Preparation of a new DABCO-based ionic liquid and investigation on its application in the synthesis of benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline derivatives

Article abstract of DOI:10.1016/j.molliq.2017.07.080

In this article, we report the preparation of a new ionic liquid from the reaction of DABCO and sulfuric acid and its characterization using FT-IR, Mass and NMR spectroscopy. This ionic liquid is air- and water-stable and affordable. Afterward this reagen

Full text of DOI:10.1016/j.molliq.2017.07.080

Accepted Manuscript
Preparation of a new DABCO-based ionic liquid and investigation
on its application in the synthesis of benzimidazoquinazolinone
and pyrimido[4,5-b]-quinoline derivatives
Farhad Shirini, Mohaddeseh Safarpoor Nikoo Langarudi, Nader
Daneshvar, Maryam Mashhadinezhad, Nazanin Nabinia
PII:
DOI:
Reference:
S0167-7322(17)32308-5
doi: 10.1016/j.molliq.2017.07.080
MOLLIQ 7658
To appear in:
Journal of Molecular Liquids
Received date:
Revised date:
Accepted date:
27 May 2017
12 July 2017
20 July 2017
Please cite this article as: Farhad Shirini, Mohaddeseh Safarpoor Nikoo Langarudi, Nader
Daneshvar, Maryam Mashhadinezhad, Nazanin Nabinia , Preparation of a new DABCO-
based ionic liquid and investigation on its application in the synthesis of
benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline derivatives, Journal of
Molecular Liquids (2017), doi: 10.1016/j.molliq.2017.07.080
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ACCEPTED MANUSCRIPT
Preparation of a new DABCO-based ionic liquid and
investigation on its application in the synthesis of
benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline
derivatives
Farhad Shirini,a,b* Mohaddeseh Safarpoor Nikoo Langarudia, Nader Daneshvarb, Maryam
Mashhadinezhada, Nazanin Nabiniaa
a Department of Chemistry, College of Science, University of Guilan, Rasht, 41335-19141, Iran, Tel/Fax: +981313233262; e-mail:
shirini@guilan.ac.ir (and also fshirini@gmail.com).
b Department of Chemistry,College of Science, University of Guilan, University Campus 2, Rasht, Iran
Abstract— In this article, we report the preparation of a new ionic liquid from the reaction of DABCO and sulfuric acid and its
characterization using FT-IR, Mass and NMR spectroscopy. This ionic liquid is air- and water-stable and affordable. Afterward this reagent
is used for the synthesis of benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline derivatives as a catalyst. The results shows the
applicability of the prepared reagent as a reusable catalyst without losing its activity. This procedure possesses some advantages such as
ease of preparation of the catalyst, simple work-up procedure, short reaction times, excellent yields and use of nontoxic and inexpensive
catalyst.
Keywords: DABCO, ionic liquids, benzimidazoloquinazolinones, pyrimido[4,5-b]-quinolines, 2-aminobenzimidazole, 6-amino-1,3-
dimethyluracil.
1. Introduction
Recently, organocatalysts has been utilized in organic reactions increasingly. It is due to the inimitable advantages such as their
potential to use in large scale production, industries, and complete asymmetric synthetic processes as well as their availability and
low cost. Also, lack of transition-metal brings them at the heart of green chemistry [1].
One of these organocatalysts is 1,4-diazabicyclo[2.2.2]octane (DABCO) which has been used as a weak base [2, 3] or a ligand
[4, 5] in many organic reactions. Besides, DABCO possesses some unique properties such as being inexpensive, high reactive and
easy to handle. In addition using this reagent the products can be obtained in excellent yields with high selectivity [6-10]. In recent
years, DABCO, as a cage-like compound with medium‐hindrance, has been used for the synthesis of a new class of ionic liquids
[11-21]. Not only these ionic liquids have been utilized for the promotion of some organic transformations but also some of them
have been used as potent antimicrobial and antibacterial agents [22]. In addition, DABCO-based ionic liquids can be recycled easily
and the great diversity of these reagents lead to new porous materials with novel structures and properties [16].
Nowadays, multi-component reactions (MCRs) have been authenticated by industries as well as academia. In these strategies,
three or more reactants are combined in situ to produce the desired products. Having many suitable advantages associated with
these strategies, MCRs have been known as economic and time-saving processes. The length of a reaction, which depends on the
number of chemical bonds being broken or created, can be descended by cut the steps. Although MCRs intensely have been
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appreciated due to their effects on drug discoveries, few drugs have been marked and developed by these strategies, which is why
organic chemists focus on using MCRs to shorten the synthetic pathway of pharmaceutically-active products [23-25].
Quinazoline and quinazolinone derivatives are known for their interesting pharmaceutical activities such as antihypertensive [26-
28], analgesic and anti-inflammatory [29, 30], antihistaminic [31, 32], anticancer [33], and anti-HIV [34] activities. Arterial
diseases caused many deaths throughout a year. High blood pressure has been identified as the major risk factor which causes these
diseases. Doxazosin mesylate, a compound which contains the quinazoline skeleton, is an alpha blocker used to treat high blood
pressure and benign prostatic hyperplasia (BHP) (Fig.1).
6-Amino-1,3-dimethyluracil is a valuable building block for the synthesis of several bioactive heterocycles such as
pyrimido[4,5-b]quinolines, pyrido[2,3-d]pyrimidines [35], and pyrimido[4,5-d]pyrimidines [36]. Quinolines are important class of
heterocyclic alkaloids which have been used in pharmaceutical industries in order to prepare bioactive drugs such as Quinine,
Chloroquine, Luotonine-A, and Camptothecin. Moreover, quinoline derivatives have been utilized in flavoring agents and in
luminescence chemistry (Fig. 2) [37].
In continuation of our research group effort to introduce some new DABCO-based ionic liquids as inexpensive, eco-friendly, and
easily-preparable reagents [16, 18, 38], we have tried to prepare [H2-DABCO][HSO4]2 as a new acidic ionic liquid, and investigate
its ability in the promotion of the synthesis of benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline derivatives. Before this
work, several synthetic methods and catalysts have been reported to obtain these types of compounds including H6P2W18O62 18H2O
[39], sulfamic acid [40], 1-butyl-3-methylimidazolium bromide ([bmim]Br) [41], iodine [42], p-toluenesulfonic acid [43],
Fe3O4@chitosan [44], acetic acid [45], nano-SiO2 [46], and [PVP-SO3H]HSO4 [47] (for the synthesis of benzimidazoquinazolinone
derivatives), 1-n-butyl-3-methylimidazolium bromide ([bmim]Br) [48], cellulose sulfuric acid [49], indium(III) chloride [50], p-
toluenesulfonic acid [37], nano-Fe3O4 [51], and 1,3-disulfonic acid imidazolium hydrogen sulfate [52], (for the synthesis of
pyrimido[4,5-b]-quinoline derivatives). Despite indubitable benefits of these methods, our new procedure includes some advantages
such as use of using a cheap, reusable and easily-preparable ionic liquid, clean process, short reaction times, high yields, easy work-
up, and use of water as a green solvent.
2. Experimental
2.1. Materials
Several materials, most of which are aldehyde, were used in this procedure. All of aldehydes, dimedone, malononitrile, and
barbituric acid were purchased from Merck chemical company (Munich) and were used without further purification. The purity of
them were monitored by thin layer chromatography (TLC). DABCO (CAS: 280-57-9, MW: 112.17 g/gmol, assay ≥ 99% w/w %)
and sulfuric acid (CAS: 7664-93-9, MW: 98.08 g/gmol, assay ≥ 99.99 v/v %) were purchased from Sigma-Aldrich (Mumbai). Both
assays were reported by company and were not examined more. All solvents were prepared from Merck (Munich) and were kept
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sealed in airtight bottles as well to minimize the absorption of atmosphere moisturize. Moreover, they had gotten distilled before
being used.
2.2. Characterization techniques
Products were characterized by their physical constants, comparison with authentic samples and IR and NMR spectroscopy. The
purity determination of the substrate and reaction monitoring were accomplished by TLC on silics-gel polygram SILG / UV 254
plates. Melting points were measured by electrothermal IA9100 melting point apparatus in capillary tubes. The starting temperature
of the approximate melting range was input via the keyboard and the melting point range was spotted visually. FT-IR spectra were
recorded on a Perkin-Elmer spectrum BX series and KBr pellets were used for solid samples. Mass spectra were obtained on
1
Agilent Technologies 5975C spectrometer via mass selective detector (MSD) operating at an ionization potential of 70 eV. H
NMR and 13C NMR spectra were determined on Bruker AV-400 using TMS (0.00 ppm) as internal standard and DMSO-d6 as
solvent.
2.3. Preparation of 1,4-diazabicyclo[2.2.2]octane-1,4-diium hydrogen sulfate {[H2-DABCO][HSO4]2}
In a 100 mL round-bottomed flask, 1,4-diazabicyclo[2.2.2]octane (DABCO) (1.05 g, 9.4 mmol) was dissolved in 50 mL dry
dichloromethane. Then this mixture was stirred in an ice-bath for 1 min and a stoichiometric amount of sulfuric acid (99.99%, 1
mL, 18.8 mmol) was added drop-wise to it within 25 min. After the addition, the mixture was heated to reflux with constant stirring
for 24 h. Then the solvent was decanted and the resulting white solid was frequently washed with diethyl ether (3 × 15) to obliterate
non-ionic residues. After all, the obtained ionic liquid was dried under vacuum to achieve [H2-DABCO][HSO4]2 in 95% yield (2.74
g) (Fig. 3). The purity of the product was determined by melting point, Mass, FT-IR, 1H NMR and 13C NMR.
Spectral data for [H2-DABCO][HSO4]2: White solid; M.p. 65 °C; MS: m/z = 308(M+); FT-IR (KBr, cm-1) max: 3400-2400, 1229,
1165, 849, 576; 1H NMR (400 MHz, DMSO-d6): (ppm) 3.59 (s, 6H), 6.64 (s, 1H, NH), 13.88 (s, 1H, HSO4); 13C NMR (100 MHz,
DMSO-d6): (ppm) 43.4.
2.4. General procedure for the synthesis of benzimidazoquinazolinone derivatives
A 25 mL round-bottomed flask was charged with aromatic aldehyde 1 (1 mmol), dimedone 2 (1 mmol), 2-aminobenzimidazole
o
3 (1 mmol) and [H2-DABCO][HSO4]2 (0.097 mmol, 0.030 g). Then the mixture was stirred under solvent-free conditions at 100 C.
After completion of the reaction, as identified by TLC (n-hexane : etheylacetate; 8:2), the mixture was cooled to room
temperature and washed with distilled water (5 mL). Finally, the residue was dissolved in hot ethanol and pure product afford
after recrystallization in high yield (5a-s).
2.5. General procedure for the synthesis of pyrimido[4,5-b]-quinoline derivatives
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[H2-DABCO][HSO4]2 (0.16 mmol, 0.050 g) was added to a magnetically stirred mixture of the aromatic aldehyde 1 (1 mmol),
1,3-diketone 2 (1 mmol), and 6-amino-1,3-dimethyluracil 4 (1 mmol) in aqueous ethanol (2:1). Meanwhile, the process of the
reaction was monitored by TLC (n-hexane : etheylacetate; 2:8). When the reaction was completed, the mixture was cooled to room
temperature and then filtered off and recrystallized from ethanol to obtain the solid product (6a-n).
3. Results and discussion
In this project and in continuation of our previous works on the preparation and use of new DABCO-based ionic liquids in the
promotion of organic transformations [16, 18, 38, 53-55], we wish to report the preparation of another efficient member of this
family of catalysts formulated as [H2-DABCO][HSO4]2 and its applicability in the synthesis of two types of biologically important
compounds. After preparation the structure of [H2-DABCO][HSO4]2 is identified by FT-IR, 1H and 13C NMR and mass spectra.
3.1. Characterization of the catalyst
3.1.1. FT-IR analysis
The FT-IR spectra of DABCO and [H2-DABCO][HSO4]2 are compared in Fig. 4. On the basis of this comparison it is
determined that the absorption bond at 3416 cm-1 can be related to N-H stretching vibration, the broad peak in the range of 2400-
3400 cm-1 can be ascribed to O-H stretching vibration, the characteristic peaks at 1229 and 1165 cm-1 can be assigned to the
asymmetric and symmetric stretching vibrations of S-O, respectively, and absorption which appeared at 576 cm-1 can be related to
SO2 scissors. It is clear that these absorptions do not appear in the FT-IR spectra of DABCO.
3.1.2. Mass spectroscopy
The mass spectrum of [H2-DABCO][HSO4]2 is shown in Fig. 5. The molecular ion peak (M+) appeared at m/e = 308 with
relative intensity of 3.85 is corresponded with molecular weight of the catalyst. Other ion peaks at m/e = 112 (30.75) (DABCO),
m/e = 80 (33.65)(SO3), m/e = 64 (39.42) (SO2), m/e = 48 (30.77) (SO) and the base peak at m/e = 43 (100)(NH(CH2)2) are also
observed clearly.
3.1.3. NMR spectroscopy
It could be expected from the 1H NMR spectrum of [H2-DABCO][HSO4]2 to show two singlet peaks for acidic hydrogens. These
-
peaks are appeared at 13.88 and 6.64 ppm relating to HSO4 and N-H, respectively. Another singlet peak appeared at 3.59 ppm
corresponded with aliphatic CH2 (Fig. 6).
As it can be expected, the aliphatic carbons of [H2-DABCO][HSO4]2 are located at 43.4 ppm in the 13C NMR spectrum (Fig. 7).
3.2. Catalytic activity
After ensuring about the synthesis of [H2-DABCO][HSO4]2, the applicability of this reagent in the acceleration of some of the
organic transformations was identified in the synthesis of benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline derivatives. To
optimize the reaction conditions, a variety amounts of the catalyst, temperatures and solvents were applied in the synthesis of
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benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline derivatives of 4-chlorobenzaldehyde. The obtained results are tabulated
in Tables 1.
Although omitting solvent improved yields and times in the synthesis of 12-(4-chlorophenyl)-3,3-dimethyl-3,4,5,12-
tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolin-1(2H)-one (5b), the yield was trace without using the catalyst under the optimized
conditions (Table 1, entry 15). Moreover, this experiment was carried out for the synthesis of 5-(4-chlorophenyl)-1,3,8,8-
tetramethyl-5,8,9,10-tetrahydropyrimido[4,5-b]quinoline-2,4,6(1H,3H,7H)-trione (6b) and the result demonstrated the importance
of use of the catalyst to promote the reaction (Table 1, entry 30). After optimization of the reaction as shown in Scheme 1, different
types of aromatic aldehydes containing both electron-donor and -withdraw groups were used for the synthesis of
benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline derivatives under these conditions (Table 2). All reaction were performed
under mild conditions in high yields during acceptable reaction times. The reactions which were checked by aliphatic aldehydes
lead to a mixture of unidentified products. So the method is not useful for these types of compounds.
Afterwards it was essential that the catalytic efficiency of [H2-DABCO][HSO4]2 be compared with previous methods in order to
clear up the merit of the catalyst. For this reason, the synthesis of 12-(4-chlorophenyl)-3,3-dimethyl-3,4,5,12-
tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolin-1(2H)-one
(5b)
and
5-(4-chlorophenyl)-1,3,8,8-tetramethyl-5,8,9,10-
tetrahydropyrimido[4,5-b]quinoline-2,4,6(1H,3H,7H)-trione (6b) were selected as model reactions and were compared in terms of
the catalyst amount, reaction times and turnover frequency (TOF) with some procedures which were reported for the synthesis of
benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline derivatives previously (Table 3). In this table the efficiency of [H2-
DABCO][HSO4]2 not only is compared with different types of catalysts but also with some of the other DABCO-based ionic
liquids. It is clear that [H2-DABCO][HSO4]2 promoted the reaction in less time and more yield than other mentioned DABCO-based
ionic liquids. Although [DABCO](SO3H)2(HSO4)2 achieved the best TOF, the reaction using this reagent is completed in longer
times. A comparison between the promoting effect of [H2-DABCO][H2PO4]2 and [H2-DABCO][HSO4]2 shows that [H2-
DABCO][H2PO4]2 is not able to complete both reactions after appropriate time (Table 3, entries 11 and 19) while [H2-
DABCO][HSO4]2 accelerates the reactions in shorter times and higher yields, clarifying its applicability as an adequate catalyst for
the promotion of these multicomponent reactions.
The proposed mechanism is depicted in Scheme 2 according to the literature [59] for the synthesis of benzoxanthene derivatives
using a Brønsted acidic ionic liquid (BAIL) such as [H2-DABCO][HSO4]2. At first step of this mechanism, [H2-DABCO][HSO4]2 is
activated the aldehyde 1 by hydrogen bonding. Then a Knoevenagel condensation occur between activated aldehyde a and enol b.
In continue, the generated intermediate c change to a Knoevenagel condensation product d. In route 1, intermediate d, which is
activated by the ionic liquid, contributes in a Michael addition with N3 of 2-aminobenzimidazole and produces the intermediate e.
An intra-molecular cyclization in intermediate e, continued by lose of water, produces the requested products (5a-s). On the other
hand, the effect of amino group of 2-aminobenzimidazole 3 to carbonyl group in intermediate d, can be resulted in intermediate f.
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Removal of H+ from N1 lead to an intra-molecular cyclization in intermediate f producing (5a-s) products through route 2. Besides,
product (6a-n) can be produced when 6-amino-1,3-dimethyluracil 4 engaged in a Michael addition with intermediate d in order to
prepare intermediate g. By removing of H+ from g, the ionic liquid promotes an intra-molecular cyclization to form the intermediate
h. Finally, this intermediate loses water to release (6a-n, route 3).
3.3. Reusability of the catalyst
To investigate the reusability of the catalyst, the synthesis of 12-(4-chlorophenyl)-3,3-dimethyl-3,4,5,12-
tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolin-1(2H)-one
(5b)
and
5-(4-chlorophenyl)-1,3,8,8-tetramethyl-5,8,9,10-
tetrahydropyrimido[4,5-b]quinoline-2,4,6(1H,3H,7H)-trione (6b) were selected as models. After completion of the reaction, the
catalyst was recovered by filtration of the reaction mixture and evaporation of water under vacuum up to 70 oC (in the synthesis of
12-(4-chlorophenyl)-3,3-dimethyl-3,4,5,12-tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolin-1(2H)-one, water was added after the
completion of the reaction). Finally, the residue was washed by diethyl ether and reused 3 times for both reactions. As shown in
Figs. 8 and 9, the products were obtained with the least change in reaction time and yield.
As shown in Figs. 8 and 9, the catalytic activity of [H2-DABCO][HSO4]2 decreases after 3 runs. Although it can be related to
degradation of some acidic groups in the catalyst, it preserves its structure virtually. In Fig.10, a comparison between the FT-IR of
DABCO, neat catalyst, and reused catalyst was shown. The FT-IR of reused catalyst validates this claim that the structure of reused
catalyst is nearer to the neat catalyst than DABCO and illustrates that it does not degrade and lose all its acidic groups.
4. Conclusion
In this study, [H2-DABCO][HSO4]2 was synthesized by a straightforward protocol and utilized to promote the preparation of
benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline derivatives. The present protocol show some advantages such as high
yields, reduced reaction times, no by-product, clean and simple work-up, not using excess amount of the substrate, and use of a
reusable catalyst.
Acknowledgments
We are thankful to the Research Council of University of Guilan for the partial support of this research.
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50. J. M. Khurana, A. Chaudhary, B. Nand, A. Lumb, Tetrahedron Lett. 53 (2012) 3018-3022.
51. F. Nemati, R. Saeedirad, Chin. Chem. Lett. 24 (2013) 370-372.
52. K. Mohammadi, F. Shirini, A. Yahyazadeh, RSC Adv. 5 (2015) 23586-23590.
53. F. Shirini, M. S. N. Langarudi, M. Seddighi, O. G. Jolodar, Res. Chem. Intermed. 41 (2015) 8483-8497.
54. N. Seyyedi, F. Shirini, M. S. N. Langarudi, RSC Adv. 6 (2016) 44630-44640.
55. O. Goli-Jolodar, F. Shirini, M. Seddighi, J. Mol. Liq. 224 (2016) 1092-1101.
56. B. Insuasty, A. Salcedo, J. Quiroga, R. Abonia, M. Nogueras, J. Cobo, S. Salido, Heterocycl. Commun. 10 (2004) 399-
404.
57. A. Shaabani, E. Farhangi, A. Rahmati, Comb. Chem. High Throughput Screening 9 (2006) 771-776.
58. Q. Shao, Sh. Tu, Ch. Li, L. Cao, D. Zhou, Q. Wang, B. Jiang, Y. Zhang, W. Hao, Heterocyclic. Chem. 45 (2008) 411-416.
8

ACCEPTED MANUSCRIPT
59. H. R. Shaterian, M. Ranjbar, K. Azizi, J. Mol. Liq. 162 (2011) 95-99.
9

ACCEPTED MANUSCRIPT
Fig. 1 The structure of Doxazosin mesylate
10

ACCEPTED MANUSCRIPT
Fig. 2 The structures of Quinine, Chloroquine, Luotonine-A, and Camptothecin
11

ACCEPTED MANUSCRIPT
Fig. 3. Preparation of [H2-DABCO][HSO4]2
12

ACCEPTED MANUSCRIPT
OH stretching of the HSO4 group
200
180
160
140
120
100
80
60
40
4000
3500
3000
2500
2000
1500
1000
500
Wavenumber cm -1
Fig. 4 The FT-IR spectra of DABCO and [H2-DABCO][HSO4]2
13

ACCEPTED MANUSCRIPT
Fig. 5 The mass spectrum of [H2-DABCO][HSO4]2
14

ACCEPTED MANUSCRIPT
Hydrogens of CH2
Hydrogens of NH
-
Hydrogens of HSO4
Fig. 6 The 1H NMR spectrum of [H2-DABCO][HSO4]2
15

ACCEPTED MANUSCRIPT
Carbons of CH2
Fig. 7 The 13C NMR spectrum of [H2-DABCO][HSO4]2
16

ACCEPTED MANUSCRIPT
Fig. 8. Reusability of [H2-DABCO][HSO4]2 in the synthesis of 12-(4-chlorophenyl)-3,3-dimethyl-3,4,5,12-
tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolin-1(2H)-one 5b
17

ACCEPTED MANUSCRIPT
Fig. 9. Reusability of [H2-DABCO][HSO4]2 in the synthesis of 5-(4-chlorophenyl)-1,3,8,8-tetramethyl-5,8,9,10-
tetrahydropyrimido[4,5-b]quinoline-2,4,6(1H,3H,7H)-trione 6b
18

ACCEPTED MANUSCRIPT
1.6
1.4
1.2
1.0
0.8
0.6
0.4
DABCO
Catalyst
Reused Catalyst
4000
3500
3000
2500
2000
1500
1000
500
Wavenumber cm-1
Fig. 10 The FT-IR of DABCO, neat catalyst, and reused catalyst
19

ACCEPTED MANUSCRIPT
Scheme 1. Synthesis of benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline derivatives catalyzed by [H2-
DABCO][HSO4]2 under optimized conditions
20

ACCEPTED MANUSCRIPT
Scheme 2 Proposed mechanism for the synthesis of benzimidazoquinazolinone (routes 1 and 2) and pyrimido[4,5-b]-quinoline
(route 3) derivatives in the presence of [H2-DABCO][HSO4]2.
21

ACCEPTED MANUSCRIPT
Table 1. Optimization of the amount of the catalyst, temperature and solvent in the synthesis of benzimidazoquinazolinone (entries
1-15) and pyrimido[4,5-b]-quinoline (entries 16-30) derivative of 4-chlorobenzaldehyde.
Entry
1
2
3
4
5
6
7
8
Amount of catalyst (mol %)
Solvent
CH2Cl2
CH2Cl2
CH3CN
CH3CN
H2O
H2O
C2H5OH
C2H5OH
C2H5OH : H2O (1:1)
---
---
---
---
---
---
CH2Cl2
CH2Cl2
CH3CN
CH3CN
H2O
H2O
C2H5OH
C2H5OH
C2H5OH : H2O (1:1)
C2H5OH : H2O (2:1)
C2H5OH : H2O (2:1)
C2H5OH : H2O (2:1)
C2H5OH : H2O (2:1)
C2H5OH : H2O (2:1)
C2H5OH : H2O (2:1)
Temp. (oC) Time (min) Conversation yield (%)
0.0065
0.016
0.0065
0.022
0.0097
0.022
0.022
0.022
0.016
0.022
0.016
0.0097
0.0065
0.0097
---
0.022
0.032
0.022
0.032
0.022
0.022
0.022
0.022
0.022
0.022
0.022
0.016
0.032
0.097
---
r.t.
Reflux
r.t.
Reflux
r.t.
Reflux
r.t.
Reflux
reflux
100
100
100
180
180
180
180
180
180
180
100
180
18
Trace
Trace
Trace
Trace
Trace
Trace
Not completed
100(70)a
Not completed
100(90)
100(93)
100(95)
100(90)
100(93)
Trace
Trace
Trace
Trace
Trace
Not completed
Not completed
Not completed
Not completed
100(75)
100(80)
100(90)
100(93)
100(90)
100(85)
Trace
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
20
20
23
20
100
120
100
r.t.
180
240
240
240
240
240
240
240
240
180
100
70
Reflux
r.t.
Reflux
r.t.
Reflux
r.t.
Reflux
Reflux
Reflux
75
75
70
75
70
75
75
120
240
a isolated yields
22

ACCEPTED MANUSCRIPT
Table 2. Preparation of benzimidazoquinazolinone (entries 1-19) and pyrimido[4,5-b]-quinoline (entries 20-33) derivatives using
[H2-DABCO][HSO4]2 as the catalyst.
M.P. (oC)
Time
(min)
Yield
(%)a
Entry Aldehyde
Product
MS
Ref.
Found
Rep.
343.17 (100),
344.17 (23),
345.18 (2.7),
344.17 (1.1)
1
2
C6H5CHO
5a
5b
20
20
90
95
>300
368
56
377.13 (100.0),
379.13 (32.0),
378.13 (23.8),
380.13 (7.6),
379.14 (2.7),
378.13 (1.1)
4-ClC6H4CHO
>300
>300
>300
393
56
57
57
377.13 (100.0),
379.13 (32.0),
378.13 (23.8),
380.13 (7.6),
379.14 (2.7),
378.13 (1.1)
3
4
3-ClC6H4CHO
2-ClC6H4CHO
5c
22
25
90
91
>300
>300
377.13 (100.0),
379.13 (32.0),
378.13 (23.8),
380.13 (7.6),
379.14 (2.7),
378.13 (1.1)
5d
411.09 (100.0),
413.09 (63.9),
412.09 (23.8),
414.09 (15.2),
415.08 (10.2),
413.10 (2.7),
416.09 (2.4),
415.09 (1.7),
412.09 (1.1)
5
2,4-diClC6H3CHO
5e
25
87
>300
>300
58
421.08 (100.0),
423.08 (97.3),
424.08 (23.1),
422.08 (16.2),
422.08 (7.6),
425.08 (1.4),
423.09 (1.4),
425.08 (1.2),
422.08 (1.1),
424.07 (1.1),
423.09 (1.1)
6
4-BrC6H4CHO
5f
20
95
>300
369
56
23

ACCEPTED MANUSCRIPT
361.16 (100.0),
362.16 (23.8),
363.17 (2.7),
362.16 (1.1)
7
4-FC6H4CHO
5g
20
90
>300
>300
58
388.15 (100.0),
389.16 (23.8),
390.16 (2.7),
389.15 (1.5)
8
4-NO2C6H4CHO
3-NO2C6H4CHO
4-MeOC6H4CHO
3-MeOC6H4CHO
5h
5i
30
35
33
37
90
85
90
87
>300
>300
>300
>300
335
56
58
56
57
388.15 (100.0),
389.16 (23.8),
390.16 (2.7),
389.15 (1.5)
9
>300
389
373.18 (100.0),
374.18 (24.9),
375.19 (2.7),
374.18 (1.1)
10
11
5j
373.18 (100.0),
374.18 (24.9),
375.19 (2.7),
374.18 (1.1)
5k
>300
357.18 (100.0),
358.19 (24.9),
359.19 (3.0),
358.18 (1.1)
12
13
14
4-MeC6H4CHO
2-MeC6H4CHO
4-OHC6H4CHO
5l
27
35
35
90
85
90
>300
>300
>300
359
56
57
39
357.18 (100.0),
358.19 (24.9),
359.19 (3.0),
358.18 (1.1)
5m
5n
>300
>300
359.16 (100.0),
360.17 (23.8),
361.17 (2.7),
360.16 (1.1)
24

ACCEPTED MANUSCRIPT
386.21 (100.0),
387.21 (26.0),
388.22 (2.7),
387.21 (1.5)
15
16
17
4-NMe2C6H4CHO
5o
5p
5q
40
45
45
83
80
90
>300
>300
>300
304-308
>300
44
46
47
382.18 (100.0),
383.18 (26.0),
384.19 (2.7),
383.18 (1.5)
Indole-3-
carbaldehyde
393.18 (100.0),
394.19 (28.1),
395.19 (3.8),
394.18 (1.1)
2-Naphthaldehyde
4-SMeC6H4CHO
344-346
389.16 (100.0),
390.16 (24.9),
391.15 (4.5),
391.16 (2.7),
392.16 (1.1),
390.15 (1.1)
18
5r
55
85
>300
>300
342-344
48
368.16 (100.0),
369.17 (24.9),
370.17 (2.7),
369.16 (1.5)
19
20
21
4-CNC6H4CHO
5s
6a
6b
25
65
70
90
90
93
340-343
268-270
292-294
47
49
48
365.17 (100.0),
366.18 (22.7),
367.18 (2.5),
366.17 (1.1)
269-
270
C6H5CHO
399.13 (100.0),
401.13 (32.0),
400.14 (22.7),
402.14 (7.3),
401.14 (2.5),
400.13 (1.1)
287-
290
4-ClC6H4CHO
399.13 (100.0),
401.13 (32.0),
400.14 (22.7),
402.14 (7.3),
401.14 (2.5),
400.13 (1.1)
22
2-ClC6H4CHO
6c
85
85
>300
>300
48
25

ACCEPTED MANUSCRIPT
443.08 (100.0),
445.08 (97.3),
446.09 (22.1),
444.09 (16.2),
444.09 (6.5),
445.09 (1.2),
447.09 (1.2),
447.09 (1.2),
444.08 (1.1),
446.08 (1.1),
445.09 (1.1)
285-
287
23
4-BrC6H4CHO
6d
80
95
281-283
48
383.16 (100.0),
384.17 (22.7),
385.17 (2.5),
384.16 (1.1)
230-
232
24
25
4-FC6H4CHO
6e
80
90
90
234-236
222-224
49
49
m/z: 410.16
(100.0%),
411.16
224-
226
4-NO2C6H4CHO
6f
(22.7%),
120
412.17 (2.5%),
411.16 (1.5%),
412.16 (1.0%)
410.16 (100.0),
411.16 (22.7),
412.17 (2.5),
411.16 (1.5),
412.16 (1.0)
222-
224
26
27
3-NO2C6H4CHO
2-NO2C6H4CHO
6g
6h
135
150
92
85
220-223
287-290
49
52
410.16 (100.0),
411.16 (22.7),
412.17 (2.5),
411.16 (1.5),
412.16 (1.0)
280-
285
379.19 (100.0),
380.19 (23.8),
381.20 (2.7),
380.19 (1.1)
28
29
4-MeC6H4CHO
6i
6j
135
90
95
>300
>300
>300
48
35
371.10 (100.0),
373.10 (32.0),
372.11 (20.5),
374.10 (6.6),
373.11 (2.0),
372.10 (1.1)
4-ClC6H4CHO
60
310-313
26

ACCEPTED MANUSCRIPT
355.13 (100.0),
356.14 (20.5),
357.14 (2.0),
356.13 (1.1)
30
31
4-FC6H4CHO
6k
75
90
90
>300
>300
311-312
301-303
35
35
382.13 (100.0),
383.13 (20.5),
384.13 (2.0),
383.12 (1.5),
384.13 (1.0)
4-NO2C6H4CHO
6l
100
382.13 (100.0),
383.13 (20.5),
384.13 (2.0),
383.12 (1.5),
384.13 (1.0)
244-
248
32
33
3-NO2C6H4CHO
4-MeC6H4CHO
6m
6n
100
125
85
95
250-252
274-276
52
35
351.16 (100.0),
352.16 (21.6),
353.17 (2.2),
352.16 (1.1)
270-
272
a Isolated yields
27

ACCEPTED MANUSCRIPT
Table 3. Comparison of the activity of [H2-DABCO][HSO4]2 with other reported catalysts in the synthesis of 12-(4-chlorophenyl)-
3,3-dimethyl-3,4,5,12-tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolin-1(2H)-one (5b, entries 1-12) and 5-(4-chlorophenyl)-1,3,8,8-
tetramethyl-5,8,9,10-tetrahydropyrimido[4,5-b]quinoline-2,4,6(1H,3H,7H)-trione (6b, entries 13-20).
Amount
(mol)
---
---
---
Time
(min)
90
480
4
Entry Catalyst
Conditions
Yield (%)
TOF (s-1) Ref.
1
2
3
4
5
---
C2H5OH/ reflux
Solvent-free/ 110 oC
H2O/ MW
CH3CN/ reflux
CH3CN/ reflux
66
83
94
94
90
---
---
---
10.4
2000
56
57
58
39
40
--- a
---
H6P2W18O62.18H2O
Sulfamic Acid
1-Butyl-3-
0.01
15
15
5×10-5
6
methylimidazolium
bromide ([bmim]Br)
Fe3O4@chitosan
Nano‑ SiO2
14×10-4
Solvent-free/ 100 oC
10
91
108.33
41
7
8
0.002 g
0.15
C2H5OH/ 40 oC
CH3CN/ r. t.
150
18
90
91
---
44
0.56
46
This
work
This
work
This
work
This
work
9
[DABCO](SO3H)2(Cl)2
2×10-4
Solvent-free/ 100 oC
Solvent-free/ 100 oC
Solvent-free/ 100 oC
Solvent-free/ 100 oC
75
95
93
105.56
77500
---
10
11
12
[DABCO](SO3H)2(HSO4)2 2×10-5
60
Not
completed
[H2-DABCO][H2PO4]2
[H2-DABCO][HSO4]2
1.9×10-4
9.7×10-5
180
20
95
90
816.15
1-Butyl-3-
13
methylimidazolium
bromide ([bmim]Br)
Cellulose sulfuric acid
Indium(III) chloride
p-Toluenesulfonic acid
Fe3O4@SiO2-SO3H
1,3-disulfonic
2 mL
Solvent-free/ 95 oC
210
---
48
14
15
16
17
0.06 g
0.2
0.2
Solvent-free/ 90 oC
H2O/ reflux
30
60
150
25
96
91
89
92
---
49
50
37
51
0.13
0.049
---
H2O/ 90 oC
0.02 g
H2O/ 70 oC
acid imidazolium hydrogen 2.5×10-4
sulfate [dsim]HSO4
C2H5OH/ 70 oC
51
91
404.44
52
18
Not
completed
This
work
This
work
19
20
[H2-DABCO][H2PO4]2
2.3×10-4
H2O: C2H5OH (2:1)/ 75 oC
H2O: C2H5OH (2:1)/ 75 oC
240
70
---
[H2-DABCO][HSO4]2
1.6×10-4
93
138.39
a) In this procedure, aldehyde (1 mol), dimedone (1 mol) and malononitrile (1.1 mol) were used.
28

ACCEPTED MANUSCRIPT
Graphical abstract
29