Elsevier

Tetrahedron

Volume 76, Issue 14, 3 April 2020, 131078
Tetrahedron

Synthesis of 1-(2-bromo-1-arylethyl)-1H-benzotriazoles via NBS promoted addition of 1H-benzotriazole to alkene: Relevance in benzotriazole ring cleavage

https://doi.org/10.1016/j.tet.2020.131078Get rights and content

Highlights

  • A novel and expeditious one-pot synthesis of 1-(2-bromo-1-arylethyl)-1H-benzotriazoles has been devised by reacting styrene with 1H-benzotriazole in presence of NBS in anhydrous CH2Cl2 at room temperature.

  • The resulted compounds undergo E2-ellimination to afford respective 1-(1-phenylvinyl)-1H-benzotriazoles.

  • 1-(1-Phenylvinyl)-1H-benzotriazole underwent benzotriazole ring cleavage (BtRC) under free radical condition to produce phenanthridine.

Abstract

A cost-effective and expeditious one-pot synthesis of 1-(2-bromo-1-arylethyl)-1H-benzotriazoles has been devised by reacting styrene and their derivatives with 1H-benzotriazole in presence of N-bromosuccinimide in anhydrous CH2Cl2 at room temperature. Further, the resulted compounds undergo E2-ellimination to afford the respective 1-(1-aryl-vinyl)-1H-benzotriazoles. At the end, 1-(1-phenylvinyl)-1H-benzotriazoles underwent benzotriazole ring cleavage (BtRC) under free radical condition to produce phenanthridine as the final product.

Introduction

Benzotriazole is pertaining significantly diverse role in organic chemistry since last four decades in the form of reagents, ligands, and intermediates to produce a large number of molecules having widespread applications [[1], [2], [3]]. The industrial applications in terms of utilizing the scaffold can be demonstrated as corrosion inhibitor and anti-tarnish agent for copper and its alloys [4] as fixing agents in photographic emulsions, as reagent in analytical determination of silver and use in anti-freeze and water coolant systems [3]. Remarkable bio-importance of benzotriazole moiety, such as, antibacterial, antifungal, antiviral, anti-inflammatory, antihypertensive, analgesic, etc., shows its broad relevance in the synthesis of biologically active compounds [[5], [6], [7], [8], [9], [10], [11]]. Molecules containing benzotriazole ring have also exhibited potential anti-tubercular[12], anti-tumor [13], anti-proliferative [14], and anesthetic activities [15]. Benzotriazole ring cleavage (BtRC) methodology is one of the trending methods with the advantage of time as it is an interesting approach for an easy access to diverse series of compounds having pharmaceutical importance [[1], [2], [3],[16], [17], [18], [19], [20], [21], [22], [23]]. Pre-reported reaction conditions includes thermolysis, photolysis, organo-metallic reagents oxidants and free radical reagents, resulted in the desired cleavage of the relatively stable benzotriazole ring, exhibiting fascinating chemistry [[24], [25], [26], [27], [28], [29], [30]]. Economically effective, chemically stable and non-toxic nature of benzotriazole moiety makes it appreciable approach in the organic synthesis which has been explored to generate galaxy of libraries comprising of diverse scaffolds. Thus it plays important role in drug discovery and development [[31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43]]. Several research groups, most notably, the Katritzky group explored the interesting features of benzotriazole methodology since last four decades span. Previously, we also have employed BtRC approach for the synthesis of diverse benzothiazoles, benzoxazoles and amide derivatives [[18], [19], [20], [21], [22], [23]].

Therefore, to achieve a new method to prepare benzotriazole-based reagents is of paramount importance, where benzotriazole ring cleavage has been successfully explored as a starting material in several reactions [[16], [17], [18], [19], [20], [21], [22], [23]]. Herein, we wish to disclose a new synthetic protocol for the facile synthesis of 1-(2-bromo-1-arylethyl)-1H-benzotriazoles from styrene. Further their representative application in benzotriazole ring cleavage (BtRC) aimed to respective phenanthridine under free radical condition (Scheme 1).

Section snippets

Results and discussion

A prototype reaction for the synthesis of 1-(2-bromo-1-phenylethyl)-1H-benzotriazole 3a and 1-(2-bromo-1-phenylethyl)-2H-benzotriazole 3a’ was set-up. For which styrene (1.0 equiv.) was treated with 1.0 equiv. of N-bromosuccinimide (NBS) in anhydrous dichloromethane and after 30 min, 1.0 eq. of 1H-benzotriazole was added and the reaction was further stirred for 5 h. White solid compounds 3a and 3a′ were isolated in 27% yield (Scheme 2).

Then after, we look forward for the optimization, thus the

Conclusions

In conclusion, we have developed a practical synthesis of 1-(2-bromo-1-phenylethyl)-1H-benzotriazole using styrenes and 1H-benzotriazole, which further undergoes E2-ellimination and free radical benzotriazole ring opening to produce phenanthridine. This approach is straightforward, easy to execute, and metal-free condition and thus can be explored in further investigation for the development of biologically relevant heterocycles.

Experimental

All the solvents and reagents were taken of pure grade. Thin-layer chromatography (TLC) was performed on, pre-coated aluminium plates and spots were evaluated using UltraViolet lamp (λ max = 254 nm). The solvents were evaporated at temperature <50 °C. Column chromatography was carried out using silica gel (230–400 mesh, Merck). Distilled n-hexane and ethyl acetate were used for the column chromatography. 1H and 13C NMR were recorded at 500 and 125 MHz, respectively. The chemical shifts are

Conflicts of interest

The authors have no competing interests to declare.

Acknowledgments

The author thanks Science and EngiEngineeringneering Research Board (SERB), Department of Science & Technology, New Delhi (Grant No. EMR/2016/001123) for the funding. The authors sincerely thank CISC-Banaras Hindu University for providing spectroscopic studies of the developed molecules. M.S. acknowledge to BHU for the fellowship.

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