12 (s, 1H), 3.96 (q, 2H, CH2O), 2.23 (s, 3H), 1.09 (t, 3H). IR (KBr):
3239, 3116, 2977, 1712, 1640, 1461, 1288, 1091, 782 cm−1.
5‑Ethoxycarbonyl‑6‑methyl‑4‑(4‑bromophenyl)‑3,4‑dihydropyrimidine‑2(1H)‑one
1
(5d) H NMR (500 MHz, DMSO-d6): δ 9.23 (s, 1H), 7.76 (s, 1H), 7.53 (d, 2H), 719
(d, 2H), 5.12 (s, 1H), 3.96 (q, 4H), 2.24 (s, 3H), 1.10 (t, 3H). IR (KBr): 3235, 3116,
2981, 1712, 1616, 1403, 1292, 1222, 1091, 779 cm− 1
.
1
5‑Ethoxycarbonyl‑6‑methyl‑4‑(2‑thienyl)‑3,4‑dihydropyrimidine‑2(1H)‑one (5k) H
NMR (500 MHz, DMSO-d6): δ 9.30 (s, 1H, NH), 7.89 (s, 1H, NH), 6.88-7.35 (m,
ArH), 5.41 (s, 1H), 2.21 (s, 3H), 1.18 (t, 3H). IR (KBr): 3332, 3235, 3116, 2977,
1700, 1643, 1419, 1307, 1226, 1095, 786 cm−1.
5‑Eth1oxycarbonyl‑6‑methyl‑4‑(4‑nitrophenyl)‑3,4‑dihydropyrimidine‑2(1H)‑one
(5g) H NMR (500 MHz, CDCl3): δ 9.34 (s, 1H), 8.22 (d, 2H), 7.88 (s, 1H, NH),
7.51 (s, 1H), 5.27 (s, 1H), 4.006 (q, 4H), 2.26 (s, 3H), 1.10 (t, 3H). IR (KBr): 3232,
3120, 2981, 1704, 1643, 1523, 1349, 1299, 1318, 1095, 782 cm−1.
Conclusion
In this research, we have described the preparation, characterization and catalytic
application of {[SO3H–Pyrazine–SO3H]Cl2} in the synthesis of xanthenediones and
DHPMs under solvent-free conditions. Ease of preparation and handling of the cata-
lyst, generality, easy workup procedure, high yields, short reaction times, reusability
of catalyst and absence of organic solvents are the attractiveness of the developed
procedure.
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