An Efficient Access to 5‐(1, 2, 3‐Triazol‐1‐yl)isoxazoles – Previously Unknown Structural Type of Triazole‐isoxazole Hybrid Molecule. Issue 9 (4th August 2022)

• Record Type: Journal Article
• Authors: Vasilenko, Dmitry A.; Dronov, Sevastian E.; Grishin, Yuri K.; Averina, Elena B.
• Is Part Of: Asian journal of organic chemistry. Volume 11:Issue 9(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-08-04
• Subjects: aromatic nucleophilic substitution -- 5-azidoisoxazole -- CuAAC reaction -- 5-nitroisoxazole -- triazole; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; 547.005
• DOI: 10.1002/ajoc.202200355
• Languages: English
• ISSNs: 2193-5807

Abstract

Abstract: Since isoxazole and triazole have significant applications in pharmaceutical chemistry, the synthesis of hybrid isoxazole‐triazole molecules has attracted great attention. In the present study, an efficient method for the synthesis of 5‐azidoisoxazoles has been developed via chemoselective nitro‐group substitution of 3‐EWG‐5‐nitroisoxazoles with sodium azide through the aromatic nucleophilic substitution reaction. The resulting 5‐azidoisoxazoles are employed in CuACC‐reaction with a variety of alkynes, providing a straightforward approach for the synthesis of previously unknown structure type of biologically relevant 5‐(1, 2, 3‐triazol‐1‐yl)isoxazoles. Both reactions proceed with excellent yields and functional group tolerance under mild conditions. Abstract : A facile two‐step method was elaborated for the synthesis of previously unknown 5‐(1, 2, 3‐triazol‐1‐yl)isoxazoles via the chemoselective SN Ar reaction of the nitro‐group of available 3‐EWG‐5‐nitroisoxazoles with the sodium azide and subsequent CuAAC reaction of resulting 5‐azidoizoxazoles with variety of alkynes. Both reactions provide excellent chemical yields, broad scope of substrates, mild conditions and high functional group tolerance.