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Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?
Lukáš Marek1, Jiří Váňa1, Jan Svoboda1
1Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, CZ532 10 Pardubice, Czech Republic.
Beilstein Journal of Organic Chemistry
|June 22, 2023
Summary
Researchers explored reactions of thioamides with bromo-isoquinoline derivatives. Optimal acidity of intermediate thioiminium salts is key for successful Eschenmoser coupling reactions, influencing product distribution.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- Thioamides are versatile nucleophiles in organic synthesis.
- Isoquinoline derivatives are important heterocyclic scaffolds.
- Understanding reaction pathways is crucial for developing new synthetic methodologies.
Purpose of the Study:
- To investigate the reactions of thiobenzamide and thioacetamide with specific bromo-isoquinoline derivatives.
- To identify factors influencing product distribution in these reactions.
- To elucidate the mechanism of the Eschenmoser coupling reaction in this context.
Main Methods:
- Systematic variation of reaction conditions: base, solvent, thiophile, and temperature.
- Analysis of product distribution using spectroscopic techniques.
- Investigation of structure-medium effects on reaction outcomes.
Main Results:
- Identified conditions favoring Eschenmoser coupling, Hantzsch thiazole synthesis, and elimination to nitriles.
- Determined that the acidity balance of nitrogen and carbon atoms in α-thioiminium salts is critical for Eschenmoser coupling.
- Established structure/medium dependencies for product selectivity.
Conclusions:
- The Eschenmoser coupling reaction's success is contingent upon achieving an optimal acidity balance in intermediate α-thioiminium salts.
- Reaction conditions and substrate structure significantly dictate the formation of different products.
- This study provides insights into controlling synthetic pathways for complex heterocyclic compounds.
Keywords:
Eschenmoser coupling reactionHantzsch thiazole synthesisisoquinolin-4-onesprimary thioamidesstructure–reactivity relationshipsMore Related Videos
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