Organic Chemistry

acetamide

704 CHAPTER 17 Carbonyl Compounds I

17.15 Reactions of Amides

Amides are very unreactive compounds, which is comforting, since proteins are com-

posed of amino acids linked together by amide bonds (Section 23.11). Amides do not

react with halide ions, carboxylate ions, alcohols, or water because, in each case,

the incoming nucleophile is a weaker base than the leaving group of the amide

(Table 17.1).

Amides do, however, react with water and alcohols if the reaction mixture is heated in

the presence of an acid. The reason for this will be explained in Section 17.16.

Molecular orbital theory can explain why amides are unreactive. In Section 17.3,

we saw that amides have an important resonance contributor in which nitrogen shares

its lone pair with the carbonyl carbon—the orbital that contains the lone pair overlaps

the empty orbital of the carbonyl group (Figure 17.3). This overlap lowers the

energy of the lone pair—it is neither basic nor nucleophilic—and it raises the energy

of the orbital of the carbonyl group, making it less reactive to nucleophiles

(Figure 17.5).

An amide with an group can be dehydrated to a nitrile. Dehydrating reagents

commonly employed for this purpose are , , and.

P 2 O 5

CH^80 °C

3 CH 2 NH 2

C CH 3 CH 2 C N

O

P 2 O 5 POCl 3 SOCl 2

NH 2

p*

p*

++

+

+

CH 3

H 2 O

HCl

∆

HCl

∆

CH 3

CH 3 CH 2 NH 3

+ CH 3 CH 2 OH + CH 3 NH 3

NHCH 2 CH 3 OH

NHCH 3 OCH 2 CH 3

N-ethylacetamide

N-methylbenzamide

C

O

C

O

C

O

C

O

+ CH 3 OH no reaction

N-methylbenzamide

CH 3 CH 2 NHCH 2 CH 3

+ H 2 O no reaction

N-ethylpropanamide

NHCH 3

C

O

C

O

CH 3 NHCH 2 CH 2 CH 3 + Cl− no reaction

N-propylacetamide

CH 3 CH 2 N(CH 3 ) 2 + CH 3 O− no reaction

N,N-dimethylpropionamide

C

O

C

O

C

O

3-D Molecule:

N-Methylbenzamide