CuFe₂O₄ nanoparticles: a magnetically recoverable and reusable catalyst for the synthesis of quinoline and quinazoline derivatives in aqueous media

Abstract

The synthesis of quinoline and quinazoline derivatives is attempted using magnetically separable and reusable CuFe₂O₄ nanoparticles in aqueous media. Nano sized CuFe₂O₄ was prepared by the thermal decomposition of Cu(NO₃)₂ and Fe(NO₃)₃ in water in the presence of sodium hydroxide and confirmed by X-ray diffraction patterns (XRD), scanning electron microscopy images (SEM) and transmission electron microscopy (TEM). The catalytic activity of CuFe₂O₄ nanoparticles was evaluated in aqueous media and the results show its applicability as a green, reusable and promising catalyst in organic synthesis.

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1. Introduction

Magnetic nanoparticles (NPs) are of great interest for researchers from a wide range of disciplines, including magnetic fluids,¹ catalysis,² data-storage³ and environmental remediation.⁴ Nanocatalysis is a rapidly growing field which involves using nanomaterials as catalysts for a variety of organic reactions. Up to now, many investigations have been done on nanocatalysis, but there still remains the challenge of the recovery of the nanocatalysts from the reaction mixture. For this purpose, the use of magnetic NPs has emerged as a viable solution; their insoluble and paramagnetic nature enables an easy and efficient separation of the catalysts from the reaction mixture with an external magnet. Magnetic separation is an attractive alternative for filtration or centrifugation as it prevents the loss of catalyst and the reusability increases. This makes the catalyst cost-effective and promising for industrial applications. On the other hand, the use of water as a medium for organic reactions has a number of potential advantages because water is the most abundant, cheap, non-hazardous, non-toxic solvent. In addition to this, the isolation of the organic products can be performed by simple phase separation.

Quinoline and its derivatives have been widely used as an anti-malarial,^1,2 anti-inflammatory,³ anti-bacterial,⁴ anti-asthmatic,⁵ and anti-hypertensive.⁶ In addition, quinazoline derivatives are an important class of N-containing heterocyclic compounds because of their wide range of biological and physiological activities, such as antibacterial,⁷ anti-tubercular,⁸ anticancer⁹ and antiviral activities.¹⁰

To date, several methods for quinolines synthesis have been reported, including the Doebner–Miller synthesis¹¹ from anilines and α,β-unsaturated carbonyl compounds in the presence of an oxidizing agent, the Friedländer annulation¹² from ortho-acyl-arylamines and aldehydes/ketones (must contain an α-methylene group) and the Combes synthesis¹³ from arylamines and 1,3-dicarbonyl compounds. Among these methods, the Friedländer annulation is still one of the most simple and direct approaches for the synthesis of poly-substituted quinolines.^14–27

Also, a variety of synthetic methods have been developed for the preparation of quinazolines, such as the Bischler cyclization,²⁸ the reaction of 2-aminoarylalkanone O-phenyl oximes with aldehydes under microwave conditions in presence of 1-ethyl-3-methylimidazolium hexafluorophosphate,²⁹ condensation of 2-aminocarbonyl compounds and benzylic amines in presence of I₂/tert-butyl hydroperoxide (TBHP),³⁰ graphite oxide/TBHP,³¹ CAN/TBHP,³² CuO NPs supported on kaolin³³ and condensation of 2-aminobenzophenone, aromatic aldehydes and ammonium acetate in presence of I₂.³⁴

Although all these methods are effective, they have some serious disadvantages, such as tedious work-up procedures, the use of expensive or toxic metal catalysts and solvents, long reaction times and the formation of side products. Thus, the development of a simple, eco-benign and low cost protocol for a one-pot synthesis of quinoline and quinazoline derivatives still remains an attractive goal for researchers.

In continuation of our previous studies on developing improved methodologies for organic reactions,³⁵ herein, we wish to report an efficient and eco-friendly method for the synthesis of quinolines and quinazolines in the presence of CuFe₂O₄ NPs as catalysts in aqueous media (Scheme 1).

Scheme 1 Synthesis of quinolines and quinazolines in the presence of CuFe₂O₄ NPs.

2. Results and discussion

In order to determine the most appropriate reaction conditions and evaluate the catalytic activity of CuFe₂O₄ NPs, initially, a model reaction was carried out with the aim of preparing quinoline 3a (Scheme 2) by the condensation of 2-aminobenzophenone 1 (1 mmol) and dimedone 2 (1 mmol) using different quantities of CuFe₂O₄ NPs in water at 80 °C (Table 1).

Scheme 2 The reaction of 2-aminobenzophenone with dimedone as the model reaction.

Table 1 Optimization of the reaction conditions for the synthesis of compound 3a

Entry	Catalyst	Time (min)	Solvent	Temp. (°C)	Yield^a (%)
a The yields refer to the isolated product.
1	—	120	H2O	80	Trace
2	1 mol%	85	H2O	80	45
3	2 mol%	64	H2O	80	60
4	3 mol%	52	H2O	80	68
5	4 mol%	43	H2O	80	85
6	5 mol %	32	H2O	80	95
7	6 mol %	40	H2O	80	95
8	5 mol %	45	H2O	25	75
9	5 mol %	35	H2O	50	85
10	5 mol %	45	EtOH	80	72
11	5 mol %	55	CH3CN	80	65
12	5 mol %	58	THF	80	70

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In the absence of catalyst, product 3a was produced in water with very a low yield after 120 min at 80 °C (Table 1, entry 1), but, upon addition of a catalytic amount (1 mol%) of CuFe₂O₄ NPs the yield increased to 45% in 85 min (Table 1, entry 2). Having observed the catalytic acceleration effect of CuFe₂O₄ NPs, we slowly increased the amount of catalyst for optimization studies (Table 1). It was observed that 5 mol% of CuFe₂O₄ NPs gave a maximum yield (95%) after 32 min (Table 1, entry 6). Moreover, the increase in the amount of catalyst did not improve the results to an appreciable extent (Table 1, entry 7). Also, we carried out the model reaction at various temperatures ranging from 25 to 80 °C, which demonstrated 80 °C as the optimum temperature. Also, the model reaction in other solvents, such as EtOH, CH₃CN and THF, was inefficient and gave the product in lower yields (Table 1, entries 10–12). Thus, using 5 mol% of CuFe₂O₄ NPs in water at 80 °C was selected as the optimized condition for the synthesis of quinoline 3a.

To show the generality of this method, various α-methylene ketones were reacted with 2-aminoaryl ketones under the optimized condition. The results are summarized in Table 2. In all cases the corresponding substituted quinolines were obtained in excellent yields and short reaction times (Table 2). Also, cyclic ketones such as cyclopentanone and cyclohexanone successfully reacted with 2-aminoaryl ketones to afford the respective quinolines with high yields (Table 2, entries 7,8,12 and 14).

Table 2 Synthesis of quinoline derivatives catalyzed by CuFe₂O₄ NPs^a

Entry	2-Aminoketone	Ketone	Product^b	Time (min)	Yield^c (%)
a Reaction conditions: 2-aminoketone (1 mmol), carbonyl compound (1 mmol) and CuFe2O4 NPs (5 mol%) water (2 mL), 80 °C.b All compounds are known and their structures were established from their spectral data and melting points compared to the literature values.c Isolated yield.
1				32	95 (ref. 22)
2				38	90 (ref. 17)
3				32	92 (ref. 22)
4				36	89 (ref. 22)
5				38	85 (ref. 22)
6				35	90 (ref. 17)
7				37	92 (ref. 22)
8				39	88 (ref. 17)
9				28	92 (ref. 22)
10				32	95 (ref. 22)
11				34	92 (ref. 22)
12				34	84 (ref. 22)
13				33	90 (ref. 17)
14				32	86 (ref. 17)
15				34	88 (ref. 17)

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After the successful application of CuFe₂O₄ NPs in the synthesis of quinolines, we examined the efficacy of this catalyst in the preparation of quinazolines (Scheme 3).

Scheme 3 The reaction of 2-aminobenzophenone, benzaldehyde and ammonium acetate as the model reaction.

To optimize the reaction conditions for the synthesis of quinazoline derivatives, the condensation of 2-aminobenzophenone 1 (1 mmol), benzaldehyde 4 (1 mmol) and ammonium acetate (1 mmol) was selected as the model reaction in an aqueous medium at 80 °C (Table 3). In the absence of catalyst, only a trace amount of 2,4-diphenylquinazoline 5a was obtained in water even after 10 h (Table 3, entry 1). The yield of product 5a increased when 1 mol% of catalyst was used (Table 3, entry 2). The model reaction was carried out in the presence of different amounts of catalyst and the best results were obtained when the reaction was performed in the presence of 5 mol% of catalyst in water at 80 °C (Table 3, entry 6). Various solvents such as EtOH, MeCN, CH₂Cl₂, THF and H₂O were also examined. Among the different solvents, water proved to be the best medium for this reaction (Table 3).

Table 3 Optimization of the three-component reaction 2-aminobenzophenone, benzaldehyde and ammonium acetate

Entry	Catalyst loading	Solvent	Time (h)	Yield^a (%)
a The yields refer to the isolated product.
1	—	H2O	10	Trace
2	1 mol%	H2O	7	65
3	2 mol%	H2O	5	78
4	3 mol%	H2O	4	85
5	4 mol%	H2O	3	90
6	5 mol %	H2O	1	95
7	6 mol %	H2O	1	95
8	5 mol %	EtOH	5	82
9	5 mol %	MeCN	7	80
10	5 mol %	CH2Cl2	6	75
11	5 mol %	THF	5	85

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Encouraged by these remarkable results, and in order to show the generality and scope of this new protocol, a variety of quinazolines were synthesized in the presence of a catalytic amount of CuFe₂O₄ NPs under similar conditions. The results are summarized in Table 4. Under similar reaction conditions, various aromatic aldehydes afforded the corresponding products in high yields. The effect of the substituent 2-aminobenzophenone and aldehyde derivatives on the reaction time and yield has also been examined. In the presence of electron withdrawing groups at the 5th position of 2-aminobenzophenone, the reaction time increased compared with electron donating groups (Table 4, entries 7–14).

Table 4 Synthesis of quinazoline derivatives catalyzed by CuFe₂O₄ NPs^a

Entry	2-Aminoketone	Aldehyde	Product^b	Time (min)	Yield^c^,^34 (%)
a Reaction conditions: 2-aminoketone (1 mmol), aldehyde (1 mmol), ammonium acetate (1 mmol), CuFe2O4 NPs (5 mol%) water (2 mL), 80 °C.b All compounds are known and their structures were established from their spectral data and melting points compared to the literature values.c Isolated yield.
1				60	95
2				43	95
3				48	90
4				38	92
5				62	97
6				70	90
7				82	95
8				80	97
9				65	90
10				70	90
11				40	95
12				45	92
13				90	92
14				90	90

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The possibility of recycling the catalyst was also examined. For this reason, the reaction of aminobenzophenone 1 (1 mmol) with dimedone 2 (1 mmol) in the presence of 5 mol% CuFe₂O₄ NPs was studied to give the analogous product 3,3-dimethyl-9-phenyl-3,4-dihydroacridin-1(2H)-one 3a. After completion of the reaction (monitored by TLC), the catalyst was separated from the reaction mixture with an external magnet and washed with distilled water (2 mL) and ethanol (2 mL) two times, dried in an oven and reused successively 5 times without any significant loss of activity (Table 5).

Table 5 Reusability studies of the catalysts for the synthesis of compound 3a (Table 2, entry 1)^a

a Reaction condition: 2-aminobenzophenone (1 mmol), dimedone (1 mmol), CuFe2O4 NPs (5 mol%), water (2 mL), 80 °C.b Isolated yield.
The number of experiments	1	2	3	4	5
Isolated yield^b (%)	95	94	92	92	88

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A plausible mechanism for the formation of quinolines using CuFe₂O₄ NPs as the catalyst is shown in Fig. 1.³⁶ First, the carbonyl groups of 2-aminoaryl and α-methylene ketones are activated by CuFe₂O₄ NPs followed by the aldol condensation between these compounds that leads to intermediate I. This intermediate is then converted to intermediate II via the removal of H₂O and protonation of the carbonyl group. Thereafter, intermediate II, via the ring closure between the amine group and the protonated carbonyl group, converts to intermediate III, which is followed by the water elimination of intermediate III to give the quinoline derivatives.

Fig. 1 The proposed mechanism for the synthesis of quinolines using CuFe₂O₄ NPs.

A possible mechanism for the synthesis of quinazolines using CuFe₂O₄ NPs as the clean catalyst is shown in Fig. 2.³⁷ The coordination of CuFe₂O₄ NPs with the carbonyl groups of 2-aminoaryl ketones and aldehydes could increase the electrophilicity of carbonyl carbons and enhance the subsequent nucleophilic attack of the amine group and NH₄OAc. Afterwards, the condensation of aldehyde with the amine leads to aldimine A and then this intermediate, by the attack of NH₄OAc to the keto group of benzophenone, leads to ketimine B. Thereafter, intermediate B, via the ring closure, converts to intermediate C, which is followed by aromatization through dehydration in conjunction with oxygen from the air to give the quinazoline derivatives in good to excellent yields.

Fig. 2 The proposed mechanism for the synthesis of quinazolines using CuFe₂O₄ NPs.

3. Experimental

All reagents were prepared from analytical reagent grade chemicals unless specified otherwise and purchased from the Merck Company. Melting points were measured with an Electrothermal 9100 apparatus. The samples were analyzed using FT-IR spectroscopy (using a Perkin Elmer 65 in KBr matrix in the range of 4000–400 cm⁻¹). ¹H and ¹³C NMR spectra were recorded on a BRUKER DRX-400 AVANCE spectrometer using tetramethylsilane (TMS) as an internal standard.

3.1. Preparation of CuFe₂O₄ NPs

CuFe₂O₄ NPs were prepared by thermal decomposition of Cu(NO₃)₂ and Fe(NO₃)₃ in water in the presence of sodium hydroxide. Briefly, to a solution of Fe(NO₃)₃·9H₂O (3.34 g, 8.2 mmol) and Cu(NO₃)₂·3H₂O (1 g, 4.1 mmol) in 75 mL of distilled water, 3 g (75 mmol) of NaOH dissolved in 15 mL of water were added at room temperature over a period of 10 min, during which a reddish-black precipitate was formed. Then the reaction mixture was warmed to 90 °C and stirred. After 2 h, it was cooled to room temperature and the magnetic particles so formed were separated by a magnetic separator. It was then washed with water (3 × 30 mL) and the catalyst was kept in an air oven overnight at 80 °C. Then the catalyst was ground with a pestle and mortar and kept in a furnace at 700 °C for 5 h (step up temperature 20 °C min⁻¹), and then slowly cooled to room temperature. 820 mg of magnetic CuFe₂O₄ NPs were obtained.

3.2. Catalyst characterizations

The systematic characterization of the CuFe₂O₄ NPs catalyst was carried out with X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The X-ray diffraction analysis was done in a Philips PW 1830 X-ray diffractometer with a CuKα source (λ = 1.5418 Å) in a range of Bragg's angle (5–60°) at room temperature. The X-ray diffraction pattern of the calcined sample (Fig. 3) perfectly matches with the expected cubic spinel structure of CuFe₂O₄ NPs. The average crystallite size (L) was calculated from the X-ray line broadening using the (311) peak and Debye–Sherrer's equation; L = 0.89λ/β cos θ; β is the FWHF and λ is the wavelength of the radiation and L was found to be 10.3 nm. Scanning electron micrograph (SEM) pictures were taken using a JEOL JSM-5300 microscope (acceleration voltage10 kV). The sample powder was deposited on a carbon tape before mounting on a sample holder. In order to reduce the charge developed on the sample, gold sputtering was done in 3 min. The SEM of the CuFe₂O₄ NPs sample is shown in Fig. 4a. As indicated in this figure, small agglomerated nanoparticles with a disordered surface morphology are observed. The transmission electron micrographs (TEM) were obtained with a Philips CM-10 microscope. The CuFe₂O₄ NPs samples for TEM were prepared by dispersing the powdered sample in ethanol by sonication and then drop drying on a copper grid (400 mesh) coated with a carbon film. As the TEM figure shows, the average size of the particles resulting from this method is approximately 5–15 nm. The particle sizes obtained from TEM are in good agreement with the XRD measurement (Fig. 4b).

Fig. 3 X-ray diffraction pattern of CuFe₂O₄ NPs.

Fig. 4 (a) SEM image of CuFe₂O₄ NPs, (b) TEM image of CuFe₂O₄ NPs.

3.3. General procedure for the synthesis of quinolines

A mixture of 2-aminoketone (1 mmol), carbonyl compound (1 mmol), CuFe₂O₄ NPs (5 mol%) in water (2 mL) and the reaction mixture was heated at 80 °C. Completion of the reactions was monitored by TLC (n-hexane–ethyl acetate 8 : 2). After completion of the reaction, the catalyst was separated from the reaction mixture using an external magnet and water (5 mL) was added to the resulting reaction mixture followed by extraction with EtOAc. The formation of products was related by comparing the melting points, IR and NMR data with authentic samples and the literature data.

1-(2-Methyl-4-phenylquinolin-3-yl)ethanone (Table 2, entry 3). IR (KBr): 3184, 2986, 1702, 1413, 1352, 865 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ = 2.12 (s, 3H), 2.75 (s, 3H), 7.24–7.69 (m, 8H), 8.10 (d, J = 8.1 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ = 22.4, 30.2, 32.5, 123.8, 125.5, 127.0, 128.3, 128.8, 129.2, 135.6, 146.8, 152.7, 204.1; HRMS calc. C₁₈H₁₅NO: 261.1346, found: 261.1334.

Ethyl 2-methyl-4-phenylquinoline-3-carboxylate (Table 2, entry 5). IR (KBr): 3445, 2923, 2865, 1692, 1563, 1402, 1226, 1025, 762, 605 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ = 1.04 (t, J = 7.1 Hz, 3H), 2.83 (s, 3H), 4.11 (q, J = 7.2 Hz, 2H), 7.52 (m, 6H), 7.59 (d, J = 8.2 Hz, 1H), 7.75 (t, J = 7.9 Hz, 1H), 8.12 (d, J = 8.1 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ = 14.1, 24.2, 62.3, 125.1, 126.1, 126.5, 128.2, 128.7, 128.9, 129.1, 131.3, 136.5, 147.3, 147.8, 155.4; HRMS calc. C₁₉H₁₇NO₂ + H⁺: 292.1378, found: 292.1369.

9-Phenyl-2,3-dihydro-1H-cyclopenta[b]quinoline (Table 2, entry 8). IR (KBr): 3073, 2943, 2867, 1583, 1479, 759, 712 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 1.82–1.89 (m, 2H), 1.96–2.11(m, 2H), 2.65 (t, J = 6.5 Hz, 2H), 3.19 (t, J = 6.8 Hz, 2H), 7.16–7.24 (m, 4H), 7.38–7.59 (m, 4H), 7.96 (d, J = 8.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ = 29.6, 23.5, 28.2, 34.6, 125.7, 125.9, 127.3, 128.5, 128.9, 129.4, 129.7, 137.2, 146.4, 146.7, 159.1; HRMS calc. C₁₈H₁₅N + H⁺: 246.1245, found: 246.1253.

7-Chloro-3,4-dihydro-3,3-dimethyl-9-phenylacridin-1(2H)-one (Table 2, entry 9). IR (KBr): 3068, 2875, 1644, 1576, 1493, 1089, 765 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ = 1.12 (s, 3H), 1.18 (s, 3H), 2.59 (s, 2H), 3.36 (s, 2H), 7.15–7.22 (m, 2H), 7.54 (d, J = 2.8 Hz, 1H), 7.51–7.56 (m, 3H), 7.53 (dd, J = 8.7, 2.5 Hz, 1H), 8.02 (d, J = 8.7 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ = 27.8, 32.5, 49.1, 54.2, 123.4, 126.8, 127.8, 128.0, 128.3, 128.6, 130.2, 132.5, 132.8, 136.9, 147.4, 150.2, 162.3, 198.6; HRMS calc. C₂₁H₁₈ClNO + H⁺: 336.1156, found: 336.1143.

2-Chloro-5,6,7,8-tetrahydro-9-phenylacridine (Table 2, entry 12). IR (KBr): 3023, 2955, 1632, 1587, 1482, 1183, 722 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ = 1.78–1.83 (m, 2H), 2.01–2.09 (m, 2H), 2.62 (t, J = 6.5 Hz, 2H), 3.21 (t, J = 6.6 Hz, 2H), 7.20 (dd, J = 7.2, 1.7 Hz, 2H), 7.29 (d, J = 2.4 Hz, 2H), 7.58–7.49 (m, 4H), 8.02 (d, J = 8.9 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ = 22.6, 23.1, 28.2, 34.5, 124.6, 127.4, 128.0, 128.9, 129.1, 129.2, 129.5, 130.1, 131.3, 137.2, 144.7, 145.8, 159.5; HRMS calc. C₁₉H₁₆ClN + H⁺: 293.1024, found: 293.1015.

9-Methyl-1,2,3,4-tetrahydroacridine (Table 2, entry 13). IR (KBr): 3182, 2948, 1569, 1486, 1149, 1029, 756 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ = 1.72–1.76 (m, 4H), 2.32 (s, 3H), 2.63 (t, J = 8.1 Hz, 2H), 3.12 (t, J = 7.8 Hz, 2H), 7.24–7.85 (m, 4H); ¹³C NMR (100 MHz, CDCl₃) δ = 13.4, 23.3, 23.8, 26.7, 34.2, 123.1, 125.2, 126.2, 128.4, 128.9, 141.1, 146.4158.3; HRMS calc. C₁₄H₁₅N + H⁺: 199.1652, found: 199.1643.

3.4. General procedure for the synthesis of quinazolines

A mixture of 2-aminoketone (1 mmol), aldehydes (1 mmol) and ammonium acetate (0.07 g, 1 mmol) was added to CuFe₂O₄ NPs (5 mol%) in water (2 mL) and the reaction mixture was heated at 80 °C, while the air was bubbled into the reaction mixture. Completion of the reactions was monitored by TLC (n-hexane–ethyl acetate 9 : 1). After completion of the reaction, the catalyst was separated from the reaction mixture with an external magnet and water (5 mL) was added to the resulting reaction mixture followed by extraction with EtOAc. The formation of products was related by comparing the melting points, IR and NMR data with authentic samples and the literature data.

2,4-Diphenylquinazoline (Table 4, entry 1). IR (KBr): 1609, 1544, 1478, 1356, 853, 698 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ = 7.36–7.52 (m, 7H), 7.78–7.85 (m, 3H), 8.10 (t, J = 8.2 Hz, 2H), 8.56–8.68 (m, 2H); ¹³C NMR (100 MHz CDCl₃) δ = 120.9, 125.8, 127.3, 127.6, 128.3, 128.8, 130.2, 130.6, 134.4, 137.9, 138.7, 151.9, 161.5, 169.1; HRMS calc. C₂₀H₁₄N₂ + H⁺: 283.1224, found: 283.1220.

2-(4-Chlorophenyl)-4-phenylquinazoline (Table 4, entry 2). IR (KBr): 1536, 1344, 1075, 783, 706 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ = 7.49 (d, J = 7.2 Hz, 2H), 7.51–7.89 (9H, m, H–Ar), 8.15 (d, J = 7.2 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ = 121.6, 124.5, 127.9, 128.4, 128.6, 129.3, 130.3, 130.6, 130.8, 133.7, 135.6, 138.1, 138.9, 150.2, 168.3; HRMS calc. C₂₀H₁₃ClN₂ + H⁺: 317.0725, found: 317.0722.

2-(4-Nitrophenyl)-4-phenylquinazoline (Table 4, entry 4). IR (KBr): 1612, 1538, 1485, 1352, 821, 788, 712 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ = 7.71 (t, J = 5.2 Hz, 4H), 7.87–7.96 (m, 3H), 8.22 (t, J = 7.2 Hz, 2H), 8.46 (d, J = 8.1 Hz, 2H), 8.77 (d, J = 8.1, 2H); ¹³C NMR (100 MHz, CDCl₃) δ = 123.1, 123.9, 127.5, 128.2, 128.8, 129.6, 130.6, 134.5, 137.1, 143.9, 150.1, 152.3, 158.4, 169.5; HRMS calc. C₂₀H₁₃N₃O₂ + H⁺: 328.1023, found: 328.1019.

6-Chloro-2,4-diphenylquinazoline (Table 4, entry 7). IR (KBr): 3056, 1573, 1489, 1210, 862, 659 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ = 7.47–7.43 (m, 3H), 7.50–7.56 (m, 3H), 7.70 (dd, J = 3.1 and 8.9 Hz, 1H), 7.74–7.76 (m, 2H), 7.93–8.08 (m, 2H), 8.54 (dd, J = 3.2 and 8.3 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ = 122.19, 125.79, 128.59, 128.67, 128.76, 130.06, 130.23, 130.78, 130.88, 132.60, 134.51, 137.09, 137.77, 150.50, 160.47, 167.54; HRMS calc. C₂₀H₁₃ClN₂ + H⁺: 317.0826, found: 317.0815.

6-Chloro-2-(4-nitrophenyl)-4-phenylquinazoline (Table 4, entry 11). IR (KBr): 1619, 1567, 1545, 1356, 865, 782, 702 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ = 7.53 (t, J = 3.9 Hz, 3H), 7.75 (d, J = 7.1 Hz, 3H), 8.01 (t, J = 3.9 Hz, 3H), 8.23 (d, J = 8.7 Hz, 2H), 8.73 (d, J = 8.9 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ = 123.2, 124.6, 126.2, 129.1, 129.7, 130.3, 131.1, 132.4, 134.5, 135.6, 137.4, 145.2, 149.6, 150.7, 158.9, 168.6; HRMS calc. C₂₀H₁₂ClN₃O₂ + H⁺: 362.0149, found: 362.0131.

6-Nitro-2-(4-methylphenyl)-4-phenylquinazoline (Table 4, entry 14). IR (KBr): 1662, 1613, 1549, 762, 707 cm⁻¹; 1H NMR (400 MHz, CDCl₃) δ = 2.33 (s, 3H), 7.24 (d, J = 7.2 Hz, 2H), 7.56 (t, J = 3.6 Hz, 3H), 7.82 (q, J = 3.7 Hz, 2H), 8.10 (d, J = 8.7 Hz, 1H), 8.52 (d, J = 7.9 Hz, 3H), 8.96 (d, J = 2.5 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ = 23.1, 121.4, 125.1, 127.3, 128.6, 129.1, 129.8, 130.1, 130.7, 131.2, 135.3, 136.8, 143.2, 146.4, 155.5, 164.7, 169.6; HRMS calc. C₂₁H₁₅N₃O₂ + H⁺: 342.1286, found: 342.1273.

4. Conclusion

In summary, this article describes a one pot and highly efficient method for the synthesis of quinoline and quinazoline derivatives in the presence of CuFe₂O₄ NPs as reusable catalysts in water. The advantages of the present method are: (i) simplicity in the extraction of the product/substrate from the catalysts; (ii) an insignificant loss of activity by employing reused catalyst and (iii) chemoselectivity. So, the proposed methodology to use CuFe₂O₄ NPs with attractive capabilities was accomplished.

Acknowledgements

This research was supported by the Islamic Azad University, Ayatollah Amoli Branch, Amol, Iran.

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