Organic Chemistry

PROBLEM 26

Show the mechanism for the acid-catalyzed hydrolysis of an acetal.

PROBLEM 27

Explain mechanistically why an acetal or ketal can be isolated but most hydrates can’t be

isolated.

Notice that the mechanisms for imine, enamine, hydrate, and acetal (or ketal) for-
mation are similar. After the nucleophile (a primary amine in the case of imine forma-
tion, a secondary amine in the case of enamine formation, water in the case of hydrate
formation, and an alcohol in the case of acetal or ketal formation) has added to the car-
bonyl group, water is eliminated from the protonated tetrahedral intermediate, forming
a positively charged intermediate. In imine and hydrate formation, a neutral product is
achieved by losing a proton from a nitrogen and an oxygen, respectively. In enamine
formation, a neutral product is achieved by losing a proton from an In acetal
formation, a neutral compound is achieved by adding a second equivalent of alcohol.
Also notice that, because the nucleophile in hydrate formation is water, elimination of
water gives back the original aldehyde or ketone.

PROBLEM-SOLVING STRATEGY

Explain why acetals and ketals are hydrolyzed back to the aldehyde or ketone in acidic

aqueous solutions, but are stable in basic aqueous solutions.

The easiest way to approach this kind of question is to write out the structures and the mecha-

nism that describe what the question is asking. When the mechanism is written, the answer

should become apparent. In an acidic solution, the acid protonates an oxygen of the acetal.

This creates a weak base that can be expelled by the other group. When the

group is expelled, water can attack the reactive intermediate, and you are then on your way

back to the ketone (or aldehyde).

In a basic solution, the group cannot be protonated. Therefore, the group that would

have to be eliminated to reform the ketone (or aldehyde) would be the very basic

group. A group is too basic to be eliminated by the other group, which has

little driving force because of the positive charge that would be placed on its oxygen atom

if elimination were to occur.

Now continue on to Problem 28.

RCR

OCH 3

OCH 3

CH 3 O- CH 3 O

CH 3 O-

CH 3 O

+

+

+

OCH 3

OH

RCR

OCH 3

+OH

RCR

OCH 3

H 2 O

RCR

OCH 3

RCR

OCH 3

OCH 3

H 2 O

RCR

OCH 3

OH

+

RCR

OCH 3

H 2 O

OH

H H

H

+

OH

H

H

H

R R

O

+

O

H

H

C

R R

C

(CH 3 OH) CH 3 O

a-carbon.

Section 18.7 Reactions of Aldehydes and Ketones with Oxygen Nucleophiles 757

Tutorial:

Common terms, the addition

of nucleophiles to carbonyl

compounds