Practical Synthesis of N-Anilinylphenothiazines Using a Cyclic Hypervalent Iodine Coupling Reagent

Kana Yanase; Koji Morimoto; Toshifumi Dohi; Yasuyuki Kita

doi:10.1055/a-2383-0958

Synthesis, Table of Contents

Synthesis 2025; 57(04): 748-753
DOI: 10.1055/a-2383-0958

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Practical Synthesis of N-Anilinylphenothiazines Using a Cyclic Hypervalent Iodine Coupling Reagent

Kana Yanase

^aCollege of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu Shiga, 525-8577, Japan

,

Koji Morimoto ∗

^aCollege of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu Shiga, 525-8577, Japan

^bResearch Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan

,

Toshifumi Dohi

^aCollege of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu Shiga, 525-8577, Japan

^bResearch Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan

,

Yasuyuki Kita ∗

^bResearch Organization of Science and Technology, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan

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Abstract

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Abstract

An improved protocol for the synthesis of N-anilinylphenothiazines based on the coupling reaction of anilines with phenothiazines using cyclic iodine(III) reagent is presented. In the improved method, the product can be isolated and purified without using column chromatography, and the cyclic hypervalent iodine reagent can be quantitatively recovered by aliquot manipulation. The workup procedure presented here is simpler compared to previously reported ones, facilitating large-scale synthesis. The para-selective phenothiazination of nitrogen-containing heterocycles such as hydroquinoline, which is important in pharmacology, was also successfully performed.

Key words

hypervalent iodine(III) reagent - aryl C–H amination - solid–liquid separation - coupling reaction - N-anilinylphenothiazines

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References

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