The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. It is also found in many synthetic compounds such as barbiturates and the HIV drug zidovudine.

1. HETEROCYCLIC CHEMISTRY
PYRIMIDINE
PRESENTED BY
TANVI VYAS
(M.SC CHEMISTRY)

2. PYRIMIDINE:-
• Pyrimidine is the most important member of all the diazines
• Occurs widely in living organisms, Purines, uric acid, alkoxan,
barbituric acid and a mixture of anti-malarial and anti-
bacterials also contain the pyrimidine ring.
• Pyrimidine was first isolated by Gabriel and Colman in 1899.
• Since pyrimidine is symmetrical about the line passing C-2
and C-5, the positions C-4 and C-6 are equivalent and so are
N-1 and N-3.
• When a hydroxy or amino group is present at the 2-, 4-, or 6-,
position than they are tautomeric with oxo and imino
respectively.

4. PHYSICAL PROPERTIES:-
• Pyrimidine is a colorless compounds.
• , m.p. 225°C, b.p. 124°C.
• It is weakly basic (pKa 1.3) as compared to pyridine (pKa 5.2)
or imidazole (pKa 7.2). The decrease in its basicity is due to
the electron-withdrawing effect of the second nitrogen atom
present in the ring.
• Presence of alkyl groups, however, enhances the basicity,
thus 4- methylpyrimidine has pKa 2.0 while 4, 6-
dimethylpyrimidine has a value of 2.8 The 2-and 4-
aminopyrimidines are more basic with pKa 3.54 and 5.71.

5. • In these two compounds more resonance stuctures are possible in
the cation than in the neutral molecule.
• But pyrimidine ring is less aromatic compared to pyridine and
benzene. This view is corroborated by the resonance energies
which are, benzene(36 Kcal/mole, pyridine (31 Kcal/mole) and
pyrimidine (26 Kcal/mole).

6. Synthesis methods:-
• From Malonic Estes: A condensation between a malonic ester and urea
in the presence of a base to yield barbituric acid.
• Besides malonic esters, a series of other compounds such as ẞ- keto
acids or ester may be employed. Uracil, for instance, is obtained from a-
formylacetic acid (produced in situ by decarboxylation of malic acid with
conc. sulfuric acid and reaction of the B-keto acid with urea. Uracil can
be converted to pyrimidine in the following steps:

8. • 2:- Pyrimidine itself can be obtained by the decarboxylation of
pyrimidine- 4, 6-dicarboxylic acid or by the dechlorination of 2, 4-
dichloropyrimidine, equation:-
• From a, B-Unsaturated Ketones: An interesting reaction of simple
a, ẞ-unsaturated ketone with to give pyrimidines , oxidized by a
stream of air to the corresponding pyrimidine. Benzamidine and ẞ-
benzoylstyrene furnish 2, 4, 6-triphenylpyrimidine.

10. Chemical reactions:-
• Electrophilic Substitution: Pyrimidine ia also resistant to electrophilic
substitution.Bromination of pyrimidine yields 5-bromopyrimidine.The
reaction is not simple electrophilic substitution rather proceeds via a
perbromide intermediate.
•

11. • Reaction with Nucleophilic Reagents: The attack of a
nucleophile takes place easily on the pyrimidine ring similar to
pyridine, quinoline and isoquinolne. The positions suceptible to
attack are 2, 4, and 6. Pyrimidine is stable in cold alkali but in
boiling hydrazine it rearranges to pyrazole, via a ring opened
intermediate

13. •Reaction with oxidative reagent:- 4-Methylyrimidine with H₂O2 yields
4-methylpyrimidine N – oxide. This can be converted back to
pyrimidine by refluxing with phosphorus oxychloride.

14. • Reissert addition reaction appears to be fairly common in pyrimidine
N-oxides. 4-Methoxypyrimidine N-oxide on reaction with sodium
cyanide and benzoyl chloride under alkaline conditions furnishes 2-
cyano-4-methoxyprymidine.

15. • Thio-Claisen Rearrangement: Certain suitably substituted
thiopyrimidines undergo the familiar thio-Claisen rearrangement. Thus
3-methyl-4- allylthiopyrimidin-2-one on heating yields 5-allyl-3-methyl-
4-thiouracil.

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