Selective Synthesis of Azoloyl NH-1,2,3-Triazoles and Azolyl Diazoketones: Experimental and Computational Insights

Abstract

Here, we report that the reaction of enaminones, from a class of azole series, with sulfonyl azides leads to a difficult-to-separate mixture of two pairs of compounds: (1) 4-azoloyl-NH-1,2,3-triazoles with sulfonamides and (2) azolyl diazoketones with N-sulfonamidines, as a result of the implementation of two competing reactions. On one hand, the electron-donating methyl or methoxy group in the aryl para-position of arylsulfonyl azides favors the production of NH-1,2,3-triazoles together with sulfonamides. On the other hand, the use of highly electrophilic 4-nitrophenylsulfonyl azide promotes the formation of diazoketones and sulfonamidines. It is shown that the direction of each reaction is not only controlled by the nature of the initial enaminones and sulfonyl azides but also depends on the tested solvent. The problem of removing sulfonamides and amidines from the desired products was solved for the first time using new water-soluble enaminones. Based on the experimental and computational studies, the factors contributing to the selective course of alternative reactions were identified, and methods for the synthesis of azoloyl-NH-1,2,3-triazoles and azolyl diazoketones were developed. Density functional theory (DFT) results have shown that the 1,3-dipolar cycloaddition is totally driven toward one single regioisomer with a high asynchronous bond formation, and the introduction of an electron-deficient group in sulfonyl azides induces faster cycloaddition. Additionally, DFT calculations were used to gain further mechanistic insights on the reaction studied here.

4‐(Dimethylamino)Pyridinium Azide in Protic Ionic Liquid Media as a Stable Equivalent of Hydrazoic Acid

“…The low solubility of alkali metal azides in most of organic solvents requires excessive amounts of reagents and harsh reaction conditions (prolonged reaction times and high temperatures). Moreover, in processes requiring for acidic conditions, for example, (3 + 2)-cycloadditions with alkynes, (iso)nitriles, etc., furnishing NH-triazoles [4] and -tetrazoles, [5] poisonous and explosive hydrazoic acid, [6] HN 3 , is formed in situ. Some approaches for overcoming solubility issues in the case of alkali metal azides or necessity to use HN 3 equivalents were proposed.…”

A mild protocol for efficient preparation of functional molecules containing triazole

“…It has been shown that this process is an endothermic process that can form a stable five-membered triazole intermediate IV by releasing heat through ring contraction; finally, the intermediate IV undergoes hydrolysis and releases triazole product 3 to complete the catalytic cycle. Under the condition of nucleophilic base pyrrolidine, 45 the highly electrophilic sulfonyl fluoride moiety of 3 cleaved subsequently with the generation of NH-1,2,3-triazoles together with byproduct enaminyl sulfonyl fluoride. 27 …”