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

Darren Conboy; Styliana I. Mirallai; Austin Craig; Patrick McArdle; Ali A. Al-Kinani; Stephen Barton; Fawaz Aldabbagh

doi:10.1021/acs.joc.9b01427

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

Darren Conboy
, Styliana I. Mirallai
, Austin Craig
, Patrick McArdle
, Ali A. Al-Kinani
, Stephen Barton
, Fawaz Aldabbagh

Kingston University
University of Galway

Research output: Contribution to journal › Article › peer-review

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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 language	English
Pages (from-to)	9811-9818
Journal	The Journal of Organic Chemistry
Volume	84
Issue number	15
Early online date	11 Jul 2019
DOIs	https://doi.org/10.1021/acs.joc.9b01427
Publication status	Published - 2 Aug 2019

Bibliographical note

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

Keywords

Chemistry

Access to Document

10.1021/acs.joc.9b01427

Al-Kinani-A-A-43693-AAM-1Accepted author manuscript, 1.2 MBLicence: Unspecified

CCDC 1917886: Experimental Crystal Structure Determination
Conboy, Darren (Creator), Mirallai, Styliana I. (Creator), Craig, Austin (Creator), McArdle, Patrick (Creator), Al-Kinani, Ali A. (Creator), Barton, Stephen (Creator) & Aldabbagh, Fawaz (Creator), Cambridge Crystallographic Data Centre, 2019
DOI: 10.5517/ccdc.csd.cc22cq9h
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Cite this

Conboy, D., Mirallai, S. I., Craig, A., McArdle, P., Al-Kinani, A. A., Barton, S., & Aldabbagh, F. (2019). 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. The Journal of Organic Chemistry, 84(15), 9811-9818. https://doi.org/10.1021/acs.joc.9b01427

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title = "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",

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.",

keywords = "Chemistry",

author = "Darren Conboy and Mirallai, \{Styliana I.\} and Austin Craig and Patrick McArdle and Al-Kinani, \{Ali A.\} and Stephen Barton and Fawaz Aldabbagh",

note = "Note: This work was supported by Kingston University and the Irish Research Council.",

year = "2019",

month = aug,

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doi = "10.1021/acs.joc.9b01427",

language = "English",

volume = "84",

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Conboy, D, Mirallai, SI, Craig, A, McArdle, P, Al-Kinani, AA , Barton, S & Aldabbagh, F 2019, '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', The Journal of Organic Chemistry, vol. 84, no. 15, pp. 9811-9818. https://doi.org/10.1021/acs.joc.9b01427

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. / Conboy, Darren; Mirallai, Styliana I.; Craig, Austin et al.
In: The Journal of Organic Chemistry, Vol. 84, No. 15, 02.08.2019, p. 9811-9818.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Incorporating morpholine and oxetane into benzimidazolequinone anti-tumor agents

T2 - the discovery of 1,4,6,9-tetramethoxyphenazine from hydrogen peroxide and hydroiodic acid-mediated oxidative cyclizations

AU - Conboy, Darren

AU - Mirallai, Styliana I.

AU - Craig, Austin

AU - McArdle, Patrick

AU - Al-Kinani, Ali A.

AU - Barton, Stephen

AU - Aldabbagh, Fawaz

N1 - Note: This work was supported by Kingston University and the Irish Research Council.

PY - 2019/8/2

Y1 - 2019/8/2

N2 - 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.

AB - 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.

KW - Chemistry

U2 - 10.1021/acs.joc.9b01427

DO - 10.1021/acs.joc.9b01427

M3 - Article

SN - 0022-3263

VL - 84

SP - 9811

EP - 9818

JO - The Journal of Organic Chemistry

JF - The Journal of Organic Chemistry

IS - 15

ER -

Conboy D, Mirallai SI, Craig A, McArdle P, Al-Kinani AA , Barton S et al. 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. The Journal of Organic Chemistry. 2019 Aug 2;84(15):9811-9818. Epub 2019 Jul 11. doi: 10.1021/acs.joc.9b01427

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

Abstract

Bibliographical note

Keywords

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Datasets

CCDC 1917886: Experimental Crystal Structure Determination

Cite this