Sulfamic Acid Supported Magnetic Fe3O 4 Nanoparticles Catalyzed Synthesis of 3,4-Dihydropyrimidin-2(1 H)-ones/Thiones

Article abstract of DOI:10.1080/15533174.2014.900802

Sulfamic acid supported on magnetic Fe₃O₄ nanoparticles catalyzed the condensation reaction of aldehydes, 1,3-dicarbonyl compounds, and urea or thiourea in the synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones under solvent-free c

Full text of DOI:10.1080/15533174.2014.900802

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Sulfamic acid supported magnetic Fe3O4 nanoparticles
catalyzed synthesis of 3,4-dihydropyrimidin-2(1H)-
ones/thiones
Foad Shaghayeghi Toosia, Ali faranak Maghsoodia & toosi Shaghayeghia
a Department of Chemistry, Islamic Azad University, Neyshabur Branch, Neyshabur, Iran
Accepted author version posted online: 03 Feb 2015.
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To cite this article: Foad Shaghayeghi Toosi, Ali faranak Maghsoodi & toosi Shaghayeghi (2015): Sulfamic acid supported
magnetic Fe3O4 nanoparticles catalyzed synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones, Synthesis and Reactivity in
Inorganic, Metal-Organic, and Nano-Metal Chemistry, DOI: 10.1080/15533174.2014.900802
To link to this article: http://dx.doi.org/10.1080/15533174.2014.900802
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Sulfamic acid supported magnetic Fe3O4 nanoparticles catalyzed synthesis of 3,4-
dihydropyrimidin-2(1H)-ones/thiones
Foad Shaghayeghi Toosi,* Ali maghsoodi faranak, Shaghayeghi toosi
Department of Chemistry, Islamic Azad University, Neyshabur Branch, Neyshabur, Iran
E-mail: foad_toosi@yahoo.com
Abstract: Sulfamic acid supported on magnetic Fe3O4 nanoparticles catalyzed the condensation
reaction of aldehydes, 1,3-dicarbonyl compounds, and urea or thiourea in the synthesis of 3,4-
dihydropyrimidin-2(1H)-ones/thiones under solvent-free conditions. This method offers several
advantages including high yield, short reaction time, ease of separation, and recyclability of the
magnetic catalyst.
Keywords: Magnetic, Fe3O4 nanoparticles, acylation, Biginelli reaction, Dihydropyrimidin-
2(1H)-one/thione
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Introduction
Dihydropyrimidin-2(1H)-one/thione and their derivatives have attracted great attention due to
their pharmacological and therapeutic properties such as antibacterial–antihypertensive and
calcium channel blocker activity as well as behaving as neuropeptide antagonists. 1
The Biginelli reaction has received renewed interest because it is suitable for the generation of
DHPM libraries in combinatorial chemistry. 2
In order to improve the efficiency of the Biginelli reaction several catalysts such as sulfonic acid
3
4
5
6
7
functionalized silica, ion exchange resins, Ziegler–Natta, TMSCl/NaI, FeCl3/Si(OEt)4,
Biocatalysts, 8 imidazolium-tagged recyclable iron 9 have been developed.
The design and preparation of the stable magnetic solid acid catalysts in harsh catalytic
conditions is often a big challenge for chemists and is less advanced than the research in other
solid acid catalysts. 10
Recently, Clark et.al investigated effects of catalytic and solvent on the Biginelli Reaction. They
elucidated that the diketo–enol tautomerisation equilibrium of the dicarbonyl reactant dictates the
yield of the reaction. Whereas the solvent is responsible for the tautomerisation equilibrium
position, the catalyst only serves to eliminate kinetic control from the reaction. Generally, to
preserve reaction efficiency and improve sustainability, bio-derivable p-cymene was found to be
a useful solvent. The metal–enolate intermediate that results from the application of a Lewis
acidic catalyst often cited as promoting the reaction appears to hinder the reaction. In this
instance, a Brønsted acidic solvent can be used to return greater reactivity to the dicarbonyl
reagent.12
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The demand for an environmentally benign procedure with heterogeneous and reusable catalyst
prompted us to develop a safe alternate method for the synthesis dihydropyrimidin-2(1H)-
ones/thiones derivatives in the presence of Sulfamic acid supported magnetic
Fe3O4 nanoparticles as a solid heterogeneous acid catalyst.
Furthermore, in our work we applied a method based on magnetic nanoparticles facilitates the separation
of solid catalyst after catalyzing one-pot reactions.
Experimental
All reagents were purchased from Merck and Sigma-Aldrich and used without further
purification. Products were characterized by comparison physical data with known samples and
1
spectroscopic data (FT-IR, H NMR and 13C NMR). The NMR spectra were recorded on a
Bruker Avance DPX 400 MHz instrument. The spectra were measured in DMSO. FT-IR spectra
were recorded on a JASCO FT-IR 460 plus spectrophotometer. Melting points were determined
in open capillaries with a BUCHI 510 melting point apparatus.
Preparation of the magnetic Fe3O4 nanoparticles (MNPs):
Preparation of the magnetic Fe3O4 nanoparticles (MNPs) Naked Fe3O4 nanoparticles were
prepared by co precipitation of Fe3+ and Fe2+ ions with a molar ratio of 2:1. Typically,
FeCl3·6H2O (0.0216 mol) and FeCl2·4H2O(0.0108 mol) were dissolved in 100mL deionized
0
water at 85 C vigorous mechanical stirring. Then, 10mL of 25% NH4OH was quickly injected
into the reaction mixture in one portion. The addition of the base to the Fe2+/Fe3+ salt solution
resulted in the formation of the black precipitate of MNPs. The reaction continued for another 1
h. The black precipitate was washed with distilled water through magnetic decantation.
Preparation of MNPs coated by (3-aminopropyl)- triethoxysilane:
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The obtained MNPs powder (1.5 g) was dispersed in 250mL ethanol/water (volume ratio, 1:1)
solution by sonication for30 min, and then APTES (99%, 2.5 mL) was added to the mixture.
After mechanical agitation under N2 atmosphere at 40 ◦C for 4 h, the suspended substance was
separated with centrifugation. The settled product was re-dispersed in ethanol by sonication and
then was isolated with magnetic decantation for 5 times. The precipitated product (APTES–
MNPs) was dried at room temperature under vacuum.
Preparation of sulfamic acid-functionalized magnetic Fe3O4 nanoparticles (SA-MNPs):
The APTES–MNPs (500 mg) were dispersed in dry CH2Cl2 (3 mL) by ultrasonic bath for 10
min. Subsequently, chlorosulfuric acid (0.8 mL) was added dropwise over a period of 30 min at
room temperature. Hydrogen chloride gas evolved from the reaction vessel immediately. Then,
the as prepared functionalized MNPs nanoparticles were separated by magnetic decantation and
washed three times with dry CH2Cl2 to remove the unattached substrates(Scheme 2).
General procedure for the synthesis of 3,4- dihydropyrimidin-2(1H)-ones/ thiones:
A stirred mixture of arylaldehyde (1 mmol), 1,3-dicarbonyl compounds (1.2 mmol), urea or
thiourea (1.5 mmol), and sulfamic acid-functionalized magnetic Fe3O4 nanoparticles (25 mg)
o
was reacted in an oil bath at 100 C for the appropriated times (Tables 1). Completion of the
reaction was indicated by TLC. After the reaction was completed, the catalyst was separated by
an external magnet and reused for the next experiment. the crude solid product was solved in
ethylacetate, and filtered for separation of the catalyst. The catalyst was washed four times with
ethyl acetate, and then recovered catalyst was dried in oven at 100 oC for 2 h. The filtrate organic
solution was concentrated. The solid product was purified by recrystallization procedure in
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aqueous EtOH. All the products were characterized by comparison of their spectroscopic and
physical data with the authentic samples. Spectral data for selected compound:
5-Methoxycarbony-6-methyl-4-(benzo[d][1,3]dioxol-5-yl)-3,4-dihydro-pyrimidin-2-one
o
Pale yellow solid; mp 196–198 C; IR (KBr): 3367, 3220, 3012, 2952, 1712, 1692, 1644, 1488,
1459, 1436, 1231, 1099 cm-1; 1H NMR (500MHz, DMSO-d6): δ =2.25 (s, 3H, CH3), 3.53 (s, 3H,
OCH3), 5.06 (d, 1H, J = 3.2 Hz, CH), 5.98 (s, 2H, CH2), 6.67–6.85 (m, 3H, ArH), 7.68 (s, 1H,
13
NH), 9.19 (s, 1H, NH) ppm; C NMR (125 MHz, DMSO-d6): d18.5, 51.1, 53.9, 99.5, 101.3,
107.0, 108.4, 119.6, 139.1, 146.7, 147.7, 148.9, 152.4, 166.2 ppm.
5-Ethoxycarbony-6-methyl-4-(4- nitrophenyl)-3,4-dihydro-pyrimidin-2-thione
o
Pale purple solid; mp 234–235 C; IR (KBr) 3324, 3173, 2918, 1679, 1655, 1576, 1522, 1466,
1350, 1201, 1176, 1123 cm-1; 1H NMR (500MHz,DMSO-d6): δ = 1.10 (t, 3H, J = 7.1 Hz, CH3),
2.31 (s, 3H, CH3), 4.02(q, 2H, J =7.1 Hz, CH2), 5.31 (d, 1H, J= 3.5 Hz, CH), 7.48 (d, 2H,J = 8.7
Hz, ArH), 8.23 (d, 2H, J¼8.7 Hz, ArH), 9.76 (d, 1H, J = 1.2 Hz,NH), 10.49 (s, 1H, NH) ppm;
13C NMR (125MHz, DMSO-d6): d 14.7,17.7, 54.1, 60.3, 100.2, 124.5, 128.3, 146.4, 147.5,
150.86, 165.3,174.9 ppm.
Result and Discussion
Sulfamic acid supported on magnetic Fe3O4 nanoparticles has proved to be efficient catalyst for
the Biginelli condensation in a more efficiency way that minimizes the time, temperature, and
amount of catalyst, the reaction of benzaldehyde, ethyl acetoacetate, and urea was selected as
model to investigate the effects of the catalyst at different reaction temperatures and different
amounts of catalysts, SA-MNPs. The best result was obtained by carrying out the reaction with
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1.0:1.2:1.5 molar ratios of aldehyde, 1,3-dicarbonyl compounds, urea or thiourea, and 120 mg of
SA-MNPs at 100 oC.
The suggested mechanism of this transformation is shown in Scheme 2. The first step in the
mechanism is the condensation between the aldehyde and urea or thiourea, with some similarities
to the Mannich Condensation. The acyl imine intermediate generated acts as an electrophile for
the nucleophilic addition of the keto enol ether, and the ketone carbonyl of the resulting adduct
undergoes condensation with the urea or thiourea to give the cyclized Biginelli product.
Conclusion
We have developed a green and straightforward protocol for the synthesis of 3,4-
dihydropyrimidin-2(1H)-ones/thiones
using
sulfamic
acid
supported on
magnetic
Fe3O4 nanoparticles is an efficient and heterogeneous catalyst from condensation reaction of
aldehydes, 1,3-dicarbonyl compounds, and urea or thiourea under thermal solvent-free
conditions. The catalyst can be recovered from reaction mixtures by applying an external
magnetic field.
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References
1) Biginelli P, Gazz. Chim. Ital. 1893, 23, 360-416.
2) Wen P andWang Q, Synth. Commun. 2010, 40, 1209-1215.
3) Gupta R, Paul S and Gupta R, J. Mol. Catal. A: Chem. 2007, 266, 50-54.
4) Joseph J K, Jain S L and Sain B, J. Mol. Catal. A: Chem. 2006, 247, 99-102.
5) Kumar A and MauryaR A, J. Mol. Catal. A: Chem. 2007, 272, 53-56.
6) Sabitha G, Reddy G S K K, Reddy C S and Yadav J S, Synlett 2003, 858–860.
7) Cepanec I, Litvic´ M, Bartolincˇic´ A and Lovric´ M, Tetrahedron 2005, 61, 4275–4280.
8) Sharma U K, Sharma N, Kumar R, Sinha A K. Amino Acids 2013, 44, 1031–1037.
9) Ramos L M, Guido B C, Nobrega C C, RCorr J, Silva R G, Oliveira H C B, Gomes A F,
Gozzo F C, Neto B A D. Chem. Eur. J. 2013, DOI: 10.1002/chem.201204314.
10) Kong A, Wanga P, Zhanga H, YangaF, Huangc S P, Shana Y. Applied Catalysis A:
General 2012, 417– 418, 183– 189.
11) Clark J H, Macquarrie D J, Sherwood J, Chem. Eur. J. 2013, 19, 5174 – 5182.
12) Lei M, Wu D D, Wei H G and Wang Y G, Synth. Commun. 2009, 39, 475-483.
13) Shaterian H R, Hosseinian A, Ghashang M, Phosphorus, Sulfur Silicon, Relat. Elem.
2009, 184, 197-205.
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Table 1: Sulfamic acid supported on magnetic Fe3O4 nanoparticles catalyzed synthesis of 3,4
dihydropyrimidin2(1H)-ones/ thiones under solvent free conditions
Entry
R1
H
X
O
O
O
O
O
O
O
O
O
R2
R3
Yield(%)
M.P(oC)
205-206
[203-204 ]12
215-216
1
2
3
4
5
6
7
8
9
C2H5O
C2H5O
C2H5O
C2H5O
CH3O
CH3O
CH3O
CH3O
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
89
90
4-Cl
[214-215] 12
104-105
4-NO2
4-CH3O
H
85
92
83
88
86
90
82
[207-208] 12
201-203
[200-202] 12
210-212
[209-210] 12
230-233
4-NO2
4-OH
4-CH3O
H
[234-236] 12
225-227
[227-229] 12
190-192
[191-193] 12
264-265
[260-262] 13
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201-202
10
11
12
13
14
15
16
17
18
19
4-CH3O
4-CH3
4-Cl
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
80
89
88
90
84
86
78
75
80
80
[200-202] 13
256-257
O
O
[258-260] 13
258-260
O
O
O
O
S
CH3
[258-260] 13
282-283
2-Cl
CH3
[280-282] 13
260-261
4-F
CH3
[262-263] 13
236-238
4-OH
H
CH3
[235-237] 13
205-207
C2H5O
C2H5O
C2H5O
C2H5O
[206-207] 13
194-196
3-Cl
S
[196-198] 13
108-109
4-NO2
3-CH3O
S
[108-110] 13
152-154
S
[150-152] 13
195-197
20
21
4-OH
H
S
S
C2H5O
CH3O
CH3
CH3
79
84
[194-196] 13
220-222
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[221-223] 13
238-240
22
23
24
3-NO2
4-OH
S
S
S
CH3O
CH3O
CH3O
CH3
CH3
CH3
85
82
80
[237-239] 13
225-227
[226-228] 13
154-156
4-(Me)2N
[152-154] 13
aYields refer to the isolated pure products
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R1
O
X
CHO
O
O
Catalyst
R2
NH
R2
R3
H2N
NH2
T=100oC, Solvent free
R3
N
O
R1
X= O, S
H
R2= OCH3, OEt, Me
R3= , Me, OCH3, OEt, Et
Scheme 1: synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones
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X
H2N
N
CHO
+
X
Catalyst
-H2O
H
H2N
NH2
R1
R1
O
O
Catalyst
R2
R3
X
X
Catalyst
OH
O
X
H2N
NH O
H2N
NH
H
R2
R3
R3
O
R2
R1
R1
-H2O
HN
O
NH
R3
R2
R1
Scheme 2: The suggested mechanism for preparation of of 3,4- dihydropyrimidin-2(1H)-
ones/ thiones
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