A new type of SO₃H-functionalized magnetic-titania as a robust magnetically-recoverable solid acid nanocatalyst for multi-component reactions

Abstract

SO₃H-functionalized magnetic-titania nanoparticles (Fe₃O₄@TDI@TiO₂–SO₃H) have been synthesized by a two-step procedure, involving the covalent grafting of n-TiO₂ to n-Fe₃O₄ via 2,4-toluene diisocyanate as a regioselective linker (n-Fe₃O₄@TDI@TiO₂) and subsequent sulfonation using chlorosulfonic acid. The as-prepared nanocatalyst was characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) and vibrating sample magnetometry (VSM). The catalytic activity of the nanocatalyst was assessed for the synthesis of benzimidazoquinazolinones and polyhydroquinolines, in which the reaction conditions were optimized by applying central composite design (CCD) through response surface methodology. The nanocatalyst could be separated from the reaction mixture easily by magnetic decantation and reused at least six times without a noticeable degradation in catalytic activity. To the best of our knowledge, there are no literature reports on applying experimental design to optimize the reaction conditions for benzimidazoquinazolinones synthesis.

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1. Introduction

Catalysis is one of the most important fields in the realm of organic synthesis and has received extensive attention from both academia and industry.¹ Homogeneous Brønsted acid catalysts such as H₂SO₄, H₃PO₄, HF, HCl, HBr, CH₃COOH and CF₃COOH are widely used in the large-scale synthesis of industrial and fine chemicals as well as in organic transformations.^2,3 Unfortunately, these acids suffer some disadvantages due to handling problems, difficulty in their work-up and separation procedures, waste neutralization issues and so on. To address environmental and safety concerns, the replacement of corrosive and hazardous mineral acids with heterogeneous ones is one of the main tasks assigned to organic chemists for the sustainable production of chemicals.^4–6

In recent years, a great deal of attention has been paid to the preparation of heterogeneous catalysts by immobilizing homogeneous ones on various solid supports like organic polymers,^7–9 inorganic silica,^5,10,11 metal oxides^12–14 and natural supports.^15–17 However, this immobilization usually decreases the selectivity and catalytic activity.¹⁸ This drawback can be overcome by using nanomaterials as heterogeneous supports. When the size of the support is decreased to the nanometer-scale, the surface-to-volume ratio is significantly increased, which results in high accessibility for the surface-bound catalytic sites per unit area.¹⁹

Among numerous solid supports, transition-metal oxide nanoparticles have great potential due to their large amount of surface hydroxyl groups that can be used as active sites for the preparation of solid acid catalysts.^20,21 Nevertheless, separation of these nanoparticles from the reaction mixture is almost as difficult as separation using conventional methods.²² This problem is surmounted by using magnetic nanoparticles as heterogeneous supports, which can be readily separated by employing an external magnetic field. This technique is typically more effective than centrifugation or filtration as it prevents loss of the catalyst.^23–26

In our research towards designing and synthesizing novel heterogeneous nanocatalysts for organic reactions,^13,27–29 we had previously reported TiO₂-coated magnetite nanoparticle-supported sulfonic acid as an efficient, magnetically separable heterogeneous solid acid catalyst,³⁰ which was prepared through immobilizing SO₃H groups on the surface of Fe₃O₄–TiO₂ core–shell nanostructures. However, very recently, our group uncovered a unique process for the magnetization of metal oxides,³¹ in which magnetic nanoparticles were bound to nano-titania through the use of 2,4-toluene diisocyanate (TDI) as a covalent linker, due to regioselectivity of its two different isocyanate groups. The present development builds on our prior study, and aims to immobilize chlorosulfonic acid on magnetic-titania for the preparation of a non-toxic, low cost, highly efficient, stable, and magnetically recyclable Brønsted solid acid nanocatalyst. The performance of the prepared catalyst was examined in the synthesis of benzimidazoquinazolinones and polyhydroquinolines.

2. Results and discussion

The general synthetic route for the preparation of the Fe₃O₄@TDI@TiO₂–SO₃H solid acid nanocatalyst is schematically outlined in Scheme 1. Initially, Fe₃O₄ nanoparticles were prepared via a co-precipitation method.³² In the second step, Fe₃O₄ nanoparticles were treated with excessive TDI, in which the highly electrophilic carbon of the para-isocyanate group readily undergoes a nucleophilic reaction with the accessible surface hydroxyls of n-Fe₃O₄ by forming a urethane bond.^33,34 The ortho-isocyanate group is left unreacted due to the different reactivity of the two isocyanate groups, which together lead to steric hindrance in TDI.³⁵ Subsequently, the as-synthesized nano-TiO₂ (ref. 36) was added. In the same way, the surface hydroxyl groups of n-TiO₂ reacted with the preserved ortho-isocyanate group of n-Fe₃O₄@TDI, under a higher temperature and longer reaction time to prepare magnetic-titania. Ultimately, the functionalization of the remaining surface hydroxyl groups of n-TiO₂ with chlorosulfonic acid led to the formation of Fe₃O₄@TDI@TiO₂–SO₃H, a novel type of solid acid nanocatalyst. The catalyst was then characterized by FT-IR, TGA, XRD, FE-SEM, VSM and acid–base titration.

Scheme 1 Preparation of the Fe₃O₄@TDI@TiO₂–SO₃H nanocatalyst.

Characterization of Fe₃O₄@TDI@TiO₂–SO₃H nanoparticles using FT-IR spectroscopy

Fourier transform infrared spectroscopy (FT-IR) is one of the most effective techniques for characterizing the functionalization of nanoparticles. Therefore, the FT-IR spectrum for every step of the catalyst synthesis was analyzed (Fig. 1). According to our previous report,³¹ the deposition of TiO₂ nanoparticles on n-Fe₃O₄@TDI is successfully achieved (curve e) due to the disappearance of the isocyanate peak at 2262 cm⁻¹ and the differences in the fingerprinting of the IR bands in the range of 500–700 cm⁻¹ compared to curve d. Immobilization of chlorosulfonic acid on the n-TiO₂ surface is verified by the very broad band of the acidic group from 2800 to 3500 cm⁻¹ and in the absorption range of 1034–1267 cm⁻¹, which is related to O=S=O asymmetric and symmetric stretching.^13,29

Fig. 1 FT-IR spectra of (a) n-Fe₃O₄, (b) n-TiO₂, (c) TDI, (d) n-Fe₃O₄@TDI, (e) n-Fe₃O₄@TDI@TiO₂, (f) n-Fe₃O₄@TDI@TiO₂–SO₃H.

Thermogravimetric analysis

The thermogravimetric analysis (TGA) curve suggests the grafting of organic groups onto the surface of the supports through mass loss upon heating. As shown in Fig. 2, the TGA curves of both Fe₃O₄@TDI@TiO₂ (curve a) and Fe₃O₄@TDI@TiO₂–SO₃H (curve b) are similar, but differ in the amount of mass loss and the temperature range. The TGA curve of Fe₃O₄@TDI@TiO₂–SO₃H in the temperature range of 30–800 °C exhibits three mass losses. The initial mass loss up to 150 °C is caused by the removal of physically trapped solvents and water. The mass loss of about 10.74% in the range of 150–460 °C and that of 6.32% in the range of 460–650 °C, are attributed to the thermal decomposition of TDI and sulfonic acid groups, and are similar to those reported in the literature.^13,37

Fig. 2 TGA curves of (a) n-Fe₃O₄@TDI@TiO₂, (b) n-Fe₃O₄@TDI@TiO₂–SO₃H.

X-ray diffraction

The phase purity and crystal structure of the catalyst were analyzed via XRD. The cubic Fe₃O₄ structure is confirmed by the peaks at values of 2θ equal to 30.4 (220), 35.7 (311), 43.4 (400), 54.1 (422), 57.1 (511) and 62.9 (440), in accordance with JCPD 79-0417. The anatase crystalline phase of TiO₂ is matched with JCPD 89-4921 by the diffraction signals located at 2θ values equal to 25.2 (101), 37.3 (103), 37.8 (004), 38.7 (112), 48.2 (200), 54.0 (105), 55.1 (211), 62.8 (204), 68.9 (116), 70.4 (220), 75.1 (215) and 83.1 (224). The same set of characteristic peaks for Fe₃O₄ and TiO₂ is detected in the XRD pattern of the catalyst (Fig. 3d), indicating that modification has occurred and the crystallite phases are retained after treatment with acidic reagent.

Fig. 3 The X-ray diffraction patterns of (a) n-Fe₃O₄, (b) n-TiO₂, (c) n-Fe₃O₄@TDI@TiO₂, (d) n-Fe₃O₄@TDI@TiO₂–SO₃H.

Field emission scanning electron microscopy

The surface morphology, particle shape and size distribution features of n-Fe₃O₄, n-TiO₂, n-Fe₃O₄@TDI@TiO₂ and n-Fe₃O₄@TDI@TiO₂–SO₃H were examined using FE-SEM (Fig. 4). The micrographs illustrate that the catalyst particles are quasi-spherical with a larger average diameter in comparison to those of n-Fe₃O₄ and n-TiO₂. However, aggregation of the nanoparticles is observed, which occurs during the functionalization process. The results show the presence of the catalyst on the nanometer-sized particles.

Fig. 4 FE-SEM images of (a) n-Fe₃O₄, (b) n-TiO₂, (c) n-Fe₃O₄@TDI@TiO₂, (d) n-Fe₃O₄@TDI@TiO₂–SO₃H.

Vibrating sample magnetometry

The magnetic properties of the catalyst were examined at room temperature by using a vibrating sample magnetometer (VSM). The saturation magnetization value of n-Fe₃O₄@TDI@TiO₂–SO₃H is 31.9 emu g⁻¹, lower than that of the bare magnetic nanoparticles (68.4 emu g⁻¹), due to presence of a non-magnetic layer on the particle surface. However, this value still reveals its magnetic behavior, and confirms that the magnetization is still large enough for easy catalyst separation by using a magnetic stirring bar in the reaction mixture (Fig. 5).

Fig. 5 Magnetization curves of the (a) n-Fe₃O₄, (b) n-Fe₃O₄@TDI@TiO₂, (c) n-Fe₃O₄@TDI@TiO₂–SO₃H measured at room temperature.

Acid–base titration

The quantity of sulfonic acid groups on the surface of n-Fe₃O₄@TDI@TiO₂–SO₃H was determined using ion-exchange pH analysis. To do this, 100 mg of the catalyst was added to 10 mL of a 1 M NaCl solution and was stirred continuously for 24 h at room temperature. The catalyst was separated using an external magnet, and the NaCl solution was decanted and recovered. Then, two drops of a phenolphthalein solution were added to the NaCl solution and the solution was titrated against 0.01 M NaOH solution to neutrality. According to the obtained results, the loading of acidic sites was about 2.70 mmol H⁺ per g of catalyst.

Evaluating the catalytic activity of the Fe₃O₄@TDI@TiO₂–SO₃H nanoparticles

Nitrogen-containing heterocycles are of considerable interest in the agrochemical and pharmaceutical industries due to their diverse range of physiological properties. Benzimidazoquinazolinones, including both biodynamic benzimidazole and quinazoline heterosystems, are an important class of N-heterocycles that exhibit a broad spectrum of biological activities, such as antineoplastic, antihypertensive, anticancer, antihistaminic, anti-HIV and analgesic properties.^38–40 In view of the importance of this type of heterocycle, the performance of n-Fe₃O₄@TDI@TiO₂–SO₃H as a nanocatalyst was probed for the synthesis of benzimidazoquinazolinones via the condensation reaction between benzaldehyde, dimedone and 2-aminobenzimidazole under solvent-free conditions as a model reaction (Scheme 2).

Scheme 2 Synthesis of benzimidazoquinazolinones using n-Fe₃O₄@TDI@TiO₂–SO₃H as a nanocatalyst.

In order to reach optimal conditions, a response surface model (RSM) was employed and the effects of the catalyst amount (X₁), temperature (X₂) and reaction time (X₃) on the reaction yield were investigated. For each factor, 5 levels were defined. These values and their coded values are shown in Table 1.

Table 1 Parameter levels and coded values of CCD

Independent variables	Levels
	Lowest (−1.68)	Low (−1)	Central (0)	High (+1)	Highest (+1.68)
X1: catalyst amount (mg)	0	5	10	15	20
X2: temperature (°C)	30	50	70	90	110
X3: time (min)	4	8	12	16	20

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The experimental design matrix and the corresponding experimental parameters and response values are shown in Table 2.

Table 2 Conditions of predicted experiments in CCD

Run	X1	X2	X3	Yield (%)
1	−1.68	0	0	45.09
2	0	0	0	85.75
3	0	0	0	81.08
4	0	−1.68	0	39.45
5	0	0	+1.68	86.02
6	+1	+1	−1	86.77
7	0	0	0	81.23
8	+1	−1	−1	64.22
9	−1	+1	−1	72.65
10	0	0	0	84.67
11	−1	−1	−1	40.10
12	−1	+1	+1	94.76
13	0	0	−1.68	59.10
14	0	0	0	86.48
15	+1.68	0	0	81.87
16	+1	+1	+1	96.33
17	0	0	0	80.01
18	+1	−1	+1	58.98
19	−1	−1	+1	52.00
20	0	+1.68	0	94.30

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The analysis of variance (ANOVA) was used to determine the statistical significance of the constructed models and to evaluate which factor(s) significantly affect the response. From the ANOVA, as shown in Table 3, the p-values of the model and the lack of fit are lower and higher than 0.05, respectively, implying that the fitted model is significant, with a confidence level of 95%. Additionally, the results imply that all the independent variables (X₁, X₂ and X₃) and their quadratic terms (X₁², X₂² and X₃²) significantly affect the response value (yield), and a significant interaction between the catalyst amount (X₁) and time (X₃) is obvious (P < 0.05). Also, the R-squared and adj R-squared values are close to 1.0, suggesting a strong correlation between the observed and the predicted values and indicating that the regression model affords an excellent explanation of the relationship between the independent variables and the response.

Table 3 Analysis of variance for the response surface quadratic model for yield

Source	Sum of squares	df	Mean square	F value	p-Value prob > F
Model	6247.37	9	694.15	32.50	<0.0001
X1: catalyst amount	864.33	1	864.33	40.46	<0.0001
X2: temperature	3788.31	1	3788.31	177.35	<0.0001
X3: time	511.80	1	511.80	23.96	0.0006
X1X2	29.68	1	29.68	1.39	0.2658
X1X3	110.19	1	110.19	5.16	0.0465
X2X3	78.19	1	78.19	3.66	0.0848
X1^2	540.19	1	540.19	25.29	0.0005
X2^2	349.14	1	349.14	16.34	0.0024
X3^2	122.21	1	122.21	5.72	0.0378
Residual	213.61	10	21.36
Lack of fit	175.63	5	35.13	4.63	0.0591
Pure error	37.97	5	7.59
Cor total	6460.97	19
R^2 = 0.97	Adj-R^2 = 0.94			Pred-R^2 = 0.78

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The polynomial response surface models for yield, based on significant levels and actual values were obtained from the ANOVA:

Y (yield) = −123.45 + 10.06X₁ + 2.28X₂ + 5.02X₃ − 0.02X₁X₂ − 0.18X₁X₃ + 0.04X₂X₃ − 0.24X₁² − 0.01X₂² − 0.18X₃²

In this equation, the coefficients show the effect of the parameters. Therefore, the amount of catalyst can be considered as the main factor influencing the progression of the reaction.

Response surface plots facilitate the study of how process variables interact and affect the response by keeping one variable at zero and varying the other variables within the experimental range. 3D response plots of yield versus a pair of parameters are shown in Fig. 6. According to their p-values, the interaction of X₁X₃ is significant, indicating that a simultaneous increase in the amount of catalyst and the length of time cause an increase in the product yield.

Fig. 6 3-D response surfaces for the effect of factors on the reaction yield.

The main objective of this design is to determine the best reaction conditions. Based on the experimental design obtained using Design-Expert 7.0.0, the model predicted that the yield could reach 96.47% under the optimal process conditions of 12 mg of catalyst and a temperature of 85 °C, with a reaction time of 13 min.

With the optimum conditions in hand, in order to examine the generality of the reaction conditions, the study was extended to different aromatic aldehydes and 1,3-cyclic diketones as shown in Table 4.

Table 4 Synthesis of benzimidazoloquinazolines using n-Fe₃O₄@TDI@TiO₂-SO₃H^a

Entry	R^1	R^2	R^3	Time (min)	Yield^b (%)	Melting point (°C)
a Reaction conditions: 1 (1 mmol), 2 (1 mmol), 3 (1 mmol), Fe3O4@TDI@TiO2–SO3H (12 mg) under solvent-free condition at 85 °C.b Isolated yield.
1	CH3	CH3	–H	13	96	318–320 (ref. 41)
2	CH3	CH3	4-CH3	15	91	330–332 (ref. 28)
3	CH3	CH3	4-OCH3	17	88	317–318 (ref. 41)
4	CH3	CH3	4-OH	15	90	329–331 (ref. 41)
5	CH3	CH3	4-NO2	13	92	332–334 (ref. 28)
6	CH3	CH3	4-F	12	95	325–326 (ref. 28)
7	CH3	CH3	4-Cl	12	91	339–341 (ref. 41)
8	CH3	CH3	4-Br	14	93	314–315 (ref. 28)
9	CH3	CH3	4-N(CH3)2	15	90	>300 (ref. 42)
10	H	H	–H	15	93	310–312
11	H	H	4-CH3	15	90	>300 (ref. 39)
12	H	H	4-OCH3	18	90	>300 (ref. 39)
13	H	H	4-OH	16	92	>300 (ref. 39)
14	H	H	4-NO2	13	91	>300 (ref. 39)
15	H	H	4-F	13	94	>300 (ref. 39)
16	H	H	4-Cl	14	94	>300 (ref. 39)
17	H	H	4-Br	15	90	>300 (ref. 39)
18	H	H	4-N(CH3)2	13	92	>300 (ref. 39)
19	H	Ph	–H	15	95	332–335 (ref. 28)

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The results illustrate that the reaction proceeded very well within a relatively short reaction time for 1,3-cyclic diketones and both electron-releasing and electron-withdrawing substituents of aromatic aldehydes. This confirms the high efficiency of the nanocatalyst for the synthesis of a series of structurally diverse benzimidazoloquinazolines in high purity. The formation and purity of the products were confirmed by comparing their melting points with the literature values, and they were in good accordance with them. The structures of some of them were well characterized using FT-IR, ¹H NMR and ¹³C NMR spectral data.

The suggested mechanism for the synthesis of benzimidazoloquinazolines is outlined in Scheme 3. At the beginning, 1,3-cyclic ketone (I) turns into its enol form (II) and reacts with the carbonyl group of aldehyde (III), which becomes protonated and activated due to the solid acid nanocatalyst and affords (IV). Then, an α,β-unsaturated carbonyl compound forms upon the loss of water (V). Next, the α,β-unsaturated carbonyl compound undergoes a Michael addition reaction with the endocyclic nitrogen in 3-aminobenzimidazole (VI), yielding the corresponding intermediate (VII). Finally, intra-molecular cyclization and loss of a water molecule (VIII) leads to the formation of the desired enamine product (VIIII).

Scheme 3 Probable mechanism for the synthesis of benzimidazoloquinazolines in the presence of n-Fe₃O₄@TDI@TiO₂–SO₃H.

The promising results mentioned above encouraged us to extend further the scope of the catalytic performance of n-Fe₃O₄@TDI@TiO₂–SO₃H to the synthesis of polyhydroquinolines, through the one-pot four-component Hantzsch condensation of 1,3-cyclic diketones, aromatic aldehydes, ethyl acetoacetate and ammonium acetate under the optimized reaction conditions for benzimidazoquinazolinones (Scheme 4).

Scheme 4 Synthesis of polyhydroquinolines using n-Fe₃O₄@TDI@TiO₂–SO₃H as a nanocatalyst.

As shown in Table 5, different aromatic aldehydes bearing electron-withdrawing or electron-releasing substituents and various 1,3-cyclic diketones gave the desired product in good to excellent yields in a short reaction time.

Table 5 Synthesis of polyhydroquinoline derivatives using n-Fe₃O₄@TDI@TiO₂–SO₃H^a

Entry	R^1	R^2	R^3	Time (min)	Yield^b (%)	Melting point (°C)
a Reaction conditions: 1 (1 mmol), 2 (1 mmol), 5 (1 mmol), 6 (2.5 mmol), n-Fe3O4@TDI@TiO2–SO3H (12 mg) under solvent-free condition at 85 °C.b Isolated yield.
1	CH3	CH3	–H	15	95	200–202 (ref. 43)
2	CH3	CH3	4-CH3	16	92	284–286 (ref. 44)
3	CH3	CH3	4-OCH3	18	90	256–258 (ref. 43)
4	CH3	CH3	4-OH	18	92	232–235 (ref. 43)
5	CH3	CH3	2-NO2	18	88	201–203 (ref. 44)
6	CH3	CH3	3-NO2	15	91	170–172 (ref. 44)
7	CH3	CH3	4-NO2	14	94	209–211 (ref. 44)
8	CH3	CH3	4-F	10	95	181–183 (ref. 44)
9	CH3	CH3	4-Cl	12	92	245–247 (ref. 43)
10	H	H	–H	13	94	240–241 (ref. 43)
11	H	H	4-CH3	17	90	240–242 (ref. 45)
12	H	H	4-OCH3	16	88	193–194 (ref. 45)
13	H	H	4-OH	20	89	222–223 (ref. 45)
14	H	H	2-NO2	20	90	189–191 (ref. 44)
15	H	H	3-NO2	15	92	200–202 (ref. 44)
16	H	H	4-NO2	12	94	204–205 (ref. 45)
17	H	H	4-F	10	90	243–245 (ref. 45)
18	H	H	4-Cl	10	93	233–234 (ref. 45)
19	H	Ph	–H	18	87	213–214 (ref. 44)

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A possible mechanism for the synthesis of polyhydroquinolines is outlined in Scheme 5. First of all, the 1,3-cyclic dicarbonyl compound (I) converts into its enol form after tautomerisation (II) and reacts with the carbonyl group of aldehyde which is activated by the catalyst (III), to afford a knoevenagel intermediate (V). On the other side, ammonia resulting from ammonium acetate (VI) and the β-ketoester activated by the catalyst (VII) yields enamine (VIII). Afterward, the reaction between the intermediates (V) and (VIII) gives the intermediate (IX). Subsequent tautomerization, intramolecular N-cyclization and dehydration yields the hexahydroquinoline.

Scheme 5 Probable mechanism for the synthesis of polyhydroquinolines in the presence of n-Fe₃O₄@TDI@TiO₂–SO₃H.

To highlight the advantages and effectiveness of the prepared catalyst, a comparison of its catalytic activity with some previous methods is presented (Table 6). This shows that n-Fe₃O₄@TDI@TiO₂–SO₃H is more or less superior compared with previously reported catalytic systems in terms of easy separability, high activity and recyclability, in addition to high product yields in short reaction times under neat conditions. These results considerably verify the high efficiency of the present catalyst.

Table 6 Comparison of n-Fe₃O₄@TDI@TiO₂–SO₃H with other reported catalysts for the synthesis of benzimidazoquinazolinones

Entry	Catalyst	Reaction condition	Time (min)	Yield (%)	Ref.
1	I2 (10 mol%)	CH3CN/reflux	10	85	46
2	p-TsOH–H2O (15 mol%)	CH3CN/50 °C	25	95	47
3	[bmim^+][BF4^−] (3 mL)	90 °C	420	86	48
4	Fe–chitosan (20 mg)	Ethanol/40 °C	105	82	49
5	MCM-41-SO3H (20 mol%)	Ethanol/reflux	30	97	50
6	n-Fe3O4@TDI@TiO2–SO3H (12 mg)	Solvent-free/85 °C	13	96	This work

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Recycling of the catalyst

In order to develop a greener organic synthesis, the capability of the catalyst to be recovered and reused should be seriously considered. In other words, the catalyst should be able to be separated from the reaction mixture, and be reused several times. Therefore, the recoverability of n-Fe₃O₄@TDI@TiO₂–SO₃H was investigated for the model reaction of benzimidazoloquinazoline. As shown in Fig. 7, the catalyst can be reused at least six times and a conversion of 89% was still attained in the 6th run.

Fig. 7 Reusability of n-Fe₃O₄@TDI@TiO₂–SO₃H for the synthesis of benzimidazoloquinazoline.

After the fifth cycle, the recovered catalyst had a similar morphology to the fresh one (Fig. 8) and no noticeable change in structure was observed, by comparing its FT-IR spectrum to that of the fresh catalyst (Fig. 9).

Fig. 8 FE-SEM images of (a) fresh n-Fe₃O₄@TDI@TiO₂–SO₃H, (b) n-Fe₃O₄@TDI@TiO₂–SO₃H after being reused six times.

Fig. 9 FT-IR spectra of n-Fe₃O₄@TDI@TiO₂–SO₃H before use (a) and after being reused six times (b).

3. Experimental

Materials and instruments

All chemicals and reagents were purchased commercially from the Aldrich and Merck chemical companies. Solvents were dried by conventional methods. TDI was industrial grade, containing an 80 : 20 mixture of 2,4 and 2,6 isomers and was used as received. The progress of the reactions was monitored using thin layer chromatography (TLC) with silica gel 60 F254 glass plates. Melting points were measured on a Thermo scientific 9100 apparatus. FT-IR were recorded on a Shimadzu-8400 spectrometer in the range of 400–4000 cm⁻¹ using KBr pellets. Du Pont 2000 thermal analysis apparatus was used for TGA, heated from 25 °C to 800 °C with a heating rate of 10 °C min⁻¹ under an air atmosphere. XRD patterns were recorded at room temperature on a Siemens D5000 (Siemens AG, Munich, Germany) using Cu-Kα radiation. FE-SEM images were collected using a Philips XL30 instrument (Royal Philips Electronics, Amsterdam, The Netherlands) at 30 kV. The magnetite measurement was performed on a vibrating sample magnetometer (4 inch, Daghigh Meghnatis Kashan Co., Kashan, Iran) at room temperature. The NMR spectra were recorded on a Bruker Avance 300 MHz instrument.

Preparation of the magnetic Fe₃O₄ nanoparticles

The magnetic Fe₃O₄ nanoparticles were synthesized using co-precipitation method according to reported literature.³² 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 vigorous stirring and N₂ atmosphere. Then, 25% aqueous ammonia (10 mL) was added into the reaction mixture, which resulted in an immediate black precipitation of MNPs. After 30 min, the reaction was cooled to room temperature and the precipitate was separated by applying an external magnet. It was then washed several times with distilled water and dried for 48 h.

Functionalization of Fe₃O₄ nanoparticles with TDI (n-Fe₃O₄@TDI)

Both Fe₃O₄ nanoparticles (1.0 g) and TDI (1.40 g) were dissolved in 50 mL dried toluene in an ultrasonic bath for 10–15 min. Next, the reaction mixture was stirred magnetically at 95 °C for 20 h under an atmosphere of nitrogen. The powder product was separated magnetically and was carefully washed with dry toluene to remove the unreacted and physically absorbed TDI. It was then dried under vacuum at 100 °C for 4 h.

Preparation of TiO₂ nanoparticles

Nano-TiO₂ was synthesized according to the previously reported procedure, using a hydrothermal method.³⁶ NH₃·H₂O was added to a solution of TiCl₄ until the pH value reached 1.8. After 2 h stirring at 70 °C, the final solution pH was adjusted to 6 and was aged for 24 h at ambient temperature. The final powder was filtered, and rinsed with NH₄Ac–HOAc until no Cl⁻ was detected. The precipitate was separated by centrifugation, washed with ethanol and dried in a vacuum. Treatment at 650 °C for 2 h attained the TiO₂ nanoparticles.

Preparation of n-Fe₃O₄@TDI@TiO₂

1.0 g n-Fe₃O₄@TDI was dispersed in 100 mL dried toluene. Next, 0.3 g n-TiO₂ was added and the dispersion was heated at 110 °C for 48 h under constant stirring. The product, n-Fe₃O₄@TDI@TiO₂, was separated using a permanent magnet, washed with acetone and dried at 100 °C for 4 h.

Preparation of n-Fe₃O₄@TDI@TiO₂–SO₃H

1.0 g Fe₃O₄@TDI@TiO₂ nanoparticles were dispersed in 15 mL dry CH₂Cl₂. Chlorosulfonic acid (0.25 mL, 3.75 mmol) was added drop wise at room temperature over a period of 30 min. Upon completing the addition, the mixture was continuously stirred for 1 h to allow complete evolution of HCl from the reaction mixture. Then, the solvent was removed under reduced pressure and the powder was washed three times with ethanol (10 mL) to remove the unattached acid and was dried at 100 °C for 5 h.

General procedure for the synthesis of benzimidazoloquinazoline derivatives (4)

1,3-Cyclic diketone (1 mmol), aromatic aldehyde (1 mmol), 2-aminobenzimidazole (1 mmol) and catalyst (12 mg) were stirred under solvent free conditions at 85 °C. Upon completion of the reaction (monitored by TLC), the catalyst was separated by applying an external magnet (within 5 s). The reaction mixture was decanted an eluted using hot ethanol (5 mL). The products were obtained by recrystallization using ethanol solution. Percentage yields of the products were calculated as follows:

% yield = actual yield (g)/theoretical yield (g) × 100

General procedure for the synthesis of polyhydroquinoline derivatives (7)

1,3-Cyclic diketone (1 mmol), aromatic aldehyde (1 mmol), ethyl acetoacetate (1 mmol), ammonium acetate (2.5 mmol) and catalyst (12 mg) were mixed under neat condition at 85 °C in an oil bath. Upon completion of the reaction (monitored by TLC), the catalyst was separated by employing an external magnet (within 5 s). The reaction mixture was decanted and eluted using hot ethanol (5 mL). The products were obtained by recrystallization using ethanol solution. Percentage yields of the products were calculated as follows:

% yield = actual yield (g)/theoretical yield (g) × 100

General procedure for recycling n-Fe₃O₄@TDI@TiO₂–SO₃H

For evaluating the recoverability of the catalyst, the condensation of dimedone (1 mmol), benzaldehyde (1 mmol) and 2-aminobenzimidazole (1 mmol) under the optimized conditions was chosen as a model reaction. After completion of the reaction, the catalyst was separated using an external magnet, rinsed thoroughly with ethanol (2 × 5 mL) and acetone (2 × 5 mL) and dried at 70 °C for 2 h to be used for subsequent runs.

4. Conclusions

SO₃H-functionalized magnetic-titania nanoparticles (n-Fe₃O₄@TDI@TiO₂–SO₃H) were successfully synthesized and well characterized using FT-IR, TGA, XRD, FE-SEM, VSM and acid–base titration. FT-IR and TGA confirmed the successful immobilization of sulfonic acid groups. XRD showed the crystallinity retention of Fe₃O₄ and TiO₂ nanoparticles after treatment with an acidic reagent. The FE-SEM results revealed the nanometer-sized particles of the catalyst and VSM demonstrated their magnetic behavior, useful for quick magnetic separation using a conventional magnet. Moreover, according to the acid–base titration, the sulfonic acid group loading was 2.70 mmol g⁻¹. The catalyst exhibited excellent activity in the synthesis of benzimidazoquinazolinones and polyhydroquinolines under solvent-free conditions, which was optimized by CCD and afforded high to excellent yields of products. Furthermore, the catalyst could be easily separated using an external magnet, and be used repeatedly six times, which makes it a potent acidic heterogeneous nanocatalyst for chemical transformations.

Acknowledgements

We gratefully acknowledge the Faculty of chemistry of Semnan University for supporting this work.

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Footnote

† Electronic supplementary information (ESI) available: FT-IR, ¹H NMR and ¹³C NMR spectra. See DOI: 10.1039/c6ra21048a

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