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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: pfnm on March 28, 2011, 09:49:06 AM

Title: Selectively reducing aldehyde to alkane
Post by: pfnm on March 28, 2011, 09:49:06 AM

Hi,

I've got a tutorial question that asks,
"Describe two methods for the following conversion:  
4-formylcyclohexanone -> 4-methylcyclohexanone"

I thought:

- Since the aldehyde is more reactive than the carbonyl, perhaps protect the aldehyde with ethane-1,2-thiol, then protect the ketone with 1,2-ethanediol, then reduce the protected aldehyde (the diothiolane) to CH3 by H2 over Raney Nickel...then deprotect the ketone with acid.

Can I selectively protect the aldehyde, or would both the ketone and aldehyde be protected by the diothiol?

Is the method I have given reasonable?

Here is the reaction scheme of the first method:

(https://www.chemicalforums.com/proxy.php?request=http%3A%2F%2Fimg225.imageshack.us%2Fimg225%2F2567%2Freactionschemeselective.jpg&hash=38414b3425cc8a630f9a7adc80dfa7022f4f107d) (http://img225.imageshack.us/i/reactionschemeselective.jpg/)

I've had some trouble thinking of a second method. This article http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv6p0289 (http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv6p0289) says, Clemmenson reduction "is not particularly effective, however, with alicyclic and aliphatic ketones".

So would Zn(Hg) in HCl reduce the aldehyde to the alkane without affecting the cyclic ketone?

Or would the Wolff-Kishner reduction?

Thanks alot

Title: Re: Selectively reducing aldehyde to alkane
Post by: pfnm on March 30, 2011, 04:44:24 AM

I've altered this now, it seems more reasonable to go:

1. React the molecule with diothiol in the first step
2. Reduce the protected aldehyde to CH3 with H2 and Raney Nickel

Not even to bother with protecting the ketone.

And the second method would be Clemmenson because of the higher reactivity of the aldehyde.

Title: Re: Selectively reducing aldehyde to alkane
Post by: james_a on March 30, 2011, 09:55:09 AM

One small detail - you'll want to add an acid to put in the thioketal and acetal.

The Raney Nickel, Clemmensen or Wolff-Kishner methods should all work. One last method would be to reduce the aldehyde to an alcohol, turn into the tosylate, and then reduce with LiAlH4.

Title: Re: Selectively reducing aldehyde to alkane
Post by: pfnm on March 30, 2011, 02:54:20 PM

Thanks James - I've decided to not protect te ketone, but protect the aldehyde and then reduce it with Raney Ni, because I've learned that H2/Raney Ni won't reduce a ketone. But using the acid to catalyse the thioacetal I didn't include, so thanks for that.

So Clemmenson and Wolff-Kishner will both selectively reduce an aldehyde to an alkane, despite a ketone being present? Is this because the aldehyde's carbonyl C is more reactive than the ketones?

On the last method:

How would you reduce the aldehyde to an alcohol without reducing the ketone? Following the same pattern here, presumably NaBH4 or LiAlH4 will reduce an aldehyde but not a ketone, or will reduce an aldehyde much faster than a ketone?

Cheers

Title: Re: Selectively reducing aldehyde to alkane
Post by: orgopete on March 30, 2011, 10:15:23 PM

You cannot heat an unprotected ketone is KOH without suffering the consequences.

Title: Re: Selectively reducing aldehyde to alkane
Post by: nox on March 30, 2011, 11:49:42 PM

Quote from: james_a on March 30, 2011, 09:55:09 AM

One last method would be to reduce the aldehyde to an alcohol, turn into the tosylate, and then reduce with LiAlH4.

Wouldn't work unless you did an extra oxidation step at the end because:
- you'd reduce the ketone along with the tosylate
- products resulting from E2 elimination as well tosyl cleavage will be significant; Super Hydride is more suited for this reduction, but of course it will completely destroy the ketone

Another method along the same lines but avoids the selectivity issue
1. Luche reduction of ketone while leaving aldehyde untouched
2. Wolff-Kishner on the aldehyde
3. Oxidize the alcohol back to the ketone

Title: Re: Selectively reducing aldehyde to alkane
Post by: Dan on March 31, 2011, 07:04:24 PM

For giggles:

1. Pinnick oxidation
2. Arndt-Eistert
3. Barton decarboxylation