Facile synthesis of benzazoles through biocatalytic cyclization and dehydrogenation employing catalase in water

https://doi.org/10.1016/j.enzmictec.2020.109562Get rights and content

Highlights

  • Catalase, an oxidative enzyme found to catalyse cyclocondensation reaction.

  • A completely green, efficient and environmentally friendly reaction protocol.

  • Excellent yields of the desired products.

  • Good substrate scope which leads to a variety of benzazoles.

Abstract

The benzazoles are very important entities having immense biological activities, hence; the synthesis of benzazoles is one of the prime areas for synthetic chemists. In pursuit of sustainable protocol, herein an oxidative enzyme i.e. catalase mediated sustainable synthesis is presented. Catalase is a metalloenzyme which is essential for the breakdown of toxic hydrogen peroxide into water and oxygen inside the cell. Despite the higher activity and turnover number of catalase inside the cell, its activity outside the cell is unexplored. Therefore, to explore the hidden potential of catalase for catalyzing the organic transformations, here we reported a green and efficient method for synthesis of benzazoles by the cyclocondensation of o-aminothiophenol or o-phenylenediammine and various aryl aldehydes with ensuing dehydrogenation. This protocol is greener, sustainable and rapid with excellent yields of the products and in addition to this, the catalase demonstrates good functional group tolerance.

Introduction

The benzazoles are important structural motifs in organic synthesis and medicinal chemistry because of their wide synthetic as well as biological applications. Particularly, benzothiazoles and benzimidazoles are very useful. [[1], [2], [3], [4], [5]] Benzothiazole derivatives play an important role in bio-organic and medicinal chemistry because of their potent antitumor activity [[6], [7], [8], [9], [10]] and other pharmaceutical uses like, in the treatment of autoimmune disorders [11], inflammatory diseases [12,13], epilepsy [14,15], viral infections [16] and cancer [17]. In addition to this, they are widely used as an analgesic [18], antioxidants [19] and as vulcanization accelerators [20]. The benzothiazoles with substitutions at the second position are an important class of privileged bicyclic substructures owing to their potent utility as imaging agents for β-amyloid [[21], [22], [23], [24]], antituberculotic [25], chemiluminescent agents [26], calcium channel antagonistic [27], antiparasitic [28] and photosensitizers [29]. Also, the benzimidazole derivatives are of wide interest because they exhibit various biological activity like antitumor [30], antiviral [31], antimalarial [32] and anti-inflammatory [33]. Some compounds with benzimidazole nucleus such as Lansoprazole, Omeprazole, Pantoprazole and Thiobendazole are also used as drug molecules. In addition to these properties, benzimidazoles are very important intermediates in the synthesis of various organic molecules and also served as organocatalyst and as ligands for asymmetric catalysis [34]. It has also been used for food safety purposes [35].

These numerous biological and synthetic applications of the benzazoles have motivated the synthetic organic chemist to develop a greener and sustainable method for the synthesis of these heterocycles. Among the methods explored, one of the most common methods is the reaction of o-phenylenediammine or o-aminothiphenol and aldehydes under varied conditions [36].

Literature survey reveals that the condensation of o-phenylenediammine or o-aminothiphenol with varieties of substituted aldehydes, carboxylic acids, acid chlorides, nitriles has been reported in the presence of various catalysts like K2S2O8 [37], Sm(OTf)3 [38], hydrotalcite [39], Chlorotrimethylsilane [40], Ceric ammonium nitrate [CAN] [41], Amberlite IR-120 [42], VOSO4 [43], hexamethylenetetramine–bromine complex [44], Fe/CeO2–ZrO2 [45], ionic liquid [46], Bi(NO3)3 [47], Zn3(BTC)2 MOF [48], 4‐Methoxy‐TEMPO [49] and by electrosynthesis [50]. Unluckily, most of these presented methods suffer from one or more kind of limitations such as drastic reaction conditions, low yields of products, tedious workup procedures, and co-occurrence of several side reactions (Table 4). Therefore, it is required to develop a sustainable method to overcome these lingering limitations.

Enzyme catalysis has proven edge over chemical catalysis for developing sustainable processes and endorsing this, few biocatalytic routes are also reported for benzazoles e.g. lipase [51] and baker’s yeast catalyzed benzimidazoles [52] and benzothiazole [53] synthesis respectively. Inspired by this, we attempted to explore the catalytic potential of another enzyme catalase for the synthesis of benzazoles.

The Catalase is a metalloenzyme present in nearly all aerobic organisms like bacteria, plants, and animals. Since hydrogen peroxide is very toxic to the cells, the presence of catalase in the cell is very essential because it easily degrades hydrogen peroxide into nontoxic water and oxygen molecule. Catalase is an enzyme belongs to oxidoreductase class which actually is a tetramer of four polypeptide chains where each chain containing more than 500 amino acids. Its active site contains four iron-containing Heme groups that allow the enzyme to react with the hydrogen peroxide. Catalase is having highest efficiency inside the cell as a catalyst but reports on the use of catalase outside the cell are limited [[54], [55], [56], [57], [58]].

Although, it mainly catalyses the degradation of hydrogen peroxide into water and oxygen, it also catalyzes organic transformations viz. oxidations of alcohol [59] and sulfur [60]. Therefore, there is a wide scope to discover the hidden catalytic ability of catalase for organic transformations. The use of catalase in organic synthesis will have great advantages such as mild reaction condition, high turnover number, the biodegradability of the catalyst and use of an eco-friendly solvent, water, which would be the true package for green chemistry.

Therefore, here we are reporting a completely green and sustainable protocol for the synthesis of benzazole derivatives using catalase as biocatalyst. To the best of our knowledge, this is the first example of the catalase mediated synthesis of any heterocyclic compound including benzazoles.

Section snippets

Result and discussions

The catalytic performance of catalase was evaluated for the synthesis of 2-arylbenzothiazole (3a) as well as 2-arylbenzimidazole (5a). The model reaction for catalase mediated oxidative cyclocondensation was performed with benzaldehyde (8 mmol), o-aminothiphenol or o-phenylenediammine (8 mmol) as the substrates and hydrogen peroxide H2O2 (10 mmol) as an oxidant (Schemes 1 and 2).

We began our studies by optimizing the reaction conditions for the catalase mediated oxidative cyclocondensation of o

Conclusion

We have successfully developed a bio-inspired oxidative condensation employing catalase as a sustainable catalyst for the synthesis of benzazole derivatives by the reaction of o-aminothiophenol or o-phenylenediammine respectively with a variety of aromatic aldehydes in very mild conditions. Catalase catalyzes the oxidation of benzazolines into benzazoles trapping nascent oxygen generated by the decomposition of H2O2. The proposed one-pot synthetic protocol is simple, green, yet efficient for

General information

Catalase (bovine liver) was purchased from Sigma-Aldrich. All other chemicals were purchased from commercial suppliers and used as received without any further purification. Thin Layer chromatography (TLC) was performed using aluminium backed plates precoated with silica gel 60 (Merck) and were visualized by UV fluorescence. 1H NMR and 13C NMR spectra were recorded on Brucker Avance II 400-MHz spectrometer at ambient temperatures.

General experimental procedure for the synthesis of Benzazoles

A mixture of various aryl aldehydes (8 mmol), o-aminothiophenol

Acknowledgements

The presented work was supported financially by Science and Engineering Research Board (SERB/EMEQ-279/2013), New Delhi and authors are thankful for that. We are also grateful to Head, Department of chemistry, Visvesvaraya National Institute of Technology, Nagpur for providing laboratory facility. Authors are thankful to SAIF, Chandigarh University for providing spectral characterizations.

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