Ring Opening of Pyrrolinium Ions Enabled Regioselective Synthesis of 4-Alkyl N-Arylpyrazoles

Abstract

An unprecedented method for the regioselective synthesis of 1,3-diaryl 4-alkyl pyrazoles has been reported. A wide variety of 1,3-diaryl 4-alkyl pyrazoles were synthesized as a single regioisomer via a ring-opening cyclization reaction of unsaturated pyrrolinium ions in the presence of arylhydrazines. This method avoids using additional alkylation steps and hazardous oxidants that generally are essential for the synthesis of 4-alkyl N-arylpyrazoles.

One-Step Synthesis of Functionalized Pyrazolo[3,4-b]pyridines via Ring Opening of the Pyrrolinium Ion

“…Finally, it is oxidized by air oxygen to the final product 3 . It should be noted that the mechanism of our reaction is different from the mechanism suggested by Jana et al, where the first stage of the reaction is the attack of the lone pair of nitrogen atom to the exocyclic double bond of pyrroline. Notably, we did not observe the formation of the second regioisomer, which can be formed through the mechanism described by Jana et al=.…”

“…18 Finally, it is oxidized by air oxygen to the final product 3. It should be noted that the mechanism of our reaction is different from the mechanism suggested by Jana et al, 21 where the first stage of the reaction is the attack of the lone pair of Scheme 2. Synthesis of Pyrazolo [3,4-b] nitrogen atom to the exocyclic double bond of pyrroline.…”

“…As a result of our research, herein, we report the synthesis of pyrazolo­[3,4- b ]­pyridines via the reaction of 3-arylidene-1-pyrrolines with aminopyrazole derivatives. We showed that the mechanism of our reaction is different from the mechanism suggested by Jana et al For example, the first stage of the reaction is the attack of the lone electron pair of the nitrogen atom of aminopyrazole to the CN-bond of 1-pyrroline with the formation of a secondary amine, which undergoes intramolecular cyclization with the endocyclic double bond of cyclic imine. Then, there is opening of the pyrrolidine ring and oxidation to the target product.…”

“…The ability of ring opening of pyrroline ring should be noted . Quite recently, Jana et al reported on the reaction of 3-arylidene-1-pyrroline with arylhydrazines, which affords substituted pyrazoles (Scheme d). The authors suggest that the first stage of the reaction is addition of the nitrogen atom of hydrazine to the endocyclic double bond of 3-arylidene-1-pyrroline (aza-Michael reaction).…”

Organocatalytic Chemoselective C4‐Benzylation of 5‐Aminopyrazoles

“…[20] In recent developments, pyrrolinium ions have been utilized to form 4-alkylated-1-aryl-pyrazoles. [21] Despite excellent yields, existing methodologies still possess inherent limitations. Hence we have conceived a sustainable approach to the synthesis of alkylated pyrazoles from easily accessible starting precursors.…”