One-Pot Synthesis of 1-Aryl-3-trifluoromethylpyrazoles Using Nitrile Imines and Mercaptoacetaldehyde As a Surrogate of Acetylene

Abstract

A synthetically useful approach for one-pot preparation of 1-aryl-3-trifluoromethylpyrazoles using in situ generated nitrile imines and mercaptoacetaldehyde applied as 1 equiv of acetylene is presented. This protocol comprises (3 + 3)-annulation of the mentioned reagents to form 5,6-dihydro-5-hydroxy-4H-1,3,4-thiadiazine, followed by cascade dehydration/ring contraction reactions with p-TsCl. In addition, representative nonfluorinated analogues functionalized with Ph, Ac, and CO2Et groups at the C(3)-position of the pyrazole ring were also prepared by the devised method.

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

“…Meanwhile, mercaptoacetaldehyde as a surrogate of acetylene reacted with trifluoroacetonitrile imine to form 1-aryl-3-trifluoromethylpyrazoles, followed by a series of cascade annula-tion/dehydration/ring contraction reactions when treated with p-TsCl [65] (Scheme 10b).…”

Synthesis of fused 3-trifluoromethyl-1,2,4-triazoles via base-promoted [3 + 2] cycloaddition of nitrile imines and 1H-benzo[d]imidazole-2-thiols

“…11 The Jasiński group developed a strategy for the efficient synthesis of 1-aryl-3-trifluoromethylpyrazoles in one-pot, using nitrile imines and mercaptoacetaldehyde as the raw materials (Scheme 1a). 12 Although many methods for the synthesis of valuable five-membered moieties via a [3 + 2] cycloaddition strategy employing trifluoromethyl-substituted nitrile imines 13 and fused triazoles 14 have been disclosed, the direct route towards fused 3-trifluoromethyl-1,2,4-triazoles, which is available with limited methods, is rarely investigated and still high in demand. Based on the significant value of such backbones 15 and traditional conditions usually used in base-promoted [3 + 2] dipolar cycloaddition involving 2-mercapto or 2-methylthio 1 H -benzoimidazole derivatives, 16 herein, we present a novel route to access fused 3-CF 3 -1,2,4-triazoles which possibly show pharmacological activity in high efficiency using 1 H -benzo[ d ]imidazole-2-thiol 1 and fluorinated nitrile imines 2 under the promotion of a base (Scheme 1b).…”

The cyclization/rearrangement of α-hydroxy ketones with trifluoromethyl N-acylhydrazones to synthesize multi-substituted trifluoromethyloxazolines

“…However, the reaction unexpectedly led to N–N bond cleavage 8 and rearrangement of the amide fragments under acidic conditions [Scheme 1e, 3 ], which is a new method for synthesizing trifluoromethyl oxazoline derivatives and provides a new perspective on reactions involving acylhydrazones as dipoles. 9…”