This presentation outlines the Synthesis, aromatic character and reaction of Triazines

1. Synthesis, reactivity, aromatic
character and importance of
Triazines
Prepared by
Dr. Krishna swamy
Faculty
DOS & R in Organic Chemistry
Tumkur University

2. Triazines are class of nitrogen containing six membered heterocycles with molecular
formula C3H3N3.
Triazines are derived from benzene by replacement of three –CH group by three
nitrogen atoms.
This replacement results in three isomeric forms
(1) 1, 2, 3- isomer
(2) 1, 2, 4-isomer
(3) 1, 3, 5-isomer
Triazines
Replace three CH group
by three nitrogen atom

3. (1) 1, 2, 3- triazine is also called v-triazine
(2) 1, 2, 4-triazine is also called as-triazine
(3) 1, 3, 5-triazine is also called sym / s-triazine
N
N
N
N
N
N
N
N
N
Triazines

4. All the three triazine isomers are aromatic in nature.
1, 2, 3- and 1, 2, 4-triazines has almost same basicity as pyrazine whereas 1, 3, 5-
triazine less basic.
Among the three triazine isomers, 1, 2, 3-triazines are least studied compared to 1, 2, 4
and 1, 3, 5-triazine isomers because of fragility of chain and rings with contiguous
nitrogen atoms.
N
N
N
N
N
N
N
N
N

5. Till date, no compound containing the 1, 2, 3-triazines system has been isolated from
natural source.
Derivatives of 1, 2, 3-triazines are important class of heterocyclic compounds that are
useful in organic synthesis since they act as diene in inverse-demand Diels-Alder
cycloaddition.
1, 2, 3-triazines can be prepared from
(1) Tricycles
(2) Pentacycles
1, 2, 3-triazines

6. Tricycles
The rearrangement of cyclopropenyl azide is a method used for the synthesis of
monocyclic 1, 2, 3-triazine. This reaction occurs via [3+2] cycloaddition
followed by ring expansion.
N
N
N
R
R
R
N
N
N
R
R
N
R
R
R
R
N
N
N
R
R
R
N
N

7. The more general synthetic method to obtain various mono-, di- and tri-substituted
alkyl and aryl triazines is by oxidation of N-aminopyrazole with lead tetra acetate
(Pb(OAc)4). The amino nitrogen incorporated into triazine ring probably via
insertion of nitrene moiety to the N-N bond of the pyrazole ring.
Pb(OAc)4
N
N
N
R
R
R
N
N
NH2
R R
R
N
N
N
R R
R

8. Reaction with electrophilic reagents
Electrophilic reaction on the ring carbon of 1, 2, 3-triazine can not proceed because
of intensive pi-electron deficiency of the ring system.
However, electrophilic reaction proceed on the ring nitrogen of substituted 1, 2, 3-
triazines.
N
N
N
R
N
N
N
R
MeI
R
R
R
R
EtO3X
N
N
N
R
R
R
N
N
N
R
R
R
Me
Et
I
X

9. Reaction with nucleophilic reagents
1, 2, 3-triazine are highly π electron deficient and are readily attacked by
nucleophiles.
The reaction occurs exclusively at the C-4 position, even in the presence of a
substituent at C-4.
N
N
N
Cl
N
N
N
Cl
i-Pr2NH
Cl
Cl
Cl
Cl
MeONa
N
N
N
N-iPr2
Cl
Cl
N
N
N
OMe
Cl
MeO

10. Cycloaddition reaction
1, 2, 3-triazine are useful compounds that participate in cycloaddition reactions.
These compounds behaves as π -deficient dienes and undergo inverse demand
Diels-Alder addition with electron rich dienophiles.
N
N
N
Me R
N
N
Me
R
N
N
N
Me
R
N
Me
R
NEt2
NEt2
ZnBr2

11. 1, 2, 4-triazine
1, 2, 4-triazine are biologically very active compounds. Many have been tested for
use in agrochemistry or medicines.
1, 2, 4-triazines can be prepared from
(1) Other heterocycles
(2) Condensation reactions
N
N
N NH2
O
O2N
N
N
N NH2
Cl
Cl
H2N
Antibacterial and tuberculostatic activity Sodium channel blocker

12. The transformation of 1-benzohydrazonoyl-1, 2, 3-triazoles into 1, 2, 4-triazine by
heating with a slight excess of sodium hydride.
This reaction proceed via Bamford-Stevens reaction followed by the ring
enlargement by insertion of carbene gives 1, 2, 4-triazines.
N
N
N ArR
R
NaH
N
N
N
Ar
N
N
H
S
O
O
Ph
R
R N
N
N
Ar
N2
R
R N
N
N
Ar
R
R
Other heterocycles

13. The synthesis of 1, 2, 4-triazine via condensation of 1, 2-diketones with acyl
hydrazides and ammonium acetate under thermal condition.
R
R1
O
O
R2 N
H
O
NH2
N
N
N R2R
R1
NH4OAc
AcOH
Condensation reaction

14. Reaction with electrophilic reagents
The salt of simple 1, 2, 4-triazines are obtained by addition of dry acids to a solution
of the triazine in organic solvents.
Alkylation and acylation of 1, 2, 4-triazine systems have been studied extensively.
N
N
N R
N
N
N R
N
N
N RR
MeI
R R
R R
R
Me
Me
I
I
(Major) (Minor)

15. Reaction with nucleophilic reagents
The most reactive position of the 1, 2, 4-triazine is position-5. This position is easily
attacked by nucleophilic agents.
Most leaving groups in 3-, 5- and 6-positions of 1, 2, 4-triazines can be easily
substituted by carbon nucleophiles prepared from –CH acidic compounds.
N
N
N SMe
N
N
N R
N
N
N SMeAr
ArLi
DDQ
R-B(OH)2
CuMeSal
Pd(PPh3)2

16. Cycloaddition reaction
1, 2, 4-triazines behaves as electron deficient dienes and react with dienophiles such
as electron rich alkenes and alkynes.
N
N
N R1R2
R3
N R1R2
R3

17. N
NN
R1
R2
R3
N
NN
R1
R2
R3
N R1R2
R3
N2

18. 1, 3, 5-triazine
1, 3, 5-triazines have been studied extensively both theoretically and experimentally.
One of the most important applications of 1, 3, 5-triazines is in the field agricultural
field as fungicides, insecticides and herbicides.
Some representative examples includes
N
NN
HN
Cl Cl
Cl
Anilazine
(Fungicide)
N
NN
Cl
N
H
N
H
Simazine
(Herbicide)

19. 1, 3, 5-triazines are often referred by trivial names such as cyanuric acid,
cyanurates, cyanuryl chloride and melamines.
N
NN
N
NN
N
NN
N
NN
OH
HO OH
OR
RO OR
NH2
H2N NH2
Cl
Cl Cl

20. Synthesis
The best method to obtain 1, 3, 5-triazines is the reaction of ammonium acetate and
triethylformate.
N
NN
EtO
C
OEt
EtO
H
NH4OAc

21. Pinner triazine synthesis
Reaction of aryl amidines and phosgene results in the formation of 2-hydroxy-4, 6-
diaryl-s-triazines.
N
NN
Ar
OH
Ar
2
Ar NH2
NH
Cl Cl
O
Ar N
H
NH
N
H
Ar
NHO
-2HCl
-NH3

22. Trimerization of cyanogen chloride in the gas phase on activated charcoal is
probable most useful industrial route to obtain cyanuric chloride.
N N
NCl Cl
Cl

N C Cl3

23. Reaction with electrophilic reagents
Do not undergo electrophilic substitution reaction. However, under vigourous
conditions chlorination and bromination probably via nucleophilic addition reaction.
N N
N
Br2
N N
NBr Br
Br
N N
N
Cl2
N N
NCl Cl
Cl
N N
NCl Cl
120o
C
200o
C
(Major) (Minor)

24. Reaction with nucleophilic reagents
1, 3, 5-triazine are extremely sensitive to nucleophilic substitution, particularly
hydrolysis in presence of even trace of atmospheric water.
Nucleophilic attack at the aromatic 1, 3, 5-triazine results in ring cleavage.
This ring opening leads to the formation of important heterocycles like triazole and
benzimidazole.
N N
N
MeNHNH2
N N
N
N
N
N
H2N
H2N N
H
N
180o
C

25. Formylating agents
In Gatterman’s aldehyde synthesis, hydrogen cyanide can be substituted by 1, 3, 5-
triazine.
In presence of HCl, triazine undergoes electrophilic attack on aromatic compounds
like furan, pyrroles and polyhydroxy benzenes yielding an intermediate aldimine
hydrochloride which on hydrolysis afford aldehyde.
O
CH3
H3C N N
N
O
CH3
H3C
NH2
H
HCl
Cl
H2O
O
CH3
H3C
O
H

26. Several nucleophilic substitutions of halogen derivatives of 1, 3, 5-triazine take
place by displacement of chlorine atom of cyanuric chloride with different
nucleophiles.
It is possible to obtain mono-, di- (or) tri-substituted-1, 3, 5-triazines by controlling
the nature of nucleophiles (or) the reaction temperature.
N
N
N
Cl
Cl Cl
N
N
N
NHR
Cl Cl
RNH2
0o
C
R'NH2
25o
C
N
N
N
NHR
R'HN Cl
R"NH2 80o
C
N
N
N
NHR
R'HN NHR"