Heterocycles

Pyrimidine (1,3,diazine)

Dr. Taj Khan

Dept. of Pharmaceutical Chemistry, Oriental
college of pharmacy Sanpada, New Mumbai.
Heterocycles
Pyrimidine (1,3,diazine)
 Building blocks of numerous natural compounds from antibiotics to vitamins and liposacharide
bases of RNA and DNA, the most abundant being cytosine, thymine or uracil.
Anticancer comp. NH2 NH2
N N
O
F O N O N
HN HO HO
O O
O N F OH
H
HO F HO
5-FU Gemcitabin Cytarabine (ARA-C)

Antivirals
O NH2 NH2
O
HN N N
HN
O N O N O N
HO O HO O HO
O
O
N HO O HIV (RT -inhibitors)
S
N3
ddC
AZT

Barbiturates
Resonance structure of Pyrimidine:
Synthesis using Malonic ester:
Synthesis from 2,4 -dichloropyrimidine
Synthesis from Amidine
 Reactions of pyrimidine:
1)Reaction with acid:
Although weak base, can be protonated under acidic condition.
Diprotonation is also possible under acidic condition.

2) Electrophilic substitution: Resistant to E+ subs rxn

2,4,6 position e deficient so resistant for an attack.

Attack is possible on 5 position if EDG is +nt

Electrophilic substitution:
 Reactions of pyrimidine:

Sulfonation also need at least 1 EDG to be present then reaction goes at 5 position.

3) Reaction with Nu-

Easy
Position 2, 4, 6

Grignard & organo lithium add to 4 position at rt

 Reactions of pyrimidine:

Reaction with oxidising agents:

P gives low yield of Pyridine N- Oxide with peracid
But alkyl pyrimidine gives good yield of P N- Oxide
The end