Bis sulfamic acid functionalized magnetic nanoparticles as a retrievable nanocatalyst for the green synthesis of polyhydroquinolines and tetrahydrobenzopyrans

Document Type : Research Paper

Author

1 Department of Chemistry, Faculty of Science, Arak University, Arak, Iran

2 Institute of Nanosciences and Nanotechnolgy, Arak University, Arak, Iran

Abstract

Synthesis of bis sulfamic acid-grafted on silica-coated nano-Fe3O4 particles (MNPs-TBSA) as a novel core/shell hybrid organic-inorganic magnetic nanostructures, and their performance as a retrievable heterogeneous acidic catalyst is disclosed. The catalytic performance of this novel material was studied for the green synthesis of pharmaceutically valuable polyhydroquinoline and tetrahydrobenzopyran derivatives via one-pot multi-component condensation of aryl aldehydes, dimedone, ethyl acetoacetate, malononitrile and ammonium actate in ethanol as a solvent and at 70 º C. Eco-friendly method, high yield and purity of the desired products, short reaction time along with the ease of the workup procedure outlines the advantages of these new methodologies over the earlier ones. Surface and magnetic properties of the core/shell hybrid nanoparticles were characterized via field emission scanning electron microscopy (FE-SEM), X-ray diffraction measurements (XRD), the energy dispersive X-ray spectroscopy (EDS), FT-IR spectroscopy and vibrating sample magnetometer (VSM). The crystallite size of the magnetic nanoparticle is calculated to be 15.5 nm.

Keywords


INTRODUCTION

1,4-Dihydropyridyl compounds (1,4-DHPs) are valuable heterocyclic compounds in view of pharmaceuticals and drugs development [1]. 1,4-DHPs possess a wide range of biological activities such as anti-atherosclerotic, vasodilator, anti-diabetic, geroprotective, hepatoprotective and the treatment of hypertention and cardiovascular diseases [2-6]. 4H-Pyran compounds present a broad range of biological and pharmacological properties such as anticancer, anti-HIV, anti-inflammatory, anti-microbial, anti-malarial, anti-hyperglycaemic and anti-dyslipidemic activity [7-13]. Realizing the importance of 1,4-dihydropyridyl compounds and 4H-pyran derivatives, increasing interest on synthetic methods of these compounds is ongoing. The classical method for polyhydroquinoline synthesis involves a three-component coupling of an aldehyde, dicarbonyl compounds, and ammonia in acetic acid or in refluxing ethanol for long reaction times which typically leads to low yields [14-16]. Traditional processes for 4H-pyran synthesis were reported as the reaction of active methylene compounds with an aldehyde or ketone in the presence of an organic base such as piperidine or triethylamine under reflux and multiple-step conditions [17]. In recent years, several modified synthesis methods to access polyhydroquinolines [18-28], and 4H-benzo[b]pyrans [29-36], have been developed. Although some reactions are satisfactory in terms of yield, but the use of high temperatures, expensive metal precursors, catalysts that are harmful to the environment, long reaction times, harsh reaction conditions, effluent pollution and tedious workup procedures are drawbacks of these methods.

Nanotechnology is beginning to allow scientists, engineers, chemists, and physicians to work at the molecular and cellular levels to produce important advances in the life sciences and healthcare. The uses of synthetic nanomaterials have increased the scope of their application in areas of medical diagnostics, areas of material modification, degradation of environmental pollutants, chemical reaction catalysis and biotechnology [37, 38]. These widespread applications results to the necessity of nanomaterials modification into different structure with desirable features.

Organic-inorganic hybrid materials are of great interest as heterogeneous catalysts in organic synthesis, due to the functional diversity merged with thermal and mechanical stability of inorganic solids [39]. Their large surface area per unit volume, makes them interesting in the heterogeneous catalysis area; Heterogeneous catalysis in the nano-scale takes advantage of a high exposure of the active species leading to a higher efficiency of the catalyst [40]. Nevertheless, the application of heterogeneous nanocatalysts are usually limited by the inevitable loss of catalyst during the tedious separation processes, i.e. filtration or centrifugation. In this vein, easily separable magnetic nanoparticles (MNPs), e.g. Fe3O4, have demonstrated high stability, easy synthesis and functionalization alongside with high surface area, low toxicity and cost. These superb properties set magnetic nanoparticles as a target for extensive investigation as inorganic supports in the synthesis of semi-heterogeneous catalysts [41]. These metallic nanoparticles can be coated with silica shell to introduce numerous surface Si–OH groups for further modification and higher chemical and colloidal stability since the magnetically agglomeration will be diminished [42].

For the above reasons and as a part of our works on design and development of novel heterogeneous catalysts and green chemical methods [43-47], we describe the synthesis and characterization of bis-sulfamic acid-grafted magnetic nanoparticles (MNPs-TBSA) to give access to biologically interesting polyhydroquinolines and 4H-benzo[b]pyrans as a new eco-friendly method (Fig. 1). This novel designed catalyst provided a heterogeneous system with a green synthetic aspects by avoiding the use of hazardous conditions for accessing target heterocyclic compounds.

MATERIALS AND METHODS

All chemicals were purchased from Merck or Acros chemical companies and used without further purification. Melting points were measured by using capillary tubes on an electro thermal digital apparatus and are uncorrected. Known products were identified by comparison of their spectral data and melting points with those reported in the literature. Thin layer chromatography (TLC) was performed on UV active aluminum backed plates of silica gel (TLC Silica gel 60 F254). 1H and 13C NMR spectra were recorded on a Bruker Avance 300 MHz spectrometer at 300 MHz and 75 MHz, respectively. Coupling constants, J, were reported in hertz unit (Hz). IR spectra were recorded on a Unicom Galaxy Series FT-IR 5030 spectrophotometer using KBr pellets and are expressed in cm-1. Elemental analyses were performed by Vario EL equipment at Arak University. X-ray diffraction (XRD) was performed on Philips XPert (Cu-Kα radiation, λ = 0.15405 nm) over the range 2θ = 20-80° using 0.04° as the step length. Thermal gravimetric analysis (TGA) and differential thermal gravimetric (DTG) data for MNPs-TBSA were recorded on a Mettler TA4000 System under an N2atmosphere at a heating rate of 10 °C min-1. The scanning electron microscope measurement was carried out on a Hitachi S-4700 field emission-scanning electron microscope (FE-SEM).

General procedure for the synthesis of polyhydroquinolines

A mixture of dimedone (1 mmol), ethylaceto-acetate (1 mmol), aldehyde (1 mmol), ammonium acetate (1.2 mmol) and MNPs-TBSA (30 mg) as catalyst in 5 mL EtOH was heated at 70 °C and were stirred for appropriate time. After completion of the reaction as followed by TLC, the resulting solidified mixture was diluted with hot EtOH (15 mL). Then, the catalyst was separated using an external magnet, the solvent was evaporated, and the product was recrystallized with EtOH/H2O (4:1), and dried in an oven at 90 °C (Table 2).

General procedure for the synthesis of 4H-benzo[b]pyrans

A mixture of an aromatic aldehyde (1 mmol), malononitrile (1 mmol), dimedone (1 mmol) and MNPs-TBSA (30 mg) as catalyst in 5 ml EtOH was heated at 70 °C with stirring for an appropriate time. The resulting solidified mixture was diluted with hot EtOH (15 mL). Then, the catalyst was separated using an external magnet, the solvent was evaporated, and the product was recrystallized with EtOH/H2O (4:1), and dried in an oven at 90 °C (Table 4).

Selected data for desired products

6a: IR (KBr) (νmax): 3288, 2962, 1699, 1610, 1485, 1381,1211,1072 cm-11H NMR (300 MHz, DMSO-d6): δH: 0.84 (3H, s, CH3), 1.00 (3H, s, CH3), 1.13 (3H, t, J = 7.1 Hz, CH3), 2.14–2.50 (4H, m, CH2), 3.97 (2H, q, J = 7.1 Hz, CH2), 4.84 (1H, s, CH), 7.03–7.20 (5H, m, HAr), 9.07 (1H, s, NH) ppm. Anal. Calcd for C21H25NO3: C, 74.31; H, 7.42; N, 4.13. Found C, 74.63; H, 7.67; N, 4.27.

6f: IR (KBr) (νmax): 3280, 3217, 3065, 2951, 1695, 1637, 1608, 1489, 1381, 1263, 1210, 1092 cm-11H NMR (300 MHz, DMSO-d6): δH: 0.82 (3H, s, CH3), 1.00 (3H, s, CH3), 1.12 (3H, t, J = 7.0 Hz, CH3), 1.94–2.44 (4H, m, CH2), 2.29 (3H, s, CH3), 3.96 (2H, q, J = 7.0 Hz, CH2), 4.82 (1H, s, CH), 7.08–7.39 (4H, m, HAr), 9.12 (1H, s, NH) ppm. Anal. Calcd for C21H24BrNO3: C, 60.29; H, 5.78; N, 3.35. Found C, 60.47; H, 5.93; N, 3.47.

7a: IR (KBr) (νmax): 3393, 3317, 3185, 2958, 2196, 1687, 1652, 1367 cm-11H NMR (300 MHz, DMSO–d6) δH: 0.94 (3H, s, CH3), 1.04 (3H, s, CH3), 2.08 (1H, d, J = 16.0 Hz, H(CH2)), 2.23 (1H, d, J = 16.0 Hz, H(CH2)), 2.50 (2H, m, CH2), 4.11 (1H, s, CH), 7.06 (2H, br s, NH2), 7.19 (3H, m, HAr), 7.33 (2H, m, HAr) ppm. Anal. Calcd for C18H18N2O2: C, 73.45; H, 6.16; N, 9.52. Found C, 73.83; H, 6.43; N, 9.41.

7d: IR (KBr) (νmax): 3533, 3364, 3153, 2966, 2193, 1685, 1658, 1367 cm-11H NMR (300 MHz, DMSO–d6) δH: 1.00 (3H, s, CH3), 1.06 (3H, s, CH3), 2.11 (1H, d, J = 16.0 Hz, H(CH2)), 2.27 (1H, d, J = 16.0 Hz, H(CH2)), 2.47–2.61 (2H, m, CH2), 4.70 (1H, s, CH), 7.15 (2H, br s, NH2), 7.25 (1H, d, J = 8.4 Hz, HAr), 7.39 (1H, d, J = 8.4 Hz, HAr), 7.56 (1H, s, HAr) ppm. Anal. Calcd for C18H16Cl2N2O2: C, 59.52; H, 4.44; N, 7.71. Found C, 59.81; H, 4.58; N, 7.61.

RESULTS AND DISCUSSION

Preparation and characterization of the catalyst

The magnetic nanoparticle supported bis sulfamic acid catalyst (MNPs-TBSA) was prepared via sequential reactions as shown in Fig. 2. Magnetite (Fe3O4) nanoparticles were easily prepared via the chemical co-precipitation of Fe2+ and Fe3+ ions in basic solution. These were subsequently coated with silica layer (Fe3O4@SiO2) through the well-known Stober method [48]. The Fe3O4@SiO2core-shell structures were treated with 3-aminopropyltriethoxysilane (APTS), which can bind covalently to the free-OH groups at the particles surface (Fe3O4@SiO2-NH2). Triazine-functionalized silica-coated magnetite nanoparticles (MNPs-TDCl) prepared with the reaction of the 3-aminopropyl-functionalized silica-coated magnetic nanoparticles (Fe3O4@SiO2-NH2) and triazine trichloride. Reaction of the Triazine-functionalized silica-coated magnetite nanoparticles with ammonia gives the triazine diamine-functionalized silica-coated Fe3O4 nanoparticles (Fe3O4@SiO2-TDA). The supported bis-sulfamic acid catalyst (MNPs–TBSA) was prepared via the reaction of MNPs-TDA with chlorosulfonic acid.

The FT-IR spectrum of Fe3O4, Fe3O4@SiO2, Fe3O4@SiO2-NH2, Fe3O4@SiO2-TDCl, Fe3O4@SiO2-TDA and MNPs-TBSA nanoparticles in the wavenumber range of 4000-400 cm-1 is shown in Fig. 3. The magnetic Fe3O4 nanoparticles FT-IR spectra (Fig. 3a) showed the characteristic Fe−O absorption near 574 cm-1. FT-IR spectrum of Fe3O4@SiO2 displays bands at about 1084 (asymmetric stretching), 951 (symmetric stretching), 808 (in plane bending