Preparation And Characterization Of g-C3N4 @ L-Arginine As A Highly - Ecient And Recyclable Catalyst For The Synthesis of 1, 4-Dihydropyridine, 4H-Chromene, And 2, 3-Dihydro Quinazoline Derivatives

In this work, the nanocatalyst of g-C 3 N 4 @L-arginine was prepared that synthesis of it in comparison with the synthesis of other catalysts was convenient; initially, this prepared nanocatalyst was evaluated and veried by FT-IR, EDX, XRD, TGA, and FESEM analysis, and in the next step, the performance of nanocatalyst in the synthesis of 1, 4-dihydropyridine, 4H-chromene, and 2, 3-dihydro quinazoline derivatives were examined with high yield. Properties such as high thermal stability, easy separation of reaction media, use in various multicomponent reactions, and reusability have caused that this novel nanocatalyst was changed into a unique catalyst in its own age. ethyl acetoacetate dimedone and acetate (1mmol) for synthesis of Model 4-chlorobenzaldehyde dimedone and malononitrile (1mmol) for of 4H-chromene. ammonium of 2,


Introduction
In recent decades, the use of a suitable catalytic substrate has become more demanding and interesting for chemistry researchers [1][2][3][4] . Therefore, the preparation and use of catalysts with suitable substrates have been considered. g-C 3 N 4 is widely used as a heterogeneous catalytic substrate due to its advantages such as excellent physical, chemical, and thermal stability, abrasion resistance, high hardness and low density, versatile performance, low cost for synthesis, and recyclability 5,6 . Modi cation of catalysts by different groups is an important and fundamental task to improve the performance of the catalyst. For a variety of reasons, such as toxicity, high cost, etc., in organic synthesis, the use of metal-free catalysts is cost-effective, so metal-free approaches have become more preferred in recent decades 7 .
Dihydropyridines are classi ed into two classes: symmetrical and asymmetrical dihydropyridines. Asymmetrical dihydropyridines are synthesized by the reaction between an aldehyde, 2mmol of two different β-keto esters, and a nitrogen donor such as ammonium acetate or ammonia. The product of the initial reaction is dihydropyridine that can later be converted to pyridine. These compounds are an important class of antihypertensive drugs, vasodilators, Hypnotic, anti-tumor 13,14 , anti-in ammatory 15,16 , anti-diabetic, antianxiety, anti-mutation, and they are known as calcium channel blockers 17 .
Tetrahydro-4H-chromenes are an important class of heterocyclic compounds with simple structure and low side effects; that they are synthesized by the single-step condensation of aldehydes with malononitrile and dimedone 18 . Beside their various derivatives have important activities such as anticancer, antiviral, antiin ammatory, antibacterial, antifungal, antioxidant, anticoagulant; they are also used as cognitive enhancers to treat Alzheimer's disease 19,20 .
Dihydroquinazolines are the building blocks of about 150 natural alkaloids, and these compounds are prepared by the reaction between aldehydes, isotonic anhydride, and ammonium acetate. Moreover, they have a range of pharmaceutical and biological activities like anti-in ammatory, antimalarial, antibacterial, anticancer, antiviral activities 21,22 .
Hence, many efforts have been made to synthesize such high-yield compounds. There are many methods for the synthesis of these compounds that have been prepared by using various catalysts such as MCM-41@Schiff base-Co (OAC) 2 23 , Yb (NPf 2 ) 3 24 , MCM-41@serine@Cu(II) 25 , Titanium silicon oxide nanopowder 26 , Y(NO 3 ) 3 .6H 2 O 27 , and etc. Although these catalysts are effective some of them have limitations such as long reaction time, expensive reagent, and the possibility of their contamination in nal products.
Here, a new catalyst (g-C 3 N 4 @ L-arginine) with the ability to perform various multi-combination reactions with a high yield, short reaction time, recyclability, and easy separation conditions from the reaction mixture is reported

Results And Discussion
The g-C 3 N 4 @L-arginine synthesis process consists of three main steps that were shown in scheme 1. The rst step is the synthesis of nanosheet g-C 3 N 4 from melamine, which melamine was polymerized to bulk g-C 3 N 4 , then nanosheet g-C 3 N 4 is synthesized by liquid exfoliation and sonication. In the second step, the nanosheets g-C 3 N 4 was modi ed by 1, 3-dibromooropane at 100 ℃ for 24h under a nitrogen atmosphere, and in the last stage, the g-C 3 N 4 @L-arginine was prepared from the reaction between L-arginine and modi ed nanosheets g-C 3 N 4 . In this work, various techniques such as FT-IR, EDX, XRD, FESEM, and TGA have been used to identify and characterize the properties of this novel nanocatalyst, which have been examined in the following.
In Fig. 1, the FT-IR spectra of nanosheets g-C 3 N 4 and g-C 3 N 4 @L-arginine is shown. Figure 1(a) a strong and broad peak appeared in the range 3300 − 3000 cm − 1 , which 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 was 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, and the stretching vibration of C-N bonds in the ring was easily visible at 1448 and 1379 cm − 1 29,30 . In addition to the peak of 786 cm − 1 is due to the vibration of tri-s-triazine units 1 . Figure 1(b) shows that the nanosheets g-C 3 N 4 was modi ed with 1,3-dibromopropane; the peak of 3000 − 2800 cm − 1 is related to C-H stretching vibration.
In Fig. 1(c), the g-C 3 N 4 @L-arginine spectrum is presented that the existence of L-arginine on the surface of nanosheets g-C 3 N 4 is authenticated by stretching vibration of C = O (1705 cm − 1 ) and C-O (1320 − 1210 cm − 1 ) because O-H and C-H bonds already existed in the structure of modi ed nanosheets g-C 3 N 4 .
The presence of essential elements at each step of catalyst synthesis was determined by EDX analysis.
In Fig. 2(a), the presence of carbon and nitrogen elements in the structure of nanosheets g-C 3 N 4 is visible. In the next step, the presence of Br element in structure proves that nanosheets g-C 3 N 4 was modi ed by 1, 3dibromopropane ( Fig. 2(b)). Moreover, in the nal structure (g-C 3 N 4 @L-arginine), the presence of elements such as carbon, nitrogen, and oxygen con rmed the synthesis of g-C 3 N 4 @L-arginine ( Fig. 2(c)).
The morphology of nanosheets g-C 3 N 4 and g-C 3 N 4 @L-arginine was investigated by FE-SEM.
In Fig. 3 00-004-0180). According to obtained results from the observed diffraction angles, the presence of L-arginine in the catalyst structure was con rmed. Figure 5 shows the thermal stability of the synthesized g-C 3 N 4 @L-arginine in the thermal range of 50-800℃.
As could be seen, at the temperature of 100 to 200℃, bit by bit, the weight ratio has decreased, which is most likely related to the removal of water absorbed by the g-C 3 N 4 @L-arginine surface. Then, another weight loss is observed at a range of 200 to 400℃, which is due to L-arginine's separation from the desired structure. Finally, at the temperature of 400 to 700℃, we saw a downward trend in the curve, that related to decompose of nanosheets g-C 3 N 4 31 .
General procedure for the synthesis of 1, 4-dihydropyridine, 4H-chromene, and 2,3-dihydro quinazoline derivatives In this section, we evaluated the performance of the g-C 3 N 4 @L-arginine in the synthesis of 1, 4-dihydropyridine, 4H-chromene, and 2, 3-dihydro quinazoline derivatives. For this purpose, various parameters such as reaction time, amount of catalyst, and the solvent were examined ( Table 1). The reaction of 4-chlorobenzaldehyde (1mmol),ethyl acetoacetate (1mmol), dimedone (1mmol),and ammonium acetate(1mmol) for synthesis of 1,4dihydropyridine derivatives, reaction of 4-chlorobenzaldehyde(1mmol), dimedone (1mmol),and malononitrile (1mmol) for synthesis of 4H-chromene derivatives, and reaction of 4chlorobenzaldehyde (1mmol), isotonic anhydride(1mmol),and ammonium acetate(1mmol) for synthesis of 2,3-dihydro quinazoline derivatives were used as model reactions in aid of optimize the reaction condition. Initially, reactions in the absence of g-C 3 N 4 @L-arginine were investigated under different conditions, and TLC monitored the reaction process. However, as can see in Table 1, no progress was observed in the process of model reactions (Table 1,entries 1, 2). In the next step, in the presence of 1.00mg of g-C 3 N 4 @L-arginine, reaction progress was easily visible compared to its absence (Table 1,entry3), which indicates that the g-C 3 N 4 @L-arginine is a leading factor in the progress of the reaction. Then, by changing the amount of catalyst, reaction time, and solvent, the best conditions for model reactions were examined. As was seen, the time increment did not have a speci c effect in reaction progression and the optimum reaction time was 15 min for all three model reactions (Table 1,entries7,8, and 9). Furthermore, the highest yield of products was obtained in the presence of 20.00 mg of g-C 3 N 4 @L-arginine and using ethanol at 80℃ (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 optimizing the reaction states. 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.
Reusibility study of catalyst of g-C 3 N 4 @L-arginine According to the importance of recovery and recyclability factors in green chemistry, in this section, the reusability of g-C 3 N 4 @L-arginine was examined in the synthesis of 1, 3-dihydropyridine 5b, 4H-chromene 9b, and 2,3-dihydroquinazoline 13b. For this purpose, after the execution of runs 1, the catalyst of g-C 3 N 4 @Larginine was separated from reaction media, washed with ethanol, and dried in an oven at 70℃. Then it was applied again for the next runs. This work was repeated for ve-times that 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 (Figure 6).
However, EDX and FT-IR spectra of g-C 3 N 4 @L-arginine were prepared after the ve-times recycling. Which without changes of the primary structure exhibited in gure 7.
Mechanistic study of prepared nanocatalyst insynthesis of 1, 4-dihydropyridine, 4H-chromene, and 2, 3-dihydro quinazoline derivatives In schemes 2, the suitable mechanism for the formation of 1, 4-dihydropyridine, 2,3-dihydro quinazoline, and 4H-chromenederivatives are provided, that in each of the reactions, the presence of g-C 3 N 4 @L-arginine can activate the reactants and different intermediates. As can see in scheme 2(a), 1, 4-dihydropyridine derivatives can synthesize in two methods. In the rst method, aldehyde and dimedone in the presence of g-C 3 N 4 @Larginine produce intermediate I, and the intermediate II is formed from the reaction between ethyl acetoacetate and ammonium acetate. But in the second method, dimedone and ammonium acetate in the presence of g-C 3 N 4 @L-arginine produce intermediate III, and from the reaction between ethyl acetoacetate and aldehyde is formed intermediate IV, in any case, both methods ultimately lead to product V.
A suggested mechanism for the formation of 2, 3-dihydro quinazoline derivatives is shown in scheme 2(b). At rst, isotonic anhydride reacts with ammonium acetate in the presence of g-C 3 N 4 @L-arginine and produces the 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.
In scheme 2 (c), a plausible method for synthesis of 4H-chromenederivatives in the presence of g-C 3 N 4 @Larginine is presented. In this mechanism, from the reaction between aldehyde and dimedone produces intermediate I, then the addition of malononitrile lead to the formation of intermediate II, that at the end, product IV is synthesized.

Catalytic evaluation of designed nanocatalystcompared to other reported studies
In tables 5,6 and 7, the functional and performance of g-C 3 N 4 @L-arginine were compared to other catalysts for the synthesis of desired derivatives (1,4-dihydropyridine, 4H-chromene, and 2,3-dihydro quinazoline derivatives). For this comparison, various parameters such as the amount of catalyst, time reaction, temperature condition, and reaction yield were applied. According to the table provided for each of the desired reaction, the advantage of the synthesized catalyst could be seen compared to other catalysts. The catalyst of g-C 3 N 4 @L-arginine is 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 side, this nanocatalyst's performance was exceptional in the synthesis of 1, 4-dihydropyridine, 4H-chromene, and 2, 3dihydro quinazoline derivatives with higher yield and shorter reaction time.

Experimental Section
Reagents and Apparatus All chemicals were purchased from Merck and Sigma-Aldrich chemical companies. Fourier Transform Infrared (FT-IR) spectra were recorded by Tensor27, Nuclear Magnetic Resonance (NMR) data were acquired on a Varian-Inova 500MHz, x-Ray Diffraction (XRD) measurements were carried out by Dron-8, Energy-dispersive Xray (EDX) spectrum was recorded on Numerix DXP-X10P, thermal gravimetric analysis (TGA) was taken by STA 504 instrument under an argon atmosphere. Field Emission Scanning Electron Microscopy (FESEM) images were prepared with TESCAN-MIRA lll.

Preparation of bulk g-C 3 N 4 and g-C 3 N 4 nanosheets
For the synthesis of bulk g-C 3 N 4 , the melamine was heated at 550 ℃ temperature in a furnace at the ramp 2.5 ℃ min -1 in static air for 4 h. A yellow powder was obtained, which was grounded with a ball mill. For the synthesis of g-C 3 N 4 nanosheets, rst bulk g-C 3 N 4 (1.0 g) was stirred in H 2 SO 4 (20 mL) at 90 ℃ for 5 h, then diluted with ethanol (200 mL) and was stirred again at room temperature for 2 h. The resulting product was dispersed in the 100.0 mL of water/isopropanol (1:1) and sonicated for 6 h. Finally, the formed suspension was centrifuged (5000 rpm) for g-C 3 N 4 nanosheets separation.
Preparation of g-C 3 N 4 @L-arginine Nanosheets g-C 3 N 4 (1.0 g) were dispersed in dry toluene (20.0 mL) then, 1,3dibromopropane (2.0 mL) was added to the solution, and the reaction mixture was re uxed under N 2 atmosphere for 24 h. Finally, the product was ltered and was washed with ethyl acetate, and dried at room temperature. The resulting product was solved in a mixture of water and methanol (1:1) then, L-arginine (1mmol), K 2 CO 3 (1.0 mmol), and NaI (1.0 mmol) were added. The solution was stirred at room temperature for 24h; the reaction mixture was washed with water and methanol and dried at room temperature.
General procedure for the synthesis of 1, 4-dihydropyridine derivatives

Conclusions
In summary, we prepared a heterogeneous nanocatalyst of g-C 3 N 4 @-arginine. Also, nanocatalyst prepared for the synthesis of 1, 4-dihydropyridine, 4H-chromene, and 2, 3-dihydro quinazoline derivatives were used, which are important products in pharmacologically actives compounds. This nanocatalyst's most signi cant advantages consist of reusability, simple separation of the reaction mixture, use for a broad range of condensation reactions with high e ciency, and short reaction time. On the other hand, the use of an easy and convenient method for the preparation of nanocatalyst has led to the superiority of this catalyst over other reported catalysts.