1,4-Butane-Sultone Functionalized Graphitic Carbon Nitride as a Highly Efficient Heterogeneous Catalyst for the Synthesis of 2,3-Dihydroquinazolines Derivatives ^†

Abstract

1,4-Butane-sultone functionalized graphitic carbon nitride nanosheets (g-C₃N₄@Bu-SO₃H) was prepared and applied as an efficient heterogeneous catalyst for the synthesis of various quinazolines derivatives with high yield. In next step, the structure and morphology of catalyst was characterized by different analyses such as, FT-IR, EDS, XRD and FE-SEM. On the other side, considering the noticeable features of g-C₃N₄@Bu- SO₃H such as high stability, easy to synthesize, non-toxicity, excellent reusability, and so on, the synthesis of 2,3-dihydroquinazolines derivatives with numerous advantages such as short reaction time reaction condition, easy separation and etc were realized.

1. Introduction

Quinazolines and their derivatives are as a significant class of nitrogen-containing heterocyclic scaffolds that the structure of these compounds have been formed from six-membered fused rings [1]. Accordingly, these quinazolines derivatives have numerous biological activities, including anticancer, antimalaria, antimicrobial, antiviral, anti-HIV, anti-inflammatory, antifungal, acaricidal, weedicide, antidepressant, anticonvulsant, muscle relaxant, and so on [2,3]. On the other side, because of various biological values, they are utilized for synthesis of considerable drugs such as prazosin (treatment of benign prostatic obstruction) [4], geftinib (antitumor therapeutic agents) [5,6], erlotinib (EGFR inhibitor) [7], lapatinib (tyrosine kinase inhibitor) [8], alfuzosin (anticancer) [9], febrifugine (antimalaria) [10], and etc. (Scheme 1).

Recently, the preparation of 2,3-dihydroquinazolines derivatives has been heeded as the basic structure of the most bioactive medicines [11]. Therefore, to apply an effective and excellent catalyst is a noticeable approach to develop the synthesis of them with high yield. Because of various advantages such as, photocatalytic activity, wastewater treatment, organic transformation, disinfection, healthcare, environmental, electrochemical biosensor, CO₂ reduction, and H₂ generation [12,13]. Graphitic carbon nitride (g-C₃N₄) is considered as catalytic support for synthesis of different heterogeneous catalyst. In addition, Among the various catalytic methods, the use of metal-free heterogeneous catalysts is one of the best methods due to its green nature, easy synthesis and separation [14]. Although, there are different types of metal and metal-free catalysts such as PBDS-SCMNPs ionic liquid [15], Wang-OSO₃H [16], Silica sulfuric acid [17], titanium silicon oxide [18], montmorillonite-KSF [19], SrCl₂.6H₂O [20], and Y(NO₃)₃.6H₂O [21] that have been used for the synthesis of these heterocyclic derivatives but These catalysts have disadvantages and limitations such as difficult and long synthesis steps, expensive reagents, high reaction temperature, and low stability that lead to importance of the synthesis and characterization of suitable metal-free catalyst that can be beneficial for eliminating these disadvantages.

In this work, a high efficient metal-free heterogeneous catalyst (g-C₃N₄@Bu-SO₃H) was prepared and applied for synthesis of 2,3-dihydroquinazoline and its derivatives with excellent advantages consisting of short reaction time, inexpensive and available raw materials, no oxidant, and high selectivity (Scheme 2 and

Table 1. Synthesis of 2,3-dihydroquinazoline derivatives using g-C₃N₄@Bu-SO₃H metal-free catalyst.

Entry	R	Product	Time (min)	Mp (°C)	Yield
1	H	4a	15	207–210	90
2	4-Cl	4b	15	203–206	96
3	2-Cl	4c	15	205–206	95
4	4-NO2	4d	20	201–202	90
5	3-OH	4e	30	212–216	89

Reaction conditions: benzaldehyde (1 mmol), isotonic anhydride (1 mmol), and ammonium acetate (1 mmol), g-C₃N₄@Bu-SO₃H (20 mg) and ethanol (7 mL) under reflux conditions.

).

2. Experimental

2.1. Material

All chemicals were purchased from the Merck (NJ, USA) and Sigma-Aldrich (Burlington, MA, USA) Co. Fourier Transform Infrared (FT-IR) spectra were recorded on Tensor 27. 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. Field Emission Scanning Electron Microscopy (FE-SEM) images were recorder with TESCAN-MIRA III.

2.2. Preparation of Bulk g-C₃N₄ and Nanosheets

First, the melamine powder was heated at 550˚C in furnace in air atmosphere at the heating rate 2.5 °C/min for 4 h. Then, the obtained yellow powder was well ground with a mortar to obtain a blended solid powder. In next step, for the synthesis of g-C₃N₄ nanosheets, bulk g-C₃N₄ (1.0 g) was stirred with H₂SO₄ (20.0 mL) at 90 °C for 5 h. The resulting mixture was stirred by (200 mL) ethanol in room temperature at 2 h and it remained constant until all the material was settled. After 2 days, the resulting mixture was dispersed by ultrasonic probe at 300 W for 1.5 h. Eventually, the formed suspension was washed three times by ethanol and seven times by distilled water. After that, white product was dried in oven at 60 °C.

2.3. Preparation of Graphitic Carbon Nitride Nanosheets Functionalized with 1,4-Butane-Sultone (g-C₃N₄@Bu-SO₃H)

First, the g-C₃N₄ nanosheets (1.0 g) were dispersed in toluene (25 mL), after that 1,4-butane-sultone (3.0 g) was added the reaction mixture and was refluxed under nitrogen atmosphere for 6 h. Finally, the resulting product got cold in room temperature, then it was centrifuged and washed with chloroform and ethyl ether solvents, and dried in oven at 60 °C.

2.4. Selected Spectral Data

2-phenyl-2, 3-dihydro-4(1H)-quinazolinone (4a)

FT-IR (KBr, cm⁻¹): 3300, 3176, 2981, 1651, 1610, 1507, 1440, 1385, 745 cm⁻¹. ¹H NMR (500 MHz, DMSO): δ H (ppm) = 5.75 (s, 1H, CH), 6.67 (t, 1H, Ar-H), 6.74 (d, 1H, Ar-H), 7.1 (s, 1H, NH), 7.23 (t, 1H, Ar-H), 7.34 (t, 1H, Ar-H), 7.38 (t, 1H, Ar-H), 7.49 (d, 1H, Ar-H), 7.60 (d, 1H, Ar-H), 8.27 (s, 1H, CONH) (Figure 1 and Figure 2).

2-(4-chloro-phenyl)-2, 3-dihydro-1H-quinazoline-4-one (4b)

FT-IR (KBr, cm⁻¹): 3305, 3184, 3062, 1654, 1606, 1431, 1090, 749 cm⁻¹. ¹H NMR (500 MHz, DMSO): δ H (ppm) = 5.77 (s, 1H, CH), 6.68 (t, 1H, Ar-H), 6.74 (d, 1H, Ar-H), 7.1 (s, 1H, NH), 7.24 (t, 1H, Ar-H), 7.45 (d, 1H, Ar-H), 7.50 (d, 1H, Ar-H), 7.61 (d, 1H, Ar-H), 8.27 (s, 1H, CONH) (Figure 3 and Figure 4).

3. Results and Discussion

The g-C₃N₄@Bu-SO₃H heterogeneous catalyst was synthesized in just three steps (Scheme 3). In the first step, bulk g-C₃N₄ was prepared by polymerization of melamine. In the second step, the morphology of bulk g-C₃N₄ was changed to g-C₃N₄ nanoparticle. Finally, g-C₃N₄ nanoparticle was functionalized with 1,4-butane-sultone. This catalyst was proved by different analyses such as Fourier Transform Infrared (FT-IR) Spectroscopy, Energy Dispersive Spectrometer (EDS), Field Emission Scanning Electron Microscopy (FE-SEM), and X-ray diffraction analysis (XRD) [22].

The FT-IR spectra of g-C₃N₄ nanosheets (a) and g-C₃N₄@Bu-SO₃H (b) have been showed in Figure 5. A relatively strong peak in the range of 3000 to 3300 cm⁻¹ is related to stretching vibration of N–H bonds, the 1602 cm⁻¹ peak is related to C=N stretching vibration modes. The absorption peak of C–N bonds observed in rang of 1303 and 1082 cm⁻¹ that can be attributed to C–N bonds between triazine and N–H groups. On the other hand, the characteristic peaks at 1448 and 1379 cm⁻¹ are related to C–N ring bonds and finally, the peak at 784 cm⁻¹ may be related to tri-s-triazine units (Figure 5a).

In the spectrum of g-C₃N₄@Bu-SO₃H, which is shown in Figure 5b, the two peaks 2781 and 2758 cm⁻¹ are related to C–H groups in 1,4-butane-sultone. The symmetric and asymmetric stretching vibration modes of SO₂ have appeared in the regions 1220 and 1348 cm⁻¹, the characteristic peaks at 1176 and 1207 cm⁻¹ are related to S–OH bonds.

In the Figure 6a, the presence of carbon and nitrogen atoms in structure of g-C₃N₄ nanosheets was confirmed by the EDS analysis. As shown in the Figure 6b, the presence of oxygen and sulfur elements proves synthesis of desired catalyst (g-C₃N₄-Bu-SO₃H).

The morphology of g-C₃N₄ nanosheets and g-C₃N₄@Bu-SO₃H were shown by the FE-SEM images. In the Figure 7a, the g-C₃N₄ nanosheets have a relatively flat surface, while in the Figure 7b, image of g-C₃N₄@Bu-SO₃H is partly different and irregular. Therefore, this variance can verified the deposition of sultone on the g-C₃N₄ nanosheets.

The XRD pattern of g-C₃N₄ nanosheets and g-C₃N₄@Bu-SO₃H can be seen in Figure 8. Diffraction peaks at 2θ: 27.35° (002) and 13.04° (100) are related g-C₃N₄ nanosheets (Figure 8a). Also diffraction peaks at 2θ: 27.4° (002), 2θ = 17.9°, and 14.8° (100) are related to the g-C₃N₄@Bu-SO₃H that approve synthesis of this catalyst (Figure 8b).

4. Reusability

Reusability of g-C₃N₄@Bu-SO₃H catalyst was examined for synthesis of 2,3-dihydroquinazolines derivatives in four runs, the considering Figure 9, reaction yield was decreased considerably after third run.

5. Conclusions

In summary, an efficient heterogeneous catalyst (g-C₃N₄@Bu-SO₃H) was synthesized and utilized for production of 2,3-dihydroquinazolines derivatives with highly advantages such as short reaction time, mild condition, and easy separation. On the other side, this catalyst can be used and recycled for five times with high yield.