A novel method for the synthesis of benzothiazole heterocycles catalyzed by a copper–DiAmSar complex loaded on SBA-15 in aqueous media

Abstract

Cu(II)–DiAmSar complex functionalized mesoporous SBA-15 silica support was employed for the synthesis of benzothiazole heterocycles in aqueous media as a green solvent with excellent yields. The resulting novel catalyst is extraordinarily stable and inhibits leaching of the metal ions from the SBA-15 support. Furthermore, it showed good heterogeneous catalytic activity in the synthesis of the previously mentioned heterocycles and could also be recycled from the reaction mixture and reused six times. The nature of the support after the anchoring of Cu(II)–DiAmSar complex on the surface of SBA-15 nanochannels and successful anchoring were examined using X-ray diffraction, transmission electron microscopy, nitrogen physical adsorption, Fourier transform infrared studies and thermogravimetric analysis.

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1. Introduction

Mesoporous materials such as the M41, FSM and SBA families with pore sizes between 2 and 50 nm have received plenty of attention in catalysis and other areas because of their features such as high surface areas (up to 1200 m² g⁻¹), uniform and tuneable pore sizes, organic solvent tolerance and great diversity in surface functionalization.^1–3

Nanomaterials have been widely used as useful and versatile solid supports for constructing various hybrid materials for heterogeneous catalysis, as adsorbing agents, in drug delivery and in many other fields. The larger pore sizes and high thermal and physical stability of SBA-15 make it one of the most interesting supports in the family of mesoporous materials.^4–6 SBA-15 is not directly utilized as a catalyst in reactions, therefore, functionalization of SBA-15 nanomaterials using organic frameworks or complexes containing transition metal ions is applied. The covalent linkage between the support and the active site is a desirable way to avoid the leaching of metal ions. Therefore, encapsulation of the metal, especially with diamine-sarcophagine ligands (DiAmSar) which are covalently anchored^7–9 into the pores of mesoporous materials, is worth examining. Furthermore, heterogeneous catalysts are very effective from a green chemistry viewpoint, because the applied catalyst can be easily recycled and separated.^10–12

DiAmSar ligands are very appropriate for encapsulation of different metal ions, including radioisotopes and transition metals, which make them particularly well suited for radiopharmaceutical applications, diagnostic positron emission tomography (PET) imaging, and highly active in catalytic systems.^13,14 DiAmSar can also be conjugated to peptides, antibodies and biologically compatible polymers via its amine functionality and can be radiolabelled with a number of PET isotopes such as ⁶⁴Cu(II) for use in imaging interactions between molecular excavators and biological targets.^15,16

Molecules containing a benzothiazole moiety are of great interest in synthesis, because of their various biological activities, including anti-HIV,¹⁷ antibacterial,¹⁸ antitumor,¹⁹ and neuroprotective effects.²⁰ There are also some pharmaceutical drugs such as riluzole 1 (used in the treatment of amyotrophic lateral sclerosis),²¹ ethoxzolamide 2 (used for treatment of glaucoma, duodenal ulcers and as a diuretic) and dyes such as thioflavin 3 (used for staining in histology) which have benzothiazole building blocks (Fig. 1). Because these heterocycles are important in medicinal and synthetic chemistry,²² a range of approaches have been reported for the preparation of 2-substituted benzothiazoles. Most commonly these routes involve condensation reactions of 2-aminothiophenol with carbonyl derivatives such as aldehydes,²³ carboxylic acids,²⁴ acid chlorides²⁵ and esters.²⁶ However, currently reported methods suffer from one or more drawbacks such as the use of strongly oxidizing or toxic reagents. Consequently, the development of a simple, convenient and eco-friendly method would be of interest. In this study, a novel, environmentally friendly and highly active Cu(II)–DiAmSar/SBA-15 used as a reusable heterogeneous catalyst is introduced and its application in the synthesis of benzothiazole derivatives in water is investigated.

Fig. 1 Drug and dye products containing benzothiazole moieties.

2. Experimental

2.1. Materials

Acetonitrile, ethanol, formaldehyde (HCOH), sodium hydroxide (NaOH), hydrochloric acid (HCl), methanol (MeOH), stannous chloride dihydrate (SnCl₂), cobalt(II) chloride hexahydrate, sodium cyanide (NaCN), nitromethane (CH₃NO₂), ethylanediamine, a commercial grade of 2-aminothiophenol (ortho-aminothiophenol), aldehydes, poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) triblock copolymer (P123), (3-chloropropyl)trimethoxysilane (CPTMS), copper(II) acetate monohydrate Cu(OAC)₂, tetraethyl orthosilicate, and nitric acid (HNO₃) were purchased from Sigma-Aldrich, Merck and Acros chemical companies. Double distilled water was used when necessary. All materials were used without further purification. The solvents used for the synthesis were of analytical grade and were used as received. Silica gel (Merck, grade 9385, 230–400 mesh, 60 Å) for column chromatography was used as received. All other reagents were purchased from Merck and used as received unless otherwise noted. The course of the synthesis of heterocycles was followed using thin layer chromatography (TLC) on silica gel plates (Merck, silica gel 60 G F₂₅₄, ready to use), using n-hexane:ethyl acetate (4 : 1) as eluent. The eluent for the column chromatography was the same as TLC eluent.

2.2. Synthesis

2.2.1 Preparation of Cu(II)–diamsar complex anchored onto SBA-15 (Cu(II)–DiAmSar/SBA-15) (Scheme 2). SBA-15 was prepared using the procedure previously described by Zhao et al.²⁷ The synthesis of DiAmSar 7 (Scheme 1) is reported elsewhere (see also the detailed procedure on preparation in the ESI† section).^28,29 DiAmSar 7 (0.0318 mmol, 0.01 g) and methanol (20 mL) were added to a flask and stirred at room temperature for an hour. Then CPTMS (0.0318 mmol, 0.006 g) was added to the solution and the solution was stirred at room temperature for 24 hours, then copper(II) acetate monohydrate (0.0318 mmol, 0.006 g) was added and the solution was heated at 80 °C for a further six hours. Finally, activated SBA-15 was added and the resulting solution was heated for 24 hours. The solvent was evaporated using a rotary evaporator, and the blue solid obtained was dried overnight at 80 °C. The product was washed with MeOH and deionized water until it became colorless. Further drying was carried out in an oven at 80 °C for eight hours.

Scheme 1 Preparation of DiAmSar.

2.2.2 General procedure for the preparation of 2-substituted benzothiazole heterocycles in water. A round bottomed flask equipped with a magnet and condenser was charged with 2-aminothiophenol 8 (1.0 mmol), substituted benzaldehyde (1.0 mmol), the Cu(II)–DiAmSar/SBA-15 catalyst (0.005 g) and water (2 mL). The resulting mixture was stirred and heated under reflux for the appropriate times. After the reaction was completed (monitored by TLC), the reaction mass was cooled to room temperature. Finally, the crude mixture was purified by column chromatography or recrystallization in toluene to obtain the desired products. Spectral and physical data for all heterocycles are reported in the ESI.†^30–32

2.3. Characterizations

Transmission electron microscopy (TEM) was performed with an Hitachi H 700 CTEM. Fourier transform infrared (FT-IR) spectra were recorded on KBr pellets using a Jasco 4200 FT-IR spectrophotometer. X-ray diffraction experiments (XRD) were performed using a Bruker D8 ADVANCE instrument with Ni-filtered Cu Kα radiation at 1.5406 Å and data were recorded with a speed of 2° min⁻¹ with a step of 0.05°. Proton nuclear magnetic resonance (¹H-NMR) and ¹³C-NMR spectra were recorded at room temperature on a Bruker AC 300, 400 and 500 MHz spectrometers using deuterated chloroform (CDCl₃) or deuterated dimethyl sulfoxide as the NMR solvents. ¹H-NMR spectra were recorded with tetramethylsilane (0.00 ppm) as the reference and interpretation of the ¹³C-NMR spectra used the solvent central peak as the reference (for example, 77.23 ppm for CDCl₃). Chemical shifts are given in ppm. N₂ adsorption/desorption isotherms were obtained at 77.35 K using a Quantachrome Autosorb-1 instrument. Before making the measurements, the samples were outgassed at 120 °C for 12 h. The specific surface area and the pore size distributions were obtained from the desorption branch of the isotherms, using the Brunauer–Emmett–Teller (BET) method and the Barrett–Joyner–Halenda (BJH) analyses. A Shimadzu AA-6300 double beam flame atomic absorption spectrometer was used to obtain the concentration of metal ions. For this purpose, 0.1 g of the catalyst was digested by HNO₃ with stirring at room temperature for a week. Then the mixture was filtered and the solid was washed several times with water to give a colourless filtrate solution for metal measurements. The concentration of Cu(II) in the immobilized SBA-15 was 0.016 mmol g⁻¹. Thermogravimetric analysis (TGA) was carried out using a Shimadzu TGA/DTA-50 instrument equipped with a platinum pan. The samples were heated in air from 25 °C to 1000 °C with a heating rate of 10 °C min⁻¹. The weight loss was recorded as a function of temperature. Melting points were recorded using a Buchi B-540 melting point apparatus and were uncorrected.

3. Results and discussion

3.1. Characterization of Cu(II)–DiAmSar complex anchored onto SBA-15

Cu(II)–DiAmSar complex grafted on SBA-15 (Cu(II)–DiAmSar/SBA-15) was prepared according to Scheme 2. Firstly, the CPTMS entity was introduced to the DiAmSar amine functional groups. This moiety was immobilized onto SBA-15 after complexing with copper salt, using CPTMS as a reactive surface modifier through a silylation reaction.

Scheme 2 Preparation of Cu(II)–DiAmSar complex anchored on SBA-15 (Cu(II)-DiAmSar/SBA-15).

The successful anchoring of the Cu(II)–DiAmSar complex onto SBA-15 was characterized by using various physico-chemical techniques such as XRD, TEM, TGA, FT-IR and BET techniques to study the morphology, pore dimensions, functional group analysis and catalyst loading in the mesoporous material.

The quality and structural ordering of Cu(II)–DiAmSar/SBA-15 were measured using XRD. Fig. 2 shows XRD patterns of SBA-15 and Cu(II)–DiAmSar/SBA-15 samples. The XRD scheme of both SBA-15 and Cu(II)–DiAmSar/SBA-15 exhibited high intensity basal (100) peaks at (110) and (200), therefore confirming that the mesophase had hexagonal (P6mm) pore channel ordering and furthermore suggesting that the structure of mesoporous SBA-15 did not collapse by immobilization.³³ The XRD peaks of Cu(II)–DiAmSar/SBA-15 not only show lower intensities but also that it has slightly lower angles than the SBA-15 peaks. These losses in the intensities of the peaks were observed after the attachment of Cu(II)–DiAmSar revealing that silylation had indeed occurred inside the mesoporous structure of SBA-15. These results are consistent with the TEM images (Fig. 3) which also show a hexagonal mesostructure.

Fig. 2 XRD patterns of SBA-15 and Cu(II)–DiAmSar/SBA-15.

Fig. 3 TEM images of Cu(II)–DiAmSar/SBA-15: (a) in the direction of the pore axis and (b) in the perpendicular direction to the pore axis.

The TEM images of Cu(II)–DiAmSar/SBA-15 are presented in Fig. 3(a) in the direction of the pore axis and Fig. 3(b) in the perpendicular direction to the pore axis of Cu(II)–DiAmSar/SBA-15, respectively. The preservation of the cylindrical shape of the pores and the retaining of hexagonal arrays of the uniform channels indicate that the channel structure of SBA-15 is not destroyed after the anchoring of Cu(II)–DiAmSar.

Thermogravimetric analysis is a method of thermal analysis in which changes in physical and chemical properties of materials are measured as a function of increasing temperature.³⁴ TGA is commonly used to determine selected characteristics of materials that exhibit either mass loss or gain because of decomposition. Here, TGA was used for the determination of the thermal stability of the catalyst (Fig. 4). Pure siliceous SBA-15 shows a mass loss below 100 °C through the loss of adsorbed water from the surface of SBA-15. Surface condensation of hydroxyl groups typically occurs above 200–250 °C (and more). The weight losses observed for Cu(II)–DiAmSar/SBA-15 are at two temperatures: the minor weight loss was observed at 100 °C, which is because of the physically adsorbed water molecules on the surface of the SBA-15. The major weight loss between 200 °C and 700 °C (Fig. 4) is because of the thermal decomposition of anchored Cu(II)–DiAmSar moieties. According to the TGA data, the amount of grafting of DiAmSar on SBA-15 was 62 wt% (based on the initial amount of DiAmSar which was used for the anchoring).

Fig. 4 Thermogravimetric analysis results of: (a) SBA-15, (b) Cu(II)–DiAmSar/SBA-15 and (c) DiAmSar.

The FT-IR spectra of the SBA-15 and Cu(II)–DiAmSar/SBA-15 are shown in Fig. 5. The composition of the immobilized complex was demonstrated by the strongly absorbing region of 1000–1200 cm⁻¹ which is because of the stretch vibrations of the (Si–O–Si) bonds. The FT-IR spectrum of the Cu(II)–DiAmSar/SBA-15 shows a broad band between 3000 and 3700 cm⁻¹, which can be attributed to the stretching vibration absorption of the NH and OH groups. The medium band observed in the 2935 cm⁻¹ region was assigned to stretching vibrations of CH₂. The peak at 1640 and 1400–1450 cm⁻¹ in the Cu(II)–DiAmSar/SBA-15 was because of the absorption peaks of the C–N groups. These results confirmed the successful anchoring of the Cu(II)–DiAmSar complex on the SBA-15 surface.

Fig. 5 IR spectra of (a) SBA-15 and (b) Cu(II)–DiAmSar/SBA-15.

The nitrogen adsorption–desorption isotherms and pore size distributions of the corresponding samples are shown in Fig. 6. Both SBA-15 and Cu(II)–DiAmSar/SBA-15 exhibit type IV isotherm patterns with a small H₁ hysteresis loop, showing that the cage-like structure of SBA-15 was maintained even after anchoring with Cu(II)–DiAmSar.³⁵ The textural parameters of samples are shown in Table 1 and were obtained after nitrogen adsorption and desorption experiments and BJH analysis. It can be seen that decreases in BET surface area and pore volume were observed for Cu(II)–DiAmSar/SBA-15. This shows that Cu(II)–DiAmSar was immobilized inside the mesoporous structure of SBA-15.

Fig. 6 Nitrogen adsorption/desorption isotherms and corresponding pore size distribution profile (inset) of (a) SBA-15 and (b) Cu(II)–DiAmSar/SBA-15.

Table 1 Textural properties of the SBA-15 and Cu(II)–DiAmSar/SBA-15 (S_BET, specific surface area (m² g⁻¹); V_BJH, pore volume (cm³ g⁻¹); D_BJH, pore diameter (calculated from the adsorption branch) (nm))

Materials	SBET	VBJH	DBJH
SBA-15	532	0.600	6.24
Cu(II)–diamsar/SBA-15	317	0.560	7.1

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3.2. Synthesis of heterocyclic derivatives in water

To test the applicability of our catalyst in organic synthesis under green conditions, the reaction of 2-aminothiophenol 8 and benzaldehyde 9a in water and in the presence of Cu(II)–DiAmSar/SBA-15 was selected as the model reaction. Greener conditions were selected to study the reaction and the satisfactory results of the reaction in water inspired us to further investigate this transformation. Some parameters such as the amount of the catalyst and the temperature were examined to determine the efficiency of the model reaction (Table 2). For the first attempt, the reaction at room temperature was examined without the catalyst and it gave no yield of product. The best yield was obtained in the presence of 8 × 10⁻⁵ mmol of the catalyst, under reflux conditions (Table 2, entry 6).

Table 2 Screening of the reaction conditions for the reaction of 2-aminothiophenol 8 and benzaldehyde 9a^a

Entry	Catalyst (mol%)	Temperature (°C)	Time (min)	Yield (%)^b
a All reactions were run under the following conditions: 2-aminothiophenol 8 (1 mmol, 1 equiv.), benzaldehyde 9a (1.0 mmol, 1 equiv.) and catalyst (0–0.00016 mmol of only Cu(II) ions or 0–0.05 g of Cu(II)–DiAmSar/SBA-15) in water (2 mL) were heated for an appropriate time.b Gas chromatography (GC) yields.c Optimum conditions.d Isolated yield in parentheses.
1	0	rt	60	—
2	0.00008	rt	60	30
3	0.00016	rt	60	30
4	0.000008	rt	60	30
5	0.0008	60	60	50
6	0.00008	95	20	90 (89)^c^,^d
7	0.00008	80	60	65

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Using the optimized conditions, the reaction was evaluated by using various benzaldehyde derivatives (Table 3, entries 1–12). As can be seen, most of the substrates examined provided good to excellent yields with short reaction times.

Table 3 Synthesis of benzothiazole-based heterocycles catalyzed by Cu(II)–DiAmSar/SBA-15 in water^a

Entry	Amine 8	Aldehyde 9	Product	Yield^b (%)
a All reactions were run under the following conditions: 2-aminothiophenol 8 (1 mmol, 1 equiv.), benzaldehyde 9a (1.0 mmol, 1 equiv.) and catalyst (0.005 g of Cu(II)–DiAmSar/SBA-15 or 0.00008 mmol of only Cu(II) ions) in water (2 mL) were heated for 20 min.b Isolated yield.
1				90
2	8			90
3	8			85
4	8			85
5	8			88
6	8			90
7	8			88
8	8			92
9	8			88
10	8			89
11	8			87
12	8			88

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As can be seen from Table 3, very electron rich aldehydes such as 4-methoxybenzaldehyde and 3,4,5-trimethoxybenzaldehyde took part in this reaction with a high yield of the desired product (Table 3, entries 2 and 8). The proposed mechanism for the synthesis of benzothiazole derivatives is presented in Scheme 3:

Scheme 3 Proposed mechanism for the synthesis of benzothiazoles in the presence of Cu(II)–DiAmSar/SBA-15.

After examining the general scope of the reaction, our attention turned to recycling of the catalyst. It appeared that Cu(II)–DiAmSar/SBA-15 could be reused directly for a new cycle after the catalyst was first filtered, then washed with ethanol and dried at 80 °C for 60 min. The recovered catalyst was recycled and could be reused six times (Table 4).

Table 4 Investigation of the reusability of the catalyst for the preparation of 2-(phenyl)benzothiazole 10a

Run	1	2	3	4	5	6
a Isolated yield.
Yield^a (%)	90	90	90	89	89	89

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4. Conclusions

In conclusion, we have shown that functionalization of silica with diamine-sarcophagus and subsequent complexation with copper creates an easily recoverable heterogeneous catalyst. The catalyst shows good activity in water for the synthesis of benzothiazole derivatives.

Acknowledgements

The authors wish to thank Payame Noor University for its financial support of this study.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: ¹H-NMR and ¹³C-NMR spectra of heterocycles. See DOI: 10.1039/c4ra11877d

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