The Wolff-Kishner reduction uses hydrazine, a base, and a high-boiling solvent to convert an aldehyde or ketone to an alkane. The hydrazine first attacks the ketone or aldehyde, releasing water to form a hydrazone intermediate. Subsequent proton transfer steps result in the release of nitrogen gas and the formation of a carbanion, which abstracts a proton from water to produce the final alkane product.
- Reagents: Hydrazine, Base (Sodium Metal, NaOEt, etc.), High-Boiling Solvent (Ethylene Glycol, Triethylene Glycol, etc.)
- Reactant: Aldehyde or Ketone
- Product: Alkane
- Type of Reaction: Nucleophilic Addition of Hydrazine
- Bond Formation: C-C
Lab Tips
- The original procedure involves refluxing the carbonyl compound, hydrazine, and excess base in a high-boiling solvent. Water generated during the formation of the hydrazone lowers the temperature, resulting in long reaction times (50 – 100 hours) and the need to use an excess of reagents and solvent. [1]
- Reaction times can be shortened to about 3-6 hours if water and excess hydrazine are removed via distillation (once the hydrazone is formed in situ), so that the reaction temperature can rise to about 200°C (called the Huang-Minlon modification). This modification increases yields and allows the use of hydrazine hydrate along with water-soluble bases (KOH or NaOH). [1,2]
- Sterically hindered carbonyl compounds require higher reaction temperatures (Barton modification). [3,4]
- Esters, lactones, amides, and lactams are hydrolyzed under the reaction conditions. [1][1]
2. Huang, M. Simple modification of the Wolff-Kishner reaction. J. Am. Chem. Soc. 1946, 68, 2487-2488.
3. Barton et al. A Wolff-Kishner reduction procedure for sterically hindered carbonyl groups. J. Chem. Soc., Abstracts 1955, 2056.
4. Nagata, W., Itazaki, H. Simplified modification of Wolff-Kishner reduction for hindered or masked carbonyl groups. Chem. Ind. 1964, 1194-1195.
Mechanism
Top Citations
Original Paper
Related Reactions
- Clemmensen Reduction
- Corey-Bakshi-Shibata Reduction
