Abstract
Here, we report a family of polyhedral oligomeric silsesquioxanes with eight branches of 3-aminopropyltriethoxysilane tethered to nano-colloidal silica, which is characterized by 1H nuclear magnetic resonance spectroscopy, elemental analysis (CHN analysis), dynamic light scattering, scanning electron microscopy, energy-dispersive spectroscopy and thermogravimetric analysis. Furthermore, a clean, efficient, straightforward one-pot multicomponent synthetic method for the synthesis of propargylamines in good yields has been devised using nano-colloidal silica-tethered polyhedral oligomeric silsesquioxanes with eight branches of 3-aminopropyltriethoxysilane as superior catalyst under microwave irradiation.
Introduction
Propargylamines show biological properties such as antiparkinson (Yogev-Falach et al., 2003; Chen and Swope, 2005), anti-Alzheimer’s disease (Samadi et al., 2012; Bolea et al., 2013), anti-apoptotic (Maruyama et al., 2000) and bovine plasma amine oxidase inhibitors (Jeon and Sayre, 2003). Propargylamines have been utilized as significant substrates and intermediates for the preparation of diverse nitrogen compounds such as imidazolidinones (Shi and Shen, 2002), oxazolidinones (Lee et al., 2007), pyrroles (Weng et al., 2015), pyrrolidine (Morikawa et al., 2006), quinolone (Luo et al., 2005), indolines (Chernyak et al., 2010), pyridines (Penk et al., 2017) and pyrrolo[1,2-a]quinolone (Rajesh et al., 2016). Recently, studies have been reported for the synthesis of chiral allenes from chiral propargylamines by zinc iodide (Periasamy et al., 2013), silver nitrate (Lo et al., 2010), potassium gold(III) chloride (Lo et al., 2008) and zinc bromide (Periasamy et al., 2012). Therefore, the improvement of easy methods for the development of propargylamines is still favorable and in demand. The preparation of propargylamines has been reported in the presence of different catalysts including CuBr (Gommermann et al., 2003), PbS-Au (Chng et al., 2009), gold(III) salen (Lo et al., 2006), Cu(OH)x-Fe3O4 (Aliaga et al., 2010), Zn(OAc)2·2H2O (Ramu et al., 2007), copper(I) in ionic liquids (Park and Alper, 2005), copper(I)-bisimine complexes (Colombo et al., 2006), zinc dust (Kantam et al., 2007) and copper zeolites (Patil et al., 2008). In recent years, the use of nanocatalysts in multicomponent reactions is getting increased attention from synthetic chemists (Hedayati et al., 2016; Sheikhan-Shamsabadi and Ghashang, 2016). The surface of nanoparticles (NPs) can be modified through loading by desirable functionalities such as polyhedral oligomeric silsesquioxanes (POSS). Silsesquioxane is an organosilicon compound with the chemical formula [RSiO3/2]n (R=H, alkyl, vinyl, aryl, alkoxy), including an inorganic core of oxygen and silicon ~0.45 nm in diameter (Waddon and Coughlin, 2003; Heyl et al., 2010). In this study, a series of polyhedral oligomeric silsesquioxanes with eight branches of 3-aminopropyltriethoxysilane (APTPOSS) has been anchored on the surface of colloidal silica NPs. Also, we investigated an efficient and rapid method for the synthesis of propargylamines in good yields using nano-colloidal silica-tethered polyhedral oligomeric silsesquioxanes with eight branches of 3-aminopropyltriethoxysilane as high-performance catalyst under microwave irradiation (Scheme 1).
Results and discussion
The preparation steps of nano-colloidal silica-tethered polyhedral oligomeric silsesquioxanes with eight branches of 3-aminopropyltriethoxysilane have been described in Scheme 2. In the first step, Cl-POSS were synthesized by the hydrolysis of 3-chloropropyltrimethoxysilane under acidic conditions. Then, the reaction of 3-aminopropyltriethoxysilane with Cl-POSS yields APTPOSS. The reaction of nano-colloidal silica with APTPOSS afforded nano-colloidal silica @APTPOSS.
Figure 1 shows the 1H nuclear magnetic resonance (NMR) spectra for the octakis(3-chloropropyl)octasilsesquioxane (Cl-POSS) in CDCl3. The NMR spectra of Cl-POSS are consistent with the expected results.
Figure 2 shows the field emission scanning electron microscopy (FE-SEM) image of nano-colloidal silica @APTPOSS (nanocatalyst). The SEM images show the particles with diameters in the nanometer range.
The components of the APTPOSS and silica @APTPOSS were analyzed using energy-dispersive spectroscopy (EDS) (Figure 3). The EDS confirmed the presence of C, N, O and Si in the compounds, and the higher intensity of the Si peak compared with the C peak in the nanocatalyst indicates that SiO2 is loaded with APTPOSS.
Thermogravimetric analysis (TGA) evaluates the thermal stability of the nano-colloidal silica-tethered APTPOSS. The curve shows a weight loss lower than 210°C related to desorption of physically adsorbed water, while a weight loss from 210 to 560°C could be due to the decomposition of organic spacer attached to the silica NPs. Thus, the nanocatalyst was stable up to 210°C (Figure 4).
In order to study the size distribution of the nanocatalyst, dynamic light scattering (DLS) measurements of the NPs were performed, and the results are shown in Figure 5. The size distribution is centered at a value of 19.6 nm.
After the characterizations of the nanocatalyst, we studied and optimized different reaction parameters for the preparation of propargylamines by the condensation reaction of phenylacetylene, morpholine and benzaldehyde as a model reaction. To obtain the ideal reaction conditions for the synthesis of compound 4a, we studied some other catalysts and solvents which are shown in Table 1. The screening of different catalysts such as CuI, nano-ZnS, ZrOCl2, Ni(OAC)2 and nano-colloidal silica @APTPOSS revealed nano-colloidal silica @APTPOSS as the most effective catalyst to perform this reaction under microwave irradiation. In further studies on catalyst loading, we noticed that the yield of compound 4a remained almost the same when 14 mg of nano-colloidal silica @APTPOSS was used (Table 1). The use of lower catalyst loading (10 mg) afforded 4a in 83% yield.
Entry | Solvent (MWI) | Catalyst | Time (min) | Yield %b |
---|---|---|---|---|
1 | Toluene (400 W) | No catalyst | 45 | 7 |
2 | H2O (500 W) | CuI (5 mol%) | 35 | 29 |
3 | Toluene (400 W) | Nano-Fe3O4 (4 mol%) | 35 | 18 |
4 | Toluene (400 W) | ZrOCl2 (3 mol%) | 35 | 33 |
5 | Toluene (400 W) | Nano-ZnS (4 mol%) | 35 | 41 |
6 | Toluene (400 W) | Ni(OAC)2 (2 mol%) | 35 | 47 |
7 | CH2Cl2 (400 W) | Nano-colloidal silica @APTPOSS (14 mg) | 30 | 57 |
8 | THF (400 W) | Nano-colloidal silica @APTPOSS (14 mg) | 30 | 71 |
9 | Toluene (300 W) | Nano-colloidal silica @APTPOSS (14 mg) | 20 | 79 |
10 | Toluene (400 W) | Nano-colloidal silica @APTPOSS (10 mg) | 20 | 83 |
11 | Toluene (400 W) | Nano-colloidal silica @APTPOSS (12 mg) | 20 | 87 |
12 | Toluene (400 W) | Nano-colloidal silica @APTPOSS (14 mg) | 20 | 87 |
13 | Toluene (500 W) | Nano-colloidal silica @APTPOSS (12 mg) | 20 | 85 |
aPhenylacetylene (1.2 mmol), morpholine (1.2 mmol) and benzaldehyde (1 mmol).
bIsolated yield.
With these results in hand (Table 1, entry 11), we then explored the possibility of the reaction using various aromatic aldehydes as substrates. The results show that the present catalytic method is extensible to a wide diversity of substrates to create a variety-oriented library of propargylamines. In this study, microwave irradiation is utilized as a green and beneficial method for the preparation of propargylamines.
A proposed mechanism for the synthesis of propargylamines using a nanocatalyst is shown in Scheme 3. Initially, the activated aldehyde by a nanocatalyst is condensed with the secondary amine to give an iminium ion in situ, meanwhile, the nanocatalyst activates the C-H bond of the terminal alkyne to generate an active acetylide intermediate. The active acetylide intermediate then undergoes nucleophilic attack onto the iminium ion to give propargylamines. It is assumed that the catalytically active site of the catalyst contains SiO2 that acts as a Lewis acid and APTPOSS (-NH-) that acts as a Lewis base.
We also checked the reusability of nano-colloidal silica @APTPOSS as an efficient catalyst; its reusability was achieved by the reaction of phenylacetylene, morpholine and benzaldehyde and 12 mg of nano-colloidal silica @APTPOSS under optimized conditions. After completion of the reaction, the catalyst was washed with water and acetone and used with new substrates under microwave irradiation. The results showed that the nano-colloidal silica @APTPOSS can be reused several times, and it was found that product yields decreased to a small extent on each reuse (run 1, 87%; run 2, 87%; run 3, 86%; run 4, 86%; run 5, 85%; run 6, 85%).
Conclusion
In conclusion, we demonstrated an efficient method for the synthesis of propargylamines using nano-colloidal silica-tethered polyhedral oligomeric silsesquioxanes with eight branches of 3-aminopropyltriethoxysilane under microwave irradiation. The present catalyst provides active sites for the synthesis of propargylamines. The advantages of this method are the use of an efficient catalyst, recoverability of the catalyst, little catalyst loading, low reaction times, a simple procedure, high atom economy, use of microwave as a clean method and excellent yields.
Experimental
Materials and instrumentation
CHN compositions were measured by a Carlo ERBA Model EA 1108 analyzer (Perkin Elmer, Norwalk, CT, USA). We used the Milestone microwave (Microwave Labstation, MLS GmbH, ATC-FO 300) (Denmark). The TGA (Nova, USA) curves were recorded using a V5.1A DUPONT 2000. To investigate the morphology and particle size of the synthesis structure NPs, the FE-SEM (UK) images and EDS spectrum of the products were visualized by a Sigma ZEISS, Oxford Instruments field emission scanning electron microscope.
Preparation of octakis(3-chloropropyl)octasilsesquioxane
3-Chloropropyltrimethoxysilane (80 g) was added to a stirred mixture of CH3OH (1800 mL) and concentrated HCl (90 mL). The reaction mixture was stirred for 6 weeks at room temperature. Then, the resultant solution was filtered and dried to give a white solid in 37% yield. Anal. Calcd for Si8O12C24H48Cl8 (1036.9): C, 27.80; H, 4.67. Found: C, 27.74; H, 4.60. IR (KBr; ν, cm−1): 2953, 1439, 1104, 810. 1H NMR (400 MHz, CDCl3; δ, ppm): 0.82 (m, 2H), 1.87 (m, 2H), 3.55 (m, 2H).
Preparation of octakis[3-(3-aminopropyltriethoxysilane)propyl]octasilsesquioxane (APTPOSS)
First, 2 mmol (2.06 g) of Cl-POSS was added in 20 mmol (4.43 g) of 3-aminopropyltriethoxysilane and was transferred to a round-bottom flask under N2 atmosphere. The mixture was heated in an oil bath at 110°C for 2 days. After the reaction was completed, the mixture was cooled to room temperature and the mixture was filtered and washed with acetone and methanol to wash the additional reactants. Finally, the resultant pale brown precipitates were dried in a vacuum oven at 70°C for 12 h. Anal. Calcd for C96H224N8O36Si16 (2516): C, 45.82; H, 8.97; N, 4.45. Found: C, 45.56; H, 8.67; N, 4.32. IR (KBr; ν, cm−1): 2924, 1633, 1112, 1025.
Preparation of nano-colloidal silica @APTPOSS
In a typical procedure, 0.3 mL of colloidal silica NPs (LUDOX SM colloidal silica 30 wt.% suspensions in H2O) was diluted in 2 mL of deionized water. Afterward, 0.6 g of APTPOSS was dispersed in 3 mL of deionized water by ultrasonic vibration for 15 min. Then, the suspension was added slowly during 1 h to the above solution. The mixture was kept at 80°C for 1 day (Scheme 2). Finally, the nano-colloidal silica-attached APTPOSS was separated by centrifugation and washed with acetone and ethanol several times, and then, the mixture was dried in vacuum at 50°C.
General procedure for the preparation of propargylamines
A mixture of morpholine or piperidine (1.2 mmol), benzaldehydes (1 mmol), phenylacetylene (1.2 mmol) and 12 mg of nano-colloidal silica @APTPOSS (nanocatalyst) in toluene (15 mL) was irradiated in a microwave oven at 50°C and 400 W for the time indicated in Tables 1 and 2. After completion of the reaction (TLC), ethyl acetate was added. The catalyst was insoluble in ethyl acetate, and it could therefore be recycled by a simple filtration. The crude product obtained was purified by column chromatography using ethyl acetate-n-hexane to afford the pure desired product.
Entry | Amine | R | Product | Time (min) | Yield %b |
---|---|---|---|---|---|
1 | Morpholine | H | 4a | 20 | 87 |
2 | Morpholine | 4-Cl | 4b | 20 | 92 |
3 | Morpholine | 2-Me | 4c | 25 | 84 |
4 | Morpholine | 4-Me | 4d | 25 | 86 |
5 | Morpholine | 2-Cl | 4e | 20 | 89 |
6 | Piperidine | 4-NO2 | 4f | 20 | 96 |
7 | Piperidine | 4-OMe | 4g | 25 | 84 |
8 | Piperidine | 2-Cl | 4h | 25 | 92 |
9 | Piperidine | 3-Me | 4i | 25 | 87 |
10 | Piperidine | 4-Br | 4j | 20 | 95 |
11 | Piperidine | H | 4k | 20 | 89 |
12 | Piperidine | 4-Cl | 4l | 20 | 94 |
aPhenylacetylene (1.2 mmol), morpholine or piperidine (1.2 mmol) arylaldehydes (1 mmol) and nanocatalyst (12 mg) in toluene under microwave irradiation (400 W).
bIsolated yield.
Acknowledgments
The authors are grateful to the University of Kashan for supporting this work.
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