Dysprosium Incorporated Into Balsalazide Trapped Between the Functionalized Halloysite and g-C 3 N 4 as an Ecient and Heterogeneous Catalyst for the Synthesis of Chromene Derivatives

An ecient and heterogeneous novel Dy complex of balsalazide, trapped between the functionalized halloysite and g-C 3 N 4 , was successfully synthesized by post-synthetic modication approach (Dy@Hal-BS-g-C 3 N 4 ). It was characterized by several advanced analytical methods including, FT-IR, SEM, EDX, elemental mapping, XRD, ICP-OES and TGA. The as-synthesized material was catalytically explored as a novel recoverable nanocatalyst in the synthesis of an array of biologically active pyran derivatives, i.e., the 2-amino-5,10-dioxo-4-aryl-5,10-dihydro-4H-benzo[g]chromene-3-carbonitriles. Excellent yields of the desired products and facile reusability of the catalyst are the two advantageous factors in the introduction of this novel catalytic system.


Introduction
In recent times, supported nanomaterials have garnered global attention as novel nanocatalyst due to their unique role in performing catalytic reactions, which is completely different from that of their homogeneous or bulk counterparts [1][2][3][4]. Although there are numerous reports on the precious noble metal catalysis in diverse organic transformations, in supported catalysis, the support play a vital role in properly distributing the active metal sites in order to operate the special function of over the reactive substrates [5][6][7][8][9]. The main object in most of the academia research and industrial organic reactions remains to develop a designed or functionalized novel catalyst to explore it in the preparation of target molecules -in higher selectivity and lower energy necessities -and also to improve the reaction rate [10]. In this sense, the utilization of organic biomolecules or functionalized ligand modi ed catalysts can convert these manufacturing methods to safer, greener and viable procedures, with minimal waste for a variety of organic reactions [11][12][13][14][15]. The progress of sustainable and green catalytic procedures, coupled with the design of unique and environmental-friendly ways, relies pronouncedly on the improvement of catalyst achievement [16,17]. Transition metal-based nanocatalysts have been established to be competent for the organic transformations. Despite the widespread use of these nanocatalysts, the leaching of expensive or toxic metals into the desired product is one of the negative aspects of employing heterogeneous metal-based catalysts in green catalysis [16,18]. In this regard, the involvement of high surface area carbonaceous materials in the heterogeneous catalytic core seems to be a suitable sustainable solution [19][20][21][22][23][24]. 2D-layered Graphitic carbon nitride (g-C 3 N 4 ) with s-triazine core has been considered as one of the most important class of materials with unique physicochemical properties and attracted the attention of a wide variety of researchers [25][26][27][28][29]. Regarding the carbon-based materials, these polymeric compounds have great potential in industry and technology as metal-free green heterogeneous catalysts in various organic transformations [30][31][32][33][34][35].
In recent times, tubular halloysite (Hal) clay, a member of kaolinite group, has garnered great attention in catalysis science owing to a variety of important advantages, viz., thermal and chemical stability, tubular morphology, simplicity and ease of synthesis, low toxicity, ability to facile functionalization and ease of separation from the reaction medium[36 -43]. Therefore, the synthesis of complex modi ed and heterogenized Hal has received great priority, as potential catalytic support, to be used in several novel approaches [42,[44][45][46][47][48][49]. Now, with these inputs we would like to introduce a hybrid metal doped modi ed Hal suuported over high surface carbon matrix (Dy@Hal-BS-g-C 3 N 4 ) as a novel nanocomposite in the synthesis of biologically active chromene derivatives [50][51].
In our protocol, we approached a three component coupling between 2-hydroxynaphthalene-1,4-dione, an active methylene compound and diverse aldehydes to synthesize a polycyclic chromene scaffold following Knoevenagel Condensation-Michael Addition-Cyclization sequence. In this multicomponent pathway, water is only produced as the by-product. In addition, it possesses a chiral center at the phenylsubstituted carbon that can have signi cant stereochemical utilities [52][53][54]. Recently, chromenes and their derivatives have received great attention due to a broad spectrum of biological and pharmacological activities. In addition, some of these scaffolds construct the backbone of a wide range of natural products [55][56].
Considering the interesting bene ts of heterogeneous catalysts with the use of natural raw materials, herein, we propose the synthesis of an e cient and heterogeneous novel Dy@Hal-BS-g-C 3 N 4 and its application in the synthesis of such an interesting molecule by condensing various aldehydes, lawsone and ethyl 2-isocyanoacetate or malononitrile derivatives in high yield and under mild conditions.

Materials and instruments
All of the materials were obtained from Sigma-Aldrich and Merck and applied as received. To investigate the properties of the catalyst, SEM analysis was performed on a FESEM-TESCAN MIRA3 microscope with EDX attachment (TSCAN). The FT-IR spectrum was obtained using the PERKIN-ELMER-Spectrum 65 device. An ICP analyzer (Vista-pro, Varian) was used to perform ICP analysis. The XRD pattern was investigated using Cu Ka radiation (wavelength 1.78897 Angstrom, 40 keV and 40 Ma). Mettler Toledo TGA was used to perform TGA using nitrogen atmosphere. NMR spectra of organic compounds were measured with the BRUKER spectrometer.

2.2.
Typical procedure for the synthesis of Dy@Hal-BS-g-C 3 N 4 :

Fabrication of Hal-Cl
The CPTES shell was grafted on the surface of Hal layers to generate Hal-Cl according to our previously reported method [57].

Synthesis of Hal-BS
1.5 g of Hal-Cl was dispersed in 50 ml deionized water by sonication for 30 min. Then, 1.5 g of balsalazide (BS) and 2 g of NaOH were added to the dispersion and stirred at 110°C for 24 h. After completion of the reaction, the Hal-BS product was isolated out by centrifuge, washed with distillated water several times and dried at 100°C for 24 h.

Typical procedure for the synthesis of g-C 3 N 4 :
The g-C 3 N 4 was prepared by our previously reported method [58]. 5 g of urea was heated at 550°C for 3 hours in a semiclosed reactor. The yellow-colored product (g-C 3 N 4 ) was then powdered.
2.2.4. Synthesis of Hal-BS-C 3 N 4 1.5 g of g-C 3 N 4 was dispersed in deionized water (100 mL) by sonication for 30 min. Subsequently, Hal-BS was added to the reaction mixture and dispersed for another 15 min. Then, 5 mg of Na 2 CO 3 was poured into the reaction mixture and stirred at 50°C for 24 h. Eventually, the precipitated product was collected by simple ltration, washed with EtOH to remove the adhered substances and dried overnight.

Synthesis of Dy@Hal-BS-g-C 3 N 4
Finally, 1.2 g of Hal-BS-g-C 3 N 4 was taken in 15 mL deionized water followed by the addition of 0.03 g of dysprosium (III) nitrate into that. Then catalytic amount of N 2 H 4 .H 2 O was added to the reaction mixture and stirred for 12h at ambient temperature. The nal product Dy@Hal-BSg -C 3 N 4 was isolated by ltration, washed thrice with methanol and dried at 60°C in an oven for 24 h (Scheme 1).
2.3. General procedure for the synthesis of 2-amino-5,10dioxo-4-aryl-5,10-dihydro-4H-benzo[g]chromene-3carbonitrile (2a-j) A mixture of aromatic aldehydes (1 mmol), 2-hydroxy-1,4-naphthoquinone (1.0 mmol), active methylene compounds (malononitrile or ethyl cyanoacetate) (1.5 mmol) and Dy@Hal-BS-g-C 3 N 4 (20 mg) was re uxed in water at 100°C (Scheme 2). After completion (by TLC), the reaction mixture was diluted with hot ethanol to dissolve the organic substances and the catalyst was isolated by simple ltration. The pure product was recrystallized from the hot ethanolic solution and dried to obtain a pure solid. All products were known and identi ed by comparing their melting points with authentic literature.

Characterization of catalyst
The successful synthesis of Dy@Hal-BS-g-C 3 N 4 was a rmed using different techniques like FT-IR, FE-SEM, EDX, elemental mapping, XRD, ICP-OES, and TGA.
FT-IR technique has been used to identify various functional groups of Dy@Hal-BS-g-C 3 N 4 and its stepwise building. Fig. 1 illustrates the FT-IR spectra of a) Hal-Cl, b) g-C 3 N 4 , c) Balsalazide, and d) Dy@Hal-BS-g-C 3 N 4 . In Fig. 1a, the absorption bands at around 539, 1631, and 3620-3698 cm −1 are related to the stretching vibrations of Si-O-Al, Si-O, and inner -OH groups, respectively [58]. In Fig. 1b, as expected, the strong absorption at 807 cm −1 is due to the special bending vibration of triazine moiety [59]. The FT-IR spectrum of BS is in good accordance with the reported data [60] and exhibited some characteristic bands at 3371, 3039 cm −1 , (OH, NH stretching), 1699, 1631 cm −1 (acid and amide carbonyl stretching), 1579 cm −1 (C=C stretching), 1219 cm −1 (C-N stretching) and 1073 cm −1 (C-O stretching) (Fig.  1c). The FT-IR spectrum of Dy@Hal-BS-g-C 3 N 4 is presented in Fig. 1d. All the expected absorption peaks of Hal-Cl, BS and g-C 3 N 4 can be detected in this spectrum, which indicates the successful trapping of BS complex in Dy@Hal-BS-g-C 3 N 4 . The structural morphologies, particle size and shape of the Dy@Hal-BS-g-C 3 N 4 were determined using FE-SEM analysis. The corresponding image (Fig. 2) displays a tubular morphology indicating that Hal structure remained unchanged even after successful surface coating with BS and incorporation of Dy NPs (Fig. 2).
The elemental composition and their corresponding weight% was ascertained by EDX analysis (Fig. 3).
The existence of Al, Si, and O elements are ascribed to the Hal structure in Dy@Hal-BS-g-C 3 N 4 . In addition, the presence of carbon, oxygen and nitrogen elements con rm the attachment of balsalazide molecule in the targeted structure. The occurrence of Dy element peak in the EDX spectrum clearly indicates the loading of Dy on the Hal-BS-g-C 3 N 4 .
The elemental analysis study was further extended via elemental mapping of the Dy@Hal-BS-g-C 3 N 4 (Fig.   4). The outcome clearly con rms the presence of the mentioned elements in the catalyst with a suitable dispersity. The uniform distribution of active sites over the catalyst surface is very signi cant in its catalytic activity. The obtained result from elemental mapping analysis therefore agreed well with EDX data (Fig. 4).
The crystalline phase structure of Dy@Hal-BS-g-C 3 N 4 nanocomposite was examined by XRD analysis. As Thermal stability and the quantitative estimation of the trapped organic groups were investigated by TGA analysis of Dy@Hal-BS-g-C 3 N 4 over the temperature range of 25-800°C (Fig. 6). The thermograph displays three decomposition breaks and con rms the structure of Dy complex trapped between Hal and g-C 3 N 4 with various layers. As can be seen, the rst weight loss of the catalyst (~4%) occurred at about 50-120°C, related to the removal of the adsorbed water or surface hydroxyl groups. The second weight loss occurred nearly between 330-410°C (~10%), which can be assigned to the destruction of the chloropropyl groups coated on the Hal support. Again, the third and major weight loss (~50%) occurred at 450-675°C, attributed to the removal of the chemisorbed water and BS molecule. Finally, at the end of decomposition till 700°C, the total loss in weight was about 64.23. These results show good thermal stability of Dy@Hal-BS-g-C 3 N 4 .

Catalytic study
After the detailed structural characterization of the nanocomposite material (Dy@Hal-BS-g-C 3 N 4 ), its catalytic activity was investigated in the synthesis of 4H-benzo[g]chromenes. However, prior to generalizations, optimization of reaction conditions appeared very important and thus the reaction of 2hydroxy-1,4-naphthoquinone (1.0 mmol), benzaldehyde (1.0 mmol) and malononitrile (1.5 mmol) was selected as model. Subsequently, the in uence of various reaction parameters including solvent, reaction temperature and catalyst loading were examined (Table 1). It's worthy to mention that the reaction failed in the absence of Dy@Hal-BS-g-C 3 N 4 catalyst. After optimizing the catalyst loading, the effect of a number of solvents and temperature were explored. The results indicated that the presence of solvent and catalyst were very important to succeed the reaction. After comprehensive experiments, 10 mol% of Dy@Hal-BS-g-C 3 N 4 catalyst in re uxing water was considered as the optimal reaction conditions ( Table   1). Reaction conditions: Dy@Hal-BS-g-C 3 N 4 as catalyst, Solvent (5 ml) After optimization the reaction parameters, immediately we had to investigate the scope and generality of those conditions by involving diverse substrates in the reaction. Thus, we examined various electronwithdrawing and electron-releasing benzaldehydes in the Dy@Hal-BS-g-C 3 N 4 catalyzed multicomponent cyclocondensation reaction for the preparation of 4H-benzo[g]chromene derivatives. The results have been documented in Table 2. It is evident from the results that the different aldehydes are very much compatible under the reaction conditions, providing excellent yields irrespective of the functional character and geometry in positions in aromatic ring (o, m, p). Evidently, our catalytic system is very suitable in terms of the e ciency of reactions, reaction time and yields. All the derivatives were obtained in excellent yields (90-98%) and short reaction times (10-30 min). Noticebaly, the substrates with electronwithdrawing groups (NO 2 , Cl, Br and F) reacted faster than that with electron-donating substrates (Me, OMe, OH and NMe 2 ). In addition to malononitrile, ethyl cyanoacetate was also employed in the reaction, showing comparable e cacy. After isolating the pure products, they were dried and the melting pints were recorded to compare with authentic samples.

Catalyst recyclability
Catalysts, having metal complexes in their structure, play an important and effective role in industries and other applications in laboratory scale. Hence, recyclability of the catalyst to prevent waste generation is one of the most important factor in catalysis. Nevertheless, recoverability of Dy@Hal-BS-g-C 3 N 4 was evaluated on the model reaction and it was recycled up to 8 runs by simple ltration with a gradual decrease in activity from 96 to 82% in the corresponding product (Fig. 7).

Uniqueness of our protocol
In order to demonstrate the exclusivity of Dy@Hal-BS-g-C 3 N 4 as a heterogeneous catalyst in the synthesis of 4H-benzo[g]chromene derivatives, our results in the optimized model reaction conditions was compared with the reported ones, being displayed in Table 3. Evidently, as depicted there, Dy@Hal-BS-g-C 3 N 4 is the most e cient catalyst among them in terms of reaction time and yield. Signi cantly, most of the reported methods toil from the absence of commonness for the condensation reactions of the deactivated aldehydes. In addition, the reported synthetic paths have some limitations, such as requires extreme temperature or long duration, large amounts of the catalyst and, most importantly, the use of hazardous solvents.

Conclusion
In conclusion, herein, we have demonstrated an effective and successful preparation of Dy incorporated balsalazide immobilized between the functionalized halloysite and g-C 3 N 4 (Dy@Hal-BS-g-C 3 N 4 ). The novel material was characterized using various advanced analyses. Towards its application, the catalyst showed high catalytic e ciency in the synthesis of 4H-benzo[g]chromenes over a variety of aromatic aldehydes, active methylene compounds (malononitrile or ethyl cyanoacetate) and 2-hydroxy-1,4naphthoquinone in re uxing water. Easy work-up procedure, using green solvent, excellent yield, short reaction time, good tolerance of various functional groups in the introduced conditions, easy isolation of products without the involvement of tedious column chromatography and catalyst reusabilty up to 8 successive runs with only an insigni cant loss in the product yields are the advantages of this method.

Con icts of interest
There are no con icts of interest with this research work. The TGA curve of Dy@Hal-BS-g-C 3 N 4