Free Radical Synthetic Protocol for Benzothiazoles via Ring Opening of Benzotriazole: A Two‐step Organic Chemistry Experiment for Undergraduate and Postgraduate Students

Abstract

The utility and advantages of benzotriazole methodology have been described for the practical synthesis of benzothiazoles. The two‐step synthetic procedure includes nucleophilic acyl substitution followed by benzotriazole ring cleavage under the free radical condition and subsequent cyclization via elimination of molecular nitrogen (N2). This protocol requires cheap and readily available reagents, and moreover easy to handle, thus can be used to teach undergraduate and postgraduate students about the importance of benzotriazole moiety in organic synthesis, ring cleavage chemistry, cyclization reactions, and use of industrial waste in free radical reactions. Students can also learn some important and common techniques useful in organic chemistry such as monitoring of organic reaction using thin‐layer chromatography and UV, microwave (MW) technique for the synthesis, and column chromatography for the product isolation and structure determination through NMR, MS, and IR spectral analysis of the pure compounds.

Cu(I)-Catalyzed Click Chemistry in Glycoscience and Their Diverse Applications

“…Benzotriazole has several interesting and fascinating features, such as proton activation, anion generation, good leaving group tendency, and utility as synthetic auxiliary. Our group considered these advantages and explored a number of benzotriazoles and their derivatives for easy access to biologically relevant scaffolds through benzotriazole ring cleavage (BtRC) under optimized conditions. − In continuation of this, Yadav and co-workers demonstrated a convenient, mild, and high-yielding fluoride-triggered coupling reaction of various glycosyl azides with benzyne, obtained in situ from 2-(trimethylsilyl)­phenyltrifluoromethanesulfonate, to produce the respective glycoconjugated N 1 -benzotriazoles as sole product (Scheme ). …”

1,2,3-Triazole and Its Analogues: New Surrogates for Diazo Compounds

“…However, an excess amount of NaBH 4 was required to regenerate the active reagent n -Bu 3 SnH in the reaction mixture. Subsequently, they synthesized benzothiazoles 270.7 from 1-(1-pyrrolidinylthioxomethyl)-1 H -benzotriazoles 270.6 in excellent yield …”

“…Subsequently, they synthesized benzothiazoles 270.7 from 1-(1-pyrrolidinylthioxomethyl)-1H-benzotriazoles 270.6 in excellent yield. 370 In their extended studies, the toxic n-Bu 3 SnH was replaced with a metal-free and less toxic radical initiator such as (TMS) 3 SiH 371,372 or polymethylhydroxysilane (PMHS), 373 which provided the benzothiazoles in good to excellent yields (Scheme 271). Remarkably, PMHS, a cheap waste product of the silicon industry, provided a cost-effective, solvent-free, and environmentally benign way to accomplish the synthesis.…”

Silicon Industry Waste Polymethylhydrosiloxane-Mediated Benzotriazole Ring Cleavage: A Practical and Green Synthesis of Diverse Benzothiazoles

“…The benzotriazole ring cleavage (BtRC) methodology has emerged as an interesting approach for facile synthesis of a variety of compounds including heterocycles. , Reaction conditions, such as thermolysis, photolysis, organometallic reagent oxidants, and free radical reagents, cause the cleavage of the relatively stable benzotriazole ring, exhibiting fascinating chemistry. , The low cost, stability, and nontoxic nature of benzotriazole moiety makes this approach an easy and economical method for organic synthesis of a large number of valuable compounds …”

“…Our group has been involved in the exploration of interesting features of the benzotriazole methodology for the last 10 years. We have successfully employed the BtRC approach for the synthesis of benzoxazoles, benzothiazoles, and amide derivatives mainly using free radical pathway . We also presented an improved approach for the synthesis of benzothiazoles via intramolecular cyclative cleavage of the benzotriazole ring of N -thioacylbenzotriazoles by using 2.2 equiv of n Bu 3 SnH along with 5 mol % azobisisobutyronitrile (AIBN), which was further improved by our group in another report using 0.6 equiv of n Bu 3 SnH along with excess of NaBH 4 and 5 mol % AIBN (Scheme ).…”