What Is Feist-BÉNary Reaction?
The Feist-Bénary reaction represents a classic method for producing substituted furans which was first independently described by Franz Feist and Erich Bénary. The Feist-Bénary reaction stands as an essential method in heterocyclic chemistry because it enables the versatile synthesis of furan rings which are common structural components of natural products and medicinal compounds as well as functional materials. In details, under basic conditions the condensation of α-haloketones with β-dicarbonyl compounds such as β-ketoesters or β-diketones produces 2,5-disubstituted furans.
- Reagents: Bases: pyridine, triethylamine, alkoxides (e.g., naoet); Acid (for dehydration): hcl or molecular sieves; Solvents: ethanol, THF, DMF (polar aprotic or alcoholic solvents).
- Reactants: α-Haloketones; β-Dicarbonyl compounds.
- Products: 2,5-Disubstituted furans.
- Reaction type: Condensation-cyclization.
- Related reactions: Paal-Knorr furan synthesis, Knorr Pyrrole synthesis.
- Experimental Tips:
a) Chloroacetones and bromoketones are better choices because iodides can cause unwanted side reactions. β-Ketoesters (e.g., ethyl acetoacetate) or β-diketones (e.g., acetylacetone) are ideal.
b) Mild bases (e.g., pyridine, triethylamine) are optimal. Strong bases (e.g., NaOH) may hydrolyze sensitive substrates.
c) Temperature: Typically conducted at 50–100°C; prolonged heating may induce decomposition.
d) The reaction exhibits regioselectivity, favoring 2,5-disubstitution due to electronic and steric effects during cyclization.
e) Stereoelectronic factors influence the efficiency of ring closure; bulky substituents may hinder cyclization.
Fig 1. Feist-Bénary reaction and its mechanism. [1]
Mechanism of Feist-Bénary Reaction
The Feist-Bénary reaction proceeds via a stepwise nucleophilic substitution and cyclization pathway:
- Deprotonation and Nucleophilic Attack: The base causes deprotonation of the β-dicarbonyl compound which forms an enolate. The enolate reacts with the electrophilic α-carbon of the α-haloketone resulting in the removal of the halide ion (X⁻).
- Cyclization: The intermediate alkoxide undergoes intramolecular cyclization, forming the furan ring.
- Dehydration: A final dehydration step (often spontaneous or acid-catalyzed) yields the aromatic furan derivative.
"Interrupted" Feist-Bénary (IFB) Reaction
If the reaction is interrupted at the β'-hydroxydihydrofuran stage, it is called an "interrupted" Feist-Bénary (IFB) reaction. The first case of catalytic enantioselective IFB was reported. The asymmetric induction effect of diphenylpyrimidinyl-substituted quinidine derivatives was the best. The reaction can reach 98:2 diastereoselectivity and 95%ee. The use of a "proton sponge" to absorb the hydrogen bromide generated by the reaction can avoid the formation of FB products. In addition, the IFB reaction has been used to construct the core structure of zaragozic acid.
Fig 2. Schematic diagram of IFB reaction. [2]
Application Examples of Feist-Bénary Reaction
- Example 1: Somayeh Ahadi et al. developed an organocatalytically modified Feist-Bénary reaction for cyclic dicarbonyl compounds, isatin, and cyclic α-bromodicarbonyl compounds. The method afforded bispiroindole-fused dihydrofurans containing two ortho-spiro ring centers. [3]
- Example 2: The basic ionic liquid 1-butyl-3-methylimidazolium hydroxide promoted an interrupted Feist-Bénary reaction at room temperature in an organic solvent-free condition to generate various substituted hydroxydihydrofurans. The ionic liquid 1-methyl-3-pentylimidazolium bromide was used to convert hydroxydihydrofurans to furans (Feist-Bénary products) at 70-75 °C. The reaction was very clean, high yielding, and highly stereoselective. [4]
Fig 3. Synthetic examples via Feist-Bénary reaction.
Related Products
References
- Jie Jack Li. Name Reactions-A Collection of Detailed Mechanisms and Synthetic Applications, Fourth Edition, 2014, 243-244.
- Calter, Michael A. et al, Journal of the American Chemical Society, 2005, 127(42), 14566-14567.
- Ahadi, Somayeh, et al. Chemistry–A European Journal, 2013, 19(37), 12553-12559.
- Ranu, Brindaban C., et al. Tetrahedron Letters, 2008, 49(31), 4613-4617.
