Wolff-Kishner Reduction

In 1911, Nikolai Kishner added a hydrazone dropwise to a mixture of hot potassium hydroxide and a platinized porous plate, and the corresponding hydrocarbon was formed. A year later, Ludwig Wolff demonstrated that heating an ethanolic solution of semicarbazones and hydrazones in a sealed tube at approximately 180°C in the presence of sodium ethoxide gave the same result. The deoxygenation of aldehydes and ketones to their corresponding hydrocarbons is now called the Wolff-Kishner reduction.

Since the original experiments, the procedure has undergone substantial modifications to allow the use of milder reaction conditions and to expand the number of substrates, as well as to increase yields. For many years, the standard methodology involved mixing the carbonyl compound with neat hydrazine in a high-boiling solvent such as ethylene glycol in the presence of excess base such as sodium ethoxide. However, the reaction often required refluxing for several days because of the temperature-lowering effects of the water produced as a by-product of hydrazine formation.

The Huang-Minion modification involved removing the water and excess hydrazine via distillation, allowing the reaction temperature to increase once the hydrazine formation was complete. This dramatically shortened the reaction time to just a few hours and allowed the use of the less expensive reagent hydrazine hydrate, along with water-soluble bases such as sodium hydroxide.

In another modified procedure, known as the Caglioti reaction, tosylhydrazones are used with hydride reagents to obtain the corresponding alkynes.

The total synthesis of dysidiolide, the first compound found to be a natural inhibitor of protein phosphatase cdc25A, which is essential for cell proliferation, utilized the Wolff-Kishner reduction in the production of an advanced bicyclic intermediate.