Hemiacetal/Acetal Formation

[bharat008]

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During addition of alcohol to ketone in presence of acid, why doesn't KETONE act as nucleophile. I just saw the mechanism online and it shows that Ketone acts as a electrophile.

Here is the Link::

I know ketone is a electrophile but in presence of acid shouldn't it act as Nucleophile....😕

 

[dantemac]

The carbon of the C=O bond is electropositive because the =O domain sucks away all the electrons.

The attacking alcohol. -OH, is nucleophilic because it has two lone pairs (electron rich) which want to attack the electropositive carbon of the carbonyl.

 

[bharat008]

The carbon of the C=O bond is electropositive because the =O domain sucks away all the electrons.

The attacking alcohol. -OH, is nucleophilic because it has two lone pairs (electron rich) which want to attack the electropositive carbon of the carbonyl.

Yup i know that. I was just confused why not as nucleophile since the rxn is in presence of ACID. It could act as ENOL... I tried to repeat the mechanism of this rxn if it was acting as ENOL and i can get the same answer. Try it.
😕😕

By the way, i know that in this rxn its acting as electrophile but was just little confused abt why wouldn't it act as nucleophile in presence of acid by converting itself to ENOL form...

 

[chance8]

On the example, the acid is just an H+; not H3O+.

To form an enol, the ketone takes the H+ from the acid, then H2O takes an H+ from the ketone, forming the enol.

How did you get the enol from the R2O + H+?

Yup i know that. I was just confused why not as nucleophile since the rxn is in presence of ACID. It could act as ENOL... I tried to repeat the mechanism of this rxn if it was acting as ENOL and i can get the same answer. Try it.
😕😕

By the way, i know that in this rxn its acting as electrophile but was just little confused abt why wouldn't it act as nucleophile in presence of acid by converting itself to ENOL form...

 

[FROGGBUSTER]

I haven't reviewed my orgo yet but here's a guess:

The pka of a ketone is 20, while the pka of H2O is 15.7 & the pka of methanol is 15.

If the mechanism is like the one you're asking about (tautomerization to the enol form), there has to be a deprotonation at the second step. The species with the best chance of doing that de-protonation is H2O, but its pka is still considerably less than 20 (15.7). This means this step will be very slow.

You can compare that to the other mechanism's second step, where CH3OH is attacking the charged ketone. I believe this will be considerably faster, and so the reaction will go this direction.

Let me know if that makes sense.

 

[bharat008]

I haven't reviewed my orgo yet but here's a guess:

The pka of a ketone is 20, while the pka of H2O is 15.7 & the pka of methanol is 15.

If the mechanism is like the one you're asking about (tautomerization to the enol form), there has to be a deprotonation at the second step. The species with the best chance of doing that de-protonation is H2O, but its pka is still considerably less than 20 (15.7). This means this step will be very slow.

You can compare that to the other mechanism's second step, where CH3OH is attacking the charged ketone. I believe this will be considerably faster, and so the reaction will go this direction.

Let me know if that makes sense.

In your second paragraph, you mention that H20 causes deprotonation but that's not the case. Once you have hemiacetal formed from enol form, in the presence of H+; the OH on hemiacetal would be protonated and leave as a weak base. This will make the Carbon positive, then second ROH comes in and attacks forming ACETAL..

 

[FROGGBUSTER]

I'm not too familiar with the terms you're using lol 😳, but I think we're talking about different steps in the mechanism?

I drew something out and took a picture of it.


Up top (1) is the beginning of the mechanism that the link you provided shows, and down below (2) is the beginning of the mechanism that you think can occur as well.

I think the nucleophilic attack of CH3OH on the ketone happens much more readily than de-protonation of the proton by the H2O (due to the large pka differences between the ketone and H2O), and this is a step that you would have to go through to form the enol. That's why the mechanism happens the way it does.

I hope I'm not making a fool of myself haha, this is after a year of not having touched orgo.

 

[bharat008]

I'm not too familiar with the terms you're using lol 😳, but I think we're talking about different steps in the mechanism?

I drew something out and took a picture of it.

http://uploader.ws/upload/201105/IMG005_1.jpg

Up top (1) is the beginning of the mechanism that the link you provided shows, and down below (2) is the beginning of the mechanism that you think can occur as well.

I think the nucleophilic attack of CH3OH on the ketone happens much more readily than de-protonation of the proton by the H2O (due to the large pka differences between the ketone and H2O), and this is a step that you would have to go through to form the enol. That's why the mechanism happens the way it does.

I hope I'm not making a fool of myself haha, this is after a year of not having touched orgo.

Thanks Frogbuster. But the link is giving me an error. Could you attach it to this thread or something.. Thx 👍

 

[FROGGBUSTER]

blah, hold on, i ****ed up the mechanism lol.

 

[Troyvdg]

During addition of alcohol to ketone in presence of acid, why doesn't KETONE act as nucleophile. I just saw the mechanism online and it shows that Ketone acts as a electrophile.

Here is the Link::

I know ketone is a electrophile but in presence of acid shouldn't it act as Nucleophile....😕

all of these reactions are in equilibrium with one another (formation of acetals and keto-enol tautomerism)

there is no electrophile for the enol to act on even if it did form, hope this helps!

 

[bharat008]

all of these reactions are in equilibrium with one another (formation of acetals and keto-enol tautomerism)

there is no electrophile for the enol to act on even if it did from

The enol acting as nucleophile can take away the H from ROH and add that hydrogen to the least substituted carbon. RO- would act as nucleophile and attack the electrophilic carbonyl carbon...

 

[FROGGBUSTER]

i'm a ****, i screwed up the mechanism lol. but bharat, can you draw out your mechanism for us actually, so we get what you're talking about?

i'm actually unsure how you could form the first hemiacetal if it's in the enol form. wouldn't you form a C-C bond instead?

 

[Troyvdg]

The enol acting as nucleophile can take away the H from ROH and add that hydrogen to the least substituted carbon. RO- would act as nucleophile and attack the electrophilic carbonyl carbon...

? i think you might be combining mechanisms

 

[FROGGBUSTER]

The enol acting as nucleophile can take away the H from ROH and add that hydrogen to the least substituted carbon. RO- would act as nucleophile and attack the electrophilic carbonyl carbon...

I think I understand what you're saying now. The keto form is more stable than the enol form though, so the ketone primarily exists in the ketone form. I think maybe a small proportion does undergo the mechanism that you're proposing, but most of the product would be formed through the steps shown in your link.

What do the rest of you think?

 

[bharat008]

Here is the mechanism i am thinking off which could be possible

 

[FROGGBUSTER]

Here is the mechanism i am thinking off which could be possible

That probably doesn't happen under acid-catalyzed conditions. Under acid-catalyzed conditions, methanol exists as (CH3OH-H)+ & water exists as H3O+. It's very unlikely that you get formation of a negatively charged species like that.

 

[bharat008]

That probably doesn't happen under acid-catalyzed conditions. Under acid-catalyzed conditions, methanol exists as (CH3OH-H)+ & water exists as H3O+. It's very unlikely that you get formation of a negatively charged species like that.

Ohkk.. that's what i thought but just wanted to make sure.
Since, its in presence of H+; even if the enol removes the H from ROH; it would be protonated again....
Thx man.. i was thinking too hard..
FROGBUSTER you still didn't forget ochem.. haha

 

[FROGGBUSTER]

Ohkk.. that's what i thought but just wanted to make sure.
Since, its in presence of H+; even if the enol removes the H from ROH; it would be protonated again....
Thx man.. i was thinking too hard..
FROGBUSTER you still didn't forget ochem.. haha

No problem, I was confusing myself too haha.