Organic Chemistry

Section 19.18 The Malonic Ester Synthesis: Synthesis of Carboxylic Acids 821

A malonic ester synthesis forms

a carboyxlic acid with two more

carbon atoms than the alkyl halide.

19.18 The Malonic Ester Synthesis:

Synthesis of Carboxylic Acids

A combination of two of the reactions discussed in this chapter—alkylation of an
and decarboxylation of a acid—can be used to prepare car-
boxylic acids of any desired chain length. The procedure is called the malonic ester
synthesisbecause the starting material for the synthesis is the diethyl ester of mal-
onic acid. The first two carbons of the carboxylic acid come from malonic ester, and
the rest of the carboxylic acid comes from the alkyl halide used in the second step of
the reaction.

In the first part of the malonic ester synthesis, the of the diester is alkylat-
ed (Section 19.8). A proton is easily removed from the because it is flanked
by two ester groups The resulting reacts with an alkyl
halide, forming an malonic ester. Because alkylation is an reaction,
it works best with methyl halides and primary alkyl halides (Section 10.2). Heating the
malonic ester in an acidic aqueous solution hydrolyzes it to an
malonic acid, which, upon further heating, loses forming a car-
boxylic acid with two more carbons than the alkyl halide.

PROBLEM 35

What alkyl bromide(s) should be used in the malonic ester synthesis of each of the

following carboxylic acids?

a. propanoic acid c. 3-phenylpentanoic acid

b. 2-methylpropanoic acid d. 4-methylpentanoic acid

a-substituted CO 2 ,

a-substituted

a-substituted SN 2

1 pKa = 132. a-carbanion

a-carbon

a-carbon

O

C 2 H 5 OC CH 2 COC 2 H 5

1. CH 3 CH 2 O−
   2. RBr
   3. HCl, H 2 O, ∆

O

RCH 2 COH

O

diethyl malonate

malonic ester

from malonic ester

from the alkyl halide

malonic ester synthesis

a-carbon b-dicarboxylic

Tutorial:

Malonic ester synthesis

hydrolysis

removal of a proton

from the -carbon

akylation of

the -carbon

decarboxylation

OO

C 2 H 5 OC CH 2 COC 2 H 5

O O

−

C 2 H 5 OC CH COC 2 H 5

OO

C 2 H 5 OC CH +

R

COC 2 H 5 Br−

CH 3 CH 2 O−

an -substituted malonic ester

an -substituted malonic acid

HCl, H 2 O ∆

∆

RBr

OO

+ CO 2 HOC CH

R

COH

O

RCH 2 COH + 2 CH 3 CH 2 OH