Incorporating morpholine and oxetane into benzimidazolequinone anti-tumor agents: the discovery of 1,4,6,9-tetramethoxyphenazine from hydrogen peroxide and hydroiodic acid-mediated oxidative cyclizations

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    Abstract

    The reactivity of hydrogen peroxide and catalytic hydroiodic acid towards 3,6-dimethoxy-2-(cycloamino)anilines is tunable to give ring-fused benzimidazoles or 1,4,6,9-tetramethoxyphenazine in high yield. Mechanisms via a detected nitroso-intermediate are proposed for oxidative cyclization and the unexpected intermolecular displacement of the oxazine. An aqueous solution of molecular iodine is capable of the same transformations. Oxidative demethylation gave targeted benzimidazolequinones, including without cleavage of the incorporated oxetane.
    Original languageEnglish
    Pages (from-to)9811-9818
    JournalThe Journal of Organic Chemistry
    Volume84
    Issue number15
    Early online date11 Jul 2019
    DOIs
    Publication statusPublished - 2 Aug 2019

    Bibliographical note

    Note: This work was supported by Kingston University and the Irish Research Council.

    Keywords

    • Chemistry

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