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.
Notes: NH2NH2 is called “hydrazine”. The imine of hydrazine is called a “hydrazone”.
Examples
Notes: Ethylene glycol is a high boiling alcohol solvent
Mechanism (hydrazone formation)
The reaction begins by 1,2-addition of the nitrogen on the carbonyl carbon (Step 1, arrows A and B). This is followed by transfer of a proton from the nitrogen to the oxygen (Step 2, arrows C and D) and then 1,2-elimination of hydroxide (Step 3, arrows E and F). Finally the hydrogen is removed from the nitrogen in an acid-base reaction (Step 4, arrows G and H).
Notes
Here is an alternative (and probably more correct) mechanism for proton transfer
Water is a byproduct here. Acid can be used to facilitate this reaction. There are other reasonable bases that can be used to remove the proton in step 4.
Mechanism (Wolff-Kishner reaction)
The hydrazone is deprotonated by OH and the negative charge moves to the carbon (Step 1, arrows A, B, C) which is protonated (Step 2, arrows D and E), whereupon the nitrogen is deprotonated again, and nitrogen gas (N2) is lost (Step 3, arrows F, G, and H). This leaves an anion which is then protonated to give the alkane (Step 4, arrows I and J).
Notes: Ethylene glycol is also a reasonable acid to use in the last step.
Potassium (K) is not crucial here, it’s just a spectator ion.
Also note that KOH here is catalytic
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i think it is a very good way of representing this method.i like it
does this reduce alcohols to alkanes too?
no, just ketones and aldehydes
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.
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.
Great! Thank you.
And what is a role of ethylene glycol in this reaction?
The site is really great.
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.
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.