896 CHAPTER 21 More About Amines • Heterocyclic Compounds
Primary amines also can be prepared in good yields if azide ion is used as the
nucleophile in an reaction. The product of the reaction is an alkyl azide, which
can be reduced to a primary amine. (See Chapter 10, Problem 9.)Other reduction reactions also result in the formation of primary amines. For exam-
ple, the catalytic reduction of a nitrile forms a primary amine. (Recall that a nitrile can
be obtained from the reaction of cyanide ion with an alkyl halide.)Amines are obtained from the reduction of amides with (Sections 18.5 and
20.1). This method can be used to synthesize primary, secondary, and tertiary amines.
The class of amine obtained depends on the number of substituents on the nitrogen
atom of the amide.A primary amine can be obtained from the reaction of an aldehyde or a ketone with
excess ammonia in the presence of and Raney nickel. Because the imine does not
have a substituent other than a hydrogen bonded to the nitrogen, it is relatively unsta-
ble, so the amine is obtained by adding to the bond as it is formed. This is
called reductive amination.Secondary and tertiary amines can be prepared from imines and enamines by reducing
the imine or enamine. Sodium triacetoxyborohydride is a commonly used reducing
agent for this reaction.H 2
ONH+ 3 CNH Pd/CCH 3 CH 2CH 3 CH 2CHNH 2
CH 3 CH 2C
CH 3 CH 2CH 3 CH 2 CH 3 CH 2excess
unstableH 2 C“NH 2C RCH 2 NH 2
RNH 2O- LiAlH 4
- H 2 O
a primary amine
C RCH 2 NHCH 3
R NHCH 3O- LiAlH 4
- H 2 O
a secondary amine
C RCH 2 NCH 3
R NCH 3CH 3O- LiAlH 4
- H 2 O
a tertiary amineCH 3LiAlH 4SN 2(-N 3 )NH
a protonated
primary amineGabriel synthesis∆- HO− H 3 O+
- CH 3 CH 2 Br
+ Br−
phthalimide+OONCH 2 CH 3 + CH 3 CH 2 NH 3COOHCOOHOOCH 3 CH 2 CH 2 CH 2 Br
butyl bromideCH 3 CH 2 CH 2 CH 2 NN
butyl azideCH 3 CH 2 CH 2 CH 2 NH 2
butylamine−N 3 H 2
Pd/CN+CH 3 CH 2 CH 2 CH 2 Br
butyl bromideCH 3 CH 2 CH 2 CH 2 CN
pentanenitrileCH 3 CH 2 CH 2 CH 2 NH 2
pentylamineNaC
HClN H 2
Pd/C