A number of drug molecules contain a modified pyrimidine skeleton, the
best known examples being the anticancer drug 5-fluorouracil, which is
structurally similar to thymine, the antiviral drug AZT, currently being used
in the treatment of AIDS, and phenobarbital, a well known sedative.
N
N
O
H
F
H
O
N
N
O
Me
H
O
O
O
H
N 3
N
N
O
O
O
H
H
Me
5-Fluorouracil
An anticancer drug
AZT
An antiviral drug
Phenobarbital
A sedative
Two positional isomers of pyrimidine are pyridiazine and pyrazine, which
only differ structurally from pyrimidine in terms of the position of the
nitrogen atoms in the ring. These three heterocycles together with their
derivatives are known as diazines.
N
N
N
N
Pyridiazine
Pyrazine
Physical properties of pyrimidine
Pyrimidine is a weaker base than pyridine because of the presence of the
second nitrogen. Its conjugate acid is a much stronger acid (pK a ¼ 1.0). The
pK a values of the N-1 hydrogen in uracil, thymine and cytosine are 9.5, 9.8
and 12.1, respectively. Pyrimidine is a hygroscopic solid (b.p. 123–124
C,
m.p. 20–22
C) and soluble in water.
N
N
H
N
N
+
+ H +
Conjugate acid of pyrimidine
Preparation of pyrimidine
The combination of bis-electrophilic and bis-nucleophilic components is the
basis of general pyrimidine synthesis. A reaction between an amidine (urea
or thiourea or guanidine) and a 1,3-diketo compound produces corresponding pyrimidine systems. These reactions are usually facilitated by acid or
base catalysis.
4.7.4 PYRROLE, FURAN AND THIOPHENE:
161