Hemiketal and acetal formation

[yjj8817]

According to tbr, it says that hemiketal and hemiacetals formation can only occur under basic condition. Is there a reason for this?

Also, under basic condition, can the oh group connected to the carbon in hemiketal or hemiacetals leave? Or is this not possible even under basic condition because oh is a strong base?

Thanks!

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[azor ahai]

I usually see them as acid catalyzed.

 

[Cawolf]

No, if you want to produce a hemiacetal or hemiketal it needs to be under basic conditions.

Under acidic conditions the former carbonyl oxygen in the hemiacteal or hemiketal will protonate and become a leaving group, and with following nucleophilic attack by the alcohol (for a second time) - form a ketal or acetal.

 

[azor ahai]

No, if you want to produce a hemiacetal or hemiketal it needs to be under basic conditions.

Under acidic conditions the former carbonyl oxygen in the hemiacteal or hemiketal will protonate and become a leaving group, and with following nucleophilic attack by the alcohol (for a second time) - form a ketal or acetal.

Don't you want to protonate the carbonyl oxygen to make the carbonyl carbon more electrophilic? You want the alcohol to act as the nucleophile. A strong base would deprotonate the alpha hydrogen and you'd have an enolate. The reaction can proceed without a catalyst, but alcohol is a weak nucleophile so the acid catalyst helps.

 

[Cawolf]

I think you are describing the acid catalyzed mechanism.

There is also the base catalyzed mechanism where the base deprotonates the alcohol to form an alkoxide that is nucleophilic enough to attack the carbonyl carbon. The alkoxide attacks the carbonyl carbon and the carbonyl oxygen gains a negative charge from the pi electrons. The negative oxygen then deprotonates an alcohol to form the hemiactel/hemiketal.

This is not stable under any conditions, but is a useful mechanism in polysaccharide formation.

If acidic conditions were present then the alcohol group formed from the carbonyl oxygen would protonate and become a leaving group, allowing for further nucleophilic attack by an alcohol to form a ketal/acetal. Since he specifically asked about hemiacetal/hemiketal formation, it has to be under basic conditions. They do form as intermediates in the acid catalyzed pathway, but they will not be isolable.

I am sure that there is some way to do it, but as far as MCAT or first year organic courses go these are the mechanisms that I learned.

 

[azor ahai]

I think you are describing the acid catalyzed mechanism.

There is also the base catalyzed mechanism where the base deprotonates the alcohol to form an alkoxide that is nucleophilic enough to attack the carbonyl carbon. The alkoxide attacks the carbonyl carbon and the carbonyl oxygen gains a negative charge from the pi electrons. The negative oxygen then deprotonates an alcohol to form the hemiactel/hemiketal.

This is not stable under any conditions, but is a useful mechanism in polysaccharide formation.

If acidic conditions were present then the alcohol group formed from the carbonyl oxygen would protonate and become a leaving group, allowing for further nucleophilic attack by an alcohol to form a ketal/acetal. Since he specifically asked about hemiacetal/hemiketal formation, it has to be under basic conditions. They do form as intermediates in the acid catalyzed pathway, but they will not be isolable.

I am sure that there is some way to do it, but as far as MCAT or first year organic courses go these are the mechanisms that I learned.

Yeah, in general I think most reactions can be either base-catalyzed or acid-catalyzed.

Deprotonating the alcohol (since alcohol is a weak acid) would require a strong base, which may just deprotonate the alpha hydrogen of the ketone/aldehyde leading to enolate which can turn into all sorts of stuff.

I usually see it as acid-catalyzed though. LIke here.

Oh and of course you'd need to do a work-up step at the end, like adding water so you don't have any strong acids around.

 

[Cawolf]

Oh I see, by using only 1 equivalent they are saying it limits to hemiacetal formation.

That makes sense.

I was thinking in terms of unlimited alcohol presence.