Effective Synthesis of N-Alkyl-3-(Indol-3-yl)Pyrazoles from Ag₂CO₃- Catalyzed Regioselective Aza-Michael Addition of 5-(Indol-3-yl)-1HPyrazoles

Title:Effective Synthesis of N-Alkyl-3-(Indol-3-yl)Pyrazoles from Ag₂CO₃- Catalyzed Regioselective Aza-Michael Addition of 5-(Indol-3-yl)-1HPyrazoles

Volume: 21 Issue: 10

Author(s): Xue Zhang, Dashuang Luo, Xuemin Niu, Jian Mo, Haifeng Yu*Xiaobo Zhao*

Affiliation:

• College of Chemistry, Baicheng Normal University, Baicheng, Jilin 137000, China

• College of Chemistry, Baicheng Normal University, Baicheng, Jilin 137000, China

Keywords: Aza-Michael addition, carbonyl compounds, pyrazoles, regioselectivity, silver carbonate, indoles, N-functionalization.

Abstract: In this study, the synthesis of N-alkyl-3-(indol-3-yl)pyrazoles was carried out from Ag₂CO₃ catalyzed regioselective aza-Michael addition of 5-(indol-3-yl)-1H-pyrazoles to α, β-unsaturated carbonyl compounds. In the presence of 10 mol% of Ag₂CO₃, the reaction smoothly occurred in dichloroethane (DCE) at 120°C to preferentially afford a series of N-alkyl-3-(indol-3-yl)pyrazoles in high yields with good regioselectivity. It was found that 1-methyl-3-(3-methyl-1H-pyrazol-5-yl)-2-phenyl- 1H-indole, 1-benzyl-3-(3-methyl-1H-pyrazol-5-yl)-1H-indole, α, β-unsaturated ketone, and α, β- unsaturated amide exclusively gave 3-(pyrazol-3-yl)indoles in good yields. This reaction features high regioselectivity, mild reaction conditions, good substrate scope and yields, and a commercially available catalyst. Meanwhile, the reaction was also proven to be quite practical by the gram-scale synthesis of N-alkyl-3-(indol-3-yl)pyrazoles in excellent yields with good regioselectivity.

Cite this article as:

Zhang Xue, Luo Dashuang, Niu Xuemin, Mo Jian, Yu Haifeng*, Zhao Xiaobo*, Effective Synthesis of N-Alkyl-3-(Indol-3-yl)Pyrazoles from Ag₂CO₃- Catalyzed Regioselective Aza-Michael Addition of 5-(Indol-3-yl)-1HPyrazoles, Letters in Organic Chemistry 2024; 21 (10) . https://dx.doi.org/10.2174/0115701786295074240305095904