Organic Chemistry

904 CHAPTER 21 More About Amines • Heterocyclic Compounds

N

H

Y

H

Y

H

+ Y

2-position

least stable

least stable

N

+

N

+

N

H

Y

H

Y

H

+ Y

N N

+

N

+

N

Y H Y H Y H

+

N N

+

+

4-position

+ Y+ 3-position

Figure 21.2N
Structures of the intermediates that
can be formed from the reaction of
an electrophile with pyridine.

Pyridine, therefore, undergoes electrophilic aromatic substitution reactions only under

vigorous conditions, and the yields of these reactions are often quite low. If the nitrogen

becomes protonated under the reaction conditions, the reactivity is further decreased be-

cause a positively charged nitrogen is more electron withdrawing than a neutral nitrogen.

We have seen that highly deactivated benzene rings do not undergo Friedel–Crafts

alkylation or acylation reactions. Therefore, pyridine, whose reactivity is similar to

that of a highly deactivated benzene, does not undergo these reactions either.

PROBLEM 18

Give the product of the following reaction:

Since pyridine is lessreactive than benzene toward electrophilicaromatic substitu-

tion, it is not surprising that pyridine is morereactive than benzene toward nucleophili-

caromatic substitution. The electron-withdrawing nitrogen atom that destabilizes the

intermediate in electrophilic aromatic substitution stabilizes it in nucleophilic aromat-

ic substitution.

CH 3 OH

CH 3 CCl

O

N

+

AlCl 3

no electrophilic aromatic substitution reaction

N

+ CH 3 CH 2 Cl

N N

Br

3-bromopyridine

30%

300 °C

FeBr 3

H 2 SO 4

+ Br 2 + HBr

N N

SO 3 H

pyridine-3-sulfonic acid

71%

230 °C

300 °C

+ H 2 SO 4 + H 2 O

N N

NO 2

3-nitropyridine

22%

+ HNO 3 + H 2 O