Microwave-assisted one-pot synthesis of octahydroquinazolinone derivatives using ammonium metavanadate under solvent-free condition

Article abstract of DOI:10.1016/j.tetlet.2010.04.118

Ammonium metavanadate (NH₄VO₃) has been shown to be an inexpensive, efficient, and mild catalyst for the one-pot synthesis of octahydroquinazolinone derivatives using dimedone, urea/thiourea, and appropriate aromatic aldehydes under

Full text of DOI:10.1016/j.tetlet.2010.04.118

Tetrahedron Letters 51 (2010) 3616–3618
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Microwave-assisted one-pot synthesis of octahydroquinazolinone
derivatives using ammonium metavanadate under solvent-free condition
*
Kirti S. Niralwad, Bapurao B. Shingate, Murlidhar S. Shingare
Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Ammonium metavanadate (NH4VO3) has been shown to be an inexpensive, efficient, and mild catalyst for
the one-pot synthesis of octahydroquinazolinone derivatives using dimedone, urea/thiourea, and appro-
priate aromatic aldehydes under microwave-irradiation.
Received 7 April 2010
Revised 24 April 2010
Accepted 28 April 2010
Available online 28 May 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Ammonium metavanadate
Biginelli reaction
Octahydroquinazolinone derivatives
Microwave-irradiation
In recent years, the Biginelli reaction has been employed for
the synthesis of octahydroquinazolinones, which used cyclic b-
diketones instead of open-chain dicarbonyl compounds. These
octahydroquinazolinone derivatives have attracted considerable
attention since they exhibit potent antibacterial activity against
Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa,1
and calcium antagonist activity.2,3
Several methods have been developed for the preparation of
quinazolinone derivatives. These routes usually involved reaction
of aldehydes with SOCl2 and pyridine, then with 2-aminobenzyl-
amine in a refluxing solvent such as benzene or xylene with
azeotropic water removal,4 refluxing in ethanol/acetic acid mix-
ture,5and by reaction in alkali media.
There are very few reports for the synthesis of octahydroqui-
nazolinone derivatives using catalysts such as TMSCl,6 Nafion-H,7
concd H2SO4,8 and ionic liquid9 Octahydroquinazolinone deriva-
tives are also synthesized in absolute ethanol but with low yields
of products (19–69%).2 However, many of these procedures suffer
from one or more disadvantages such as harsh reaction conditions,
prolonged time period, poor yields, and use of hazardous and
expensive catalysts. So the development of a clean, high-yielding,
and environmentally friendly approach is still desirable. The use
of ammonium metavanadate (NH4VO3) as an inorganic acid10
meets the demand for an economic catalyst. It is employed similar
to vanadium pentoxide11 and as a catalyst in oxidation reactions
with other cocatalysts.12 It is a reagent used in analytical chemis-
try, photographic industry, and textile industry.11 Gill and co-
workers reported the synthesis of benzimidazole13 and coumarin14
in the presence of ammonium metavanadate. Very recently, we
have reported the synthesis of
a a-
-hydroxyphosphonates15 and
aminophosphonates16 using ammonium metavanadate as a cata-
lyst in good yields.
During the last few years, ‘non-classical’ methods have been
developed in organic synthesis in order to improve yields, selectiv-
ity, and experimental conditions.17 Especially the use of microwave
technology in conjunction with the use of solvent-free conditions
allows expeditious and efficient procedures in organic synthe-
sis.18–21 However, great interest has been focused recently on
‘dry media’ synthesis using inorganic solid supports under micro-
wave-irradiation. The coupling of a microwave heating mode with
the use of solid acid has allowed the synthesis of several organic
compounds, with higher purity of products and very simplified
ease of manipulation and work-up. They clearly constitute an
eco-friendly ‘green’ approach.22
The literature survey reveals that a number of octahydroquinaz-
olinone derivatives have been synthesized by Biginelli reaction
conditions using various aldehydes but not a single reference have
been found where microwave-irradiation has been used.
In continuation of our research work of developing methods in
various organic transformations,23–25 we have developed a method-
ology for the synthesis of octahydroquinazolinone derivatives using
ammonium metavanadate, which makes use of mild catalyst under
microwave-irradiation and solvent-free conditions (Scheme 1).
The reaction of benzaldehyde (1a), dimedone (2), and urea (3)
catalyzed by ammonium metavanadate under solvent-free condi-
tions and microwave-irradiation has been considered as a standard
model reaction.
* Corresponding author. Tel.: +91 240 2403311; fax: +91 240 2400491.
E-mail address: msshingare11@gmail.com (M.S. Shingare).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.04.118

K. S. Niralwad et al. / Tetrahedron Letters 51 (2010) 3616–3618
3617
Table 3
R
Effect of microwave-irradiation powers for the synthesis of octahydroquinazolinone
derivative 4aa
CHO
O
O
Entry
Power (W)
Time (s)
Yieldb (%)
X
NH4VO3
MW
NH
1
2
3
4
180
360
540
720
70
50
40
30
87
94
86
82
H2N
NH2
O
N
H
X
R
1 (a-l)
2
3
4 (a-l)
a
Compound 1a (1 mmol) was treated with dimedone (1 mmol) and urea
(1.5 mmol) in the presence of ammonium metavanadate (10 mol %) under micro-
wave-irradiation.
Scheme 1. Synthesis of octahydroquinazolinone derivaties
b
Isolated yield.
We also screened a number of different catalysts on the model
reaction. When the reaction was carried out in the presence of
KH2PO4, alum, acidic alumina, amberlite-IR 120, sulfamic acid,
and cellulose sulfuric acid under microwave-irradiation it gave
lower yield of product even after prolonged reaction time. How-
ever, when the same reaction was conducted under microwave-
irradiation using ammonium metavanadate as a catalyst it gave
excellent yields of product in short reaction time (Table 1, entry 6).
We have studied the catalyst concentration on model reaction.
We have varied the concentration of catalyst to 5, 7, 10, and
12 mol %. The results revealed that when the reaction was carried
out in the presence of 5 and 7 mol % of catalyst it gave lower yield
of product even after prolonged reaction time. At the same time
when the concentration of catalyst was 10 mol % we got excellent
yields of product in a short span. Even after increasing the catalyst
concentration at 12 mol %, the yields of the products were found to
be constant. So, the use of 10 mol % of catalyst appears to be opti-
mal. The results obtained are summarized in (Table 2).
Table 4
Synthesis of octahydroquinazolinone derivatives catalyzed by ammonium metavana-
date under microwave-irradiationa
Entry
RCHO
X
Time (min)
Yieldb (%)
Mp (°C)
4a
4b
4c
4d
4e
4f
4g
4h
4i
H
4-Cl
O
O
O
O
O
O
O
O
S
6
5
8
7
8
7
5
7
10
12
10
11
94
92
88
92
86
85
93
90
87
83
85
86
290–293
>300
3-OMe, 4-OH
3-NO2
3-OMe
3-Cl
4-NO2
4-F
193–195
298–299
248–249
282–284
302–304
134–136
283–285
275–276
275–276
286–288
H
4j
4k
4l
4-OMe
3-Cl
4-Br
S
S
S
a
Reaction condition: 1 (a–l) (1 mmol), 2 (1 mmol), 3 (1.5 mmol) ammonium
metavanadate (10 mol%), under microwave-irradiation.
Moreover, we investigated the effect of different microwave
power settings such as 180, 360, 540, and 720 W. It was observed
that the irradiation at low power required longer time and at high
power suffered from lower yield. This indicates that the irradiation
at 360 W gives better result (Table 3, entry 2).
b
Isolated yield. All the products obtained were fully characterized by spectro-
scopic methods such as IR, 1H NMR, and mass spectroscopy and also comprised the
reference compounds.6
aldehydes containing electron-donating or electron-withdrawing
functional groups at different positions but it did not show any
remarkable differences in the yields of product and reaction time.
It was observed that the reaction of aromatic aldehydes with urea
is very fast as compared to thiourea. The results obtained in the
current method are illustrated in Table 4.
After optimizing the conditions, the generality of this method
was examined by the reaction of several substituted aldehydes,
dimedone, and urea/thiourea using ammonium metavanadate as
a catalyst under microwave-irradiation; the results are shown in
Table 4. We have carried out similar reaction with various aromatic
The role of NH4VO3 has been proposed to activate the aldehyde
by binding the oxygen atom of aldehyde with vacant ‘d’ orbital of
transition metal vanadium to achieve the stable oxidation state,
Along with this we recovered the catalyst and reused for further
reactions.26
In conclusion, ammonium metavanadate (NH4VO3) is a readily
available, inexpensive, and efficient catalyst for the synthesis of
octahydroquinazolinone derivatives. The advantages offered by
this method are solvent-free reaction conditions, short reaction
times, ease of product isolation, and high yields. We believe that
this method is a useful addition to the present methodology for
the synthesis of octahydroquinazolinone derivatives.
Table 1
Screening of catalysts on the model reactiona
Entry
Catalysts
Time (min)
Yieldb (%)
1
1
2
3
4
5
6
KH2PO4
Alum
15
15
15
15
15
15
15
20
65
52
68
54
63
94
Acidic alumina
Amberlite IR-120
Sulfamic acid
Cellulose sulfuric acid
Ammonium metavanadate
a
Reaction of benzaldehyde, dimedone, and urea in the presence of ammonium
metavanadate under microwave-irradiation and solvent-free condition.
b
Isolated yield.
Acknowledgment
The authors are thankful to The Head, Department of Chemistry,
Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, for
providing the laboratory facility.
Table 2
Effect of catalyst concentration on model reactiona
Entry
Catalyst (mol %)
Yieldb (%)
References and notes
1
2
3
4
5
7
10
12
52
65
94
94
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Reaction of benzaldehyde, dimedone, and urea in the presence of ammonium
metavanadate under microwave-irradiation and solvent-free condition.
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Isolated yield.

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