Preparation and characterization of graphitic carbon nitride-supported l-arginine as a highly efficient and recyclable catalyst for the one-pot synthesis of condensation reactions

In this work, graphitic carbon nitride-supported l-arginine (g-C3N4@l-arginine) nanocatalyst was synthesized and evaluated using FT-IR, EDX, XRD, TGA, and FESEM analyses. The performance of the prepared nanocatalyst was examined in the synthesis of 1,4-dihydropyridine, 4H-chromene, and 2,3-dihydro quinazoline derivatives. The novel g-C3N4@l-arginine nanocatalyst showed high thermal stability, easy separation from reaction media, the capability to be used in various multicomponent reactions, and acceptable reusability.


Scientific Reports
| (2021) 11:19792 | https://doi.org/10.1038/s41598-021-97360-x www.nature.com/scientificreports/ FTIR spectra of g-C 3 N 4 nanosheets (Fig. 2a) and g-C 3 N 4 @l-arginine nanocatalyst (Fig. 2b) are shown in Fig. 2. The strong and broad peak in the range of 3000-3300 cm −1 is related to stretching vibration of N-H bonds, breadth peak can be assigned to N-H groups involved in H-bonding or the presence of O-H groups due to water adsorption by nanosheets g-C 3 N 4 28,29 . The stretching vibration peak of C=N can be observed at 1602 cm −1 . The peaks at 1303 and 1082 cm −1 are attributed to the stretching vibration of C-N bonds formed between triazine and N-H groups, while the stretching vibration of C-N bonds in the ring is easily visible at 1448 and 1379 cm −1 29,30 . In addition, the peak at 786 cm −1 is associated with the vibration of tri-s-triazine units 1 (Fig. 3a). Figure 3b shows that the g-C 3 N 4 nanosheets has been modified with 1,3-dibromopropane; the peak at 3000-2800 cm −1 is related to C-H stretching vibration.
The spectrum of g-C 3 N 4 @l-arginine is presented in Fig. 3c in which the existence of l-arginine on the surface of g-C 3 N 4 nanosheets can be confirmed based on the 1705 cm −1 and 1307 cm −1 peaks relating to the stretching  The presence of carbon and nitrogen elements in the structure of g-C 3 N 4 nanosheets is visible in Fig. 4a. The presence of Br element in the structure proves that g-C 3 N 4 nanosheets have been modified by 1,3-dibromopropane (Fig. 4b). Finally, the presence of carbon, nitrogen, and oxygen in the final structure (g-C 3 N 4 @l-arginine) confirmed the synthesis of g-C 3 N 4 @l-arginine nanocatalyst (Fig. 4c).
The morphology of g-C 3 N 4 nanosheets and g-C 3 N 4 @l-arginine was investigated by FE-SEM. Figure 5a-d shows FE-SEM images of g-C 3 N 4 nanosheets. As shown in Figs. 5a-c, the g-C 3 N 4 nanosheets have a smooth and flat surface, while in Fig. 5d, g-C3N4 nanosheets are irregular and connected together. FE-SEM images of g-C 3 N 4 @l-arginine are shown in Fig. 5e-h. It can be seen from Fig. 5e-g that g-C 3 N 4 nanosheets have a flake-like morphology with a relatively rough surface, mainly due to the presence of l-arginine on the surface of g-C 3 N 4 nanosheets. In Fig. 5h, more irregular-shape g-C 3 N 4 nanosheets with tiny particles on the surface are observed, which again confirms the deposition of l-arginine on the g-C 3 N 4 nanosheets.
XRD patterns of g-C 3 N 4 nanosheets and g-C 3 N 4 @l-arginine are shown in Figs. 6a and 4b, respectively. The diffraction peaks at 2θ = 27.69 and 15.96 (Fig. 6a) prove the successful synthesis of g-C 3 N 4 nanosheets 1,7,28 , while the diffraction peaks at 2θ = 6.07, 10.85, 12.21, 23.60, and 30.97 (Fig. 6b) correspond to l-arginine (JCPDS card no. 00-004-0180), confirming the presence of l-arginine on the surface of g-C 3 N 4 nanosheets. Figure 7 shows the thermal stability of the synthesized g-C 3 N 4 @l-arginine in the range of 50-800 °C. As can be seen, the weight ratio has gradually decreased by increasing the temperature from 100 to 200 °C, which is most likely related to the removal of water absorbed on the surface of g-C 3 N 4 @l-arginine. Then, another weight loss is observed in the range of 200 to 400 °C, which is attributed to the separation of l-arginine from the structure. Finally, there is another weight loss in the range of 400 to 700 °C due to the decomposition of g-C 3 N 4 nanosheets 31 .
Model reactions. The performance of the prepared g-C 3 N 4 @l-arginine nanocatalyst was evaluated for the synthesis of 1,4-dihydropyridine, 4H-chromene, and 2,3-dihydro quinazoline derivatives. For this purpose, various parameters such as reaction time, catalyst concentration, and the solvent were examined ( Table 1). The reaction of 4-chlorobenzaldehyde (1 mmol), ethyl acetoacetate (1 mmol), dimedone (1 mmol), and ammonium acetate (1 mmol) for the synthesis of 1,4-dihydropyridine derivatives, the reaction of 4-chlorobenzaldehyde (1 mmol), dimedone (1 mmol), and malononitrile (1 mmol) for the synthesis of 4H-chromene derivatives, and the reaction of 4-chlorobenzaldehyde (1 mmol), isotonic anhydride (1 mmol), and ammonium acetate (1 mmol) for the synthesis of 2,3-dihydro quinazoline derivatives were considered as model reactions with and without g-C 3 N 4 @l-arginine nanocatalyst under different conditions. The reaction progress was monitored by Thin-layer    www.nature.com/scientificreports/ chromatography (TLC). As can be seen in Table 1 (entries 1 and 2), no progress was observed for the model reactions without nanocatalyst. By introducing 1.00 mg of g-C 3 N 4 @l-arginine (Table 1, entry 3), however, the model reactions occurred easily. Then, the influence of other parameters including catalyst concentration, reaction time, and solvent were examined. As can be seen, time had not significant effect on the reaction progress, thus 15 min was considered as the optimum reaction time for all the model reactions (Table 1, entries 7, 8, and  9). Furthermore, the highest product yield was obtained using ethanol as solvent at 80 °C in the presence of 20.00 mg of g-C 3 N 4 @l-arginine (Table 1, entry 5). In the following, various aldehydes were applied for the synthesis of 1,4-dihydropyridine, 4H-chromene, and 2,3-dihydro quinazoline derivatives under optimal reaction conditions. Based on model reactions that are provided in Tables 2, 3 and 4, a wide range of different derivatives of the desired multicomponent reactions were prepared with high yield.

Reusability of g-C 3 N 4 @l-arginine nanocatalyst.
According to the importance of recovery and recyclability in green chemistry, in this section, the reusability of g-C 3 N 4 @l-arginine was examined for the synthesis of 1,3-dihydropyridine 5b, 4H-chromene 9b, and 2,3-dihydroquinazoline 13b products. For this purpose, after the first reaction (run 1), g-C 3 N 4 @l-arginine catalyst was separated from the reaction media, washed with ethanol, and dried in an oven at 70 °C. Then, the catalyst was reused for the next run. This was repeated for five times and the obtained yields were acceptable for catalytic reactions, and although performed reaction yields were decreased at each run bit by bit, in run 5th, the observed decrement was impressive in comparison with other runs (Fig. 8). EDX and FTIR spectra after the 5th run showed no significant changes in the primary structure of the g-C 3 N 4 @l-arginine nanocatalyst, as shown in Fig. 9.
Mechanistic study of the prepared nanocatalyst in the synthesis of 1,4-dihydropyridine, 4H-chromene, and 2,3-dihydro quinazoline derivatives. In Fig. 10, the suitable mechanism for the formation of 1,4-dihydropyridine, 2,3-dihydro quinazoline, and 4H-chromene derivatives are provided. In each reaction, the presence of g-C 3 N 4 @l-arginine can activate reactants and different intermediates. As can be seen in Fig. 10a, 1,4-dihydropyridine derivatives can be synthesized in two methods. In the first method, aldehyde and dimedone produce intermediate I in the presence of g-C 3 N 4 @l-arginine, and the intermediate II is formed from the reaction between ethyl acetoacetate and ammonium acetate. But in the second method, dimedone and ammonium acetate produce intermediate III in the presence of g-C 3 N 4 @l-arginine, and the reaction between ethyl acetoacetate and aldehyde forms intermediate IV. Both methods ultimately lead to the formation of product V. www.nature.com/scientificreports/ A suggested mechanism for the formation of 2,3-dihydro quinazoline derivatives is shown in Fig. 10b. At first, isotonic anhydride reacts with ammonium acetate in the presence of g-C 3 N 4 @l-arginine and produces intermediate I, then aldehyde activates by g-C 3 N 4 @l-arginine and adds to intermediate II. Finally, after removing H, the desired product IV is synthesized. Figure 10c presents a probable method for the synthesis of 4H-chromene derivatives in the presence of g-C 3 N 4 @l-arginine is. In this mechanism, intermediate I is produced from the reaction between aldehyde and dimedone. Then, addition of malononitrile leads to the formation of intermediate II. At last, product IV is obtained. Table 2. Synthesis of 1,4-dihydropyridine derivatives using g-C 3 N 4 @l-arginine nanocatalyst. Reaction conditions: benzaldehyde (1 mmol), ethyl acetoacetate (1 mmol), dimedone (1 mmol), and ammonium acetate (1 mmol), g-C 3 N 4 @l-arginine (20 mg) and ethanol (7 mL Table 3. Synthesis of 4H-chromene derivatives using g-C 3 N 4 @l-arginine nanocatalyst. Reaction conditions: Reaction of benzaldehyde (1 mmol), dimedone (1 mmol), and malononitrile (1 mmol) g-C 3 N 4 @l-arginine (20 mg) and ethanol (7 mL) under reflux conditions.  Tables 5, 6 and 7 show the performance of g-C 3 N 4 @l-arginine in comparison with the catalysts reported in the literature for the synthesis of 1,4-dihydropyridine, 4H-chromene, and 2,3-dihydro quinazoline derivatives. For this purpose, various parameters such as catalyst concentration, reaction time, reaction temperature, and reaction yield were investigated. According to the data presented in each table, g-C 3 N 4 @l-arginine can be considered as a unique heterogonous nanocatalyst that can be used in a wide range of condensation reactions in addition to simple separation conditions of the reaction mixture. On the other hand, this nanocatalyst exceptionally showed higher synthesis yield at shorter reaction times.

Experimental
Reagents and apparatus. All chemicals were purchased from Merck and Sigma-Aldrich Co. Fourier Transform Infrared (FTIR) spectra were recorded on Tensor27. Nuclear Magnetic Resonance (NMR) data were acquired on a Varian-Inova 500 MHz. X-Ray Diffraction (XRD) patterns were obtained using Dron-8 diffractometer. Energy-dispersive X-ray (EDX) spectrum was recorded on Numerix DXP-X10P. Thermal gravimetric Table 4. Synthesis of 2,3-dihydroquinazoline derivatives using g-C 3 N 4 @l-arginine nanocatalyst. Reaction conditions: benzaldehyde (1 mmol), isotonic anhydride (1 mmol), and ammonium acetate (1 mmol), C 3 N 4 @l-arginine (20 mg) and ethanol (7 mL  Preparation of bulk g-C3N4 and g-C3N4 nanosheets. For the synthesis of bulk g-C 3 N 4 , the melamine was heated at 550 °C in a furnace at the heating rate of 2.5 °C min −1 in static air for 4 h. A yellow powder was obtained which was then grounded in a ball mill. For the synthesis of g-C 3 N 4 nanosheets, bulk g-C 3 N 4 (1.0 g) was first stirred in H 2 SO 4 (20 mL) at 90 °C for 5 h. The solution was then diluted with ethanol (200 mL) and stirred again at room temperature for 2 h. The resulting product was dispersed in 100.0 mL water/isopropanol (1:1) solution and sonicated for 6 h. Finally, the formed suspension was centrifuged at 5000 rpm to separate g-C 3 N 4 nanosheets.
Then, the reaction mixture was refluxed under N 2 atmosphere for 24 h after addition of 1,3-dibromopropane (2.0 mL). Finally, the product was filtered and washed with ethyl acetate, and dried at room temperature. The resulting product was dissolved in a mixture of water and methanol (1:1) followed by the addition of l-arginine (1 mmol), K 2 CO 3 (1.0 mmol), and NaI (1.0 mmol). The solution was stirred at room temperature for 24 h. the reaction mixture was then washed with water and methanol and dried at room temperature.

Conclusions
In summary, heterogeneous g-C 3 N 4 @-arginine nanocatalyst was prepared and used for the synthesis of 1,4-dihydropyridine, 4H-chromene, and 2,3-dihydro quinazoline derivatives as important products in pharmacologically active compounds. The main advantages of this nanocatalyst is its reusability, simple separation from the reaction mixture, applicability for a broad range of high efficiency condensation reactions, and short reaction time. In addition, the use of an easy and convenient method for the preparation of the nanocatalyst is another advantage of this catalyst over other reported catalysts.     Table 7. Comparison of catalytic activity of g-C 3 N 4 @l-arginine with other reported catalysts for the synthesis of 2,3-dihydro quinazoline derivatives . Reaction condition: 4-chlorobenzaldehyde (1mmol), isotonic anhydride (1mmol), and ammonium acetate (1mmol), g-C 3 N 4 @l-arginine catalyst (20.00 mg), and ethanol (7 mL) under reflux.