Synthesis and application of novel urea–benzoic acid functionalized magnetic nanoparticles for the synthesis of 2,3-disubstituted thiazolidin-4-ones and hexahydroquinolines

Abstract

In this work, we reported the synthesis and application of a new urea–benzoic acid containing ligand [(OEt)₃Si(CH₂)₃–urea–benzoic acid] for the functionalization of silica coated magnetic nanoparticles. The resulting structure, namely Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid, was characterized through different techniques including FT-IR, SEM, EDX-Mapping, VSM and TGA/DTG analysis. Then, Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid was applied as a heterogeneous dual acidic and hydrogen bonding catalyst for the synthesis of 2,3-disubstituted thiazolidin-4-ones and hexahydroquinolines under mild and green reaction conditions. More importantly, all of the desired products were obtained with relatively good yields. Also, the catalyst was recovered and reused for four successive runs without significant reduction in yield of the model reaction.

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Introduction

Since the first introduction of hydrogen bond interactions by Pauling, they have been a subject of extensive research in modern science and technology.^1,2 Moreover, hydrogen bond interactions govern many intermolecular and intramolecular interactions.^3,4 The reason behind the special behaviours of numerous molecules in biological systems can be explained by hydrogen bonding phenomenon.⁵ Hydrogen bond interactions have prominent role in numerous relevant areas of chemistry such as enzymatic catalysis,⁶ supramolecular chemistry,⁷ materials technology,⁸ crystal engineering⁹ and proton transfer reactions.¹⁰ Meanwhile, hydrogen bond-based organocatalysis has been increasingly promoted by chemists. In this regard, (thio)-ureas, squaramides, phosphoric acid derivatives and guanidines can be used as donor of hydrogen bonding.¹¹ Recently, hydrogen bonding catalysis manners have been applied in many catalytic organic reactions such as Friedel–Crafts,¹² Mannich,¹³ Diels–Alder¹⁴ and multicomponent reactions.¹⁵ Urea and its derivatives as the extraordinary kinds of hydrogen bonding catalysts have potentials of both acidic and basic catalyst and can be coupled with metals.^16,17 Therefore, urea derivatives can be acts as biological catalysts in many of organic reactions.¹⁸

Due to rapid development of the heterogeneous catalysts as well as their significant benefits, magnetically recoverable solid acids as versatile and sustainable alternatives to homogeneous acids become a considerable research area.^19–22 Magnetically recoverable solid acids due to their unique advantages such as high thermal and chemical stability, chemical tunability, easy recovering and reusability, low toxicity, and high surface area have been emerged the attention of many of technologic and scientific researchers.^23–26 According to high dispersibility of magnetic nanoparticles in solvent and their small size, these materials have been converted to active catalysts in reaction media. In other words, magnetic catalysts are a bridge between heterogeneous and homogeneous catalytic systems.²⁷ Because of its relative high activity and stability, carboxylic acid functional group is an ideal active site for modification of magnetic nanoparticles (MNPs). Indeed, carboxylic acid and urea functionalized MNPs can provide a suitable heterogeneous catalyst for promoting many of organic reactions.^28,29 Moreover, the existence of both urea and carboxylic acid within a single catalytic system enhances its capabilities in chemical processes.³⁰

Chemical methods based on multicomponent synthetic strategy provide a forceful and rapid synthetic route for the synthesis of diverse compounds.³¹ Multicomponent synthetic methods have promising approaches due to their unique merits such as high atom economy, available starting materials, efficiency of the protocol, selectivity and facility in the synthesis of complex molecules. Especially, due to ease of work, good efficiency, high atom and step economy and selectivity, catalytic applications of functionalized magnetic nanoparticles in multicomponent reactions have been noticed by chemists.^32,33

1,4-Dihydropyridine derivatives which are widely found in natural products represent exceptional pharmacological activities, and therefore received considerable attention in synthetic chemistry.^34–36 Hexahydroquinolines as one of the main important family of 1,4-dihydropyridines, have been studied profoundly.^37–39 Several critical biological applications and therapeutic activities such as antiplasmodial,⁴⁰ antimalarial,⁴¹ antidiabetic,⁴² anticancer,⁴³ bronchodilator,⁴⁴ antiatherosclerotic,⁴⁵ vasodilator,⁴⁶ antibacterial properties⁴⁷ and calcium channel blockers in cardiovascular disease treatment⁴⁸ have been devoted for these versatile compounds. The structure of some biologically active hexahydroquinolines derivatives is sketched in the Scheme 1.

Scheme 1 Some of biologically active examples of hexahydroquinolines (a) thiazolidine bearing molecules (b).

Nitrogen/sulfur-containing heterocycles with innumerable advantages in agricultural industry and medicinal chemistry are lucrative molecules for any researchers which are involved.^49–52 In this instance, thiazolidine-4-one derivatives as magic example of sulfur-containing heterocycles, have decisive roles in many functional materials, pharmaceuticals and natural products.^53–56 Alternatively, extensive applications of thiazolidines as antiinflammatory,⁵⁷ cardiovascular,⁵⁸ anticancer,⁵⁹ antimicrobial,⁶⁰ antioxidant,⁶¹ antimycobacterial,⁶² COX-1 inhibitor⁶³ and antiviral activities⁶⁴ are privileged property of these materials (Scheme 1).

With the light of this background and also our previous investigations in the areas of catalytic applications of magnetic nanoparticles in the preparation of heterocyclic compounds,^18,38,65 we designed and synthesized of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid and applied it as recoverable catalyst for the synthesis of hexahydroquinolines and 2,3-disubstituted thiazolidin-4-ones (Schemes 2 and 3).

Scheme 2 Representation of the synthetic route of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid.

Scheme 3 Preparation of hexahydroquinolines and 2,3-disubstituted thiazolidin-4-ones by using Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid as catalyst.

Results and discussion

Since that hydrogen bonding catalyst are great demand and due to our experiences in the synthesis and application of urea containing catalysts,^15,66 it was decided to investigate the obtained results from various characterization techniques from the structure, morphology and physical properties of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid in details.

Firstly, FT-IR technique was applied for characterization of the Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid and its related intermediates. In FT-IR spectrum of Fe₃O₄, the broad peak about 3394 cm⁻¹ is related to OH groups in the surface of Fe₃O₄ and the significant peak of Fe–O bond is appeared at 634 cm⁻¹. In FT-IR spectrum of Fe₃O₄@SiO₂, the diagnostic peak of Si–O–Si is well shown in 1104 cm⁻¹. According to FT-IR spectrum of (OEt)₃Si(CH₂)₃–urea–benzoic acid, the stretching vibration of NH of urea is appeared in 3326 cm⁻¹ and the broad acidic peak of benzoic acid is shown in the range of 2669–3326 cm⁻¹. Moreover, high intensity peaks in 1690 and 1559 cm⁻¹ confirm the presence of C=O and C=C groups. Finally, in FT-IR spectrum of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid, the observed changes in comparison to previous steps and presence of significant peak at 1677 cm⁻¹ and existence of acidic broad peak in the range of 2500–3500 cm⁻¹ confirm the successful synthesis of the described catalyst (Fig. 1).

Fig. 1 FT-IR spectra of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid and its related intermediates.

Scanning electron microscopy (SEM) images were applied for investigation of the morphology and size of the catalyst. As these images show (Fig. 2), the catalyst has spherical morphology and the sizes of catalyst are in the range of 31–179 nm.

Fig. 2 SEM image of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid.

In order to confirm the existence of the expected elements including Fe, Si, C, N and O, energy-dispersive X-ray spectroscopy (EDX) analysis was used. According to the observed results, all of mentioned awaited elements are verified (Fig. 3). Also, elemental mapping analysis was applied to confirm the EDX analysis and indicating of particle dispersion (Fig. 4).

Fig. 3 EDX analysis of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid.

Fig. 4 Displaying the scattering of elements in Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid.

In another study, VSM analysis was applied for investigation of magnetic properties of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid and its related intermediates. The results show an order decrease of magnetic properties from Fe₃O₄ to the target catalyst. This well confirms the addition of organic layers onto the surface of Fe₃O₄ (Fig. 5). Also, the amount of saturation of the Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid (about of 25 emu g⁻¹) helps to easily separate the catalyst from the reaction mixture.

Fig. 5 Comparison of the results of VSM analysis for Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid and its related intermediates.

Achieved data form thermogravimetric and differential thermogravimetric analysis (TGA/DTG) displayed that Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid was stable up to 280 °C under N₂ atmosphere (Fig. 6). The slight weight loss in the range of 100–150 °C is related to the removal of trapped solvents and the major weight loss in 280 °C was attributed to destruction of organic layers. A total weight loss up to 23% indicates that a significant amount of the catalyst contained organic layers.

Fig. 6 TGA/DTG analysis of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid.

After the characterization of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid, we investigated and optimized various reaction parameters such as solvent, temperature and amount of catalyst for the synthesis of 2,3-disubstituted thiazolidin-4-ones. The model reaction was carried out via one-pot three component condensation reaction between of 4-chloro benzaldehyde, benzo[d]thiazol-2-amine and 2-mercaptoacetic acid. At first, different temperatures such as 90, 80, 70 and 60 °C were applied for the model reaction. According to results, 80 °C was selected as optimized temperature. After that, several amounts of catalyst were used. The results indicate that the 10 mg of catalyst is the best amount. Finally, the role of solvent for the model reaction were explored. For this purpose, the reactions were performed under solvent-free conditions and in various protic and aprotic solvents. The results showed that the solvent-free conditions have the best yield (Table 1). Also, the obtained results from the optimizing of the reaction conditions for the synthesis of molecule 2h (as model reaction for the preparation of hexahydroquinolines) are embedded in Table 2. The results indicating that best data were achieved under the solvent free conditions at 70 °C in the presence of 10 mg of catalyst (entry 3).

Table 1 Optimizing of the reaction conditions for the synthesis of 1b^a

Entry	Solvent	Temperature (°C)	Catalyst loading (mg)	Time (min)	Yield^b (%)
a Reaction conditions: 4-cholorobenzaldehyde (1 mmol, 0.140 g), benzo[d]thiazol-2-amine (1 mmol, 0.150 g) and 2-mercaptoacetic acid (1 mmol, 0.092 g).b Related to isolated yields.c Optimal data.
1	—	90	10	15	88
2	—	80	15	15	87
3^c	—	80	10	15	85
4		80	5	30	72
5	—	80	—	15	Trace
6	—	80	7	15	75
7	—	80	20	15	87
8	—	80	—	120	50
9	—	70	10	30	70
10	—	60	10	100	56
11	H2O	Reflux	10	60	—
12	EtOH	Reflux	10	60	66
13	n-Hexane	Reflux	10	60	40
14	EtOAc	Reflux	10	60	—
15	CH2Cl2	Reflux	10	60	—

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Table 2 Optimizing of the reaction conditions for the synthesis of 2h^a

Entry	Solvent	Temperature (°C)	Catalyst loading (mg)	Time (min)	Yield^b (%)
a Reaction conditions: 4-cholorobenzaldehyde (1 mmol, 0.140 g), 5,5-dimethylcyclohexane-1,3-dione (1 mmol, 0.140), ethyl acetoacetate (1 mmol, 0.130 g), ammonium acetate (1 mmol, 0.078 g).b Related to isolated yields.c Optimal data.
1	—	90	10	10	92
2	—	80	15	10	90
3^c	—	70	10	10	91
4		70	5	30	80
5	—	70	—	10	Trace
6	—	70	7	10	82
7	—	70	20	10	92
8	—	70	—	120	60
9	—	60	10	30	70
10	—	50	10	100	20
11	H2O	Reflux	10	60	—
12	EtOH	Reflux	10	60	45
13	n-Hexane	Reflux	10	60	—
14	EtOAc	Reflux	10	60	50
15	CH2Cl2	Reflux	10	60	—

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Under the optimized reaction conditions (10 mg of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid as catalyst and solvent-free conditions at 80 °C) the substrate scope for the general validity of 2,3-disubstituted thiazolidin-4-ones and hexahydroquinolines was explored. Hereupon, assortment of aromatic aldehydes with electron-poor and electron-rich aryl groups, aromatic and aliphatic amines and 2-mercaptoacetic acid were applied for the synthesis of 2,3-disubstituted thiazolidin-4-one derivatives (Table 3). Likewise, variety of aromatic aldehydes with electron-poor and electron-rich aryl groups, ethyl acetoacetate, 5,5-dimethylcyclohexane-1,3-dione and ammonium acetate were used for the synthesis of hexahydroquinoline derivatives (Table 4).

Table 3 Synthesis of 2,3-disubstituted thiazolidin-4-ones in the presence of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid as catalyst^a

a Reaction conditions: arylaldehyde (2 mmol), amine (2 or 1 mmol) and 2-mercaptoacetic acid (2 mmol, 0.184 g), solvent-free, 80 °C, catalyst = 10 mg, reported yields are referred to isolated yields.

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Table 4 Synthesis of hexahydroquinolines in the presence of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid as catalyst^a

a Reaction conditions: arylaldehyde (1 mmol), 5,5-dimethylcyclohexane-1,3-dione (1 mmol, 0.140), ethyl acetoacetate (1 mmol, 0.130 g), ammonium acetate (1 mmol, 0.078 g), solvent-free, 70 °C, catalyst = 10 mg, reported yields are referred to isolated yields.

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Due to privileged character of magnetic nanoparticles in recycling and reusing, we investigated the recoverability of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid in the model reaction. After running and completing each of the reactions, the resulting mixture was dissolved in 10 mL of hot ethanol and catalyst was separated from the mixture of reaction by using an external magnet. It was washed three times with ethanol. After that, the recovered catalyst was desiccated under air conditions. This process was repeated for four times without significant reduction in efficiency (Fig. 7).

Fig. 7 Recovering test of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid in the synthesis of 1b.

In a separate study, according to suggested mechanism for the synthesis of 2,3-disubstituted thiazolidin-4-ones (Scheme 5), in the presence of catalyst, the carbonyl group of benzaldehyde was activated and reacted with benzo[d]thiazol-2-amine which leads to formation of intermediate a. In the second step, via the reaction of intermediate a with 2-mercaptoacetic acid, the intermediate b was formed. Finally, due to nucleophilic intermolecular cyclization and removing of H₂O, the desired product 1a was obtained (Scheme 4).

Scheme 4 The suggested mechanism for the synthesis of 1a in the presence of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid as catalyst.

Also, we suggested a plausible mechanism for the synthesis of hexahydroquinolines and 2,3-disubstituted thiazolidin-4-ones. According to sketched mechanism for the synthesis of hexahydroquinolines (Scheme 5), the carbonyl group of benzaldehyde was activated by catalyst and undergoes a nucleophilic attack from the enol form of 5,5-dimethylcyclohexane-1,3-dione. This reaction leads to formation of Knoevenagel adduct d. Also, the released ammonia from thermal dissociation of ammonium acetate was reacted with ethyl acetoacetate and intermediate e was formed. In the next step, through the reaction between of intermediates d and e, the intermediate f was performed. After that, through a tautomerization process and nucleophilic intermolecular cyclization, the intermediate h was obtained. Then, through removing of H₂O, the target product 2a was performed. It is worthy to mention that, authors believed that due to the strong resonance interaction between lone pair electrons of nitrogen atom with two carbonyl groups as strong acceptors. Therefore, there is no effectual interaction between lone pair electrons of nitrogen and σ* orbital of sp³ C–H bond. Herein, anomeric effect was not occurred.⁷² Thus, vinylogous anomeric-based oxidation⁷² is not effective alone for the oxidation of hexahydroquinolines to their corresponding aromatized pyridines.

Scheme 5 The plausible mechanism for the synthesis of 2a in the presence of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid as catalyst.

Experimental

General experimental procedure for the synthesis of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid

Initially, into a 10 mL round-bottomed flask containing 4-amino-benzoic acid (5 mmol, 0.686 g), 3-isocyanatopropyltriethoxysilane (5 mmol, 2.237 g) was added and then the resulting mixture was stirred for 1h under solvent-free conditions at room temperature. After completing of the reaction, the precipitate was washed and purified by n-hexane/dichloromethane (3 : 10) and dried at room temperature in a short time to give (OEt)₃Si(CH₂)₃–urea–benzoic acid (yield: 92%). Then, Fe₃O₄ and Fe₃O₄@SiO₂ was synthesized according to our reported procedure.^18a After that, into a 100 mL round-bottomed flask, Fe₃O₄@SiO₂ (1.0 g) and (OEt)₃Si(CH₂)₃–urea–benzoic acid (2.0 mmol, 0.768 g) were added and the reaction was proceeded under toluene reflux for 12 hours to give Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid. Then, final product was separated with external magnet and washed with n-hexane (50 mL) and EtOH (20 mL) and dried in air conditions.

Experimental route for the preparation of 2,3-disubstituted thiazolidin-4-ones

To the mixture of aldehyde derivatives (2 mmol), amine derivatives (2 mmol for 2-aminobenzothiazole and 1 mmol for ethylene diamine or phenylene diamine), 2-mercaptoacetic acid (2 mmol, 0.184 g) in a 10 mL round-bottomed flask, 0.01 g of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid as catalyst was added. The mixture of reaction was placed in an oil bath and stirred under solvent-free conditions at 80 °C. The progress of the reaction was monitored by TLC technique (ethyl acetate/n-hexane as eluent, 1 : 1). After completing of the reaction, 10 mL of hot EtOH was added to the reaction mixture. After dissolving all of materials in EtOH except catalyst, the catalyst was separated from the mixture of reaction by an external magnet. Finally, the desired products were washed with EtOH and desiccated at 80 °C to obtain a pure solid.

Experimental procedure for the preparation of hexahydroquinolines

Into a 10 mL round-bottomed flask, 5,5-dimethylcyclohexane-3,1-dione (1 mmol, 0.14 g), aromatic aldehyde (1 mmol), ethyl acetoacetate (1 mmol, 0.13 g), ammonium acetate (1 mmol, 0.078) and 0.01 g of Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid as catalyst were added. The mixture of reaction was then stirred under solvent-free conditions at 80 °C. The progress of the reaction was evaluated using the TLC technique (ethyl acetate/n-hexane as eluent, 1 : 1). After completing of the reaction, 10 mL of hot EtOH was added to the reaction mixture. All materials except catalyst was completely dissolved and catalyst was removed from the mixture of reaction by an external magnet. Finally, the desired products were washed with EtOH and dried at 80 °C to obtain a pure solid.

Selected spectral data

(OEt)₃Si(CH₂)₃–urea–benzoic acid. M. p.: 276–278 °C, FT-IR (KBr, ν, cm⁻¹): 3326, 3188, 2978, 1690, 1559, 1171. ¹H NMR (301 MHz, DMSO) δ 12.49 (s, 1H), 8.80 (s, 1H), 7.84 (d, J = 9 Hz, 2H), 7.52 (d, J = 9 Hz, 2H), 6.33 (t, J = 6 Hz, 1H), 3.75 (q, J = 7 Hz, 6H), 3.10 (q, J = 6.6 Hz, 2H), 1.51 (p, J = 7.7 Hz, 2H), 1.16 (t, J = 7 Hz, 9H), 0.57 (t, J = 9 Hz, 2H). ¹³C NMR (76 MHz, DMSO) δ 167.6, 155.2, 145.4, 130.9, 123.2, 117.0, 58.2, 42.2, 23.7, 18.6, 7.7.

3-(Benzo[d]thiazol-2-yl)-2-phenylthiazolidin-4-one (1a). M.p. = 172–174 °C, FT-IR (KBr, ν, cm⁻¹): 3067, 1696, 1573, 1504, 1441, 1373, 1270. ¹H NMR (301 MHz, DMSO) δ 8.03 (d, J = 9 Hz, 1H), 7.67 (d, J = 9 Hz, 1H), 7.40–7.27 (m, 7H), 6.93 (s, 1H), 4.30 (d, J = 15 Hz, 1H), 4.04 (d, J = 18 Hz, 1H). ¹³C NMR (76 MHz, DMSO) δ 172.2, 156.5, 148.1, 141.6, 131.5, 129.2, 128.5, 126.9, 125.9, 124.9, 122.4, 121.8, 63.2, 32.4.

3-(Benzo[d]thiazol-2-yl)-2-(4-chlorophenyl)thiazolidin-4-one (1b). M.p. = 202–204 °C, FT-IR (KBr, ν, cm⁻¹): 3060, 1693, 1594, 1367, 1498, 1280. ¹H NMR (301 MHz, DMSO) δ 8.04 (d, J = 6 Hz, 1H), 7.69 (d, J = 9 Hz, 1H), 7.49–7.33 (m, 6H), 6.94 (s, 1H), 4.33 (d, J = 15 Hz, 1H), 4.06 (d, J = 15 Hz, 1H). ¹³C NMR (76 MHz, DMSO) δ 172.1, 156.5, 148.1, 140.7, 133.0, 131.8, 129.2, 128.0, 126.9, 124.9, 122.5, 121.8, 62.6, 32.3.

3-(Benzo[d]thiazol-2-yl)-2-(2-chlorophenyl)thiazolidin-4-one (1c). M.p. = 155–157 °C, FT-IR (KBr, ν, cm⁻¹): 3386, 3061, 1705, 1590, 1444, 1276, 1050. ¹H NMR (301 MHz, DMSO) δ 8.07 (d, J = 6 Hz, 1H), 7.68 (d, J = 9 Hz, 1H), 7.59 (d, J = 6 Hz, 1H), 7.44–7.26 (m, 4H), 7.14 (d, J = 6 Hz, 1H), 7.00 (s, 1H), 4.23 (d, J = 18 Hz, 1H), 4.10 (d, J = 15 Hz, 1H). ¹³C NMR (76 MHz, DMSO) δ 172.3, 156.4, 148.1, 137.9, 131.8, 131.6, 130.6, 130.2, 128.3, 126.9, 125.6, 125.0, 122.5, 121.9, 60.8, 32.1.

3,3′-(Ethane-1,2-diyl)bis(2-phenylthiazolidin-4-one) (1f). M.p. = 196–200 °C, FT-IR (KBr, ν, cm⁻¹): 3034, 1662, 1450, 1430, 1270, 1153. ¹H NMR (301 MHz, DMSO) δ 7.39–7.30 (m, 10H), 5.70 (s, 2H), 3.84 (d, J = 15 Hz, 2H), 3.64 (d, J = 15 Hz, 2H), 3.55 (dd, J = 12, J = 6, 2H), 2.67 (dd, J = 15, J = 6, 2H). ¹³C NMR (76 MHz, DMSO) δ 171.4, 140.3, 129.4, 129.3, 127.5, 62.9, 32.2.

3,3′-(Ethane-1,2-diyl)bis(2-(4-methylphenyl)thiazolidin-4-one) (1h). M.p. = 200–202 °C, FT-IR (KBr, ν, cm⁻¹): 3324, 2999, 1668, 1573, 1407, 1266. ¹H NMR (301 MHz, DMSO) δ 7.21–7.15 (m, 8H), 5.64 (s, 2H), 3.81 (dd, J = 15, 3 Hz, 2H), 3.62 (d, J = 15 Hz, 2H), 3.50 (dd, J = 15, 6 Hz, 2H), 2.61 (dd, J = 15, J = 6, 2H). ¹³C NMR (76 MHz, DMSO) δ 171.3, 138.7, 137.2, 129.9, 127.5, 62.8, 32.2, 21.3.

Ethyl 2,7,7-trimethyl-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (2a). M.p. = 200–202 °C, FT-IR (KBr, ν, cm⁻¹): 3275, 3076, 2961, 1699, 1604, 1489, 1213. ¹H NMR (301 MHz, DMSO) δ 9.11 (s, 1H, NH), 7.22–7.06 (m, 5H, Aromatic), 4.88 (s, 1H, CH), 3.99 (q, J = 7.0 Hz, 2H, CH₂), 2.47–2.31 (m, 1H), 2.19 (d, J = 15, 1H), 1.99 (d, J = 15, 1H), 1.14 (t, J = 7 Hz, 3H), 1.02–0.98 (m, 3H), 0.86 (s, 3H). ¹³C NMR (76 MHz, DMSO) δ 194.7, 167.3, 150.0, 148.1, 145.5, 128.2, 127.9, 126.2, 110.5, 104.1, 59.5, 50.7, 36.3, 32.6, 29.6, 26.9, 18.8, 14.6.

Ethyl 4-(4-methoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (2f). M.p. = 247–250 °C, FT-IR (KBr, ν, cm⁻¹): 3276, 3078, 2957, 1701, 1605, 1508, 1380. ¹H NMR (301 MHz, DMSO) δ 9.04 (s, 1H), 7.08 (d, J = 6 Hz, 2H, aromatic), 6.76 (d, J = 6 Hz, 2H, aromatic), 4.82 (s, 1H, CH), 4.0 (q, J = 7 Hz, 2H, CH₂), 3.69 (s, 3H, OCH₃), 2.53–2.30 (m, 5H), 2.19 (d, J = 15 Hz, 1H), 1.99 (d, J = 15 Hz, 1H), 1.16 (t, J = 7.1 Hz, 3H), 1.03 (s, 3H), 0.88 (s, 3H). ¹³C NMR (76 MHz, DMSO) δ 194.8, 167.4, 157.8, 149.7, 145.1, 140.5, 128.9, 113.6, 110.7, 104.4, 59.5, 55.3, 50.8, 35.4, 32.6, 29.6, 27.0, 18.8, 14.7.

Ethyl 4-(4-methoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (2g). M.p. = 238–240 °C, FT-IR (KBr, ν, cm⁻¹): 3293, 3083, 2958, 1667, 1612, 1487, 1217. ¹H NMR (301 MHz, DMSO) δ 8.90 (s, 1H, NH), 7.04–6.93 (m, 4H, aromatic), 4.63 (s, 1H, CH), 3.75 (d, J = 6 Hz, 2H, CH₂), 2.23–1.73 (m, 7H), 0.92–0.61 (m, 9H). ¹³C NMR (76 MHz, DMSO) δ 194.7, 167.1, 150.1, 147.1, 145.9, 130.7, 129.8, 128.2, 110.2, 103.6, 59.6, 50.7, 36.1, 32.6, 29.6, 26.9, 18.8, 14.6.

Conclusion

In summary, we have reported concise and significant protocols for the preparation of hexahydroquinolines and 2,3-disubstituted thiazolidin-4-onederivatives using Fe₃O₄@SiO₂@(CH₂)₃–urea–benzoic acid as a novel and reusable nanomagnetic catalyst. Furthermore, the described catalyst was characterized by several techniques. By using various amines and aldehydes the broad substrate scope for the general validity of 2,3-disubstituted thiazolidin-4-ones and hexahydroquinolines was investigated. Our method was able to produce a relatively wide range of functionalized thiazolidinones and hexahydroquinolines under mild reaction conditions while products have relatively good yields.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

We thank the Bu-Ali Sina University and Iran National Science Foundation [(INSF), Grant Number: 98001912] for financial support to our research group.

References

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Footnote

† Electronic supplementary information (ESI) available. See https://doi.org/10.1039/d2ra02205b

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