Bronsted acidic ionic liquids: New, efficient, and green promoter system for the synthesis of 4(3H)-quinazolinones

Article abstract of DOI:10.1080/00397911003640108

A simple, inexpensive, and efficient new synthesis of 4(3H)-quinazolinones from the reaction of 2-aminobenzamide with aroyl chlorides in the presence of two new halogen-free Brnsted acidic ionic liquids, 3-methyl-1-(4-sulfonic acid)butylimidazolium hydrogen sulfate [(CH₂)₄SO ₃HMIM][HSO₄] and 1-(4-sulfonic acid) butylpyridinium hydrogen sulfate [(CH2)4SO3HPY][HSO4], green and reusable catalysts, with excellent product yields under solvent-free conditions is reported. The products could be separated simply from the catalyst, and the catalyst could be recycled without noticeably decreasing the catalytic activity.

Full text of DOI:10.1080/00397911003640108

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Brønsted Acidic Ionic Liquids: New,
Efficient, and Green Promoter
System for the Synthesis of 4(3H)-
Quinazolinones
Majid M. Heravi a , Niloofar Tavakoli-Hoseini b & Fatemeh F.
Bamoharram b
a Department of Chemistry, School of Sciences, Alzahra University,
Vanak, Tehran, Iran
b Department of Chemistry, Faculty of Sciences, Islamic Azad
University, Mashhad Branch, Mashhad, Iran
Version of record first published: 31 Jan 2011.
To cite this article: Majid M. Heravi, Niloofar Tavakoli-Hoseini & Fatemeh F. Bamoharram (2011):
Brønsted Acidic Ionic Liquids: New, Efficient, and Green Promoter System for the Synthesis of 4(3H)-
Quinazolinones, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 41:5, 707-714
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Synthetic Communications1, 41: 707–714, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003640108
BRØNSTED ACIDIC IONIC LIQUIDS: NEW, EFFICIENT,
AND GREEN PROMOTER SYSTEM FOR THE
SYNTHESIS OF 4(3H)-QUINAZOLINONES
Majid M. Heravi,1 Niloofar Tavakoli-Hoseini,2 and
Fatemeh F. Bamoharram2
1Department of Chemistry, School of Sciences, Alzahra University,
Vanak, Tehran, Iran
2Department of Chemistry, Faculty of Sciences, Islamic Azad University,
Mashhad Branch, Mashhad, Iran
Abstract A simple, inexpensive, and efficient new synthesis of 4(3H)-quinazolinones from
the reaction of 2-aminobenzamide with aroyl chlorides in the presence of two new
halogen-free Brønsted acidic ionic liquids, 3-methyl-1-(4-sulfonic acid)butylimidazolium
hydrogen sulfate [(CH2)4SO3HMIM][HSO4] and 1-(4-sulfonic acid) butylpyridinium
hydrogen sulfate [(CH2)4SO3HPY][HSO4], green and reusable catalysts, with excellent
product yields under solvent-free conditions is reported. The products could be separated
simply from the catalyst, and the catalyst could be recycled without noticeably decreasing
the catalytic activity.
Keywords 2-Aminobenzamide; aroyl chlorides; Brønsted acidic ionic liquids; 4(3H)-
quinazolinones
INTRODUCTION
4(3H)-Quinazolinones are an important class of fused heterocycles with an
array of biological activities such as inhibition of humane erythrocyte purine nucleo-
side phosphorylase[1] and poly(ADP-ribose) polymerase,[2] treatment of diabetes and
obesity,[3] and antagonist,[4] antitumor,[5] anti-inflammatory,[6] insecticidal, and anti-
microbial activity.[7] They are also important building blocks in the total synthesis of
Received September 23, 2009.
Address correspondence to Majid M. Heravi, Department of Chemistry, School of Sciences,
Alzahra University, Vanak, Tehran, Iran. E-mail: mmh1331@yahoo.com
707

708
M. M. HERAVI, N. TAVAKOLI-HOSEINI, AND F. F. BAMOHARRAM
Scheme 1. Synthesis of 4(3H)-quinazolinones.
natural products[8] and are the constituents of some isolated naturally occurring
alkaloids.[9] A small number of quinazolinones have been reported as potent che-
motherapeutic agents in the treatment of tuberculosis.[10] The antihyperlipidemic
activities of these compounds were also investigated.[11] There are several methods
for the synthesis of 4(3H)-quinazolinones using I2=KI,[12] NaHSO3,[13] P-toluene-
sulfunic acid=2,3-dichloro-5,6-dicyanobenzoquinonce (DDQ),[14] CuCl2,[15] FeCl3,[16]
Ga(OTf)3,[17] Bi(TFA)3-[nbp]),[18] Sc(OTf)3,[19] H-Y zeolites,[20] and Preyssler nano-
particles[21] as catalysts. Though these methodologies are quite useful, most of the
methods encounter some limitations, such as expensive catalysts, longer reaction
times, and harsh reaction conditions. Therefore, the development of simple, efficient,
clean, high-yielding, and environmentally friendly approaches using new catalysts
for the synthesis of these compounds is an important task for organic chemists.
Ionic liquids (ILs), recognized as environmentally benign media, have been
widely applied in many reactions as catalysts or dual catalyst–solvents because of
their low vapor pressure, reusability, and high thermal and chemical stability.[22,23]
The introduction of Brønsted acidic functional groups into cations or anions of
the ILs, especially the SO3H-functional groups, obviously enhanced their acidities
and water solubilities.[24–27] Therefore, Brønsted acidic ILs can be used as highly
efficient acid catalysts. Moreover, their polar nature makes them useful under
solvent-free conditions. In fact, the use of Brønsted acidic ILs as catalysts is an area
of ongoing activity. However, development and exploration of these catalysts are
currently in the preliminary stages.
In continuation of our previous works on the applications of reusable acid cat-
alysts in the synthesis of organic compounds,[28–31] herein we report a simple method
for the green synthesis of 4(3H)-quinazolinones from reaction of 2-aminobenzamide
with aroyl chlorides in the presence of Brønsted acidic ILs at 90 ꢀC under
solvent-free conditions (Scheme 1).
RESULTS AND DISCUSSION
For our investigations, two Brønsted acidic ILs, 3-methyl-1-(4-sulfonic acid)-
butylimidazolium hydrogen sulfate [(CH2)4SO3HMIM][HSO4] (IL1) and 1-(4-
sulfonic acid)butylpyridinium hydrogen sulfate [(CH2)4SO3HPY][HSO4] (IL2), were
prepared according to the 12 literature procedure.[32,33]
Initially to optimize the reaction conditions, the reaction of 2-aminobenzamide
with 4-chlorobenzoyl chloride was used as a model reaction. Therefore, a mixture of
2-aminobenzamide (5 mmol) and benzoyl chloride (5 mmol) was heated on an oil

SYNTHESIS OF 4(3H)-QUINAZOLINONES
709
Figure 1. Brønsted acidic IL1 structure.
Figure 2. Brønsted acidic IL2 structure.
bath at 90 ꢀC under various reaction conditions. In the absence of the catalysts, the
product 3c was obtained in a trace amount after 15 min, whereas in a presence of a
catalytic amount of the catalysts (2 mol%), the product 3c was formed in a very short
period of time with excellent yield.
Also, the reaction was carried out in various solvents and also under
solvent-free conditions (Table 1). As shown in Table 1 for IL1, in comparison to con-
ventional methods the yield of the reaction under solvent-free conditions is greater
and the reaction time is shorter. Also, the yield increased as the reaction temperature
was raised, and at 90 ꢀC the product 3c was obtained in excellent yield. In the other
studies, all the reactions were carried out at 90 ꢀC in the presence of 2 mol% of the
ILs under solvent-free conditions.
To evaluate the generality of this model reaction, we prepared a range of
4(3H)-quinazolinones under the optimized reaction conditions. In all cases, the
expected products were obtained in excellent yields in very short reaction times.
The results are shown in Table 2.
Table 1. Synthesis of compound 3c in the presence of [(CH2)4SO3HMIM][HSO4]
(2 mol%) in different solvents at reflux temperature (for entry 6 at 90 ꢀC)
Entry
Solvent
Time (min)
Yield (%)a
1
2
3
4
5
6
EtOH
CH2Cl2
THF
5
8
80
74
68
64
55
94
8
CH3CN
H2O
Solvent-free
12
12
1
aIsolated yields.

710
M. M. HERAVI, N. TAVAKOLI-HOSEINI, AND F. F. BAMOHARRAM
Table 2. Synthesis of 4(3H) quinazolinones 3a–h in the presence of IL1 and IL2 (2 mol%) under
solvent-free conditions at 90 ꢀC
Time (min)
(IL1=IL2)
Yield (%)b
(IL1=IL2)
Entry
Aroyl chloride
Productsa
Mp (ꢀC)
1
1=2
94=92
96=94
235–237[12]
2
3
4
5
6
7
1=<1
316–318[12]
306–307[12]
209–211[12]
248–249[12]
242–244[12]
1=<1
96=95
88=85
90=88
96=96
98=96
2=4
2=3
2=4
1=1
353–351[12]
(Continued )

SYNTHESIS OF 4(3H)-QUINAZOLINONES
711
Table 2. Continued
Time (min)
(IL1=IL2)
Yield (%)b
(IL1=IL2)
Entry
Aroyl chloride
Productsa
Mp (ꢀC)
8
1=1
90=88
362–364[12]
aAll the products were known and characterized by 1H NMR and IR spectral data and by comparison
with authentic samples.[12]
bIsolated yields.
CONCLUSION
In conclusion, we have reported a new catalytic method for the synthesis of
4(3H)-quinazolinones from the reaction of 2-aminobenzamide with aroyl
chlorides in the presence of Brønsted acidic ILs as efficient, reusable, and eco-
friendly homogeneous catalysts. The catalysts can be reused after a simple workup,
with a gradual decline of their activity being observed. High yields, short reaction
times, simplicity of operation, and easy workup are some advantages of this
protocol.
EXPERIMENTAL
All chemicals were commercially available and used without further purifi-
cation. The Brønsted acidic ILs were synthesized according to the literature. Melting
points were recorded on an Electrothermal type 9100 melting-point apparatus. The
infrared (IR) spectra were obtained on a 4300 Shimadzu spectrophotometer as KBr
1
disks. The H NMR spectra (100 and 500 MHz) were recorded on Bruker AC100
and Bruker DRX500 spectrometers.
Typical Procedure for the Prepration of Brønsted Acidic Ionic Liquid
[(CH2)4SO3HMIM][HSO4] (IL1)
A mixture of 1-methylimidazole (0.2 mol) and 1,4-butane sultone (0.2 mol) was
charged into a 150-mL conical flask. The mixture was stirred at room temperature
for 4 days until it became solid. The white solid zwitterion was washed repeatedly
with ether, filtered to remove nonionic residues, and dried in vacuum. Then, a stoi-
chiometric amount of concentrated sulfuric acid (98%, 10.9 mL) was added dropwise
to the white solid zwitterion slowly at 0 ꢀC. The mixture was stirred at 80 ꢀC for 6 h.
The product was washed with diethyl ether and dried in vacuo at 50 ꢀC for 2 h to get
the viscous clear ILs.
Brønsted acidic ionic liquid [(CH2)4SO3HPY][HSO4] (IL2) was prepared with a
similar procedure.

712
M. M. HERAVI, N. TAVAKOLI-HOSEINI, AND F. F. BAMOHARRAM
General Procedure for the Synthesis of 4(3H)-Quinazolinones from
the Reaction of 2-Aminobenzamide with Aroyl Chlorides Using
Brønsted Acidic Ionic Liquid
To a mixture of 2-aminobenzamide (5 mmol) and aroyl chlorides (5 mmol),
2 mol% IL was added. The reaction mixture was heated on the oil bath at 90 ꢀC
for a few minunets. The progress of the reaction was monitored by thin-layer chro-
matography (TLC). After completion of the reaction, the mixture was poured into
ice-cold water and stirred thoroughly, which resulted in precipitation of the desired
product. The precipitated solid was filtered and washed with ethanol and water. The
pure product was obtained by recrystallization from ethanol. The structure of the
1
products was confirmed by H NMR, IR spectra, and comparison with authentic
samples prepared by reported methods.[12]
Recycling the Catalysts
All of these catalysts are soluble in water and therefore could be recycled from
the filtrate. Catalysts were recovered by evaporation of the water, washed with
diethyl ether, dried at 50 ꢀC under vacuum for 1 h, and reused in another reaction
without appreciable reduction in the catalytic activity. Such procedure applied for
3c in the presence of IL1 in a second run resulted in 94% yield.
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