Organic Chemistry

PROBLEM 29

a. Which of the following reactions would lead to the formation of an amide?

b. For those reactions that do form amides, what could you do to improve either the rate of

amide formation or the yield of the amide product?

PROBLEM 30

Propose a mechanism for the reaction of an amide with thionyl chloride to form a nitrile.

(Hint:In the first step of the reaction, the amide is the nucleophile and thionyl chloride is

the electrophile.)

Section 17.15 Reactions of Amides 705

resonance contributors

isolated

lone pair

energy-stabilized

(delocalized) “lone pair”

new higher-energy

antibonding orbital

Energy

CO π∗

isolated C

antibonding

orbital

O π∗

R NH 2

C

O

R NH 2

C

O−

+

Figure 17.5

The filled nonbonding orbital

containing nitrogen’s lone pair

overlaps the empty antibonding

molecular orbital of the carbonyl

group. This stabilizes the lone pair,

making it less reactive, and raises

the energy of the orbital of the

carbonyl group, making it less able

to react with nucleophiles.

p*

p*

+

R

1.

2.

3.

4.

5.

6.

CH 3 NH 2

OH

C

O

+

R

CH 3 NH 2

OCH 3

C

O

+

R

CH 3 NH 2

CH 3 O−

OCH 3

C

O

+

R

CH 3 NH 2

O−

C

O

+

R

CH 3 NH 2

Cl

C

O

+

R

CH 3 NH 2

HO−

OCH 3

C

O

NATURE’S SLEEPING PILL

Melatonin, a naturally occurring amide, is a hor-

mone that is synthesized by the pineal gland from

the amino acid tryptophan. Melatonin regulates the dark–light

clock that governs such things as the sleep–wake cycle, body

temperature, and hormone production.

tryptophan

an amino acid

N

H

+NH

3

(^) COO−
melatonin
CH 3 O
N
H
H
N
O
Melatonin levels increase from evening to night and then
decrease as morning approaches. People with high levels of
melatonin sleep longer and more soundly than those with low
levels. The concentration of the hormone in the blood varies
with age—6-year-olds have more than five times the concen-
tration that 80-year-olds have—which is one of the reasons
why young people have less trouble sleeping than older people.
Melatonin supplements are used to treat insomnia, jet lag, and
seasonal affective disorder.