2. Diazines are the six membered heterocylic compounds derived from benzene by
replacement of two -CH group by two nitrogen atoms.
This replacement results in three isomeric forms
(1) 1, 2- isomer
(2) 1, 3-isomer
(3) 1, 4-isomer N
N
N
N
N
N
Diazines
Replace two CH group
by two nitrogen atom
3. Nomenclature of heterocyclic rings will be done by three ways
(1) Common names
(2) Replacement nomenclature
N
N
N
N
N
N
Pyridazine Pyrimidine Pyrazine
N
1, 4-diazabenzene
(p-diazabenzene)
1, 3-diazabenzene
(m-diazabenzene)
1, 2-diazabenzene
(o-diazabenzene)
N
N N
N
N
Replace two CH group
by two nitrogen atom
4. (3) Hantzsch-Wideman nomenclature
Prefix + Ring + Suffix
Type of heteroatom
Size of the ring
Degree of unsaturation of ring
Nitrogen 6-membered Aromatic
Aza in e Azine
N
N
N
N
N
N
1, 4-diazine
(p-diazine)
1, 3-diazine
(m-diazine)
1, 2-diazine
(o-diazine)
5. Diazines compounds belong to the category of π-deficient ring systems similar to
pyridine.
Diazines are aromatic in nature and lone pair on sp2 hybridized nitrogen are not
involved involved in aromatic sextet.
N
N N
N
N N
Lone pairs not involved in resonance
6. N N
N
N N
Diazines are weaker bases compared to pyridine due to inductive and electron
withdrawing effect of second nitrogen atom.
N
N
>> > >
pKa - 5.2 2.3 1.3 0.6
7. 1 N
2
N 3
4
Pyrimidine ring has symmetry along C-2 and C-5, hence C-4 & C-6 as well as N-1
& N-3 are equivalent to each other.
5
6
Pyrimidine
N
N
Pyrimidine ring system has wide occurance in nature as substituted and fused
compounds which includes nucelic acid and thiamine (Vit-B1)
NH2
N
H
N
Adenine
N
N
NH2
S
Br
N
OH
Vitamin B1
9. Acid or base catalysed condensation reaction of 1, 3-dicarbonyl compounds
with amidines or Guanidines yields pyrimidine derivatives is known as
Pinner pyrimidine synthesis.
R1
R2
O
O
H2N R3
NH
NaOEt
N
N
R2
R1
R3
Synthesis
10. R 1
R 2
O
O
H 2 N R 3
N H
N H
N
H 2
R 2
R 1
R 3
H O
O
N
R 2
R 1
O
N H
R 3
- H 2 O
H
N
R 2
R 1
O
N H 2
R 3
N
R 1
N H
R 3
H O R 2
- H 2 O
N
R 1
N
R 3
R 2
Mechanism
11. O O
NH2
NH
.HCl
K2CO3
N N
2, 4, 6-trimethyl pyrimidines
O
OEt
O
NH2
NH
.HCl
NaOH
N N
HO
2, 6-dimethyl-4-hydroxy
pyrimidine
By applying Pinner’s procedure variety of pyrimidine derivatives can be
prepared from different 1,3-dicarbonyl starting materials like acetylacetone
and ethyl acetoacetate.
13. From condensation reaction of malonic ester with urea in presence of base yields
barbituric acid which tautomerizes to trihydroxy form. Finally reaction with POCl3
followed by refluxing with hot water and Zn dust yield pyrimidine.
O E t
O
H 2 N N H 2
N H
O
O O
O E t O N H
N a O E t
O
N
N
H O
H O
O H
N
N
C l
C l
C l
N
N
P O C l 3
Z n D u s t
14. 2-substituted pyrimidines can be prepared by condensation followed by cyclization of
carboxylic acid and 1, 3-diaminopropane, subsequent dehydrogenation in presence of
catlayst give 2-substituted pyrimidines.
H2N
H2N
N
HN N
N
Ph
R-COOH R
Condensation
Cyclization
Dehydrogenation
Base
CN
3 R
N
N
2-substituted
pyrimidine
Base facilitated trimerization of alkane nitriles with free methylene group adjacent to
cyano group results in pyrimidin-4-amine derivatives.
R
NH2
R
R
15. Reactions of Pyrimidines
Pyrimidine undergoes reaction at Nitrogen as well as at Carbon similar to
Pyridine.
Electrophilic addition reaction like Protonation and alkylation occurs at ring
nitrogen
Electrophilic substitution reaction less facile because of decreased basicity and
under favorable conditions reaction occurs at 5th position.
Nucleophilic substitution takes place at 2, 4 and 6th positions.
16. Reactions at Nitrogen
Electrophilic addition at Nitrogen
Lone pair of electrons on the ring nitrogen undergoes electrophilic addition reaction
with electrophiles only at one nitrogen and under drastic condition both nitrogen
undergo electrophilic addition. This electrophilic addition results in the formation of
pyrimidinium salts.
BOTHAREAROMA
TIC
N
N
E
N
N
E
17. Protonation at Nitrogen
Pyrimidine nitrogen form mono quaternary salts with mild acid and di quaternary salts
strong acids.
N N
H
N H N
H
H
N
N
H
18. Alkylation at Nitrogen
Pyrimidine reacts with alkyl halide to give mono quaternary salts less readily
compared to pyrdine.
Dialkylation cannot be achieved with simple alkyl halides, however more reactive
trialkoxonium tetrafluoroborates converts pyrimidine to di quaternary salts.
N
N MeI N
N
Me
N
N
Et
Et3OBF4
MeOH, rt
I
Et
BF4
BF4
Reflux
19. Electrophilic substitution at carbon
Electrophilic substitution of pyrimidines is very difficult.
Hence pyrimidines are bad at undergoing electrophilic aromatic substitution but
under favorable condition pyrimidine ring reacts with electrophile only at 5th
position.
Reactions at Carbon
N
1 N
N
N
N
N
N
N
N
N
N
N
N
N
N
N 3
N1
N3
At 5th position no positive charge hence it has some electron density
21. Nucleophilic substitution reactions
Pyrimidine undergoes nucleophilic substitution reaction easily at 2, 4 and 6th
positions.
Nucleophilic substitution of hydrogen next to nitrogen requires oxidation of
resulting dihydro product to get pyrimidine.
N
N
N
NH
Nu H
N
N
Nu
Oxidation
Nu
N
N NH
Dihydro product
Ph H
N
4-Phenyl-
1, 6-dihydropyrimidine
N
Ph
N
4-Phenylpyrimidine
PhM
H3O+
M = Li, MgBr
O2
