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

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

Publication History

Received: 30 March 2024

Accepted after revision: 07 August 2024

Accepted Manuscript online:
07 August 2024

Article published online:
26 September 2024

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