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Direct four-component assembling of arylaldehydes, dimethylbarbituric acid, 4-hydroxycoumarine, and cyclic amines into complex scaffolds with three different heterocyclic rings

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Abstract

The new type of four-component tandem Knoevenagel–Michael reaction was found: assembling arylaldehydes, N,N′-dimethylbarbituric acid, 4-hydroxycoumarine, and morpholine or piperidine has been successfully carried out in alcohols, other organic solvents and water at ambient temperature without catalyst or any other additives and resulted in the selective formation of the new substituted unsymmetrical scaffold with three different heterocyclic rings in 75–98% yields. The crystal structure of morpholin-4-ium 5-[(4-hydroxy-2-oxo-2H-chromen-3-yl)(phenyl)methyl]-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate and morpholin-4-ium 5-[(4-hydroxy-2-oxo-2H-chromen-3-yl)(4-nitrophenyl)methyl]-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate was confirmed by X-ray diffraction study. Thus, this new four-component tandem Knoevenagel–Michael strategy is a selective, facile, and efficient way to unsymmetrical scaffolds with three different pharmacology active heterocyclic rings. The optimized reaction conditions and a mechanistic rationale for this multicomponent assembling are presented.

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Acknowledgements

Crystal structure determination for compound 2a was performed in the Department of Structural Studies of Zelinsky Institute of Organic Chemistry, Moscow. Crystal structure determination for compounds 2h and 4e were performed with the financial support from Ministry of Science and Higher Education of the Russian Federation using the equipment of Center for molecular composition studies of INEOS RAS and are also gratefully acknowledged.

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Authors and Affiliations

  1. N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation

    Michail N. Elinson, Anatoly N. Vereshchagin, Yuliya E. Ryzhkova & Kirill A. Karpenko

  2. A. N. Nesmeyanov Institute of Organoelements Compounds, Russian Academy of Sciences, Moscow, Russian Federation

    Ivan E. Ushakov & Aleksander S. Goloveshkin

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  1. Michail N. Elinson
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  2. Anatoly N. Vereshchagin
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  3. Yuliya E. Ryzhkova
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  4. Kirill A. Karpenko
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  5. Ivan E. Ushakov
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  6. Aleksander S. Goloveshkin
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Correspondence to Michail N. Elinson.

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Elinson, M.N., Vereshchagin, A.N., Ryzhkova, Y.E. et al. Direct four-component assembling of arylaldehydes, dimethylbarbituric acid, 4-hydroxycoumarine, and cyclic amines into complex scaffolds with three different heterocyclic rings. Monatsh Chem 152, 1327–1336 (2021). https://doi.org/10.1007/s00706-021-02849-w

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  • DOI: https://doi.org/10.1007/s00706-021-02849-w

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