Pentafluorophenylammonium triflate-CuCl2: A mild, efficient and reusable heterogeneous catalyst system for facile synthesis of 4(3H)-quinazolinones under solvent-free conditions

Article abstract of DOI:10.1007/s12039-012-0260-2

Pentafluorophenylammonium triflate (PFPAT) was found to be highly efficient, and recyclable heterogeneous catalyst for the synthesis of 4(3H)-quinazolinones by cyclocondensation reaction of 2-aminobenzamide with aryl aldehydes in the presence of CuCl₂ as co-catalyst in good to excellent yields under solvent-free conditions. The present methodology offers several advantages, such as simple procedure with an easy work-up, high yields, short reaction times, and the absence of any volatile or hazardous organic solvents. Moreover, the catalyst can be easily recovered and reused at least three times with only slight reduction in its catalytic activity.

Full text of DOI:10.1007/s12039-012-0260-2

J. Chem. Sci. Vol. 124, No. 4, July 2012, pp. 883–887. ꢀc Indian Academy of Sciences.
Pentafluorophenylammonium triflate-CuCl : A mild, efficient
2
and reusable heterogeneous catalyst system for facile synthesis
of 4(3H)-quinazolinones under solvent-free conditions
∗
NASER MONTAZERI , KHALIL POURSHAMSIAN, SOGHRA YOSEFIYAN and
SEYDEH SAMANEH MOMENI
Department of Chemistry, Tonekabon Branch, Islamic Azad University, Tonekabon 46819-89711, Iran
e-mail: montazer50@toniau.ac.ir
MS received 9 September 2011; revised 10 December 2011; accepted 11 January 2012
Abstract. Pentafluorophenylammonium triflate (PFPAT) was found to be highly efficient, and recyclable
heterogeneous catalyst for the synthesis of 4(3H)-quinazolinones by cyclocondensation reaction of 2-
aminobenzamide with aryl aldehydes in the presence of CuCl2 as co-catalyst in good to excellent yields under
solvent-free conditions. The present methodology offers several advantages, such as simple procedure with an
easy work-up, high yields, short reaction times, and the absence of any volatile or hazardous organic solvents.
Moreover, the catalyst can be easily recovered and reused at least three times with only slight reduction in its
catalytic activity.
Keywords. Pentafluorophenylammonium triflate; heterogeneous catalysis; 4(3H)-quinazolinones;
solvent-free conditions.
1
. Introduction
The potential advantages of these materials over homo-
geneous systems could lead to novel, environmentally
benign chemical procedures for academia and indus-
4
(3H)-quinazolinones are an important class of fused
21–23
heterocycles with a wide range of pharmacological and
biological activities such as antagonist, antimalarial,
antitumour, antibacterial, anti-inflammatory, insecti-
cidal, and antimicrobial activity. In addition, quina-
zolinone moiety is a building block for approximately
1
nine, deoxyvasicinone, and drugs like methaqualone
and piriqualone. Also, a small number of quinazoli-
nones have been reported as potent chemotherapeutic
agents in the treatment of tuberculosis. There are seve-
ral methods for the synthesis of 4(3H)-quinazolinones
using DDQ/DMF, Ga(OTf)3, Yb(OTf)3, I KI,
TBAB, Sc(OTf) , P-toluenesulphunic acid/DDQ,
NaHSO3, and SnCl .4H O, as catalysts. However,
most of these procedures have significant drawbacks
such as long reaction times, low yields of the prod-
ucts, harsh reaction conditions, and difficult work-up.
Therefore, the development of simple, efficient, clean,
high-yielding, and environmentally friendly approaches
using new catalysts for the synthesis of these com-
pounds is an important task for organic chemists.
try.
Application of solid acids in organic transfor-
1
2
mations is important because they have many advan-
tages including ease of products separation, recycling
of the catalyst and environmental acceptability as com-
3
4
5
6
24,25
pared to liquid acid catalysts.
50 naturally occurring alkaloids, such as glycosmi-
Recently, Tanabe et al. reported the application
7
8
9
of pentafluorophenylammonium triflate (C F NH OTf;
6
5
3
10
PFPAT) as a novel heterogeneous catalyst in organic
transformation such as esterification of carboxylic acids
11
26
with alcohols, C-acylations of enol silyl ethers or
27
ketene silyl (thio)acetals with acid chlorides and
Mukaiyama aldol and Mannich reactions using ketene
1
2
13
14
15
2/
16
17
18
28
3
silyl acetals with ketones and oxime ethers. However,
to the best of our knowledge there are no examples
on the use of PFPAT as catalyst for the synthesis of
19
20
4
2
4
(3H)-quinazolinones.
O
O
CuCl2
O
NH2
PFPAT
NH
Ar
+
Ar
H
NH
70
C
N
2
˚
Solvent-free
The development of heterogeneous catalysts for
organic synthesis has become a major area of research.
1
2a−j
3a−j
Scheme 1. Synthesis of 4(3H)-quinazolinones catalysed
by PFPAT.
∗
For correspondence
883

884
Naser Montazeri et al.
Prompted by these findings and due to our interest Table 1. Effect of PFPAT amount and temparature on the
in the synthesis of heterocyclic compounds,2
9–32
a
and in model reaction.
continuation of our previous works on the applications
Entry Catalyst (mol%) T ( C) Time (min) Yield (%)b
◦
of reusable catalysts in organic reactions,3
3–35
we report
here an efficient synthesis of 4(3H)-quinazolinones by
cyclocondensation reaction of 2-aminobenzamide with
aryl aldehydes using PFPAT as a solid acid catalyst
1
2
3
4
5
6
7
8
9
1
None
25
10
15
20
20
25
25
25
30
30
30
70
r.t
120
120
300
120
90
60
120
60
None
None
17
28
50
47
32
86
82
70
70
70
80
60
70
80
60
70
80
(scheme 1).
2. Experimental
45
120
90
All chemicals were available commercially and used
0
46
67
62
without additional purification. The catalyst was syn- 11
26
thesized according to the literature. Melting points 12
60
were recorded on an electrothermal type 9100 melting
point apparatus. The IR spectra were obtained using a
0
a1mmol 2-aminobenzamide, 1mmol benzaldehyde and
.4 mmol CuCl2 under solvent-free conditions.
Isolated yields
b
4
300 Shimadzu spectrophotometer in KBr disks. The
1
H NMR (500 MHz) spectra were recorded with a
Bruker DRX500 spectrometers.
3
. Results and discussion
2.1 Preparation of the catalyst (PFPAT)
Solvent-free conditions are especially important for
providing an eco-friendly system. The number of publi-
cations reporting solvent-free conditions for the hetero-
To a solution of 2,3,4,5,6-pentafluoroaniline (25 mmol)
in toluene (25 mL), CF SO H (25 mmol) was added
3
3
◦
at 0–5 C. The reaction mixture was stirred at the same
temperature for 30 min. After this time, the solvent was
evaporated in vacuo, the crude product was collected
and washed with hexane to give the pure catalyst in 92%
36
cyclic synthesis has increased rapidly in recent years.
One advantage of solvent-free reactions, in compari-
son to the reaction in molecular solvents, is that the
compounds formed are often sufficiently pure to cir-
cumvent extensive purification using chromatography.
Therefore, due to the increasing demand in modern
organic processes for avoiding expensive purification,
we decided to investigate the efficiency of PFPAT as
catalyst in the synthesis of 4(3H)-quinazolinones under
solvent-free conditions.
26
yield.
2.2 General procedure for the synthesis of 4(3H)-
quinazolinones 3a–j catalysed by PFPAT
A mixture of 2-aminobenzamide (1 mmol), an aromatic
At first, the synthesis of compound 3a was selected
as a model reaction to determine suitable reaction con-
ditions. The reaction was carried out by heating a
aldehyde (1 mmol) and CuCl (0.4 mmol) in the pre-
2
sence of PFPAT (0.25 mmol) as catalyst was heated on
◦
the oil bath at 70 C for 60–120 min. The reaction was
monitored by thin-layer chromatography (TLC). After
completion of the reaction, the reaction mixture was
cooled to room temperature and then water was added.
The precipitate was filtered off and recrystallized from
ethanol to give compounds 3a–j in high yields.
Table 2. Synthesis of compound 3a in the presence of
PFPAT in different solvents.
a
Entry
Solvent
T ( C) Time (min) Yield (%)b
◦
2
.3 Recycling and reusing of the catalyst
1
2
3
4
5
EtOH
MeOH
CHCl3
Reflux
Reflux
Reflux
Reflux
70
120
120
120
120
60
40
18
Trace
Trace
86
The catalyst is soluble in water and could therefore be
recycled as the filtrate. The catalyst was recovered by
evaporation of the water, washed with hexane, dried
at 50 C under vacuum for 1h and reused in another
reaction without appreciable reduction in the catalytic
activity.
PhCH3
Solvent-free
◦
a1mmol 2-aminobenzamide, 1mmol benzaldehyde, 0.4mmol
CuCl2, and 0.25mmol PFPAT under solvent-free conditions.
b
Isolated yields

4(3H)-Quinazolinones synthesis under PFPAT-CuCl2 catalysis
885
Table 3. PFPAT catalysed synthesis of 4(3H)-quinazolinones 3a–j.a
◦
m.p. ( C)
Found Reported
Entry
1
Ar
Productsb
Time (min) Yields (%)c
O
NH
N
60
60
85
81
234-236 235-23616
3
a
O
N
NH
Br
314-316 315-31616
2
Br
3
b
O
N
NH
Cl
304-306 305-30816
251-253 258-26012
210-212 209-21216
199-201 209-21115
3
4
5
6
60
50
60
60
95
91
91
88
Cl
3
c
O
N
NH
F
F
3
O
d
OMe
NH OMe
N
3
e
O
N
MeO
NH
OMe
3
f
O
N
NH
MeO
249-250 248-24915
7
8
60
60
96
92
OMe
3
g
O
NH
Me
240-242 241-24315
N
Me
3
h

886
Naser Montazeri et al.
Table 3. (continued)
◦
m.p. ( C)
Found Reported
Entry
9
Ar
Productsb
Time (min) Yields (%)c
O
O N
2
NH
346-348 351-35315
NO
2
120
89
83
N
3
i
O
N
NH
O N
360-362 363-36415
10
2
90
NO
2
3
j
a1mmol 2-aminobenzamide, 1mmol aryl aldehyde, 0.4mmol CuCl2, and 0.25mmol PFPAT at 70 C under
◦
solvent-free conditions.
b
1
All the products were characterized by IR and H NMR spectral data and comparision of their melting
points with those of authentic samples.
c
Isolated yields
mixture of 2-aminobenzamide (1 mmol) and benzalde-
In order to evaluate the generality of this model reac-
hyde (1 mmol) in the presence of CuCl (0.4 mmol) tion, we then prepared a range of 4(3H)-quinazolinones
2
under various amounts of PFPAT and solvent-free con- using several aromatic aldehydes under the optimized
ditions at different temperatures (table 1). It was found reaction conditions. In all cases, aromatic aldehydes
that the yield of compound 3a was strongly affected by with substituents carrying either electron-donating or
the catalyst amount and reaction temperature. No pro- electron-withdrawing groups reacted successfully and
duct was obtained in the absence of the catalyst PFPAT gave the expected products in excellent yields and short
(
entry 1) or in the presence of the catalyst at room tem- reaction times. The type of aldehyde had no significant
perature (entry 2) indicating that the catalyst and tem- effect on the reaction. The results are shown in table 3.
perature are necessary for the reaction. Increasing the Reusability of the catalyst was also investigated.
amount of the catalyst and reaction temperature up to For this purpose, the same model reaction was again
◦
2
5 mol% and 70 C, respectively, increased the yield of studied under optimized conditions. After the comple-
the product 3a, whereas further increase in both cata- tion of the reaction, the catalyst was recovered accord-
lyst amount and temperature was found to have an ing to the procedure mentioned in experimental section
inhibitory effect on formation of the product (entries
9
–12). Variation of the co-catalyst CuCl has no con-
2
siderable effect on the conversion of starting materi-
als, however the products are obtained contaminated
with by-products when less than 40 mol% of CuCl is
2
used. In addition, increasing the amount of this cata-
lyst to greater than 40 mol% has no considerable effect
on the purity and the yield of products. Therefore, we
concluded that CuCl could play as an oxidation cata-
2
lyst during dehydrogenation of the initially formed
products.
Also, the reaction was carried out in various solvents
(table 2). As shown in this table, the yield of the reaction
under solvent-free conditions was greater and the reac-
tion time was generally shorter than the conventional
methods.
Figure 1. Reusability of PFPAT for model reaction.

4(3H)-Quinazolinones synthesis under PFPAT-CuCl2 catalysis
887
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1
1
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The authors are thankful to Islamic Azad University,
Tonekabon Branch for financial support.
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1