FeCl3 immobilized in Al-MCM 41: An efficient catalyst system for the Biginelli reaction

Article abstract of DOI:10.1080/00397911003668596

FeCl₃ immobilized on Al-MCM-41 was found to be an efficient catalytic system for the one-pot synthesis of 3,4-dihyropyrimidinone derivatives. This is a facile and high-yielding reaction for synthesis of the 3,4-dihyropyrimidinone. The catalyst

Full text of DOI:10.1080/00397911003668596

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FeCl Immobilized in Al-MCM 41: An
3
Efficient Catalyst System for the Biginelli
Reaction
a
a
a
Hossein A. Oskooie , Majid M. Heravi , Narges Karimi & Maryam
a
H. Monjezy
a
Department of Chemistry, School of Science, Alzahra University,
Vanak, Tehran, Iran
Published online: 25 Feb 2011.
To cite this article: Hossein A. Oskooie , Majid M. Heravi , Narges Karimi & Maryam H. Monjezy (2011)
FeCl Immobilized in Al-MCM 41: An Efficient Catalyst System for the Biginelli Reaction, Synthetic
3
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:6, 826-831
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Synthetic Communications , 41: 826–831, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003668596
FeCl IMMOBILIZED IN Al-MCM 41: AN EFFICIENT
3
CATALYST SYSTEM FOR THE BIGINELLI REACTION
Hossein A. Oskooie, Majid M. Heravi, Narges Karimi, and
Maryam H. Monjezy
Department of Chemistry, School of Science, Alzahra University, Vanak,
Tehran, Iran
GRAPHICAL ABSTRACT
3
Abstract FeCl immobilized on Al-MCM-41 was found to be an efficient catalytic system
for the one-pot synthesis of 3,4-dihyropyrimidinone derivatives. This is a facile and
high-yielding reaction for synthesis of the 3,4-dihyropyrimidinone. The catalyst exhibited
remarkable reactivity and is reusable.
Keywords Biginell; 3,4-dihyropyrimidinone; Fe(III)=Al-MCM-41; three-component
condensation
INTRODUCTION
Multicomponent reactions are useful and efficient methods in organic
synthesis. The major advantages of these reactions are (1) a single purification step,
(2) greater yields yields than stepwise assembly, (3) the use of simple and diverse
precursors to construct complex molecules, and (4) the use of only a single promoter
or catalyst. Thus, the development of new multicomponent reactions is a popular
area of research in current organic chemistry and is also acceptable from a green
[1]
chemistry point of view.
,4-Dihydropyrimidin-2(1H)-ones (DHPMs) have been reported to possess
diverse pharmacological activities such as antiviral, antibacterial, and anti-
3
[2]
hypertensive activity, as well as efficiency as calcium channel modulators and
[
3]
a -antagonists. Several marine alkaloids possess anti-inflammatory and antitumor
1
a
[4]
pharmacological activities. In particular, the batzelladine alkaloids have been
[
found to be potent HIV gp-120-CD4 inhibitors.
5]
Received November 22, 2009.
Address correspondence to Majid M. Heravi, Department of Chemistry, School of Science,
Alzahra University, Vanak, Tehran, Iran. E-mail: mmh1331@yahoo.com
8
26

BIGINELLI REACTION
827
The simple and direct method for the synthesis of DHPMs reported by
Biginelli in 1893 involves the one-pot condensation of an aldehyde, a b-ketoester,
and a urea under strongly acidic conditions. However, this method suffers from poor
yields, especially in the cases of aliphatic and some substituted aromatic aldehydes.
Several improved protocols by modification of the classical one-pot approach for the
[
6]
preparation of DHPMs have been reported recently. However, some of the
reported methods also suffer from drawbacks such as unsatisfactory yields, cumber-
[
some product isolation procedures, and environmental pollution. The synthesis of
7]
[
8]
DHPM derivatives involving the use of a number of catalysts, such as InBr ,
3
[9]
tetrabutylammonium bromide (TBAB), polystyrene-poly(ethylene glycol)-sulfonic
[10]
[11]
acid (PS-PEG-SO H), and CaF2, have been reported.
3
RESULTS AND DISCUSSION
Among the various metals, iron (Fe) is the most abundant in nature and is an
indispensable species of nearly all organisms. Nature has evolved a number of metal-
loenzymes such as the heme-containing cytochrome P450 and the non-heme mono-
oxygenase. Transition-metal complexes can be stabilized, either encapsulated or
[
12–14]
grafted within microporous (zeolites) or mesoporous materials (MCMs).
They
have numerous potential applications as catalysts, photocatalysts, and gas sensors.
In this investigation, we decided to synthesize 3,4-dihydropyrimidinones via
ethyl acetoacetate 1, aldehydes 2 and urea 3 using Fe(III)=Al-MCM-41 as a hetero-
geneous and recyclable catalyst (Scheme 1).
We examined the reaction using various aldehydes, urea, and ethyl acetoace-
tate under reflux, and the results are summarized in Table 1.
Several aromatic aldehydes carrying either electron-releasing or electron-
withdrawing substituents in the ortho, meta, and para positions afforded good yields
of the products. An important feature of this procedure is the survival of a variety of
functional groups such as hydroxyl, nitro, ethers, halides and groups under the
reaction conditions.
All reaction products were isolated by infrared (IR), gas chromatography (GC)
mass spectrometry, and melting points and compared with those obtained from
authentic samples.
The reusability of the catalyst was next checked by repeating the same model
reaction three times. The results are summarized in Table 2.
To show the merits of Fe(III)=Al-MCM-41 in comparison with other reported
catalysts, we summarized some of results for the preparation of 3,4-dihydropyrimi-
dinones (4a) in Table 3, which shows that Fe(III)=Al-MCM-41 is an equally or
more efficient catalyst with respect to reaction time and yield than previously
reported ones.
Scheme 1. Synthesis of 3,4-dihydropyrimidinones.

828
H. A. OSKOOIE ET AL.
Table 1. Synthesis of compounds 4a–g by Fe(III)=Al-MCM-41
a
b
Yield (%)
ꢁ
Mp ( C) (lit.)
Entry
Product
Ar
[
7]
11]
9]
7]
7]
7]
9]
1
2
3
4
5
6
7
4a
4b
4c
4d
4e
4f
C
6
H
5
85
90
68
89
75
89
75
201–203 (202–204)
[
2-NO
4-Me-C
4-OMe-C
4-NO -C
4-Cl-C
3-NO -C
2
-C
6
H
4
220–223 (198–200)
[
6
H
4
216–219 (215–216)
[
6
H
4
202–204 (201–203)
[
2
6
H
4
208–210 (208–211)
[
6
H
4
212–214 (213–215)
[
4g
2
6
H
4
227–230 (229–231)
a
Products were characterized by comparison of their spectroscopic data (GC mass, IR,
1
mps) and H NMR with those reported in the literature.
b
Isolated yield.
Table 2. Reuse of the Fe(III)=Al-MCM-41 for synthesis of 4a
a
Entry
Time (h)
Yield (%)
1
2
3
4
4.5
5
85
80
75
a
Isolated yield.
Table 3. Comparison Fe(III)=Al-MCM-41 with reported catalysts in the synthesis of 4a
Catalyst
Catalyst loading
Solvent
Temperature
Time (h)
Yield (%)
AIKIT-5(10)
PPE
InBr
150 mg
300 mg
10 mol%
0.03 gr
CH CN
THF
3
Reflux
Reflux
Reflux
Reflux
3
15
7
96
95
98
85
3
C
CH
2
H
5
OH
CN
Fe(III)=Al-MCM-41
3
4
CONCLUSION
In conclusion, we developed an efficient and simple alternative for the pre-
paration of 3,4-dihydropyrimidinones via Fe(III)=Al-MCM-41catalysis under mild
conditions. Prominent among the advantages of this new method are operational
simplicity, good yields, recyclablity of the catalyst, and an easy workup procedure.
EXPERIMENTAL
All the chemicals were purchased from Merck Company. Melting points were
measured using a Barnstead Electrothermal instrument. GC mass analysis was
performed using an Agilent 6890 GC system, Hp-5 capillary 30 m ꢀ 530 mm ꢀ 1.5 mm
nominal. IR spectra were recorded as KBr discs on a Brucker Tensor 27 Fourier
1
transform (FT)–IR spectrometer. H NMR spectra were recorded on a Bruker AQS
Avance 300-MHz spectrometer using tetramethylsilane (TMS) as an internal standard.

BIGINELLI REACTION
829
General Procedure for the Synthesis of 3,4-Dihydropyrimidinones
A solution of ethyl acetoacetate 1 (2 mmol), aldehyde 2 (2 mmol), urea 3
3 mmol), and Fe(III)=Al-MCM-41 (0.03 g) in acetonitrile (10 ml) was heated under
(
reflux for 4 h. The progress of the reactions was monitored by thin-layer chromato-
graphy (TLC). The reaction mixture was poured into crushed ice with stirring. The
crude product was filtered, and washed with 95% hot ethanol, the catalyst was fil-
tered, and then the product recrystallized with hot ethanol to give 4.
[15]
Preparation of Catalysts Fe(III)/Al-MCM-41
Al-MCM-41 (1 g) was added to FeCl (1.5 mmol in 100 ml ethanol). The mix-
3
ture was refluxed while stirring for 8 h under a nitrogen atmosphere. The solid pro-
duct was then filtered, and soxhelet was extracted with enough absolute ethanol to
remove the weakly adsorbed metallocomplexes on the mesoporous surface. The solid
was finally dried in air at room temperature. The iron percentage present in the
[
15b]
immobilized complex=Al-MCM-41 is 0.89%.
General Procedure for Recyclability of the Catalyst
Next, we investigated the reusability and recycling of Fe(III)=Al-MCM-41. At
the end of the reaction, the catalyst could be recovered by simple filtration. The
recycled catalyst could be washed with methanol and subjected to a second run of
the reaction process. To assure that catalysts were not dissolved in acetonitrile,
the catalysts were weighted after filtration and before the next reaction. The results
show that these catalysts are not soluble in acetonitrile. In Table 2, the comparison
of efficiency of Fe(III)=Al-MCM-41 in the synthesis of 4a after three runs is
reported. As shown in Table 1, the first reaction using recovered Fe(III)=Al-MCM-
4
1 afforded a yield similar to that obtained in the first run. In the second and third
runs, the yields were gradually decreased because the active quantity of Fe(III)
decreased.
Spectral Data for Selected Compounds
5
4a). Mp 201–203 C. IR (KBr): 3111, 2955, 1705, 1649, 1613 cm ; H NMR
-Ethoxycarbonyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one
ꢂ1
ꢁ
1
(
(
CDCl , 300 MHz): d 8.17 (s, 1H, NH), 7.25 (d, 2H, J ¼ 8.6, Ar-H), 6.84 (d, 2H,
3
J ¼ 8.6, Ar-H), 5.75 (s, 1H, NH), 5.36 (d, J ¼ 2 Hz, 1H), 4.08 (q, J ¼ 7.1 Hz, 2H,
OCH ), 3.79 (s, 3H, CH ), 2.35 (s, 3H, CH ), 1.18 (t, J ¼ 7.1 Hz, 3H, OCH CH ).
2
3
3
2
3
5-Ethoxycarbonyl-6-methyl-4(2-nitrophenyl-3,4-dihydropyrimidin-2(1H)-
one (4b). Mp 220–223 C. H NMR (CDCl , 300 MHz): 7.47–8.24 (m, 5H, Ar-H
ꢁ
1
3
and NH), 5.90 (s, 1H, NH), 5.77 (s, 1H, H-4), 4.35 (q, J ¼ 7.5 Hz, 2H, OCH ),
2
2
.48 (s, 3H, CH ), 1.37 (t, J ¼ 7.5 Hz, 3H, OCH CH ).
3
2
3
5
(1H)-one (4c). Mp 216–219 C. IR (KBr): 3326, 3152, 1654, 1232, 1051 cm
-Ethoxycarbonyl-6-methyl-4(4-methylphenyl-3,4-dihydropyrimidin-
ꢂ1
ꢁ
2
;
1
H NMR (CDCl , 300 MHz): d 9.15 (s, 1H, NH), 7.80 (s, 1H, NH), 7.30–7.10
3

830
H. A. OSKOOIE ET AL.
(
1
m, 4H, Ar-H), 5.09 (s, 1H, H-4), 3.96 (q, J ¼ 7.1 Hz, 2H, OCH ), 2.23 (s, 3H, CH ),
2
3
.08 (t, J ¼ 7.1 Hz, 3H, OCH CH ).
2
3
5
-Ethoxycarbonyl-6-methyl-4(4-methoxyphenyl)-3,4-dihydropyrimidin-
ꢂ1
ꢁ
2
(1H)-one (4d). Mp 216–219 C. IR (KBr): 3223, 3106, 1710, 1668, 1605 cm
;
1
H NMR (CDCl , 300 MHz): d 7.55 (s, 1H, NH), 7.21–7.34 (m, 5H, C H ), 5.5 (s,
3
6
5
1
1
H, NH), 5.42 (d, J ¼ 2.4 Hz, 1H), 4.06–4.12 (m, 2H, OCH ), 2.37 (s, 3H, CH ),
2
3
.18 (t, J ¼ 7.1 Hz, 3H, OCH CH ).
2 3
5
-Ethoxycarbonyl-6-methyl-4(4-nitrophenyl-3,4-dihydropyrimidin-2(1H)-
ꢂ1
ꢁ
1
one (4e). Mp 208–210 C. IR (KBr): 3230, 3120, 1730, 1710, 1650 cm ; H NMR
CDCl , 300 MHz): d 9.35 (s, 1H, NH), 7.89 (s, 1H, NH), 7.47–8.23 (m, 4H, Ar-H),
(
3
5
.26 (s, 1H, H-4), 3.97 (q, J ¼ 7.0 Hz, 2H, OCH ), 2.25 (s, 3H, CH ), 1.08 (t,
2
3
J ¼ 7.0 Hz, 3H, OCH CH ).
2 3
5
-Ethoxycarbonyl-6-methyl-4(4-chlorophenyl-3,4-dihydropyrimidin-2(1H)-
1
ꢁ
one (4f). Mp 212–214 C. H NMR (CDCl , 300 MHz): d 9.24 (s, 1H, NH), 7.78 (s,
3
1
H, NH), 7.40–7.21 (m, 4H, Ar-H), 5.12 (s, 1H, H-4), 3.97 (q, J ¼ 6.9 Hz, 2H,
OCH ), 2.24 (s, 3H, CH ), 1.08 (t, J ¼ 6.9 Hz, 3H, OCH CH ).
2
3
2
3
5
-Ethoxycarbonyl-6-methyl-4(3-nitrophenyl-3,4-dihydropyrimidin-2(1H)-
ꢂ1
ꢁ
1
one (4g). Mp 227–230 C. IR (KBr): 3300, 3120, 1710, 1690, 1630 cm ; H NMR
CDCl , 300 MHz): d 9.37 (s, 1H, NH), 7.90 (s, 1H, NH), 8.10–7.64 (m, 4H, Ar-H),
(
3
5
.29 (s, 1H, H-4), 3.98 (q, J ¼ 7.0 Hz, 2H, OCH ), 2.26 (s, 3H, CH ), 1.08 (t,
2
3
J ¼ 7.0 Hz, 3H, OCH CH ).
2
3
ACKNOWLEDGMENT
We are grateful to the Alzahra University Research Council for partial support
of this work.
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