SXanthenes and benzoxanthenes are biologically important drug intermediates since they can act as antibacterial [1] and antiviral compounds [2]. These heterocycles also show interesting properties in laser technology [3], dyes [4] and pH-sensitive fluorescent materials [5]. There are numerous methods for the synthesis of these compounds by application of homogenous catalysts such as tetra-n-butylammonium fluoride (TBAF) [6], BF3/Et2O [7], ceric ammonium nitrate (CAN) [8], cyanuric acid [9], N,N’-dibromo-N,N’-1,2-ethanediylbis(p- toluenesulfonamide) [10], HClSO3 [11], HClO4-SiO2 [12], InCl3 [13], I2 [14], NaHSO4/SiO2 [15], peroxysulfuric acid (Caro’s acid)/SiO2 [16], proline triflates [17], p-toluenesulfonic acid (PTSA) [18], sulfamic acid [19], Sr(OTf)2 [20], 12- tungstophosphoric acid (TPA: H3PW12O40) [21], and Zr(HSO4)4 [22]. Many of these methods have limitations such as long reaction time, harsh reaction conditions and tedious work-up procedures. Among the most promising ways to synthesize xanthenes and benzoxanthenes, solvent-free reactions have attracted the most attention for economic reasons and pollution reduction.
However, homogeneous catalysts are difficult to apply in industrial processes because of environmental concerns and difficult work-up procedures. Thus, heterogeneous catalysts such as HClO4/SiO2 [23], mesoporous silica [24], TiO2 nanoparticles [25], zeolite [26] and Fe3O4 MNPs [27] have been applied for organic syntheses despite most suffering from a lack of surface area and difficulties in the catalyst separation [28]. Among them, Fe3O4 MNPs not only have a relatively high surface area (up to 400 m2/g), but are also capable of being easily collected by a magnet because of their magnetic properties. In addition, Fe3O4 MNPs have high thermal and mechanical stability [29, 30].
In this paper, we have developed a new and efficient method for the synthesis of DDBXs by treatment of aryl aldehydes with 2-naphthol and dimedone under solvent-free conditions at 90-110 °C in the presence of Fe3O4 MNPs (Scheme 1).
All analytical grade reagents were purchased from the Merck and Aldrich chemical companies and used without further purification. IR spectra were recorded on a Bruker IFS-66 FT-IR spectrophotometer. The elemental analysis was performed with a Thermo Finnigan Flash-1112EA microanalyzer (Italy). Magnetic separation was done by a super magnet with 1.4 T magnetic field (10 × 5 × 4 cm). The morphology of particles was observed on a Philips XL-30 scanning electron microscope (SEM) and Leo 960 transmission electron microscope (TEM). Specific surface areas were measured by the N2 adsorption technique using a Micrometitis ASPS 2010 analyzer. 1H NMR spectra were recorded on a BRUKER DRX-300 AVANCE spectrometer at 300 MHz. The XRD were obtained on a STOE diffractometer with Cu Karadiation.
The Fe3O4 MNPs were synthesized according to the previously reported procedure [28]. Briefly, FeCl3·6H2O (10.8 g, 40 mmol) and FeCl2·4H2O (4.0 g, 20 mmol) were dissolved in deionized water (100 mL), degassed with N2 for 15 min and heated to 80 °C. A solution of NH4OH (32%, 15 mL) was then added dropwise and the solid was separated after 15 min by a magnet and washed with NaCl solution (0.1 mol, 100 mL).
The MNP formation was confirmed by XRD, specific surface area measurements, SEM, TEM and EDAX microanalysis.
In a typical reaction, Fe3O4 MNPs (12 mg, 5 mol%) were added to a mixture of 2-naphthol (0.144 g, 1.0 mmol), aldehyde (1.0 mmol) and dimedone (0.168 g, 1.2 mmol) under solvent-free conditions and the mixture was heated to 110 °C. After completion of the reaction, the catalyst was separated from the solution using a magnet. The product was then separated by filtration, washed with CH2Cl2 and the crude product recrystallized from aqueous EtOH (90%) to yield the pure product, which required no further purification.
All products are known and were characterized by comparison of their physical and spectral data with authentic samples.
The reusability and stability of Fe3O4 MNPs as a catalyst were studied in several subsequent runs. After each run, the catalyst was separated from the solvent by a strong magnet and washed with MeH2Cl2, EtOH and MeCOMe, then dried under vacuum at room temperature for 4 h before reusing in the subsequent reaction.
To investigate the phase of these MNPs as well as the purity, the XRD pattern of this catalyst was recorded (Fig. 1) and compared with the JCPDS (Joint Committee on Powder Diffraction Standards) card No. 85-1436. The pattern shows peaks at 2θ = 31°, 35°, 43°, 54°, 57° and 64° that are attributed to (220), (311), (400), (422), (511) and (440) and confirm formation of the crystalline cubic spinel structure of the Fe3O4 MNPs. Since no other phase peaks could be detected in the XRD pattern, this indicates high purity in the Fe3O4 MNPs.
The purity of Fe3O4 MNPs was further investigated by EDAX microanalysis (Fig. 2). It can be seen from the microanalysis that there are no impurities and only Fe and O are detected.
Since the size and morphology of the Fe3O4 MNPs are important in their catalytic efficiency, SEM and TEM micrograph images of these particles were recorded (Fig. 3). It can be seen that spherical MNPs (35-50 nm in diameter) were obtained under an ultrasound power.
For further investigation, the size distribution of the prepared nanoparticles was obtained using a Manual Microstructure Distance Measurement program. As shown in Fig. 4, the average size of Fe3O4 MNPs produced by this method is 50-60 nm. The size of nanoparticles was calculated from the Scherrer equation and the average crystallite size was 15-19 nm.
Another important parameter in catalytic performance is the specific surface area. The single point BET (Brunauer-Emmett-Teller) analysis showed a surface area of 342 m2/g for the Fe3O4 MNPs.
To optimize the reaction conditions, the solvent-free reaction of aldehydes with 2-naphthol and dimedone were carried out at 90-110 °C in the presence of Fe3O4 MNPs under various conditions. Increasing the reaction time as well as the amount of catalyst did not improve the yield. Optimum conditions were achieved at 5 mol% Fe3O4 MNPs and 1 h reaction time (Table 1, entry 2).
DDBXs were prepared at the optimized reaction conditions by reacting 2-naphthol with different aryl aldehydes and dimedone in the presence of Fe3O4 MNPs (5 mol%) under solvent-free conditions for 1-2 h at 90-110 °C with good to excellent yields (80%-95%) (Table 2).
9,9-Dimethyl-12-phenyl-9,10-dihydro-8H-benzo[a]xanthen-11(12H)-one (g, Table 2, entry 7). M.p. 149-152 °C (lit: 151-153 °C) [32]; 1H NMR (200 MHz, CDCl3): δ = 6.9-8.0 (aromatic protons), 4.8 (1H of CH), 2.5 (2H of CH2, adjacent to the carbonyl group), 2.15 (2H of CH2), and 1.15 (6H, 2CH3).
9,9-Dimethyl-12-styryl-9,10-dihydro-8H-benzo[a]xanthen-11(12H)-one (e, Table 2, entry 5). M.p. 62-64 °C (lit: not determined) [30]; 1H NMR (200 MHz, CDCl3): δ = 6.9-8.0 (aromatic protons), 6 (2H of double bond), 4.5 (1H of CH), 2.5 (2H of CH2, adjacent to the carbonyl group), 2.2 (2H of CH2), and 1.15 (6H, 2CH3).
The NMR spectra are represented in the Supplementary Materials and the proposed mechanism for this reaction is shown in Fig. 5.
As catalyst reusability is very important from both economic and environmental points of view, the catalytic reusability of Fe3O4 MNPs was investigated in several subsequent runs. The results show that the catalyst could be reused for more than 16 successive runs without any significant decrease in conversion (Fig. 6). The high reusability of the catalyst can be explained by its high thermal and mechanical stability and vast surface area owing to an extremely high porosity.
We have demonstrated a new application of Fe3O4 MNPs as an efficient catalyst for the synthesis of xanthene derivatives. This cost-effective catalyst has the advantages of high product yields and simple work-up procedures as well as high thermal and mechanical stability.
2015, Vol. 36 Issue (3): 362-366
PDF (531 KB)
2015, Vol. 36 Issue (3): 362-366
PDF (531 KB)