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Synlett
DOI: 10.1055/a-2709-7683
DOI: 10.1055/a-2709-7683
Letter
Published as part of the Special Issue dedicated to Prof. S. Chandrasekaran on his
80th birthday
Ru-Catalyzed Domino C-4 Alkylation and Hydroxylation of Pyrazolones Using Alcohols via Borrowing-Hydrogen Catalysis
Autoren
Gefördert durch: Science and Engineering Research Board CRG/2023/002452
Funding Information This research was supported and funded by SERB (grant No. CRG/2023/002452), India.
Abstract
Herein, we developed a domino approach for the C-4-functionalization of pyrazolones, which includes sequential C-4 alkylation and C–H hydroxylation with alcohols to achieve C-4-substituted pyrazolones and pyrazoles via borrowing-hydrogen catalysis. The method is successfully facilitated in the presence of RuH2CO(PPh3)3 catalyst and sodium hydroxide as a base. Notably, this approach has been well validated with the 16 examples of C4-substituted pyrazolones with hydroxylated products and 14 examples of substituted pyrazoles, generating water as the sole, environmentally benign byproduct.
Keywords
Domino reaction - Ru-catalyst - Borrowing alkylation - C–H hydroxylation - Pyrazolones - PyrazolesPublikationsverlauf
Eingereicht: 03. Juli 2025
Angenommen nach Revision: 24. September 2025
Artikel online veröffentlicht:
31. Oktober 2025
© 2025. Thieme. All rights reserved.
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- 19 A. General procedure for C-H Hydroxylation: In a 20 mL re-sealable vial were added RuH2(CO)(PPh3)3 (5 mol%), Pyrazolone compound (0.29 mmol, 50 mg, 1 equiv), primary alcohol (2 equiv) and NaOH (6 equiv) in the presence of toluene (2 mL) as a solvent. The tube was sealed with a cap using a crimper. The reaction mixture was heated at 180 °C for 24 h in a preheated oil bath or Radleys parallel synthesizer in a sealed tube under aerobic condition. The progress of the reaction was monitored using TLC analysis. After completion of the reaction, the reaction mixture was diluted with ethyl acetate. Further, the volatile component was evaporated under a vacuum. The residue was purified using 100–200 mesh silica gel column chromatography. (EtOAc:hexane = 10:90–20:80)
- 20 B. General procedure for C-4 Alkylation: In a 20 mL re-sealable vial were added RuH2(CO)(PPh3)3 (5 mol%), Pyrazolone compound (0.29 mmol, 50 mg, 1 equiv), primary alcohol (3 equiv) and NaOH (6 equiv) in the presence of toluene (2 mL) as a solvent. The tube was sealed with a cap using a crimper. The reaction mixture was heated at 180 °C for 24 h in a preheated oil bath or Radleys parallel synthesizer in a sealed tube under inert condition. The progress of the reaction was monitored using TLC analysis. After completion of the reaction, the reaction mixture was diluted with ethyl acetate. Further, the volatile component was evaporated under a vacuum. The residue was purified using 100–200 mesh silica gel column chromatography. (EtOAc:hexane = 10:90–20:80)