Organic Chemistry

888 CHAPTER 21 More About Amines • Heterocyclic Compounds

We have seen that primary arylamines react with nitrous acid to form stable arene-

diazonium salts (Section 16.12). Arenediazonium salts are useful to synthetic chemists

because the diazonium group can be replaced by a wide variety of nucleophiles. This

reaction allows a wider variety of substituted benzenes to be prepared than can be pre-

pared solely from electrophilic aromatic substitution reactions.

Amines are much less reactive than other compounds with electron-withdrawing

groups bonded to hybridized carbons, such as alkyl halides, alcohols, and ethers.

The relative reactivities of an alkyl fluoride (the least reactive of the alkyl halides), an

alcohol, an ether, and an amine can be appreciated by comparing the values of the

conjugate acids of their leaving groups, recalling that the stronger the base, the weak-

er is its conjugate acid and the poorer the base is as a leaving group. The leaving group

of an amine is such a strong base that amines cannot undergo the substitution

and elimination reactions that alkyl halides undergo.

Protonation of the amino group makes it a weaker base and therefore a better leav-

ing group, but it still is not nearly as good a leaving group as a protonated alcohol. Re-

call that protonated ethanol is more than units more acidic than protonated

ethylamine.

So, unlike the leaving group of a protonated alcohol, the leaving group of a protonated

amine cannot dissociate to form a carbocation or be replaced by a halide ion. Proto-

nated amino groups also cannot be displaced by strongly basic nucleophiles such as

because the base would react immediately with the acidic hydrogen, and proto-

nation would convert it into a poor nucleophile.

PROBLEM 4

Why is it that a halide ion such as can react with a protonated primary alcohol, but

cannot react with a protonated primary amine?

PROBLEM 5

Give the product of each of the following reactions:

a.

catalytic

CCH H+

3

O

+ CH 3 CH 2 CH 2 NH 2

Br-

CH 3 CH 2 NH 3 HO– CH 3 CH 2 NH 2 H 2 O

+

++

HO-

pKa = − 2.4

CH 3 CH 2 OH 2

+

pKa = 11.2

CH 3 CH 2 NH 3

+

13 pKa

(-NH 2 )

pKa

sp^3

NH 2 N NCl− Nu Nu ++N 2 Cl–

−

an arenediazonium salt

HCl

NaNO 2

+

mostreactive >>∼

relative reactivities

strongest acid,

weakest conjugate

base

weakest acid,

strongest conjugate

base

least

RCH 2 F RCH 2 OH RCH 2 OCH 3 RCH 2 NH (^2) reactive
HF H 2 O RCH 2 OH NH 3
pKa = 3.2 pKa = 15.7 pKa = 15.5 pKa = 36