Synthesis of 2-arylbenzothiazoles using nano BF3/SiO2 as a reusable and efficient heterogeneous catalyst under mild conditions

2-Arylbenzothiazoles were synthesized via condensation of 2-aminothiophenol and different aldehydes catalyzed by nano silica-supported boron trifluoride (nano BF3/SiO2) as an efficient and reusable catalyst in high yields and short reaction times. The reactions proceeded at room temperature under mild conditions to afford 2-arylbenzothiazole derivatives. The pure products were identified and characterized by physical and spectroscopic data such as IR, 1H NMR, 13C NMR and Mass spectroscopy. GRAPHICAL ABSTRACT


Introduction
The synthesis, reactions and biological properties of benzothiazoles and compounds containing the benzothiazole nucleus constitute a significant part of modern heterocyclic chemistry. [1] They are well known for their biological and pharmaceutical activities such as antitumor, antiparkinsonism, [2] antimalarial, anticonvulsant, antihemintic, antifungal and analgesic. Several methods for the synthesis of 2-arylbenzothiazoles have been developed. [3,4] In general, benzothiazoles have been synthesized by the condensation of 2-aminothiophenol with carboxylic acid derivatives. [5] On the other hand, the most general approaches for 2-arylbenzothiazoles include the following; (1) oxidative cyclization of phenolic Schiff bases derived from the condensation of 2-aminothiophenols and aldehydes using various oxidants such as Sc(OTf) 3 -molecular oxygen [6] and pyridinium chlorochromate, [7] and (2) the condensation of 2-aminothiophenols with carboxylic acids under microwave irradiation in the presence of a Lewis acid. [8][9][10][11] Despite their potential utility, these methods are not environmentally friendly and suffer from one or more disadvantages for example hazardous reaction conditions, complex work-up and purification, strongly acidic conditions, high temperatures, use of toxic metal catalysts and long reaction times. Therefore, the development of a facile and mild general method to overcome these shortcomings remains a challenge for organic chemists in the synthesis of 2-arylbenzothiazoles. [12,13] In this study, in continuation of our interest on the synthesis of 2-arylbenzothiazoles, [14] and using BF 3 as a catalyst in organic reactions, [15] we decided to explore the ability of nano BF 3 /SiO 2 as a mild and non-toxic Lewis acid catalyst for the synthesis of 2-arylbenzothiazoles. Therefore, nano BF 3 /SiO 2 was used as a new catalyst for the synthesis of 2-arylbenzothiazoles by the condensation reaction of 2-aminothiophenol with aromatic aldehydes at room temperature under mild conditions.

Results and discussion
In this research, we have developed a synthetic method using nano BF 3 /SiO 2 as a reusable, efficient and eco-friendly solid acid catalyst for synthesis of 2-arylbenzothiazoles from 2-aminothiophenol and aldehydes in excellent yields at room temperature (Scheme 1). Scheme 1. Synthesis of 2-arylbenzothiazoles.
The dimension of nano catalyst was observed with the scanning electron microscope (SEM). The size of the synthesized BF 3 /SiO 2 nanoparticles was confirmed to be about 18-39 nm by scanning electron microscopy ( Figure 1).
We first screened a number of different catalysts in the reaction of 4-nitrobenzaldehyde with 2-aminothiophenol (reaction model) such as different Lewis acids, different reagents supported on solid materials, nano crystalline TiO 2 and acidic alumina. The results are shown in Table 1.
When the reaction was carried out in the presence of nano BF 3 /SiO 2 as a catalyst, the product was obtained in excellent yields and short reaction times ( Table 1, Entry 8). On the other hand, the same reaction using other catalysts gave the products in low yields even after prolonged reaction time.
In order to optimize the reaction in terms of yield and reaction time, we examined the efficiency of different reaction media and catalyst amounts in the condensation reaction of 4-nitrobenzaldehyde (1 mmol) with 2-aminothiophenol in ethanol solution. The results are given in Table 2.
In order to ascertain the scope and limitation of this method, the reaction of 2-aminothiophenol and several substituted aromatic aldehydes using the optimized method was examined at room temperature. By considering the above results, conversion of different aromatic aldehydes to the corresponding 2-arylbenzothiazoles using nano BF 3 /SiO 2 as a catalyst was investigated. The results of these reactions are summarized in Table 3.     This reaction was also carried out with BF 3 .Et 2 O as a Lewis acid for comparison with nano BF 3 /SiO 2 as a catalyst. Unfortunately, BF 3 .Et 2 O is a liquid that fumes in the air and reacts with moisture to form hydrofluoric acid making its use inconvenient and laborious. In addition, the yields of products using nano BF 3 /SiO 2 as a catalyst are considerably higher than BF 3 .Et 2 O and it is clear that it is the preferred catalyst. As can be seen from Table 3, the products were obtained in 62-95% yields and in reaction times of 20-45 min. In this reaction, the Lewis acid nano BF 3 /SiO 2 catalyst activates the carbonyl group via coordination with the oxygen atom to accelerate the nucleophilic attack of the amino group at the carbon atom of the carbonyl group.
The structure of the products was confirmed by spectroscopic methods such as IR, 1 H NMR, 13 C NMR and Mass spectroscopy. In the IR spectra, the stretching frequency of aromatic C=C bonds is observed in the region between 1475 and 1600 cm −1 . In the 1 H NMR spectra, the proton of −OH group in 2-(2-hydroxyphenyl)-benzothiazole appeared at 12.54 ppm. The signals at 6.95-8.94 are assigned to CH=CH of the aromatic rings. The hydrogen atoms of the methoxy group have a chemical shift of 3.89 ppm, and the signal around 6.77-6.79 ppm is assigned to the −N(CH 3 ) 2 group. In the 13 C NMR spectra, the aromatic carbons absorb at 110-169 ppm and the signal of 55.47 is assigned to the −OCH 3 group. The mass spectra (Electron Impact (EI)) of products have shown the corresponding molecular ion peak.
Reusability of the nano BF 3 /SiO 2 catalyst: In the next step of our study, our attention was directed toward evaluating the reusability and recycling potential of nano BF 3 /SiO 2 in these reactions. After each run, conducted for the 20 min indicated in Table 4, the catalyst was filtered from the product and washed with acetone, then dried at 90 • C for 2 hours and reused in the next reaction cycle using the optimized conditions for an additional 20 min. The recovered catalyst was active although a gradual decline was observed in its activity as its time of use was increased (Table 4).

Conclusion
In summary, a facile and mild procedure for the synthesis of 2-arylbenzothiazoles has been developed using the condensation reaction of 2-aminothiophenol and aromatic aldehydes with nano BF 3 /SiO 2 as an efficient, eco-friendly and reusable heterogeneous catalyst. The main advantages of the present synthetic protocol are mild conditions, high yields, short reaction times and easy reaction work up procedure.

Chemicals
Chemicals were purchased from the Merck, Fluka and Aldrich Chemical Companies in high purity. All of the materials were of commercial reagent grade. The solvents were purified by standard procedure.

Apparatus
The FT-IR spectra were obtained with potassium bromide pellets in the range 400-4000 cm −1 with a Perkin Elmer 550 spectrometer. Melting points were determined in open capillaries using an Elactrothermal MK 3 apparatus and are uncorrected. All 1 H NMR and 13 C NMR spectra were recorded with a Bruker DRX-400 spectrometer at 400 MHz. The NMR spectra were obtained in CDCl 3 solutions and are reported as parts per million (ppm) downfield from tetramethylsilane as an internal standard. The abbreviations used are: singlet(s), doublet (d), triplet (t) and multiplet (m). Mass spectra were recorded on an Agilent Technology (HP) MS Model: 5973 Network Mass Selective Detector, instrument by EI ionization mode with an ionization voltage of 70 eV. The SEM of nano catalyst was performed on a KYKY EM 3200 SEM instrument. The purity determination of the substrates and reaction monitoring were accomplished by TLC on silica-gel polygram SILG/UV 254 plates (from Merck Company).

Preparation of nano BF 3 /SiO 2 as catalyst
For preparation of nano BF 3 /SiO 2 , to a mixture of 0.65 g nano-silicagel and 5 ml chloroform, 0.35 g BF 3 (0.65 ml of BF 3 .Et 2 O) was added drop-wise to the reaction mixture over a period of 70 min at room temperature with stirring. Then after completion of the reaction, Et 2 O and CHCl 3 were evaporated from the reaction mixture by heating to obtain dry nano BF 3 /SiO 2 . [16][17][18]

General procedure for the synthesis of 2-arylbenzothiazoles catalyzed by nano
To a mixture of 2-aminothiophenol (1 mmol, 0.995 g) and aldehyde (1 mmol) in ethanol (10 ml), nano BF 3 /SiO 2 (0.05 g, 25 mol% BF 3 ) was added in a beaker and the reaction mixture was mixed properly with the help of a glass rod and stirred in ambient temperature for the time indicated in Table 3. The progress of the reaction was monitored by TLC (ethylacetate:hexane, 6:4), after completion of the reaction the solvent was removed under reduced pressure, then the mixture was cooled and dichloromethane (15 ml) was added to the mixture and filtered to remove the catalyst. Then the filtrate was evaporated under reduced pressure to isolate a solid residue, and recrystallized from ethanol (10 ml) to afford the corresponding products and the catalyst residue was washed with acetone and reused. All of the 2-arylbenzothiazole products were identified by physical and spectroscopic data as follows.