Preparation of 1,5‐disubstituted 4‐sulfonylpyrazoles, β‐cyano‐β‐sulfonylenamines and 5‐substituted 4‐sulfonylisoxazoles from β‐keto‐β‐sulfonylenamines

Takahashi, Masahīko; Mamiya, Tsutomu; Hasegawa, Hisao; Nagai, Takashi; Wakita, H.

doi:10.1002/jhet.5570230520

Cited by 16 publications

(1 citation statement)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, we report a mild fragmentation of the pyrazole ring [24][25][26][27] in functionalized 1H-imidazo [1,2-b]pyrazoles of type 11 induced by metalation at the 6-position with TMP 2 Zn•MgCl 2 •2LiCl (9) (Scheme 2). This reaction proceeded via zincated intermediates of type 13 and led to a series of (1,3-dihydro-2H-imidazol-2-ylidene)malononitriles of type 14.…”

Section: Introductionmentioning

confidence: 99%

Selective functionalization of the 1H-imidazo[1,2-b]pyrazole scaffold. A new potential non-classical isostere of indole and a precursor of push–pull dyes

et al. 2021

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

Selective functionalization of the 1H-imidazo[1,2-b]pyrazole scaffold. A new potential non-classical isostere of indole and a precursor of push–pull dyes

et al. 2021

View full text Add to dashboard Cite

show abstract

Switchable Reactivity: The Site-Selective Functionalization of Trifluoromethyl-Substituted Pyrazoles

et al. 2002

View full text Add to dashboard Cite

Keywords: Heterocycles / Bromopyrazoles / Carboxylation / Hydrogen/metal exchange / Halogen/metal exchange / Organolithium intermediatesModern organometallic methods enable the regioflexible conversion of simple heterocyclic starting materials into families of isomers and congeners. Depending on the choice of the reagent, 1-methyl-5-(trifluoromethyl)pyrazole (1) undergoes deprotonation and subsequent carboxylation mainly or exclusively at either the 4-position of the heterocycle or at the nitrogen-attached methyl group. Similarly, 1-phenyl-5-(trifluoromethyl)pyrazole (5) and 3-methyl-1-phenyl-5-(trifluoromethyl)pyrazole (8) are selectively attacked by lithium diisopropylamide at the heterocyclic 4-position and by butyllithium concomitantly at the 4-position and the ortho position Efficacy and versatility make organometallic methods particularly suitable for the functionalization of olefinic, aromatic and heterocyclic core structures. [1Ϫ2] The metalation of pyrazole, N-alkylpyrazoles and N-phenylpyrazole at the 5-position has been repeatedly reported. [3Ϫ10] The trapping products qualify as valuable intermediates for the synthesis of pharmaceuticals and agrochemicals. To probe further the intriguing steric and electronic properties of the CF 3 group, [11Ϫ12] we have turned our attention to trifluoromethyl-substituted pyrazoles. Previously, 5-methyl-1-phenyl-3-(trifluoromethyl)pyrazole, 3-methyl-1-phenyl-5-(trifluoromethyl)pyrazole and 1-phenyl-3,4-bis(trifluoromethyl)pyrazole have been treated with butyllithium, and metalation at the 4-position of the azole ring has been achieved to the extent of 0%, 11% and 95%, respectively. [13] Under similar conditions, 3-chloro-1-methyl-5-(trifluoromethyl)pyrazole was found to undergo 4-lithiation and subsequent carboxylation in 75% yield. [14] Although (trifluoromethyl)pyrazoles are readily accessible by condensation [15Ϫ27] or [3 ϩ 2] cycloaddition [28] reactions, only one out of eight model substrates studied, 3-methyl-1-phenyl-5-(trifluoromethyl)pyrazole, [29] could be prepared according to a literature procedure. The isolation of 1-methyl-5-(trifluoromethyl)pyrazole (1) in 76% yield has also been reported. However, these results were not reproducible. In reality, 4-ethoxy-1,1,1-trifluoro-3-butene-2-one [a] 2913 of the phenyl ring. In contrast, metalation of 1-methyl-3-(trifluoromethyl)pyrazole (2) occurs only at the 5-position, whatever the organometallic or metal amide base. Further sites become accessible to functionalization if bromine is introduced into the heterocyclic or aromatic ring. This has been demonstrated with 4-bromo-1-methyl-5-(trifluoromethyl)pyrazole (3), 4-bromo-1-methyl-3-(trifluoromethyl)pyrazole (4), 4-bromo-1-methyl-5-(trifluoromethyl)pyrazole (7) and 1-(2-bromophenyl)-5-(trifluoromethyl)pyrazole (6). and methylhydrazine afforded a 3:7 mixture (up to 98%) of pyrazole 1 and the regioisomeric 1-methyl-3-(trifluoromethyl)pyrazole (2). A convenient separation of the two components could be accomplished after short reaction times when 4,5-dihydro-...

show abstract

Synthesis of Sulfonated 5‐Aminopyrazoles by I₂/Benzoyl Peroxide‐Mediated Tandem Reaction

Cheng

Chen

et al. 2018

Adv Synth Catal

View full text Add to dashboard Cite

show abstract

Preparation of 1,5‐disubstituted 4‐sulfonylpyrazoles, β‐cyano‐β‐sulfonylenamines and 5‐substituted 4‐sulfonylisoxazoles from β‐keto‐β‐sulfonylenamines

Abstract: The sulfonyl ketones (I) react with the dimethylformamide acetal (II) to produce the enamines (III).

Cited by 16 publications

References 16 publications

Selective functionalization of the 1H-imidazo[1,2-b]pyrazole scaffold. A new potential non-classical isostere of indole and a precursor of push–pull dyes

Selective functionalization of the 1H-imidazo[1,2-b]pyrazole scaffold. A new potential non-classical isostere of indole and a precursor of push–pull dyes

Switchable Reactivity: The Site-Selective Functionalization of Trifluoromethyl-Substituted Pyrazoles

Synthesis of Sulfonated 5‐Aminopyrazoles by I₂/Benzoyl Peroxide‐Mediated Tandem Reaction

Contact Info

Product

Resources

About

Preparation of 1,5‐disubstituted 4‐sulfonylpyrazoles, β‐cyano‐β‐sulfonylenamines and 5‐substituted 4‐sulfonylisoxazoles from β‐keto‐β‐sulfonylenamines

Abstract: The sulfonyl ketones (I) react with the dimethylformamide acetal (II) to produce the enamines (III).

Cited by 16 publications

References 16 publications

Selective functionalization of the 1H-imidazo[1,2-b]pyrazole scaffold. A new potential non-classical isostere of indole and a precursor of push–pull dyes

Selective functionalization of the 1H-imidazo[1,2-b]pyrazole scaffold. A new potential non-classical isostere of indole and a precursor of push–pull dyes

Switchable Reactivity: The Site-Selective Functionalization of Trifluoromethyl-Substituted Pyrazoles

Synthesis of Sulfonated 5‐Aminopyrazoles by I2/Benzoyl Peroxide‐Mediated Tandem Reaction

Contact Info

Product

Resources

About

Synthesis of Sulfonated 5‐Aminopyrazoles by I₂/Benzoyl Peroxide‐Mediated Tandem Reaction