Synthesis and characterization of glucosulfonic acid supported on Fe₃O₄ nanoparticles as a novel and magnetically recoverable nanocatalyst and its application in the synthesis of polyhydroquinoline and 2,3-dihydroquinazolin-4(1H)-one derivatives

Abstract

Glucosulfonic acid immobilized on Fe₃O₄ magnetic nanoparticles (GSA@MNPs) have been reported as an efficient and magnetically reusable nanocatalyst for the clean and one-pot synthesis of polyhydroquinoline and 2,3-dihydroquinazolin-4(1H)-one derivatives, with short reaction times in good to high yields in ethanol. After completing the reactions the catalyst was easily separated from the reaction mixture using an external magnetic field and reused for several consecutive runs without significant loss of catalytic efficiency. This new catalyst was characterized using FT-IR spectroscopy, TGA, XRD, VSM, TEM, EDS and SEM.

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1. Introduction

The immobilization of homogeneous catalysts on various support materials, such as organic polymers and inorganic silica and other metal oxides, to combine the advantages of both homogeneous and heterogeneous catalysis have been widely used as useful recoverable and reusable catalysts for organic synthesis.¹ Nanoparticulate supports can be used to efficiently bridge the gap between homogeneous and heterogeneous catalysis.² However, the supported nanocatalyst may need to be isolated from the products using difficult, time consuming and expensive conventional techniques, such as filtration or centrifugation.³ This drawback can be overcome by using magnetic nanoparticles (MNPs), which can be easily and rapidly separated from the reaction mixture with the assistance of an external magnet.⁴ Magnetic nanoparticles are a highly favourable material for the attachment of homogeneous inorganic and organic containing catalysts.⁵ More importantly, magnetic separation of the MNPs is more effective and easier than filtration or centrifugation, and is a simple, economical, and clean separation method that is promising for industrial applications.^6–8 One of the most promising MNP supports for the development of high performance catalyst supports is superparamagnetic iron oxide.⁹ The notable advantages of Fe₃O₄ NPs are simple synthesis, ready availability, low cost, high surface area, low toxicity, operational simplicity and much easier and more effective separation than filtration or centrifugation.¹⁰ Therefore, Fe₃O₄ NPs are considered as ideal supports for the heterogenization of homogeneous catalysts.¹¹ The outstanding potential of Fe₃O₄ nanoparticles has stimulated the extensive development of synthetic technologies, which can be broadly classified. Among them, the chemical coprecipitation method for preparation of Fe₃O₄ is very simple and efficient.¹² However, many supports, such as mesoporous silica or nanoparticles, require high temperature for calcination and a lot of time and tedious conditions to prepare.^13–16

The large active surface area of magnetic nanoparticles and their superparamagnetic properties leads to the agglomeration of the bare nanoparticles of iron oxides. Therefore, coating the catalyst surface with an organic or inorganic shell is an appropriate strategy to prevent agglomeration.¹⁷ More importantly, an organic coat over the iron nano-core imparts various desirable properties, such as thermal and chemical stability, high mechanical tolerance and ease of functionalization.¹⁸ On the other hand, terminal amine or hydroxyl groups in the extrinsic surface layers can be functionalized to convert a homogeneous catalyst into a heterogeneous catalytic system. In recent years, impressive efforts have been made in the development of new catalytic systems which are immobilized onto Fe₃O₄.^19–25

Polyhydroquinoline and 2,3-dihydroquinazolinone derivatives are very well-known molecules that include a six-membered heterocyclic ring, which have been reported to possess a wide range of biological properties and pharmaceutical activities.^9,10 Polyhydroquinoline (PHQ) derivatives contain a large family of medicinally important compounds that have attracted much attention because of their diverse pharmacological and therapeutic properties, such as vasodilator, hepatoprotective, antiatherosclerotic, bronchodilator, antitumor, geroprotective and antidiabetic activities, and also their ability to modulate calcium channels.^26,27 Thus, the synthesis of these heterocycles has become an area of great interest. Also, 2,3-dihydro-4(1H)-quinazolinones are important bicyclic heterocycles which have emerged as versatile biologically active compounds possessing applications as diuretic, vasodilating, tranquilizing, antitumor, antidefibrillatory, antibiotic, antihistaminic, anticonvulsant, anticancer, herbicidal, plant growth regulation and antihypertensive agents.^4,10,28 They are also reported to possess the ability to inhibit enzymes of biological importance.²⁹ In addition, these compounds can be easily oxidized to their quinazolin-4(3H)-one analogues,¹⁰ which also include important pharmacologically active compounds. Generally, 2,3-dihydroquinazolin-4(1H)-ones are prepared using the reductive cyclization of aldehydes or ketones with 2-aminobenzamide in the presence of acid catalysts.^9,29

For these reasons, many methods have been developed, including microwave and ultrasound irradiation techniques using various catalytic systems.^26–29 However, most of these processes suffer from one or several drawbacks, such as longer reaction time, tedious workup, harsh reaction conditions, unsatisfactory yields, and the use of a large quantity of environmentally toxic and expensive catalysts. On the other hand, the toxicity of magnetic glyconanoparticles has been investigated and they have been revealed to be non-toxic at high concentration, and this is safe and positive from the point of view of the environment and green chemistry.³⁰

In addition, some of these catalysts cannot be recovered and reused again. Thus, there is a necessity to develop a simple and efficient method for the synthesis of polyhydroquinolines and 2,3-dihydroquinazolin-4(1H)-ones in high yields under mild reaction conditions.

2. Results and discussion

2.1. Catalyst preparation

In continuation of our studies,³¹ herein we report a simple and efficient method for the synthesis of polyhydroquinolines and 2,3-dihydroquinazolin-4(1H)-ones in the presence of catalytic amounts of GSA@MNPs in ethanol under reflux conditions. The details of the preparation procedure of the supported catalyst are presented in Scheme 1. Initially, the magnetic core of Fe₃O₄ nanoparticles has been prepared by a chemical coprecipitation technique using FeCl₃·6H₂O and FeCl₂·6H₂O in basic solution at 80 °C.^4,9 Ultimately, after coating the Fe₃O₄ nanoparticles with gluconic acid solution, the functionalization of the facial hydroxyl groups with chlorosulfonic acid led to supported glucosulfonic acid on Fe₃O₄ nanoparticles (GSA@MNPs).

Scheme 1 Synthesis of GSA@MNPs.

2.2. Catalyst characterization

The catalyst has been characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR) and a Vibrating Sample Magnetometer (VSM).

The morphology and size of the catalyst was evaluated using scanning electron microscopy and transmission electron microscopy. It can be seen that most of the particles are quasi-spherical with an average diameter of about 10 nm (Fig. 1). To investigate the catalyst characterization state of the supported sulfonic acid species, the synthesized catalyst was analyzed using EDS. As shown in Fig. 2, the EDS spectrum of the catalyst showed the presence of S, O and C species in the catalyst (Fig. 2).

Fig. 1 TEM (a and b) and SEM (c) images of GSA@MNPs.

Fig. 2 EDS spectrum of GSA@MNPs.

The formation of a magnetite crystal phase in the glucosulfonic acid-coated Fe₃O₄ aggregate powder was identified from the X-ray diffraction pattern (Fig. 3). As seen in Fig. 3, the iron oxide phase was identified from the XRD patterns by the peak positions at 30.2 (2 2 0), 35.5 (3 1 1), 43.0 (4 0 0), 57.1 (5 1 1) and 62.9 (4 4 0), which were in agreement with the standard data of magnetite.³²

Fig. 3 The XRD pattern of GSA@MNPs.

One indication of the bond formation between the Fe₃O₄ and the catalyst can be inferred from thermogravimetric analysis (TGA). Fig. 4 shows the TGA curves for bare Fe₃O₄ nanoparticles (blue curve), gluconic acid-coated nanoparticles (red curve) and the catalyst-treated nanoparticles (green curve). The magnetite-only curve reveals little in terms of mass loss. Loss of strongly adsorbed water and dehydration of surface hydroxy groups occurs at approximately 250 °C. The weight loss at temperatures below 200 °C is due to the removal of physically adsorbed solvent and surface hydroxyl groups. The weight loss of about 2% between 260 and 350 °C may be associated with the thermal crystal phase transformation from Fe₃O₄ to γ-Fe₂O₃ (ref. 33) and decomposition of sulfonic acid and formation of sulfur dioxide.³⁴ Organic groups have been reported to desorb at temperatures above 260 °C. The gluconic acid-coated magnetite nanoparticles (GA@MNPs) are found to show a mass percentage loss of about 12%, while the catalyst-loaded particles have the greatest mass loss, at 28%.

Fig. 4 TGA diagram of (blue line) Fe₃O₄ NPs, (red line) GA@MNPs and (green line) GSA@MNPs.

Successful functionalization of the Fe₃O₄ NPs can be inferred using the FT-IR technique. The FT-IR spectrum of the GSA@MNPs shows several peaks that are characteristic of a functionalized glucosulfonic acid, which clearly differs from those of the unfunctionalized Fe₃O₄ nanomagnets and GA@MNPs nanoparticles (Fig. 5). The FT-IR spectrum for the Fe₃O₄ alone shows a stretching vibration at 3420 cm⁻¹ which incorporates the contributions from both symmetrical and asymmetrical modes of the O–H bonds that are attached to the surface of the magnetic nanoparticles. The strong bands at low wavenumbers (≤700 cm⁻¹) come from the vibrations of the Fe–O bonds of iron oxide.⁴ The presence of an adsorbed water layer is confirmed by a stretch for the vibrational mode of water found at 1631 cm⁻¹. In the FT-IR spectrum of the GA@MNPs, the presence of the anchored glucosulfonic acid group is confirmed by C–H stretching vibrations that appear at 2970 and 2850 cm⁻¹ and also O–H stretching vibration modes as a broad band that appears at 3400 cm⁻¹. Reaction of the GA@MNPs with chlorosufonic acid produces GSA@MNPs in which the presence of the SO₃H moiety is asserted by 998–1220 cm⁻¹ bands in the FT-IR spectrum. Also, vibrations in the range of 2850–3500 cm⁻¹ are attributed to the terminal acidic groups. In addition, in the spectrum of the GSA@MNPs the peak at 3405 cm⁻¹, which is overlapped by the C–H stretching vibration, is probably attributable to the SO₃–H groups.⁹ All of these bands reveal that the surface of the Fe₃O₄ nanoparticles is successfully modified with glucosulfonic acid.

Fig. 5 FT-IR spectra of (a) Fe₃O₄ NPs, (b) GA@MNPs and (c) GSA@MNPs.

As superparamagnetic particles are beneficial for magnetic separation, the magnetic properties of the MNPs and GSA@MNPs were characterized using a VSM. The room temperature magnetization curves of the GSA@MNPs are shown in Fig. 6. The magnetic measurements show that the GSA@MNPs have a saturated magnetization value of 49 emu g⁻¹.

Fig. 6 Magnetization curve for GSA@MNPs at room temperature.

2.3. Catalytic study

As a part of our ongoing program directed towards the development of new methods for the catalytic activity of GSA@MNPs in organic reactions, we were interested in finding a simple and efficient method for the one-pot synthesis of polyhydroquinoline derivatives using magnetic nanoparticles bonded to glucosulfonic acid (GSA@MNPs) as a magnetically recoverable nanocatalyst in ethanol (Scheme 2).

Scheme 2 GSA@MNPs catalyzed the one-pot synthesis of polyhydroquinoline derivatives.

The reaction conditions for the one-pot synthesis of polyhydroquinoline derivatives was optimized from the reaction of 4-chlorobenzaldehyde with dimedone, ammonium acetate and ethylacetoacetate under the influence of different amounts of GSA@MNPs in ethanol as a model reaction (Table 1). It is noteworthy that only 50% of the desired product was isolated using a TLC plate in the absence of the catalyst after 200 min at 80 °C (Table 1, entry 1). As shown in Table 1, 4-chlorobenzaldehyde (1 mmol), dimedone (1 mmol), ethylacetoacetate (1 mmol) and ammonium acetate (1.2 mmol) in the presence of a catalytic amount of GSA@MNPs (0.05 g) in ethanol under reflux conditions were found to be the ideal reaction conditions for the one-pot synthesis of polyhydroquinoline derivatives.

Table 1 Optimization of the conditions for synthesis of polyhydroquinolines via the condensation of 4-chlorobenzaldehyde, dimedone, ethylacetoacetate and ammonium acetate as a model reaction in ethanol for 200 min

Entry	Catalyst (mg)	Temperature (°C)	Yield^a (%)
a Isolated yield.
1	—	80	41
2	0.02	80	54
3	0.03	80	61
4	0.04	80	77
5	0.05	80	94
6	0.05	60	67
7	0.05	—	Trace

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The reaction of various benzaldehyde derivatives, including electron-donating and electron-withdrawing groups on the aromatic ring, with dimedone, ethylacetoacetate and ammonium acetate was then investigated to confirm the generality of the present method. The polyhydroquinoline derivatives were obtained in high yields. The results of this study are summarized in Table 2. The effect of the substitution present on the aromatic aldehyde on the reaction rate and the overall yield was also studied. As shown, a variety of benzaldehydes bearing electron-donating (Table 2, entries 2–6) and electron-withdrawing (Table 2, entries 7–10) substituents were successfully employed to prepare the corresponding polyhydroquinoline derivatives in excellent yields.

Table 2 Synthesis of polyhydroquinolines catalyzed by GSA@MNPs in ethanol at 80 °C

Entry	Product	Time (min)	Yield^a (%)	Melting point (°C)	Ref.
a Isolated yield.
1		240	90	218–220	36
2		250	92	176–179	9
3		260	89	252–254	9
4		200	88	230–232	36
5		250	94	249–250	9
6		200	88	204–205	35
7		300	80	176–178	27
8		280	91	251–252	9
9		210	93	184–186	9
10		200	94	238–239	35

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The mechanism of this reaction is shown in Scheme 3.³⁷ The role of the catalyst comes in the Knoevenagel-type coupling of the aldehydes with the active methylene compounds and in the Michael-type addition of the intermediates to give the final product.

Scheme 3 The proposed mechanism of the synthesis polyhydroquinoline derivatives in the presence of GSA@MNPs.

In the second part of our study on the application of the catalytic activity of GSA@MNPs in organic synthesis, we were interested in finding a simple and efficient method for the synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives, under the influence of GSA@MNPs as a reusable nanocatalyst with short reaction times in good to excellent yields in ethanol under reflux conditions, using the cyclocondensation reaction of aldehydes and anthranilamide (Scheme 4).

Scheme 4 GSA@MNPs catalyzed the synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives.

The reaction conditions for the synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives was optimized using the cyclocondensation reaction of anthranilamide (1 mmol) and 4-chlorobenzaldehyde (1 mmol) in ethanol in the presence of different amounts of GSA@MNPs as a model reaction over a wide range of temperatures (Table 3). As shown in Table 3, 4-chlorobenzaldehyde (1 mmol) in the presence of a catalytic amount of GSA@MNPs (0.01 g) in ethanol at 80 °C were found to be the ideal reaction conditions for the synthesis 2,3-dihydroquinazolin-4(1H)-ones. In order to show the activity of the GSA@MNPs, we carried out the cyclocondensation of 4-chlorobenzaldehyde with anthranilamide in the absence of catalyst, in which the reaction did not occur even after a prolonged reaction time (Table 3, entry 1).

Table 3 Optimization of the conditions for synthesis of 2,3-dihydroquinazolin-4(1H)-ones via the condensation of 4-chlorobenzaldehyde with anthranilamide as a model reaction in ethanol for 50 min

Entry	Catalyst (g)	Temperature (°C)	Yield^a (%)
a Isolated yield.b No reaction.
1	—	80	—^b
2	0.005	80	45
3	0.007	80	67
4	0.01	80	99
5	0.01	60	72
6	0.01	—	Trace

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After the optimization of the reaction conditions, various aldehydes including several different functional groups were reacted under the optimum conditions and the corresponding 2,3-dihydroquinazolin-4(1H)-one compounds were obtained in good to excellent yields. The results of these studies are summarized in Table 4. As shown, a variety of benzaldehydes bearing electron-donating (Table 4, entries 2–6) and electron-withdrawing (Table 4, entries 7–10) substituents were successfully employed to prepare the corresponding 2,3-dihydroquinazolin-4(1H)-one derivatives in excellent yields. The experimental procedure is very simple and convenient, and has the ability to tolerate a variety of other functional groups, such as hydroxyl, halide, nitro, alkyl and alkoxy, under the reaction conditions.

Table 4 Synthesis of 2,3-dihydroquinazolin-4(1H)-ones catalyzed by GSA@MNPs in ethanol at 80 °C

Entry	Product	Time (min)	Yield^a (%)	Melting point (°C)	Ref.
a Isolated yield.
1		55	90	221–223	4
2		75	94	190–192	9
3		25	96	275–278	10
4		70	92	228–230	9
5		75	93	167–169	4
6		25	98	211–213	10
7		35	99	197–199	10
8		65	96	197–199	9
9		50	99	202–204	4
10		80	91	190–192	10

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2.4. Comparison of the catalyst

To show the merit of glucosulfonic acid@Fe₃O₄ in comparison with other reported catalysts, we summarize several results for the preparation of 2-(4-chlorophenyl)-2,3-dihydoquinazolin-4(1H)-one from 4-chlorobenzaldehyde and anthranilamide in Table 5. It is obvious that the catalyst showed a good reaction time and higher yield than other catalysts used in the literature. Also, the new catalyst is comparable in terms of price, non-toxicity, stability and ease of separation.

Table 5 Comparison results of glucosulfonic acid@Fe₃O₄ with other catalysts for the reaction of anthranilamide and 4-chlorobenzaldehyde

Entry	Catalyst (mol%)	Time (min)	Yield (%)	Conditions [Ref.]
1	2-Morpholino ethanesulfonic acid (10)	180	89	Ethanol, 60 °C
		12	92	Ethanol, MW (600 W) [ref. 38]
2	Propylphosphonic anhydride (0.5 mmol)	10	87	CH3CN, sealed tube [ref. 39]
3	[hnmp][HSO4] (5)	28	83	Solvent-free, 80 °C [ref. 40]
	[NMP][HSO4] (5)	22	84
	[NMP][H2PO4] (5)	38	79
4	[Bmim]PF6 (2 mL)	40	90	Ionic liquid, 75 °C [ref. 41]
5	Co–carbon nanotubes (0.008 g)	12	91	Solvent-free, rt [ref. 42]
6	H3PW12O40 (0.1)	10	90	H2O, rt [ref. 43]
7	Poly(4-vinylpyridine) supported acidic ionic liquid (0.2 g)	8	90	Ethanol, rt, ultrasonic irradiation [ref. 44]
8	β-Cyclodextrin-SO3H (0.1 mmol)	30	83	H2O, rt [ref. 45]
9	Citric acid (0.4 mmol), acidic Al2O3 (0.5 g)	15	85	Solvent-free, rt, grinding [ref. 46]
10	Glucosulfonic acid@Fe3O4 (0.01 g)	50	99	Ethanol, reflux [this work]

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2.5. Recyclability of the catalyst

The GSA@MNPs, as a magnetically reusable nanocatalyst, can be easily recycled for repeated synthesis of polyhydroquinoline. For practical purposes the ability to easily recycle the catalyst is highly desirable. To investigate this issue, the recyclability of the catalyst was examined for the reaction of 4-chlorobenzaldehyde with dimedone, ethylacetoacetate and ammonium acetate as a model reaction in ethanol using 0.05 g of catalyst. We found that this catalyst demonstrated remarkably excellent reusability; after the completion of the reaction, the catalyst was easily and rapidly recovered from the reaction mixture using an external magnet. The remaining magnetic nanocatalyst was washed with ethanol to remove residual product and the reaction mixture decanted (Fig. 7). Then, the reaction vessel was charged with fresh 4-chlorobenzaldehyde, dimedone, ethylacetoacetate and ammonium acetate and subjected to the next run. As shown in Fig. 8, the catalyst was used over 6 runs without any significant loss of activity. The average isolated yield for 6 successive runs was 96%, which clearly demonstrates the practical recyclability of this catalyst. In addition, one of the attractive features of this novel catalyst system is the rapid (within 5 s) and efficient (100%) separation of the catalyst using an appropriate external magnet, which minimizes the loss of catalyst during separation.

Fig. 7 Image showing that GSA@MNPs can be separated using an applied magnetic field. A reaction mixture in the absence (left) or presence (right) of a magnetic field.

Fig. 8 The recycling experiment of GSA@MNPs in the condensation of 4-chlorobenzaldehyde, dimedone, ethylacetoacetate and ammonium acetate.

3. Conclusions

In summary, we have demonstrated that GSA@MNPs can be used as a green, efficient and reusable nanocatalyst for the synthesis of a wide range of polyhydroquinoline and 2,3-dihydroquinazolin-4(1H)-one derivatives in ethanol under reflux conditions. The advantages of these protocols are the use of commercially available, eco-friendly, cheap and chemically stabile materials, the operational simplicity, practicality and good to high yields. The product separation and catalyst recycling are easier and simpler with the assistance of an external magnet. The catalyst can be reused 6 times with little loss of activity.

4. Experimental

4.1. Preparation of the Fe₃O₄ magnetic nanoparticles

The free Fe₃O₄ NPs were prepared using chemical precipitation of Fe³⁺ and Fe²⁺ ions with a molar ratio of 2 : 1. Typically, FeCl₃·6H₂O (5.838 g, 0.0216 mol) and FeCl₂·4H₂O (2.147 g, 0.0108 mol) were dissolved in 100 mL deionized water at 80 °C under N₂ atmosphere and vigorous mechanical stirring conditions. Then, 10 mL of 25% NH₄OH was added to the reaction mixture. After 30 minutes, the reaction mixture was cooled to room temperature. After completion of the reaction, the nanoparticles (Fe₃O₄) were washed two times with distilled water and a 0.02 M solution of NaCl, and each time was decanted with an external magnet.

4.2. Preparation of magnetic nanoparticles bonded with gluconic acid (GA@MNPs)

The obtained Fe₃O₄ NPs (2 g) were dispersed in 15 mL water, and dissolved by sonication for 30 min, and then gluconic acid solution (8 mL) was added to the reaction mixture. The reaction mixture was stirred under N₂ atmosphere at 80 °C for 8 h. Then, the final product was separated by magnetic decantation and washed with ethanol to remove the unattached substrate. The nanoparticle product (GA@MNPs) was dried at room temperature.

4.3. Preparation of supported glucosulfonic acid on Fe₃O₄ magnetic nanoparticles (GSA@MNPs)

The GA@MNPs (0.5 g) were dispersed in dry n-hexane (5 mL) using an ultrasonic bath for 20 min. Subsequently, chlorosulfonic acid (1.2 mL) was added drop-wise over a period of 30 min and the mixture was stirred for 4 h at room temperature. Then, the final product was separated by magnetic decantation and washed twice with dry n-hexane, ethanol and n-hexane, respectively, to remove the unattached substrate. The product (GSA@MNPs) was stored in a refrigerator prior to use.

4.4. General procedure for the synthesis of polyhydroquinoline derivatives

A mixture of aldehyde (1 mmol), dimedone (1 mmol), ethylacetoacetate (1 mmol), ammonium acetate (1.2 mmol) and GSA@MNPs (0.05 g) was stirred in ethanol under reflux conditions and the progress of the reaction was monitored by TLC. After completion of the reaction, the catalyst was separated using an external magnet and washed with ethyl acetate. Then, the solvent was evaporated and the product recrystallized in ethanol, from which the pure polyhydroquinoline derivatives were obtained in good to excellent yields.

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

A mixture of GSA@MNPs (0.01 g), anthranilamide (1 mmol) and aldehyde (1 mmol) was stirred at 80 °C in ethanol (2 mL). The progress was monitored by TLC. After completion of the reaction, the reaction mixture was cooled to room temperature. CH₂Cl₂ (2 × 5 mL) was added and the catalyst was separated using an external magnet. CH₂Cl₂ was evaporated under reduced pressure to afford the essentially pure products and all products were recrystallized in ethanol for further purification.

4.6. Characterization data of selected compounds

Ethyl-4-(4-ethoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (entry 2, Table 2). Mp: 176–179 °C. IR (KBr) cm⁻¹: 3446, 3276, 3198, 1684, 1607, 1494. ¹H NMR (400 MHz, DMSO-d₆): δ_H = 7.28–7.19 (m, 2H), 6.74–6.72 (d, J = 8, 2H), 5.80 (s, 1H), 4.99 (s, 1H), 4.07–4.05 (t, J = 4, 2H), 3.97–3.96 (t, J = 3.6, 2H), 2.39–2.15 (m, 7H), 1.38–1.37 (m, 3H), 1.21–1.20 (m, 3H), 1.07 (s, 3H), 0.95 (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 2). Mp: 252–254 °C. IR (KBr) cm⁻¹: 3276, 3276, 3246, 3208, 1702, 1648, 1423. ¹H NMR (400 MHz, DMSO-d₆): δ_H = 9.04 (s, 1H), 7.05–7.03 (d, J = 8, 2H), 7.00–6.98 (d, J = 8, 2H), 4.82 (s, 1H), 4.00–3.95 (q, J = 7.2, 2H), 2.45–2.41 (d, J = 16, 1H), 2.31–2.27 (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 2). Mp: 249–250 °C. IR (KBr) cm⁻¹: 3278, 3246, 3208, 1701, 1649, 1423. 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), 4.80 (s, 1H), 4.02–3.96 (q, J = 7.2, 2H), 3.69 (s, 3H), 2.52–2.45 (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 2). Mp: 204–205 °C. IR (KBr) cm⁻¹: 3280, 3213, 1696, 1645, 1452. 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), 4.80 (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), 2.35–2.27 (m, 4H), 2.22–2.18 (d, J = 16, 1H), 2.03–1.99 (d, J = 16, 1H), 1.20–1.16 (t, J = 6.8, 3H), 1.03 (s, 3H), 0.90 (s, 3H) ppm.

Ethyl-4-(4-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (entry 8, Table 2). Mp: 251–252 °C. IR (KBr) cm⁻¹: 3276, 3243, 3207, 1703, 1649, 1421. 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, 2H), 4.84 (s, 1H), 4.01–3.96 (q, J = 6.8, 2H), 2.52–2.46 (d, J = 26.4 1H), 2.31–2.27 (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.

2-(4-Methylphenyl)-2,3-dihydroquinazolin-4(1H)-one (entry 4, Table 4). Mp: 228–230 °C. IR (KBr) cm⁻¹: 3313, 1658, 1611, 1439. ¹H NMR (400 MHz, DMSO-d₆): δ_H = 8.21 (s, 1H), 7.62–7.59 (d, J = 7.5, 1H), 7.38–7.35 (d, J = 7.5, 2H), 7.26–7.14 (m, 3H), 7.03 (s, 1H), 6.75–6.64 (m, 2H), 5.71 (s, 1H), 2.49–2.42 (s, 3H) ppm.

2-(4-Ethoxyphenyl)-2,3-dihydoquinazolin-4(1H)-one (entry 5, Table 4). Mp: 167–169 °C. IR (KBr) cm⁻¹: 3301, 1650, 1613, 1443. ¹H NMR (400 MHz, DMSO-d₆): δ_H = 7.95–7.94 (b, 1H), 7.52–7.50 (m, 2H), 7.34 (s, 1H), 7.26 (s, 1H), 6.95–6.90 (m, 3H), 6.68–6.67 (m, 1H), 5.85 (s, 1H), 5.75 (s, 1H), 4.07–4.05 (q, J = 4, 2H), 1.46–1.44 (s, 3H) ppm.

2-(3,4-Dimethoxyphenyl)-2,3-dihydoquinazolin-4(1H)-one (entry 6, Table 4). Mp: 211–213 °C. IR (KBr) cm⁻¹: 3335, 1671, 1610, 1436. ¹H NMR (400 MHz, DMSO-d₆): δ_H = 8.21 (s, 1H), 7.64–7.62 (d, J = 7.6, 1H), 7.28–7.24 (t, J = 0.8, 1H), 7.15 (d, J = 1.6, 1H), 7.04–6.97 (m, 2H), 6.95 (s, 1H), 6.78–6.76 (d, J = 8, 1H), 6.72–6.67 (t, J = 1.2, 1H), 5.71 (s, 1H), 3.77 (s, 3H), 3.76 (s, 3H) ppm.

2-(4-Bromophenyl)-2,3-dihydoquinazolin-4(1H)-one (entry 8, Table 4). Mp: 197–199 °C. IR (KBr) cm⁻¹: 3310, 1656, 1608, 1433. ¹H NMR (400 MHz, DMSO-d₆): δ_H = 8.17–8.14 (m, 1H), 7.80–7.78 (m, 1H), 7.63–7.59 (m, 3H), 7.47–7.44 (m, 2H), 7.30–7.24 (m, 1H), 6.77–6.72 (d, J = 19.2, 1H), 6.71–6.68 (m, 1H), 5.76 (s, 1H) ppm.

2-(4-Chlorophenyl)-2,3-dihydoquinazolin-4(1H)-one (entry 9, Table 4). Mp: 202–204 °C. IR (KBr) cm⁻¹: 3309, 1655, 1611, 1435. ¹H NMR (400 MHz, DMSO-d₆): δ_H = 8.29 (s, 1H), 7.61–7.43 (m, 5H), 7.26–7.20 (t, J = 7.5, 1H), 7.12 (s, 1H), 6.75–6.63 (m, 2H), 5.75 (s, 1H) ppm.

2-(2-Nitrophenyl)-2,3-dihydoquinazolin-4(1H)-one (entry 10, Table 4). Mp: 190–192 °C. IR (KBr) cm⁻¹: 3372, 1667, 1613, 1517, 1453, 1342. ¹H NMR (400 MHz, DMSO-d₆): δ_H = 8.26 (s, 1H), 8.10–8.08 (d, J = 8, 1H), 7.89–7.87 (d, J = 8, 1H), 7.83–7.80 (t, J = 0.8, 1H), 7.70–7.63 (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.

Acknowledgements

This work was supported by the research facilities of Ilam University, Ilam, Iran.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ra08952b

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