Synthesis of 3,5-Disubstituted Pyrazoles via Cope-Type Hydroamination of 1,3-Dialkynes

Abstract

An efficient method for the synthesis of 3,5-disubstituted pyrazoles is described. The reactions of 1,3-dialkynes with hydrazine proceeded smoothly in dimethyl sulfoxide under mild reaction conditions to produce 3,5-disubstituted pyrazoles in satisfactory to excellent yields. A one-pot procedure of the transformation has been developed.

Symmetric 3,5-pyrazole and isoxazole heterocycles comprising a bent core unit: synthesis and mesomorphic characterisation

“…[28,29] The diaryldiacetylenes 3 and 4 were converted into 3,5-disubstituted pyrazoles 7 and 8 in the presence of hydrazine hydrate, via the Cope-type reaction. [30] The disappearance of 2140 cm −1 wave number peak for acetylene group in infrared spectrum confirmed the formation of 3,5-substituted pyrazole from the diarydiacetylenes. Further, confirmation was obtained by other spectroscopic analysis.…”

Synthesis of 1,3,5-Trisubstituted Pyrazoles by the Cope-Type Hydroamination of 1,3-Dialkynes with Alkylhydrazines

“…The reaction of 1a with methylhydrazine sulfate was performed under the same reaction conditions as for the reaction of 1a with hydrazine (in DMSO at 60°C for 20 h). 8 The desired product, 5-benzyl-1-methyl-3-phenyl-1H-pyrazole (2a), was obtained in only 6% yield (entry 1). Subsequent analysis of the reaction temperature indicated that 110°C was the most suitable temperature to produce 2a in 65% yield (entry 6).…”

“…8 This reaction proceeded smoothly in dimethyl sulfoxide (DMSO) in the absence of strong acid, strong base, and transition metal. From mechanistic analysis of this reaction, we anticipated that the intermolecular Cope-type hydroamination reaction of 1,3-dialkynes with alkylhydrazines (NH 2 NHR) might also occur to produce 1,3,5-disubstituted pyrazoles.…”

Synthesis of Heterocycle‐Bridged Peptidic Macrocycles through 1,3‐Diyne Transformations

“…[7] The reaction of 1,3-diynes with S-nucleophiles can lead to thioenynes or thiophenes, [8][9][10][11][12][13][14][15][16] and analogous hydration or hydroamination reactions give rise to furans [15][16][17][18] or pyrroles. [17,18] Also, 1,2-bisnucleophiles such as hydrazine and hydroxylamine have been used to prepare pyrazoles [21,22] and isoxazoles, [23] but such conversions have never been applied on peptidic substrates. It has been shown that related reactions of alkyl-substituted 1,3-diynes often result in a drastic drop in yield relative to those obtained for aromatic substituted thiophenes [8] or furans.…”