Tandem Cycloaddition of Azides to 3,3-Diaminoacrylonitriles (2-Cyanoacetamidines) and Cornforth-Type Rearrangement as an Approach to 5‑Amino-1,2,3-triazole-4‑N‑substituted Imidamides

• Published in: Journal of organic chemistry Vol. 88; no. 13; pp. 8163 - 8174
• Main Authors: Silaichev, Pavel S., Beryozkina, Tetyana V., Ilkin, Vladimir, Novikov, Mikhail S., Dehaen, Wim, Bakulev, Vasiliy A.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 07-07-2023
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.3c00151

An efficient base-catalyzed, metal-free method for the synthesis of 5-amino-1,2,3-triazole-4-N-sulfonyl- and arylimidamides, directed by the structure of the amidine group, has been developed. It is based on a previously unknown tandem process involving cycloaddition reaction to 3,3-diaminoacrylonitriles (2-cyanoacetamidines) with aryl­(alkyl)­sulfonyl or aryl azides and Cornforth-type rearrangement. During the reaction optimization, different factors were found to facilitate the title reaction, which include the use of a strong base and N-mono- or N,N′-disubstituted 3,3-diaminoacrylonitriles. The reaction is tolerant to variously N-monosubstituted and N,N′-disubstituted 3,3-diaminoacrylonitriles and to various aryl- and aryl/alkyl sulfonyl azides. The developed method has a broad scope and can be applied to obtain a variety of 5-amino-1,2,3-triazole-4-carbimidamides bearing at the N1 position alkyl, allyl, propargyl, benzyl, cycloalkyl, and heteroaryl substituents and sulfonyl and aryl substituents at the amidine group. Post-cyclization reactions of prepared 5-amino-1,2,3-triazoles with DMF-DMA DMA-DMF leads to 1,2,3-triazolo­[4,5-d]­pyrimidines, 8-aza purine analogues demonstrating the applicability of the prepared compounds in organic synthesis.