Environmentally friendly cyclotrimerization of substituted acetophenones catalyzed by a new nanocomposite of γ-Al₂O₃ nanoparticles decorated with H₅PW₁₀V₂O₄₀

Abstract

A highly efficient and simple procedure for the synthesis of substituted benzenes is described. A range of aryl and alkyl ketones were used to conduct triple condensation reactions in the presence of a catalytic amount of nano-Al₂O₃/H₅PW₁₀V₂O₄₀ as an efficient and recyclable catalyst under solvent-free conditions. The supported heterogeneous catalyst was characterized using SEM, XRD, DLS, UV-Vis and FT-IR spectroscopy. All condensation reactions were completed in a suitable time compared to existing methods without formation of any undesirable 1,2,4-trisubstituted by-products. The entire synthetic sequence is cost-effective, environmentally benign, and possesses convenient generality, which makes the method meritorious as a valid contribution to the existing methods in the field of highly substituted benzene synthesis.

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1. Introduction

Screening new efficient, high yielding, and environmentally benign synthetic transformations based on the principles of green chemistry and sustainability has been one of the major challenges of the past decades.^1–4 Moreover, in the context of extending green synthetic strategies, solvent-free conditions are also a promising and essential facet of green chemistry through diminishing the consumption of hazardous organic solvents in a scaled-down reaction and achieving energy savings.

Polyarylated benzene propellers have attracted a great deal of enthusiasm in cutting edge carbon nanotechnology, developing new efficient molecular rotors, and production of new electroluminescent materials for flat panel displays.⁵ 1,3,5-Triarylbenzenes are important polycyclic aromatic compounds displaying potential applications in chemical industries such as nanomaterials,⁶ photovoltaic resisting materials,⁷ conducting polymers,⁸ electroluminescent devices,⁹ and various conjugated polyaromatics.¹⁰ A number of synthetic strategies have been developed previously to construct 1,3,5-triarylbenzenes. The most common methods include the metal catalyzed cyclotrimerization of alkynes,^11–14 cross coupling reactions of aryl halides,^15–18 and triple self-condensation of aryl methyl ketones in the presence of an acidic catalyst such as HCl,¹⁹ SiCl₄,²⁰ TiCl₄,²¹ para-toluenesulfonic acid,²² Bi(OTf)₃·4H₂O,²³ zirconocenebis(perfluoroctanesulfonate)s,²⁴ ethylenediamine or trifluoroacetic acid.²⁵ Condensation of aryl acetones mediated by Lewis acids provides an alternative pathway which only supplies C₃-symmetrical 1,3,5-triarylbenzenes. However, in spite of their potential utility, these methods typically suffer from one or more disadvantages such as problematic substrates, use of a stoichiometric amount of catalyst, production of excessive waste, moisture sensitivity, specialized handling requirements, tedious workup, lack of generality, requirement of a transition metal as well as complicated ligands, and non-recyclability of the catalyst. Therefore, investigation of green routes by using renewable catalytic systems to synthesize 1,3,5-triarylbenzenes is highly desirable.

Heteropolyacids are strong and environmentally benign acid catalysts which contain sufficient acidic sites and have been explored as prominent catalysts in organic transformations.^26–28 These inorganic metal–oxygen clusters bear high dispersion of negative charge over many atoms of the polyanion by exploiting strong Brønsted acid sites over the outer surface of the polyanion. However, some of their inherent drawbacks such as high solubility in aqueous solution and continuous leakage during operation limit the scope of their practical applications. To overcome these restrictions, heterogenization of the heteropolyacid through immobilization onto different weakly acidic or non-basic carriers is recommended. Up to now, several solid acids such as zeolites,^27,28 MCM-41,²⁹ MCM-48,³⁰ and SBA-15 (ref. 31) have been reported to support heteropolyacids via immobilization.

γ-Al₂O₃ is perhaps one of the most important nanomaterials employed as support for metal catalysts and is considered as a promising material for a variety of applications due to its distinctive chemical, mechanical, and thermal properties.³² Therefore, γ-Al₂O₃ could be a good candidate to accommodate and deposit heteropolyacids and produce effective catalysts in organic synthesis by consideration of either Lewis and/or Brønsted acidic characteristics.³²

To continue our efforts in the development of one-pot syntheses^33–35 for various biologically important compounds and owing to the importance of 1,3,5-triarylbenzenes, herein an effective route for the preparation of these compounds is disclosed via the triple self-condensation of aryl methyl ketones in the presence of a new heterogeneous catalyst composed of nano-γ-Al₂O₃ and H₅PW₁₀V₂O₄₀ (HPA) under solvent-free conditions (Scheme 1). The present solvent-free methodology is effective and provides only the desired C₃-symmetrical 1,3,5-triarylbenzenes in high yields by employing a simple, economic, and reusable heterogeneous catalyst without producing waste.

Scheme 1 General formula for the cyclotrimerization of acetophenones.

2. Experimental

2.1. Materials and methods

All reagents and starting materials were commercially available and used as received. Hydrophilic γ-aluminum oxide nanopowder (>99%) was purchased from NanoSany Corporation, Iran. The progress of reactions was monitored by TLC on silica gel polygram SIL G/UV 254 plates. Melting points were recorded on a Bamstead Electrothermal type 9200 melting point apparatus. Scanning electron microscope (SEM) micrographs and energy-dispersive X-ray (EDX) analysis were obtained using a LEO 440i microscope (acceleration voltage 26 kV). Transmission electron microscopy (TEM) images were obtained using a Philips Zeiss-EM10C transmission electron microscope with an accelerating voltage of 80 kV. X-ray diffraction patterns were obtained on a PW1840 (PHILIPS) diffractometer with Cu Kα radiation at 40 keV and 30 mA with a scanning rate of 3° min⁻¹ in a 2θ range from 1° to 80°. Hydrodynamic particle size analysis of nano-γ-Al₂O₃/H₅PW₁₀V₂O₄₀ in an ethanol suspension was determined by measuring dynamic light scattering using a Zeta Sizer-HT (Brookhaven). Fourier transform infrared (FT-IR) spectra were recorded on an 8700 Shimadzu Fourier Transform spectrophotometer in the region of 400 to 4000 cm⁻¹ using KBr pellets. Ultraviolet-visible spectra were recorded on a Photonix UV-Vis Array spectrophotometer, Model Ar 2015, Iran. The tungsten and vanadium content of the nanocatalyst was determined using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) conducted on a Varian Vista-Pro model ICP-MS spectrometer. A freeze dryer, Model FD-10, Pishtaz Equipment Engineering Co, Iran, was used for drying the prepared nanocomposites. ¹H and ¹³C NMR spectra were recorded on a Bruker AVANCE instrument operated at 300 MHz using TMS as an internal reference. All products were identified by comparison of their spectral and physical data with those previously reported.³⁶ H₅PW₁₀V₂O₄₀·30H₂O was prepared according to reported procedures.³⁷

2.2. Surface modification of γ-alumina nanoparticles with different modifiers

Surface modification was performed by adding 0.9 g of nano-alumina to 0.1 g of the modifier dissolved in 5 ml of methanol. Then, the resulting solution was stirred for 6 h at room temperature. Finally, the mixture was heated gently to 40 °C until a white solid material was achieved. The resulting composites were dried at 80 °C for 8 h.

2.3. Preparation of γ-Al₂O₃/H₅PW₁₀V₂O₄₀ nanocomposite

H₅PW₁₀V₂O₄₀ was supported on γ-Al₂O₃ nanoparticles via wet impregnation method. In this procedure, 0.9 g of nano-alumina was dispersed in 5 ml of a methanolic solution of HPA (0.1 g/5 ml). This mixture was stirred at room temperature for 6 h, which was supposed to be long enough to attain equilibrium of the adsorption–desorption processes. The resultant mixture was dried slowly at 40 °C until a white solid material was attained. Then, the sample was kept at 80 °C for 8 h for complete drying. To study effect of drying conditions on the catalytic efficacy of the nanocomposite, a freeze drying technique was compared with the usual classic drying in an oven at 80 °C under air. The results obtained demonstrate no obvious improvement in catalyst efficiency under the freeze drying conditions.

2.4. General procedure for the cyclotrimerization of acetophenones into 1,3,5-triphenylbenzenes

In a typical reaction, acetophenone (1 mmol) and γ-Al₂O₃/HPA (0.02 g) were added to a small test tube and the reaction mixture was stirred at 90 °C for the required time. After completion of the reaction, as indicated by TLC using n-hexane/ethyl acetate 3 : 1 as an eluent, the reaction mixture was cooled to 25 °C, then hot ethanol was added and the mixture was stirred for 5 min. The insoluble catalyst was isolated via simple filtration. The filtrate containing water, as the only by-product of the cyclotrimerization, was concentrated under reduced pressure and finally the obtained crude product was purified through re-crystallization in EtOH : H₂O (3 : 1) as confirmed by an intense single spot in TLC. The pure products were specified based on the spectral data and determination of their melting points.³⁶

2.5. Calculation of pH_pzc (point of zero charge pH)

The pH_pzc is a point at which the surface acidic or basic functional groups no longer affect the pH value of the solution. The effect of surface modification with HPA on the acidity of γ-Al₂O₃ was studied by calculating pH_pzc for both γ-Al₂O₃/HPA and γ-Al₂O₃ nanoparticles. The pH of a series of NaCl solutions (50 ml, 0.01 M) was adjusted to a value between 2 and 12 by the addition of HCl (0.1 M) or NaOH (0.1 M) solutions in closed Erlenmeyer flasks. Then, pH of the solutions was defined as the initial pH (pH_I). Thereafter, 0.2 g of the modified γ-Al₂O₃/HPA (or unmodified γ-Al₂O₃) was added and the final pH (pH_F) was measured after 48 h. Finally, the values of pH_F vs. pH_I and also pH_I vs. pH_I were plotted and the intersect of the lines provided the pH_pzc.³⁸

2.6. Representative spectral data of 1,3,5-triarylbenzenes

2.6.1. 1,3,5-Triphenylbenzene. Light yellow solid; mp 172–174 °C. IR (KBr): v_max = 3051, 1650, 1496, 1432, 1126, 759, 699 cm⁻¹. ¹H NMR (CDCl₃): δ = 7.18 (3H, s); 7.72 (6H, m); 7.50 (6H, m); 7.42 (3H, m).

2.6.2. 1,3,5-Tris(4-methylphenyl)benzene. White solid; mp 177–179 °C. IR (KBr): v_max = 3018, 2921, 1611, 1512, 1489, 1110, 813 cm⁻¹. ¹H NMR (CDCl₃): δ = 2.43 (s, 9H, CH₃), 7.29 (d, J = 8.0 Hz, 6H, ArH), 7.60 (d, J = 8.0 Hz, 6H, ArH), 7.74 (s, 3H, ArH).

2.6.3. 1,3,5-Tris(4-methoxyphenyl)benzene. White solid; mp 141–143 °C. IR (KBr): v_max = 2954, 2917, 2849, 1603, 1463, 1377, 1261, 1099, 803 cm⁻¹. ¹H NMR (CDCl₃): δ = 3.81 (s, 9H, OCH₃), 6.92–7.60 (m, 12H, ArH), 7.75 (s, 3H, ArH).

2.6.4. 1,3,5-Tris(4-chlorophenyl)benzene. Light yellow solid; mp 247–249 °C. IR (KBr): v_max = 3046, 1599, 1492, 1382, 1092, 1011, 814 cm⁻¹. ¹H NMR (CDCl₃): δ = 7.46 (d, J = 8.4 Hz, 6H, ArH), 7.61 (d, J = 8.4 Hz, 6H, ArH), 7.70 (s, 3H, ArH).

2.6.5. 1,3,5-Tris(4-bromophenyl)benzene. White solid; mp 263–264 °C. IR (KBr): v_max = 3043, 1595, 1489, 1379, 1075, 1007, 809 cm⁻¹. ¹H NMR (CDCl₃): δ = 7.54 (d, J = 8.1 Hz, 6H), 7.61 (d, J = 8.2 Hz, 6H), 7.69 (s, 3H).

2.6.6. 1,3,5-Tris(4-hydroxyphenyl)benzene. White solid; mp 237–239 °C. IR (KBr): v_max = 2953, 2918, 2848, 1606, 1460, 1378, 1263, 1097, 802 cm⁻¹. ¹H NMR (CDCl₃): δ = 3.81 (s, 9H), 6.94–7.41 (m, 12H), 7.79 (s, 3H).

2.6.7. 1,3,5-Tris(4-nitrophenyl)benzene. White solid; mp 151–152 °C. IR (KBr): v_max = 3043, 1595, 1489, 1379, 1085, 1007, 849 cm⁻¹. ¹H NMR (CDCl₃): δ = 7.56 (d, J = 8.1 Hz, 6H), 7.62 (d, J = 8.2 Hz, 6H), 7.70 (s, 3H).

3. Results and discussion

3.1. Characterization and physicochemical properties of γ-Al₂O₃/HPA nanoparticles

The physicochemical and morphological properties of the supported γ-Al₂O₃/H₅PW₁₀V₂O₄₀ catalyst were investigated by means of FT-IR, UV-Vis, SEM, XRD, and DLS. The most informative technique for the investigation of the surface interactions between H₅PW₁₀V₂O₄₀ and nano-γ-Al₂O₃ is FT-IR. The spectra of free H₅PW₁₀V₂O₄₀ (A), HPA impregnated nano-γ-Al₂O₃ (B), and nano-γ-Al₂O₃ (C) were recorded for structural characterization purposes (Fig. S1†). The Keggin heteropolyacid shows four characteristic bands in the range of 750–1100 cm⁻¹.³⁹ The observed bands at around 778–785 and 850–890 cm⁻¹ are assigned to W–O–W. The peaks about 950–998 and 1070–1090 cm⁻¹ are associated with M=O and P–O bonds, respectively, which distinctively indicate the neat structure of the Keggin framework for the heteropolyacid. In the FT-IR spectrum of γ-Al₂O₃/H₅PW₁₀V₂O₄₀, these four peaks slightly overlap with those of γ-Al₂O₃. However, spectrum (B) confirms that loading of HPA occurred and H₅PW₁₀V₂O₄₀ was successfully immobilized on the pores of the nano-γ-Al₂O₃ support.

The morphology of the γ-Al₂O₃/H₅PW₁₀V₂O₄₀ nanocatalyst was investigated using SEM and TEM microscopy (Fig. 1). The TEM and SEM images show that the mean particle size of the catalyst was clearly <40 nm. According to the TEM micrograph, the two observed morphologies are due to γ-Al₂O₃ (rod-like) and H₅PW₁₀V₂O₄₀ (sheet-like) nanoparticles (Fig. 1c). Actually, by introducing HPA into γ-Al₂O₃, no significant effect on the homogeneity of the material occurred and the structure of the nano-alumina was maintained. Concerning the chemical composition of γ-Al₂O₃/H₅PW₁₀V₂O₄₀, energy dispersive X-ray (EDX) analysis was obtained (Fig. S2†). The analysis of EDX spectrum proves the existence of tungsten, vanadium, oxygen, and aluminium in the nanocatalyst; therefore, immobilization of the heteropolyacid onto the nano γ-Al₂O₃ is justified.

Fig. 1 SEM micrograph of γ-Al₂O₃ (a), and SEM (b) and TEM (c) images of γ-Al₂O₃/H₅PW₁₀V₂O₄₀. (a) is reproduced with permission.⁴⁸

Fig. 2 displays wide-angle XRD patterns of the pure heteropolyacid (a), bare γ-Al₂O₃ (b) and heteropolyacid loaded γ-Al₂O₃/HPA (c). The unmodified γ-Al₂O₃ exhibits peaks at 37.5, 39.6, 45.7 and 67.5° which are attributed to the typical pattern of γ-alumina (Fig. 2b). These peaks are also evident for the modified γ-Al₂O₃/HPA (Fig. 2c). However, most of the peaks corresponding to the heteropolyacid are absent or are strongly weakened in the XRD pattern of γ-Al₂O₃/HPA. These findings indicate that HPA clusters were too small or were successfully finely dispersed onto the γ-alumina surface rather than existing as the free crystalline solid acid.⁴⁰

Fig. 2 X-ray diffraction patterns of pure H₅PW₁₀V₂O₄₀ (a), γ-Al₂O₃ (b), and γ-Al₂O₃/H₅PW₁₀V₂O₄₀ (c) nanoparticles.

The UV-Vis spectrum of HPA in methanol displays an absorption peak at 236 nm, which is assigned to the charge-transfer absorption in the heteropoly cage (Fig. 3). To find the extent of H₅PW₁₀V₂O₄₀ that can be loaded on the support, UV-Vis spectra of solutions containing HPA before and after addition of γ-alumina were obtained. For this purpose, 0.1 g of γ-Al₂O₃ was suspended in a 40 ml methanol solution of HPA with an initial concentration of 2500 ppm. The suspension was stirred for 120 min and absorption spectra were recorded for the solution after removing the solid catalyst by filtration (Fig. 3). Evidently, most of the heteropolyacid content was adsorbed on the alumina surface after 90 min. After stirring the solution and comparing with calibration curves for standard solutions, 0.026 mmol of H₅PW₁₀V₂O₄₀ was loaded per gram of the γ-Al₂O₃ support.

Fig. 3 Stacked plot of UV-Vis spectral changes with time after the addition of H₅PW₁₀V₂O₄₀ to γ-Al₂O₃.

For confirmation of HPA loading on the support, 0.01 g of the heterogeneous nanocatalyst Al₂O₃/H₅PW₁₀V₂O₄₀ was analyzed by ICP-MS. The results indicate the presence of 0.22 μmol H₅PW₁₀V₂O₄₀. This finding is in good agreement with the results from UV-Vis analysis.

Finally, hydrodynamic particle size analysis of γ-Al₂O₃/H₅PW₁₀V₂O₄₀ was performed by measuring the dynamic light scattering of the nanoparticles in ethanol (Fig. S3†). The particle size histogram of the nanocatalyst shows that most of the particles range in size from 25–60 nm and possess an average size of 30 nm.

3.2. Equilibrium studies and adsorption isotherms

The equilibrium relationships between γ-Al₂O₃, as the adsorbent, and H₅PW₁₀V₂O₄₀, as the adsorbate, and the adsorption behavior of the heteropolyacid could be described by an adsorption isotherm. The shape of the isotherm not only provides information on the adsorption affinity of HPA, but also provides relevant information about adsorption spontaneity and the stability of adsorbent–adsorbate interactions.

The amount of the Keggin heteropolyacid adsorbed onto γ-Al₂O₃ nanoparticles was calculated by studying the adsorption isotherm based on Freundlich and Langmuir patterns and the experimental data were fitted linearly.^41,42 The Langmuir isotherm theory assumes monolayer coverage of the adsorbate over a homogenous adsorbent surface leading to surface homogeneity of the adsorbent; whereas the Freundlich adsorption isotherm is an indication of the surface heterogeneity of the adsorbent. According to the Langmuir adsorption model, the maximum adsorption would be due to the saturated monolayer of solute molecules on the adsorbent surface. The non-linear expression of the Langmuir model is given by eqn (1):

q = abC_e/(1 + bC_e) (1)

where constants “a” and “b” are the Langmuir constants showing the capacity and energy of adsorption, respectively, and can be calculated from non-linear fitting. Therefore, “a” is the maximum amount of adsorbate per unit weight of sorbent to form a complete monolayer on the surface (mg g⁻¹) and corresponds to the free energy or net enthalpy of adsorption. Moreover, “b” is a constant related to the energy of adsorption and indicates the stability of the adsorbate–adsorbent composite. The applicability of Langmuir and Freundlich adsorption isotherms in the interaction of HPA with γ-alumina is determined based on the correlation coefficient (R²). The calculations indicate that the reported experimental data correlates better with the Langmuir isotherm (Fig. S4 and Table S1†).

3.3. Calculating the pH_pzc of γ-Al₂O₃

Point of zero charge (pH_pzc) is the value at which the surface of a solid inorganic material bears a net neutral charge. At pH_pzc, the surface acidic (or basic) functional groups no longer contribute to the pH value of the solution.⁴³ It encompasses positive charge in solution with pH < pH_pzc; whereas, in solution with pH > pH_pzc negative charge would be developed at the surface of the mineral compound. Therefore, changes to the protonation–deprotonation characteristics of Al–OH groups in the framework of γ-Al₂O₃ as a result of HPA loading caused some structural transformation which altered the pH_pzc and therefore the equilibrium pH of the suspension.⁴⁴ The pH_pzc for γ-Al₂O₃ was analyzed to evaluate the effect of HPA loading on the acidity of the nano γ-alumina surface. The lower pH_pzc for the modified γ-Al₂O₃/HPA (pH_pzc = 5.7) compared to unmodified γ-Al₂O₃ confirms an increment in the acidity of nano-alumina after surface modification with the heteropolyacid (Fig. S5†).

3.4. Catalytic tests

3.4.1. Effects of some surface modifiers on the catalytic activity of γ-Al₂O₃. Effects of the nature and chemistry of different surface modifiers on the catalytic activity of γ-Al₂O₃ in the preparation of 1,3,5-triphenylbenzene were subjected to study. The two Keggin heteropolyacids H₃PW₁₂O₄₀ and H₅PW₁₀V₂O₄₀ with comparable acidity were loaded on γ-Al₂O₃ through a simple wet impregnation method, then the prepared heterogeneous catalysts were applied in the above-mentioned condensation reaction. The results show their pronounced catalytic activity compared to bare γ-Al₂O₃ (Table 1, entry 1) and free heteropolyacids (entries 5–6). Moreover, the surface of γ-Al₂O₃ was also modified with CeO₂. The nanocomposite (CeO₂/Al₂O₃) has an improved catalytic activity over that of γ-Al₂O₃ (entry 4); but, less than nano-alumina modified with the two above heteropolyacids.

Table 1 Effects of some surface modifiers on the catalytic activity of γ-Al₂O₃ nanoparticles in the preparation of 1,3,5-triphenylbenzene^a

Entry	Modifier	Nanocomposite	Yield%
a Reaction conditions: 1 mmol of acetophenone was mixed with 0.02 g of the nanocatalyst under solvent free conditions at 90 °C for 2.5 h.b 0.45 μmol of the heteropolyacids were used. Note that the mean value of 0.024 mmol HPA is considered per 1.07 g of the nanocatalyst.
1	—	γ-Al2O3	35
2	H3PW12O40	H3PW12O40/Al2O3	75
3	H5PW10V2O40	H5PW10V2O40/Al2O3	85
4	CeO2	CeO2/Al2O3	70
5	H3PW12O40^b	—	<3
6	H5PW10V2O40^b	—	<3

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3.4.2. Studying catalyst amount on the cyclotrimerization reaction. To find the optimized reaction conditions and studying the catalytic activity of γ-Al₂O₃/H₅PW₁₀V₂O₄₀ compared with bulk γ-Al₂O₃, a model reaction with acetophenone was explored with different amounts of the above catalysts (Table 2). First of all, the condensation reaction was inefficient in the absence of catalyst (entry 1) and <1% of product was attained after 2.5 h. Moreover, 5 mg of bulk alumina was inefficient and did not attain a detectable amount of product after 2.5 h, whereas the same amount of γ-Al₂O₃/H₅PW₁₀V₂O₄₀ provided a 50% yield under similar reaction conditions after 2.5 h. However, the yield was increased by enhancing the catalyst amount for both the bulk and surface modified nano-alumina. Results shown in Table 2 clearly confirm that the modified nano-alumina behaved better than the bare γ-Al₂O₃. The best yield was achieved in the presence of 20 mg of the heterogeneous catalyst, due to the proportional increase in the number of active sites. However, beyond a catalyst loading of 20 mg, no significant improvement in percentage yield was observed.

Table 2 Cyclotrimerization of acetophenone with modified and unmodified γ-Al₂O₃ nanoparticles^a

Entry	Nanocatalyst (mg)	HPA (μmol) content	Yield (%)
			γ-Al2O3 (nano)	γ-Al2O3/HPA (nano)
a Reaction conditions: 1 mmol of acetophenone was mixed with the desired amount of catalyst under solvent-free conditions at 90 °C for 2.5 h.
1	—	—	n. d.	n. d.
2	5	0.11	—	50
3	10	0.22	15	63
4	15	0.33	22	77
5	20	0.44	35	85
6	30	0.66	38	85

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3.4.3. Effect of temperature on the cyclotrimerization reaction. The effect of temperature on the condensation of acetophenone was investigated under the standard reaction conditions. Expectedly, the yield of product was negligible at 25 °C and <25% yield was attained after 2.5 h; whereas, percentage yield was increased with increasing the reaction temperature and the best yield of 85% was attained at 90 °C (Fig. S6†). A further increase in temperature to 120 °C did not afford a significant enhancement in product yield, therefore because of the technical and experimental facilities, 90 °C was chosen for all condensation reactions.

3.4.4. Effect of reaction time on the cyclotrimerization reaction. The effect of reaction time was also studied in the condensation of acetophenone under the optimized reaction conditions. As expected, the yield was increased with time and most of the reaction progress was attained after 90 min, however, the time of 150 min was selected in all cases to reach the best yield. A further increase in reaction time did not enhance percentage yield significantly (Fig. S7†).

3.4.5. Studying the generality of the cyclotrimerization reaction. In the next step, to assess the scope and generality of the present methodology, different acetophenones were subjected to the cyclotrimerization reaction under the optimized conditions. Thus, a range of structurally different substituted acetophenones were condensed to supply the corresponding products. As shown in Table 3, both electron withdrawing and electron releasing substituents on the aromatic ring show good activity towards the condensation reaction. Noteworthy, the present method was effective in the cyclotrimerization of p-nitro-acetophenone, as a strongly electron withdrawing substituted acetophenone, which has been difficult to cyclotrimerize by other methods (entry 4).¹⁵

Table 3 Synthesis of different 1,3,5-triphenylbenzene derivatives catalyzed by surface modified γ-Al₂O₃/H₅PW₁₀V₂O₄₀^a

Entry	R	Time (h)	Yield (%)	Mp (°C)	Product	Ref.
a Reaction conditions: substrate (1 mmol), 90 °C, 0.02 g of γ-Al2O3/H5PW10V2O40, solvent-free conditions. All products were known and were identified by comparison of their spectral and physical data with those previously reported.
1	H	2.5	85	172–174	(Ph)3C6H3	36d
2	4-OMe	2.5	60	141–143	(4-OMePh)3C6H3	36d
3	4-Br	2	85	263–264	(4-BrPh)3C6H3	23
4	4-NO2	2.5	68	151–152	(4-NO2Ph)3C6H3	36a
5	4-Me	3	82	177–179	(4-MePh)3C6H3	23
6	4-OH	3.5	77	237–239	(4-OHPh)3C6H3	36a
7	4-Cl	2.5	93	247–249	(4-ClPh)3C6H3	36d

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3.4.6. Comparison of the efficacy of the present methodology with some reported methods. To explore the capability of the present methodology among that of other reported methods for the preparation of the title compounds, the synthesis of 1,3,5-triphenylbenzene was considered in the presence of some reported catalysts in terms of mol% of the catalyst, temperature, reaction time, and percentage yield (Table 4). Accordingly, the present methodology is clearly superior over the mentioned protocols considering the above variables.

Table 4 Comparison of the catalytic activity of γ-Al₂O₃/H₅PW₁₀V₂O₄₀ with some reported catalysts towards the cyclotrimerization of acetophenone

Entry	Catalyst	Catalyst (mol%)	Solvent	Time (h)	Temp. (°C)	Yield (%)	Ref.
a DBSA: 4-dodecylbenzenesulfonic acid.
1	H3PMo12O40	5	Ethanol	5	Reflux	87	21
2	SnCl4	10	Ethanol	24	Reflux	55	45
3	CuCl2	8	Free	4	155	76	46
4	DBSA^a	20	Free	3	130	60	47
5	HCl	10	Ethanol	11	Reflux	45	46
6	Amberlyst 15	30	Toluene	10	Reflux	60	36b
7	γ-Al2O3/HPA	0.02 g	Free	2.5	90	85	This work

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3.4.7. Studying the reusability of γ-Al₂O₃/H₅PW₁₀V₂O₄₀. To explore the reusability of γ-Al₂O₃/H₅PW₁₀V₂O₄₀ in the condensation reaction, cyclotrimerization of acetophenone was studied under the optimized reaction conditions. The catalyst was easily separated from the reaction mixture. Then, after washing with chloroform, the catalyst was dried in air and was further dried in a vacuum oven at 100 °C for 8 h. Finally, the recycled catalyst was reused in another condensation reaction. The findings prove that catalytic activity similar to that of the fresh catalyst was observed and no significant loss of activity was detected (Fig. 4). Moreover, to ensure reproducibility of the transformation, repeated typical experiments were carried out under identical reaction conditions. The obtained yields were found to be reproducible within ±3% variation.

Fig. 4 Reusability of γ-Al₂O₃/H₅PW₁₀V₂O₄₀ in the cyclotrimerization of acetophenone.

3.4.8. Hot filtration test. To confirm that the catalytic activity was generated from the heterogeneous nanocatalyst, and not from leached heteropolyacid in the reaction mixture, a hot filtration test was undertaken. In this technique, the condensation reaction of acetophenone (1 mmol) in the presence of catalyst (γ-Al₂O₃/HPA, 0.02 g) was performed under solvent-free conditions at 90 °C for 0.5 h. In this step, the yield of the product was 31%. Then, the solid catalyst was filtered off under hot conditions and with the filtrate, which was obtained after separation of the catalyst, the reaction was continued for another 2 h at the same reaction temperature. However, an inappreciable increase in the yield (35%) was observed. This result confirmed the heterogeneous nature of the nanocatalyst in this condensation reaction and that no significant leaching of the heteropolyacid occurred during the course of the reaction.

3.4.9. Suggesting a plausible reaction pathway. A plausible reaction pathway for the synthesis of 1,3,5-triarylbenzenes is proposed in Scheme S1.† The reaction possibly proceeded through protonation of the aryl methyl ketone to form the intermediates (A) and (B) in the presence of the nanocatalyst. The reaction between these intermediates followed by dehydration, produced an α,β-unsaturated carbonyl compound (C). Activation of (C) by the catalyst and subsequent reaction with (A) led to the generation of (D) that on subsequent dehydration followed by prototropic shift in the presence of catalyst afforded (E). 6-p electrocyclization of (E) led to (F) which upon dehydration afforded the desired product (G) and released the catalyst for the next catalytic cycle.²⁷

γ-Al₂O₃ nanoparticles with a relatively high specific surface of >138 m² g⁻¹ have two types of Lewis and Brönsted acidic sites.⁴⁸ The catalytic activity of the nanoparticles would be associated with the improved acidic properties of the surface after modification with the heteropolyacid. Lewis-type acid sites of alumina are formed during the dehydration process by combination of the two surface hydroxyl groups.⁴⁹ Considering previous work,⁵⁰ it is assumed that the heteropolyacid is physisorbed onto the surface of γ-Al₂O₃. However, strong Brönsted acid sites may be formed by the reaction between H₅PW₁₀V₂O₄₀ and the hydroxyl groups present on the surface of γ-Al₂O₃. Therefore, the approach of modifying a γ-Al₂O₃ surface with HPA can increase the concentration of the surface acidic sites.^51,52

4. Conclusions

In conclusion, γ-Al₂O₃/H₅PW₁₀V₂O₄₀ is recommended as a useful, efficient, and recyclable heterogeneous catalyst for the cyclotrimerization of substituted aacetophenones to afford only C₃-symmetrical 1,3,5-triarylbenzenes in high yields. The presented simple protocol shows several advantages over some reported literature methods from economic and environmental points of view, such as operational simplicity, no need to be protected from the atmosphere, short reaction time, mild reaction conditions, and good yields. Moreover, water was the only by-product of this reaction and the used catalyst was recyclable. This safe and clean procedure would be an acceptable candidate for automated applications.

Acknowledgements

Partial financial support from the Research Councils of Hakim Sabzevari University and Islamic Azad University of Tehran, North Branch is greatly appreciated.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra07141d

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