8
$\begingroup$

The following is from Organic Chemistry-2 for JEE Advanced by KS Verma:

α- or β-keto acids do not undergo Clemmensen reduction.

My reasoning was that the double bonds are in conjugation which makes them reluctant to participate in such reactions. However, this doesn't seem to be the case with β-keto acids which makes me suspect that my line of reasoning might be incorrect.

What is the reason for this behavior?

$\endgroup$
1
  • 2
    $\begingroup$ Consider possible tautomers of the beta-keto acid $\endgroup$
    – Andrew
    Mar 20 at 15:20
1
+50
$\begingroup$

The likely reason for this is a steric hindrance. The Clemmensen reduction is very vulnerable to hindrance. See the image below: enter image description here

There was also another reaction conducted that had a 67% yield for a gamma keto acid with resonance. See the image below:

enter image description here

Therefore, the main factor that makes α- or β-keto acids not undergoing Clemmensen reduction is likely not because of resonance, but primarily of steric hinderance. But this also may raise another question, why doesn't the carboxylic acid group get reduced? The reason for this is that the carbon in a carboxylic acid is not quite partially positive because OH is an electron-donating group. The mechanism involves a transfer of an electron from zinc to the partially positive carbon atom, which, as mentioned, carboxylic acid doesn't have.

However, even for diketones, the Clemmensen reduction doesn't often yield what one would expect. See the image below:

enter image description here

The reason is because of the mechanism. In the mechanism, radicals are formed on the carbonyl carbon. However, if you have a diradical, they can come together and form a bond if they are close enough. This is just some extra information.

The source I took the images from: https://www.sciencedirect.com/topics/chemistry/clemmensen-reduction#

Extra papers I found that may be helpful: https://d.lib.msu.edu/etd/37284/datastream/OBJ/view https://pubs.acs.org/doi/abs/10.1021/jo01017a512

$\endgroup$
3
  • $\begingroup$ I would agree with your argument for alpha keto acids. However Im skeptical for the beta case. I dont think steric hindrance should create trouble there. What do you say? $\endgroup$
    – newbie105
    Mar 21 at 14:48
  • $\begingroup$ I don't think a definite answer exists for this case @newbie105 because the mechanism of clemmensen reduction is not fully understood yet. $\endgroup$
    – User688539
    Mar 21 at 15:36
  • $\begingroup$ Yes, there is still research into the Clemmensen reduction and I could not find any paper on the reduction of beta-keto acids. It is just that the Clemmensen reduction has shown to be greatly affected by steric effects, as shown in the first image where a methyl group on an alpha carbon prevented the reduction of that ketone. And from my second picture, a gamma keto acid was still reduced with a relatively good yield. So I would say that Beta keto acids likely does not lead to good yields because of steric hindrance. However, there needs to be more research for there to be a definitive answer. $\endgroup$
    – M.L
    Mar 21 at 18:58

Not the answer you're looking for? Browse other questions tagged or ask your own question.