Organic Chemistry

Section 19.19 The Acetoacetic Ester Synthesis: Synthesis of Methyl Ketones 823

Tutorial:

Acetoacetic ester synthesis

The mechanisms for the acetoacetic ester synthesis and the malonic ester synthesis
are similar. The last step in the acetoacetic ester synthesis is the decarboxylation of a
substituted acetoacetic acid rather than a substituted malonic acid.

PROBLEM 37 SOLVED

Starting with methyl propanoate, how could you prepare 4-methyl-3-heptanone?

Because the target molecule has several more carbon atoms than the starting material, a

Claisen condensation appears to be a good way to start this synthesis. The Claisen conden-

sation forms a ester that can be alkylated at the desired carbon because it is flanked

by two carbonyl groups. Acid-catalyzed hydrolysis will form a 3-oxocarboxylic acid that

will decarboxylate when heated.

PROBLEM 38

What alkyl bromide should be used in the acetoacetic ester synthesis of each of the fol-

lowing methyl ketones?

a. 2-pentanone c. 4-phenyl-2-butanone

b. 2-octanone

b-keto

methyl propanoate

4-methyl-3-heptanone

O

CH 3 CH 3 COCH 3

O

CH 3 CH 3 CCHCH 2 CH 2 CH 3

?

CH 3

hydrolysis

removal of a proton

from the -carbon

alkylation of

the -carbon

decarboxylation

−

HCl, H 2 O

O O

CH 3 CCH 2 COC 2 H 5

O O

CH 3 CCHCOC 2 H 5

O O

CH 3 CCHCOC 2 H 5

R

O O

CH 3 CCHCOH

O

CH 3 CCH 2 R +

R

CH 3 CH 2 O− RBr

∆

∆

+ Br−

CO 2 +CH 3 CH 2 OH

∆

1. CH 3 O−


2. H 3 O+
   
   
   1. CH 3 O−
   
   
   2. CH 3 CH 2 CH 2 Br
   
   
   
   

HCl, H 2 O

CH 3

CH 3

CH 2 CH 2 CH 3

O CH 3

CH 3 CH 3 COCH 3

OO

CH 3 CH 3 C CH COCH 3

O

CH 3 CH 3 CCHCH 2 CH 2 CH 3

OO

CH 3 CH 3 C C COCH 3