Organic Chemistry

806 CHAPTER 19 Carbonyl Compounds III

PROBLEM 16

What reagents would you use to prepare the following compounds?

19.11 The Aldol Addition

In Chapter 18, we saw that aldehydes and ketones are electrophiles and therefore react

with nucleophiles. In the preceding sections of this chapter, we have seen that when a

proton is removed from the of an aldehyde or a ketone, the resulting anion is

a nucleophile and therefore reacts with electrophiles. An aldol additionis a reaction in

which bothof these activities are observed: One molecule of a carbonyl compound—

after a proton is removed from an —reacts as a nucleophileand attacks the

electrophiliccarbonyl carbon of a second molecule of the carbonyl compound.

An aldol addition is a reaction between two molecules of an aldehydeor two mole-

cules of a ketone. When the reactant is an aldehyde, the addition product is a

which is why the reaction is called an aldol addition (“ald”for

aldehyde,“ol”for alcohol). When the reactant is a ketone, the addition product is a

Because the addition reaction is reversible, good yields of the addi-

tion product are obtained only if it is removed from the solution as it is formed.

In the first step of an aldol addition, a base removes an from the carbonyl

compound, creating an enolate. The enolate adds to the carbonyl carbon of a second

molecule of the carbonyl compound, and the resulting negatively charged oxygen is

protonated by the solvent.

a-proton

OOHO

HO−

a -hydroxyaldehyde

aldol additions

2 CH 3 CH 2 CH CH 3 CH 2 CH

CH 3

CHCH

OOHO

HO−

a -hydroxyketone

2 CH 3 CCH 3 CH 3 C

CH 3

CH 2 CCH 3

b-hydroxyketone.

b-hydroxyaldehyde,

RCHCR

O

a nucleophile an electrophile

RCH 2 CR

−

O

a-carbon

a-carbon

OO

a. b. CH 3 CCH 2 CH 2 CH(COCH 2 CH 3 ) 2

O

O

CCH 3

CH 3 C

O

CH

3-D Molecules:

-Hydroxyaldehyde;

b-Hydroxyketone

b

The new bond formed in an aldol
addition is between the of one
molecule and the carbon that formerly
was the carbonyl carbon of the other
molecule.

A-carbon

C¬C

OO O− O

HO− CH 3 CH 2 CH

O

a -hydroxyaldehyde

CH 3 CH 2 CH CH 3 CHCH

CH 3

CH 3 CH 2 CH CHCH

OH O

CH 3

CH 3 CH 2 CH CHCH

HO−

H 2 O

−

mechanism for the aldol addition