Organic Chemistry

PROBLEM 31

List the following amides in order of decreasing reactivity toward acid-catalyzed hy-

drolysis:

17.17 Hydrolysis of an Imide: The Gabriel Synthesis

An imideis a compound with two acyl groups bonded to a nitrogen. The Gabriel

synthesis, which converts alkyl halides into primary amines, involves the hydrolysis

of an imide.

In the first step of the reaction, a base removes a proton from the nitrogen of

phthalimide. The resulting nucleophile reacts with an alkyl halide. Because this is an

reaction, it works best with primary alkyl halides (Section 10.2). Hydrolysis of the

N-substituted phthalimide is catalyzed by acid. Because the solution is acidic, the final

products are a primary alkyl ammonium ion and phthalic acid. Neutralization of the

ammonium ion with base forms the primary amine. Notice that the alkyl group of

the primary amine is identical to the alkyl group of the alkyl halide.

Only one alkyl group can be placed on the nitrogen because there is only one hy-

drogen bonded to the nitrogen of phthalimide. This means that the Gabriel synthesis

can be used only for the preparation of primary amines.

PROBLEM 32

What alkyl bromide would you use in a Gabriel synthesis to prepare each of the following

amines?

a. pentylamine c. benzylamine

b. isohexylamine d. cyclohexylamine

O

NH

O

phthalimide

phthalic acid

primary

amine

primary alkyl

ammonium ion

an N-substituted

phthalimide

HCl, H 2 O

HO

+

O

NR Br−

+ RNH 2

COO−

COO−

+

+

RNH 3

COOH

COOH

O

O

N−

O

−

HO−

RBr

∆

SN 2

SN 2

Gabriel synthesis

RCH 2 Br RCH 2 NH 2

708 CHAPTER 17 Carbonyl Compounds I

3-D Molecule:

Phthalimide

CH 3 CNH

O

CH 3 CNH

NO 2

O

CH 3 CNH NO 2

O

CH 3 CNH

O

AB C D