Master Organic Chemistry Reaction Guide

Wolff Kishner Reaction – conversion of ketones/aldehydes to alkanes

Description: The Wolff-Kishner is a reaction for converting carbonyls (such as ketones and aldehydes) into alkanes.
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Further Reading

  1. Chemischen Institut der Universität Jena: Methode zum Ersatz des Sauerstoffatoms der Ketone und Aldehyde durch Wasserstoff. [Erste Abhandlung.]
    Wolff, L. Lieb. Ann. Chem. 1912 394 (1), 86
    DOI: 10.1002/jlac.19123940107
    The original paper by Ludwig Wolff on the reduction of aldehydes and ketones with hydrazine.
  2. The Wolff-Kishner Reaction of Hydrazones
    Szmant, H. H.; Harmuth, C. H. Am. Chem. Soc.1964, 86 (14), 2909
    DOI: 10.1021/ja01068a028
    A very nice Physical Organic study on the decomposition of hydrazones, involving Hammett plots (a classic tool in Physical Organic Chemistry), determining the relationship between the electron density of the carbonyl carbon and the mechanism.
  3. Reduction of Steroid Ketones and other Carbonyl Compounds by Modified Wolff-Kishner Method
    Huang-Minlon Am. Chem. Soc.1949, 71 (10), 3301
    DOI: 10.1021/ja01178a008
    A one-pot modification for the Wolff-Kishner reaction that involves distilling off the excess water and hydrazine before heating the hydrazine. This results improved yields and significantly shorter reaction times.
  4. REDUCTION OF KETONES BY USE OF THE TOSYLHYDRAZONE DERIVATIVES: ANDROSTAN-17 β-OL
    Caglioti Org. Synth. 1972,52, 122
    DOI: 10.15227/orgsyn.052.0122
    Due to the harsh conditions involved in the standard Wolff-Kishner reduction, a number of variations have been developed with milder conditions more amenable for organic synthesis. The use of tosylhydrazide instead of hydrazine allows much gentler reaction conditions – the tosylhydrazone can be reduced with NaBH4 in refluxing methanol (68 °C vs. 200 °C!).

Comments

Comment section

28 thoughts on “Wolff Kishner Reaction – conversion of ketones/aldehydes to alkanes

  1. Yes, but for a Wolff-Kishner reaction that does not imply the use of a strong base (i.e. hydroxide), would water be able to deprotonate that amine in step one to give the N-N double bond? I ask because in the synthesis of the drug Amiodarone, they do not specify basic conditions. Rather, they allude that they use hydrazine hydrate only.

    1. Water isn’t basic enough to deprotonate. The pKa of the hydrazone hydrogens is about 22, whereas that of H3O(+) is -2. The equilibrium would be 24 orders of magnitude in opposition to the desired reaction.
      I found a publicly available reference to the synthesis here: : http://bit.ly/J2TCRA
      Although they don’t specifiy basic conditions in the reaction scheme, it’s not uncommon to leave out details such as base, solvent and heat. The Wolff Kishner is generally a very unfavorable reaction as it is – it requires heating at 180 degrees C or more – so I am nearly 100% certain that they merely omitted writing base in the scheme here.

    1. Ethylene glycol serves as a solvent here. It has a very high boiling point (~200 degrees C); the fact that the reaction needs to be heated so much is why this solven tis used.

      1. Good question. One reason I’ve read is the greater strength of the C-O (pi) bond as opposed to the C-C (pi) bond. I’m not sure this is the whole picture but it is at least a component.

    1. I suppose you could use potassium carbonate but it will not deprotonate ethylene glycol irreversibly; at 200 degrees C, however, the reaction should still proceed well.

  2. In the Wolff kishner we first convert ketone or aldehyde to hydrazone. Hydrazone formation is done in acid medium. Now if we have a carbonyl compound with an Acetal and Ketone, will the acetal be also reduced in Wolff kishner due to equilibrium being established in during hydrazone formation (acid medium form ketone and ketone formed along with original one will react to form two Hydrazone sites, which can be reduced in proceeding step with strong base. Couldn’t find any answer to this.

    Thanks in advance!

      1. It really makes sense, low H2O – complete acetal side of equilibrium. Thanks from saving me from a headache. And great site.

    1. Probably because the acid and base need to be able to reach each other, which is generally not possible unless they are 5 or 6 atoms apart. So I would use an external base / external acid to perform the proton transfer.
      In fairness that is probably a better way to do it, but it takes forever to write out. My approach is a bit of a short cut.

  3. Sir, what will be the product if we imply wolf kishner reaction on carboxylic acids with ketone group like
    CH3-CO-COOH.
    Does it will just reduce ketone group only or will react will acid group also?
    Please reply!

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