One-Pot Three-Component Synthesis of 2,3-Dihydroquinazolin-4(1H)-Ones in the Presence of a Molecular Sieve Supported Lanthanum Catalyst

Article abstract of DOI:10.1007/s10562-016-1734-5

Abstract: A series of 2,3-dihydroquinazolin-4(1H)-ones have been synthesized with good to excellent yields by one-pot reaction using isatoic anhydride, aldehydes, and ammonium acetate or amines in acetonitrile in the presence of 4 ? molecular sieve modified with lanthanum(III) as an efficient heterogeneous catalyst. The catalyst could be reused without evident loss of activity. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s10562-016-1734-5

Catal Lett
DOI 10.1007/s10562-016-1734-5
One-Pot Three-Component Synthesis of 2,3-Dihydroquinazolin-
4(1H)-Ones in the Presence of a Molecular Sieve Supported
Lanthanum Catalyst
1
1
´
•
Agnes Magyar Zolt a´ n Hell
Received: 9 March 2016 / Accepted: 10 March 2016
Ó Springer Science+Business Media New York 2016
Abstract A series of 2,3-dihydroquinazolin-4(1H)-ones
have been synthesized with good to excellent yields by
one-pot reaction using isatoic anhydride, aldehydes, and
ammonium acetate or amines in acetonitrile in the presence
inflammatory and analgesic, antitumor, anticancer,
antibacterial, and diuretic activities [1–5]. In addition,
these compounds can be oxidised to their corresponding
quinazolin-4(3H)-one analogues, which are also biologi-
cally important heterocycles and can be found in some
natural products [6]. Due to their importance, several
strategies have been developed for the synthesis of 2,3-
dihydroquinazolinones. One possible route is the conden-
˚
of 4 A molecular sieve modified with lanthanum(III) as an
efficient heterogeneous catalyst. The catalyst could be
reused without evident loss of activity.
Graphical Abstract
O
O
O
O
N H
H
3
+
La /4A
+
+
NH OAc
4
N
H
O
N
H
R
R
Keywords Heterogeneous catalysis Á Quinazolinones Á
Lanthanum Á Molecular sieve
sation of aryl, alkyl, and heteroaryl aldehydes with
anthranilamide in the presence of p-toluenesulfonic acid as
a catalyst [7, 8]. The synthesis of 2,3-dihydroquinazoli-
nones was also achieved by reductive cyclisation of o-ni-
trobenzamide or o-azidobenzamide [9, 10]. Other methods
including desulfurization of 2-thioxo-4(3H)-quinazoli-
nones [11], reaction of isatoic anhydride with Schiff bases
[12], condensation of anthranilamide with benzyl [8], and a
two-step synthesis starting from isatoic anhydride and
amines, followed by annulation with ketones [13] was also
reported. A more attractive and atom-efficient strategy for
the preparation of 2,3-dihydroquinazolinones is through a
one-pot, three-component reaction of isatoic anhydride,
amines, and aldehydes. Multicomponent reactions (MCRs)
have some advantages over classical reaction strategies,
such as lower costs, shorter reaction time, and less side
1
Introduction
2
,3-Dihydroquinazolinons represent a highly important
group of heterocycles possessing a wide range of phar-
macological and biological properties such as anti-
&
Zolt a´ n Hell
zhell@mail.bme.hu
1
Department of Organic Chemistry and Technology, Budapest
University of Technology and Economics, M }u egyetem rkp.
3
., Budapest 1111, Hungary
123

´
A. Magyar, Z. Hell
products, as well as environmentally more friendly aspects.
In 2005, Salehi and Dabiri reported first an MCR method
for the synthesis of 2,3-dihydro-4(1H)-quinazolinones from
isatoic anhydride, aldehydes, and amines [14, 15].
Numerous protocols have been developed recently for the
synthesis using homogeneous catalysts such as strontium
chloride [16], Zn(PFO) [17], Ga(OTf) [18], molecular
were examined without sputtering with gold and weren’t
fixed on a carbon tape.
XRF investigation was made on a Canberra isotope
1
25
excitation instrument with SCD, using
source.
I as exciting
GC–MS measurements were performed on an Agilent
6890 N-GC-5973 N-MSD chromatograph, using
a
2
3
iodine [19], copper-benzenesulfonate [20], aluminium-
methanesulfonate [21]. The use of ionic liquids was also
reported for this conversion [22–24]. Recently solid acid
catalysts, such as cation exchange resin [25], starch sulfate
30 m 9 0.25 mm Restek, Rtx-5SILMS column with a film
layer of 0.25 lm. The initial temperature of column was
45 °C for 1 min, followed by programming at 10 °C/min
up to 310 °C and a final period at 310 °C (isothermal) for
17 min. The temperature of the injector was 250 °C. The
[
[
26], silica sulfuric acid [27], silica-bonded S-sulfonic acid
1
28], PTSA-formaldehyde copolymer [29], b-cyclodextrin-
carrier gas was He and the operation mode was splitless. H
SO H [30], magnetic Fe O nanoparticles [31, 32], Al/
3 3 4
NMR spectra were made on BRUKER Avance-300
Al O nanoparticles [33], CuO nanoparticles using soni-
2 3
instrument using TMS as internal standard in DMSO-D or
6
cation [34], nano indium-oxide [35], montmorillonite K-10
36], and Amberlyst-15 microwave-assisted [37] have also
CDCl3.
[
Melting points were determined on Gallenkamp appa-
ratus and were uncorrected.
been reported. However, some of these procedures have
certain limitations such as harsh reaction conditions,
expensive or large amount of catalyst, long reaction time,
high reaction temperature, tedious work-up, and low yields.
The catalysts described in the literature are mainly acidic
what can cause problems in the case of acid sensitive
compounds. Thus, the development of novel methods for
the synthesis of dihydroquinazolin-4(1H)-ones might have
great importance because of their potential biological and
pharmaceutical activities.
2.1 Preparation of the Catalyst
˚
4A
molecular sieve (4A) was impregnated with
La(NO ) 9 6H O as follows: 1 mmol of the metal salt
3
3
2
was dissolved in 100 mL of deionised water and stirred
with 1 g 4A at room temperature for 24 h. The solid was
filtered, washed with deionised water and with acetone,
then dried in an oven at 150 °C for 1 h.
Our research group works on the development of new
heterogeneous catalytic methods for the preparation of
organic compounds using supported metal catalysts. Dur-
ing this work several metals, such as palladium [38–41],
nickel [42], copper [43–45] or titanium [46] on different
2.2 Determination of the pH of the Catalyst
The catalyst (1 g) was stirred in 30 mL deionised water
under continuous measuring of the pH. The values were
accepted after reaching a constant value at least during
˚
supports (Mg:La 3:1 mixed oxide, 4 A molecular sieve)
were used successfully in different organic syntheses. In
this paper we report a method for the one-pot three-com-
ponent synthesis of 2,3-dihydroquinazolin-4(1H)-ones
10 min.
˚
promoted by a heterogeneous, 4 A molecular sieve sup-
ported lanthanum catalyst under mild basic conditions.
2.3 Typical Reaction Conditions
2.3.1 General Procedure for the One-Pot Synthesis
2
Experimental
of Quinazolin-4(3H)-Ones from Aldehydes
Morphology of the catalyst samples was investigated by a
JEOL 6380LVa (JEOL, Tokyo, Japan) type scanning
electron microscope and elemental mapping was also
accomplished using the energy-dispersive X-ray detector of
the equipment. Each specimen was fixed by conductive
double-sided carbon adhesive tape and sputtered by gold
A typical reaction was carried out in a 10 mL flask. Isatoic
anhydride (2 mmol), aldehyde (2 mmol), ammonium
3
?
acetate (2.4 mmol), La /4A (0.2 g) and acetonitrile
(3 mL) were stirred at reflux temperature for 24 h. The
progression of the reaction was monitored by TLC. After
completion, the solid was filtered, and washed with ace-
tone, then the filtrate was evaporated. The residue was
suspended in diethyl ether, the precipitated solid was fil-
(
using a JEOL 1200 instrument). Applied accelerating
voltage and working distance were between 15 and 30 kV
and 10 and 12 mm, respectively. In the case of the com-
parison of the fresh and the used catalysts, the samples
1
tered and subjected to GC–MS analysis and/or H NMR
spectroscopy.
1
23

One-Pot Three-Component Synthesis of 2,3-Dihydroquinazolin-4(1H)-Ones in the Presence…
2
.3.2 General Procedure for the One-Pot Synthesis
of Quinazolin-4(3H)-Ones from Acetals
2.3.4.4 2,3-Dihydro-2-(2-Fluorophenyl)-4(1H)-Quinazoli-
1
none (4f) White solid. H NMR, DMSO-d : d = 8.24 (s,
6
1
H), 7.64 (d, J = 9.9 Hz, 1 H), 7.54 (t, J = 7.2 Hz, 1 H),
To a solution of isatoic anhydride (2 mmol), benzaldehyde
dimethylacetal (2 mmol), ammonium acetate (2.4 mmol)
7.42 (q, J = 8.1 Hz, 1 H), 7.23 (q, J = 7.2 Hz, 3 H), 7.04
(s, 1 H), 6.67-6.76 (m, 2 H), 6.06 (s, 1 H).
3
?
or benzylamine (2 mmol) in 3 mL acetonitrile La /4A
0.2 g) was added. The mixture was stirred for 24 h at
(
2.3.4.5 2-(3-Bromophenyl)-2,3-Dihydro-4(1H)-Quinazoli-
1
reflux temperature. The progression of the reaction was
monitored by TLC. After completion, the solid was filtered,
and washed with acetone, then the filtrate was evaporated.
The residue was suspended in diethyl ether, the precipitated
none (4g) White solid. H NMR, DMSO-d : d = 8.38 (s,
6
1 H), 7.67 (s, 1 H), 7.61 (d, J = 6.9 Hz, 1 H), 7.53 (d,
J = 8.1 Hz, 1H), 7.50 (d, J = 15.1 Hz, 1 H), 7.35 (t,
J = 7.8 Hz, 1 H), 7.20–7.28 (m, 2 H), 6.76 (d, J = 8.4 Hz,
1 H), 6.68 (t, J = 7.5 Hz, 1 H), 5.77 (s, 1 H).
1
solid was filtered and subjected to H NMR spectroscopy.
2
.3.3 General Procedure for the One-Pot Synthesis
of Quinazolin-4(3H)-Ones from Ketones
2.3.4.6 2,3-Dihydro-2-(3-Nitrophenyl)-4(1H)-Quinazoli-
1
none (4j) Pale yellow solid. H NMR, DMSO-d6:
d = 8.54 (s, 1 H), 8.37 (s, 1 H), 8.21 (d, J = 4.8 Hz, 1 H),
7.95 (d, J = 4.8 Hz, 1 H), 7.71 (t, J = 4.8 Hz, 1 H), 7.63
(d, J = 4.8 Hz, 1 H), 7.35 (s, 1 H), 7.27 (d, J = 4.8 Hz, 1
H), 6.79 (d, J = 4.8 Hz, 1 H), 6.70 (t, J = 4.8 Hz, 1 H),
5.95 (s, 1 H).
A mixture of isatoic anhydride (2 mmol), ketone (2 mmol),
ammonium acetate (2.4 mmol) or benzylamine (2 mmol)
3
?
and La /4A (0.2 g) in acetonitrile (3 mL) were stirred at
reflux temperature for 24 h. The progression of the reaction
was monitored by TLC. After completion, the solid was
filtered, and washed with acetone, then the filtrate was
evaporated. The residue was suspended in diethyl ether, the
precipitated solid was filtered and subjected to GC–MS
2.3.4.7 2,3-Dihydro-2-[4-(Dimethylamino)phenyl)]-4(1H)-
1
Quinazolinone (4l) White solid. H NMR, DMSO-d6:
d = 8.05 (s, 1 H), 7.60 (d, J = 6.9 Hz, 1 H), 7.30 (d,
J = 8.7 Hz, 2 H), 7.22 (t, J = 6.9 Hz, 1H), 6.90 (s, 1 H),
6.63 – 6.74 (m, 4 H), 5.63 (s, 1 H), 2.87 (s, 6 H).
1
analysis and H NMR spectroscopy.
1
All products have satisfactory spectral data ( H NMR,
MS). The spectral data of the known compounds were
identical with those reported in the literature.
2.3.4.8 2,3-Dihydro-2-Phenyl-3-(Phenylmethyl)-4(1H)-
1
Quinazolinone (6) White solid. H NMR, DMSO-d6:
2
.3.4 Representative Physical and Spectroscopic Data
of the Products
d = 7.72 (d, J = 4.8 Hz, 1 H), 7.22–7.40 (m, 12 H),
6.65–6.69 (m, 2 H), 5.75 (s, 1 H), 5.34 (d, J = 12.6 Hz, 1
H), 3.83 (d, J = 9.3 Hz, 1 H).
2
.3.4.1 2-(4-Chlorophenyl)-2,3-Dihydro-4(1H)-Quinazoli-
1
none (4a) White solid. H NMR, DMSO-d : d = 8.32 (s,
2.3.4.9 2,3-Dihydro-2-Ethyl-2-Methyl-4(1H)-Quinazolinone
1
6
1
H), 7.60 (d, J = 6.9 Hz, 1 H), 7.49 (d, J = 8.4 Hz, 2 H),
(8a) H NMR, DMSO-d6, selected data: d = 7.83 (dd,
J = 1.2 Hz, J = 7.8 Hz, 1 H), 7.35 (dd, J = 1.2 Hz,
7
.47 (d, J = 8.4 Hz, 2 H), 7.25 (t, J = 8.4 Hz, 1 H), 7.13
1
2
1
(
s, 1 H), 6.76 (d, J = 8.1 Hz, 1 H), 6.68 (t, J = 7.8 Hz, 1
J2 = 7.8 Hz, 1 H), 1.80 (q, J = 7.5 Hz, 2 H), 1.48 (s, 3 H),
0.98 (t, J = 7.2 Hz, 3 H).
H), 5.77 (s, 1 H).
2
.3.4.2 2,3-Dihydro-2-(3-Methoxyphenyl)-4(1H)-Quina-
1
zolinone (4e) White solid.
d = 8.29 (s, 1 H), 7.60 (d, J = 4.5 Hz, 1 H), 7.29 (t,
J = 5 Hz, 1 H), 7.25 (t, J = 5 Hz, 1 H), 7.13 (s, 1 H), 7.06
H
NMR, DMSO-d6:
3 Results and Discussion
3
?
The structure of the La /4A catalyst was investigated by
scanning electron microscopy. The characteristic cubocta-
hedron shape of the molecular sieve support can be seen on
Figs. 1, 2. The particles are well defined both in shape and
size. The lanthanum is evenly distributed on the surface of
the support. EDS showed 3.65 w/w% lanthanum on the
surface. The lanthanum content determined by ICP-OES
was 3.88 w/w%. The catalyst has slightly basic properties,
its pH value is 8.40 (see Experimental).
(
m, 2H), 6.90 (dd, J = 6 Hz, J = 1 Hz, 1 H), 6.75 (d,
1 2
J = 4.8 Hz, 1 H), 6.68 (t, J = 4.2 Hz, 1 H), 5.72 (s, 1 H),
3
.74 (s, 3H).
2
.3.4.3 2,3-Dihydro-2-(4-Methoxyphenyl)-4(1H)-Quina-
1
zolinone (4e) White solid.
d = 8.17 (s, 1 H), 7.61 (d, J = 6.9 Hz, 1 H), 7.42 (d,
J = 8.7 Hz, 2 H), 7.25 (t, J = 8.4 Hz, 1 H), 7.00 (s, 1 H),
H
NMR, DMSO-d6:
6
.93 (d, J = 8.7 Hz, 2 H), 6.73 (d, J = 8.1 Hz, 1 H), 6.67
From the nitrogen adsorption/desorption measurements
2
the specific surface of the catalyst is 35 m /g.
(
t, J = 7.5 Hz, 1 H), 5.70 (s, 1 H), 3.74 (s, 3H).
123

´
A. Magyar, Z. Hell
To study the effect of the solvent on the condensation
reaction, isatoic anhydride, 4-chlorobenzaldehyde and
ammonium acetate were used in a 1:1:1,2 molar ratio and
3
?
were reacted in the presence of 0.2 g La /4A catalyst in
mL of different solvents. The results are shown in
Table 1.
Acetonitrile gave the best yield in the reaction (entry 5).
3
The product has a weak solubility in ethanol, thus we tried
to increase its amount in the reaction mixture. But in this
case the yield of 4a decreased significantly, and a new
product appeared. GC–MS investigation of the reaction
mixture showed that this was 4-chlorobenzaldehyde
diethylacetal. Toluene and xylene showed weaker results.
Thus, in the further experiments we used acetonitrile in a
24 h reaction.
Fig. 1 SEM image of the catalyst
Next, we studied the reaction of different aldehydes. The
results are summarized in Table 2.
The reactions gave generally good to excellent isolated
yields. In the case of 2-nitro- and 4-nitro-benzaldehyde
The catalyst was tested in the multicomponent reaction
of isatoic anhydride, aldehydes and ammonium acetate
yielding 2,3-dihydroquinazolinones. This reaction has been
described as an acid-catalysed cyclisation. In the literature
there are examples for the use of a lanthanum-compound as
the catalyst for this cyclisation such as lanthanum-triflate
(entries 9 and 11) the lower yields may be explained by the
weak solubility of the products, thus they remained at the
surface of the catalyst during the workup. The use of
acetonitrile in regard of 4-dimethylamino-benzaldehyde
didn’t prove to be efficient, higher yield could be obtained
using ethanol as solvent (entry 12). In the reaction of sal-
icylaldehyde the lower yield obtained in ethanol might be
[
18], lanthanum-benzenesulfonate [20] and lanthanum-
methanesulfonate [21], these catalysts are both acidic in
nature.
Fig. 2 SEM image of a catalyst (upper left), distribution of the lanthanum on the particle (lower left) and the standard quantitative analysis of the
catalyst (right) (magnification: 95000)
1
23

One-Pot Three-Component Synthesis of 2,3-Dihydroquinazolin-4(1H)-Ones in the Presence…
Table 1 Reaction of isatoic anhydride, 4-chloro-benzaldehyde and ammonium acetate in different solvents
O
O
O
O
H
NH
La3+/4A
+
+
NH OAc
4
N
H
O
N
H
Cl
1
2a
3
4a
Cl
a
Entry
Solvent
Yield of 4a (%)
1
2
3
4
5
Ethanol
60
40
54
64
Ethanol (10 mL)
Xylene
Toluene
b
Acetonitrile
68 (84)
2
a
mmol isatoic anhydride, 2 mmol benzaldehyde, 2.4 mmol ammonium acetate, 0.2 g catalyst, 3 mL solvent, reflux temperature, 14 h
Isolated yield
b
2
4 h reaction time
explained by the formation of a H-bond between aldehyde
function and the hydroxyl group (entry 13).
We investigated the reaction of different ketones instead
of aldehydes, the results are shown in Table 3. In the case
of ethyl methyl ketone (entry 1), based on the NMR
spectra, regardless the reaction time the yield was
approximately 50 %. Using ethyl methyl ketone in excess,
the yield of the desired products decreased, probably due to
aldol-type side reactions. Benzylamine instead of ammo-
nium acetate gave low yield (entry 2). Acetophenone gave
moderate yield even if the reaction time was 48 h (entry 3).
The reusability of the catalysts was examined in the
reaction of isatoic anhydride, benzaldehyde and ammo-
nium acetate. After the reaction the solid was filtered and
washed with hot acetone, then heated at ca. 150 °C for 1 h.
The yields in the 1st and 2nd runs were 85 and 76 %,
respectively. We examined the crude product by XRF to
determine whether the leached metal resulted the lower
yield, but no lanthanum could be detected. We investigated
the used catalyst by scanning electron microscopy and EDS
to determine the background of the decreased activity of
the catalyst. The SEM and EDS records showed rectangle
shaped crystals with high carbon content (Fig. 5), subse-
quently the reason of the decreasing activity might be the
weak solubility of the products. Sampling the catalyst
particles the EDS results confirmed that there was no dif-
ference in the metal content of the fresh and the used
catalyst. Thus we changed the recycling process of the
catalyst. The used catalyst was stirred in boiling acetone
for 5 h, filtered, then heated at ca, 150 °C for 1 h. The
lanthanum content of this sample determined by ICP-OES
was 3.79 w/w%. The thus treated catalyst was tested in the
model reaction. There was no significant difference in the
yields.
Although the reaction has been described generally with
acidic catalysts, in our case the slightly basic heteroge-
neous catalyst gave good results. As the EDS measurement
showed, the lanthanum is located on the surface of the
support, forming potentially acidic sites. The reaction may
happen on these parts of the catalysts. Meanwhile the bulk
basic phase may help to avoid the potential disadvanta-
geous, acid-catalysed side reactions or a possible decom-
position if an acid-sensitive compound or functional group
is present.
According to the reported mechanisms both for
homogeneous [16] and heterogeneous methods [31, 32],
we propose a plausible mechanism for the cyclisation.
Thus first isatoic anhydride is activated by the cation
3
?
(
here La ). This is followed by N-nucleophilic attack of
ammonium acetate (or the respective amine) on the
carbonyl group. After a loss of carbon dioxide the
yielded 2-amino-benzamide reacts with the activated
aldehyde
A
affording the intermediate B, the
intramolecular cyclisation of this intermediate results
intermediate C, finally 1,5-proton transfer gives the
product 4 (Fig. 3). The intermediate 2-amino-benzamide
could be shown in the GC–MS spectra of the reaction
mixture of isatoic anhydride, ammonium acetate and
benzaldehyde.
We examined the reaction with benzaldehyde dimethy-
lacetal instead of benzaldehyde. The corresponding 4b was
formed with excellent yields (Fig. 4). Replacing ammo-
nium acetate by benzylamine, the disubstituted derivative 6
was formed also with excellent yield.
123

´
A. Magyar, Z. Hell
Table 2 The reaction of isatoic anhydride, different aldehydes and ammonium acetate
O
O
O
O
NH
H
3
+
+
+
La /4A
NH OAc
4
N
H
O
N
H
R
1
2
3
4
R
a
Entry
1
R
Product
Yield (%)
84
Mp (°C)
O
4-Cl
199–200 (198–200 [25])
NH
N
H
Cl
4
a
O
2
H
85
213–214 (218–219 [18])
NH
N
H
4
b
O
3
2-Cl
65
200–202 (202–204 [25])
NH
Cl
N
H
4
O
c
4
3-MeO
93
141–143
NH
O
N
H
4
d
O
5
4-MeO
85
189–190 (192–193 [18])
NH
N
H
O
4
e
O
6
2-F
86
186–188 (189–193 [47])
NH
F
N
H
4
f
1
23

One-Pot Three-Component Synthesis of 2,3-Dihydroquinazolin-4(1H)-Ones in the Presence…
Table 2 continued
a
Entry
7
R
Product
Yield (%)
90
Mp (°C)
O
3-Br
[220 (229–230 [33])
NH
Br
N
H
4
g
O
8
4-Br
86
199–201 (205.7–206.3 [22])
NH
N
H
Br
4
h
O
9
2-NO
3-NO
2
60
90
187–188 (193–194 [18])
213–215 (216–217 [18])
NH
NO
2
N
H
4
i
O
1
0
2
NH
NO2
N
H
4
j
O
c
1
1
2
4-NO
2
47
(213–214 [18])
NH
N
H
NO2
4
k
O
b
1
4-NMe
2
47, 80
202–204 (207–209 [25])
NH
N
H
N
4
O
l
b
c
1
3
2-OH
45
(218–219 [48])
NH
OH
N
H
4
m
2
mmol isatoic anhydride, 2 mmol benzaldehyde, 2.4 mmol ammonium acetate, 0.2 g catalyst, 3 mL acetonitrile, reflux temperature, 24 h
a
Isolated yield
b
c
In ethanol
Decomposed above 200 °C
123

´
A. Magyar, Z. Hell
3
+
O
La
O
O
A
R
R
1
H
N
H
O
2
+
NH
4
OAc/R NH
2
La3+
NH2
N
H
O
- CO
2
1
:
OH
+
O
OH
La3+
N
R
R
R
N
+
N
1,5-H transfer
N
R1
3+
N
H
R1
La
N
R1
_
3
+
La
2
R= R or H
B
C
4
Fig. 3 Proposed mechanism of the reaction
O
O
O
O
O
NH
3
+
La /4A
+
NH OAc
4
N
H
O
Ph
CH CN
N
H
3
1
5
4
b
Y= 85%
3
+
La /4A
O
Ph
NH2
CH CN
N
Ph
3
N
H
Ph
6
Y= 90%
Fig. 4 The condensation reaction with benzaldehyde dimethylacetal
1
23

One-Pot Three-Component Synthesis of 2,3-Dihydroquinazolin-4(1H)-Ones in the Presence…
Table 3 The reaction of isatoic anhydride, ammonium acetate/benzylamine and different ketones
O
O
O
NH OAc
4
R1
O
N
3
+
+
+
La /4A
or
R2
R3
CH CN
3
R1
NH2
N
H
O
N
H
R2
R3
8
1
3
7
Entry
1
R
–
1
R
2
R
3
2
Reaction time (h)
Product
Yield (%)
a
O
CH
3
C
H
5
6
*50
1
1
2
0
5
4
NH
N
H
8
a
b
15
O
2
3
a
C
6
H
5
CH
2
CH
3
C
2
H
5
24
N
N
H
8b
a
O
–
CH
3
C
6
H
5
24
33
a
4
8
57
NH
N
H
8
c
1
Conversion determined from the H NMR spectra
b
Based on the GC–MS examination of the product
4
Conclusions
˚
In conclusion, lanthanum on 4 A molecular sieve support
proved to be useful catalyst for the one-pot, three component
synthesis of 2,3-dihydroquinazolin-4(1H)-ones under mild,
slightly basic conditions, which is unprecedented in the lit-
erature. The catalyst could be prepared simply and can be
reused with good result after a treatment with boiling acetone.
´
Acknowledgments A. M. is grateful to Chinoin Pharmaceuticals
Ltd. for the financial support.
References
1
. Sadanandam YS, Reddy KRM, Rao AB (1987) Eur J Org Chem
2:169–173
2
Fig. 5 SEM image of the used catalyst
123

´
A. Magyar, Z. Hell
2
3
. Hamel E, Lin CM, Plowman J, Wang HK, Lee KH, Paull KD
1996) Biochem Pharmacol 51:53–59
25. Wang M, Zhang TT, Gao JJ, Liang Y (2012) Chem Het Compd
48:897–902
26. Shaterian HR, Rigi F (2015) Res Chem Intermed 41:721–738
27. Dabiri M, Salehi P, Baghbanzadeh M, Zolfigol MA, Agheb M,
Heydari S (2008) Cat Comm 9:785–788
(
. Hour MJ, Huang LJ, Kuo SC, Xia Y, Bastow K, Nakanishi Y,
Hamel E, Lee KH (2000) J Med Chem 43:4479–4487
. Alaimo RJ, Russell HE (1972) J Med Chem 15:335–336
. Parish HA, Gilliom RD, Purcell WP, Browne RK, Spirk RF,
White HD (1982) J Med Chem 25:98–102
4
5
28. Khodabakhsh N, Reza MM, Salimeh M (2011) Chin J Chem
29:1417–1422
6
. Maskey RP, Shaaban M, Grun-Wollnu I, Laatsch H (2004) J Nat
Prod 67:1131–1134
. Sharma SD, Kaur V (1989) Synthesis 9:677–680
. Moore JA, Sutherland GJ, Sowerby R, Kelly EG, Palermo S,
Webster W (1969) J Org Chem 34:887–892
29. Saffar-Teluri A, Bolouk S (2010) Monatsh Chem 141:1113–1115
30. Shaterian HR, Rigi F (2014) Res Chem Intermed 40:2983–2999
31. Toosi FS, Khakzadi M (2015) Res Chem Intermed 41:311–317
32. Zhang Z-H, L u¨ H-Y, Yang S-H, Gao J-W (2010) J Comb Chem
12:643–646
7
8
9
. Su W, Yang B (2002) Aust J Chem 55:695–697
33. Kassaee MZ, Rostamizadeh S, Shadjou N, Elahe Motamedi E,
Esmaeelzadeh M (2010) J Het Chem 47:1421–1424
34. Zhang J, Ren D, Ma Y, Wang W, Wu H (2014) Tetrahedron
70:5274–5282
35. Santra S, Rahman M, Roy A, Majee A, Hajra A (2014) Cat
Commun 49:52–57
1
0. Shi D, Rong L, Wang J, Zhuang Q, Wang X, Hu H (2003)
Tetrahedron Lett 44:3199–3201
1
1
1
1
1. Khurana JM, Kukreja G (2003) J Heterocycl Chem 40:677–679
2. Rao VB, Ratnam CV (1979) Indian J Chem Sect B 18B:409
3. Yale HL (1977) J Heterocycl Chem 14:1357–1359
4. Salehi P, Dabiri M, Zolfigol MA, Baghbanzadeh M (2005)
Synlett 7:1155–1157
36. Salehi P, Dabiri M, Baghbanzadeh M, Bahramnejad M (2006)
Synth Commun 36:2287–2292
1
1
1
1
1
2
2
2
2
2
5. Dabiri M, Salehi P, Otokesh S, Baghbanzadeh M, Kozehgary G,
Mohammadi AA (2005) Tetrahedron Lett 46:6123–6126
6. Wang M, Zhang TT, Liang Y, Gao JJ (2011) Chin Chem Lett
37. Surpur MP, Singh PR, Patil SB, Samant SD (2007) Synth
Commun 37:1965–1970
38. Cwik A, Hell Z, Figueras F (2006) Adv Synth Catal 348:523–530
2
2:1423–1426
39. Cwik A, Hell Z, Figueras
47:3023–3026
F (2006) Tetrahedron Lett
7. Wang LM, Hu L, Shao J-H, Yu J, Zhang L (2008) J Fluorine
Chem 129:1139–1145
8. Chen J, Wu D, He F, Liu M, Wu H, Ding J, Su W (2008)
Tetrahedron Lett 49:3814–3818
9. Rostamizadeh S, Amani AM, Aryan R, Ghaieni HR, Shadjou N
40. Cwik A, Hell Z, Figueras F (2005) Org Biomol Chem
3:4307–4309
41. N e´ meth J, Hell Z (2013) React Kinet Mech Catal 111:115–121
42. Kiss A, Hell Z, B a´ lint M (2010) Org Biomol Chem 8:331–335
43. Fodor A, Kiss A, Debreczeni N, Hell Z, Gresits I (2010) Org
Biomol Chem 8:4575–4581
44. Kiss A, Hell Z (2013) Synth Commun 43:1778–1786
45. Kiss A, Hell Z (2011) Tetrahedron Lett 52:6021–6023
´
46. Magyar A, Nagy B, Hell Z (2015) Cat Lett 145:1876–1879
47. Wang X-S, Yang K, Zhang M-M, Yao C-S (2010) Synth Com-
mun 40:2633–2646
48. Tang J-H, Shi D-X, Zhang L-J, Zhang Q, Li J-R (2010) Synth
Commun 40:632–641
(
2008) Synth Commun 38:3567–3576
0. Wang M, Zhang TT, Liang Y, Gao JJ (2012) Monatsh Chem
43:835–839
1. Song Z, Liu L, Wang Y, Sun X (2012) Res Chem Intermed
8:1091–1099
2. Chen J, Su W, Wu H, Liu M, Jin C (2009) Green Chem
:972–975
1
3
9
3. Darvatkar NB, Bhilare SV, Deorukhkar AR, Raut DG, Salunkh
MM (2010) Green Chem Lett Rev 3:301–306
4. Fard MAB, Mobinikhaledi A, Hamidinasab M (2014) Synth
React Inorg Metal-Org Nano-Metal Chem 44:567–571
1
23