Organic Chemistry

Section 21.11 Biologically Important Heterocycles 907

3-D Molecules:

Quinoline; Isoquinoline

PROBLEM 21

Rank the following compounds in order of decreasing ease of removing a proton from a

methyl group:

Quinoline and Isoquinoline
Quinoline and isoquinoline are known as benzopyridinesbecause they have both a
benzene ring and a pyridine ring. Like benzene and pyridine, they are aromatic com-
pounds. The values of their conjugate acids are similar to the of the conjugate
acid of pyridine. (In order for the carbons in quinoline and isoquinoline to have the
same numbers, the nitrogen in isoquinoline is assigned the 2-position, not the lowest
possible number.)

21.11 Biologically Important Heterocycles

Proteins are naturally occurring polymers of acids (Chapter 23). Three of the
20 most common naturally occurring amino acids contain heterocyclic rings: Proline
contains a pyrrolidine ring, tryptophan contains an indole ring, and histidine contains
an imidazole ring.

Imidazole
Imidazole, the heterocyclic ring of histidine, is the first heterocyclic compound we
have encountered that has two heteroatoms. Imidazole is an aromatic compound be-
cause it is cyclic and planar, every carbon in the ring has a porbital, and the cloud
contains threepairs of electrons (Section 15.1). The electrons drawn as lone-pair
electrons on N-1 (see p. 896) are part of the cloud because they are in a porbital,
whereas the lone-pair electrons on N-3 are not part of the cloud because they are in
an sp^2 orbital, perpendicular to the porbitals.

p

p

p

p

+NH

3

CH 2 CHCOO−

N

H

N COO−

HH

+ NNH

proline tryptophan histidine

+NH 3

CH 2 CHCOO−

a-amino

quinoline

isoquinoline

+

+

+

H+

N

H

N

+ H+

NH N

54

(^81)
3
2
6
7
5 4
8 1
3
2
6
7
pKa = 4.85
pKa = 5.14
pKa pKa
N
CH 3
N

• I−
  CH 3
  CH 2 CH 3
  N
  CH 3
  Tutorial:
  Recognizing common
  heterocyclic rings in complex
  molecules