acetals and ketals

[MedGrl@2022]

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Why are acetals and ketals nonreactive to nucleophiles? Is it steric hindrance, a less positive carbon atom, a combination of the two?

Also when studying for the MCAT should I be able to draw out the mechanisms?

 

[Pre-Med Village]

As with other ethers, acetals and ketals are stable to bases/nucleophiles because alkoxide is a strong base, making it a poor leaving group. Acidic, aqueous conditions change things, forming an alcohol leaving group, which allow for the reversal, or de-protection steps, of acetal/ketal formation.

I hope this helps!

 

[MedGrl@2022]

As with other ethers, acetals and ketals are stable to bases/nucleophiles because alkoxide is a strong base, making it a poor leaving group. Acidic, aqueous conditions change things, forming an alcohol leaving group, which allow for the reversal, or de-protection steps, of acetal/ketal formation.

I hope this helps!

Hey. Thank you for your response. I just want to make sure that I understand something. Alkoxides are strong bases due to the electron donating alkyl group which would destabilize the negatively charged oxygen atom, right? Thus, acetals and ketals are are susceptible to acidic conditions because the oxygen can become protonated which would result in an alcohol leaving group.

Can Acetals, Ketals and their hemi counterparts be polar (due to the negatively charged oxygen groups)? But this does not make the carbon positively charged at all? Or it is too sterically hindered?

Also, in order to change a hemiacetal or hemiketal into a acetal or ketal the conditions MUST be acidic and NOT basic because the acid must protonate the alcohol on the hemiacetal or hemiketal in order it to form water (a good leaving group) then a second alcohol or base can attack the newly formed carbocation in order to complete the reaction into a acetal or ketal.

 

[Pre-Med Village]

Hey. Thank you for your response. I just want to make sure that I understand something. Alkoxides are strong bases due to the electron donating alkyl group which would destabilize the negatively charged oxygen atom, right? Thus, acetals and ketals are are susceptible to acidic conditions because the oxygen can become protonated which would result in an alcohol leaving group.

The electron donating character of the alkyl group does cause alkoxide to be a stronger base than hydroxyl, but hydroxyl isn't that great a leaving group anyway, so there is more to it. A small atom like oxygen (2nd period) isn't a stable (low internal energy) anion. Although it's very electronegative, the small size causes oxygen to be a bit high energy as an anion. Think about how it takes more work to compress a negative charge into a small volume. Why is chloride the conjugate base of a strong acid, but fluoride the conjugate base of a weak acid? Additionally, there isn't as much access to the anion for stabilization through solvation. A bigger anion presents much more surface for the positive poles of water, so if oxygen were bigger, hydroxyl (and alkoxyl) would be stabilized by interacting with many more solvent molecules.

Can Acetals, Ketals and their hemi counterparts be polar (due to the negatively charged oxygen groups)? But this does not make the carbon positively charged at all? Or it is too sterically hindered?

The positively charged carbon might attract suitors and make an intermediate lower energy, but if the reaction isn't thermodynamically favored overall, it won't be favored by equilibrium. Steric hindrance isn't so great an issue.

Also, in order to change a hemiacetal or hemiketal into a acetal or ketal the conditions MUST be acidic and NOT basic because the acid must protonate the alcohol on the hemiacetal or hemiketal in order it to form water (a good leaving group) then a second alcohol or base can attack the newly formed carbocation in order to complete the reaction into a acetal or ketal.

That sounds right. All the best.

 

[lilmc]

Hey guys, I have another question about ketals that I hope you can answer! Can chromic acid oxidize a ketal? I thought ketals could not be oxidized, but then I ran into a problem with chromic acid where it was. Is this solely because of the acid in chromic acid?

Also, I see you posted a year ago. I hope you did really well on the mcat!!