N'-[2,2,2-trifluoroethylidene]-4-(trifluoromethyl)benzene-1-sulfonohydrazide

CAS 3060319-85-6, Cat. No EN300-52863357
Reagent for decarboxylative trifluoroethylation

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N'-[2,2,2-trifluoroethylidene]-4-(trifluoromethyl)benzene-1-sulfonohydrazide (para-TFHZ-Tfs) is a bench-stable sulfonyl hydrazone derived from trifluoroacetaldehyde, developed as a formal trifluoroethyl (–CH₂CF₃) transfer reagent under visible-light conditions¹. Under photocatalytic conditions, alkyl radicals—most commonly generated by decarboxylation of aliphatic carboxylic acids - add to the C=N bond of the sulfonyl hydrazone. The resulting alkylated hydrazide then undergoes light-induced diazene fragmentation, extruding N₂ and a sulfinate to furnish trifluoroethylated products. This two-step, one-pot sequence cleanly converts R-CO₂H into R-CH₂CF₃, providing a distinct retrosynthetic disconnection compared to classical CF₃ methods. The reagent is not a CF₃ source but a C1-homologative CF₃ equivalent, formally delivering –CH₂CF₃. The methodology demonstrates broad applicability to primary, secondary, and tertiary aliphatic carboxylic acids, as well as cyclic amines, heterocycles, amino acids, peptides, and complex drug-like molecules. The protocol tolerates halogens, esters, amides, carbamates, alcohols, protected amines, and heteroaromatics and is suitable for late-stage functionalization. The reagent shows high chemoselectivity for radical addition and favors the desired radical fragmentation pathway under light, suppressing competing anionic fluoride-elimination processes. The reagent can also undergo [3+2] annulation with 4-nitroisoxazoles to form trifluoromethylpyrazolo [3,4-d]isoxazoles².

Synonyms: para-TFHZ-Tfs; (E)-N'-(2,2,2-trifluoroethylidene)-4-(trifluoromethyl)benzenesulfonohydrazide; benzenesulfonic acid, 4-(trifluoromethyl)-, 2-(2,2,2-trifluoroethylidene)hydrazide; 4-(trifluoromethyl)benzenesulfonic acid 2-(2,2,2-trifluoroethylidene)hydrazide