Tribromide ion immobilized on magnetic nanoparticle as a new, efficient and reusable nanocatalyst in multicomponent reactions

Abstract

Tetraethyldiethylenetriamine tribromide magnetic nanoparticles (MNPs-TEDETA tribromide) are synthesised and characterized as an efficient, new, metal free and magnetically reusable nanocatalyst for the synthesis of 2,3-dihydroquinazolin-4(1H)-one and polyhydroquinoline derivatives. The synthesized catalyst was characterized using FT-IR, TGA, XRD, EDX, VSM and SEM analyses.

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1 Introduction

There are two main kinds of catalysis systems, heterogeneous and homogeneous, and each of them has advantages and drawbacks. For example, the benefits of heterogeneous catalysts are: easy synthesis, easy separation, efficient recycling, easy product purification, and the disadvantages include: insufficient catalytic surface, low activity and leaching. Meanwhile, homogeneous catalysts have benefits such as: high activity and high selectivity, but they have disadvantages such as: laborious product purification, difficulty in recycling and recovery of the catalyst, and deactivation of the catalyst towards the end of the reaction.^1–3 Because the catalysts are often expensive, the reuse and separation of them are very important. To overcome these drawbacks, magnetic nanoparticles (MNPs), which are often low cost, have easy and clean separation from the reaction mixture with an external magnet,^4–6 unique properties, potential applications in a variety of fields,⁷ simple synthesis, high surface area, low toxicity and are readily available, are preferred.⁸

Multicomponent reaction (MCR) condensations are a chemical reaction where three or more simple substrates react to give highly selective products that retain the majority of the atoms of the starting materials.⁹ MCRs are an important subclass of tandem reactions which have advantages such as a convergent nature, milder reaction conditions, simplicity, high atom economy, easy techniques, shorter reaction time, are environmentally friendly, a lower cost and energy conservation.^10,11 In the past decade the methodologies of MCRs have emerged as being very efficient ways to access heterocycles.¹²

Polyhydroquinoline and 2,3-dihydroquinazolinone derivatives are very well-known molecules that include a six membered N-heterocyclic ring. These compounds have been reported to possess a vast range of biological properties and pharmaceutical activities.^8,13 2,3-Dihydroquinazolinones are a class of N-heterocycles that have attracted much attention because of their broad spectrum of pharmacological, biological¹⁴ and medicinal activities such as being antibacterial, antifertility, antitumor, antifibrilatory, vasodilatory, antifungal, and analgesic.^15,16 In addition, quinazolines are oxidized into quinazolin-4(3H)-ones analogs, which are known to be important biologically active heterocyclic compounds.¹⁷ 2,3-Dihydroquinazolin-4(1H)-one analogues have been synthesized using several catalysts such as: copper(II) chloride/iron(II,III) oxide (CuCl₂/Fe₃O₄)-tetraethyldiethylenetriamine (TEDETA),⁴ glucosulfonic acid immobilized on Fe₃O₄ MNPs (GSA@MNPs),¹⁴ BiBr₃,¹⁸ 2-morpholinoethanesulfonic acid (MES),¹⁹ SiO₂–FeCl₃,²⁰ boehmite silica sulfuric acid (boehmite-SSA),²¹ boehmite silica dopamine sulfamic acid (boehmite-Si-DSA).²²

Some of these methodologies for the synthesis of 2,3-dihydroquinazolin-4(1H)-one which have been previously reported had expensive reagents, tedious work-ups, high reaction temperatures, harsh reaction conditions and low yields. Thus, development of a versatile and simple procedure is a highly desired goal in the synthesis of 2,3-dihydroquinazolin-4(1H)-ones.^16,23 Although some of the analogue nanoparticles prepared by other authors were previously reported,^24,25 the main novelty of this research is it is the first report of MNPs-TEDETA tribromide without any transition metals being used as the catalyst for MCRs.

In this work, the aim was to develop an efficient synthetic process, for the synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives using a one-pot, two-component condensation of anthranilamide and aldehydes catalysed by MNPs-TEDETA tribromide in ethanol (EtOH) under reflux conditions and synthesis of polyhydroquinoline by MCRs of aldehyde, dimedone, ethyl acetoacetate (EtOAc), ammonium acetate and MNPs-TEDETA tribromide as catalyst in poly(ethylene glycol) (PEG) at 80 °C.

2 Results and discussion

2.1 Catalyst preparation

In this paper a new and efficient method for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones and polyhydroquinolines in the presence of catalytic amounts of MNPs-TEDETA tribromide is reported. Scheme 1 details the synthesis procedure of the catalyst. Initially the black precipitate of the magnetic nano particles of Fe₃O₄ have been prepared using a mixture of FeCl₃·6H₂O and iron(II) chloride tetrahydrate (FeCl₂·4H₂O) in 30% ammonium hydroxide (NH₄OH) under a N₂ atmosphere at 80 °C.^4,13 Then, Fe₃O₄ NPs were coated with (3-chloropropyl)trimethoxysilane (CPTMS) solution. In the next step, the mixture of TEDETA and triethylamine (Et₃N) was added to the MNPs-CPTMS under reflux with dry toluene. Finally, the TEDETA functionalized MNPs (MNPs-TEDETA) obtained were reacted with hydrogen bromide (HBr) and bromine (Br₂) to give MNPs-TEDETA tribromide.

Scheme 1 Synthesis of MNPs-TEDETA tribromide.

2.2 Catalyst characterization

All reagents and solvents were purchased from Merck and Aldrich chemical companies. The synthesised catalyst was characterized using X-ray diffraction (XRD, MMA-Mini Materials Analyzer, GBC-Difftech), Fourier transform infrared spectroscopy (FT-IR, Bruker, Germany), scanning electron microscopy (SEM, MIRA3 field emission scanning electron microscope (FESEM), Tescan), energy dispersive X-ray (EDX, MIRA3 FESEM, Tescan), thermogravimetric analysis (TGA, Pyris Diamond differential scanning calorimeter, Perkin-Elmer, UK), and vibrating sample magnetometry (VSM, MDKFD).

As seen in Fig. 1, the position of all the peaks in the XRD pattern of MNPs-TEDETA tribromide and the recovered catalyst were in agreement with the standard XRD pattern of Fe₃O₄. As shown the catalyst and the recovered catalyst were identified from the peak positions at 2θ = 21.33, 35.20, 41.55, 50.65, 63.19, 67.52, 74.53 and 2θ = 21.32, 35.09, 41.45, 50.53, 63.27, 67.81, 74.58, respectively. These peaks with the corresponding reflections of (111), (220), (311), (400), (422), (511) and (440) indicated that the surface modification of the Fe₃O₄ NPs does not lead to their phase change, even after recovery and they all match well with the data for the standard Fe₃O₄ sample.²⁶ Also this pattern indicated that the crystalline inverse cubic spinel structures are protected during the functionalization of the MNPs.

Fig. 1 XRD pattern of MNPs-TEDETA tribromide and recovered catalyst.

Fig. 2 shows the FT-IR spectra for the MNPs, MNPs-CPTMS, MNPs-TEDETA, and MNPs-TEDETA tribromide. The IR spectrum of the Fe₃O₄ alone indicates the bond stretching vibration at 3401 cm⁻¹ belongs to O–H bonds which are attached to the surface iron atoms and a peak appears at 1625 cm⁻¹ which belongs to the stretching vibrational mode of an adsorbed H₂O layer. Also the peak that appeared at 579 cm⁻¹ comes from vibrations of Fe–O bonds.^14,27

Fig. 2 FT-IR spectra for the MNPs (a), MNPs-CPTMS (b), MNPs-TEDETA (c), and MNPs-TEDETA tribromide (d).

The IR spectrum of MNPs-CPTMS [Fig. 2(b)] shows the peak at 577 cm⁻¹ which is assigned to the Fe–O vibration. The band formation between MNPs and the 3-chloropropylsilica group is confirmed by the Fe–O–Si absorption band that appears at near 999 cm⁻¹.²⁸ The peaks at 2880 cm⁻¹ and 2972 cm⁻¹ are attributed to C–H stretching vibrations.^27,29

As shown in Fig. 2(c), the presence of bands at 575 cm⁻¹ and 997 cm⁻¹ are assigned to the Fe–O vibration^14,27 and Fe–O–Si absorption,²⁸ respectively. The peaks at 2947 cm⁻¹ and 2999 cm⁻¹ regions are attributed to the C–H stretching vibrations.²⁹

The IR spectrum of the MNPs-TEDETA tribromide [Fig. 2(d)] indicates that the bonds at 564 cm⁻¹ and 627 cm⁻¹ are assigned to the vibrations of Fe–O bonds. The presence of a band at 1630 cm⁻¹ belongs to the stretching vibrations of C–N⁺.²⁴ This IR spectrum also shows the peaks at 1040 cm⁻¹ and 1116 cm⁻¹ which are assigned to the SiO–H and Si–O–Si groups.³⁰ The presence of bands in the 2923 cm⁻¹ and 2981 cm⁻¹ regions are assigned to the C–H stretching vibrations.^27,29 For the peak of Br–Br indicated, which is exhibited below 400 cm⁻¹, another FT-IR spectrum was captured in the region below 400 cm⁻¹. As shown in Fig. 2, the peaks at 197 and 264 cm⁻¹ are assigned to Br₃.

The SEM image was used to investigate the morphology and size of the catalyst particles. This confirmed that the catalyst was made up of uniform sized particles with an average diameter of less than 10 nm and also that the shape of the MNPs-TEDETA tribromide is spherical (Fig. 3).

Fig. 3 SEM images of the MNPs-TEDETA tribromide.

The EDX spectrum of the catalyst indicates the elements present (Br, C, Fe, N, O, and Si) in the MNPs-TEDETA tribromide. Fig. 4(a) shows the EDX spectrum of the recovered catalyst and Fig. 4(b) shows the EDX spectrum of the recovered catalyst.

Fig. 4 EDX spectrum for MNPs-TEDETA tribromide (a), recovered catalyst (b).

The bond formation between the NPs and the catalyst can be inferred from the TGA results. The TGA curves of the MNPs-TEDETA tribromide and bare Fe₃O₄ nanoparticles are shown in Fig. 5. The mass loss at temperatures below 200 °C is because of the removal of physically adsorbed surface hydroxyl groups and solvent. The weight loss of 7% for MNPs-TEDETA tribromide between 205 and 636 °C is associated with the thermal decomposition of organic groups grafted to Fe₃O₄.

Fig. 5 TGA profile of Fe₃O₄ (a) and MNPs-TEDETA tribromide (b).

VSM analysis is employed for the measurement of the magnetic properties of MNPs and MNPs-TEDETA tribromide. As shown in Fig. 6, the bare MNPs and MNPs-TEDETA tribromide both show excellent paramagnetism but because of the coating of silica and the layer of the attached catalyst, the bare MNPs had a higher magnetic value in comparison with the MNPs-TEDETA tribromide.

Fig. 6 VSM analysis of Fe₃O₄ (a) and MNPs-TEDETA tribromide (b).

2.3 Catalytic study

After characterizing the MNPs-TEDETA tribromide, its efficiency as nanocatalyst in organic reactions such as synthesis of 2,3-dihydroquinazolin-4(1H)-one and polyhydroquinoline derivatives was investigated. First, to optimize the reaction conditions for the synthesis of 2,3-dihydroquinazolin-4(1H)-one, the condensation of 4-chlorobenzaldehyde (1 mmol) with 2-aminobenzamide and MNPs-TEDETA tribromide as catalyst was used as a model reaction (Scheme 2). The reactions were carried out in the presence of different amounts of catalyst and 2-aminobenzamide and various solvents. The best results were obtained with a molar ratio of 1 : 1.05 for aldehyde : 2-aminobenzamide and 0.05 g of MNPs-TEDETA tribromide in EtOH under reflux conditions (Table 1, entry 3).

Scheme 2 MNPs-TEDETA tribromide catalysis of the one-pot synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives.

Table 1 Optimization conditions for the condensation of 4-chlorobenzaldehyde (1 mmol) and 2-aminobenzamide in EtOH^a

Entry	2-Aminobenzamide (mmol)	Catalyst (g)	Solvent	Temperature (°C)	Yield^b (%)
a 80 min.b Isolated yield.c NR = no reaction.
1	1.05	0.03	EtOH	80	63
2	1.05	0.04	EtOH	80	69
3	1.05	0.05	EtOH	80	95
4	1.05	0	EtOH	80	NR^c
5	1.05	0.06	EtOH	80	93
6	1.1	0.05	EtOH	80	88
7	1	0.05	EtOH	80	81
8	1.05	0.05	EtOH	70	70
9	1.05	0.05	H2O	80	NR
10	1.05	0.05	CH2Cl2	80	37
11	1.05	0.05	EtOAc	80	45
12	1.05	0.05	n-Hex	80	15
13	1.05	0.05	PEG	80	Trace
14	1.05	0.05	Acetone	80	32

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In general, the choice of solvent can have a significant effect on the performance of a reaction. Solvents can have an effect on solubility and reaction rates. To determine if this was the case, the synthesis of 2,3-dihydroquinazolin-4(1H)-one using different solvent (polar and non-polar) such as: acetone, CH₂Cl₂, EtOAc, EtOH, H₂O, n-Hex, and PEG was monitored. The green solvent of H₂O was applied but no product was obtained (no reaction). Also with PEG there was only a trace yield of product. Although acetone, CH₂Cl₂, EtOAc, and n-Hex are not safe solvents, they were investigated further. As shown in Table 1, these solvents had low yield (15–45%) and were not suitable for this MCR. Among solvents tested, EtOH was the best solvent because it significantly improved the yield and it is safer than using acetone, CH₂Cl₂, EtOAc, or n-Hex. Also in several methods reported previously for the synthesis of 2,3-dihydroquinazolin-4(1H)-one, the solvent of reaction was EtOH.^14,19,21,31

The reaction of the various benzaldehyde derivatives was then investigated. The 2,3-dihydroquinazolin-4(1H)-one derivatives were obtained in high yields. The results of this study are summarized in Table 2. As shown, a variety of benzaldehydes bearing electron donation and electron withdrawing substituents were successfully employed to prepare the corresponding 2,3-dihydroquinazolin-4(1H)-one derivatives with excellent yields.

Table 2 Synthesis of 2,3-dihydroquinazolin-4(1H)-ones catalyzed by MNPs-TEDETA tribromide in EtOH and at 80 °C

Entry	Product	Time (min)	Yield^a (%)	Mp^b (°C)	Reference
a Isolated yield.b Mp = melting point.
1		80	95	198–200	22
2		35	99	210–211	22
3		60	70	174–177	22
4		120	92	170–172	4
5		65	95	204–206	31
6		90	82	189–191	22
7		60	96	226–227	22
8		130	80	187–190	21
9		90	99	192–193	21

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The plausible mechanism for the formation of 2-aryl-2,3-dihydroquinazolinone-4(1H)-one was proposed and is shown in Scheme 3. The carbonyl group in aldehyde was activated by the catalyst. Then the anthranilamide reacted with the activated aldehyde and the intermediate I is formed. After dehydration of intermediate I, the imine intermediate II is generated. Finally the intramolecular cyclization of imine intermediate II produced the final product.³²

Scheme 3 The proposed mechanism of the synthesis of 2-aryl-2,3-dihydroquinazolinone-4(1H)-one.

In the second part of this work, finding a method for the one-pot synthesis of polyhydroquinoline derivatives using MNPs-TEDETA tribromide as a recoverable nanocatalyst in PEG as a green solvent (Scheme 4) was investigated.

Scheme 4 Synthesis of polyhydroquinoline derivatives catalyzed by MNPs-TEDETA tribromide.

To optimize the reaction conditions for the one-pot synthesis of polyhydroquinoline derivatives, 4-chlorobenzaldehyde with dimedone, ammonium acetate and EtOAc was used as a model reaction in the presence of different organic solvents and different amounts of catalyst and ammonium acetate at various temperatures and conditions (Table 3).

Table 3 Optimization the reaction conditions for the synthesis of polyhydroquinoline using of 4-chlorobenzaldehyde, dimedone, ammonium acetate, EtOAc and catalyst as a model reaction

Entry	Catalyst (g)	Ammonium acetate (mmol)	Solvent	Temperature (°C)	Time (min)	Yield^a (%)
a Isolated yield.
1	0.04	1.2	PEG	80	300	78
2	0.05	1.2	PEG	80	120	92
3	0.06	1.2	PEG	80	140	93
4	0	1.2	PEG	80	120	20
5	0.05	1.2	PEG	60	120	55
6	0.05	1.2	PEG	100	120	67
7	0.05	1.1	PEG	80	120	74
8	0.05	1	PEG	80	120	70
9	0.05	1.2	H2O	80	120	Trace
10	0.05	1.2	EtOH	80	120	61
11	0.05	1.2	EtOAc	80	120	50

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As shown in entry 2 of Table 3 after the optimization of the reaction conditions, 4-chlorobenzaldehyde (1 mmol), dimedone (1 mmol), EtOAc (1 mmol) and ammonium acetate (1.2 mmol) in the presence of 0.05 g MNPs-TEDETA tribromide in PEG showed better results in terms of the reaction yield and rate.

In this reaction, various benzaldehyde derivatives were employed. As shown in Table 4, the polyhydroquinoline derivatives were obtained in high yields.

Table 4 Synthesis of polyhydroquinoline catalyzed by MNPs-TEDETA tribromide in PEG and at 80 °C

Entry	Product	Time (min)	Yield^a (%)	Mp (°C)	Reference
a Isolated yield.
1		120	92	235–238	14
2		210	89	248–250	14
3		250	86	250–252	14
4		240	90	224–226	14
5		240	82	252–254	14
6		150	90	199–200	29
7		200	80	230–232	29
8		290	75	217–219	29
9		210	87	189–191	14
10		300	86	176–178	14

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Scheme 5 shows the mechanism of the synthesis of polyhydroquinoline derivatives.¹⁴ The role of the catalyst comes in the condensation of aldehydes with the active methylene compounds (Knoevenagel condensation) to give an α,β-unsaturated compound and the Michael-type addition of the intermediates to produce the polyhydroquinoline.

Scheme 5 The proposed mechanism of synthesis of polyhydroquinoline derivatives by MNPs-TEDETA tribromide.

2.4 Recyclability of the catalyst

The recyclability of the catalyst was studied using a model reaction between 2-aminobenzamide and 4-chlorobenzaldehyde in the presence of catalyst in the reflux of EtOH under the optimization conditions. After completion of the reaction, the product was dissolved in hot EtOH. Then the catalyst was separated from the product using an external magnet. Then EtOH was removed using evaporation. Finally, the pure product was obtained by recrystallizing if from the EtOH. The recycled catalyst was dried and used for further runs and its activity did not show any significant decrease even after six runs (Fig. 7).

Fig. 7 Recovery of the catalyst in the synthesis of 2,3-dihydroquinazolin-4(1H)-ones.

2.5 Hot filtration

A hot filtration technique for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones was also studied. A hot filtration technique for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones was investigated, using 4-chlorobenzaldehyde (1 mmol), 2-aminobenzamide (1.05 mmol) and MNPs-TEDETA tribromide (0.05 g) and refluxing the mixture in EtOH. This reaction was carried out for 80 min and the product yield was 95%. The reaction was repeated and product yield in a reaction time of 40 min was 53%. In another reaction, the reaction repeated and after 40 min, the catalyst was separated by an external magnet and washed with hot EtOH, then the solution was allowed to go on reacting for the remaining 40 min with stirring. After purification, the product yield was 55%.

2.6 Comparison of the catalysts

To demonstrate the advantages of MNPs-TEDETA tribromide, in comparison with other reported catalysts, the results of the preparation of 2-(3,4-dimethoxyphenyl)-2,3-dihydoquinazolin-4(1H)-one from 3,4-dimethoxybenzaldehyde and anthranilamide were compared with the previous reports in the literature. As shown in Table 5, these results indicated the efficiency of the proposed methodology in terms of the reaction yield and rate as compared to the results in the literature reports. The prepared catalyst in this work is a metal free catalyst.

Table 5 Comparison of the results obtained using MNPs-TEDETA tribromide with results obtained for other catalysts, for the reaction of anthranilamide and 3,4-dimethoxybenzaldehyde

Entry	Condition	Time (min)	Yield (%)	Ref.
a This work.
1	CuCl2/Fe3O4-TEDETA (0.005 g), EtOH, reflux	30	96	4
2	GSA@MNPs (0.01 g), EtOH, reflux	25	98	14
3	BiBr3 (5 mol%), acetonitrile, RT	30	84	18
4	MES (10 mol%), EtOH, 60 °C/microwave irradiation	180/12	86/88	19
5	SiO2–FeCl3 (0.005 g), solvent free, 80 °C	42 h	90	20
6	Boehmite-SSA (0.03 g), EtOH, reflux	130	88	21
7	Boehmite-Si-DSA (0.03 g), EtOH, reflux	60	96	22
8	MNPs-TEDETA tribromide (0.05 g), EtOH, 80 °C	35	99	^a

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3 Conclusions

In summary, MNPs-TEDETA tribromide were synthesized for use as a new, reusable and efficient catalyst for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones by the condensation between various aldehydes and anthranilamide in the presence of MNPs-TEDETA tribromide and EtOH at 80 °C. The MNPs-TEDETA tribromide were also investigated for use in the synthesis of polyhydroquinoline via a one-pot, multicomponent condensation reaction between aldehyde, dimedone, EtOAc, ammonium acetate and MNPs-TEDETA tribromide as catalyst in PEG at 80 °C. The benefits of the catalyst are its novelty, easy preparation, functionalization without the necessity of difficult conditions, easy separation by an external magnet, and low toxicity and price. Also the catalyst can be reused six times without any significant loss of its activity.

4 Experimental

4.1 Preparation of the magnetic Fe₃O₄ nanoparticles (MNPs)

A mixture of FeCl₃·6H₂O (5.858 g) and FeCl₂·4H₂O (2.221 g) was dissolved in 100 mL of deionized water until the salts dissolved completely. Then, 10 mL of 30% NH₄OH was added in to the reaction mixture under a N₂ atmosphere for about 30 min at 80 °C with vigorous mechanical stirring. NPs of Fe₃O₄ were collected and washed with doubly distilled water (five times).¹³

4.2 Preparation of MNPs coated with 3-chloropropyltrimethoxysilane (MNPs-CPTMS)

CPTMS (1.5 mL) was added to the magnetic Fe₃O₄ nanoparticles (0.5 g) in 50 mL EtOH/H₂O (1 : 1) under a N₂ atmosphere at 40 °C for about eight hours. Then, the final product was separated using an external magnet. For removal of the unattached substrates, the product was washed with EtOH and then dried at room temperature (RT).

4.3 Preparation of MNPs-TEDETA tribromide

TEDETA (2 mmol) was added to Et₃N (4 mmol) at RT for 30 minutes. The MNPs-CPTMS were added to the mixture in dry toluene under reflux conditions for 24 h. MNPs-TEDETA were prepared after washing with deionized water and EtOH and dried overnight. In the next step, HBr (47%) was added to the MNPs-TEDETA and the mixture was stirred for an hour. Ultimately Br₂ in carbon tetrachloride was added to the mixture and stirred for 6–7 h. Then the MNPs-TEDETA tribromide was collected using an external magnet and washed with doubly distilled water and EtOH.

4.4 General procedure for the synthesis of 2,3 dihydroquinazolin-4(1H)-ones derivatives

A stirred mixture of aldehyde (1 mmol), 2-aminobenzamide (1.05 mmol) and MNPs-TEDETA tribromide (0.05 g), was reacted under reflux with EtOH. After the completion of the reaction, which was monitored using thin-layer chromatography (TLC), the product was dissolved in hot EtOH, and then the catalyst was separated from the product using an external magnet. Then EtOH was removed by evaporation. Finally, the pure products were obtained by recrystallization in EtOH.

4.5 General procedure for the synthesis of polyhydroquinoline derivatives

A mixture of aldehyde (1 mmol), dimedone (1 mmol), EtOAc (1 mmol), ammonium acetate (1.2 mmol) and MNPs-TEDETA tribromide (0.05 g) was stirred in PEG at 80 °C. The progress of the reaction was monitored by TLC. After completion of the reaction, the catalyst was separated using an external magnet and then product was extracted with ethyl acetate. Finally, the solvent was evaporated and all the products were recrystallized in EtOH, and the pure products were obtained in good to excellent yields.

4.6 Characterization data of all compounds

2-(4-Chlorophenyl)-2,3-dihydoquinazolin-4(1H)-one (entry 1, Table 2). Proton nuclear magnetic resonance (¹H-NMR) (400 MHz, deuterated dimethyl sulfoxide; DMSO-d₆): δ_H: 8.29 (s, 1H), 7.60–7.41 (m, 5H), 7.25–7.20 (t, J = 7.5, 1H), 7.12 (s, 1H), 6.75–6.63 (m, 2H), 5.75 (s, 1H) ppm.

2-(3,4-Dimethoxyphenyl)-2,3-dihydoquinazolin-4(1H)-one (entry 2, Table 2). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 8.21 (s, 1H), 7.64–7.61 (d, J = 1.6, 1H), 7.29–7.25 (t, J = 8, 1H), 7.15–7.14 (d, J = 1.6, 1H), 7.03–6.97 (m, 2H), 6.95 (s, 1H), 6.78–6.76 (d, J = 8, 1H), 6.72–6.68 (t, J = 1.2, 1H), 5.71 (s, 1H), 3.77 (s, 3H), 3.76 (s, 3H) ppm.

2-(4-Methoxyphenyl)-2,3-dihydoquinazolin-4(1H)-one (entry 3, Table 2). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 8.22 (s, 1H), 7.66–7.63 (m, 1H), 7.46–7.44 (d, J = 8.8, 2H), 7.29–7.24 (m, 1H), 7.04 (s, 1H), 6.99–6.69 (d, J = 1.2, 2H), 6.78–6.76 (d, J = 8, 1H), 6.70–6.68 (t, J = 7.2, 1H), 5.74 (s, 1H), 3.77 (s, 3H) ppm.

2-(4-Ethoxyphenyl)-2,3-dihydoquinazolin-4(1H)-one (entry 4, Table 2). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 7.95–7.94 (b, 1H), 7.51–7.50 (m, 2H), 7.34 (s, 1H), 7.27 (s, 1H), 6.94–6.90 (m, 3H), 6.68–6.67 (m, 1H), 5.85 (s, 1H), 5.75 (s, 1H), 4.08–4.06 (q, J = 8, 2H), 1.46–1.44 (s, 3H) ppm.

2-(4-Fluorophenyl)-2,3-dihydoquinazolin-4(1H)-one (entry 5, Table 2). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 8.32 (s, 1H), 7.65–7.63 (m, 1H), 7.59–7.54 (m, 2H), 7.30–7.23 (m, 3H), 7.13 (s, 1H), 6.79–6.77 (d, J = 0.8, 1H), 6.69–6.67 (t, J = 8, 1H) 5.80 (s, 1H) ppm.

2-(4-Bromophenyl)-2,3-dihydoquinazolin-4(1H)-one (entry 6, Table 2). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 8.17–8.14 (m, 1H), 7.79–7.77 (m, 1H), 7.63–7.59 (m, 3H), 7.48–7.45 (m, 2H), 7.29–7.23 (m, 1H), 6.77–6.72 (d, J = 19.2, 1H), 6.70–6.67 (m, 1H), 5.76 (s, 1H) ppm.

2-(4-Methylphenyl)-2,3-dihydroquinazolin-4(1H)-one (entry 7, Table 2). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 8.21 (s, 1H), 7.63–7.60 (d, J = 7.5, 1H), 7.38–7.35 (d, J = 7.5, 2H), 7.25–7.13 (m, 3H), 7.03 (s, 1H), 6.74–6.63 (m, 2H), 5.71 (s, 1H), 2.49–2.42 (s, 3H) ppm.

2-(2-Nitrophenyl)-2,3-dihydoquinazolin-4(1H)-one (entry 8, Table 2). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 8.25 (s, 1H), 8.10–8.08 (d, J = 8, 1H), 7.90–7.87 (d, J = 8, 1H), 7.83–7.79 (t, J = 0.8, 1H), 7.69–7.63 (m, 2H), 7.30–7.26 (m, 1H), 7.04 (s, 1H), 6.81 (d, J = 1.2, 1H), 6.77–6.72 (m, 1H), 6.36 (m, 1H) ppm.

2-(3-Nitrophenyl)-2,3-dihydoquinazolin-4(1H)-one (entry 9, Table 2). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 8.57 (s, 1H), 8.40–8.39 (t, J = 1.6, 1H), 8.24–8.21 (m, 2H), 7.98–7.96 (d, J = 7.6, 1H), 7.74–7.70 (t, J = 8, 1H), 7.66–7.64 (m, 1H), 7.38 (s, 1H), 7.32–7.28 (m, 1H), 6.83–6.81 (d, J = 8, 1H), 6.74–6.70 (m, 1H), 5.98 (s, 1H) ppm.

Ethyl-4-(4-chlorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (entry 1, Table 4). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 9.13 (s, 1H), 7.25–7.28 (m, 2H), 7.17–7.19 (m, 2H), 4.86 (s, 1H), 4.01–3.96 (q, J = 7.2, 2H), 2.46–2.41 (d, J = 16.8, 1H), 2.31–2.28 (m, 4H), 2.21–2.17 (d, J = 16, 1H), 2.01–1.97 (d, J = 16, 1H), 1.15–1.12 (t, J = 7.2, 3H), 1.02 (s, 3H), 0.85 (s, 3H) ppm.

Ethyl-4-(4-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (entry 2, Table 4). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 9.14 (s, 1H), 7.41–7.39 (d, J = 8.4, 2H), 7.13–7.11 (d, J = 8.4, 2H), 4.84 (s, 1H), 4.01–3.95 (q, J = 6.8, 2H), 2.52–2.46 (d, J = 26.4, 1H), 2.31–2.28 (m, 4H), 2.21–2.17 (d, J = 16, 1H), 2.01–1.97 (d, J = 16, 1H), 1.15–1.11 (t, J = 7.2, 3H), 1.02 (s, 3H), 0.84 (s, 3H) ppm.

Ethyl-4-(4-methylphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (entry 3, Table 4). ¹H NMR (400 MHz, DMSO-d₆): δ_H: 9.04 (s, 1H), 7.05–7.03 (d, J = 8, 2H), 7.00–6.97 (d, J = 8, 2H), 4.81 (s, 1H), 4.01–3.95 (q, J = 6.8, 2H), 2.44–2.40 (d, J = 16, 1H), 2.30–2.26 (m, 4H), 2.21–2.15 (m, 4H), 2.10–1.96 (d, J = 16, 1H), 1.17–1.13 (t, J = 6.8, 3H), 1.02 (s, 3H), 0.86 (s, 3H) ppm.

Ethyl-4-(4-methoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (entry 5, Table 4). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 9.04 (s, 1H), 7.08–7.06 (d, J = 8.4, 2H), 6.77–6.75 (d, J = 8.4, 2H), 4.81 (s, 1H), 4.01–3.96 (q, J = 7.2, 2H), 3.68 (s, 3H), 2.45–2.41 (d, J = 29.2, 1H), 2.31–2.29 (m, 4H), 2.20–2.16 (d, J = 16, 1H), 2.01–1.97 (d, J = 16.4, 1H), 1.17–1.14 (t, J = 7.2, 3H), 1.02 (s, 3H), 0.87 (s, 3H) ppm.

Ethyl-4-(3,4-dimethoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (entry 6, Table 4). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 9.05 (s, 1H), 6.79–6.76 (m, 2H), 6.65–6.63 (d, J = 8, 1H), 4.81 (s, 1H), 4.04–3.99 (q, J = 7.2, 2H), 3.69–3.68 (d, J = 4.4, 5H), 2.47–2.42 (d, J = 17.2, 2H), 2.35–2.29 (m, 4H), 2.22–2.18 (d, J = 16, 1H), 2.03–1.99 (d, J = 16, 1H), 1.20–1.16 (t, J = 7.2, 3H), 1.03 (s, 3H), 0.90 (s, 3H) ppm.

Ethyl-4-(4-hydroxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (entry 7, Table 4). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 9.05 (s, 1H), 8.99 (s, 1H), 6.95–6.93 (d, J = 8.8, 2H), 6.58–6.55 (m, 2H), 4.75 (s, 1H), 4.02–3.98 (m, 2H), 2.44–2.40 (d, J = 16.8, 1H), 2.30–2.26 (m, 4H), 2.19–2.15 (d, J = 16, 1H), 2.00–1.96 (d, J = 16, 1H), 1.17–1.14 (t, J = 7.2, 3H), 1.02 (s, 3H), 0.87 (s, 3H) ppm.

Ethyl-4-(phenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (entry 8, Table 4). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 9.08 (s, 1H), 7.22–7.17 (m, 4H), 7.10–7.06 (m, 1H), 4.88 (s, 1H), 4.02–3.97 (q, J = 7.2, 2H), 2.46–2.42 (d, J = 17.2 1H), 2.33–2.29 (t, J = 8.8, 4H), 2.21–2.17 (d, J = 16, 1H), 2.02–1.98 (d, J = 16, 1H), 1.16–1.13 (t, J = 7.2, 3H), 1.03 (s, 3H), 0.86 (s, 3H) ppm.

Ethyl-4-(4-fluorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (entry 9, Table 4). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 9.11 (s, 1H), 7.20–7.17 (m, 2H), 7.04–7.00 (t, J = 8.8, 2H), 4.87 (s, 1H), 4.02–3.96 (q, J = 7.2, 2H), 2.46–2.41 (d, J = 16.8, 1H), 2.32–2.28 (m, 4H), 2.21–2.17 (d, J = 16, 1H), 2.02–1.98 (d, J = 16, 1H), 1.15–1.12 (t, J = 7.2, 3H), 1.02 (s, 3H), 0.85 (s, 3H) ppm.

Ethyl-4-(3-nitrophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (entry 10, Table 4). ¹H-NMR (400 MHz, DMSO-d₆): δ_H: 9.25 (s, 1H), 8.12–8.10 (d, J = 8.4, 2H), 7.45–7.43 (d, J = 8.4, 2H), 4.99 (s, 1H), 4.01–3.95 (q, J = 7.2, 2H), 2.48–2.44 (d, J = 17.2, 1H), 2.34–2.30 (d, J = 16.8, 4H), 2.22–2.18 (d, J = 16, 1H), 2.02–1.98 (d, J = 16, 1H), 1.14–1.11 (t, J = 7.2, 3H), 1.02 (s, 3H), 0.84 (s, 3H) ppm.

Acknowledgements

The financial support for this research work from the Ilam University, Ilam, Iran is gratefully acknowledged.

References

1. J. Govan and Y. K. Gun’ko, Nanomaterials, 2014, 4, 222.
2. A. Naghipour and A. Fakhri, Catal. Commun., 2016, 73, 39.
3. A. Ghorbani-Choghamarani and M. Norouzi, Appl. Organomet. Chem., 2016, 30, 140.
4. A. Ghorbani-Choghamarani and M. Norouzi, J. Mol. Catal. A: Chem., 2014, 395, 172.
5. Y. Zhu, L. P. Stubbs, F. Ho, R. Liu, C. P. Ship, J. A. Maguire and N. S. Hosmane, ChemCatChem, 2010, 2, 365.
6. A. Rostami, B. Tahmasbi, F. Abedi and Z. Shokri, J. Mol. Catal. A: Chem., 2013, 378, 200.
7. M. Ghorbanloo, R. Tarasi, J. Tao and H. Yahiro, Turk. J. Chem., 2014, 38, 488.
8. A. Rostami, B. Tahmasbi, H. Gholami and H. Taymorian, Chin. Chem. Lett., 2013, 24, 211.
9. M. Hajjami, A. Ghorbani-Choghamarani and F. Gholamian, Bulg. Chem. Commun., 2015, 47, 119.
10. B.-H. Chen, J.-T. Li and G.-F. Chen, Ultrason. Sonochem., 2015, 23, 59.
11. J. Safari and S. Gandomi-Ravandi, J. Mol. Struct., 2014, 1072, 173.
12. M. Wang, T. T. Zhang, Y. Liang and J. J. Gao, Monatsh. Chem., 2012, 143, 835.
13. A. Ghorbani-Choghamarani and G. Azadi, RSC Adv., 2015, 5, 9752.
14. M. Hajjami and B. Tahmasbi, RSC Adv., 2015, 5, 59194.
15. B. Zhang, L. Shi and R. Guo, Catal. Lett., 2015, 145, 1718.
16. A. Saffar-Teluri and S. Bolouk, Monatsh. Chem., 2010, 141, 1113.
17. Z. Karimi-Jaberi and R. Arjmandi, Monatsh. Chem., 2011, 142, 631.
18. K. R. Gopinath, H. S. Shekar, K. J. Rajendraprasad, H. Nagabhushana and M. Krishnappa, World J. Pharm. Pharm. Sci., 2016, 5, 1272.
19. V. B. Labade, P. V. Shinde and M. S. Shingare, Tetrahedron Lett., 2013, 54, 5778.
20. M. Ghashang, K. Azizi, H. Moulavi-Pordanjani and H. R. Shaterian, Chin. J. Chem., 2011, 29, 1617.
21. A. Ghorbani-Choghamarani and B. Tahmasbi, New J. Chem., 2016, 40, 1205.
22. M. Hajjami, A. Ghorbani-Choghamarani, R. Ghafouri-Nejad and B. Tahmasbi, New J. Chem., 2016, 40, 3066.
23. A. Davoodnia, S. Allameh, A. R. Fakhari and N. Tavakoli-Hoseini, Chin. Chem. Lett., 2010, 21, 550.
24. A. Rostami, Y. Navasi, D. Moradi and A. Ghorbani-Choghamarani, Catal. Commun., 2014, 43, 16.
25. S. Otokesh, E. Kolvari, A. Amoozadeh and N. Koukabi, RSC Adv., 2015, 5, 53749.
26. M. Hajjami and S. Kolivand, Appl. Organomet. Chem., 2016, 30, 282.
27. A. Ghorbani-Choghamarani, Z. Darvishnejad and B. Tahmasbi, Inorg. Chim. Acta, 2015, 435, 223.
28. B. Atashkar, A. Rostami and B. Tahmasbi, Catal. Sci. Technol., 2013, 3, 2140.
29. A. Ghorbani-Choghamarani, B. Tahmasbi, P. Moradi and N. Havasi, Appl. Organomet. Chem., 2016, 30, 619.
30. H. Cao, J. He, L. Deng and X. Gao, Appl. Surf. Sci., 2009, 255, 7974.
31. M. Singh and N. Raghav, Bioorg. Chem., 2015, 59, 12.
32. F. Havasi, A. Ghorbani-Choghamarani and F. Nikpour, Microporous Mesoporous Mater., 2016, 224, 26.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra15474c

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