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Electrophilic ipso-substitution in uracil derivatives

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Abstract

Treatment of 5-iodo-1,3,6-trimethyluracil with 50% H2SO4 gives 1,3,6-trimethyluracil; with 5-bromo-1,3,6-trimethyluracil, a mixture of 1,3,6-trimethyluracil and 6-bromomethyl-1,3-dimethyluracil is obtained. 5-Chloro-1,3,6-trimethyluracil remains inert under these conditions. According to the DFT modeling of the reactions of 5-halo-1,3,6-trimethyluracils, a nucleophilic agent can abstract either Hal+ or the methyl proton from the carbocation formed by protonation of the starting halouracil at position 5, which accounts for the formation of two products from the 5-bromo derivative. Under similar conditions, 6-methyluracil dibromohydrin yields N-bromo-5-bromo-6-hydroxymethyluracil. Bromination or chlorination of 5-hydroxymethyl- or 5-formyl-6-methyluracils follows the ipso-substitution scheme leading to 6-methyluracil 5-halo- and 5,5-dihalohydrins.

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Authors and Affiliations

  1. Institute of Organic Chemistry, Ufa Scientific Center of the Russian Academy of Sciences, 71 prosp. Oktyabrya, 450054, Ufa, Russian Federation

    I. B. Chernikova, S. L. Khursan, L. V. Spirikhin & M. S. Yunusov

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  1. I. B. Chernikova
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  2. S. L. Khursan
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  3. L. V. Spirikhin
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  4. M. S. Yunusov
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Correspondence to M. S. Yunusov.

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Dedicated to Academician of the Russian Academy of Sciences M. P. Egorov on the occasion of his 60th birthday.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2445–2453, Novemer, 2013.

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Chernikova, I.B., Khursan, S.L., Spirikhin, L.V. et al. Electrophilic ipso-substitution in uracil derivatives. Russ Chem Bull 62, 2445–2453 (2013). https://doi.org/10.1007/s11172-013-0354-0

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  • DOI: https://doi.org/10.1007/s11172-013-0354-0

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