The Gewald reaction refers to the condensation of ketones or aldehydes with α-cyanoesters in the presence of elemental sulfur to yield polysubstituted 2-aminothiophene derivatives. Discovered and named after the German chemist Karl Gewald, it is a significant method for constructing polysubstituted 2-aminothiophenes.
This reaction enables the efficient one-step synthesis of 2-aminothiophenes with diverse substitution patterns. 2-Aminothiophenes are widely found in pharmaceuticals, agrochemicals, and functional materials due to their notable biological activities and synthetic utility. The reaction features mild conditions, broad substrate compatibility, and high structural diversity, making it a widely applied strategy in heterocyclic chemistry.
- Reagent: Sulfur, base
- Reactants: Ketone or aldehyde, α-cyanoester
- Product: 2-Aminothiophene
- Reaction Type: Condensation
Lab Tips
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Finely powdered and dry elemental sulfur (S₈) is recommended for better dispersion.
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Ketones (e.g., acetophenone) are generally more stable and easier to handle than aldehydes, often giving higher yields with fewer side reactions.
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Electronic effects influence reactivity and yield; α-cyanoesters with electron-withdrawing groups perform better. Ethyl cyanoacetate is commonly used.
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Common solvents include ethanol, methanol, isopropanol, THF, and DMF.
Mechanism
Original Paper
Top Citations
Related Reactions
Related Products
- Acetophenone, 98% (CAS 98-86-2)
- Benzaldehyde, 98% (CAS 100-52-7)
- Ethyl cyanoacetate, 99% (CAS 105-56-6)
- Morpholine, 99% (CAS 110-91-8)
- Triethylamine, 99% (CAS 121-44-8)
- Nickel(II) acetylacetonate, 96% (CAS 3264-82-2)
- Ethanol, 99.5% (CAS 64-17-5)
- Tetrahydrofuran, 99.5% (CAS 109-99-9)
艳 李
