Regioselective Synthesis of 5-Trifluoromethyl 1,2,4-Triazoles via [3 + 2]-Cycloaddition of Nitrile Imines with CF3CN

Abstract

We herein describe a general approach to 5-trifluoromethyl 1,2,4-triazoles via the [3 + 2]-cycloaddition of nitrile imines generated in situ from hydrazonyl chloride with CF3CN, utilizing 2,2,2-trifluoroacetaldehyde O-(aryl)oxime as the precursor of trifluoroacetonitrile. Various functional groups, including alkyl-substituted hydrazonyl chloride, were tolerated during cycloaddition. Furthermore, the gram-scale synthesis and common downstream transformations proved the potential synthetic relevance of this developed methodology.

Fluorine‐Containing Functional Group‐Based Energetic Materials

“…Therefore, a common strategy utilized to construct trifluoromethyl group‐based energetic materials is to introduce both a trifluoromethyl moiety and detonation groups or rings. Among the fluorine‐containing functional groups used in energetic materials, the trifluoromethyl moiety has been widely reported and explored with extensive theoretical research and investigations regarding its practical applications [89–91] …”

“…Among the fluorinecontaining functional groups used in energetic materials, the trifluoromethyl moiety has been widely reported and explored with extensive theoretical research and investigations regarding its practical applications. [89][90][91] Trifluoromethyl-based triazole derivatives were reported as insensitive energetic materials by Shreeve's group in 2021 (Scheme 5). [92] The reaction route combined 1-amino-1hydrazino-2,2-dinitroethylene (28, HFOX) as a precursor and monocarboxylic trifluoroacetic acid (TFA) to yield 3-(dinitromethyl)-5-(trifluoromethyl)-1H-1,2,4-triazole (30), 3-(trinitromethyl)-5-(trifluoromethyl)-1H-1,2,4-triazole (31), and nitrogen-rich energetic salts (32-34).…”

Synthesis of 2-trifluoromethyl thiazoles via [3 + 2] cycloaddition of pyridinium 1,4-zwitterionic thiolates with CF3CN

“…27 The utility of pyridinium 1,4-zwitterionic thiolates in synthesis has been recently developed by Zhai's group in a variety of cycloaddition reactions. 28–30 On the basis of our recent studies on the synthesis of trifluoromethylated heterocycles using trifluoroacetonitrile generated from 2,2,2-trifluoroacetaldehyde O -(aryl)oxime, 31–34 we predicted a similar mechanistic pathway for the reaction of pyridinium 1,4-zwitterionic thiolates with CF 3 CN, to generate 2-trifluoromethyl thiazoles (Scheme 1b).…”

Synthesis of 2-trifluoromethyl benzimidazoles, benzoxazoles, and benzothiazoles via condensation of diamines or amino(thio)phenols with CF3CN

“…29 Also, we have recently demonstrated new efficient protocols for assembling a range of novel five-membered nitrogen-containing heterocycles using in situ generated trifluoroacetonitrile from 2,2,2-trifluoroacetaldehyde O-(aryl)oxime. [30][31][32][33] On the basis of these previous studies, especially on the synthesis of benzothiazoles and their structural analogues by the condensation of 2-aminothiophenol and nitriles, [34][35][36] and our continued interest in trifluoromethylated heterocycle synthesis, [37][38][39][40][41] we further became interested in designing efficient methodologies for the synthesis of 2-trifluoromethyl benzimidazoles and benzothiazoles via condensation of diamines or amino(thio)phenols with CF 3 CN (Scheme 1b).…”