Organic Chemistry

758 CHAPTER 18 Carbonyl Compounds II

PROBLEM 28

a. Would you expect hemiacetals to be stable in basic solutions? Explain your answer.

b. Acetal formation must be catalyzed by an acid. Explain why it cannot be catalyzed by

c. Can the rate of hydrate formation be increased by hydroxide ion as well as by acid?

Explain.

18.8 Protecting Groups

Ketones (or aldehydes) react with 1,2-diols to form five-membered ring ketals (or ace-

tals) and with 1,3-diols to form six-membered ring ketals (or acetals). Recall that five-

and six-membered rings are formed relatively easily (Section 11.11). The mechanism

is the same as that shown in Section 18.7 for acetal formation, except that instead of

reacting with two separate molecules of alcohol, the carbonyl compound reacts with

the two alcohol groups of a single molecule of the diol.

If a compound has two functional groups that will react with a given reagent and

you want only one of them to react, it is necessary to protect the other functional group

from the reagent. A group that protects a functional group from a synthetic operation

that it would not otherwise survive is called a protecting group.

If you have ever painted a room with a spray gun, you may have taped over the

things you do not want to paint, such as baseboards and window frames. In a simi-

lar way, 1,2-diols and 1,3-diols are used to protect the carbonyl group of aldehydes

and ketones. The diol is like the tape. For example, in the synthesis of the following

hydroxyketone from the keto ester, can reduce both functional groups of a

keto ester, and the one that you don’t want to react—the keto group—is the more

reactive of the two.

If the keto group is converted to a ketal, only the ester group will react with

The protecting group can be removed by acid-catalyzed hydrolysis after the

ester has been reduced. It is critical that the conditions used to remove a protecting

group do not affect other groups in the molecule. Acetals and ketals are good protect-

ing groups because, being ethers, they do not react with bases, reducing agents, or ox-

idizing agents.

LiAlH 4.

COCH 3

?

OOO

CH 2 OH

LiAlH 4

HCl

O O

CH 3 CH 2 CCH 2 CH 3 HOCH 2 CH 2 OH + H 2 O

++HOCH 2 CH 2 CH 2 OH H 2 O

+ OO

C

CH 3 CH 2 CH 2 CH 3

HCl

O

O

1,2-ethanediol

1,3-propanediol

CH 3 O-.