A simple and convenient synthesis of [1,2,4]triazolo/benzimidazolo quinazolinone and [1,2,4]triazolo[1,5-a]pyrimidine derivatives catalyzed by DABCO-based ionic liquids

Article abstract of DOI:10.1007/s13738-017-1125-x

DABCO-based ionic liquids were utilized for the preparation of [1,2,4]triazolo/benzimidazolo quinazolinone and [1,2,4]triazolo[1,5-a]pyrimidine derivatives in the adequate procedures. These methods involve three-component reaction between aldehydes, β-dik

Full text of DOI:10.1007/s13738-017-1125-x

J IRAN CHEM SOC
DOI 10.1007/s13738-017-1125-x
ORIGINAL PAPER
A simple and convenient synthesis of [1,2,4]triazolo/benzimidazolo
quinazolinone and [1,2,4]triazolo[1,5‑a]pyrimidine derivatives
catalyzed by DABCO‑based ionic liquids
Narges Seyyedi1 · Farhad Shirini1 · Mohaddeseh Safarpoor Nikoo Langarudi1 ·
Setareh Jashnani1
Received: 15 October 2016 / Accepted: 13 April 2017
© Iranian Chemical Society 2017
Abstract DABCO-based ionic liquids were utilized for
the preparation of [1,2,4]triazolo/benzimidazolo quina-
zolinone and [1,2,4]triazolo[1,5-a]pyrimidine deriva-
tives in the adequate procedures. These methods involve
three-component reaction between aldehydes, β-diketones
and 3-amino-1,2,4-triazole or 2-aminobenzimidazole
in the presence of 1,4-disulfo-1,4-diazabicyclo[2.2.2]
octane-1,4-diium chloride ([DABCO](SO3H)2(Cl)2) and
1,4-disulfo-1,4-diazabicyclo[2.2.2]octane-1,4-diium dihy-
drogen sulfate ([DABCO](SO3H)2(HSO4)2) as reusable and
economical catalysts at 100 °C. These methods also show
eco-friendly characters by elimination of solvent. Any by-
product was not prepared through this method, and prod-
ucts were separated by a simple workup procedure. The
other noticeable benefts of these procedures are excellent
yields, short reaction times, mild reaction conditions and
use of available and inexpensive materials.
Introduction
In recent years, combinatorial chemistry is widely devel-
oped due to its wide applications in generation of drugs.
It has appeared as a powerful tool to accelerate genera-
tion, identifcation and optimization of lead compounds
in the drug discovery processes [1–3]. Nitrogen-contain-
ing heterocycles have been utilized in the pharmaceuti-
cal and agrochemical industries widely because of their
varied physiological properties [4]. Among these types
of compounds, quinazoline derivatives possess important
pharmacological activities such as antihypertensive [5],
antidiabetics [6], anti-infammatory [7], antifertility [8],
anticonvulsant [9], anticancer [10] and anti-HIV [11].
Besides, benzimidazoles and triazoles are the important
structural motif in the skeleton of some biologically active
molecules [12–14]. For example, some antifungal medica-
tions including fuconazole, itraconazole and albaconazole
are adequate examples which possess triazole motif in
their structures (Fig. 1).
Although many methods are reported to prepare these
compounds, such as refuxing in DMF [15–17] or EtOH [18,
19], solvent-free condition [20], microwave irradiation [21–
23], H6P2W18O62·18H2O [24], sulfamic acid (NH2SO3H)
[25], 1-n-butyl- 3-methylimidazolium tetrafuoroborate
([Bmim]BF4) [26], 1-butyl-3-methylimidazolium bromide
([bmim]Br) [27], molecular iodine (I2) [28], chitosan-based
composite magnetic nanocatalyst [29], p-toluenesulfonic acid
[30], acetic acid [31], nano-SiO2 [32] and sulfonic acid func-
tionalized nanoporous silica (SBA–Pr–SO3H) [33], many of
them suffer from some disadvantages such as use of expen-
sive and hazardous catalysts [24, 29, 32, 33] or solvent [15–
17, 21], harsh conditions [15–20], long reaction time [18, 20,
29] and low yields [15–17, 19, 20]. However, some of these
methods are roughly good, but yet it is necessary to improve
Keywords 1,4-Diazabicyclo[2.2.2]octane (DABCO) ·
DABCO-based ionic liquids · Multi-component reactions
(MCRs) · Quinazoline derivatives · 3-Amino-1,2,4-
triazole · 2-Aminobenzimidazole
Electronic supplementary material The online version of this
article (doi:10.1007/s13738-017-1125-x) contains supplementary
material, which is available to authorized users.
* Farhad Shirini
shirini@guilan.ac.ir
1
Department of Chemistry, College of Science, University
of Guilan, Rasht 41335, Islamic Republic of Iran
1 3

J IRAN CHEM SOC
Fig. 1 Some antifungal medications possessing the triazole nucleus
procedures to achieve a simple, effcient, inexpensive and
nontoxic procedure with readily available reagents.
Products were characterized by their physical constants in
comparison with authentic samples, IR and NMR spectros-
copy. The purity determination of the substrates and reac-
tion monitoring were accomplished by TLC on silica-gel
polygram SILG/UV 254 plates.
One-pot strategies are well known in organic synthesis
as effcient processes to access complex molecules without
isolating intermediates [34]. These reactions are more inter-
esting for organic chemists because of avoiding sequential
separation and purifcation processes that could save time
and resources while increasing chemical yield. As one of
the most popular and widely used one-pot strategies, multi-
component reactions (MCRs) are powerful tools in the syn-
thesis of condensed heterocycle molecules. In these reac-
tions, three or more ingredients mix together to provide a
product containing the same elements of the all reactants.
These reactions can be a very elegant and rapid way to
obtain complex structures in a single synthetic through-
put from simple building blocks and show high selectivity
[35–37].
MCRs gave this opportunity to chemists that could elim-
inate toxic organic solvents from reaction media. Recently,
chemists were interested to research about solid-state reac-
tions as they offer potential reduction in environmental pol-
lution with the elimination of solvents [38, 39]. According
to green chemistry principles [40], elimination of solvents
can cause to lower toxicity and hazard, decrease waste and
save time and resources in the chemical processes.
Nowadays, room-temperature ionic liquids (RTILs) have
been used as alternative ‘green’ solvents instead of hazard-
ous traditional organic solvents, due to their properties such
as non-fammability, negligible vapor pressure, high ther-
mal stability, solvating ability and easy recyclability. They
have the potential to be highly polar yet non-coordinating
[41–45].
Instrumentation
Melting points were measured by a Büchi B-545 apparatus
in open capillary tubes. FT-IR spectra were recorded on a
1
Perkin-Elmer spectrum BX series. H NMR and 13C NMR
spectra were determined on Bruker AV-400 spectrometers
using TMS as internal standard
Preparation of [DABCO](HSO3)2(Cl)2 and [DABCO]
(SO3H)2(HSO4)2
Chlorosulfonic acid (1.75 g, 15 mmol) was added dropwise
to a round-bottom fask (100 mL) containing 1,4-diazabi-
cyclo[2.2.2]octane (DABCO) (0.841 g, 7.5 mmol) in dry
CH2Cl2 (50 mL), over a period of 5 min in an ice bath.
After the completion of addition, the reaction mixture
was stirred for 2 h and then stood for 5 min, and then,
CH2Cl2 was decanted. The residue was washed with dry
diethyl ether (3 × 50 mL) and dried under vacuum to
give [DABCO](HSO3)2(Cl)2 as a white solid in 98%
yield [46]. At the second step and in a round-bottom fask
(100 mL) containing [DABCO](HSO3)2(Cl)2 (0.864 g,
2.5 mmol) equipped with a gas inlet tube for conducting
HCl gas over an adsorbing solution (i.e., water), sulfuric
acid (99.99%, 0.49 g, 5 mmol) was added dropwise over
a period of 5 min in an ice bath. After the addition was
completed, the reaction mixture was left for 6 h to give
[DABCO](SO3H)2(HSO4)2 as a white solid in 95% yield
[47] (Fig. 2). The product was formed quantitatively and
in high purity as assessed by melting point, mass, Ham-
Experimental
General
1
mett acidity, FT-IR, H NMR, 13C NMR and elementary
Chemicals were purchased from Fluka, Merck and Aldrich
Chemical Companies. Yields refer to the isolated products.
analysis.
1 3

J IRAN CHEM SOC
1,4‑disulfo‑1,4‑diazabicyclo[2.2.2]octane‑1,4‑di‑
ium chloride ([DABCO](SO3H)2(Cl)2) White solid;
M.p.: 75 (°C); IR (KBr, υ, cm−1) 3500–2800 (O–H,
broad), 1177 (S–O), 881 (S–N), 854 (S–O); 1H NMR
(400 MHz, DMSO-d6): δ (ppm) 3.58 (6H, s, CH2), 7.72
(1H, s, SO3H); 13C NMR (100 MHz, DMSO-d6): δ (ppm)
43.2; MS: m/z = 345 (M+); H0 = 1.37; Anal. Calcd for
C6H14Cl2N2O6S2: C, 20.88; H, 4.09; Cl, 20.54; N, 8.12; O,
27.81; S, 18.57.
were characterized by conventional spectroscopic meth-
ods. Physical and spectral data for new compounds are
represented below.
9‑(4‑Bromophenyl)‑5,6,7,9‑tetrahydro‑[1,2,4]
triazolo[5,1‑b]quinazolin‑8(4H)‑one 8q White powder;
M.p.: 306–308 (°C); IR (KBr, υ, cm−1) 3429 (N–H),
3129 (CH-arom), 2883 (CH-aliph), 1648 (C=O), 1578
1
(N–H), 621 (C–Br); H NMR (400 MHz, DMSO-d6): δ
(ppm) 1.89–2.01 (2H, m, CH2), 2.22–2.34 (2H, m, CH2),
2.61–2.71 (2H, m, CH2), 6.23 (1H, s, CH), 7.18 (2H, d,
J = 8.4 Hz, CH-Ph), 7.49 (2H, d, J = 8.4 Hz, CH-Ph),
7.71 (1H, s, CH-triazole), 11.21 (1H, s, NH); 13C NMR
(100 MHz, DMSO-d6): δ (ppm) 21.1, 26.8, 36.7, 44.4,
57.7, 106.6, 121.3, 129.7, 131.6, 141.3, 147.1, 150.6,
153.2, 193.8; Anal. Calcd for C15H13BrN4O: C, 52.19;
H, 3.80; Br, 23.15; N, 16.23; O, 4.63.
1,4‑disulfo‑1,4‑diazabicyclo[2.2.2]octane‑1,4‑diium
dihydrogen sulfate ([DABCO](SO3H)2(HSO4)2) White
solid; M.p.: 70 (°C); FT-IR (KBr, υ, cm−1) 3500–2800
(O–H, broad), 1287 (S–O), 1177 (S–O), 883 (S–N), 854
(S–O); 1H NMR (400 MHz, DMSO-d6): δ (ppm) 3.59 (6H,
s, CH2), 6.97 (1H, s, SO3H), 14.14 (1H, s, HSO4); 13C NMR
(100 MHz, DMSO-d6): δ (ppm) 43.2; MS: m/z = 467(M+);
H0 = 0.43; Anal. Calcd for C6H16N2O14S4: C, 15.38; H,
3.44; N, 5.98; O, 47.82; S, 27.38.
9‑(2‑Nitrophenyl)‑5,6,7,9‑tetrahydro‑[1,2,4]
triazolo[5,1‑b]quinazolin‑8(4H)‑one 8s White pow-
der; M.p.: 300–304 (°C); IR (KBr, υ, cm−1) 3444 (N–H),
3213 (CH-arom), 2910 (CH-aliph), 1643 (C=O), 1569
General procedure for the preparation
of benzimidazoquinazolinone derivatives
1
(NO2), 1357 (NO2); H NMR (400 MHz, DMSO-d6): δ
(ppm) 1.88–1.99 (2H, m, CH2), 2.17–2.27 (2H, m, CH2),
2.64–2.67 (2H, m, CH2), 6.98 (1H, s, CH), 7.30 (1H, d,
J = 1.2 Hz, CH-Ph), 7.49 (1H, dt, J1 = 7.6 Hz, J2 = 0.8 Hz,
CH-Ph), 7.61 (1H, dt, J1 = 7.6 Hz, J2 = 1.2 Hz, CH-Ph),
7.73 (1H, s, CH-triazole), 7.86 (1H, dd, J1 = 8 Hz,
J2 = 1.2 Hz, CH-Ph), 11.32 (1H, s, NH); 13C NMR
(100 MHz, DMSO-d6): δ (ppm) 21.1, 26.8, 36.4, 53.4,
106.19, 124.4, 129.4, 129.8, 133.8, 135.3, 147.2, 149.0,
150.8, 153.7, 193.9; Anal. Calcd for C15H13N5O3: C, 57.87;
H, 4.21; N, 22.50; O, 15.42.
A mixture of aromatic aldehyde 1 (1.0 mmol), dimedone
2 (1.0 mmol), 2-aminobenzimidazole 3 (1.0 mmol) and
[DABCO](HSO3)2(Cl)2 (0.2 mmol, method A) or [DABCO]
(SO3H)2(HSO4)2 (0.02 mmol, method B) was stirred at
100 °C for the appropriate time. The progress of the reac-
tion was followed by TLC (n-hexane/ethyl acetate—8:2).
After completion, the obtained solid mixture was washed
with cooled water (2 × 2 mL) to separate the catalyst. Then,
warm ethanol (3 mL) was added to the reaction media, and
the solid product was fltered and dried in air.
Results and discussions
General procedure for the preparation
of triazoloquinazolinone derivatives
In recent years, preparation and use of N-sulfonic acids
have become an important part of our ongoing research
program [48–55]. In continuation of these studies and
of the mentioned diffculties in the synthesis of quina-
zolinone derivatives, herein we wish to report new and
straightforward one-pot procedures to prepare quina-
zolinone derivatives using [DABCO](SO3H)2(Cl)2 and
[DABCO](SO3H)2(HSO4)2 as effcient ionic liquids
and compare the ability of these catalysts in the studied
reactions.
A
mixture of aromatic aldehyde 1 (1.0 mmol),
3-amino-1,2,4-triazole 5 (1.0 mmol), β-diketones (dime-
done 2, 1,3-cyclohexadione 6 or ethyl acetoacetate 7)
(1.0 mmol) and [DABCO](HSO3)2(Cl)2 (0.2 mmol,
method A) or [DABCO](SO3H)2(HSO4)2 (0.02 mmol,
method B) was stirred at 100 °C for the appropriate
time. After completion of the reaction, as indicated by
TLC (n-hexane/ethyl acetate—8:2), a thick precipitate
would be obvious. Then cooled water (2 × 2 mL) was
added to the reaction media to separate the catalyst.
After washing with water, warm ethanol (3 mL) was
added and the solid product was fltered to give the pure
product; afterward, it was dried in air. The pure products
At frst, to fnd the best reaction conditions and
amount of the catalysts, the reaction of 4-chlorobenza-
ldehyde, dimedone and 2-aminobenzimidazole in the
presence of [DABCO](HSO3)2(Cl)2 (method A) and
1 3

J IRAN CHEM SOC
Table 1 Effect of temperature, amount of the catalyst and solvent in the synthesis of 12-(4-chlorophenyl)-3,3-dimethyl-3,4,5,12-tetrahyd-
robenzo[4,5]imidazo[2,1-b]quinazolin-1(2H)-one 4b ([DABCO](SO3H)2Cl2 and [DABCO](HSO3)2(HSO4)2 are A and B, respectively)
Entry
Solvent
Condition/temperature (°C)
Catalyst (mmol)
Time (min)
Yield (%)
A
A
B
A
B
B
1
CH2Cl2
r. t.
0.14
0.29
0.14
0.29
0.14
0.20
0.20
0.20
0.20
0.20
0.11
0.20
0.20
0.20
0.04
0.11
0.04
0.11
0.04
0.11
0.04
0.04
0.04
0.04
0.11
0.02
0.04
0.02
180
180
180
180
180
180
180
150
120
90
180
180
180
180
180
180
180
130
105
70
Trace
Trace
2
CH2Cl2
Refux
r. t.
Trace
Trace
3
CH3CN
Trace
Trace
4
CH3CN
Refux
50
Trace
Trace
5
H2O
Trace
Not complete
Not complete
100 (70)a
100 (75)
100 (75)
100 (85)
100 (85)
100 (93)
100 (93)
100 (93)
6
H2O
Refux
Refux
r. t.
Trace
7
EtOH: H2O (1:1)
Not complete
100 (78)
100 (75)
100 (80)
100 (87)
100 (95)
100 (93)
100 (93)
8
EtOH
9
EtOH
Refux
Grinding/100 °C
100 °C
100 °C
100 °C
120 °C
10
11
12
13
14
–
–
–
–
–
100
75
100
60
75
65
75
60
a
Isolated yield
Scheme 1 Synthesis of benzimidazoquinazolinone derivatives using [DABCO](SO3H)2Cl2 (method A) and [DABCO](HSO3)2(HSO4)2 (method
B)
Scheme 2 [DABCO](SO3H)2Cl2 (method A) and [DABCO](HSO3)2(HSO4)2 (method B) catalyzed the synthesis of [1,2,4]triazolo/benzimida-
zolo quinazolinone and [1,2,4]triazolo[1,5-a]pyrimidine derivatives
1 3

J IRAN CHEM SOC
Table 2 Preparation of triazolo/
benzimidazoquinazolinone and
triazolopyrimidine derivatives
using [DABCO](SO3H)2Cl2
(method A) and [DABCO]
(HSO3)2(HSO4)2 (method B) as
the catalysts
Entry
Ar
Pro.
R
Amine Time (min) Yield
(%)a
M. p. °C
Found
A
B
A
B
Rep. [Refer-
ences]
1
C6H5
4a
4b
4c
4d
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
80
75 90 90 >300
60 95 93 >300
65 90 87 >300
65 80 85 >300
85 90 90 >300
60 90 95 >300
65 85 90 >300
368 [19]
2
4-ClC6H4
3-ClC6H4
2-ClC6H4
75
80
393 [19]
3
>300 [20]
>300 [20]
>300 [22]
369 [19]
4
85
5
2,4-diClC6H3 4e
105
90
6
4-BrC6H4
4f
7
4-FC6H4
4g
4h
4i
80
>300 [22]
335 [19]
8
4-NO2C6H4
3-NO2C6H4
4-MeC6H4
2-MeC6H4
4-MeOC6H4
3-MeOC6H4
4-OHC6H4
135 110 90 85 >300
155 125 83 83 >300
9
>300 [20]
359 [19]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
4j
120
100
90 87 90 >300
90 80 80 >300
4k
4l
>300 [20]
389 [19]
130 100 87 85 >300
140 100 83 85 >300
165 120 90 90 >300
180 135 80 78 >300
175 120 80 75 >300
4m
4n
>300 [20]
>300 [24]
304–307 [29]
>300 [32]
4-NMe2C6H4 4o
3-Indole-
C6H5
4p
8a
8b
95
65
75 83 80 238–240 248–250 [16]
60 90 93 295–297 303–305 [25]
4-ClC6H4
2,4-diClC6H3 8c
100
95
85 90 87 >300
323–325 [28]
4-BrC6H4
4-FC6H4
8d
8e
8f
70 83 85 285–289 284–288 [25]
70 90 85 285–290 279–281 [26]
90
4-NO2C6H4
3-NO2C6H4
2-NO2C6H4
4-MeC6H4
2-MeC6H4
4-MeOC6H4
3-MeOC6H4
4-OHC6H4
2-Naphthyl
C6H5
125 100 90 80 290–294 284–285 [16]
140 100 85 78 253–258 266–269 [24]
140 120 80 75 283–285 290–292 [28]
8g
8h
8i
100
105
130
110
90 80 85 260–264 264–269 [25]
85 85 81 295–299 >300 [20]
90 80 85 219–221 222–224 [16]
8j
8k
8l
95 80 83 >300
>300 [20]
>300 [24]
8m
8n
8o
8p
8q
8r
135 120 85 90 >300
165 140 85 83 284–287 287–290 [24]
90
90
70 90 90 296–300 >300 [20]
75 90 90 294–296 — [27]
80 87 85 306–308 New
4-ClC6H4
4-BrC6H4
3-NO2C6H4
2-NO2C6H4
4-MeC6H4
4-MeOC6H4
C6H5
H
H
100
H
150 135 80 78 292–296 >300 [20]
150 130 80 80 300–304 New
8s
8t
H
H
120
145 120 90 85 306–308 >300 [20]
100 90 83 85 191–192 190–192 [26]
120 100 80 80 255–259 263–264 [26]
90 80 83 >300
>300 [20]
8u
8v
8w
8x
8y
H
EAAb
EAA
EAA
EAA
4-NO2C6H4
4-MeC6H4
4-MeOC6H4
105
120
75 85 78 237–241 246–248 [26]
80 80 75 232–236 220–223 [26]
a
Isolated yields
b
Ethyl acetoacetate
1 3

J IRAN CHEM SOC
[DABCO](SO3H)2(HSO4)2 (method B) was selected as
a model system. As presented in Table 1, among tested
solvents in different conditions the best result that was
obtained under solvent-free condition at 100 °C (method
B) was selected as a model system. As presented in
Table 1, among tested solvents in different conditions the
best result was obtained under solvent-free condition at
100 °C (Scheme 1).
Afterward and on the basis of the above-mentioned
results, we also utilized the optimized conditions for the
synthesis of triazoloquinazolinone and triazolopyrimi-
dine derivatives by replacing 3-amino-1,2,4-triazole with
2-aminobenzimidazole using a variety of β-diketones as
represented in Scheme 2.
Fig. 3 Reusability of [DABCO](HSO3)2(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 4b
Therefore, different derivatives of the stated compounds
were prepared with different aromatic aldehydes and the
outcomes are listed in Table 2. The time of the reaction
was within 75–180 min for [DABCO](SO3H)2Cl2 (method
A) and 60–140 min for [DABCO](HSO3)2(HSO4)2
(method B), and high yields of [1,2,4]triazolo/benzimida-
zolo quinazolinones and [1,2,4]triazolo[1,5-a]pyrimidines
were attained in the presence of both of the catalysts.
It is worthwhile and eco-friendly that a catalyst could
be recyclable. For this reason, we chose a model reac-
tion to investigate the reusability of both of the catalysts.
Synthesis of 12-(4-chlorophenyl)-3,3-dimethyl-3,4,5,12-
tetrahydrobenzo [4, 5] imidazo[2,1-b]quinazolin-1(2H)-
one 4b was tested under the optimized reaction con-
ditions using [DABCO](SO3H)2Cl2 (method A) and
[DABCO](HSO3)2(HSO4)2 (method B), respectively.
After completion of the reaction, the solid product was
washed with water to separate the catalyst. Then, the fl-
trate was evaporated under vacuum up to 70 °C, and the
obtained catalyst was washed with diethyl ether, dried
and reused at least for the same reaction. The recycled
reagents were reused for three runs with only the modest
loss of effciency. The obtained results are demonstrated
in Figs. 2 and 3.
To compare the effciency of [DABCO](HSO3)2(Cl)2
and [DABCO](HSO3)2(HSO4)2 in Table 3, the reaction
times, yields and amounts of the catalysts in the synthe-
sis of 4a, 8a, 8o and 8v are compared with other previous
procedures. The comparative results showed that the syn-
thesis of these compounds in the presence of [DABCO]
(HSO3)2(Cl)2 and [DABCO](HSO3)2(HSO4)2 is car-
ried out in good times and yields and lowest amount of
the catalyst; moreover, use of extra amount of substrates
was prevented, which was why this procedure became
affordable.
Based on our observations and according to the previous
reports, a possible mechanism for the synthesis of quina-
zolinone derivatives is shown in Scheme 3. At the frst step,
a Knoevenagel condensation occurs between activated
aldehyde a and enol c to prepare intermediate d. After this
step, the reaction can accomplish in two routes (I, II). If
intermediate d loses water, route I can take place produc-
ing α,β-unsaturated carbonyl compound e. Then, Michael
addition reaction of nitrogen number 2 in amine 5 makes
intermediate f. An intra-molecular cyclization in f happens,
and it loses water to produce observed quinazolinone 8.
This reaction can follow through route II, if the carbonyl
group in d activated by H from the ionic liquid. Difference
between routes I and II is in the initial attack of the nitro-
gen atom of amine. In route II, amino group instead of N2
engages in reaction. The intermediate h undergoes intra-
molecular cyclization to give the desired products [30–32].
As shown in Scheme 3, during the reaction, both
DABCO-based ionic liquids participated in the reaction
by producing H+ in medium. H+ was consumed and pro-
duced repeatedly until the reaction was completed, and ulti-
mately, ILs were separated by workup procedure without
consuming.
Fig. 2 Reusability of [DABCO](HSO3)2(Cl)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 4b
1 3

J IRAN CHEM SOC
Table 3 Compared performance of various catalysts with [DABCO](HSO3)2(Cl)2 and [DABCO](HSO3)2(HSO4)2 in the synthesis of quina-
zolinone derivatives (4a, entries 1–16; 8a, entries 17–30; 8o, entries 31–34; 8v, entries 35–38)
Entry
Catalyst/amount (mol%)
Conditions
Time (min)
Yield (%)a
TOF
References
(min−1
)
1
2
–
DMF/refux
5
90
420
4
65
64
85
93
95
96
94
94
84
90
–
–
[15]
[18]
[20]
[22]
[23]
[24]
[25]
[27]
[28]
[29]
–
EtOH/refux
b
3
–
Solvent free/110 °C
H2O/MW
–
4
–
–
5
Silica gel
MW (150 W)/120 °C
CH3CN/Refux
CH3CN/80 °C
Solvent free/100 °C
CH3CN/Refux
EtOH/40 °C
3
–
6
H6P2W18O62.H2O/1
Sulfamic acid/0.005
[Bmim]Br/0.1
Iodine/10
15
15
5
640
7
125,333.3
8
18800
84
9
10
90
10
Fe3O4@chitosan/2
–
(mg mmol−1
)
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
p-Toluenesulfonic acid/15
Acetic acid/8.7
CH3CN/40–50 °C
Solvent free/60 °C
CH3CN, r.t.
25
20
25
10
12
80
75
30
240
4
95
94
95
90
94
90
90
76
93
90
95
95
92
93
81
96
95
96
90
83
80
90
90
90
90
56
80
83
85
25.33
54.02
25.33
–
[30]
[31]
Nano-SiO2/15
[32]
SBA–Pr–SO3H/0.05 (g)
Fe3O4@clay/5 (mg)
[DABCO](HSO3)2(Cl)2/0.02
[DABCO](HSO3)2(HSO4)2/0.002
–
Solvent free/100 °C
H2O/r.t.
[33]
–
[56]
Solvent free/100 °C
Solvent free/100 °C
DMF/refux
5625
60,000
–
This work
This work
[16]
b
–
Solvent free/110 °C
MW (150 W)/120 °C
CH3CN/refux
–
[20]
Silica gel
–
[23]
H6P2W18O62.H2O/1
Sulfamic acid/0.005
[Bmim]BF4/15
30
30
11
20
10
30
25
30
5
316.67
633,333.3
55.76
4650
[24]
CH3CN/80 °C
[25]
Grinding/r. t.
[26]
[Bmim]Br/0.1
Solvent free/100 °C
CH3CN/refux
[27]
Iodine/10
81
[28]
p-Toluenesulfonic acid/15
Acetic acid/8.7
CH3CN/40–50 °C
Solvent free/60 °C
CH3CN, r.t.
21.33
43.68
21.33
–
[30]
[31]
Nano-SiO2/15
[32]
SBA–Pr–SO3H (0.05 g)
[DABCO](HSO3)2(Cl)2/0.02
[DABCO](HSO3)2(HSO4)2/0.002
–
Solvent free/100 °C
Solvent free/100 °C
Solvent free/100 °C
Solvent free/110 °C
Solvent free/100 °C
Solvent free/100 °C
Solvent free/100 °C
EtOH/refux
[33]
95
75
240
30
90
70
420
12
100
90
4368.42
53,333.3
This work
This work
[20]
b
–
[Bmim]Br/0.1
3000
5000
45,000
–
[27]
[DABCO](HSO3)2(Cl)2/0.02
[DABCO](HSO3)2(HSO4)2/0.002
HCl/1–2 drops
This work
This work
[18]
[Bmim]BF4/15
Grinding/r. t.
44.44
4150
47,222.2
[26]
[DABCO](HSO3)2(Cl)2/0.02
[DABCO](HSO3)2(HSO4)2/0.002
Solvent free/100 °C
Solvent free/100 °C
This work
This work
a
Isolated yields
b
In this procedure, aldehyde (3 mol), β-diketones (1 mol) and 2-aminobenzimidazole/3-amino-1,2,4-triazole (1.1 mol) were used
1 3

J IRAN CHEM SOC
Scheme 3 Proposed mechanism for the synthesis of quinazolinone derivatives in the presence of [DABCO](HSO3)2Cl2 and [DABCO]
(HSO3)2(HSO4)2
Acknowledgements We are thankful to the University of Guilan
Research Council for the partial support of this work.
Conclusions
In conclusion, in this study two effcient and environ-
mentally benign ionic liquids, [DABCO](HSO3)2(Cl)2
References
and [DABCO](HSO3)2(HSO4)2, were utilized for the
synthesis of different types of quinazolinone deriva-
tives. These reagents are green, easy to prepare and
inexpensive catalysts that can accelerate the synthesis of
triazoloquinazolinone and benzimidazoquinazolinones
through a simple procedure from aromatic aldehydes,
varied β-diketones and 2-aminobenzimidazole/3-
amino-1,2,4-triazole; besides, [1,2,4]triazolo[1,5-a]
pyrimidines derivatives were synthesized in this proce-
dure by using ethyl acetoacetate. After completion of
the reaction, use of extra amount of substrates and any
solvent was prevented. The applied methods show some
advantages including operational simplicity, high yields,
no by-products and easy workup due to no need of col-
umn chromatography for isolation. On the other hand,
applied conditions for the preparation of the catalysts
and quinazolinone derivatives are kinder and milder than
available methods.
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