An Ultrasonic Accelerated Three-Component Condensation By KCC-1: A High Mechanical Stability Silica Nanospheres As A Good Catalyst For Ultrasonic Irradiation


 Fibrous nano-silica sphere (KCC-1) has appeared as a good and efficient catalyst for ultrasonic irradiation conditions in chemical reactions. This catalyst has the unique properties such as a fibrous surface morphology, high surface area and high mechanical stability. The results indicated that the KCC-1 nanocatalyst could be used as high-performance catalysts under high temperature and pressure condition in organic reaction under ultrasonic irradiation. Morphology, structure, and composition of the fibrous nano-silica sphere were described by N2 adsorption–desorption analysis, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), thermogravimetric analysis (TGA) and Fourier-transform infrared spectroscopy (FT-IR). In this work, we used KCC-1@NH2 nanosilica as a basic catalyst for the preparation of chromenes under ultrasonic irradiation conditions for the first time. The recyclability, nontoxicity and high stability of the catalyst, combined with low reaction times and excellent yields, make the present protocol very useful for the synthesis of the title products under ultrasonic conditions. The produced products were confirmed via 1H NMR, 13C NMR, FT-IR analysis.


Introduction
In recent years, many studies have been concentrated on increasing the performance of organic catalytic synthesis because of their applicable importance. One of the progressive strategies which have recently attracted considerable attention is the usage of ultrasound conditions with heterogeneous catalysts. 2-Amino-4H-chromenes are an important class for further development in medicinal and organic synthesis studies due to their potency and a wide spectrum of biological activities including cancer therapy 1,2 , antiviral 3,4 , antitumor 5 and sex hormone 6 . For example (Figure 1), pyranopyranone (1) as an ancestor for the blood anticoagulant warfarin, 7 (4H-chromen-4-yl)cyanoacetate (2) as inhibitor of Bcl-2 protein and apoptosis inducer 8 and benzopyrane (3) has been known for anticancer therapeutic. 9 Also compounds 4 and 5 showed in Figure 1 the maximum inhibitory effect against the HT29 human colon cancer cells. 10 Chromenes have been used for the treatment of different diseases of connective tissues, diabetes, psoriasis, pernicious anemia, ulcerous colitis, and chronic hepatitis. 11 These derivatives are employed as a building block of many natural products 12,13 , food additives, Pigments, Pesticides, cosmetic agents and potentially biodegradable agrochemicals 14 .
The preparation of 2-Amino-4H-Chromenes has been reported using various conditions and catalysts such as piperidine 15,16 , piperazine 17 , triethyl amine 18 , IL 19 , MCM-41 20 , K 2 CO 3 21 . Most of the reported methods need long reaction times, use of toxic solvents, low yields, non-reusable catalysts and stoichiometric reagents. In the present paper, we utilized acoustic cavitation. That is a physical phenomenon that helps chemical reactions under ultrasound irradiation. Ultrasound has been known as signi cant for green and remarkable synthetic methods. [22][23][24] The ultrasound approach reduces times, increases yields of products by creating the activation energy in micro surroundings. 25,26 This phenomenon is generally contained the construction, growth, and transient implosive collapse of the gas and vapour lled microbubbles. The physical and chemical effects of cavitation are exciting for various applications. 27 This method indicates bubble-sphere interaction on a microscale. In the synthesis of brous nano-silica (KCC-1), we can control particle size, ber density, surface area and pore volume of KCC-1 and tune by changing various reaction parameters, such as the concentrations of urea, CTAB, 1-pentanol, reaction time, temperature, solvent ratio, and even outside stirring time. 34 KCC-1 can be used as catalyst support, sorbent or carrier. Due to the unique properties of silica is used in various organic reactions, [35][36][37][38] drug delivery systems and biomedical applications, 39 optoelectronic devices, 40 modern industries, 41-44 gas capture, solar energy harvesting 45,46 and many others. All in all, it is the brous morphology of KCC-1 that produces better accessibility of the active sites for enhanced catalytic activities and recovery e ciencies. As well as the mechanical and thermal stability of KCC-1 that provides the better heterogeneous catalyst for ultrasonic irradiation conditions. We chosed, the ultrasonic route for the synthesis of 2-amino chromenes with modi ed dendritic silica nanosphere with amine groups present on the surface (KCC-1@NH 2 ) and distinct factors such as time of ultrasonic reaction and power of ultrasound utilized for optimizing the condition of reaction.

Results And Discussion
Structural analysis of the KCC-1@NH 2 nanocatalyst In this study, rst brous nanosilica spheres was prepared with the methods was reported by Bayal and coworkers. 34 In the second stage, a NH 2 shell using APTES (aminopropyltriethoxysilane) was coated on the nanosilica core. The KCC-1@NH 2 nanocatalyst was as an e cient basic catalyst for the preparation of 2-Amino-4H-chromenes (scheme 1).
The IR patterns of different stages of nanosilica preparation are showed in Fig. 2. The characteristic peaks of the silica-based materials could be observed in the range of 1092 to 1150 cm −1 representing the Si-O-Si asymmetric stretching while a Si-OH peak is observed at 812 cm −1 , which represents the stretching vibration and symmetric bending (Fig. 2b). In addition, the peaks at around 2930 cm −1 can be assigned to the -CH stretching frequency derived from the CH 2 groups of the alkyl chains (Fig. 2c). These FT-IR spectral features indicated the successful functionalization of APTES over KCC-1.
The XRD pattern of nanosilica spheres (KCC-1@NH 2 ) is depicted in Fig. 3. This gure reveals high phase purity of the nanocatalyst and has a perfect agreement with the reported XRD pattern for nanosilica spheres (KCC-1@NH 2 ) (JCPDS No. 71-1232). The XRD pattern of KCC-1@NH 2 includes peaks from SiO 2 and Organic layer on this catalyst. The average crystalline size of the nanocatalyst was calculated to be 8 nm that was obtained from FWHM Scherrer's formula.
Energy Dispersive Spectroscopy (Fig. 4) con rmed the presence of Si, O, C and N in the nanocatalyst. By the scanning electron microscopy (SEM) image, morphology, and particle size of brous nanosilica spheres (KCC-1@NH 2 ) is con rmed (Fig. 5). Figure 5a indicates a FE SEM image of nanosphere KCC- Nitrogen adsorption-desorption isotherms analysis and BJH pore size distributions are done to evaluate the surface and structure properties of KCC-1@NH 2 ( Figure 6). According to the International Union of Pure and Applied Chemistry (IUPAC) classi cation, this catalyst indicated characteristic type IV curve, which is consistent with literature reports on standard brous silica spheres. H2 type hysteresis loop in the relative pressure ranges from 0.4 to 1.00, is attributed to mesopore materials. For KCC-1@NH 2 , the BET surface areas were 297 m 2 g −1 ; pore diameters were 8.32 nm; and pore volumes 0.62 cm 3 g −1 , respectively.
The thermal behavior of nanosilica spheres (KCC-1@NH 2 ) is shown in Figure 7. The TG pro le exhibits two steps of weight loss. The initial mass loss of 5% accrued with an endothermic peak in DTA curve is revealed in the temperature range of 80-144°C. It can be related to the release of physically absorbed water or solvent on the surface of the KCC-1@NH 2 and other raw materials. The second mass loss of 20% in a wide temperature range of 440-640°C was overlapping a broad endothermic DTA peak. It corresponds mainly to the thermal decomposition of the organic group. The results of the thermal analysis expressed that the thermal decomposition of organic moiety completed at a temperature of 823°C.  (Table 1).

Synthesis
With reference to the results shown in Table 1, the optimized quantity of nanocatalyst for this synthesis is 0.05g (Table 1, entry 5). In an effort to obtain better yields and the most effective solvent, various solvents were used for the synthesis of chromenes. The examination of solvent was demonstrated that ethanol as protic solvent is the best condition for the Knoevenagel condensation of benzaldehydes and malononitrile compounds ( Evaluation of thermal and ultrasound conditions shows that the ultrasonic approach is very effective for this synthesis is presented in Table 1. When the 2-Aminochromenes derivatives were synthesized under the heating method (entry 10, Table 1), they were produced in lower yields at higher reaction times, but performing these reactions under sonication conditions created excellent yields of 2-Aminochromenes at short times. Therefore, because of its basic green chemistry conception, the shock wave and microjet generated by the cavitation, this method is more environmentally benign. During the ultrasonic irradiation, KCC-1@NH 2 nanocatalyst like a wall for the transmission of the bubble, is dispersed in the reaction and affords more sites for the generation of the number of micro-bubbles. Increasing of micro-cavities may advance the helpfulness of the ultrasound approach to the formation of 2-Aminochromenes. [35][36][37][38] In continues, to detect the suitable power of ultrasonic irradiation for this reaction, it was tested under different powers of ultrasound irradiation as shown in Table 2. In the end, this reaction is effectively proceeded by 0.05g of KCC-1@NH 2 nanocatalyst with the power of 80 W of ultrasonic irradiation. Really in ultrasound irradiation the number of active cavitation bubbles and size of the individual bubbles is to increase. As a result, collapse temperature was increased and accelerated the synthesis of 2-aminochromenes derivatives reaction. Various substituted 2-Aminochromenes were prepared by nanocatalyst using the obtained optimized condition ( Table 3). The results were indicated that aromatic aldehydes with electron-withdrawing groups reacted much more faster compared to those with electro-donating groups.
A rational mechanism for the preparation of 2-Aminochromens under ultrasonic irradiation by the KCC-1@NH 2 nanocatalyst is illustrated in Scheme 3. At rst, a complex was formed between the carbonyl group of aldehyde and the NH 2 group of nanocatalysts. Also, acidic hydrogen of malononitrile was

Reusability of KCC-1@NH 2 nanocatalyst
Reusability and recoverability of Nanosilica spheres (KCC-1@NH 2 ) are known as one of the most important properties of the catalyst under ultrasonic conditions. After the completion of reaction, 5 mL of acetone was added to the reaction mixture. The product solved in acetone and nanosilica was recycled via ltration. The reusability of our catalyst was tested for the model reaction, and it was found that product yields lessened only Nanosilica spheres (KCC-1@NH 2 ) are recoverable without a considerable loss of catalytic activity (Fig. 8). It was very important to us that the catalyst was stable in ultrasonic irradiation conditions. Accordingly, we investigated the morphology and particle size of the nanocatalyst before use and after reuse six times in reaction by SEM image as presented in Figures 5b and 5c. According to the gures, the morphology of the nanoparticles stayed unchanged. We believe this is also the possible reason for the extreme stability of the brous nanosilica spheres for ultrasonic irradiation conditions.
In Table 4 was showed different reports in the literature for the synthesis of 2-amino chromenes. Table 4 represents the differences between their results (entries 1-4) and the results of the present research (entry 5). As can be seen the proposed method in this work is the best condition for the synthesis of 2-amino chromenes derivatives. The properties such as mild reaction condition, high yields of 2-amino chromenes, easy recovery of the nanosilica by ltration, reusability of the catalyst for 6 times without signi cant loss of catalytic performance, short reaction times and environmentally benign of this method makes better than other previous methods. The main drawback of other procedures is a non-reusable catalyst, long reaction time, di culty in separation of catalyst from the reaction mixture and low e ciency.

Experimental Section
Substances and method They were used immediately without further ltration and distilled water was used throughout the test.
In this reaction, we were applied the ultrasonic irradiation using a multiwave ultrasonic generator (Sonicator 3200; Bandelin, MS 73, Germany), armed by a converter/transducer and titanium oscillator

Preparation of Fibrous Nanosilica Spheres (KCC-1)
Bayal and coworkers reported the methods of synthesizing of KCC-1 34 . Brie y, 1 g CTAB was added to 10 mL deionized water and after 0.6 g urea was added to the ask, the mixture was stirred for about 3 h at room temperature. Then, the mixture of 2 g TEOS, 1.5 mL hexanol and 30 mL cyclohexane was added to the ask and sonicated for 30 min. Later, the mixture was re uxed at 120 • C for 4 h and afterward re uxed at 80 • C for 24 h. Then, the mixture was cooled to room temperature and centrifuged to collect the KCC-1 as white Sediment. The collected KCC-1 was washed several times with water and ethanol and dried at 60 • C for 24 h. Finally, KCC-1 was calcinated at 550 • C for 6 h to remove the CTAB as a templating agent. For this mechanism, urea was added to hydrolyze the TEOS to produce negatively charged (SiO 4 ) 4 − silicate. Using of CTAB persuades the silicate molecules to form self-assembled linear structures where the CTAB helps to the aggregating of the silicates. 32,47 Preparation of KCC-1@NH 2 To functionalize the KCC-1 surface with NH 2 moieties, 0.02 g of KCC-1 was dispersed on 1.

Conclusion
In the current study, we introduced dendritic silica nanomaterials (KCC-1) with brous pore structure possess as a mild, e cient, high activity and stability catalyst for the one-pot synthesis of 2-Amino chromenes by multicomponent reactions under ultrasonic irradiation. This enhancement in activity was explained on the basis of the excellent accessibility of the active sites due to the open and exible brous structure of KCC-1, as well as the different amine groups present on the surface. The novel brous nanosilica spheres (KCC-1) nanocatalyst was characterized using FT-IR, SEM, TEM, EDX, XRD, TGA and BET techniques. The catalyst showed excellent e ciency and could convert >92% of the substrates to the target molecules. We believe, our procedure will nd important applications in the synthesis of 2-Amino chromenes, which represents a major advantage for reactions from the stability of this catalyst and short reaction time for synthesis of heterocyclic compounds using ultrasonic irradiation. This method offers several advantages including heterogeneous, easy separation, thermal stability, high surface area and resistance of the catalyst under ultrasonic irradiation, short reaction time, simple experimental workup procedure, lower loading of the catalyst compared with the other methods, easy product separation, and puri cation, which makes it a suitable process for the synthesis of 2-amino chromens.