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Study of the cyclization of N-hydroxy- and N-methoxy-N-(2-oxoalkyl)amides

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Abstract

Efficient methods for the preparation of 1-hydroxy-1,5-dihydro-2H-pyrrol-2-ones and 1-hydroxy-1,6-dihydropyridine-2,5-diones on the basis of N-hydroxy-N-(2-oxoalkyl)amides are reported. The reaction of N-hydroxy-N-(2-oxoalkyl)amides in the presence of 3 eq. of t-BuOK was found to lead to 1-hydroxy-1,5-dihydro-2H-pyrrol-2-ones. A decrease in the base content to 1.5 eq. or less leads to increase in 1-hydroxy-3-phenyl-1,6-dihydropyridine-2,5-dione content in the reaction products due to oxidation of the starting compounds by atmospheric oxygen and their subsequent transformation. Using the examples of chloroacetohydroxamic acids, we demonstrated the possibility of nucleophilic substitution and subsequent cyclization to 1-hydroxy-1,5-dihydro-2H-pyrrol-2-one derivatives. To study the possible mechanism of radical cyclization of N-hydroxy-N-(2-oxoalkyl) amides to 1,6-dihydropyridine-2,5-dione, the supposed reactive center (hydroxamic group) was blocked. It was shown that the protection of the N-hydroxy group by methylation of N-hydroxy-N-(2-methyl-3-oxobutan-2-yl)-2-phenylacetamide to N-methoxy-2-phenylacetamide in its further reaction with 0.5 eq. of t-BuOK results in the formation of intermediate 4-hydroxy-1-methoxy-3-phenylpyrrolidin-2-one. The desired 1-methoxy-1,5-dihydro-2H-pyrrol-2-one was obtained when using an excess of t-BuOK. Formation of N-methoxy-1,6-dihydropyridine-2,5-diones as a result of radical oxidative cyclization described earlier was not detected.

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Acknowledgement

Authors would like to acknowledge the Multi-Access Chemical Service Center SB RAS for spectral and analytical measurements and Research Resource Center "Natural Resource Management and Physico-Chemical Research" (University of Tyumen) with the financial support of the Ministry of Science and Higher Education of the Russian Federation (contract no. 05.594.21.0019, unique identification number RFMEFI59420X0019).

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Correspondence to Ivan V. Kulakov.

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Kulakov, I.V., Palamarchuk, I.V., Nikolaenkova, E.B. et al. Study of the cyclization of N-hydroxy- and N-methoxy-N-(2-oxoalkyl)amides. Chem. Pap. 75, 4517–4525 (2021). https://doi.org/10.1007/s11696-021-01673-0

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  • DOI: https://doi.org/10.1007/s11696-021-01673-0

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