Serendipity as a Driving Force in the Synthesis of Isatins Substituted with Electron-Donating Groups

Semen S. Bondarenko; Anatolii M. Fedorchenko; Tetiana V. Druzhenko; Kostiantyn P. Melnykov; Yulian M. Volovenko; Dmytro M. Volochnyuk; Serhiy V. Ryabukhin

doi:10.1055/a-2382-4428

Synthesis, Table of Contents

Synthesis 2024; 56(22): 3431-3442
DOI: 10.1055/a-2382-4428

paper

Serendipity as a Driving Force in the Synthesis of Isatins Substituted with Electron-Donating Groups

Semen S. Bondarenko

^aEnamine Ltd., Winston Churchill Street 78, Kyiv 02094, Ukraine URL: www.enamine.net

^bTaras Shevchenko National University of Kyiv, Volodymyrska Street 64, Kyiv 01601, Ukraine

,

Anatolii M. Fedorchenko

^aEnamine Ltd., Winston Churchill Street 78, Kyiv 02094, Ukraine URL: www.enamine.net

,

Tetiana V. Druzhenko

^aEnamine Ltd., Winston Churchill Street 78, Kyiv 02094, Ukraine URL: www.enamine.net

^bTaras Shevchenko National University of Kyiv, Volodymyrska Street 64, Kyiv 01601, Ukraine

,

Kostiantyn P. Melnykov

^aEnamine Ltd., Winston Churchill Street 78, Kyiv 02094, Ukraine URL: www.enamine.net

^bTaras Shevchenko National University of Kyiv, Volodymyrska Street 64, Kyiv 01601, Ukraine

,

Yulian M. Volovenko

^bTaras Shevchenko National University of Kyiv, Volodymyrska Street 64, Kyiv 01601, Ukraine

,

Dmytro M. Volochnyuk

^aEnamine Ltd., Winston Churchill Street 78, Kyiv 02094, Ukraine URL: www.enamine.net

^bTaras Shevchenko National University of Kyiv, Volodymyrska Street 64, Kyiv 01601, Ukraine

^cInstitute of Organic Chemistry, National Academy of Sciences of Ukraine, Academik Kukhar Street 5, Kyiv 02660, Ukraine

,

Serhiy V. Ryabukhin ∗

^aEnamine Ltd., Winston Churchill Street 78, Kyiv 02094, Ukraine URL: www.enamine.net

^bTaras Shevchenko National University of Kyiv, Volodymyrska Street 64, Kyiv 01601, Ukraine

^cInstitute of Organic Chemistry, National Academy of Sciences of Ukraine, Academik Kukhar Street 5, Kyiv 02660, Ukraine

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Abstract

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Dedicated to the Ukrainian Air Defense Forces who made this publication possible

Abstract

An efficient synthetic procedure for the synthesis of isatins was found after careful analysis of the serendipitous results of the unexpected products obtained by aromatic nucleophilic substitution when it was attempted to introduce 6-fluoroisatins to the classic Pfitzinger reaction. Attentive analysis of these results led to elaborating a methodology for synthesizing electron-enriched isatins, including those with hydroxy-, alkoxy-, alkylthio-, and dialkylamino-substituted aromatic rings. Limitations of the method were established. The reaction conditions were optimized according to the understanding of water’s role. Finally, the classic Pfitzinger reaction procedure was modified to yield the expected 2-substituted 7-fluoroquinoline-4-carboxylic acids.

Key words

EDG-substituted isatins - aromatic nucleophilic substitution - Pfitzinger reaction - water effect - quinolines

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References

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