Domino-reactions of isatins with 5-aminopyrazoles and 2,2-dimethyl-1,3-dioxane-4,6-dione

N I Zemlyana,T M Karnozhitska,V I Musatov,V V Lipson,O V Mazepa,T L Pavlovska

doi:10.24959/ophcj.18.950

Abstract

Aim. To determine the direction of the interaction of isatins with 5-amino-pyrazoles and 2,2-dimethyl-1,3-dioxane-4,6-dione under different conditions.Results and discussion. The domino-reactions of isatins, 5-aminopyrazoles and 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum’s acid) in the alcoholic medium are completed by formation of a mixture of pyrazolo[3,4-b]pyridine-4-spiroindolinones and 3-(5-aminopyrazol-3-yl)-3-hydroxy-2-oxindolines with the predominant content of spiro compounds. 3-(5-Aminopyrazol-4-yl)-3-hydroxy-2-oxindolines may turn into pyrazolo[3,4-b]pyridine-4-spiroindolinones very slowly only as a result of retrograde fragmentation to isatin and aminopyrazole in the presence of Meldrum’s acid.Experimental part. The mixtures of pyrazolo[3,4-b]pyridine-4-spiroindolinones and 3-(5-aminopyrazol-3-yl)-3-hydroxy-2-oxindolines separated by crystallization were obtained by boiling in methanol of the equimolar quantity of isatins, 5-aminopyrazoles and Meldrum’s acids. The yield for spiro compounds is 26-82 %, and for 3-(5-aminopyrazole-3-yl)-3-hydroxy-2-oxindolines it is 5-23 %. The transformation of the latter into the spiro compound in the presence of Meldrum’s acid occurs with prolonged boiling in the alcoholic medium and is accompanied with extremely low yields. The structure of all compounds synthesized has been proven by 1H NMR, mass spectra and elemental analysis.Conclusions. It has been found that in the three-component reactions of isatins, 5-aminopyrazoles and 2,2-dimethyl-1,3-dioxane-4,6-dione there are two competing directions of the interaction of isatin with nucleophiles. One of them is the nucleophilic addition of the C4 reaction center of aminopyrazole to the carbonyl group of isatin, which results in 3-(5-aminopyrazol-4-yl)-3-hydroxy-2-oxidolines. Another one is the Knoevenagel condensation of isatin with dioxane-4,6-dione – a domino process that starts formation of the predominant reaction products – pyrazolo[3,4-b]pyridine-4-spiroindolinones.

Highlights

The domino-reactions of isatins, 5-aminopyrazoles and 2,2-dimethyl-1,3-dioxane-4,6dione (Meldrum’s acid) in the alcoholic medium are completed by formation of a mixture of pyrazolo[3,4-b] pyridine-4-spiroindolinones and 3-(5-aminopyrazol-3-yl)-3-hydroxy-2-oxindolines with the predominant content of spiro compounds. 3-(5-Aminopyrazol-4-yl)-3-hydroxy-2-oxindolines may turn into pyrazolo[3,4-b]pyridine4-spiroindolinones very slowly only as a result of retrograde fragmentation to isatin and aminopyrazole in the presence of Meldrum’s acid
The mixtures of pyrazolo[3,4-b]pyridine-4-spiroindolinones and 3-(5-aminopyrazol3-yl)-3-hydroxy-2-oxindolines separated by crystallization were obtained by boiling in methanol of the equimolar quantity of isatins, 5-aminopyrazoles and Meldrum’s acids
The structure of all compounds synthesized has been proven by 1H NMR, mass spectra and elemental analysis

Summary

Introduction

А інший – конденсація ізатину з діоксан-4,6-діоном за Кньовенагелем започатковує доміно-процес, який завершується утворенням переважних продуктів реакції – піразоло[3,4-b]піридин-4-спіроіндолінонів. Ключові слова: піразоло[3,4-b]піридин-4-спіроіндолінони; 3-(5-амінопіразол-4-іл)-3-гідрокси-2-оксіндоліни; ізатини; 5-амінопіразоли; 2,2-диметил-1,3-діоксан-4,6-діон; доміно-реакції The domino-reactions of isatins, 5-aminopyrazoles and 2,2-dimethyl-1,3-dioxane-4,6dione (Meldrum’s acid) in the alcoholic medium are completed by formation of a mixture of pyrazolo[3,4-b] pyridine-4-spiroindolinones and 3-(5-aminopyrazol-3-yl)-3-hydroxy-2-oxindolines with the predominant content of spiro compounds.

Results

Conclusion