Scholarly article on topic 'Green synthesis of 3,4-dihydropyrimidinones using nano Fe 3 O 4 @meglumine sulfonic acid as a new efficient solid acid catalyst under microwave irradiation'

Green synthesis of 3,4-dihydropyrimidinones using nano Fe 3 O 4 @meglumine sulfonic acid as a new efficient solid acid catalyst under microwave irradiation Academic research paper on "Chemical sciences"

CC BY-NC-ND
0
0
Share paper
Academic journal
Journal of Saudi Chemical Society
OECD Field of science
Keywords
{"Nano Fe3O4@meglumine sulfonic acid" / "3 / 4-Dihydropyrimidin-2(1H)-ones" / "Multicomponent reactions" / "Microwave irradiation" / "One pot synthesis" / "Heterogeneous catalyst"}

Abstract of research paper on Chemical sciences, author of scientific article — Leila Moradi, Maryam Tadayon

Abstract Design, synthesis and characterization of nano Fe3O4@meglumine sulfonic acid as a new solid acid catalyst for the simple and green one pot multicomponent synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones was studied. New solid acid catalyst was prepared through a clean and simple protocol and characterized using FTIR, VSM, TGA, SEM, elemental analysis (CHN) and XRD techniques. Heterogenization of homogeneous catalyst as a green approach is a useful method for enhancing the efficiency of catalyst. Presented study was a new method for attachment of homogeneous highly soluble catalyst (meglumine sulfate) to the magnetite nanoparticle surfaces for preparing a heterogeneous and effective catalyst. Obtained heterogeneous and reusable solid acid catalyst has high performance in the synthesis of Biginelli compounds. The reaction was performed under microwave irradiation as a rapid and green condition. Easy work up as well as excellent yield (90–98%) of products in short reaction times (40–200s) and reusable catalyst are the main advantages of presented procedure. Reaction products were characterized in details using physical and chemical techniques such as melting point, 1H NMR, 13C NMR and FTIR.

Academic research paper on topic "Green synthesis of 3,4-dihydropyrimidinones using nano Fe 3 O 4 @meglumine sulfonic acid as a new efficient solid acid catalyst under microwave irradiation"

Accepted Manuscript

Original article

Green Synthesis of 3,4-dihydropyrimidinones using nano Fe3O4@meglumine sulfonic acid as a new efficient solid acid catalyst under microwave irradiation

Leila Moradi, Maryam Tadayon

PII: DOI:

Reference:

S1319-6103(17)30085-6 http://dx.doi.org/10.1016/joscs.2017.07.004 JSCS 893

To appear in:

Journal of Saudi Chemical Society

Received Date: Revised Date: Accepted Date:

31 May 2017

10 July 2017

11 July 2017

Journal of Saudi Chemical Society

Please cite this article as: L. Moradi, M. Tadayon, Green Synthesis of 3,4-dihydropyrimidinones using nano Fe3O4@meglumine sulfonic acid as a new efficient solid acid catalyst under microwave irradiation, Journal of Saudi Chemical Society (2017), doi: http://dx.doi.org/10.1016/joscs.2017.07.004

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Green Synthesis of 3,4-dihydropyrimidinones using nano Fe3O4@meglumine sulfonic acid as a new efficient solid acid

catalyst under microwave irradiation

Leila Moradi, Maryam Tadayon Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, P.O. Box 8731753153, Kash

Lan, Islamic

Abstract

Design, synthesis and characterization of nano Fe3O4@meglumine sulfonic acid as a new solid acid catalyst for the simple and green one pot multicomponent synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones was studied. New solid acid catalyst was prepared through a clean and simple protocol and characterized using FTIR, VSM, TGA, SEM, elemental analysis (CHN) and XRD techniques. Heterogenization of homogeneous catalyst as a green approach is a usful method for enhance the efficiency of catalyst. Presented study was a new method for attachment of highly soluble catalyst (meglumine sulfate) to the magnetit nanoparticl surfaces. Obtained heterogeneous and reusable solid acid catalyst has high performance in the synthesis of Biginelli compounds. The reaction was performed under microwave irradiation as a rapid and green condition. Easy work up as well as excellent yield (90-98%) of products in short reaction times (40-200 second) and reusable catalyst are the main advantages of presented procedure. Reaction products were characterized in detailes using physical and chemical techniques such as melting point, 1HNMR, 13CNMR and FTIR. A/

Keywords: Nano Fe3O4@meglumine sulfonic acid, 3, 4-dihydropyrimidin-2(1H)-ones, multicomponent reactions, microwave irradiation, One pot synthesis, Heterogeneous catalyst.

1. Introduction

Multi-component reactions (MCRs) are one of the most important methods in organic synthesis and medicinal chemistry because of their wide range of applications and significant advantages over conventional linear type syntheses [1]. Compared with conventional methods of organic synthesis, MCRs have the advantages such as high-selectivity, higher yield and diversity by varying reaction substrates and simple work-up procedures.

Biginelli reaction as one of the most well-known one-pot multicomponent reactions, was reported in 1893 by Pietro Biginelli through the multicomponent condensation of an aldehyde, p-ketoester and urea in the presence of acidic catalyst to yield 3,4-dihydro-pirimidin-2(1H)-ones (3,4-DHPs) [2]. These heterocyclic compounds, have exhibited a wide range of biological and pharmacological activities such as antibacterial, antiviral and antitumor effects [3-12].

Different catalytic methods have been reported for the synthesis of 3,4-DHPs, using improved procedures such as the microwave condition [13], ultrasonic irradiation [14,15], potassium phthalimide [16], NH4Cl [17], Lewis acids such as BF3.Et2O, ZrCl4, Cu(OTf)2 [18], nano-ZnO [19], Bronsted acidic ionic liquids [20], Ionic liquid-based ordered mesoporous organosilica-supported copper [21] and MWCNT-SO3H [22].

Some of these procedures require stoichiometric amounts of catalysts, expensive reagents, harsh reaction conditions, prolonged time period and high temperatures that produced environmental pollution or give unsatisfactory yield.

The development of solid acid systems utilizing inexpensive, clean, environmentally benign and commercially available catalysts has been a challenge in organic synthesis. In this research, Fe3O4@meglumine sulfonic acid (Fe3O4@MSA) as a new, high efficient and green solid acid catalyst has been prepared and used for the synthesis of 3,4-DHPs under MW irradiation (scheme 1). Recently, Nano Fe3O4-supported sulfonic acid has been reported as a solid acid catalyst in the Biginelli condensation such as sulfonated-phenylacetic acid coated Fe3O4 nanoparticles [23], Nano-y-Fe2O3@SO3H [24] and Fe3O4@silica sulfuric acid [25]. Although in these reported studies, solvent free conditions under conventional heating have been applied as Appropriate conditions, but Our presented method provided a fast and clean conditions with excellent yield of products under microwave irradiation. In fact, high performance reusable solid acid nanocatalyst with high percentage of sulfonic acid groups (in compare with other solid acidi catalysts), due to special structure of meglumine, in addition to short

as a ne

reaction times furnishd a green strategy for Biginelli synthesis which can be considered as a new, green and scalable method.

Scheme 1

2. Experimental

2.1. Chemicals and apparatus

nsidered a /

All chemicals were obtained from Merck and Sigma-Aldrich and used as received. Melting points were determined in an open capillary using a Thermo Scientific 9300 apparatus. 1H NMR and 13C NMR spectra were recorded in DMSO-d6 and

CDCl3 using Bruker DRX-400 and 100 MHz, respectively. Infrared (IR) spectra were recorded with a Perkin-Elmer FTIR 550 spectrometer. The elemental analyses (CHN) were obtained from a Carlo ERBA model EA 1108 analyzer carried out on Perkin-Elmer 240C analyzer. Reactions were performed with a milestone ETHOS EZ microwave oven, keeping irradiation power fixed and monitoring the internal reaction temperature. Magnetic properties were characterized by a vibrating sample magnetometer (VSM, MDKFD) at room temperature.

2.2. Preparation of Fe3O4@meglumine

To prepare the Fe3O4 nanoparticles, a mixture of FeCl2.4H2O (1.0 g) and FeCl3.6H2O (2.6 g) was dissolved in 20 ml distilled water. Then, 15 ml of 25% NH4OH was injected dropwise in to the reaction mixture with constant stirring for 30 min under N2 atmosphere. Generated instant black precipitate of Fe3O4 nanoparticles separated by magnetic field and washed three times with distilled water and dried at 80°C. In order to prepare Fe3O4/Si(CH2)3Cl, 1 g of magnetite nanoparticles was added to 1 ml (5 mmol) CPTS dissolved in 100 ml dried toluene. The mixture was stirred for 18 h at 60°C. Obtained Fe3O4/Si(CH2)3Cl was separated by magnetic field, washed with toluene and dried. For preparation of Fe3O4@meglumine, 0.5 g of Fe3O4/Si(CH2)3Cl was added to 1.0 g meglumine dissolved in 100 ml dry THF and refluxed for 4h at 60°C. Final product, was

separated using a magnet and washed with THF and dried (scheme 2).

2.3. Preparation of Fe3O4@meglumine sulfonic acid (Fe3O4@MSA)

0.5 g Fe3O4@meglumine was added to 20 ml dry chloroform (in ice water bath). 0.4 ml chlorosulfonic acid was injected dropwise in to the reaction mixture within 1h. The resulting mixture was mechanically stirred for 2h and then washed with ethanol and finally dried under 90°C (Scheme 2).

Scheme 2

2.3. General procedure for the synthesis of 3,4-dihydropyridinone/thiones

0.025 g of Fe3O4@MSA was added to a homogeneous mixture of aldehyde (1 mmol), p-dicarbonyl (1 mmol) urea or thiourea (1.2 mmol) in a 5 ml of water/ethanol (1:1) under microwave irradiation (400 w, 80°C). The reaction progress was monitored by thin layer chromatography (TLC). After the completion of the reaction, the nano magnetite based catalyst was separated by magnet and for separation of the reaction product, 2 ml ethanol was added and then poured on crushed ice and then obtained solid product was separated by simple filtration, washed with EtOH and dried (scheme 1).

3.3. Spectral Data

5-(Ethoxycarbonyl)-4-(4-chlorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (5a)

White crystals: m.p 210-212°C; IR (KBr) umax: 3242.04 (NH), 3120.12 (NH), 2974.87 (C-H aliphatic), 1706.52 (C=O), 1640.66, 1465.23 (C=C aromatic), 1221.17, 1095.89(C-O) cm-1. 1H NMR (DMSO-d6, 400 MHz): 5 1.08 (t, J=7.2Hz, 3H, CH3), 2.27 (s, 3H, CH3), 3.99 (q, J=7.2Hz, 2H, CH2), 5.14 (s, 1H, CH), 7.23 (d, J=5Hz, 2H, Ar-H), 7.35 (d, J=5Hz, 2H, Ar-H), 7.79 (s, 1H, NH), 9.27 (s, 1H, NH) ppm. 13C NMR (DMSO-d6, 100 MHZ): 5 14.28, 18.32, 54.71, 60.21, 104.35, 119.09, 130.25, 142.86, 151.45, 151.35, 158.86, 164.62 ppm. Anal. Calcd. for C14H15ClN2O3: C, 56.95; H, 5.09; N, 9.49; Found: C, 56.80; H, 5.01; N, 9.44. MS (m/z ): 294.81 (M+).

5-(Ethoxycarbonyl)-4-(2,4-dichlorophenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (5b)

White crystals: m.p 249-251°C; IR (KBr) umax: 3358.87 (NH), 3221.54 (NH), 2970.82(C-H aliphatic), 1700.52 (C=O), 1643.66, 1456.50(C=C aromatic), 1226.66, 1097.18 (C-O) cm-1; 1H NMR (DMSO-d6,400 MHz): 5 0.98 (t, J=7.76Hz, 3H, CH3), 2.27 (s, 3H, CH3), 3.88 (q, J=7.76Hz, 2H, CH2), 5.57 (s, 1H, CH), 7.31 (d, J=5.14Hz, 1H, Ar-H), 7.41 (d, J=5.14Hz, 1H, Ar-H), 7.56 (s, 1H, Ar-H), 7.76 (s, 1H, NH), 9.31 (s, 1H, NH) ppm. 13C NMR (DMSO-d6, 100 MHZ): 5 14.19, 18.75, 54.96, 61.11, 101.43, 126.95, 127.92, 128.91, 131.23, 141.76, 142.95, 153.27, 158.74, 165.15; Anal. calcd. for C14H14Cl2N2O3: C, 50.91; H, 4.24; N, 8.48; Found: C, 50.86; H, 4.21; N, 8.42. MS (m/z ): 330.32 (M+).

5-(Ethoxycarbonyl)-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one (5c)

White crystals: m.p 203-205°C; IR (KBr) umax: 3241.77 (NH), 3111.63 (NH), 2953.58(C-H aliphatic), 1705.54(C=O), 1648.63, 1458.54(C=C aromatic), 1223.38, 1090.64(C-O) cm-1; 1H NMR (DMSO-d6,400 MHz): 5 1.19 (t, J=7.08 Hz, 3H CH3), 2.34 (s, 3H, CH3), 3.79 (s, 3H, CH3), 4.08 (q, J=7.08Hz, 2H, CH2), 5.35 (s, 1H, CH), 5.58(s, 1H, NH), 6.84(d, 2H, J=6.56 Hz, Ar-H), 7.25 (d, J=6.56 Hz, 2H, Ar-H), 7.86 (s, 1H, NH) ppm. 13C NMR (DMSO-d6, 100 MHZ): 5 14.12, 18.65, 56.02, 56.36, 58.96, 102.04, 113.79, 128.17, 136.13, 146.18, 152.48, 158.78, 164.99 ppm. Anal. calcd. for C15H18N2O4: C, 62.07; H, 6.21; N, 9.66; Found: C, 61.96; H, 6.18; N, 9.48. MS (m/z): 290.28 (M+).

5-Ethoxycarbonyl- 6-methyl-4-(4-hydroxyphenyl)-3,4-dihydropyrimidin-2(1H)-One (

Yellow crystals: m.p 228-229°C; IR (KBr) umax: 3340.81 (NH), 3126.12 (NH), 2980.40(C-H aliphatic), 1692.11(C=O), 1640.32, 1454.15 (C=C aromatic), 1226.68, 1099.40 (C-O) cm-1; 1H NMR (DMSO-d6,400 MHz): 5 1.06 (t, J=8.28 Hz, 3H, CH3), 2.21 (s, 3H, CH3), 3.97 (q, J=8.28Hz, 2H, CH2), 5.01 (s, 1H, CH), 6.7 (d, J=8.5 Hz, 2H, Ar-H), 7.01 (d, J=8.5Hz, 2H, Ar-H), 7.62 (s, 1H, NH), 9.12 (s, 1H, NH), 9.34 (s, 1H, OH) ppm. 13C NMR (DMSO-d6, 100 MHZ): 5 14.01, 17.65, 55.12, 58.36, 101.13, 114.88, 128.12, 134.16, 146.86, 152.98, 156.79, 164.98; Anal. calcd. for C14H16N2O4 C, 60.87; H, 5.79; N, 10.14; Found: C, 60.84; H, 5.75; N, 10.11. MS (m/z): 276.19 (M+).

lydropynn

Ethyl 6-methyl-2-oxo-4-p-tolyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate(5e)

White crystals: m.p 212-214°C; IR (KBr) umax: 3243.91(NH), 3115.11 (NH), 2979.65(C-H aliphatic), 1706.59(C=O), 1647.44, 1460.09 (C=C aromatic), 1223.94, 1090.38(C-O) cm-1; 1H NMR (DMSO-d6,400 MHz): 5 1.06 (t, J=9.2 Hz, 3H, CH3), 2.21 (s, 3H, CH3), 2.24 (s, 3H, CH3), 3.96 (q, J=9.2Hz, 2H, CH2), 5.06 (s, 1H, CH), 7.05 (m, 4H, Ar-H), 7.67 (s, 1H, NH), 9.16 (s, 1H, NH) ppm. 13C NMR (DMSO-d6, 100 MHZ): 5 14.11, 17.68, 21.03, 54.13, 58.98, 99.12, 126.18, 128.76, 136.43, 142.65, 148.39, 152.25, 166.39; Anal. calcd. for C15H18N2O4: C, 65.70; H, 6.57; N, 10.22; Found: C, 65.66; H, 6.54; N, 10.19. MS (m/z): 274.34 (M+).

hoxycarbo

5-Ethoxycarbonyl-4-(2-thienyl)-6-methyl-3,4- dihydropyrimidin-2(1H)-one (5f)

White crystals: m.p 213-215°C; IR (KBr) umax: 3241.54(NH), 3114.05(NH), 2933.62 (C-H aliphatic), 1706.85(C=O), 1650.39, 1423.28 (C=C aromatic), 1227.50,1094.18(C-O) cm-1; 1H NMR (DMSO-d6,400 MHz): 5 1.25 (t, J=6.2 Hz, 3H, CH3), 2.34 (s, 3H, CH3), 4.16 (q, J=6.2 Hz, 2H, CH2), 5.7 (s, 1H, CH), 5.92 (s, 1H, NH), 7.19(m, 3H, Ar-H), 7.99 (s, 1H, NH) ppm. 13C NMR (DMSO-d6, 100 MHZ): 5 14.21, 17.71, 49.87, 59.32, 99.82, 124.18, 124.86, 126.36, 148.84, 148.98, 152.31, 165.06 ppm. Anal. calcd. for C12H14N2O3S: C, 54.14; H, 5.26; N, 10.53; Found: C, 54.11; H, 5.23; N, 10.49. MS (m/z): 266.12 (M+)

Ethyl 1,2,3,4-tetrahydro-6-methyl-2-thioxo-4-paratolyl pyrimidine-5 carboxilate (5g)

White crystals: m.p 191-193°C; IR (KBr) umax: 3324.56 (NH), 3174.65 (NH), 2981.5 (C-H aliphatic), 1674.69 (C=O), 1575.2,1462.61 (C=C aromatic), 1185.51, 1116.39 (C-O) cm-1; 1H NMR (DMSO-d6,400 MHz): 5 1.17 (t, J=5.54 Hz, 3H, CH3), 2.32 (s, 3H, CH3), 2.35 (s, 3H, CH3), 4.09 (q, J=5.54 Hz, 2H, CH2), 5.35 (s, 1H, CH), 7.14 (m, 4H, Ar-H), 7.46 (s, 1H, NH), 8.12 (s, 1H, NH). 13C NMR (DMSO-d6, 100 MHZ): 5 13.68, 14.92, 18.12, 48.17, 60.18, 104.34, 125.38, 126.64, 127.89, 129.83, 136.27, 143.36, 152.26, 165.28, 178.13 ppm. Anal. Calcd for C15H18N2O2S: C, 62.09; H, 6.21; N, 9.65; Found: C, 61.98; H, 6.19; N, 9.61. MS (m/z): 290.23 (M+)

Ethyl 6-methyl-4-(3-nitrophenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (

Yellow crystals: m.p 223-225°C; IR (KBr) umax: 3330.33 (NH), 3218.68 (NH), 2965.55 (C-H aliphatic), 1705.54 (C=O), 1628.06, 1455.99 (C=C aromatic), 1345, 1222.25 (C-O) cm-1; 1H NMR (DMSO-d6,400 MHz): 5 1.06 (t, J=7.73 Hz, 3H, CH3), 2.25 (s, 3H, CH3), 3.97 (q, J=7.73Hz, 2H, CH2), 5.27 (s, 1H, CH), 7.65 (m, 2H, Ar-H), 7.9(s, 1H, Ar-H), 8.12 (d, 1H, Ar-H), 8.06 (s, 1H, NH), 9.38 (s, 1H, NH) ppm. 13C NMR (DMSO-d6, 100 MHZ): 5 14.18, 18.63, 55.85, 59.96, 102.66, 126.38, 127.84, 128.63, 130.51, 135.52, 144.75, 153.46, 159.62, 165.36 ppm. Anal. calcd. for C14H15N3O5: C, 55.08; H, 4.79; N, 13.77; Found: C, 54.92; H, 4.89; N, 13.82. MS (m/z): 305.20 (M

5-Ethoxycarbonyl-4-phenyl-6-methyl-3,4- dihydropyrimidin-2(1H)-one (5i)

White crystals: m.p 203-205°C; IR (KBr) umax: 3244.13 (NH), 3116.31 (NH), 2976.75 (C-H aliphatic), 1702.38 (C=O), 1645.89, 1462.74 (C=C aromatic), 1222.27, 1091.29 (C-O) cm-1; 1H NMR (DMSO-d6,400 MHz): 5 1.08 (t, J=6.8 Hz , 3H, CH3), 2.23 (s, 3H, CH3), 3.96 (q, J=6.8 Hz , 2H, CH2), 5.1 (s, 1H, CH), 7.2-7.3 (m, 5H, Ar-H), 7.7(s, 1H, NH), 9.1(s, 1H, NH) ppm. 13C NMR (DMSO-d6, 100 MHZ): 5 14.15, 18.12, 54.99, 60.44, 101.15, 113.34, 113.67, 125.42, 126.92, 129.73, 131.73, 150.52, 155.91, 164.87 ppm. Anal. calcd. for C14H15N2O3: C, 64.62; H, 6.15; N, 10.77; Found: C, 64.60; H, 6.11; N 10.71. MS (m/z): 260.22 (M+).

hoxycarbo

5-Ethoxycarbonyl-4-phenyl-6-methyl-3,4-dihydropyrimidin-2(1H)-thione (5j)

Yellow crystals: m.p 205-207°C; IR (KBr) umax: 3326.55 (NH), 3175.59 (NH), 2981.15 (C-H aliphatic), 1670.56 (C=O), 1571.84, 1462.25 (C=C aromatic), 1191.71, 1114.63 (C-O) cm-1; 1H NMR (DMSO-d6, 400 MHz): 5 1.28 (t, J=7.6Hz, 3H, CH3), 2.31 (s, 3H, CH3), 3.94 (q, J=7.6 Hz, 2H, CH2), 5.12 (s, 1H, CH), 7.22-7.43 (m, 5H, Ar-H), 7.71(s, 1H, NH), 9.11(s, 1H, NH) ppm. 13C NMR (DMSO-d6, 100 MHZ): 5 14.25, 18.99, 54.92, 60.31, 101.02, 113.24, 115.62, 125.42, 127.18, 129.82, 131.61, 150.72, 162.67, 180.54 ppm. Anal. calcd. for C14H16N2O2S: C, 60.87; H, 5.79; N, 10.14; Found: C, 60.84; H, 5.75; N, 10.11. MS (m/z): 276.12 (M+).

5-Ethoxycarbonyl-6-methyl-4-(4-nitrophenyl)-3,4-dihydropyrimidin-2(1H)-one (5k)

White crystals: m.p 207-209°C; IR (KBr) umax: 3236.8 (NH), 3117.62 (NH), 2980.68 (C-H aliphatic), 1702.12 (C=O), 1643.98, 1460.69 (C=C aromatic), 1347.77,1093.14 (C-O) cm-1; 1H NMR (DMSO-d6,400 MHz): 5 1.2 (t, J=7.2 Hz, 3H, CH3), 2.3 (s, 3H, CH3), 4.1(q, J=7.2 Hz, 2H, CH2), 5.5 (s, 1H, CH), 7.5 (d, J=8.4 Hz, 2H, Ar-H), 8.2 (d, J=8.4 Hz, 2H, Ar-H), 7.7(s, 1H, NH), 5.8 (s, 1H, NH) ppm. 13CNMR (DMSO-d6, 100MHZ): 5 14.25, 18.79, 56.03, 60.22, 101.65, 118.21, 130.42, 138.39, 152.33, 153.47, 159.24, 165.91 ppm. Anal. calcd. for C14H15N3O5. C, 53.33; H, 4.76, N, 16.51; Found: C, 55.08; H, 4.79; N, 13.77; Found: C, 55.12; H, 4.71; N, 13.75. MS (m/z): 305.35(M+).

ound: C, 5

.95 (NH),

7,7-dimethyl-4-phenyl-3,4,7,8-tetrahydroquinazoline-2,5(1H,6H)-dione (6l)

Yellow crystals: m.p 287-289°C; IR (KBr) umax: 3317.72 (NH), 3257.95 (NH), 2961.52 (C-H aliphatic), 1706.17 (C=O),1672.55 (C=O), 1607.95, 1444.68(C=C aromatic) cm-1; 1H NMR (DMSO-d6,400 MHz): 5 0.86 (S, 3H, CH3), 0.99 (S, * CH, 2.°, ^ „ CH. 2 24 * 2H CH, „ * ™ H. ,H. CH. ,,0 » ,H. CH, 7^J0 * 5* Ar-H), 7.74 (S, 1H, NH), 9.45 (S, 1H, NH); 13C NMR (DMSO-d6, 100 MHz,): 5 27.3, 29.22, 32.75, 50.28, 52.43, 107.86, 126.69, 127.58, 128.76, 145.09, 152.39, 152.84, 193.32 ppm. Anal. Calcd for C16H18N2O2: C, 71.11; H, 6.67; N, 10.37; Found: C, 71.08; H, 6.61; N 10.32. MS (m/z): 270.21(M+)

7,7-Dimethyl-4-(3-nitro-phenyl)-4,6,7,8-tetrahydro-1.ff,3#-quinazoline-2,5-dione (6m)

White crystals: m.p 295-297°C; IR (KBr) umax: 3353.25 (NH), 3228.50 (NH), 2959.50 (C-H aliphatic), 1702.39 (C=O),1628.51 (C=O), 1528.89, 1475.39 (C=C aromatic) cm-1; 1H NMR (DMSO-d6,400 MHz): 5 0.87 (S, 3H, CH3), 1.0(S, 3H,CH3), 2.09 (d, J=9.6 Hz, 1H,CH2), 2.22 (d, J=9.6 Hz, 1H, CH2), 2.30 (d, J=10.13 Hz, 1H, CH2), 2.45 (d, J=10.13 Hz, 1H, CH2), 5.30 (S, 1H, CH), 7.67 (m, 2H, Ar-H), 7.94 (S, 1H, NH), 8.9 (m, 4H, Ar-H), 9.65 (S, 1H, NH) ppm. 13C NMR (DMSO-d6, 100 MHz,): 5 19.11, 25.23, 27.32, 30.67, 30.75, 36.94, 48.43, 50.26, 107.12, 124.68, 127.78, 135.16, 138.98, 146.89, 172.88, 192.12 ppm. Anal. Calcd. for C16H17N3O4: C, 60.95; H, 5.40; N, 13.33; Found: C, 60.92; H, 5.36; N, 13.29. MS (m/z): 315.19(M+).

7,7-Dimethyl-4-phenyl-2-thioxo-2,3,4,6,7,8-hexahydro-1.ff- quinazolin-5-azone (6n)

Yellow crystals: m.p 280-282°C; IR (KBr) umax: 3260.67 (NH), 3177.45 (NH), 2958.62 (C-H aliphatic), 1621.11 (C=O), 1567.03, 1459.08 (C=C aromatic) cm-1; 1H NMR (DMSO-d6, 400 MHz): 5 0.86 (3H, S, CH3), 1.0 (3H, S, CH3), 2.06 (1H, d, J=9.45Hz, CH2), 2.19 (1H, d, J=9.45 Hz, CH2), 2.48 (2H, m, CH2), 5.15 (1H, S, CH), 7.18-7.32 (5H, m, Ar-H), 9.69 (1H, S, NH), 10.59(1H, S, NH) ppm. 13C NMR (DMSO-d6, 100 MHz,): 5 26.69, 28.81, 32.04, 49.92, 51.86, 108.12, 126.48, 127.53,

128.65, 143.58, 148.48, 174.86, 193.52 ppm. Anal. Calcd. for C16H18N2OS: C, 67.13; H, 6.29; N, 9.80; Found: C, 67.10; H, 6.33; N, 9.77. MS (m/z ): 286.57(M+).

4-(4-Chloro-phenyl)-7,7-dimethyl-4,6,7,8-tetrahydro-1#,3#-quinazoline-2,5-dione (6o)

White crystals: m.p 297-299°C; IR (KBr) umax: 3321.44 (NH), 3246.52 (NH), 2960.74 (C-H aliphatic), 1707.62 (C=O), 1674.60 (C=O), 1615.46, 1445.43 (C=C aromatic) cm-1; 1H NMR (DMSO-d6, 400 MHz): 5 0.85 (S, 3H, CH3), 0.99(S, 3H, CH3), 2.02 (d, J=4.6 Hz, 1H, CH2), 2.19 (d, J=4.6 Hz, 1H, CH2), 2.26 (d, J=13.6 Hz, 1H, CH2), 2.41 (d, J=13.6 Hz, 1H, CH2), 5.13 (S, 1H, CH), 7.37 (m, 4H, Ar-H), 7.8 (s, 1H, NH), 9.53 (S, 1H, NH) ppm. 13C NMR (DMSO-d6, 100 MHz,): 5 16.34, 27.12, 47.34, 48.15, 53.92, 114.12, 128.75, 132.36, 140.54, 142.16, 157.64, 198.32 ppm. Anal. Calcd for C16H17ClN2O2: C, 63.05; H, 5.62; N, 9.19; Found: C, 62.97; H, 5.58; N, 9.20. MS (m/z ): 305.11(^

7,7-Dimethyl-2-thioxo-4-p-tolyl-2,3,4,6,7,8-hexahydro-1^-quinazolin-5-one (6p)

Yellow crystals: m.p 297-299°C; IR (KBr) umax: 3231.30 (NH), 3166.47 (NH), 2957.69 (C-H aliphatic), 1629.57 (C=O), 1571.08, 1460.45 (C=C aromatic) cm-1; 1H NMR (DMSO-d6, 400 MHz): 5 0.85 (S, 3H, CH3), 0.99(S, 3H, CH3), 2.04 (d, J=5.81 Hz, 1H, CH2), 2.18 (d, J=5.81 Hz, 1H, CH2), 2.23 (s, 3H, CH3), 2.44 (m, 2H, CH2), 5.15 (S, 1H, CH), 7.1 (m, 4H, Ar-H),9.64 (s, 1H, NH), 10.54 (S, 1H, NH) ppm. 13C NMR (DMSO-d6, 100 MHz,): 5 19.12, 25.16, 27.32, 30.71, 36.93, 48.27, 51.06, 107.12, 124.75, 135.13, 138.95, 147.18, 173.18, 192.10 ppm. Anal. Calcd. for C17H20N2OS: C, 68.00; H, 6.67; N, 9.33; Found: C, 67.96; H, 6.64; N, 9.35. MS (m/z ): 300.24(M+).

7,7-Dimethyl-4-p-tolyl-4,6,7,8-tetrahydro-1^, 3H-quinazoline-2,5-dione (6q)

Yellow crystals: m.p 300°C; IR (KBr) umax: 3253.33 (NH), 2959.10 (C-H aliphatic), 1709.05 (C=O), 1674.95 (C=O),1614.96-1479.95 (C=C aromatic) cm-1; 1H NMR (DMSO-d6, 400 MHz): 5 0.86 (S, 3H, CH3), 0.99(S, 3H, CH3), 1.97 (d, J=10.88 Hz, 1H, CH2), 2.18 (m, 2H, CH2), 2.23 (s, 3H, CH3), 2.4 (d, J=10.88 Hz, 1H, CH2), 5.07 (S, 1H, CH), 7.08 (m, 4H, Ar-H), 7.72 (s, 1H, NH), 9.43 (S, 1H, NH) ppm. 13C NMR (DMSO-d6, 100 MHz,): 5 17.00, 21.15, 27.32, 47.32, 48.16, 53.78, 114.34, 127.56, 130.23, 136.62, 139.95, 142.58, 157.45, 198.21 ppm. Anal. Calcd. for C17H20N2O2: C, 71.83; H, 7.04; N, 9.86; Found: C, 71.80; H, 7.11; N, 9.84. MS (m/z ): 284(M+).

3. Results and discussion

The characterization of the catalyst was carried out by FTIR, elemental analysis (CHNS), SEM and TGA techniques. FTIR spectrum of magnetite nanoparticles is presented in Figure 1a. O-H stretching vibration at 3398.49 cm-1, O-H bending vibration near 1624.47 cm-1 and also the Fe-O stretching vibration at about 582.67 cm-1, were observed in this pattern. The FT-

IR spectrum of meglumine (Figure 1b) shows a broad band at 3331.74 and 3249.30 cm-1 which corresponds to the stretching vibrations of N-H and O-H groups. Peaks appeared at 2916.16 cm-1 and 2854.21 cm-1 are from C-H stretching vibrations. The bands at 1633.74 is assigned to N-H bending vibration. The bands at 1048.09 and 1238.66 cm-1 displays the stretching vibration of the C-O and C-N bonds respectively.

FTIR of Fe3O4@meglumine display in Figure 1c. From the comparison between 1a and 1c spectra, it is clearly observed that most of main signes in FTIR of meglumine, existed in 1c spectrum and this proved that meglumine was chemically attached to the magnetic nanoparticle surfaces. On the other hand, the stretching vibrations of Si-C and Si-O was appeared at 1245 and 1035 cm-1 respectively and covered with absorbtion peaks of C-O and C-N groups of meglumine (attached on magnetic nanoparticle).

The FTIR spectra of Fe3O4@MSA is presented in 1d. The broad peak at 3321.55 cm-1 assigned to acidic O-H stretching vibration. Also absorption peaks at 1198.25 cm-1, 1035.2 cm-1 and 662.49 cm-1 are from S=O and S-O groups respectively. These results confirmed that Fe3O4@MSA was prepared successfully.

Furthermore, FTIR consequences were further confirmed with other chracterization methods include VSM, elemental analysis (CHNS), XRD, TGA and SEM techniques.

Magnetic properties of Fe3O4 nanoparticles and Fe3O4@MSA were measured by VSM method at room temperature (Fig. 2). Specific magnetization versus applied magnetic field curve of Fe3O4@MSA indicates a saturation magnetization value of 20 emug-1, that is lower than that of the bare magnetic nanoparticles (33 emug-1) due to modification with meglumine sulfate. This result could be attributed to the surface spin effect on Fe3O4 nanoparticles caused by modification, which subsequently

decrease the saturation

magnetiza

ization value.

Fig. 2

Thermo gravimetric analysis (TGA) was used to determine the percent of organic functional groups attached onto the surfaces of the magnetic nanoparticles (Fig 3). The TGA curve of Fe3O4@MSA shows a weight loss of about 5% below 200oC which is related to the removal of water. The weight loss of 20% appearing from 200 to 800 °C, is attributed to thermal decomposition of meglumine sulfionic acid molecules attached on Fe3O4 nano particles.

Fig. 3

To confirm the crystalline structure of Fe3O4 nanoparticles and modified nano Fe3O4, XRD analysis was applied. As shown in Figure 4, it is clearly seen that main peaks at 29 value of 27.36°, 36.03°, 46.18°, 56.77° and 62.95° assign to 200, 311, 400, 422 and 511 Bragg reflection, are according to standard pattern for crystalline magnetite with spinel structure. The average

diameter of nano particles was about 73 nm which was calculated from Debaye Scherrer's equation. Also, it is concluded that the chemical process of modification did not influence on the crystality, diameter and structure of magnetic nanoparticles.

Fig. 4

Figure 5 presented the SEM images of Fe3O4 nanoparticles and Fe3O4@MSA. According to SEM images, Fe3O4 nano particles have mean size about 75 nm with a good distribution. SEM image of Fe3O4@MSA show that the meglumine sulfonic acid layer attached on nanoparticle surfaces, is very thin due to the particle size of modified magnetite nanoparticles is not larger than raw Fe3O4. These results are in agreement with the XRD patterns.

Fig. 5

In order to complete the characterization of solid acid catalyst, elemental analysis was applied. Obtained percentages of carbon, hydrogen, nitrogen and sulfur contents of Fe3O4@MSA were 10.66, 9.28, 1.35, and 28.8 respectively. These results confirmed the functionalization of Fe3O4 nanoparticles with meglumine sulfonic acid.

After Characterization and demonstrated the structure and morphology of nano solid acid catalyst, we examined the efficiency of obtained solid catalyst in synthesis of 3,4-DHP derivatives under microwave irradiation.

Initially, the reaction of 4-nitrobenzaldehyde (1mmol), ethyl acetoacetate (1mmol) and urea (1.2 mmol) was mentioned as model reaction. A solvent effect on reaction was examined along with catalyst amounts. Based on the results in Table 1, 0.025 g of Fe3O4@MSA was considered as the optimum amount of catalyst in EtOH/H2O as solvent.

Table 1.

After the optimization of solvent and catalyst amount, we further examined the effects of the microwave power on the yield of the reaction. From obtained results depicted in Table 2, optimized power of microwave oven was 400W (entry 4) at 80°C.

Table 2

Regarding to the obtained desiered reaction conditions, we developed the presented method for the reaction between benzaldehyde derivatives, ethyl acetoacetate (or dimedone) and urea (or thiourea) in the presence of optimum amount of ctalyst. As shown in Table 3, products have high to excellent yields both in case of aldehydes bearing electron donating and electron withdrawing groups in short times. On the other hand, the yield of reaction using aldehydes containing electron withdrawing group in para position, was the best. Products were characterized using physicsl and spectroscopic methods such as melting point, :HNMR and 13CNMR techniques.

Table 3

The efficiency of Fe3O4@MSA in compare with nano Fe3O4, meglumine, meglumine sulfate, Fe3O4@meglumine and some of reported acid functionalized Fe3O4 nanoparticles in thermal and microwave conditions was studied. As shown in Table 4, the highest yield of the reaction was achieved in the presence of Fe3O4@MSA in a short time both in thermal and

microwave irradiation (entry 4). In Presented method, we try to convert the high efficient homogeneous catalyst (meglumine sulfate [32]) to heterogeneous one (Fe3O4@MSA) with a lot of sulfonated groups, good reusability and high yield of product in short time of reaction.

Table 4

A plausible mechanism for the formation of 3,4-DHPs is shown in Scheme 3. Fe3O4@MSA has a main role in reaction, by activating the aldehyde (1). This is followed by nucleophilic addition of urea to forming the intermediate (2). Then, this intermediate absorbed a proton from solid acid catalyst and in continue, interacts with ethyl acetoacetate enol form to produce an open chain intermediate (3), which is followed by cyclization and dehydration to afford 3,4-DHP (Sche me 3).

Scheme 3

4-DHP (S

Finally, the reusability of catalyst was examined. In this way, the model reaction was performed under optimal conditions. After the complition of reaction, the catalyst was separated, washed with ethanol, dried and reused in next reaction. The recycling was repeated four times. Results in Figure 6 demonstrated that the catalyst have high efficiency even after 4 step reused.

Fig. 6

Conclusion

In conclusion, a facile and efficient procedure for the synthesis of 3,4-dihydropyrimidinone/ thiones has been prepared using Fe3O4@MSA as an environmental friendly solid acidic organocatalyst under microwave condition. The noticeable benefits of this methodology are reusability of catalyst, easy workup procedure, being safe and clean and having good to high yields of the final products.

lity of ca

/ nling, I. Ug

Biginelli, Syntl f. U. May

References

[1] A. Dömling, I. Ugi, Multicomponent reactions with isocyanides, Angew. Chem. Int. Ed. 105 (2000) 3168-3210.

[2] P. Biginelli, Synthesis of 3,4-dihydropyrimidin-2(1H)-ones, Gazz. Chim. Ital. 23 (1893) 360-413.

[3] T. U. Mayer, T. M. Kapoor, S. J. Haggarty, R. W. King, S. L. Schreiber, T. J. Mitchison, Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen, Science. 286 (1999) 971-974.

[4] Z. Maliga, T. M. Kapoor, T. Mitchison, Evidence that monastrol is an allosteric inhibitor of the mitotic kinesin Eg5, J. Chem. Biol. 9 (2002) 989-996.

[5] J. C. Barrow, P. G. Nantermet, H. G. Selnick, K. L. Glass, K. E. Rittle, K. F. Gilbert, T. G, Steele, C. F. Homnick, R. M. Freidinger, R. W. Ransom, P. Kling, D.Reiss, T. P. Broten, T.W. Schorn, R.S. Chang, S. S. O'Malley, T. V. Olah, J. D. Ellis, A. Barrish, K. Kassahun, P. Leppert, D. Nagarathnam, C. Forray, In vitro and in vivo evaluation of dihydropyrimidinone C-5

amides as potent and selective aiA receptor antagonists for the treatment of benign prostatic hyperplasia, J. Med. Chem. 43 (2000) 2703-2718.

[6] C. Goldstein, J. C. Schroeder, J. P. Fortin, J. M. Goss, S.E. Schaus, M. Beinborn, A.S. Kopin, Two Naturally Occurring

Mutations in the Type 1 Melanin-Concentrating Hormone Receptor Abolish Agonist-Induced Signaling, J. Pharm. Exp. Ther.

335 (2010) 799-806.

[7] K. S. Atwal, B. N. Swanson, S. E. Unger, D. M. Floyd, S. Moreland, A. Hedberg, B. C. O'Reilly, Dihydropyrimidine calcium channel blockers 3,3-carbamoyl-4-aryl-1,2,3,4-tetrahydro-6-methyl-5-pyrimidinecarboxylic acid esters as orally effective antihypertensive agents, J. Med. Chem. 34 (1991) 806-811.

8. M. Matache, C. Dobrota, N. D. Bogdan, I. Dumitru, L. L. Ruta, C. C. Paraschivescu, I. C. Farcasanu, I. Baciu, D. P. Funeriu, Synthesis of fused dihydro-pyrimido[4,3-^]coumarins using Biginelli multicomponent reaction as key step, Tetrahedron, 65 (2009) 5949-5957.

9. Y. X. Da, Z. Zhang, Z. J. Quan, Intermolecular cyclocondensation reaction of 3,4- dihydropyrimidine-2-thione under the Mitsunobu reaction conditions, Chin. Chem. Lett. 22 (2011) 679-682.

10. T. N. Akhaja, J. P. Raval, synthesis, in vitro evaluation of tetrahydropyrimidine-isatin hybrids as potential antibacterial, antifungal and anti-tubercular agents, Chin. Chem. Lett. 23 (2012) 446-449.

11. S. Rostamnia, K. Lamei, Diketene-based neat four-component synthesis of the dihydropyrimidinones and dihydropyridine backbones using silica sulfuric acid (SSA), Chin. Chem. Lett. 23 (2013) 930-932.

12. M. M. Heravi, N. Karimi, H. Hamidi, H. A. Oskooie, Cu/SiO2: A recyclable catalyst for the synthesis of octahydroquinazolinone, Chin. Chem. Lett. 24 (2013) 143-144.

13. K. K. Pasunooti, H. Chai, C. N. Jensen, B. K. Gorityala, S. Wang, X. W. Liu, A microwave-assisted, copper-catalyzed three-component synthesis of dihydropyrimidinones under mild conditions, Tetrahedron Lett. 52 (2011) 80-84.

14. J. T. Li, J. F. Han, J. H. Yang, T. S. Li, An efficient synthesis of 3, 4-dihydropyrimidin-2-ones catalyzed by NH2SO3H under ultrasound irradiation, Ultrason. Sonochem. 10 (2003) 119-122.

15. R. Pagadala, S. Maddila, S. B. Jonnalagadda, Eco-efficient ultrasonic responsive synthesis of pyrimidines/pyridines, Ultrason. Sonochem. 21 (2014) 472-477.

16. H. Kiyani, M. Ghiasi, Solvent-free efficient one-pot synthesis of Biginelli and Hantzsch compounds catalyzed by potassium phthalimide as a green and reusable organocatalyst, Res. Chem. Intermed. 41 (2015) 5177-5203.

17. A. Shaabani, A. Bazgir, F. Teimouri, Ammonium chloride-catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2-(1H)-ones under solvent-free conditions, Tetrahedron Lett. 44 (2003) 857-859.

18. A. S. Paraskar, G. K. Dewkar, A. Sudalai, Cu(OTf)2: a reusable catalyst for high-yield synthesis of 3,4-dihydropyrimidin-2(1H)-ones, Tetrahedron Lett. 44 (2003) 3305-3308.

19. F. Tamaddon, S. Moradi, Controllable selectivity in Biginelli and Hantzsch reactions using nano ZnO as a structure base catalyst, J. Mol. Catal. A 370 (2013) 117-122.

20. J. Safari, Z. Zarnegar, Bransted acidic ionic liquid based magnetic nanoparticles: a new promoter for the Biginelli synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones, New. J. Chem. 38 (2014) 358-365.

21. D. Elhamifar, F. Hosseinpoor, B. Karimi, S. Hajati, Ionic liquid-based ordered mesoporous organosilica-supported copper

as a novel and efficient nanocatalyst for the one-pot synthesis of Biginelli products, Micropor. Mesopor. Mat. 204 (2015) 269275.

22. L. Moradi, G. R. Najafi, H. Saeidiroshan, New method for preparation of MWCNT-SO3H as an efficient and reusable

catalyst for the solvent-free synthesis of 3,4-dihydropyrimidin-2(1^)-ones/thiones, Iranian J. Catal. 5 (2015) 357-364.

23. F. Zamani, E. Izadi, Synthesis and characterization of sulfonated-phenylacetic ac id coated Fe3O4 nanoparticles as a novel acid magnetic catalyst for Biginelli reaction, Catal. Commun. 42 (2013) 104-108.

24. E. Kolvar, N. Koukab, O. Armandpour, A simple and efficient synthesis of 3,4-dihydropyrimidin-2-(1H)-ones via Biginelli reaction catalyzed by nanomagnetic-supported sulfonic acid, Tetrahedron. 70 (2014) 1383-1386.

25. A.R. Kiasat, J. Davarpanah, Fe3O4@Silica sulfuric acid core-shell composite as a novel nanomagnetic solid acid: synthesis, characterization and application as an efficient and reusable catalyst for one-pot synthesis of 3,4-dihydropyrimidinones/thiones under solvent-free conditions, J. Res. Chem. Intermed. 41 (2015) 2991- 3001.

26. T. Boumoud, B. Boumoud, S. Rhouati, A. Belfaitah, A. Debache, P. Mosset, A Novel Catalyst for One-Pot Synthesis of Substituted 3,4-Dihydropyrimidin-2-(1H)-ones via Biginelli Reaction Under Solvent-Free Conditions, Acta. Chim. Slov. 55, (2008) 617-622.

in-2-(1H)

uan, J. T. Wan uan, J. T. Wan

27. M. L. Pang, Y. F. Yuan, J. T. Wang, Indium(III)tribromide: An Excellent Catalyst for Biginelli Reaction, Chin. Chem. Lett. 13 (2002) 921-922

28. T. Boumoud, B. Boumoud, S. Rhouati, A. Belfaitah, A. Debache, P. Mosset, An efficient and recycling catalyst for the one-pot three-component synthesis of substituted 3,4-dihydropyrimidin-2(1H)-ones, E. J. Chem. 5 (2008) 688-695.

29. R. J. Kalbasi, A. M. Massah, R. D. Daneshvarnejad, Preparation and characterization of bentonite/PS-SO3H nanocomposites as an efficient acid catalyst for the Biginelli reaction, Appl. Clay. Sci. 55 (2012) 1-9.

30. S. Kirti, B. Bapurao, S. Murlidhar, Microwave-assisted one-pot synthesis of octahydroquinazolinone derivatives using ammonium metavanadate under solvent-free condition, Tetrahedron Lett. 51 (2010) 3616-3618.

31. A. Shaabani, A. Sarvary, A. Rahmati, A. H. Rezayan, ionic liquid/silica sulfuric acid promoted fast synthesis of a Biginelli-Like scaffold reaction, Lett. Org. Chem. 4 (2007) 68-71.

32. L. Moradia, K. Rabieib, F. Belali, Meglumine sulfate catalyzed solvent-free one-pot synthesis of coumarins under microwave and thermal conditions, Synth. Commun. 46 (2016) 1283-1291.

Table 1. Effect of the solvents and Fe3O4@MSA amounts on the yield of 5ka

10 11 12

+ HNANH Fe3O4@MSA EtO ^H (5k)

Entry Catalyst (g)

Solvent

Time (s) Yield (%)b

0.01 EtOH 60

0.01 EtOH/H2O (1:1) 50

0.01 MeOH 60

0.01 CH3CN 60

0.015 EtOH 50

0.015 EtOH/H2O (1:1) 40

0.015 MeOH 50

0.02 EtOH 40

0.02 EtOH/H2O (1:1) 50

0.025 EtOH 40

0.025 EtOH/H2O (1:1) 40

0.03 EtOH/H2O (1:1) 40

75 88 80 72

91 98 95

4-Nitrobenzaldehyde (1mmol), ethyl acetoacetate (1mmol), urea (1.2 mmol) in 5 ml of solvent, under MW irradiation (400 w) and 80 °C. [b] Isolated yield

Table 2. Table 2. Effects of the microwave power on the formation of 5ka

Entry Power (w) Time (sec) Yield (%)b

1 300 40 86

2 300 60 90

3 400 30 93

4 400 40 98

5 600 40 94

)MSA in 5

[a] 4-Nitrobenzaldehyde (1mmol), ethyl acetoacetate (1mmol), urea (1.2 mmol) in the presence of 0.025 g of Fe3O4@MSA in 5 ml EtOH/H2O and 80°C.

[b] Isolated yield

Table 3. Synthesis of 3,4-DHPs using Fe3O4@MSA under microwave irradiation3

EtO 'NH

li Fe3O4@ MSA

• H2N nh2 MW

X=O, S

MSA: Meglumine sulfonic acid

Product

ß-Dicarbonyl Time (s) Yield (%)b

m.p (°C)

5a 5b 5c 5d 5e 5f 5g 5h 5i

5k 61 6m 6n 6o 6p 6q

p-Cl O,p-Cl2 P-Ome P-OH p-Me 2-Thiopheny1c o-Me m-NO2 H H

p-NO2d

H m-NO2

H p-Cl p-Me p-Me

O O O O O O S O O S O O O S O S O

85 115 100 90 95 110 100 75 50 70 40/110' 60 90 75 160 220 200

95 90 95 95

96 98/95

95 94 94

210-212 [26] 249-251 [26] 203-205 [26] 228-229 [26]

212-214 [26]

213-215 [27] 191-193 [28] 223-225 [29] 203-205 [26] 205-207 [26] 207-209 [22] 287-289 [29] 295-297 [30] 280-282 [30] 297-299 [30] 297-299 [31]

300 [31]

[a] benzaldehyde derivative (lmmol), ß-diketone (1mmol) and urea or thiourea (1.2 mmol) in 5 ml EtOH/H2O under MW irradiation (power of 400 w and 80 °C).

[b] Isolated Yeild

[c] 2-thiophenal was applied as aldehyde

[d] 10 mmol of aldehyde, 10 mmol ethylacetoacetate, 12 mmol of urea in 40 ml EtOH/H2O was applied under MW irradiation with power of 400 w and 80°C.

Table 4. Comparison of Fe3O4@MSA and several catalysts in thermal and microwave conditiona for synthesis of

Thermal condition

Microwave conditionc

Catalyst

Time (h) Yield (%)b Time (s) Yield (%)d/Ref.

1 meglumine sulfonic acid 1.30 92 50 92

2 Nano Fe3O4 8 71 300 85

3 Fe3O4@meglumine 11 50 300 56

4 Fe3O4@MSA 1.30 96 40 98

5 meglumine 18 67 300 42

6 Nano-y-Fe2O3@SO3H 3.30 82 30 95 [24]

7 Fe3O4@silica sulfuric acid 25 min 92 - - [25]

8 Fe3O4@PAA-SO3He 115 92 - - [23]

tiated-ph

tid 80°C

l acetoace

[a] 4-nitrobenzaldehyde (1mmol), ethyl acetoacetate (1mmol) and urea (1.2 mmol) in 5 ml EtOH/H2O using optimized amount of every catalyst.

[b] 100°C

[c] Power of 400w and 8

[d] Isolated yield

[e] sulfonated-phenylacetic acid coated Fe3O4

EtO NH

, H2N NH2

Fe3O4@ MSA

5(a-k)

X=O, S

MSA: Meglumine sulfonic acid

6(l-q)

Scheme 1

Eta TT NH

Me^-N^o

|| "j H Fe3O4@MSA

H U . -H2O

h2n nh2

l_l Fe3O4@MSA

-H2O O H I Cyclization

Me^N^O HO NH O

Me OEt

Q. „ OK, Me

N NH2 H2

Scheme 3

•i ' ------- x

Fig. 2

Fig. 3

Fig. 5

Fig. 6

Figures and schemes Captions:

Scheme 1. Synthesis of 3,4-DHPs using FesO4@MSA

Scheme 2. Schematic process for the preparation of Fe3O4@MSA

Scheme 3. A plausible mechanism for the Biginelli reaction in the presence of Fe3O4@MSA Figure 1. FTIR of: a) Fe3O4 nanoparticles, b) meglumine, c) Fe3O4@meglumine and d) Fe3O4@MSA Figure 2. Magnetic curve of a) Fe3O4 nanoparticles and b) Fe3O4@MSA Figure 3. TGA curves of Fe3O4 nanoparticles and Fe3O4@MSA Figure 4. XRD patternes of a) nano Fe3O4 and b) Fe3O4@MSA Figure 5. SEM image of: a) Fe3O4 and b) Fe3O4@MSA nanoparticles Figure 6. Reusability of Fe3O4@MSA in the Biginelli reaction on the synthesis of 5

s of 5k f