A Convenient and Efficient Synthesis of Benzotriazoles and Benzisoxazolines Using Anew Hypervalent Iodine-Benzyne Precursor

Abstract

Reaction of (phenyl) [o-(trimethylsilyl)phenyl]iodonium triflate with organic azides and nitrones using Bu 4 NF gave benzotriazoles and benzisoxazolines in high yields, respectively. This reaction indicates that benzyne is generated under mild conditions and efficiently trapped with the 1,3-dipoles to give heterocyclic compounds.Recently much attention has been paid to the use of hypervalent iodine compounds in organic synthesis (1-7). Previously we have found that (phenyl)[o-(trimethylsilyl)phenyl]iodonium triflate (1) acts as an excellent benzyne precursor and generates benzyne quantitatively by a simple treatment of o-(trimethylsilyl)phenyliodonium triflate 1 with Bu 4 NF under very mild conditions as shown in Scheme 1 (8).The merits of the use of the hypervalent iodine-benzyne precursor 1 includes (a) the stability of the precursor 1, (b) no requirement of a strong base or high temperature, and (c) the quantitative generation of benzyne under mild conditions.If the hypervalent iodine-benzyne precursor 1 can be applied to the reactions with 1,3-dipoles such as azides and nitrones, the reaction of 1 will provides a useful methodology for synthesis of heterocyclic skeletons.In this paper, we report an efficient and convenient synthesis of benzotriazoles and benzisoxazolines by means of the hypervalent iodine-benzyne precursor 1. 1 100% Scheme 1. 205 Brought to you by | Purdue University Libraries Reaction of o-(trimethylsilyl)phenyliodonium triflate 1 with aryl azides (2a-d) could be conducted in CH 2 CI 2 simply by adding Bu 4 NF. A solution of 1 and aryl azides in CH 2 CI 2 was treated with aTHF solution ofBu 4 NF at 0 °C and the reaction mixture was stirred at room temperature for 20 min. Separation by column chromatography on silica gel gave 1-arylbenzotriazoles (3a-d) in high yields. The results are given in Table 1.This reaction was applied to ethyl 2-azidopropionate (2 e)and 2-azido-1-octadecene (21), which reacted with benzyne generated from 1 to yield the corresponding benzotriazoles (3 e and f). As shown in Table 1, o-(trimethylsilyl)phenyliodonium triflate 1 is a useful reagent for benzotriazole synthesis. Even in the reaction of athermally unstable vinyl azide or an azide bearing functional ester group, 1 acts as the benzyne precursor and undergoes the 1,3-dipolar cycloaddition efficiently.Abstract: New synthetic routes for antimicrobial mesoionics 4-methyl-1.3.4-thiadiazolium-2-aminide and 4-aryl-1.3.4thiadiazolium-2-aminide and their precursors are reported. Through the reported procedure, antimicrobial 1,4-diaroylthiosemicarbazides can be obtained in high purity degree.

Organic Azides: An Exploding Diversity of a Unique Class of Compounds

“…Related to this reaction are the additions of arynes to azides, which lead to benzotriazoles, as Huisgen and co‐workers were able to show quite early 215. 232, 233 Trimethylsilylacetylene234 and a number of strained or electronically activated alkynes react with organoazides at room temperature or below, whereas with many other alkynes the reaction must be carried out at elevated temperatures in the absence of catalysts. The cycloaddition of immobilized alkynes with organic azides has also been carried out on soluble polymers235 (Scheme ) and on polystyrene resins 236.…”

Organische Azide – explodierende Vielfalt bei einer einzigartigen Substanzklasse

“…Verwandt mit diesen Reaktionen sind die Cycloadditionen von Aziden an Arine, die zu Benzotriazolen führen, wie Huisgen und Mitarbeiter schon früh zeigten 215. 232, 233 Trimethylsilylacetylen234 und einige gespannte oder elektronisch aktivierte Alkine reagieren mit organischen Aziden schon bei Raumtemperatur oder darunter, bei vielen anderen Alkinen ist dagegen in Abwesenheit von Katalysatoren eine Reaktionsführung bei erhöhter Temperatur erforderlich. Die Cycloaddition von organischen Aziden an immobilisierte Alkine wurde auch an löslichen Polymeren235 (Schema ) und an Polystyrol‐Harzen236, 237 durchgeführt.…”

Elemental step thermodynamics of various analogues of indazolium alkaloids to obtaining hydride in acetonitrile

“…The analogues of indazolium alkaloids 1 + -4 + , 44,45 5 + , 46 and 6 + -7 + (ref. 47) were synthesized according to the literature, respectively, and the detailed synthetic routes are provided in the ESI. † The analogues of indazolium alkaloids (1 + -7 + ) are all known compounds.…”