CuO/ZnO@N-GQDs@NH2 nanocomposite as superior catalyst for the synthesis of pyrimidine-triones

Document Type : Research Paper

Authors

1 Young Researchers and Elite Club, Kashan Branch, Islamic Azad University, Kashan, Iran

2 Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan

Abstract

CuO / ZnO@N - GQDs@NH2 nanocomposite (copper (II) oxide / zinc oxide @ Nitrogen-doped graphene quantum dots @ aminated) as superior catalyst has been applied for the synthesis of pyrimidine - trions by three-component reactions of N, N- dimethylbarbituric acid, benzaldehydes and para-methyl aniline or para-methoxy aniline under reflux condition in water. The catalyst has been characterized by SEM (scanning electron microscope), FT - IR (Fourier-transform infrared spectroscopy), XRD (X - ray powder diffraction), TGA (Thermogravimetric analysis), EDS (Energy-dispersive X-ray spectroscopy), and XPS (X - ray photoelectron spectroscopy). The best results were gained in H2O and we found the convincing results for the synthesis of pyrimidine - trions in the presence of CuO / ZnO @ N - GQDs @ NH2 nanocomposite (5 mg) under reflux conditions. This technique prepares several benefits containing green reaction conditions, great yields in concise times, the retrievable of the nanocatalyst and low nanocatalyst loading.

Keywords

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INTRODUCTION

Pyrimidines show anti-cancer [1], glucosidase inhibitor [2], antioxidant [3], anti-microbial [4] and anaesthetic activities [5]. The detection of an effective procedure for the synthesis of pyrimidines is a drastic challenge. The preparation of pyrimidines has been studied using catalysts including Indium(III) chloride [6], tungstophosphoric acid [7], potassium carbonate [8], tosylic acid [9] and 1-N-butyl-3-methylimidazolium hexafluorophosphate [10]. Each of these procedures may have its own advantages, but also suffer from apparent drawbacks such as prolonged reaction times, complicated work-up, low yield, or hazardous reaction conditions. Despite the availability of these ways, there remains enough choice for a capable and reusable catalyst with high catalytic activity for the preparation of pyrimidines. Metal oxides represent a wide class of materials that have been researched significantly due to their unique attributes, and they are used in many fields [11-12]. Graphene quantum dots (GQDs) have gained intensive attention owing to the remarkable features [13-14]. Potential applications of GQDs were recently reviewed on the basis of experimental and theoretical investigations [15-16]. Preparation of highly efficient nanocomposite catalysts for the synthesis of organic compounds is still an attractive challenge. To attain larger surface area, nanocatalysts are functionalized by active groups [17-18]. The decoration of the nanoparticles with GQDs prevents the aggregation of fine particles and thus increases the efficient surface area and number of reactive sites for an effective catalytic reaction [19-20]. Recently the use of environmental and green catalysts which can be easily recycled has received significant attention. Besides, environmental advantages, such recoverable catalysts can also provide a platform for heterogeneous catalysis, green chemistry, and environmentally benign protocols in the near future [21-23]. Herein, we report the use of CuO/ZnO@N-GQDs@NH2 nanocomposite as effective catalyst for the preparation of pyrimidine-trions by three-component reactions of N,N-dimethylbarbituric acid, benzaldehydes and 4-methyl aniline or 4-methoxy aniline under reflux condition in water (Scheme 1).

EXPERIMENTAL

Chemicals and apparatus

All organic materials were purchased commercially from Sigma-Aldrich and Merck. Powder X-ray diffraction (XRD) was performed on a Philips diffractometer of X’pert Company with monochromatized Cu Kα radiation (λ = 1.5406 Å). Microscopic morphology of nanocatalyst was visualized by SEM (MIRA3). The thermogravimetric analysis (TGA) curves are registered by V5.1A DUPONT 2000. The IR spectra were recorded on FT-IR Magna 550 apparatus using with KBr plates. The Energy-Dispersive X-ray Spectroscopy (EDS) measurement was carried out with the SAMX analyzer. X-ray photoelectron spectroscopy (XPS) spectra were measured on an ESCA-3000 electron spectrometer. NMR spectra were obtained by a Bruker 400 MHz spectrometer (1H NMR at 400 Hz, 13C NMR at 100 Hz) in DMSO-d6 using TMS as an internal standard.

Preparation of CuO/ZnO nanoparticles

Cu(OAC)2·2H2O and Zn(OAC)2·4H2O in a 1:1 molar ratio were dissolved in deionized water. Afterward, the appropriate amount of aqueous sodium hydroxide solution (0.70 M) was added to the above solution until the pH value reached 10. Then, the transparent solution was placed in an autoclave at 120 °C for 5 h. The obtained precipitate was washed twice with methanol and dried at 70 °C for 4 h. Finally, the product was calcined at 600 °C for 3 h.

Preparation of CuO/ZnO@N-GQDs nanocomposite

Citric acid (1.0 g) was dissolved in 20 mL deionized water, and stirred to form a clear solution. After that, 0.3 mL ethylene diamine was added. Then, 0.10 g CuO/ZnO nanoparticles were added to the mixture. The mixture was stirred at room temperature for 5 minutes. Then, the solution was transferred to a 50 mL Teflon lined stainless steel autoclave. The sealed autoclave was heated to 180°C for 9 hours in an electric oven. Finally, the nanostructured CuO/ZnO @ N-GQDs were obtained, washed several times with deionized water (10 mL) and ethanol (10 mL), and then dried in an oven at 70 °C until constant weight was achieved.

Preparation of CuO/ZnO@N-GQDs@NH2 nanoc-omposite

The CuO/ZnO@N-GQDs nanocomposite (1.0 g) was added to a solution of 3-aminoprop-yltriethoxysilane (2.0 mmol, 0.44 g) in dry toluene (20 mL) and refluxed for 24 h. After the reaction was complete, the aminated-CuO/ZnO@N-GQDs were separated using a centrifuge, washed with double-distilled water (10 mL) and anhydrous ethanol (10 mL), and dried at 80 ºC for 8 h to give the nanocomposite having surface bound amino groups, CuO/ZnO@N-GQDs@NH2.

General procedure for the synthesis of pyrimidines

A mixture of N,N-dimethylbarbituric acid (1 mmol), benzaldehydes (1 mmol) and para-methyl aniline or para-methoxy aniline (1 mmol) and CuO/ZnO @N-GQDs@NH2 nanocomposite (5 mg) was heated in water (5 mL) under reflux conditions. The reaction was monitored by TLC. The formed precipitate was isolated by filtration. The product was dissolved in DMF (8 mL) and the catalyst was filtered. Then, water (5 mL) was added to the filtrate which resulted in the crystallization of the product. The resulting crystalline structure was filtered and dried with a vacuum pump. Spectral data of 4a and 4b compounds are presented:

Spectra data

5-((2-amino-5-methylphenyl)(2-nitrophenyl) methyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (4a): Yellow solid. m. p. 183-185 °C. FT-IR (KBr): ν = 3324, 3319, 2920, 1688, 1552, 1352 cm-1. – 1H NMR (400 MHz, [D6]DMSO): δ (ppm) = 2.98 (s, 3H, CH3), 3.34 (s, 6H, 2CH3), 5.34 (d, J = 8.2 Hz, 1H, CH), 5.45 (d, J = 8.2 Hz, 1H, CH), 6.98-7.46 (m, 7H, ArH), 9.17 (s, 2H, NH2). – 13C NMR (100 MHz, [D6]DMSO): δ (ppm) = 25.14, 31.74, 32.18, 43.72, 54.15, 121.22, 121.23, 125.18, 129.05, 129.12, 136.82, 136.84, 139.07, 142.21, 148.17, 154.16, 170.02.– Analysis for C20H20N4O5: calcd. C, 60.60, H, 5.09, N, 14.13; Found C, 60.54; H, 5.02; N, 14.03%.

5-((2-amino-5-methoxyphenyl)(4-(methylthio)phenyl)methyl)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (4b): Yellow solid. m. p. 190-192 °C – IR (KBr): ν = 3412, 2915, 1682, 1491, 1443, 815 cm-1. – 1H NMR (400 MHz, [D6]DMSO): δ (ppm) = 2.05 (s, 3H, CH3), 2.48 (s, 3H, CH3), 2.82 (s, 6H, 2CH3), 4.94 (d, J = 9.2 Hz, 1H, CH), 5.12 (d, J = 9.2 Hz, 1H, CH), 6.32-7.25 (m, 9H, ArH and NH2). – 13C NMR (100 MHz, [D6]DMSO): δ (ppm) = 22.14, 27.92, 28.55, 50.52, 59.14, 64.55, 121.97, 124.93, 125.86, 126.07, 127.55, 127.93, 128.07, 135.04, 138.13, 139.84, 142.55, 148.73, 164.60, 169.62.– Analysis for C21H23N3O4S: calcd. C, 61.00, H, 5.61, N, 10.16, S, 7.75; Found C, 61.07, H, 5.74, N, 10.18, S, 7.84 %.

RESULTS AND DISCUSSION

A facile hydrothermal way was utilized for the preparation of N-GQDs [24]. Amino-functionalized graphene quantum dots were prepared using 3-aminopropyltriethoxysilane. XRD pattern of CuO/ZnO@N-GQDs@NH2 nanocomposite is indicated in Fig. 1. XRD pattern confirms presence of both CuO (JCPDS No.80-1268) and ZnO (JCPDS No 80-0075).

SEM images of CuO/ZnO and CuO/ZnO@N-GQDs@NH2 nanocomposite are indicated in Fig. 2. SEM images of the CuO/ZnO@N-GQDs@NH2 nanocomposite presented the formation of uniform particles, and the energy-dispersive X-ray spectrum (EDS) confirmed the presence of Cu, Zn, N, O and C species in the structure of the nanocomposite (Fig. 3).

FT-IR spectra of CuO/ZnO, CuO/ZnO@N-GQDs and CuO/ZnO@N-GQDs@NH2 nanoco-mposite are shown in Fig. 4. The absorption peak at 3320 cm-1 is related to the stretching vibrational absorptions of OH. The peaks at 450 and 509 cm-1 corresponded to the Zn-O and Cu-O bonds, respectively. The characteristic peaks at 3400 cm-1 (O-H stretching vibration), 1660 cm-1 (C=O stretching vibration), 1100 cm-1 (C-O-C stretching vibration) appear in the spectrum of Figure 4b. The peak at approximately 1475-1580 cm-1 is attributed to C=C bonds. The peaks at 1560 and 3350cm-1 are related to the bending and stretching vibrational absorptions of N-H, respectively (Fig 4c).

Thermogravimetric analysis (TGA) considers the thermal stability of the CuO/ZnO@N-GQDs@NH2 nanocomposites (Figure 5). The curve indicates a weight loss from 200 to 600 ºC, that is attributed to the oxidation, degradation of N-GQD and decomposition of the organic spacer grafting to the N-GQD surface.

X-ray photoelectron spectroscopy (XPS) analysis of CuO/ZnO @N-GQDs@NH2 nanocomposite was indicated in Figure 6. In the wide-scan spectrum of nanocatalyst, the predominant components are Zn2p (1030-1055 eV), Cu2p (940-970 eV), O 1s (530.8 eV), N 1s (400 eV) and C 1s (286.2 eV).

Generally, the peak centered at 284.5 eV is assigned to graphitic sp2 C (C-C/C=C), the peaks located at 285.8 and 287.6 eV represent sp3 C (C-C, C-O, C-N), and carbonyl C (C=O), and the peak at 288.5 eV is attributed to the carboxylate C(O)-O [25].

We commenced our investigation by testing the reaction of N,N-dimethylbarbituric acid, 4-chlorobenzaldehyde and 4-methoxy aniline as a model reaction. To obtain the ideal reaction conditions for the synthesis of compound 4c, we studied the different catalysts and solvents which are shown in Table 1. Screening of diverse catalysts containing NiO, NaHSO4, ZrO2, Et3N, CuO/ZnO, CuO/ZnO@N-GQDs and CuO/ZnO@N-GQDs@NH2 nanocomposite revealed CuO/ZnO@N-GQDs@NH2 nanocomposite (5 mg) as the most effective catalyst to perform this reaction under reflux condition in water (Table 1). Seeking of the reaction scope demonstrated that various aromatic aldehydes can be utilized in this method (Table 2). These results showed that aromatic aldehydes with electron-withdrawing groups reacted faster than aldehydes with electron-releasing groups as expected.

The reusability of CuO/ZnO@N-GQDs@NH2 nanocomposite was tested for the synthesis of 4c and it was found that product yields reduced to a small extent on each reuse (run 1, 94%; run 2, 94%; run 3, 93%; run 4, 93%; run 5, 92%; run 6, 92%;).

A proposed mechanism for the synthesis of pyrimidine-triones using CuO/ZnO@N-GQDs@NH2 nanocomposite is indicated in Scheme 2. At the start, N,N-dimethylbarbituric acid is reacted with benzaldehyde to form intermediate (I) via condensation reaction. Intermediate (I), in the presence of CuO/ZnO@N-GQDs@NH2 nanocomposite, is condensed with aniline to form intermediate (II). The migration of the hydrogen atom will create the final product (Scheme 2).

CONCLUSION

In conclusion, we demonstrated an efficient way for the preparation of pyrimidine-triones through three-component reaction of N,N-dimethylbarbituric acid, benzaldehydes and para-methyl aniline or para-methoxy aniline under reflux condition in water. The salient features of this protocol are: great yields, concise reaction times, retrievability of the catalyst, and little nanocatalyst loading.

CONFLICT OF INTEREST

The authors confirm that this article content has no conflict of interest.

 

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Nanochemistry Research
Volume 6, Issue 1
June 2021
Pages 10-17

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