Received: June 10, 2015 | Accepted: June 24, 2015 | Web Released: July 4, 2015
CL-150569
Copper-catalyzed Facile Synthesis of Unsymmetrical TriazineTriazole Conjugates
Zhenhua Wang, Xiu Wang, Guofang Zhang, Weiqiang Zhang,* and Ziwei Gao*
Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering,
Shaanxi Normal University, Xi’an 710062, P. R. China
(
E-mail: zwgao@snnu.edu.cn, zwq@snnu.edu.cn)
A series of unsymmetrical triazinetriazole conjugates were
prepared by the copper-catalyzed cycloaddition reactions of 2-
azide-4,6-dimethoxy-1,3,5-triazine with terminal alkynes under
mild reaction conditions. The heterocyclic conjugates were
characterized as 1,4-substitution products. The UVvis and
photoluminescence properties of the triazine-based molecules
were evaluated.
Cl
R1
N
N
N
Nucleophilic Substitution
HR1
N
N
N
Cl
Cl
R1
Cl
NaN3
R1
N
R1
N
N
N
N
Click Reaction
R2
N
N
The electron-withdrawing core of 1,3,5-triazines allows
N
N3
1
6
R2
N
ready synthesis of molecular conjugates with C3v symmetry.
R1
R1
1
By conjugating to heterocyclic rings such as pyridine, carbazole,
and thiophene, the triazine derivatives exhibited unprecedented
1a R =OMe
1b R1=
-MeOC H
79
10,11
luminescence,
nonlinear optical response
and strong
p
6
4
12
coordination ability to transition metals. Exploring a flexible
synthetic strategy is essential for access to a broad array of
functional triazine compounds. The cyclotrimerization of arylni-
triles furnished 2,4,6-tripyridyl-1,3,5-triazines,13 which showed
thermally activated delayed fluorescence, and versatile coordi-
nation modes to transition metals.1 Palladium-catalyzed cross-
coupling reactions, such as Sonogashira coupling, Suzuki
Miyaura coupling, Stille coupling,16 and Negishi coupling,
successfully constructed the heterocyclic triazines by using the
nucleophiles of pyridyl, carbazolyl, or thiophenyl groups. The
copper(I)-catalyzed 1,2,3-triazole formation from azides and
terminal acetylenes is a powerful tool for the generation of privi-
leged medicinal scaffolds, due to its high degree of depend-
ability, complete specificity, and the biocompatibility of the
Scheme 1. Synthesis of unsymmetrical triazinetriazole conjugates
via “Click Reaction.”
and 1b were prepared in high yields with a modified literature
4,15
24
method. In DMF, both 2-chloro-4,6-dimethoxy-1,3,5-triazine
and 2-chloro-4,6-bis(4-methoxyphenyl)-1,3,5-triazine reacted
with sodium azide at room temperature, which afforded 1a
and 1b with 87% and 88% yield, respectively (Scheme 1).
The preparation of 1,2,3-triazoles from organic azides and
terminal alkynes, in particular (CuAAC) reaction, has witnessed
a true explosion since the discovery of copper(I) species as
17
2
2,25
outstanding and selective catalysts for this reaction.
Under
thermal condition, the triazole-forming cycloaddition usually
1
8
22
reactants. The unsymmetrical triazine triazoles can be con-
results in a mixture of the 1,4- and 1,5-regioisomers. We
1
9,20
structed by “Click Reaction” of triazine alkynes with azides.
found that copper halides with the assistance of triethylamine
successfully catalyze the cycloaddition reaction between the
triazine azides 1a and 1-ethynyl-4-methoxybenzene (Table 1,
Entries 13). The CuX (X = Cl, Br, and I) catalyzed click
reaction in dichloromethane gave over 90% yield of product for
3 h, while 80% yield was obtained in the case of Cu2O (Table 1,
Entry 4). Then, we examined the effect of bases in the reaction.
The results indicated that aliphatic amines, DIPEA and triethyl-
amine are more reactive than pyridine. These experimental
results confirmed that triethylamine was the best of the bases.
Solvent effects were evaluated. In the polar solvents, such as
CH2Cl2, MeCN, and THF, the reactions afforded the products
with 98, 94, and 80% yield, (Table 1, Entries 1, 7, and 9),
respectively. The low yield in toluene might be due to the
insolubility of the Cu catalyst in nonpolar solvent.
Next, we explored the scope and limitation of this method.
By using the optimized reaction conditions, we were able to
apply Cu-catalyzed cycloaddition to a range of conjugate targets,
including different kinds of substituted-1,3,5-triazine mono-
azides and also alkynes substituted by aryl or alkyl groups. All
of them except 3,3-dimethylbut-1-yne (Table 2, Entry 7) afford-
ed the desired products in excellent yields.
Recently, the unsymmetrical triazines have drawn a great
interest since such molecular architectures increase the number
of the conformers and the amount of free energy for crystal-
lization, which favors the stability of amorphous film for high-
2
1
performance devices. These complicated triazine heterocycles
were prepared with difficulty by either classic trimerizations of
organic nitriles or Pd-catalyzed CC cross-coupling reactions
of triazine halides. Until now, few studies on the cyclization
reactions of triazine azides and terminal alkynes have been
reported, which might provide an interesting alternative syn-
thetic route to unsymmetrical triazine triazole compounds. In
this paper, we developed a facile synthetic procedure for
unsymmetrical triazine conjugates by copper(I)-catalyzed cyclo-
addition reaction of alkyne-triazines and monoazides. Molecular
structures of the triazine-based molecules were confirmed and
their UVvis and photoluminescence properties have been
determined.
Azides possess extraordinary stability towards water, oxy-
2
2
gen, and a majority of organic synthetic conditions. The
spring-loaded nature of the azide group remains invisible unless
a good dipolarophile is favorably presented.23 Triazine azides 1a
© 2015 The Chemical Society of Japan | 1333
Wang, Zhenhua
