Synthesis of some 1,3,5-triazine derivatives

Article abstract of DOI:10.3987/COM-06-10671

Some derivatives of 1,3,5-triazine were prepared with excellent yields by nucleophilic reactions between cyanuric chloride and some nucleophiles under mild conditions.{A figure is presented}.

Full text of DOI:10.3987/COM-06-10671

HETEROCYCLES, Vol. 68, No. 4, 2006
807
HETEROCYCLES, Vol. 68, No. 4, 2006, pp. 807 - 810. © The Japan Institute of Heterocyclic Chemistry
Received, 11th January, 2006, Accepted, 28th February, 2006, Published online, 3rd March, 2006. COM-06-10671
SYNTHESIS OF SOME 1,3,5-TRIAZINE DERIVATIVES
Davood Azarifar* and Ali Forghaniha
Chemistry Department, School of Science, Bu-Ali Sina University, 65174,
Hamadan, Iran. E-mail: azarifar@basu.ac.ir
Abstract- Some derivatives of 1,3,5-triazine were prepared with excellent yields by
nucleophilic reactions between cyanuric chloride and some nucleophiles under mild
conditions.
Available data on 2,4,6-trichloro-1,3,5-triazine, or cyanuric chloride (1), suggest that it is a highly
reactive halogen compound, almost like an acid chloride.1 It is of great synthetic importance in the
preparation of 1,3,5-triazine derivatives,2 and industrially important in forming the basis of a wide range
of complex dyestuffs (Procoin and Cibacron dyes) as an stable unit to which can be attached two or
three dyestuffs, and which can even be covalently linked to fiber cellulose.3,4 Cyanuric chloride has also
been widely employed in organic synthesis as a versatile reagent to effect various transformations such
as the conversion of carboxylic acids to their different derivatives,5,6 oxidation of alcohols,7 and
dehydration of amides8 and aldoximes to nitriles under very mild conditions.9 Also, aryl sulfoxides have
been subjected to deoxygenation to aryl sulfides by cyanuric chloride in dioxane under reflux
condition.10 Polymers containing the 1,3,5-triazine moieties exhibit an unusual combination of
properties such as high softening temperature and thermal stability together with higher solubility.11
Electron-accepting property of the 1,3,5-triazine, that could be altered upon substitution with
nucleophiles,12 has made it to be so valuable as a bridging agent in synthetic reactive dyes,13,14 and other
biologically active compounds.15-17 It has been shown that, the substitution of the first chlorine atom in
the cyanuric chloride by most nucleophiles usually occurs under very mild conditions, whereas the
second and third chlorine atoms are replaced increasingly more severely.11,18
In continuation of our previously reported work on the nucleophilic reactions of the cyanuric chloride
with various nucleophiles,19 we have observed that the reactions of cyanuric chloride with 4-
aminophenyl ether (2) and 4,4΄-methylenedianiline (3) occur in CH2Cl2 under very mild conditions at
room temperature to produce (4,6-dichloro-1,3,5-triazin-2-yl)-4-aminophenyl ether (4) and 4,4'-
methylenedi[N-(4,6 dichloro-1,3,5-triazin-2-yl)]aniline (5) respectively in high yields (Scheme 1). All
attempts to substitute the remaining chlorines on the 1,3,5-triazine ring of these products by different

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HETEROCYCLES, Vol. 68, No. 4, 2006
nucleophiles such as imidazole, pyrazole, piperidine and morpholine under various conditions resulted
in the formation of several mixed products in very low yields, so that they couldn't be characterized.
Scheme 1
Cl
Cl
N
N
N
Cl
Cl
N
CHCl3/rt
N
HN
NH
X
H N
+
N
X
NH
2
2
N
N
N
Cl
Cl
Cl
(4) X=O
(5) X=CH2
(2) X=O
(3) X=CH2
(1)
In addition, it was shown that the cyanuric chloride can readily undergo reactions with N-
methylmorpholine in CH2Cl2 at room temperature to afford 1,3,5-triazine-2,4,6-tris(N-
methylmorpholinium) chloride (6) as an insoluble product in high yield, whereas the reaction with
morpholine to produce 2,4,6-tris(1-morpholino)-1,3,5-triazine (7) required more vigorous condition
(Scheme 2). The greater reactivity of the cyanuric chloride towards N - methylmorpholine compared
Scheme 2
Cl
CH
O
3
O
+
N
N
N
N
+
N
Cl
l
C
H
C
H
l
C
C
CH2Cl2/ rt
N
N
3
3
N
+
3
O
N
N
+
Cl
CH
3
l
C
(6)
O
O
O
N
N
N
N
l
l
C
C
H
fusion
-HCl
N
+
3
N
N
O
N
N
N
l
C
(7)
O
with morpholine itself is possibly attributed to the positive charge generated on morpholine nitrogen
atom upon its attachment to the 1,3,5-triazine ring which renders the remaining chlorine atoms more
reactive towards the subsequent replacements. It is, however, interesting to note that when cyanuric
chloride is refluxed with N-methylmorpholine for almost one hour, demethylation occurs to produce
2,4,6-tris(1-morpholino)-1,3,5-triazine (7) in quantitative yield. This is evidenced by disappearance of
the methyl group signals shown in the 1H-NMR and 13C-NMR spectra of the compound (6).

HETEROCYCLES, Vol. 68, No. 4, 2006
809
EXPERIMENTAL
Chemicals were purchased from Fluka, Merck and Aldrich chemical companies and purified prior to
13
use.1H NMR and CNMR spectra were recorded with JEOL FX 90Q (90 MHz) and Bruker DRX 500
AVANCE (500 MHz) spectrometer. IR spectra were recorded using a Perkin Elmer GX FT-IR
spectrophotometer. Melting points were determined on a Stuart SMP3 apparatus and reported
uncorrected. Elemental analyses were performed on a Perkin Elmer 2400 microanalyser. MS spectra
were recorded on a GCMS-QP 1100 EX spectrometer.
(4,6-Dichloro-1,3,5-triazin-2-yl)-4-aminophenyl ether (4): A mixture of 4-aminophenyl ether (0.2 g, 1
mmol), cyanuric chloride (0.369 g, 2 mmol) and sodium carbonate (0.26 g, 2.5 mmol) in chloroform (30
mL) was stirred at rt. The reaction was completed in 10 min as monitored by TLC. The resulting
reaction mixture was evaporated, the residue was dissolved in acetone (30 mL) and filtered. Then the
filtrate was dried over anhydrous MgSO4, filtered and evaporated to leave a solid product which was
1
recrystallized from ethanol, yield 0.46 g (93%); mp 232-233 ºC; H-NMR (CDCl3): δ 7-7.55 (8H, dd,
13
J=9.8 and 31.9 Hz, Ar), 7.46-7.55 (2H, 2NH); C-NMR (CDCl3): δ 119.56 (C3), 123.19 (C2), 131.23
(C4), 154.78 (C1), 164.16 (C ipso triazine), 172.55 (C-Cl) ; IR (KBr): 3278 (N-H), 1615, 1497 (Ar),
1551 (N-H) (cm-1); MS (EI): m/z 496 (M+); Anal. Calcd for C18H10N8OCl4: C, 43.58; H, 2.01; N, 22.58;
Found: C, 43.61; H, 1.98; N, 22.65.
4,4΄-Methylenedi[N-(4,6-dichloro-1,3,5-triazin-2-yl)]aniline
(5):
A
mixture
of
4,4'-
methylenedianiline (0.198 g, 1 mmol), cyanuric chloride (0.369 g, 2 mmol) and sodium carbonate (0.26
g, 2.5 mmol) in chloroform (20 mL), was stirred at rt. The reaction was completed in 5 min as monitored
by TLC. Then the resulting reaction mixture was filtered, the filtrate was dried over anhydrous NaSO4,
filtered and evaporated to yield a solid residue which was recrystallized from ethanol, yield 0.47 g
1
(95%); mp 248-249 ºC; H-NMR (CDCl3): δ 3.96 (2H, s, CH2), 7.24 (8H, m, Ar), 7.66 (2H, s, 2NH);
13C-NMR (CDCl3): δ 40.80 (CH2), 121.58 (C3), 129.72 (C2), 133.99 (C4), 138.46 (C1 ), 164.10 (C ipso
triazine), 171.39 (C-Cl) ; IR (KBr): 3361 (N-H), 1613, 1507 (Ar), 1560 (N-H) (cm-1); MS (EI): m/z 494
(M+); Anal. Calcd for C19H12N8Cl4: C, 46.19; H, 2.43; N, 22.67; Found: C, 46.24; H, 2.38; N, 22.74.
1,3,5-Triazine-2,4,6-tris(N-methylmorpholinium) chloride (6): A mixture of cyanuric chloride
(0.369 g, 2 mmol) and N-methylmorpholine (0.8 mL, 7 mmol) in methylene chloride (15 mL) was
stirred at rt for 1 h. After the reaction was completed (TLC), the resulting mixture was filtered, the
filtrate was dried over anhydrous MgSO4 and filtered. Evaporation of the filtrate gave a solid which was
1
recrystallized from ethanol, yield 1.0 g (93%); mp 130-131 ºC; H-NMR (D2O): δ 3.53 (3H, s, CH3),
3.92 (6H, m, 2-OCH2-, 2-NCH-), 4.50 (2H, d, J=8.6 Hz, 2-NCH-); 13C-NMR (D2O): δ 55.12 (CH3),
59.66 (CH2O), 62.08 (CH2N), 169.69 (C triazine) ; IR (KBr): 1589, 1506, 1461, 1361, 1386, 1267, 1114
(cm-1); Anal. Calcd for C16H33N3O3Cl3: C, 45.59; H, 7.83; N, 9.96. Found: C, 45.65; H, 7.79; N, 10.08.
2,4,6-Tris(1-morpholino)-1,3,5-triazine (7): A mixture of cyanuric chloride (0.369 g, 2 mmol) and N -

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HETEROCYCLES, Vol. 68, No. 4, 2006
methylmorpholine (1.2 mL, 10 mmol) in CH2Cl2 (20 mL) was refluxed for 1 h. The resulting mixture
was let to cool to rt and then evaporated to yield a solid which was recrystallized from ethanol to give
white solid product (7), yield 1.26 g (91%); mp 283-285 ºC (decomp) [lit.,20 mp 284-285 ºC (decomp)].
ACKNOWLEDGMENT
We wish to thank the University of Bu-Ali Sina, Hamadan, Iran, for financial support to carry out this
research.
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