@article{Zemlyana_Karnozhitska_Pavlovska_Mazepa_Musatov_Lipson_2018, title={Domino-reactions of isatins with 5-aminopyrazoles and 2,2-dimethyl-1,3-dioxane-4,6-dione}, volume={16}, url={https://ophcj.nuph.edu.ua/article/view/ophcj.18.950}, DOI={10.24959/ophcj.18.950}, abstractNote={<p class="a"><strong><span lang="EN-GB">Aim. </span></strong><span lang="EN-GB">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.</span></p><p class="a"><span lang="EN-GB"><strong>Results and discussion.</strong> </span><span lang="EN-GB">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-</span><span lang="EN-GB">b</span><span lang="EN-GB">]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-</span><span lang="EN-GB">b</span><span lang="EN-GB">]pyridine-4-spiroindolinones very slowly only as a result of retrograde fragmentation to isatin and aminopyrazole in the presence of Meldrum’s acid.</span></p><p class="a"><span lang="EN-GB"><strong>Experimental part.</strong> </span><span lang="EN-GB">The mixtures of pyrazolo[3,4-</span><span lang="EN-GB">b</span><span lang="EN-GB">]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 <sup>1</sup>H NMR, mass spectra and elemental analysis.</span></p><p class="a"><strong><span lang="EN-GB">Conclusions. </span></strong><span lang="EN-GB">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 C</span><sup><span lang="EN-GB">4</span></sup><span lang="EN-GB"> 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-</span><span lang="EN-GB">b</span><span lang="EN-GB">]pyridine-4-spiroindolinones.</span></p>}, number={4(64)}, journal={Journal of Organic and Pharmaceutical Chemistry}, author={Zemlyana, N. I. and Karnozhitska, T. M. and Pavlovska, T. L. and Mazepa, O. V. and Musatov, V. I. and Lipson, V. V.}, year={2018}, month={Dec.}, pages={3–10} }