Journal of Molecular Liquids 243 (2017) 302–312

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Journal of Molecular Liquids

journal homepage: www.elsevier.com/locate/molliq

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 Langarudi a, Nader Daneshvar b,
Maryam Mashhadinezhad a, Nazanin Nabinia a
a
Department of Chemistry, College of Science, University of Guilan, Rasht 41335-19141, Iran
b
Department of Chemistry, College of Science, University of Guilan, University Campus 2, Rasht, Iran

a r t i c l e i n f o a b s t r a c t

Article history: In this article, we report the preparation of a new ionic liquid from the reaction of DABCO and sulfuric acid and its
Received 27 May 2017 characterization using FT-IR, Mass and NMR spectroscopy. This ionic liquid is air- and water-stable and afford-
Received in revised form 12 July 2017 able. Afterward this reagent is used for the synthesis of benzimidazoquinazolinone and pyrimido[4,5-b]-quino-
Accepted 20 July 2017
line derivatives as a catalyst. The results show the applicability of the prepared reagent as a reusable catalyst
Available online 29 July 2017
without losing its activity. This procedure possesses some advantages such as ease of preparation of the catalyst,
Keywords:
simple work-up procedure, short reaction times, excellent yields and use of nontoxic and inexpensive catalyst.
DABCO © 2017 Elsevier B.V. All rights reserved.
Ionic liquids
Benzimidazoloquinazolinones
Pyrimido[4,5-b]-quinolines
2-Aminobenzimidazole
6-Amino-1,3-dimethyluracil

1. Introduction ionic liquids can be recycled easily and the great diversity of these re-
agents leads to new porous materials with novel structures and
Recently, organocatalysts has been utilized in organic reactions properties [16].
increasingly. It is due to the inimitable advantages such as their po- Nowadays, multi-component reactions (MCRs) have been au-
tential to use in large scale production, industries, and complete thenticated by industries as well as academia. In these strategies,
asymmetric synthetic processes as well as their availability and low three or more reactants are combined in situ to produce the desired
cost. Also, lack of transition-metal brings them at the heart of green products. Having many suitable advantages associated with these
chemistry [1]. strategies, MCRs have been known as economic and time-saving pro-
One of these organocatalysts is 1,4-diazabicyclo[2.2.2]octane cesses. The length of a reaction, which depends on the number of
(DABCO) which has been used as a weak base [2,3] or a ligand [4,5] chemical bonds being broken or created, can be descended by cut
in many organic reactions. Besides, DABCO possesses some unique the steps. Although MCRs intensely have been appreciated due to
properties such as being inexpensive, high reactive and easy to han- their effects on drug discoveries, few drugs have been marked and
dle. In addition using this reagent the products can be obtained in ex- developed by these strategies, which is why organic chemists focus
cellent yields with high selectivity [6–10]. In recent years, DABCO, as on using MCRs to shorten the synthetic pathway of
a cage-like compound with medium-hindrance, has been used for pharmaceutically-active products [23–25].
the synthesis of a new class of ionic liquids [11–21]. Not only these Quinazoline and quinazolinone derivatives are known for their in-
ionic liquids have been utilized for the promotion of some organic teresting pharmaceutical activities such as antihypertensive [26–28],
transformations but also some of them have been used as potent an- analgesic and anti-inflammatory [29,30], antihistaminic [31,32], anti-
timicrobial and antibacterial agents [22]. In addition, DABCO-based cancer [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,
⁎ Corresponding author at: Department of Chemistry, College of Science, University of
a compound which contains the quinazoline skeleton, is an alpha
Guilan, Rasht 41335-19141, Iran. blocker used to treat high blood pressure and benign prostatic hyper-
E-mail address: [email protected] (F. Shirini). plasia (BHP) (Fig. 1).

http://dx.doi.org/10.1016/j.molliq.2017.07.080
0167-7322/© 2017 Elsevier B.V. All rights reserved.
 F. Shirini et al. / Journal of Molecular Liquids 243 (2017) 302–312 303

6-Amino-1,3-dimethyluracil is a valuable building block for the syn-

thesis of several bioactive heterocycles such as pyrimido[4,5-b]quino-
lines, 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 bioac-
tive 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-
Fig. 1. The structure of Doxazosin mesylate. DABCO][HSO4]2 as a new acidic ionic liquid, and investigate its ability

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

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

304 F. Shirini et al. / Journal of Molecular Liquids 243 (2017) 302–312

Fig. 4. The FT-IR spectra of DABCO and [H2-DABCO][HSO4]2.

in the promotion of the synthesis of benzimidazoquinazolinone and reaction times, high yields, easy work-up, and use of water as a
pyrimido[4,5-b]-quinoline derivatives. Before this work, several syn- green solvent.
thetic methods and catalysts have been reported to obtain these types
of compounds including H 6 P2 W18 O62 18H2 O [39], sulfamic acid 2. Experimental
[40], 1-butyl-3-methylimidazolium bromide ([bmim]Br) [41], iodine
[42], p-toluenesulfonic acid [43], Fe3 O4 @chitosan [44], acetic acid 2.1. Materials
[45], nano-SiO2 [46], and [PVP-SO3H]HSO4 [47] (for the synthesis of
benzimidazoquinazolinone derivatives), 1-n-butyl-3- Several materials, most of which are aldehyde, were used in this pro-
methylimidazolium bromide ([bmim]Br) [48], cellulose sulfuric cedure. All of aldehydes, dimedone, malononitrile, and barbituric acid
acid [49], indium(III) chloride [50], p-toluenesulfonic acid [37], were purchased from Merck chemical company (Munich) and were
nano-Fe3O4 [51], and 1,3-disulfonic acid imidazolium hydrogen sul- used without further purification. The purity of them was monitored
fate [52], (for the synthesis of pyrimido[4,5-b]-quinoline deriva- by thin layer chromatography (TLC). DABCO (CAS: 280-57-9, MW:
tives). Despite indubitable benefits of these methods, our new 112.17 g/gmol, assay ≥ 99% w/w %) and sulfuric acid (CAS: 7664-93-9,
procedure includes some advantages such as use of using a cheap, re- MW: 98.08 g/gmol, assay ≥ 99.99 v/v %) were purchased from Sigma-
usable and easily-preparable ionic liquid, clean process, short Aldrich (Mumbai). Both assays were reported by company and were

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

 F. Shirini et al. / Journal of Molecular Liquids 243 (2017) 302–312 305

Fig. 6. The 1H NMR spectrum of [H2-DABCO][HSO4]2.

not examined more. All solvents were prepared from Merck (Munich) 2.2. Characterization techniques
and were kept sealed in airtight bottles as well to minimize the absorp-
tion of atmosphere moisturize. Moreover, they had gotten distilled be- Products were characterized by their physical constants, comparison
fore being used. with authentic samples and IR and NMR spectroscopy. The purity

Fig. 7. The 13C NMR spectrum of [H2-DABCO][HSO4]2.

306 F. Shirini et al. / Journal of Molecular Liquids 243 (2017) 302–312

Table 1 2.3. Preparation of 1,4-diazabicyclo[2.2.2]octane-1,4-diium hydrogen sul-

Optimization of the amount of the catalyst, temperature and solvent in the synthesis of fate {[H2-DABCO][HSO4]2}
benzimidazoquinazolinone (entries 1–15) and pyrimido[4,5-b]-quinoline (entries 16–
30) derivative of 4-chlorobenzaldehyde.
In a 100 mL round-bottomed flask, 1,4-diazabicyclo[2.2.2]octane
Entry Amount of catalyst Solvent Temp. Time Conversation (DABCO) (1.05 g, 9.4 mmol) was dissolved in 50 mL dry dichlorometh-
(mol%) (°C) (min) yield (%)
ane. Then this mixture was stirred in an ice-bath for 1 min and a stoi-
1 0.0065 CH2Cl2 r.t. 180 Trace chiometric amount of sulfuric acid (99.99%, 1 mL, 18.8 mmol) was
2 0.016 CH2Cl2 Reflux 180 Trace
added drop-wise to it within 25 min. After the addition, the mixture
3 0.0065 CH3CN r.t. 180 Trace
4 0.022 CH3CN Reflux 180 Trace was heated to reflux with constant stirring for 24 h. Then the solvent
5 0.0097 H2O r.t. 180 Trace was decanted and the resulting white solid was frequently washed
6 0.022 H2O Reflux 180 Trace with diethyl ether (3 × 15) to obliterate non-ionic residues. After all,
7 0.022 C2H5OH r.t. 180 Not completed the obtained ionic liquid was dried under vacuum to achieve [H2-
8 0.022 C2H5OH Reflux 100 100 (70)a
9 0.016 C2H5OH:H2O (1:1) reflux 180 Not completed
DABCO][HSO4]2 in 95% yield (2.74 g) (Fig. 3). The purity of the product
10 0.022 – 100 18 100 (90) was determined by melting point, Mass, FT-IR, 1H NMR and 13C NMR.
11 0.016 – 100 20 100 (93) Spectral data for [H2-DABCO][HSO4]2: white solid; M.P. 65 °C; MS:
12 0.0097 – 100 20 100 (95) m/z = 308 (M+); FT-IR (KBr, cm− 1) υmax: 3400–2400, 1229, 1165,
13 0.0065 – 100 23 100 (90)
849, 576; 1H NMR (400 MHz, DMSO-d6): δ (ppm) 3.59 (s, 6H), 6.64 (s,
14 0.0097 – 120 20 100 (93)
15 – – 100 180 Trace 1H, NH), 13.88 (s, 1H, HSO4); 13C NMR (100 MHz, DMSO-d6): δ (ppm)
16 0.022 CH2Cl2 r.t. 240 Trace 43.4.
17 0.032 CH2Cl2 Reflux 240 Trace
18 0.022 CH3CN r.t. 240 Trace
19 0.032 CH3CN Reflux 240 Trace
2.4. General procedure for the synthesis of benzimidazoquinazolinone
20 0.022 H2O r.t. 240 Not completed
21 0.022 H2O Reflux 240 Not completed derivatives
22 0.022 C2H5OH r.t. 240 Not completed
23 0.022 C2H5OH Reflux 240 Not completed A 25 mL round-bottomed flask was charged with aromatic aldehyde
24 0.022 C2H5OH:H2O (1:1) Reflux 180 100 (75)
1 (1 mmol), dimedone 2 (1 mmol), 2-aminobenzimidazole 3 (1 mmol)
25 0.022 C2H5OH:H2O (2:1) Reflux 100 100 (80)
26 0.022 C2H5OH:H2O (2:1) 75 70 100 (90)
and [H2-DABCO][HSO4]2 (0.097 mmol, 0.030 g). Then the mixture was
27 0.016 C2H5OH:H2O (2:1) 75 70 100 (93) stirred under solvent-free conditions at 100 °C. After completion of
28 0.032 C2H5OH:H2O (2:1) 75 70 100 (90) the reaction, as identified by TLC (n-hexane:etheylacetate; 8:2), the
29 0.097 C2H5OH:H2O (2:1) 75 120 100 (85) mixture was cooled to room temperature and washed with distilled
30 – C2H5OH:H2O (2:1) 75 240 Trace
water (5 mL). Finally, the residue was dissolved in hot ethanol and
a
Isolated yields. pure product afford after recrystallization in high yield (5a–s).

determination of the substrate and reaction monitoring were accom-

plished by TLC on silica-gel polygram SILG/UV 254 plates. Melting 2.5. General procedure for the synthesis of pyrimido[4,5-b]-quinoline
points were measured by electrothermal IA9100 melting point appara- derivatives
tus in capillary tubes. The starting temperature of the approximate
melting range was input via the keyboard and the melting point range [H2-DABCO][HSO4]2 (0.16 mmol, 0.050 g) was added to a mag-
was spotted visually. FT-IR spectra were recorded on a Perkin-Elmer netically stirred mixture of the aromatic aldehyde 1 (1 mmol), 1,3-
spectrum BX series and KBr pellets were used for solid samples. Mass diketone 2 (1 mmol), and 6-amino-1,3-dimethyluracil 4 (1 mmol)
spectra were obtained on Agilent Technologies 5975C spectrometer in aqueous ethanol (2:1). Meanwhile, the process of the reaction
via mass selective detector (MSD) operating at an ionization potential was monitored by TLC (n-hexane:etheylacetate; 2:8). When the re-
of 70 eV. 1H NMR and 13C NMR spectra were determined on Bruker action was completed, the mixture was cooled to room temperature
AV-400 using TMS (0.00 ppm) as internal standard and DMSO-d6 as and then filtered off and recrystallized from ethanol to obtain the
solvent. solid product (6a–n).

Scheme 1. Synthesis of benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline derivatives catalyzed by [H2-DABCO][HSO4]2 under optimized conditions.
 F. Shirini et al. / Journal of Molecular Liquids 243 (2017) 302–312 307

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.

Entry Aldehyde Product MS Time Yield M.P. (°C) Ref.

(min) (%)a
Found Rep.

1 C6H5CHO 5a 343.17 (100), 344.17 (23), 345.18 (2.7), 344.17 (1.1) 20 90 N300 368 [56]

2 4-ClC6H4CHO 5b 377.13 (100.0), 379.13 (32.0), 378.13 (23.8), 380.13 (7.6), 379.14 (2.7), 20 95 N300 393 [56]
378.13 (1.1)

3 3-ClC6H4CHO 5c 377.13 (100.0), 379.13 (32.0), 378.13 (23.8), 380.13 (7.6), 379.14 (2.7), 22 90 N300 N300 [57]
378.13 (1.1)

4 2-ClC6H4CHO 5d 377.13 (100.0), 379.13 (32.0), 378.13 (23.8), 380.13 (7.6), 379.14 (2.7), 25 91 N300 N300 [57]
378.13 (1.1)

5 2,4-diClC6H3CHO 5e 411.09 (100.0), 413.09 (63.9), 412.09 (23.8), 414.09 (15.2), 415.08 25 87 N300 N300 [58]
(10.2), 413.10 (2.7), 416.09 (2.4), 415.09 (1.7), 412.09 (1.1)

6 4-BrC6H4CHO 5f 421.08 (100.0), 423.08 (97.3), 424.08 (23.1), 422.08 (16.2), 422.08 20 95 N300 369 [56]
(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)

7 4-FC6H4CHO 5g 361.16 (100.0), 362.16 (23.8), 363.17 (2.7), 362.16 (1.1) 20 90 N300 N300 [58]

8 4-NO2C6H4CHO 5h 388.15 (100.0), 389.16 (23.8), 390.16 (2.7), 389.15 (1.5) 30 90 N300 335 [56]

9 3-NO2C6H4CHO 5i 388.15 (100.0), 389.16 (23.8), 390.16 (2.7), 389.15 (1.5) 35 85 N300 N300 [58]

10 4-MeOC6H4CHO 5j 373.18 (100.0), 374.18 (24.9), 375.19 (2.7), 374.18 (1.1) 33 90 N300 389 [56]

11 3-MeOC6H4CHO 5k 373.18 (100.0), 374.18 (24.9), 375.19 (2.7), 374.18 (1.1) 37 87 N300 N300 [57]

12 4-MeC6H4CHO 5l 357.18 (100.0), 358.19 (24.9), 359.19 (3.0), 358.18 (1.1) 27 90 N300 359 [56]

13 2-MeC6H4CHO 5m 357.18 (100.0), 358.19 (24.9), 359.19 (3.0), 358.18 (1.1) 35 85 N300 N300 [57]

(continued on next page)

308 F. Shirini et al. / Journal of Molecular Liquids 243 (2017) 302–312

Table 2 (continued)

Entry Aldehyde Product MS Time Yield M.P. (°C) Ref.

(min) (%)a
Found Rep.

14 4-OHC6H4CHO 5n 359.16 (100.0), 360.17 (23.8), 361.17 (2.7), 360.16 (1.1) 35 90 N300 N300 [39]

15 4-NMe2C6H4CHO 5o 386.21 (100.0), 387.21 (26.0), 388.22 (2.7), 387.21 (1.5) 40 83 N300 304–308 [44]

16 Indole-3-carbaldehyde 5p 382.18 (100.0), 383.18 (26.0), 384.19 (2.7), 383.18 (1.5) 45 80 N300 N300 [46]

17 2-Naphthaldehyde 5q 393.18 (100.0), 394.19 (28.1), 395.19 (3.8), 394.18 (1.1) 45 90 N300 344–346 [47]

18 4-SMeC6H4CHO 5r 389.16 (100.0), 390.16 (24.9), 391.15 (4.5), 391.16 (2.7), 392.16 (1.1), 55 85 N300 342–344 [48]
390.15 (1.1)

19 4-CNC6H4CHO 5s 368.16 (100.0), 369.17 (24.9), 370.17 (2.7), 369.16 (1.5) 25 90 N300 340–343 [47]

20 C6H5CHO 6a 365.17 (100.0), 366.18 (22.7), 367.18 (2.5), 366.17 (1.1) 65 90 269–270 268–270 [49]

21 4-ClC6H4CHO 6b 399.13 (100.0), 401.13 (32.0), 400.14 (22.7), 402.14 (7.3), 401.14 (2.5), 70 93 287–290 292–294 [48]
400.13 (1.1)

22 2-ClC6H4CHO 6c 399.13 (100.0), 401.13 (32.0), 400.14 (22.7), 402.14 (7.3), 401.14 (2.5), 85 85 N300 N300 [48]
400.13 (1.1)

23 4-BrC6H4CHO 6d 443.08 (100.0), 445.08 (97.3), 446.09 (22.1), 444.09 (16.2), 444.09 80 95 285–287 281–283 [48]
(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)

24 4-FC6H4CHO 6e 383.16 (100.0), 384.17 (22.7), 385.17 (2.5), 384.16 (1.1) 80 90 230–232 234–236 [49]

25 4-NO2C6H4CHO 6f m/z: 410.16 (100.0%), 411.16 (22.7%), 412.17 (2.5%), 411.16 (1.5%), 120 90 224–226 222–224 [49]
412.16 (1.0%)
 F. Shirini et al. / Journal of Molecular Liquids 243 (2017) 302–312 309

Table 2 (continued)

Entry Aldehyde Product MS Time Yield M.P. (°C) Ref.

(min) (%)a
Found Rep.

26 3-NO2C6H4CHO 6g 410.16 (100.0), 411.16 (22.7), 412.17 (2.5), 411.16 (1.5), 412.16 (1.0) 135 92 222–224 220–223 [49]

27 2-NO2C6H4CHO 6h 410.16 (100.0), 411.16 (22.7), 412.17 (2.5), 411.16 (1.5), 412.16 (1.0) 150 85 280–285 287–290 [52]

28 4-MeC6H4CHO 6i 379.19 (100.0), 380.19 (23.8), 381.20 (2.7), 380.19 (1.1) 135 90 N300 N300 [48]

29 4-ClC6H4CHO 6j 371.10 (100.0), 373.10 (32.0), 372.11 (20.5), 374.10 (6.6), 373.11 (2.0), 60 95 N300 310–313 [35]
372.10 (1.1)

30 4-FC6H4CHO 6k 355.13 (100.0), 356.14 (20.5), 357.14 (2.0), 356.13 (1.1) 75 90 N300 311–312 [35]

31 4-NO2C6H4CHO 6l 382.13 (100.0), 383.13 (20.5), 384.13 (2.0), 383.12 (1.5), 384.13 (1.0) 100 90 N300 301–303 [35]

32 3-NO2C6H4CHO 6m 382.13 (100.0), 383.13 (20.5), 384.13 (2.0), 383.12 (1.5), 384.13 (1.0) 100 85 244–248 250–252 [52]

33 4-MeC6H4CHO 6n 351.16 (100.0), 352.16 (21.6), 353.17 (2.2), 352.16 (1.1) 125 95 270–272 274–276 [35]

a
Isolated yields.

3. Results and discussion 1165 cm− 1 can be assigned to the asymmetric and symmetric
stretching vibrations of S\\O, respectively, and absorption which ap-
In this project and in continuation of our previous works on the peared at 576 cm−1 can be related to SO2 scissors. It is clear that these
preparation and use of new DABCO-based ionic liquids in the promotion absorptions do not appear in the FT-IR spectra of DABCO.
of organic transformations [16,18,38,53–55], we wish to report the
preparation of another efficient member of this family of catalysts for- 3.1.2. Mass spectroscopy
mulated as [H2-DABCO][HSO4]2 and its applicability in the synthesis of The mass spectrum of [H2-DABCO][HSO4]2 is shown in Fig. 5. The
two types of biologically important compounds. After preparation the molecular ion peak (M+) appeared at m/e = 308 with relative intensity
structure of [H2-DABCO][HSO4]2 is identified by FT-IR, 1H and 13C NMR of 3.85 is corresponded with molecular weight of the catalyst. Other ion
and mass spectra. 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
3.1. Characterization of the catalyst (100) (NH(CH2)2) are also observed clearly.

3.1.1. FT-IR analysis 3.1.3. NMR spectroscopy

The FT-IR spectra of DABCO and [H2-DABCO][HSO4]2 are compared It could be expected from the 1H NMR spectrum of [H2-
in Fig. 4. On the basis of this comparison it is determined that the ab- DABCO][HSO4]2 to show two singlet peaks for acidic hydrogens. These
sorption bond at 3416 cm−1 can be related to N\\H stretching vibration, peaks are appeared at 13.88 and 6.64 ppm relating to HSO− 4 and
the broad peak in the range of 2400–3400 cm− 1 can be ascribed to N\\H, respectively. Another singlet peak appeared at 3.59 ppm
O\\H stretching vibration, the characteristic peaks at 1229 and corresponded with aliphatic CH2 (Fig. 6).
310 F. Shirini et al. / Journal of Molecular Liquids 243 (2017) 302–312

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).

Entry Catalyst Amount (mol) Conditions Time (min) Yield (%) TOF (s−1) Ref.

1 – – C2H5OH/reflux 90 66 – [56]
2 –a – Solvent-free/110 °C 480 83 – [57]
3 – – H2O/MW 4 94 – [58]
4 H6P2W18O62·18H2O 0.01 CH3CN/reflux 15 94 10.4 [39]
5 Sulfamic acid 5 × 10−5 CH3CN/reflux 15 90 2000 [40]
6 1-Butyl-3-methylimidazolium bromide ([bmim]Br) 14 × 10−4 Solvent-free/100 °C 10 91 108.33 [41]
7 Fe3O4@chitosan 0.002 g C2H5OH/40 °C 150 90 – [44]
8 Nano-SiO2 0.15 CH3CN/r.t. 18 91 0.56 [46]
9 [DABCO](SO3H)2(Cl)2 2 × 10−4 Solvent-free/100 °C 75 95 105.56 This work
10 [DABCO](SO3H)2(HSO4)2 2 × 10−5 Solvent-free/100 °C 60 93 77,500 This work
11 [H2-DABCO][H2PO4]2 1.9 × 10−4 Solvent-free/100 °C 180 Not completed – This work
12 [H2-DABCO][HSO4]2 9.7 × 10−5 Solvent-free/100 °C 20 95 816.15 This work
13 1-Butyl-3-methylimidazolium bromide ([bmim]Br) 2 mL Solvent-free/95 °C 210 90 – [48]
14 Cellulose sulfuric acid 0.06 g Solvent-free/90 °C 30 96 – [49]
15 Indium(III) chloride 0.2 H2O/reflux 60 91 0.13 [50]
16 p-Toluenesulfonic acid 0.2 H2O/90 °C 150 89 0.049 [37]
17 Fe3O4@SiO2-SO3H 0.02 g H2O/70 °C 25 92 – [51]
18 1,3-Disulfonic acid imidazolium hydrogen sulfate [dsim]HSO4 2.5 × 10−4 C2H5OH/70 °C 15 91 404.44 [52]
19 [H2-DABCO][H2PO4]2 2.3 × 10−4 H2O: C2H5OH (2:1)/75 °C 240 Not completed – This work
20 [H2-DABCO][HSO4]2 1.6 × 10−4 H2O: C2H5OH (2:1)/75 °C 70 93 138.39 This work
a
In this procedure, aldehyde (1 mol), dimedone (1 mol) and malononitrile (1.1 mol) were used.

As it can be expected, the aliphatic carbons of [H2-DABCO][HSO4]2 previously (Table 3). In this table the efficiency of [H2-DABCO][HSO4]2
are located at 43.4 ppm in the 13C NMR spectrum (Fig. 7). 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-
3.2. Catalytic activity DABCO][HSO4]2 promoted the reaction in less time and more yield
than other mentioned DABCO-based ionic liquids. Although
After ensuring about the synthesis of [H2-DABCO][HSO4]2, the ap- [DABCO](SO3H)2(HSO4)2 achieved the best TOF, the reaction using
plicability of this reagent in the acceleration of some of the organic this reagent is completed in longer times. A comparison between the
transformations was identified in the synthesis of promoting effect of [H2-DABCO][H2PO4]2 and [H2-DABCO][HSO4]2
benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline deriva- shows that [H2-DABCO][H2PO4]2 is not able to complete both reactions
tives. To optimize the reaction conditions, a variety amounts of the after appropriate time (Table 3, entries 11 and 19) while [H2-
catalyst, temperatures and solvents were applied in the synthesis DABCO][HSO4]2 accelerates the reactions in shorter times and higher
of benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline deriv- yields, clarifying its applicability as an adequate catalyst for the promo-
atives of 4-chlorobenzaldehyde. The obtained results are tabulated tion of these multicomponent reactions.
in Table 1. The proposed mechanism is depicted in Scheme 2 according to
Although omitting solvent improved yields and times in the the literature [59] for the synthesis of benzoxanthene derivatives
synthesis of 12-(4-chlorophenyl)-3,3-dimethyl-3,4,5,12- using a Brønsted acidic ionic liquid (BAIL) such as [H 2 -
tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolin-1(2H)-one (5b), the DABCO][HSO4]2. At first step of this mechanism, [H2-DABCO][HSO4]2
yield was trace without using the catalyst under the optimized condi- is activated the aldehyde 1 by hydrogen bonding. Then a
tions (Table 1, entry 15). Moreover, this experiment was carried out Knoevenagel condensation occur between activated aldehyde a and
for the synthesis of 5-(4-chlorophenyl)-1,3,8,8-tetramethyl-5,8,9,10- enol b. In continue, the generated intermediate c change to a
tetrahydropyrimido[4,5-b]quinoline-2,4,6(1H,3H,7H)-trione (6b) and Knoevenagel condensation product d. In route 1, intermediate d,
the result demonstrated the importance of use of the catalyst to pro- which is activated by the ionic liquid, contributes in a Michael addi-
mote the reaction (Table 1, entry 30). After optimization of the reaction tion with N3 of 2-aminobenzimidazole and produces the intermedi-
as shown in Scheme 1, different types of aromatic aldehydes containing ate e. An intra-molecular cyclization in intermediate e, continued
both electron-donor and -withdraw groups were used for the synthesis by lose of water, produces the requested products (5a–s). On the
of benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline deriva- other hand, the effect of amino group of 2-aminobenzimidazole 3
tives under these conditions (Table 2). All reaction were performed to carbonyl group in intermediate d, can be resulted in intermediate
under mild conditions in high yields during acceptable reaction times. f. Removal of H+ from N1 lead to an intra-molecular cyclization in in-
The reactions which were checked by aliphatic aldehydes lead to a mix- termediate f producing (5a–s) products through route 2. Besides,
ture of unidentified products. So the method is not useful for these types product (6a–n) can be produced when 6-amino-1,3-dimethyluracil
of compounds. 4 engaged in a Michael addition with intermediate d in order to pre-
Afterwards it was essential that the catalytic efficiency of [H2- pare intermediate g. By removing of H+ from g, the ionic liquid pro-
DABCO][HSO4]2 be compared with previous methods in order to clear motes an intra-molecular cyclization to form the intermediate h.
up the merit of the catalyst. For this reason, the synthesis of 12-(4- Finally, this intermediate loses water to release (6a–n, route 3).
chlorophenyl)-3,3-dimethyl-3,4,5,12-
tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolin-1(2H)-one (5b) and 5- 3.3. Reusability of the catalyst
(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 To investigate the reusability of the catalyst, the synthesis of 12-
selected as model reactions and were compared in terms of the catalyst (4-chlorophenyl)-3,3-dimethyl-3,4,5,12-
amount, reaction times and turnover frequency (TOF) with some proce- tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolin-1(2H)-one (5b) and
dures which were reported for the synthesis of 5-(4-chlorophenyl)-1,3,8,8-tetramethyl-5,8,9,10-
benzimidazoquinazolinone and pyrimido[4,5-b]-quinoline derivatives tetrahydropyrimido[4,5-b]quinoline-2,4,6(1H,3H,7H)-trione (6b)
 F. Shirini et al. / Journal of Molecular Liquids 243 (2017) 302–312 311

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.

Fig. 8. Reusability of [H2-DABCO][HSO4]2 in the synthesis of 12-(4-chlorophenyl)-3,3- Fig. 9. Reusability of [H2-DABCO][HSO4]2 in the synthesis of 5-(4-chlorophenyl)-1,3,8,8-
dimethyl-3,4,5,12-tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolin-1(2H)-one 5b. tetramethyl-5,8,9,10-tetrahydropyrimido[4,5-b]quinoline-2,4,6(1H,3H,7H)-trione 6b.
312 F. Shirini et al. / Journal of Molecular Liquids 243 (2017) 302–312

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Supplementary data to this article can be found online at http://dx.

doi.org/10.1016/j.molliq.2017.07.080.

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