Organic Chemistry

908 CHAPTER 21 More About Amines • Heterocyclic Compounds

The resonance energy of imidazole is significantly less

than the resonance energy of benzene ( or ).

Imidazole can be protonated because the lone-pair electrons in the orbital are

not part of the cloud. Since the conjugate acid of imidazole has a of 6.8, imida-

zole exists in both the protonated and unprotonated forms at physiological pH

This is one of the reasons that histidine, the imidazole-containing amino acid, is an im-

portant catalytic component of many enzymes (Section 24.9).

Neutral imidazole is a stronger acid than neutral pyrrole

because of the second ring nitrogen.

Notice that both protonated imidazole and the imidazole anion have two equivalent

resonance contributors. This means that the two nitrogens become equivalent when

imidazole is either protonated or deprotonated.

PROBLEM 22

Give the major product of the following reaction:

PROBLEM 23

List imidazole, pyrrole, and benzene in order of decreasing reactivity toward electrophilic

aromatic substitution.

N NCH 3 + Br 2

FeBr 3

HN+ NH HN NH+

HN NH

protonated imidazole

NN

N

−−NN

N

imidazole anion

δ+δ+

resonance hybrid

δ−δ−

resonance hybrid

NN+ H+

−

NNH

pKa = 14.4

1 pKa' 172

1 pKa=14.4 2

HN NH

+

NNH H+ +

pKa = 6.8

1 7.3 2.

p pKa

sp^2

NNH

+

−

NNH

+

−

+ NNH −NNH+

−

NNH

(^321)
45
resonance contributors of imidazole
36 kcal>mol 151 kJ>mol
14 kcal>mol(59 kJ>mol),
N N H
orbital structure of imidazole
these
electrons
are part of
the cloud
these electrons
are in an sp^2 orbital
perpendicular
to the p orbitals