Green synthesis of 2-aryl benzothiazole heterogenous catalyzed by MoO₃ nanorods

1 Introduction

2-Aryl benzothiazoles and their derivatives exhibit a wide range of biological properties which have led to continuous interest in the field of medicinal chemistry. 2-Aryl benzothiazoles exhibit antimicrobial [1, 2], antibiotic [3], antiviral [4], antiinflammatory [5], antifungal [6], antitumor [7], [8], anticonvulsant [9] and antiparasitic [10] activities, are antagonists [11] and are used in the treatment of Alzheimer disease [11]. They exhibit nanomolar inhibitory activity against human cancer cells [12] and several enzymes such as aldose’s reducates [13], H⁺-K⁺ ATPase [14], protease [15] and carbonic anhydrase [16]. Benzothiazoles also exhibit physiological activities like H37Rv inhibition [17], elastase inhibition [18] and cytotoxicity towards P₃₃₈ cells [19].

The synthesis of 2-aryl benzothiazoles involves condensation of 2-aminothiophenol with aldehyde, acid chloride, carboxylic acid, ester, aryl bromide and coupling with aryl boronic acid. The condensation of 2-aminothiophenol and aldehyde has been reported by using various catalysts such as NiO₂ [20], Cu NP [21], CuCl [22], MnO₂/SiO₂ [23] and ceric ammonium nitrate, etc. [24].

However, most of these procedures of synthesis of benzothiazoles are associated with some disadvantages such as tedious reaction, expensive catalyst, multistage processes and loss of catalyst and the use of hazardous and carcinogenic solvents like nitrobenzene and dioxane, which are harmful to the environment and also to humans. Therefore, it is necessary to study the reaction by some green methods, which is efficient and simple. The present study involves synthesis of 2-aryl benzothiazoles by using MoO₃ nanorods, which is efficient, simple and environmentally benign.

2 Materials and methods

2.4 Synthesis of 2-aryl benzothiazole

A mixture of 2-aminothiophenol (1 mmol), aromatic aldehyde (1 mmol) and MoO₃ nanorods (100 mg) was stirred at 80°C for 2 h to obtain a crude product (3a-m, Scheme 1). The progress of reaction was monitored by thin layer chromatography (TLC). After completion of the reaction, the crude product was dissolved by adding ethanol and the MoO₃ nanorods were separated by centrifuging, followed by decantation. MoO₃ nanorods were dried in vacuum desiccators and the crude product recrystallized in ethanol. The recrystallized product analysis by ¹H NMR and ¹³C NMR spectra was recorded on a Bruker AVIII HD-300 MHz FT-NMR spectrometer with CDCl₃ as a solvent. The chemical shift values were recorded as δ (ppm units) relative to tetramethylsilane (Me₄Si) as an internal standard.

Scheme 1:

Synthesis of 2-aryl benzothiazole.

3 Results and discussion

The UV-visible absorption spectrum recorded for MoO₃ nanoparticles capped with TBAB at 18 mA current density exhibited maximum absorption at 642 nm, as shown in Figure 1, which can be attributed to the surface plasmon resonance peak of MoO₃ nanoparticles. A broad peak around 642 nm can be attributed to wide size distribution of nanoparticles formed in the solution. The broadening of the surface plasmon resonance peak was due to the agglomeration of the nanoparticles in the sample and high width of these particles distributed. The particles showed hardly any change in the absorption spectra, even after a month of ageing time, indicating the highly stable nature of particles.

Figure 1:

UV-visible Spectrum of MoO₃ nanoparticles capped with 0.1 M tetra butyl ammonium bromide (TBAB) at 18 mA current density.

XRD was employed to examine the crystal structure of prepared MoO₃ nanorods. As shown in Figure 2, all the diffraction peaks can be indexed to the orthorhombic lattice system with lattice parameter (a=3.96 Å, b=13.85 Å, c=3.696 Å, JCPDS: 35-0609). The strong diffraction peaks of MoO₃ appear at 23.21, 25.72, 27.31, 33.78, 39.00, 46.31, 49.27, 55.20 and 57.67, which correspond to (110), (040), (021), (111), (060), (061), (002), (112) and (171) planes, respectively. The observed planes at (040) and (060) show very strong peaks of the MoO₃ nanorods indicating the highly anisotropic growth as well as the preferred orientation of the nanorods.

Figure 2:

X-ray diffraction (XRD) pattern of MoO₃ nanorods.

The IR spectrum (Figure 3) of MoO₃ nanorods shows broad peaks at 3432 cm^-1 and 1633 cm^-1 due to the stretching and bending vibration of hydroxyl groups adsorbed on the surface. The peak at 1470 cm^-1 is due to the ammonium ion bending mode of vibration. The C-N linkage in R₄N⁺ ion gives a medium band at 1038 cm^-1 due to C-N stretching vibration. The peak at 949 cm^-1 is due to the terminal Mo=O bond, which indicates the layered orthorhombic phase [26] and absorption at 848 cm^-1 and 597 cm^-1 are of the stretching and bending mode of vibration of Mo-O-Mo. The spectrum also contains distinct peaks at 496 cm^-1 and 669 cm^-1, which correspond to the mixed phase that contain molybdenum and molybdenum oxide.

Figure 3:

IR Spectrum of MoO₃ nanorods.

SEM analysis gives morphology of MoO₃ nanorods (Figure 4) which depicts that most of the rods have a belt shape and a few are cylindrical wires. Energy dispersive spectra were also recorded to determine the chemical composition of MoO₃ nanorods, which show that the nanorods contain 55.02% of molybdenum and 44.98% of oxygen measured in atomic percentage of elements.

Figure 4:

(A) Scanning electron microscopy (SEM) micrograph and (B) energy dispersive X-ray spectroscopy (EDS) of MoO₃ nanorods.

We report here a very simple process for the synthesis of 2-aryl benzothiazoles by condensation of 2-aminothiophenol with aromatic aldehyde under solvent free conditions catalyzed by MoO₃ nanorods. In the present work, an attempt was made to optimize the reaction conditions by using 2-aminothiophenol (1 mmol) 1 and 4-bromobenzaldehyde (1 mmol) 2b as model reaction at different solvents and amounts of catalyst used. In order to investigate the best results in terms of yield and reaction time, we examined the efficiency of different reaction media and the amount of catalyst required. From Table 1, it can be seen that loading of 100 mg of MoO₃ nanorod catalyst was adequate for smooth condensation of 2-aminothiophenol and 4-bromobenzaldehyde under solvent free conditions at 80°C. There was a considerable increase in the yield of product when the amount of catalyst was increased from 50 mg to 100 mg; above 100 mg, no considerable change in reaction time and yield of the product was observed.

The catalyst was recovered by simple work-up using the centrifugation method, washed with ethanol and reused for three successive reactions. The corresponding yield for each cycle is mentioned in Table 2.

Under optimization reaction conditions, we obtained 95% yield of 2(4-bromo-aryl) benzothiazole within 40 min. In Table 3, it can be seen that the reaction time and the product yield depend on the substituents introduced on substrates. For instance, the condensation of 2-aminothiophenol having strong electron withdrawing groups (F, Cl, Br, NO₂, OH) in the para position gave the desired product with good yield and a shorter reaction time than meta substituted product and electron donor groups (CH₃, OCH₃).

4 Conclusion

We developed efficient MoO₃ nanorod catalysts for the synthesis of 2-aryl benzothiazole with a high yield of product in a short reaction time and much less amount of catalyst. This catalyst showed excellent activity during four consecutive runs without appreciable loss of activity. Furthermore, this method is of interest in the context of environmentally greener and safer processes.