[Chump0]

Hello everyone,

I am stuck on a question (again) and would like some help, as always I have done my research and come to the point where I got stuck. The question goes as followed:

A simple ketone (e.g. Propanone) is readily reduced by borohydride, e.g. NaBH4, but an ester (e.g. methyl methanoate) is not. Show the mechanism of the reactions and based on this offer an explanation for the difference in reactivity.

The mechanism for the Ketone reduction:


Or

I think it’s the second one because in the question it’s not mentioned that ethanol is present as a reagent.

As for what I know is that NaBH4 will reduce many organic carbonyls, which include ketones and aldehydes. However it is not a strong enough reducing agent to reduce esters. For that usually LiAlH4 (lithium aluminium hydride) is used. Therefore I am not sure what the mechanism of the ester is with BH4.

So I thought let’s look at the mechanism of ester with LiAlH4, which goes as followed:


What I see is that there are two reduction processes to receive the final product.  While the reduction of an ketone only has one. Does this explain the difference in reactivity? So why isn’t it possible, or is it less reactive, to use NaBH4 to reduce an ester?

[Doc Oc]

What you want to consider is the reactivity of the starting materials.  Remember in the discussion of aldehyde vs ketone reactivity?  This is a similar situation.  So what's the main difference between the ketone and ester?  The oxygen of the ester.  Again, remember what was said about ketones vs aldehydes, the electron donating properties of the alkyl group stabilize the carbonyl carbon and make the ketone less reactive than the aldehyde.  Now look at an ester, it's actually got lone pair electrons.  The double bond delocalizes between the two oxygens, and that makes the carbonyl very unreactive (ie; the starting material is very stable).  So look at the first part of the mechanism you drew with LiAlH4.  You're converting the ester into an aldehyde.  Something that's very stable becomes something less stable.  That takes a lot of energy to do, and NaBH4 is a weak hydride source.

[Chump0]

What you want to consider is the reactivity of the starting materials.  Remember in the discussion of aldehyde vs ketone reactivity?  This is a similar situation.  So what's the main difference between the ketone and ester?  The oxygen of the ester.  Again, remember what was said about ketones vs aldehydes, the electron donating properties of the alkyl group stabilize the carbonyl carbon and make the ketone less reactive than the aldehyde.  Now look at an ester, it's actually got lone pair electrons.  The double bond delocalizes between the two oxygens, and that makes the carbonyl very unreactive (ie; the starting material is very stable).  So look at the first part of the mechanism you drew with LiAlH4.  You're converting the ester into an aldehyde.  Something that's very stable becomes something less stable.  That takes a lot of energy to do, and NaBH4 is a weak hydride source.

Ok, but why is LiAlH4 more reactive? I know it's not part of the question, but it's good to understand that. And would the mechanism of the ester with NaBH4 be the same as with LiAlH4?

[Doc Oc]

The explanations vary (someone else feel free to chime in), but basically Al is less electronegative that B so the hydride is more easily donated, if that makes sense.  Similarly, the lone pair of nitrogen is much more nucleophilic than a lone pair of oxygen because nitrogen is less electronegative.

[movies]

There is another factor to consider: Can you explain why NaBH₄ does not reduce esters, but LiBH₄ will achieve this reduction?  As an added hint, adding a chelating ether like 12-crown-4 substantially hinders carbonyl reduction with LiAlH₄.  Why do you think that is?

[Chump0]

There is another factor to consider: Can you explain why NaBH₄ does not reduce esters, but LiBH₄ will achieve this reduction?  As an added hint, adding a chelating ether like 12-crown-4 substantially hinders carbonyl reduction with LiAlH₄.  Why do you think that is?

Is this question meant for me? I'm a 1st year undergraduate.. The only thing that shoots in my mind right now is polydentate ligands for the 12-crown-4

[movies]

Sure, it is meant for you.  I am just giving you some experimental observations and I want to see if you can figure out what I am getting at.

So to follow your first inclination, what is the crown ether ligating to and how do you think that would affect reactivity?

[Chump0]

Sure, it is meant for you.  I am just giving you some experimental observations and I want to see if you can figure out what I am getting at.

So to follow your first inclination, what is the crown ether ligating to and how do you think that would affect reactivity?

I'm not sure, but a wild guess maybe Lithium. The fact is that 12-crown-4 is a Lithium Ionophore.

[movies]

Right!  So if 12-crown-4 takes the lithium out of the picture, and you observe that the reduction reaction is hindered, what do you think that tells you about the role of the Li ion in the reaction?

[Chump0]

Right!  So if 12-crown-4 takes the lithium out of the picture, and you observe that the reduction reaction is hindered, what do you think that tells you about the role of the Li ion in the reaction?

Lithium is an electrophile and it is needed in the reaction to stabilize charges. If it's not present the reaction will not occur.
Is that correct....?

[movies]

Almost – I think you have the right idea, but I would say that it is about the Lewis acidity of the cations.  Li binds pretty tightly to carbonyls, while Na or K, which have a more diffuse charge, will not bind as strongly and therefore the carbonyl will not be activated toward attack by an H^–